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El Editor. "Derechos humanos ; La situación del país." ECA: Estudios Centroamericanos 51, no. 573-574 (August 31, 1996): 709–21. http://dx.doi.org/10.51378/eca.v51i573-574.6693.
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ТРЕТЬЯКОВА, А. С. "РАСПРЕДЕЛЕНИЕ ВИДОВОГО СОСТАВА РАСТЕНИЙ В ЕСТЕСТВЕННЫХ И АНТРОПОГЕННЫХ МЕСТООБИТАНИЯХ Г. ЕКАТЕРИНБУРГА, "БОТАНИЧЕСКИЙ ЖУРНАЛ"." Ботанический журнал, no. 11 (2014): 1277–82. http://dx.doi.org/10.1134/s1234567814110081.
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Показано, что общий вектор преобразования флоры на урбанизированных территориях выражается в сокращении индигенных видов, увеличении доли апофитных и адвентивных. В растительных сообществах естественных местообитаний встречается более 75 % видов урбанофлоры Екатеринбурга - 709 видов. Среди них преобладают аборигенные виды (87 %), а адвентивные виды играют второстепенную роль. В составе растительных группировок антропогенных местообитаний насчитывается 613 видов, среди них заметно сокращается число аборигенных видов (49 %) и соответственно увеличивается число адвентивных: 51 против 13 % в естественных местообитаниях. Растительные сообщества естественных местообитаний сохраняют соответствующее их ценотическому статусу своеобразие флористического состава, а для растительных группировок антропогенных местообитаний характерна низкая флористическая специфичность.
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Drenowatz, Clemens, Olivia Wartha, Jochen Klenk, Susanne Brandstetter, Martin Wabitsch, and Jürgen Steinacker. "Differences in Health Behavior, Physical Fitness, and Cardiovascular Risk in Early, Average, and Late Mature Children." Pediatric Exercise Science 25, no. 1 (February 2013): 69–83. http://dx.doi.org/10.1123/pes.25.1.69.
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This study examined the association between biological maturity, CVD risk, fitness and health behavior in 709 (359 male, 350 female) 8-year-old children (range: 6.3–8.9 years). Sports participation and sedentary behavior was assessed via parent questionnaire. Height and weight was measured and maturity status was predicted based on % of adult-height reached. Fitness was assessed via a test battery and CVD risk was determined using mean arterial pressure, cholesterol and intra-abdominal fat. BMIpercentiles (BMIPCT) differed significantly among early, average and late maturing children. Early maturing children displayed a higher CVD risk profile (0.5 vs. -0.2), lower fitness scores (-0.4 vs. 0.2), and spent more time watching TV (51 vs. 43 min/day) compared with their peers. After controlling for BMIPCT differences remained only for fitness in boys and TV time in girls.
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Caylan, Refik, Ali Titiz, Maurizio Falcioni, Guiseppe De Donato, Alessandra Russo, Abdelkader Taibah, and Mario Sanna. "Myringoplasty in Children: Factors Influencing Surgical Outcome." Otolaryngology–Head and Neck Surgery 118, no. 5 (May 1998): 709–13. http://dx.doi.org/10.1177/019459989811800529.
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Age, size, and site of perforation, condition of the ear, status of the contralateral ear, grafting materials, and more are considered factors influencing the success rates in myringoplasties in children. The ambivalence in results is mainly due to nonhomogeneous patient groups. In an effort to compose groups as homogeneous as possible for analysis of influencing factors, a retrospective study of 51 pediatric myringoplasty cases (51 ears) was undertaken. All patients had perforations caused by simple chronic otitis media. The overall surgical success rate was 82.3% at 18 months, and for young (5 to 10 years) and older (11 to 16 years) children it was 77.2% and 86.2%, respectively. Anterior, central, and total perforations healed without significant differences. Outcome in unilateral perforations was better than bilateral: 96.9% and 55%, respectively ( p < 0.01). Discharging ears (100%) healed better compared with dry ears (75%) ( p < 0.05). Analysis of the literature also revealed significant difference in success rates of discharging and dry ears: 92.5% and 80.6%, respectively ( p < 0.01). We conclude that, contrary to comments in the literature, discharging ears in children favor good outcome and they should be operated on regardless of age and site of perforation. However, in bilateral perforations results may not be so rewarding. (Otolaryngol Head Neck Surg 1998;118:709–13.)
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Tian, Erming, Joshua Epstein, Pingping Qu, Christoph Heuck, Frits van Rhee, Maurizio Zangari, Antje Hoering, Jeffery Sawyer, Bart Barlogie, and Gareth J. Morgan. "Deletion of TP53 (17p13) Is Associated with Poor Outcome for Newly Diagnosed High-Risk Multiple Myeloma." Blood 126, no. 23 (December 3, 2015): 2982. http://dx.doi.org/10.1182/blood.v126.23.2982.2982.
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Abstract Introduction In multiple myeloma (MM), deletion of chromosome 17 p13 (del17p) is a poor prognostic feature. The percentage of cells carrying an abnormality has been reported to be important with thresholds of 20% being taken generally but thresholds as high as 60% being suggested more recently. We have reported previously in the Total Therapy (TT)-2 trial (NCT00083551) for newly diagnosed (ND) MM that del17p is an adverse prognostic factor (Blood 112: 4235). The TT3 trial (NCT00081939) incorporated Brtezomib into tandem Melphalan-based autotransplants with DT-PACE for induction/consolidation and Thalidomide and Dexamethasone for maintenance to treat patients with newly diagnosed MM. In more recent iterations of these trials following the introduction of novel agents in induction and during maintenance the impact of carrying del17p has not been studied. In particular we have stratified patients into low- or high-risk molecular subgroups based on the GEP-70 (TT4 protocol [NCT00734877] or TT5 protocol [NCT00869232], respectively). We have used interphase FISH (iFISH) to detect the presence of del17p in baseline bone marrow samples. Method The iFISH slides were prepared with bone marrow aspirates after removing erythrocytes. A specific TP53 probe at chromosome 17 arm p13 combined with a control probe for the ERBB3 locus (HER2, 17q12), in different colors, were hybridized to bone marrow cells. Myeloma PCs were identified by restricted Kappa or Lambda immunoglobulin light-chain staining. We investigated role of 20% cutoffs per ≥100 tumor cells for significant deletion of the TP53 probe. Kaplan-Meier analysis was used to estimate the distributions of overall survival (OS) and progression-free survival (PFS) during the follow-ups. OS was calculated from registration until the date of decease. PFS was similarly calculated, but also incorporated progressive disease as an event. Results We examined 709 baseline samples from TT3, 4, and 5 trials with the two probes at chromosome 17. Overall, 66 of 709 patients (9.3%) had deletion of TP53 locus, including 44 of the 591 (7.5%) of low-risk patients and 20 of the 118 (17.0%) high-risk patients (Table). The range of TP53-deleted cells among newly diagnosed patients is 20-99% (median=75%) overall; 35-100% (median=62%) in TT3-low-risk; 30-97% (median=80%) in TT3-high-risk; 21-99% (median=76%) in TT4; and 20-97% (median=81%) in TT5. Deletion of TP53 was associated with significant shorter OS and PFS in HR patients treated on TT3. The 3 year estimated OS of patients for TT3-HR with del17p was 33% compared with 56% for TT3-LR with del17p, and PFS of patients for TT3-HR with del17p was 25% compared with 51% for TT3-LR with del17p (Figure). The comparison of TT4 to TT5 continued showing short OS in HR patients treated on TT5. The 3 year estimated OS of patients for HRMM with del17p was 17% compared with 75% for TT5 patients without deletion (p=0.0008). But, del17p was neutral in LR patients treated on TT4 (Figure). Conclusion Since the introduction of novel agents during various stages of the disease and a focus on HRMM and LRMM defined by GEP70 we show that while TP53 deletion is an adverse prognostic factor for patients with HRMM it is no longer prognostically relevant in LRMM. Table 1. Patients with iFISH results GEP-70 riskLow ≤0.66 High >0.66 Deletion TP53 in 20-59% PCs (n/N [%]) Deletion TP53 in ≥60% PCs (n/N, [%]) Total TT3 (N=329) Low=256 9/329, [2.7%] 9/329, [2.7%] 18/329, [5.5%] High=73 3/329, [0.9%] 9/329, [2.7%] 12/329, [3.7%] TT4 (N=313) Low=313 5/313, [1.6%] 21/313, [6.7%] 26/313, [8.3%] High=0 0 0 0 TT5 (N=67) Low=22 2/67, [3.0%] 0 2/67, [3.0%] High=45 0 8/67, [11.9%] 8/67, [11.9%] Sum (N=709) Low=591 (83.4%) 14/709, [2.0%] 30/709, [4.2%] High=118 (16.6%) 3/709, [0.4%] 17/709, [2.4%] 66/709 (9.3%) Figure 1. Figure 1. Disclosures Tian: University of Arkansas for Medical Sciecnes: Employment. Epstein:University of Arkansas for Medical Sciences: Employment. Qu:Cancer Research and Biostatistics: Employment. Heuck:Millenium: Other: Advisory Board; Janssen: Other: Advisory Board; Celgene: Consultancy; Foundation Medicine: Honoraria; University of Arkansas for Medical Sciences: Employment. van Rhee:University of Arkansa for Medical Sciences: Employment. Zangari:University of Arkansas for Medical Sciences: Employment; Millennium: Research Funding; Onyx: Research Funding; Novartis: Research Funding. Hoering:Cancer Research and Biostatistics: Employment. Sawyer:University of Arkansas for Medical Sciences: Employment. Barlogie:University of Arkansas for Medical Sciences: Employment. Morgan:Weismann Institute: Honoraria; CancerNet: Honoraria; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; MMRF: Honoraria; University of Arkansas for Medical Sciences: Employment; Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees.
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Tiến Kiên, Nguyễn. "Nghiên cứu ứng dụng số liệu mưa vệ tinh mô phỏng lũ khu vực trung lưu sông Mã." Vietnam Journal of Hydrometeorology 709, no. 1 (January 25, 2020): 51–62. http://dx.doi.org/10.36335/vnjhm.2020(709).51-62.
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Ellis, Frank. "Growing points in radiotherapy since 1930. The 65th Mackenzie Davidson Memorial Lecture 1984." British Journal of Radiology 60, no. 709 (January 1987): 51–68. http://dx.doi.org/10.1259/0007-1285-60-709-51.
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Mastboim, Niv Samuel, Tanya Gottlieb, Isaac Srugo, Alain Gervaix, Meital Paz, Roy Navon, Olga Boico, et al. "2624. Viral Pneumonia in Children: Facing the Challenge Using the Host Response." Open Forum Infectious Diseases 6, Supplement_2 (October 2019): S914. http://dx.doi.org/10.1093/ofid/ofz360.2302.
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Abstract Background Diagnosing viral pneumonia in children is challenging. Chest radiographic imaging and clinical findings cannot reliably distinguish viral from bacterial pneumonia. Furthermore, pathogen-based diagnosis is limited by inaccessible site of infection and high asymptomatic detection rates. The objectives of this analysis were twofold: first, to establish pneumonia etiology by applying a rigorous expert panel process, and second, to evaluate whether a novel host-immune signature that integrates viral induced proteins TRAIL and IP-10 together with bacterial CRP, can accurately differentiate viral from bacterial pneumonia. Methods This analysis included 1025 febrile children enrolled in two multi-center clinical studies that evaluated the host-immune signature performance: ‘Curiosity’ study (Oved et al., PLoS One 2015) and ‘Pathfinder’ study (Srugo et al., Pediatrics 2017). Pneumonia etiology – viral or bacterial – was determined by a panel of 3 independent experts, after reviewing patients’ clinical, laboratory, microbiological, and radiological data. Only cases with majority panel assignment were included. The host-signature generated one of the three results: viral, equivocal or bacterial, based on predetermined cut-offs. Results A total of 709 children were eligible for analysis and had an expert panel etiology determination. Of them, 114 were diagnosed with pneumonia: 51 assigned viral and 63 assigned bacterial (Figure 1). The signature separated viral from bacterial pneumonia with a sensitivity of 94% (95% CI: 85%–99%) and specificity of 95% (85%–99%) with 14% equivocal test results. Out of the 51 children diagnosed with viral pneumonia by the expert panel, 40 (78%) were given antibiotics, and 43 (83%) underwent chest x-ray evaluation. The signature correctly classified 42 of these 51 viral children, indicating its potential to reduce antibiotic overuse rates by 4.4-fold (from 78% to 18%; P < 0.001) and chest x-ray examination by 4.8-fold (from 83% to 18%; P < 0.001). Conclusion The TRAIL/IP-10/CRP signature exhibits high accuracy for diagnosing viral pneumonia in children. The signature’s potential to safely decrease unnecessary antibiotics and chest radiographic imaging should be examined in future utility studies. Disclosures All authors: No reported disclosures.
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Flores, Claudio J., and Luis Augusto Casanova. "Prognostic factors for overall survival in non-Hodgkin lymphomas: Nonlinear effect of continuous covariates." Journal of Clinical Oncology 31, no. 15_suppl (May 20, 2013): e19538-e19538. http://dx.doi.org/10.1200/jco.2013.31.15_suppl.e19538.
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e19538 Background: To evaluate prognostic factors in patients with primary non-Hodgkin lymphomas (NHL). Methods: We retrospectively analyzed prognostic factors (PFs) for overall survival (OS) in 2160 patients (pts) with NHL treated at INEN between 1990-2002. PFs were determinate according to Cox model with P-splines. Results: The median age was 54 years (range 14 - 96) and 51% were male. The majority of the pts had good performance status (73%, WHO 0-1). The Ann Arbor stage was I-II in 51%, III-IV in 49% and B symptoms were present in 38% of the pts. The hemoglobin (Hb) was low in 48%. Leukocytes (WBC), lymphocytes and LDH were elevated in 17.7%, 7.7% and 60% of pts, respectively. Of all patients, 709 (32.8 %) pts had died. The median follow-up was 12.6 months, with a median survival of 61.8 months and the survival rate at 5 and 10 years of 51.2 % and 41.7 % respectively. PFs identified were: age, sex, zubrod, clinical stage, Hb, leukocytes, lymphocytes and LDH. The following table shows the p-value and hazard ratio (HR). The effect of continuous covariates in the log(HR) is non-linear. The cutoff points of highest (HR >1) match the clinically defined ones, which are: age >60yrs, Hb<12g/dl and LDH >240UI/L. Both leukocytes and lymphocytes have two higher risk breakpoints: leukocytes >3x103 and >10x103, lymphocytes <20% and >60%. Conclusions: PFs for OS in our group of pts were similar to other reports in NHL. Age, Hb, leukocytes, and lymphocytes are relevant to OS, which showed a nonlinear effect in the log (HR). [Table: see text]
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Hamako, Jiharu, Sachiyo Nishida, Shosaku Nomura, Yoshihiro Fujimura, Masayuki Ito, Yasuhiro Ozeki, Koiti Titani, and Taei Matsui. "Purification and Characterization of Kaouthiagin, a von Willebrand Factor-Binding and -Cleaving Metalloproteinase from Naja kaouthia Cobra Venom." Thrombosis and Haemostasis 80, no. 09 (1998): 499–505. http://dx.doi.org/10.1055/s-0037-1615236.
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SummaryA von Willebrand factor (vWF)-binding and -cleaving metalloproteinase, termed “kaouthiagin”, was purified from the venom of cobra snake Naja kaouthia. Kaouthiagin is a monomer with a molecular mass of about 46 kDa and 51 kDa under non-reducing and reducing conditions, respectively, and the N-terminal amino acid sequence is homologous to high molecular mass snake venom metalloproteinases. Kaouthiagin bound to vWF in a divalent ion-independent manner, but the reduced kaouthiagin failed to interact with vWF, suggesting that the protein conformation maintained by intrachaindisulfide linkages of the molecule is essential for the binding to vWF. Neither botrocetin nor bitiscetin, vWF-binding modulators from another snake venom, interfered with the binding between kaouthiagin and vWF, but a monoclonal antibody VW92-3 specific to the N-terminal region of vWF (residues 1-910) inhibited the binding. Without affecting platelet GPIb/IX and GPIIb/IIIa, kaouthiagin specifically cleaved vWF between residues Pro-708 and Asp-709 in a divalent ion-dependent manner to diminish the multimeric structure of vWF in plasma, resulting in the loss of ristocetin-induced platelet aggregability and the collagen-binding activity of vWF. These results indicate that kaouthiagin is a unique metalloproteinase which specifically binds to and cleaves vWF at a specific site and that it will be a useful tool for functional dissection of vWF.
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Cope, RL. "Rich but varied?: Lynch, Mary Jo, ed ‘Research questions for the twenty-first century’,Library trendsvol 51 n°4 (2003): pp499–709 [entire issue]. US$28.00 soft ISSN 00242594." Australian Library Journal 53, no. 3 (August 2004): 308–9. http://dx.doi.org/10.1080/00049670.2004.10721659.
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Kleiv, Ø., A. Folkestad, J. Høkedal, K. Sørensen, and E. Aas. "Estimation of upward radiances and reflectances at the surface of the sea from above-surface measurements." Ocean Science 11, no. 5 (October 2, 2015): 779–88. http://dx.doi.org/10.5194/os-11-779-2015.
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Abstract. During 4 field days in the years 2009–2011, 22 data sets of measurements were collected in the inner Oslofjord, Norway. The data consist of recordings of spectral nadir radiances in air and water as well as spectral downward irradiance in air. The studied wavelengths are 351, 400, 413, 443, 490, 510, 560, 620, 665, 681, 709 and 754 nm. The water-leaving radiance and the reflected radiance at the sea surface have been obtained from the measured nadir radiances in air and water, where the latter radiance has been extrapolated upwards to the surface. For comparison we present a simpler and much faster method that determines the water-leaving and reflected radiances solely from above-surface measurements of upward nadir radiance and downward irradiance. This new method is based on an assumption about similarity in spectral shape of the radiance reflected at the surface, and it makes use of the small ratio between water-leaving and reflected radiances at 351 and 754 nm in the Oslofjord. A comparison between the quantities determined by the two mentioned methods shows that the average relative deviations between their results are less than or equal to 15 % for the reflected radiance, at the studied wavelengths. The average relative deviation of the water-leaving radiance at 560 nm is 24 %. These results are obtained for a cloudiness range of 1–8 oktas (12.5–100 %) and solar zenith angles between 37 and 51°. We consider these to be acceptable uncertainties for a first check of satellite products in the inner Oslofjord.
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Love, R. R., N. V. Dinh, T. T. Quy, N. D. Linh, E. M. Hade, G. S. Young, and D. Jarjoura. "Survival with adjuvant surgical oophorectomy and tamoxifen in premenopausal women with operable breast cancer." Journal of Clinical Oncology 25, no. 18_suppl (June 20, 2007): 552. http://dx.doi.org/10.1200/jco.2007.25.18_suppl.552.
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552 Background: Reports of randomized trials evaluating adjuvant ovarian suppression or ablation with and without tamoxifen are limited in number, useful comparative data and long-term follow-up. Methods: From 1993–99 we recruited 709 Vietnamese and Chinese premenopausal women with clinical stage II-III operable breast cancer to a multi-site randomized prospective clinical trial of immediate pre-mastectomy adjuvant surgical oophorectomy followed by tamoxifen for 5 years (n=356) or mastectomy alone with the same combined hormonal therapy on recurrence of disease (n=353).The primary study endpoints were disease-free and overall survival.This report provides analyses for an extended follow-up period after 5 years. Results: With a median follow up of 7 years, disease-free and overall survival were significantly better with adjuvant therapy (log-rank p-values of 0.0003 and 0.0002). Ten year DFS probabilities of 62% and 51% (95%CI 4–22%), and OS probabilities of 70% and 52% (95% CI 6–34%) between adjuvant and observation groups were observed. In the estrogen receptor positive patient subset, 5 and 10 year DFS probabilities were 83% and 61%, and 66% and 47%; and 5 and 10 year OS probabilities were 88% and 74% and 82% and 74% in adjuvant and observation groups respectively. Conclusions: In women with estrogen receptor positive operable breast cancers, 5 and 10 year disease free and overall survival rates following adjuvant oophorectomy and tamoxifen compare favorably with those from other adjuvant regimens. In estrogen receptor positive patients, the hazard function with adjuvant therapy increases after year six. No significant financial relationships to disclose.
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Love, Richard R., Nguyen Van Dinh, Tran Tu Quy, Nguyen Dieu Linh, Nguyen Dinh Tung, Tien-zhen Shen, Erinn M. Hade, Gregory S. Young, and David Jarjoura. "Survival After Adjuvant Oophorectomy and Tamoxifen in Operable Breast Cancer in Premenopausal Women." Journal of Clinical Oncology 26, no. 2 (January 10, 2008): 253–57. http://dx.doi.org/10.1200/jco.2007.11.6061.
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PurposeWorldwide, approximately 750,000 new cases of breast cancer are diagnosed annually in premenopausal women with limited economic resources. Longer-term survival benefits from adjuvant therapies in such women with operable breast cancer are unknown.Patients and MethodsFrom 1993 to 1999, we recruited 709 premenopausal women with operable breast cancer to a multisite randomized clinical trial of adjuvant oophorectomy and tamoxifen for 5 years or observation and this combined hormonal therapy on recurrence.ResultsWith a median follow-up of 7.0 years, disease-free and overall survival were significantly improved with the adjuvant treatment (log-rank P = .0003 and .0002, respectively). Five year disease-free survival (DFS) probabilities of 74% and 61% (95% CI for difference, 7% to 21%) and overall survival (OS) rates of 78% and 71% (95% CI for difference, 1% to 21%) were observed in the adjuvant and observation groups. Ten-year DFS probabilities of 62% and 51% (95% CI for difference, 4% to 22%) and OS probabilities of 70% and 52% (95% CI for difference, 6% to 34%) between adjuvant and observation groups, respectively, were observed. In the subset of estrogen receptor–positive patients, 5-year DFS probabilities were 83% and 61%, and 10-year DFS probabilities were 66% and 47%, while 5-year OS probabilities were 88% and 74%, and 10-year OS probabilities were 82% and 49% in the adjuvant and observation groups, respectively.ConclusionIn premenopausal women with operable breast cancer not selected for estrogen receptor status or with estrogen receptor–positive tumors, 5- and 10-year DFS and OS rates are significantly improved following adjuvant oophorectomy and tamoxifen.
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Kindler, Christoph H., Spencer C. Yost, and Andrew T. Gray. "Local Anesthetic Inhibition of Baseline Potassium Channels with Two Pore Domains in Tandem." Anesthesiology 90, no. 4 (April 1, 1999): 1092–102. http://dx.doi.org/10.1097/00000542-199904000-00024.
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Background Recently, a new structural family of potassium channels characterized by two pore domains in tandem within their primary amino acid sequence was identified. These tandem pore domain potassium channels are not gated by voltage and appear to be involved in the control of baseline membrane conductances. The goal of this study was to identify mechanisms of local anesthetic action on these channels. Methods Oocytes of Xenopus laevis were injected with cRNA from five cloned tandem pore domain baseline potassium channels (TASK, TREK-1, TOK1, ORK1, and TWIK-1), and the effects of several local anesthetics on the heterologously expressed channels were assayed using two-electrode voltage-clamp and current-clamp techniques. Results Bupivacaine (1 mM) inhibited all studied tandem pore potassium channels, with TASK inhibited most potently. The potency of inhibition was directly correlated with the octanol: buffer distribution coefficient of the local anesthetic, with the exception of tetracaine, to which TASK is relatively insensitive. The approximate 50% inhibitory concentrations of TASK were 709 microM mepivacaine, 222 microM lidocaine, 51 microM R(+)-ropivacaine, 53 microM S(-)-ropivacaine, 668 microM tetracaine, 41 microM bupivacaine, and 39 microM etidocaine. Local anesthetics (1 mM) significantly depolarized the resting membrane potential of TASK cRNA-injected oocytes compared with saline-injected control oocytes (tetracaine 22+/-6 mV rs. 7+/-1 mV, respectively, and bupivacaine 31+/-7 mV vs. 6+/-4 mV). Conclusions Local anesthetics inhibit tandem pore domain baseline potassium channels, and they could depolarize the resting membrane potential of cells expressing these channels. Whether inhibition of these channels contributes to conduction blockade or to the adverse effects of local anesthetics remains to be determined.
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Maclean, W., R. Singh, P. Mackenzie, D. White, S. Benton, J. Stebbing, T. Rockall, and I. Jourdan. "The two-week rule colorectal cancer pathway: an update on recent practice, the unsustainable burden on diagnostics and the role of faecal immunochemical testing." Annals of The Royal College of Surgeons of England 102, no. 4 (April 2020): 308–11. http://dx.doi.org/10.1308/rcsann.2020.0019.
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Introduction Survival for colorectal cancer is improved by earlier detection. Rapid assessment and diagnostic demand have created a surge in two-week rule referrals and have subsequently placed a greater burden on endoscopy services. Between 2009 and 2014, a mean of 709 patients annually were referred to Royal Surrey County Hospital with a detection rate of 53 cancers per year giving a positive predictive value for these patients of 7.5%. We aimed to assess what impact the 2015 changes in National Institute for Health and Care Excellence referral criteria had on local cancer detection rate and endoscopy services. Methods A prospectively maintained database of patients referred under the two-week rule pathway for April 2017–2018 was sub-analysed and the data cross-referenced with all diagnostic reports. Findings There were 1,414 referrals, which is double the number of previous years; 80.6% underwent endoscopy as primary investigation and 62 cancers were identified, 51 being of colorectal and anal origin (positive predictive value 3.6%). A total of 88 patients were diagnosed, with other significant colorectal disease defined as high-risk adenomas, colitis and benign ulcers. Overall, a total of 10.6% of our two-week rule patients had a significant finding. Since the 2015 referral criteria, despite a dramatic rise in two-week rule referrals, there has been no increase in cancer detection. It has placed significant pressure on diagnostic services. This highlights the need for a less invasive, cheaper yet sensitive test to rule out cancer such as faecal immunochemical testing that can enable clinicians to triage and reduce referral to endoscopy in symptomatic patients.
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Reman, Oumedaly, Arnaud Pigneux, Francoise Huguet, Norbert Vey, Andre Delannoy, Nathalie Fegueux, Stephane de Botton, et al. "Central Nervous System Involvement in Adult Acute Lymphoblastic Leukemia (ALL) at Diagnosis and/or at First Relapse: Results from the GET-LALA Group." Blood 110, no. 11 (November 16, 2007): 4326. http://dx.doi.org/10.1182/blood.v110.11.4326.4326.
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Abstract Outcome of adult ALL with central nervous system (CNS) involvement is not clearly defined. We studied 104 patients presenting with CNS involvement at diagnosis among 1493 patients (7%) included into the LALA-87 or LALA-94 trials, and 109 patients (9% of first remitters) presenting CNS disease at the time of first relapse among the 709 relapsing patients (15%) included initially in these trials. Treatment of patients presenting CNS involvement at diagnosis consisted in initial chemotherapy completed by 18 double or triple intrathecal injections associated with 15 to 20 Gy cranial irradiation, followed when possible by intensification by allogeneic or autologous stem cell transplantation (SCT). At diagnosis, 43 patients (41%) presenting with CNS involvement had T-lineage ALL, 53 (51%) had B-lineage ALL (of whom 9 were diagnosed as Philadelphia (Ph) chromosome positive ALL), 8 had undifferentiated ALL or unknown immunophenotype. Eighty-seven of 104 (84%) patients with CNS involvement at diagnosis achieved complete remission (CR). Fifty-three patients underwent SCT (25 allogeneic SCT from matched related or unrelated donor, 28 autologous SCT). Overall survival at 7 years was 34% in those with CNS involvement at diagnosis versus 29% (p = NS) for those without. DFS at 7 years was 35% versus 28% (p = NS). There were no significant differences between patients with CNS involvement and those without CNS involvement regarding T lineage ALL, B lineage ALL (including or not Ph ALL). There were also no significant differences regarding patients who underwent transplantation as consolidation intensification, while in patients receiving only chemotherapy patients without initial CNS involvement had a better outcome (p = 0.01). Among the 709 patients with primary relapse, 66 patients (61%) presented a CNS relapse combined with bone marrow relapse, whereas 17 relapses (15%) and 26 relapses (24%) were CNS relapses combined with another extramedullary relapse or isolated CNS relapses respectively. Median time to relapse was 6.7 months (range, 1–62) in patients with CNS relapse versus 11.2 months (1.7–111) in relapsing patients without CNS involvement. Eleven patients (10%) with CNS relapse had CNS involvement at diagnosis, while 98 patients were diagnosed with CNS disease only at the time of first relapse. Overall, 38 out of 109 patients with CNS relapse (35%) achieved CR. The median OS was 6.3 months. Outcome was similar in terms of CR proportion and OS in relapsing patients without CNS involvement. The 2-year OS rates did not show any difference among patients with CNS relapse who had CNS involvement at diagnosis and those with CNS disease only diagnosed at the time of first relapse.Overall, CNS leukemia in adult ALL is uncommon at diagnosis. Patients have a similar outcome than those who did not present with CNS involvement. However, patients benefit from intensification therapy by autologous or allogeneic SCT. CNS leukemia at first relapse are also uncommon but probably underestimated. Outcome is particularly poor as this of all adult ALL in first relapse.
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Hognert, Helena, Finn Egil Skjeldestad, Kristina Gemzell-Danielsson, Oskari Heikinheimo, Ian Milsom, Øjvind Lidegaard, and Ingela Lindh. "Ecological study on the use of hormonal contraception, abortions and births among teenagers in the Nordic countries." BMJ Open 8, no. 10 (October 2018): e022473. http://dx.doi.org/10.1136/bmjopen-2018-022473.
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ObjectivesCompare hormonal contraceptive use, birth and abortion rates among teenagers in the Nordic countries. A secondary aim was to explore plausible explanations for possible differences between countries.DesignEcological study using national registry data concerning births and abortions among all women aged 15–19 years residing in Denmark, Finland, Iceland, Norway and Sweden 2008–2015. Age-specific data on prescriptions for hormonal contraceptives for the period 2008–2015 were obtained from national databases in Denmark, Norway and Sweden.SettingDenmark, Finland, Iceland, Norway and Sweden.ParticipantsWomen 15–19 years old in all Nordic countries (749 709) and 13–19 years old in Denmark, Norway and Sweden (815 044).ResultsBoth annual birth rates and abortion rates fell in all the Nordic countries during the study period. The highest user rate of hormonal contraceptives among 15–19-year-olds was observed in Denmark (from 51% to 47%) followed by Sweden (from 39% to 42%) and Norway (from 37% to 41%). Combined oral contraceptives were the most commonly used methods in all countries. The use of long-acting reversible contraceptives (LARC), implants and the levonorgestrel-releasing intrauterine systems, were increasing, especially in Sweden and Norway. In the subgroup of 18–19-year-old teenagers, the user rates of hormonal contraceptives varied between 63% and 61% in Denmark, 56% and 61% in Norway and 54% and 56% in Sweden. In the same subgroup, the steepest increase of LARC was seen, from 2% to 6% in Denmark, 2% to 9% in Norway and 7% to 17% in Sweden.ConclusionsBirth and abortion rates continuously declined in the Nordic countries among teenagers. There was a high user rate of hormonal contraceptives, with an increase in the use of LARC especially among the oldest teenagers.
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Bashar, Mohammad Abul, Md Emdadul Haque, and Md Ziaul Islam. "Nutritional Status and Health Related Quality of Life Of Chronic Kidney Disease Patients." Journal of Preventive and Social Medicine 40, no. 2 (December 12, 2022): 44–51. http://dx.doi.org/10.3329/jopsom.v40i2.61796.
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Background: Chronic kidney disease is a steadily growing health problem. Malnutrition is common in this irreversible state of kidney failure. The CKD along with malnutrition adversely affect the HRQOL of the patients. This study was conducted to assess the association between nutritional status and HRQOL of CKD patients. Methods: This cross-sectional study was conducted among 220 CKD patients at Gonoshasthaya Dialysis Centre in Dhaka of Bangladesh during the period from July 2019 to June 2020. Data were collected purposively by using a semi-structured questionnaire with face to face interview, physical examinations and review of medical records. Results: In this study, majority of the patients were male (67.7%) and mean (±SD) age was 47.59±12.51 years. The patients were higher in proportion (60.0%) in stage 5. Mean (±SD) duration of CKD was 3.8 (±1.83) years. Based on SGA score, majority of the patients (81.8%) were mild to moderately malnourished while 5.5% were severely malnourished. Overall mean (±SD) score of HRQOL was 47.07 (±14.89). The score was higher (53.84±13.60) in KDCS followed by MCS (45.99±21.06) and PCS (41.35±14.92). Mean (±SD) score of HRQOL was 33.27±9.80, 45.67±14.26 and 61.96±9.16 in severely malnourished, mild to moderately malnourished and well-nourished patients respectively (F = 24.191, p < .001). Correlation between mean score of HRQOL and SGA score was positively significant (r= .709, p<.001). Age, income, family member, duration of CKD, hemoglobin, serum albumin and SGA score together accounted for 65.6% variability of HRQOL score (R2 = 0.656, adjusted R2 = 0.645, (F= 57.829, p <.001) with the SGA score recording a higher beta value (beta = 0.474, p <.001). Conclusion: The study found, most of the patients were malnourished with a low level of HRQOL score. Correlation between the mean score of HRQOL and SGA score was significant and strongly positive. JOPSOM 2021; 40(2): 44-51
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Kontopantelis, Evangelos, Maria Panagioti, Tracey Farragher, Luke A. Munford, Rosa Parisi, Claire Planner, Sharon Spooner, Alice Tse, Darren M. Ashcroft, and Aneez Esmail. "Consultation patterns and frequent attenders in UK primary care from 2000 to 2019: a retrospective cohort analysis of consultation events across 845 general practices." BMJ Open 11, no. 12 (December 2021): e054666. http://dx.doi.org/10.1136/bmjopen-2021-054666.
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ObjectiveTo describe the distribution of consultations at the practice level and examine whether increases are uniform or driven by people who consult more frequently.DesignRetrospective cohort study.SettingUK general practice data from the Clinical Practice Research Datalink (CPRD) GOLD database.Participants1 699 709 314 consultation events from 12 330 545 patients, in 845 general practices (1 April 2000 to 31 March 2019).MethodsConsultation information was aggregated by financial year into: all consultations/all staff; all consultations/general practitioners (GPs); face-to-face consultations/all staff; face-to-face consultations/GPs. Patients with a number of consultations above the 90th centile, within each year, were classified as frequent attenders. Negative binomial regressions examined the association between available practice characteristics and consultation distribution.ResultsAmong frequent attenders, all consultations by GPs increased from a median (25th and 75th centile) of 13 (10 and 16) to 21 (18 and 25) and all consultations by all staff increased from 27 (23–30) to 60 (51–69) over the study period. Approximately four out of ten consultations of any type concerned frequent attenders and the proportion of consultations attributed to them increased over time, particularly for face-to-face consultations with GPs, from a median of 38.0% (35.9%–40.3%) in 2000–2001 to 43.0% (40.6%–46.4%) in 2018–2019. Regression analyses indicated decreasing trends over time for face-to-face consultations and increasing trends for all consultation types, for both GPs and all staff. Frequent attenders consulted approximately five times more than the rest of the practice population, on average, with adjusted incidence rate ratios ranging between 4.992 (95% CI 4.917 to 5.068) for face-to-face consultations with all staff and 5.603 (95% CI 5.560 to 5.647) for all consultations with GPs.ConclusionsFrequent attenders progressively contributed to increased workload in general practices across the UK from 2000 to 2019. Important knowledge gaps remain in terms of the demographic, social and health characteristics of frequent attenders and how UK general practices can be prepared to meet the needs of these patients.
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Fletcher, Stephen, Michael Strong, and Anthony Villar. "An Investigation of the Effects of Variations in Mentor-Based Induction on the Performance of Students in California." Teachers College Record: The Voice of Scholarship in Education 110, no. 10 (October 2008): 2271–89. http://dx.doi.org/10.1177/016146810811001003.
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Background/Context Policy makers are concerned about teacher shortages and the high rate of attrition among new teachers. Mentor-based induction has been shown to reduce the numbers of new teachers leaving schools or the profession. However, staying in the profession does not mean that new teachers are effective in helping students learn. Purpose/Objective/Research Question/Focus of Study The purpose of the project was to study how variations in new teacher support programs are related to changes in student achievement. Research Design Three districts that had participated in the New Teacher Center training program were asked to be a part of a study about program effectiveness. Using data collected from interviews with district officials, the programs of the districts were categorized based on the mentor/novice ratio. This ratio was selected because it has implications for mentor selection, mentor training, and contact time between mentors and new teachers. Districts also provided achievement data for students taught by new teachers in Grades 2–6. Population/Participants/Subjects Three school districts in California agreed to participate in the study. The number of participants in the three districts included, respectively, 17 new teachers and 424 students; 31 new teachers and 709 students; and 51 new teachers and 1,288 students. Data Collection and Analysis Two types of data were used for the study. First, a numerical score was created for each program based on the mentor/novice ratio. Second, achievement scores from two consecutive spring testing periods were obtained from districts for students taught by new teachers in the elementary grades. Districts were treated as separate case studies, with student achievement being in terms of student and class variables. For one district, we also compared class level achievement for teachers with different years of experience. Conclusions/Recommendations Mentor-based induction may have a positive effect on student achievement if the program allows for weekly contact and mentor selectivity is high.
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Huang, Lyndon G., Juquan Song, Kassandra K. Corona, Kendall Wermine, Elvia L. Villarreal, Phillip H. Keys, Giovanna De La Tejera, et al. "735 Early Treatment with NSAIDs Improves Blood Clotting Function in Severely Burned Patients." Journal of Burn Care & Research 43, Supplement_1 (March 23, 2022): S173—S174. http://dx.doi.org/10.1093/jbcr/irac012.288.
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Abstract Introduction The risk of coagulopathy is increased in severe burns. Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly prescribed in burn patients to relieve pain and reduce inflammation. This study investigates the impact of NSAIDs on burn induced coagulopathy in severely burned patients. Methods Severe burn patients (total body surface area [TBSA] >20%) were identified with TriNetX, a North American federated health research network from 51 health-care organizations (HCOs) and categorized for those receiving NSAIDs during the first week following injury; those with NSAID use prior to injury were excluded. NSAIDs included in this study were ibuprofen, oxaprozin, indomethacin, aspirin, diclofenac, celecoxib, and naproxen. Burn induced coagulopathy was defined as international normalized ratio (INR) levels ≥1.5. Statistical significance of the rate of burn-induced coagulopathy in the week following injury among the two groups was analyzed with measures of association using chi-squared tests. Results We identified 709 severely burned patients receiving NSAIDS during the week after burn and 1,032 severely burned patients without NSAID use. Among those receiving NSAIDs, ibuprofen and aspirin were the most prescribed at rates of 80% and 36%, respectively. After cohort matching, the risk of burn induced coagulopathy was significantly decreased in patients taking NSAIDs (17.7%) compared to patients not receiving NSAIDs (32.3%) (p< 0.0001). The protective nature of NSAIDs was greatest on the same day (p=0.0002) and first day following burn injury (p=0.0026). On average, those not taking NSAIDs had an elevated risk of developing coagulopathy compared to those who did as %TBSA increased in 10% intervals. This observation was confirmed in a linear regression analysis with slopes of 0.0453 and 0.0293, respectively. Furthermore, patients taking NSAIDs were less likely to develop sepsis (p=0.0046) and thrombocytopenia (p=0.0003) and die the first week following injury (p< 0.0001). Conclusions The early protective effects of NSAIDs at reducing the risk of coagulopathy occurs during the acute phase of burns, though selection bias cannot be excluded. The potential risk of burn induced coagulopathy increased more with %TBSA in patients without NASIDs.
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Mathiasen, R. "First Report of Durangan Dwarf Mistletoe, Arceuthobium vaginatum subsp. durangense, on Pinus cooperi and P. engelmannii in Mexico." Plant Disease 91, no. 9 (September 2007): 1201. http://dx.doi.org/10.1094/pdis-91-9-1201a.
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The Durangan dwarf mistletoe (Arceuthobium vaginatum subsp. durangense Hawksw. & Wiens, Viscaceae) parasitizes several species of pines (Pinus spp., Pinaceae) in the Mexican states of Durango, Sinaloa, and Jalisco (1,3). This mistletoe has primarily been reported from the western edge of the Sierra Madre Occidental in eastern Sinaloa and western Durango, but its distribution there is not well documented (3). In March 2007, I found Durangan dwarf mistletoe parasitizing Pinus engelmannii Carr., approximately 25 km north of Mexico Route 40 (24°00′51″N, 105°26′48″W, elevation 2,200 m), and on P. cooperi Blanco approximately 90 km north of Route 40 (24°24′40″N, 105°35′26″W, elevation 2,710 m) along the road to San Miguel de las Cruces, Durango. These populations are approximately 50 and 80 km northeast of the closest known population of Durangan dwarf mistletoe west of Buenos Aires along Route 40 in extreme western Durango. Infection of P. engelmannii was severe on 25 trees, but only severe on two trees of P. cooperi. No mortality associated with infection by Durangan dwarf mistletoe was observed at either location. Infection caused large, nonsystemic witches' brooms on P. engelmannii, but no brooms were observed on infected P. cooperi. To my knowledge, this is the first report of Durangan dwarf mistletoe on P. cooperi and P. engelmannii, and the first report of this mistletoe from the central Sierra Madre Occidental (3). Although Hawksworth and Wiens (2,3) treated Durangan dwarf mistletoe as a species (A. durangense Hawksw. & Wiens), I use the earlier classification of Durangan dwarf mistletoe as a subspecies of Mexican dwarf mistletoe (A. vaginatum (Willd.) Presl subsp. vaginatum) (1) because of recent molecular evidence (4) and morphological similarities with Mexican dwarf mistletoe. The principal difference between these mistletoes is that plants of Durangan dwarf mistletoe are bright orange while those of Mexican dwarf mistletoe are dark brown to black (1–3). Specimens of Durangan dwarf mistletoe on Pinus engelmannii and P. cooperi have been deposited at the Deaver Herbarium, Northern Arizona University, Flagstaff (Accession Nos. 76455 and 76456, respectively). References: (1) F. G. Hawksworth and D. Wiens, Brittonia 17:213, 1965. (2) F. G. Hawksworth and D. Wiens. Phytologia 66:3, 1989. (3) F. G. Hawksworth and D. Wiens. USDA For. Serv. Agric. Handb. 709, 1996. (4) D. L. Nickrent et al. Am. J. Bot. 91:125, 2004.
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Lipinska, Wiktoria, Katarzyna Grochowska, Jakub Karczewski, Emerson Coy, and Katarzyna Siuzdak. "Catalytic Activity of Au-Cu Alloy on TiO2 Nanotubes for Alcohol Oxidation." ECS Meeting Abstracts MA2023-02, no. 47 (December 22, 2023): 2327. http://dx.doi.org/10.1149/ma2023-02472327mtgabs.
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First fuel cell was discovered 180 years ago and still the ideal, namely cheap and effective catalytic materials are highly required. Such device allows to convert chemical energy into electrical one without pollutant gasses emission. In the case of alcohol fuel cells, methanol, ethanol, ethylene glycol and glycerine are considered as a power source. Platinum is commonly used for alcohol electrocatalyst, because of its high activity and stability. However, due to the high cost and limited supply platinum should be replaced by material that small amount is enough to reach satisfactory catalytic effect. In our work, we present the activity of gold-copper modified titania nanotubes toward electrocatalytic alcohol oxidation [1]. The material is fabricated using three steps such as: 1) anodization of Ti plate, 2) thin 10 nm AuCu alloy layer magnetron sputtering, and 3) rapid thermal annealing in an argon atmosphere [2]. Scanning electron microscopy confirmed the presence of well-ordered TiO2 nanotubes (TiNT) with diameter of 101 ± 13 nm and length of 709± 53 nm. After AuCu alloy magnetron sputtering and thermal treatment spherical nanoparticles were formed on NT surface. Based on top view SEM images the diameter of gold copper nanoparticles is equal to 38 ± 5 nm. However, the TEM images showed that diameter of nanoparticles changes from 5 nm to 60 nm (Figure 1a-d) where the bigger particles are on the top of the nanotubes. Applied fabrication procedure allowed us to obtain electrode material that can be used in methanol, ethylene glycol or glycerine oxidation. The highest catalytic activity of AuCu alloy was obtained for glycerine oxidation. Prepared material exhibited 90 times higher current density after glycerine addition to the alkaline solution than pure TiNT (Figure 1e). Furthermore, higher current density towards alcohol oxidation was registered for thermally annealed sample (an-AuCu/TiNT) than for non-annealed one (n-AuCu/TiNT). Cyclic voltammetry measurements for the an-AuCu/TiNT in glycerine solution at different scan rates confirmed diffusion controlled process. The oxidation peak current density located at +0.3 V and +1 V grows up to 120 mV/s with slope of 51 and 81 µA/cm2 respectively, which confirmed more privilege process at +1 V vs. Ag/AgCl/0.1M KCl. We believe that the information reported in our work provide wider knowledge about new and more efficient electrodes for alcohol oxidation. Research is financed by National Science Centre (Poland): Grant No. 2019/35/N/ST5/02604 [1] W. Lipińska et al. Journal of Materials Science, 57 (2022) 13345, DOI:10.1007/s10853-022-07471-7 [2] W. Lipińska et al. ACS Applied Materials & Interfaces, 13 (2021) 52967, DOI:10.1021/acsami.1c16271 Figure 1
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Chorna, V. V., S. S. Khliestova, V. M. Podolian, Ye M. Ivashkevych, V. M. Syvak, V. V. Slobodian, A. V. Tomashevskyi, and Yu K. Humeniuk. "Діагностика психічного стану здобувачів вищої медичної освіти як основна детермінанта їх професійного самовизначення." Ukrainian Journal of Military Medicine 3, no. 3 (September 30, 2022): 71–82. http://dx.doi.org/10.46847/ujmm.2022.3(3)-071.
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Мета роботи полягає у проведенні діагностики психічного стану здобувачів вищої медичної освіти за адаптованою методикою Г. Айзенка для узагальнення їх професійного самовизначення під час фахової підготовки, гендерні особливості діагностичних показників їхніх особистісних якостей та адаптивності до навчання.
Матеріали та методи. Вивчали соціально-психологічні і психологічні характеристики кандидатів на навчання ЗВО за допомогою методики вивчення темпераменту (за опитувальником Г. Айзенка) та методики діагностики самооцінки психічних станів (адаптований варіант методики Г. Айзенка) за програмою підготовки офіцерів запасу медичної служби для професійно-психологічного відбору згідно наказу Міністерства оборони України, Міністерства охорони здоров’я України та Міністерства освіти і науки України №322/631/709 2016 р. Методи дослідження – контент-аналіз освітньо-професійних програм медичних закладів вищої освіти, бібліосемантичний, аналітичний, системного підходу
Результати. Дослідження проводилось на базі кафедри медицини катастроф та військової медицини Вінницького національного медичного університету ім. М. І. Пирогова. У експериментальній роботі брали участь 96 здобувачів медичного закладу вищої освіти, 4 курсу, медичного та медико-психологічного факультетів, із них осіб чоловічої статі – 51%, осіб жіночої статі – 49%. Першим етапом дослідження було визначення темпераменту здобувачів вищої медичної освіти. Другим етапом дослідження стало визначення самооцінки психічної готовності здобувачів до професійної діяльності лікаря. Третій етап дослідження полягав у визначенні соціально-психологічних, психічних характеристик особистості майбутнього лікаря та оцінки їх адаптаційних здібностей, що відображають інтегральні особливості психічного і соціального розвитку. Була застосована методика (Багаторівневий особовий опитувальник) «БОО «Адаптивність-200»».
Висновки. Середній рівень фрустрації і середній рівень ригідності становив 100% і 58% відповідно у здобувачів жіночої статі, які потребують консультації лікаря психолога або психотерапевта для проведення корекції задля зменшення негативних змін характеру та розвитку агресивності, невпевненості в собі та байдужості до навчання, для покращення професійного самовизначення під час фахової підготовки. Понижений рівень нервово-психічної стійкості та поведінкової регуляції у 78% чоловіків проявляються нестабільним рівнім працездатності і можуть зашкодити у професійної діяльності та адаптації до нових життєвих змінах як наприклад військові дії і може бути ризиком погіршення функціонального стану організму. Особливо небезпечні прояви при надзвичайно високих психічних навантаженнях можливо можуть проявитись у 2% (із них 50% чоловіків і 50% жінок) здобувачів ЗВО, що може призвести до зриву професійної діяльності. У 2% здобувачів ЗВО (по 50% як у чоловіків так і у жінок) встановлено низький рівень комунікативних здібностей щодо важкого пристосування в новий колектив, до нових навчальних вимог через ускладнення в побудові міжособистісних контактів з оточуючими, неадекватної самооцінки; схильності до підвищеної конфліктності, яким вкрай необхідне проведення психокорекції.. Недостатній рівень соціалізації мають 2% респондента ЗВО і 1% мають низький рівень соціалізації, який характеризується відсутністю прагнення дотримуватися загальноприйнятих норм поведінки, не орієнтуючись на думку оточуючих, в них переважають егоцентричні тенденції, що може зашкодити в надзвичайній ситуації для пацієнтів. Відзначена наявність окремих ознак суїцидальної схильності у 12% здобувачів ЗВО через труднощі у міжперсональних взаємостосунках з ровесниками.
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Mathiasen, R., A. Sediles, and S. Sesnie. "First Report of Arceuthobium hondurense and Sruthanthus deppeanus in Nicaragua." Plant Disease 90, no. 11 (November 2006): 1458. http://dx.doi.org/10.1094/pd-90-1458c.
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The Honduran dwarf mistletoe, Arceuthobium hondurense Hawksw. & Wiens (Viscaceae), is one of the rarest dwarf mistletoes known in Central America (1,2). It is only known from four general areas in Honduras, but has also been reported from three locations in southern Mexico (2,3). At one time, A. hondurense was thought to be in danger of extinction (1). During March 2006, we found three new populations of this rare dwarf mistletoe in the Cordillera Dipilto in northern Nicaragua (Department Nueva Segovia). One population was approximately 11 km northeast of San Fernando (13°44′55″N, 86°19′07″W; elevation 1,130 m), the second population was approximately 9 km north of Mozonte (13°44′09″N, 86°24′54″W; elevation 1,415 m), and the third population was approximately 6 km southwest of Depilto (13°42′51″N, 86°32′22″W; elevation 1,340 m). Honduran dwarf mistletoe was parasitizing Pinus tecunumanii Equiluz & J.P. Perry at each of these locations, and at the Mozonte population, it was also infecting P. oocarpa Schiede ex Schlecht. Only a few pines were infected at each of these localities and no pine mortality associated with dwarf mistletoe infection was observed. However, even lightly infected trees had large witches' brooms and some trees were severely broomed. These populations are 50 to 65 km southeast of the nearest population of Honduran dwarf mistletoe in Honduras and they represent the southern most populations of Arceuthobium spp. in the New World (1). The mistletoe, Struthanthus deppeanus (Cham. & Schlecht.) Bl. (Loranthaceae), also parasitizes pines in Central America and southern Mexico (3). We observed this mistletoe parasitizing P. tecunumanii at the San Fernando location described above, on P. oocarpa approximately 7 km north of Mozonte (13°43′57″N, 86°24′49″W; elevation 1,490 m), and on P. oocarpa approximately 3 km southwest of Dipilto (13°43′40″N, 86°31′56″W; elevation 1,170 m). Again, only a few pines were infected at each of these locations, and we did not observe pine mortality associated with infection by S. deppeanus. S. deppeanus does not cause the formation of witches' brooms on infected pines, but the mistletoe plants are often greater than 1 m long so they are easily observed. This mistletoe was most common southwest of Depilto. To our knowledge, this is the first report of A. hondurense and S. deppeanus in Nicaragua. Specimens of A. hondurense and S. deppeanus from Nicaragua have been deposited at the Deaver Herbarium, Northern Arizona University, Flagstaff (Accession Nos. 81561–81567). References: (1) F. Hawksworth and D. Wiens. Dwarf mistletoes: Biology, pathology, and systematics. USDA For. Serv. Agric. Handb. 709, 1996; (2) R. Mathiasen and J. Melgar, Plant Disease 90:685, 2006; (3) R. Mathiasen et al. Madrono 50:115, 2003.
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Madero Velázquez, L., P. Zapater, C. Mira, V. Jovani, M. Andrés, M. Aguas, E. Vicens, et al. "P493 Do antiTNF or Ustekinumab trough levels correlate with joint extraintestinal manifestations activity in Inflammatory bowel disease patients?" Journal of Crohn's and Colitis 18, Supplement_1 (January 1, 2024): i984—i985. http://dx.doi.org/10.1093/ecco-jcc/jjad212.0623.
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Abstract Background Inflammatory spondyloarthritis(SpA) are the most common extraintestinal manifestations (EIM) associated to inflammatory bowel disease (IBD), with a prevalence of 20-50% for axial SpA(axSpA) and 5-20% for peripheral(pSpA). AntiTNF is the optimal therapy in axSpA intolerant or refractory to NSAIDs, also effective in pSpA. An optimal trough level has not been yet established in this clinical setting. Aim, to evaluate the correlation between antiTNF and UST trough levels and joint EIM activity in IBD patients. Methods Prospective, multicenter,cohort study. IBD patients diagnosed with articular EIM under antiTNF or Ustekinumab(UST) for at least 6 months were included. Blood samples were obtained just before administering the drug(trough levels), and a simultaneous evaluation by a rheumatologist and a gastroenterologist, was performed. Definitions: inactive AxSp=ASDAS-CRP<1.3 and BASDAI<2, inactive pSp=arthritis, enthesitis and dactylitis=0, active AxSp=ASDAS-CRP >2.1 and BASDAI>4, active pSp= artritis, entesitis o dactilitis > 0. Aim, to evaluate the correlation between antiTNF and UST trough levels and joint EIM activity in IBD patients. Results A total of 135 patients were included: mean age 51 ± 15, 59 (43.7%)women), 80% CD. 60(44.4%) patients presented axSpA, 50(37%) pSpA and 25(18.5%) mixed. 12(8.9%) had active IBD. Table 1 summarizes the patients' main demographic and clinical characteristics distributed by SpA activity. Fifty-three(39%) were on infliximab (IFX), 61(45.2%), on adalimumab (ADA) and 22 (16.3%) on UST treatment. NSAIDs treatment(12.7% vs 3.1%, p<0.05), higher fecal calprotectin(FC)(486 ± 709 vs 228.2 ± 297, p<0.05), and the prior use of biologics(33.8% vs 17.6%, p<0.05) were more frequent among active vs inactive SpA patients. No differences between IFX(7.05 ± 4.16 vs 5.79± 4.05, p=ns), ADA(7.98 ± 4.20 vs 9.51 ± 6.15 p=ns) and UST levels(3.39 ± 3.47 vs 3.08 ±2.69, p=ns), were found between active and inactive SpA patients, even when were distributed by type of SpA(axSpA/mixed and pSpA). Body mass index(b:-0,29, p=0.01)FC(b:-0,28, p=0.01), and intensified therapy(b:-0,28, p=0.01) were associated to higher IFX levels in the whole SpA cohort. Patients with axSpA or mixed were articular active more frequently than pSpA patients(82% vs 18%, p <0.05). IBD activity was correlated to articular activity only among pSpA patients(2% active IBD in inactive pSpA vs 20% active IBD in active pSpA patients, p=0.03). Conclusion AntiTNF and UST trough levels are not correlated to joint activity in patients with IBD and SpA. In our study more than 80% of patients with active SpA were inactive regarding IBD. Only pSpA patients presented correlation between IBD and articular activities.
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Xie, Xuemei, Marwa Manai, Jon A. Fuson, Troy Pearson, Dileep R. Rampa, Debu Tripathy, Jangsoon Lee, and Naoto T. Ueno. "Abstract P4-08-01: Targeting CDK7 enhances the antitumor efficacy of enzalutamide in androgen receptor-positive triple-negative breast cancer." Cancer Research 83, no. 5_Supplement (March 1, 2023): P4–08–01—P4–08–01. http://dx.doi.org/10.1158/1538-7445.sabcs22-p4-08-01.
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Abstract Background: Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer. Among TNBC subtypes, the luminal androgen receptor (LAR) subtype expresses high levels of androgen receptor (AR), tends to be less proliferative, and generally responds poorly to neoadjuvant therapy. Previous studies have shown that AR inhibition suppressed proliferation of AR+ or LAR subtype TNBC cells and tumor growth in xenograft models. Thus, AR is a promising therapeutic target for this TNBC subtype. Here, we identified kinase targets for enhancing the antitumor efficacy of the AR inhibitor enzalutamide in preclinical models and investigated the underlying molecular mechanisms. Methods: We performed a nonbiased high-throughput kinome siRNA screening (targeting 709 genes) to identify a synergistic partner for enhancing the antitumor efficacy of the AR inhibitor enzalutamide in AR+ LAR TNBC. The growth inhibitory effects of enzalutamide alone or combined with kinase inhibitors were determined using the sulforhodamine B staining assay and clonogenic assay. The effect of treatments on the expression of target proteins of interest was examined by Western blot analysis. Results: Enzalutamide was not effective as a single agent to inhibit the proliferation of AR+ TNBC cells (IC50 >15 µM in MDA-MB-453, CAL-51, CAL-148, MFM223, HCC2185, SUM149, SUM159, and SUM185 cells). Nonbiased high-throughput kinome siRNA screening identified PI3K/AKT/mTOR, cell cycle, and JNK pathways as potential canonical targets for combination with enzalutamide to enhance its antitumor efficacy in AR+ LAR TNBC. Among these pathways, inhibition of cell cycle progression using the CDK7 inhibitor UD-017 showed the most synergistic anti-proliferation effect with enzalutamide in AR+ LAR MDA-MB-453 (50.61% reduction in proliferation compared with enzalutamide alone, P < 0.001; and 48.98% reduction in proliferation compared with UD-017 alone, P < 0.001) and SUM185 (40.41% reduction in proliferation compared with enzalutamide alone, P < 0.05; and 42.76% reduction in proliferation compared with UD-017 alone, P < 0.05) TNBC cells. Furthermore, CDK7 knockdown using siRNA significantly enhanced the sensitivity of MDA-MB-453 (60.98%, P < 0.01) and SUM185 (30.99%, P < 0.01) cells to enzalutamide, and AR knockdown significantly enhanced the sensitivity of MDA-MB-453 (32.64%, P < 0.01) and SUM185 (43.62%, P < 0.01) cells to UD-017, in both cases with a sensitivity similar to that of enzalutamide plus UD-017. This result suggests that the synergy of enzalutamide and UD-017 results from specific targeting of AR and CDK7. Downstream target analysis revealed that the combination of enzalutamide and UD-017 dramatically reduced the expression of c-MYC. c-MYC knockdown using siRNA dramatically suppressed colony formation in both MDA-MB-453 and SUM185 cells at a degree similar to that of enzalutamide plus UD-017, whereas c-MYC overexpression reversed the synergistic effect of the combination treatment. This result suggests that UD-017 synergizes with enzalutamide through inhibition of c-MYC–mediated tumorigenesis. Conclusion: Our results suggest that enzalutamide synergizes with UD-017 by inhibiting c-MYC–mediated oncogenic activity. These in vitro data warrant future in vivo studies of the antitumor synergy of enzalutamide plus UD-017 in AR+ LAR TNBC models. Citation Format: Xuemei Xie, Marwa Manai, Jon A. Fuson, Troy Pearson, Dileep R. Rampa, Debu Tripathy, Jangsoon Lee, Naoto T. Ueno. Targeting CDK7 enhances the antitumor efficacy of enzalutamide in androgen receptor-positive triple-negative breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-08-01.
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Pipe, Steven, Paul van der Valk, Peter Verhamme, Peter Kampmann, Frank W. G. Leebeek, Michiel Coppens, Karina Meijer, et al. "Long-Term Bleeding Protection, Sustained FIX Activity, Reduction of FIX Consumption and Safety of Hemophilia B Gene Therapy: Results from the HOPE-B Trial 3 Years after Administration of a Single Dose of Etranacogene Dezaparvovec in Adult Patients with Severe or Moderately Severe Hemophilia B." Blood 142, Supplement 1 (November 28, 2023): 1055. http://dx.doi.org/10.1182/blood-2023-187624.
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Introduction: Etranacogene dezaparvovec (formerly AMT-061) is the first approved gene therapy for hemophilia B in the US and Europe. It is an adeno-associated virus serotype 5 (AAV5) vector containing a codon-optimized, highly active factor IX (FIX) Padua R338L transgene under the control of the liver-specific promoter LP-1. The pivotal phase 3 HOPE-B clinical trial (NCT03569891) of etranacogene dezaparvovec demonstrated superiority of bleeding protection compared to standard of care FIX prophylaxis up to 24 months post-treatment; long-term follow-up from Year 2 post-administration onward is currently ongoing. Aim: To report long-term efficacy and safety data of etranacogene dezaparvovec from the HOPE-B trial over a period of 3 years post-treatment. Methods: In this pivotal phase 3 open-label, single-arm trial, adult male participants with severe or moderately severe hemophilia B (FIX ≤2%), with or without preexisting AAV5 neutralizing antibodies (NAbs), were infused with a single dose (2×10 13 gc/kg) of etranacogene dezaparvovec, following a ≥6-month lead-in period of receiving their usual FIX prophylaxis. Efficacy (bleeding rates, aPTT-based FIX activity levels, FIX consumption) and safety data (adverse events [AEs]) during Years 1, 2, and 3 post-treatment with etranacogene dezaparvovec are reported. Results: Of 54 participants who received etranacogene dezaparvovec, 52 completed 36 months of follow-up. Mean annualized bleeding rate (ABR) for all bleeds during Months 7-36 post-treatment was significantly reduced by 64% (mean ABR 1.52) compared with the ≥6-month lead-in period (mean ABR 4.17; P=0.0004). Total number of bleeds (all types) were 136 during the ≥6-month lead-in period and decreased to 55 during Year 1, 48 during Year 2, and 37 during Year 3 post-treatment. Median [range] bleeds per participant decreased from 2.0 [0-10] during the lead-in period and remained stable to 0.0 [0-4] during Year 1, 0.0 [0-10] during Year 2, and 0.0 [0-8] during Year 3. Superior bleeding protection was in line with the level of transgene-derived endogenous FIX expression. The mean±SD (median; range) endogenous FIX activity level (ie. in the absence of exogenous FIX exposure) of participants was 41.5 IU/dL ±21.7 (39.9; 5.9-113, n=50) at Year 1, 36.7 IU/dL ±19.0 (33.9; 4.7-99.2, n=50) at Year 2, and sustained at 38.6 IU/dL ±17.8 (36.0; 4.8-80.3, n=48) at Year 3 post-treatment. Pharmacodynamic profile was not significantly different in participants with AA5 NAb undetected or titer ≤1:678. At 3 years post-treatment, 51 (94%) remained free of continuous FIX prophylaxis. One participant who lacked efficacy (highest AAV5 NAbs titer of 1:3212) and 1 who received a 10% partial dose of treatment did not discontinue prophylaxis; 1 participant eventually had his FIX levels declined to 2-5% range; his bleeding phenotype returned, and he resumed prophylaxis per protocol at month 30 post-treatment. During Year 2 and Year 3 post-treatment, 37 (70%) and 39 (75%) participants received no FIX infusion, respectively. Overall mean annualized FIX consumption decreased by 96% over 3 years post-treatment compared to the ≥6-month lead-in period (-246,763 IU/kg/participant, including those receiving FIX prophylaxis post-treatment; P<0.0001). During the 3 years post-dose, all participants experienced at least 1 treatment-emergent AE (TEAE); of 709 events, 541 (76%) were mild, 137 (19%) were moderate, and 31 (4%) were severe. There were no serious AEs related to treatment [a serious AE of hepatocellular carcinoma (HCC) and a death were reported previously before Year 2 and determined to be unrelated to treatment]. A total of 38/54 (70%) participants experienced 96 treatment-related TEAEs, of which 95% occurred before 6 months post-treatment. The most common AE was an increase in alanine transaminase (ALT), for which 9 (16.7%) participants received supportive care with reactive corticosteroids for a mean duration of 81.4 days (SD: 28.6; range: 51-130 days). No new deaths, no new HCC, and no late treatment-related ALT elevations or thromboembolic events were reported. Conclusion: Long-term follow-up during the HOPE-B trial has shown that a single-dose of etranacogene dezaparvovec resulted in long-term endogenous FIX Padua expression and superior bleeding protection compared to FIX prophylaxis in participants without or with AAV NAb titer ≤1:678, with a favorable safety profile over 3 years post-administration.
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Kawashiri, S. Y., Y. Endo, A. Nishino, T. Shimizu, Y. Ueki, N. Eiraku, A. Okada, et al. "FRI0098 ASSOCIATION BETWEEN THE SEROLOGIC STATUS OF ISOTYPE-SPECIFIC AUTOANTIBODIES AND THERAPEUTIC EFFICACY IN RHEUMATOID ARTHRITIS PATIENTS TREATED WITH ABATACEPT: A PROSPECTIVE ULTRASOUND COHORT STUDY IN JAPAN." Annals of the Rheumatic Diseases 79, Suppl 1 (June 2020): 628.1–628. http://dx.doi.org/10.1136/annrheumdis-2020-eular.2269.
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Background:The presence of anti-cyclic citrullinated protein antibodies (ACPA) and anti-carbamylated protein (anti-CarP) antibody is specific for rheumatoid arthritis (RA). Recently, it was reported that the serological status of ACPA is associated with the therapeutic response of the T-cell co-stimulation blocker abatacept (1, 2). However, it is currently unclear whether the serological status of each isotype levels of these autoantibodies before treatment introduction or the changes during treatment are associated with the therapeutic response of abatacept.Objectives:To evaluate longitudinal changes in the isotypes of ACPA and anti-CarP in RA patients treated with abatacept, and associations between the baseline serological status/ these changes and clinical response/ ultrasonographic response.Methods:This study is part of an ongoing non-randomized multicenter prospective cohort study of patients with active RA who received biological or targeted DMARD therapy at 13 participating rheumatology centers from the Kyushu region of Japan since June 2013 (3). As of the present report, we enrolled 43 consecutive Japanese patients with active RA who have introduced treatment with abatacept and had finished the first 12-month observation period. We evaluated disease activity by clinical composite measure and ultrasound score at baseline, 3, 6, 9 and 12 months. In ultrasound of bilateral hands from 22 sites, the findings obtained by gray-scale (GS) and power Doppler (PD) assessments were graded on a semi-quantitative scale from 0 to 3 and the sum of GS or PD scores was used as the total GS or PD score. The serum levels of IgG/IgM/IgA-type of ACPA and anti-CarP were measured by the ELISA method in Leiden University Medical Center. We evaluated the association between serologic status of autoantibodies and clinical /ultrasonographic therapeutic efficacy.Results:The median age was 72 years, and the disease duration was 54 months. Methotrexate was concomitant in 22 (51%). Sixteen (37%) patients had a history of previous use of biological DMARDs. Nineteen (44%) and 23 (54%) patients achieved SDAI remission and PD remission (total PD score =0) at 12 months, respectively. The serum levels of all isotypes of ACPA/anti-CarP significantly decreased at 12 months from baseline. The reduction of IgM-ACPA level significantly correlated with the reduction of SDAI (rs=0.33, p=0.031) and total PD score (rs=0.49, p=0.0007). Both clinical and ultrasonographic therapeutic responses were better in patients with the detectable IgM-ACPA at baseline than in patients without that (Figure): the reduction of SDAI (p=0.0078) and that of total PD score (p=0.0079) were significantly larger in the former than in the latter. All isotype of anti-CarP did not associate with therapeutic response.Conclusion:Treatment of abatacept induced to the reduction of the autoantibody levels. The IgM-ACPA level at baseline and the change in IgM-ACPA associated with both clinical and ultrasonographic therapeutic response in patients treated with abatacept. IgM-ACPA, compared with usual IgG-ACPA, better reflects the treatment response of abatcept in patients with RAReferences:[1]Ann Rheum Dis. 2016;75:709, 2) RMD Open. 2018;4:e000564, 3)Arthritis Care Res (Hoboken). 2018;70:1719.Acknowledgments:We have acknowledged for all the members of Kyushu multicenter rheumatoid arthritis ultrasound prospective observational cohort study group.Disclosure of Interests:Shin-ya Kawashiri Grant/research support from: This work was supported by Bristol-Myers Squibb and Ono Pharmaceutical. co., Yushiro Endo: None declared, Ayako Nishino: None declared, Toshimasa Shimizu: None declared, Yukitaka Ueki: None declared, Nobutaka Eiraku: None declared, Akitomo Okada: None declared, Naoki Matsuoka: None declared, Tamami Yoshitama: None declared, Hideki Nakamura: None declared, Mami Tamai: None declared, Tomoki Origuchi: None declared, Rene Toes: None declared, Thomas Huizinga Grant/research support from: Ablynx, Bristol-Myers Squibb, Roche, Sanofi, Consultant of: Ablynx, Bristol-Myers Squibb, Roche, Sanofi, Atsushi Kawakami: None declared
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Harty, T., D. Dahly, S. Costelloe, M. O’ Shaughnessy, and S. Harney. "AB0335 INCIDENT CHRONIC KIDNEY DISEASE IN PATIENTS WITH RHEUMATOID AND PSORIATIC ARTHRITIS – A COMPARATIVE ANALYSIS." Annals of the Rheumatic Diseases 82, Suppl 1 (May 30, 2023): 1350.2–1351. http://dx.doi.org/10.1136/annrheumdis-2023-eular.5818.
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BackgroundPatients with inflammatory joint conditions have a high prevalence of comorbidities including chronic kidney disease (CKD) [1]. The data pertaining to CKD in rheumatoid arthritis (RA) is limited [2], however and its association with psoriatic arthritis (PsA) remains unclear. Renal disease in RA and PsA is clinically important as it can lead to restrictions in the management of the primary disease, and is also associated with increased all-cause morbidity and mortality [3].ObjectivesTo determine and compare the rate of incident CKD in patients with rheumatoid and psoriatic arthritis and to determine the rate of estimated glomerular filtration rate (eGFR) change over time.MethodsPatients with RA and PsA who were first diagnosed between 1st January 2005 and 31st December 2010 were included in this retrospective, longitudinal analysis. All eGFR values, calculated using the Modification of Diet in Renal Disease equation, for each patient were collected from time of diagnosis until 31stDecember 2020. Demographic details, disease-specific characteristics, the presence of cardiovascular disease at baseline and anti-rheumatic drug use at each appointment were recorded. Generalized additive models (GAMs) were used to smooth the eGFR trajectories for each patient, and mixed-effects models were then used to estimate crude linear trends in eGFR across the period of observation. The primary outcome measure was diagnosis of CKD, defined as patient’s eGFR falling below 60ml/min/m 2 for a period of at least 90 days in their smoothed eGFR trajectory.ResultsThe patient sample (n = 159) included 114 RA and 45 PSA patients. RA patients were less likely to be male (39 vs 51%, p = 0.2) and older (mean age at baseline 52 vs 46 years, p < 0.001) than PsA patients. They also tended to have moderately lower eGFR upon initial observation (78 vs 83 ml/min/m2, p = 0.07). Baseline comorbidity profiles were broadly similar between the two groups. Treatment profiles were also similar, but with RA patients prescribed DMARDs at 69% of their appointments on average vs 56% in PSA patients (p = 0.003). There were 22 incident cases of CKD in the RA patients (19%), vs 7 in the PSA patients (16%, p = 0.6), and 17 RA patients died during the observation period (15%) vs 2 PSA patients (4.4%, p = 0.07). Results from a sex- and age-adjusted mixed effects models suggested that eGFR trajectories tended to slowly decline on average in PSA patients (-0.22 ml/min/m2 per year, p vs no trend = 0.14), but increased on average (0.79 ml/min/m2 per year) among RA patients (p for interaction < 0.001).ConclusionIncident CKD diagnosis was high in both patient populations. While rate of eGFR decline was greater in patients with PsA, overall rates of CKD diagnosis did not differ significantly. Monitoring of kidney function should be an important part of management of inflammatory joint conditions, as the majority of these patients non-steroidal inflammatory drugs and immunosuppressive therapies which may be contraindicated or require dose adjustment if renal impairment is present.References[1] Ziade, N., El Khoury, B., Zoghbi, M. et al. Prevalence and pattern of comorbidities in chronic rheumatic and musculoskeletal diseases: the COMORD study. Sci Rep 10, 7683 (2020).https://doi.org/10.1038/s41598-020-64732-8[2] Raksasuk S, Ungprasert P. Patients with rheumatoid arthritis have an increased risk of incident chronic kidney disease: a systematic review and meta-analysis of cohort studies. Int Urol Nephrol. 2020 Jan;52(1):147-154. doi: 10.1007/s11255-019-02346-4. Epub 2019 Dec 9. PMID: 31820358.[3] GBD Chronic Kidney Disease Collaboration. Global, regional, and national burden of chronic kidney disease, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet. 2020 Feb 29;395(10225):709-733. doi: 10.1016/S0140-6736(20)30045-3. Epub 2020 Feb 13. PMID: 32061315; PMCID: PMC7049905Acknowledgements:NIL.Disclosure of InterestsNone Declared.
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Krönke, Jan, Richard Schlenk, Kai-Ole Jensen, Karina Eiwen, Marianne Habdank, Daniela Späth, Jürgen Krauter, et al. "Identification of Clinically Relevant Predictive MRD Checkpoints in AML Patients with NPM1 Mutations: A Study of the AML Study Group (AMLSG)." Blood 114, no. 22 (November 20, 2009): 1586. http://dx.doi.org/10.1182/blood.v114.22.1586.1586.
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Abstract Abstract 1586 Poster Board I-612 Background Mutations in the nucleophosmin 1 (NPM1) gene represent the most frequent gene mutations in acute myeloid leukemia (AML), with highest frequency (50-60%) in cytogenetically normal (CN)-AML. Several studies have shown the applicability and prognostic value of an NPM1 mutation (NPM1mut)-based assay for detection of minimal residual disease (MRD). So far, there are no studies evaluating the prognostic value of NPM1mut MRD levels in a large controlled cohort of AML patients (pts) enrolled on prospective clinical trials. Aims To evaluate the prognostic value of NPM1mut MRD levels in younger (16 to 60 years) AML pts harbouring NPM1 mutations type A, B or D, and to assess the influence of concurrent FLT3 internal tandem duplications (ITD). Methods All pts were enrolled in the prospective AMLSG 07-04 and AML HD98A treatment trials. Treatment comprised double induction therapy with ICE (idarubicin, cytarabine, etoposide) followed by high-dose cytarabine-based consolidation, autologous or allogeneic stem cell transplantation. Levels of NPM1mut expression ratios, defined as NPM1mut copies per 104ABL copies, were determined by RQ-PCR using TaqMan technology. Dilution series showed a maximum sensitivity of 10-6 and high specificity as no wildtype NPM1 could be detected. Results A total of 1079 samples, [bone marrow (BM), n=1062; peripheral blood, n= 17) from 212 pts were analyzed at diagnosis, after each treatment cycle, during follow-up and at relapse (median number of samples per pt, n=4; range, 1-16). NPM1mut expression ratios at diagnosis varied between 1.1×104 and 10.4×106 (median, 6.9×105). Pretreatment transcript levels were not associated with clinical characteristics (e.g., age, white cell counts, BM blasts) and did not impact on relapse-free (RFS) and overall survival (OS). Following the first induction cycle, the median decrease of the MRD level ratio normalized to pretreatment levels was 4.21×10-3, independent of the presence of concurrent FLT3-ITD (p=0.39). After the 2nd induction cycle, the median reduction of MRD levels was significantly stronger in the FLT3-ITDneg group (6.75×10-5) compared with the FLT3-ITDpos group (4.19×10-4) (p=0.003) and this differential effect was observed throughout consolidation therapy. For evaluation of the prognostic impact of NPM1mut MRD levels, we compared patients achieving PCR-negativity with those with positive values at different checkpoints. The first reliable checkpoint was after double-induction therapy: the cumulative incidence of relapse (CIR) at 4 years of PCR-negative patients (n=27) was 0% compared with 48% (SE, 4.4%, p<0.00001) for PCR-positive patients (n=105). This translated into a significant better OS (p=0.0005). The second checkpoint was after completion of consolidation therapy (first measurement during follow-up period). Again, 4-year CIR was significantly (p<.00001) lower in the PCR-negative group with 11% (SE, 6.5%) compared with 51% (SE, 4.8%) in PCR-positive patients, again translating in a significantly better OS (p<.00001). In addition, the level of NPM1mut expression ratio at any time point examined after completion of therapy correlated with the risk of relapse, since 20 of 22 pts with a value above 1000 NPM1mut/104ABL copies relapsed after a median interval of 90 days (range, 11-709 days). The remaining 2 pts had increasing levels at last follow-up but are still in continuous complete remission (CR). In a few cases relapse prediction appeared to be limited due to inadequate increase of NPM1mut expression levels or to loss of NPM1 mutation at the time of relapse (n=5). On the other hand, we observed a number of pts (n=17) in continuous CR who had intermittent low (<1000 NPM1mut/104ABL copies) NPM1mut expression ratios. Conclusions The levels of NPM1mut expression at two distinct checkpoints, after double induction therapy and after completion of consolidation therapy, can be used as a prognostic factor in NPM1mut AML pts. The adverse outcome of pts carrying a concurrent FLT3-ITD is reflected by a significant lower reduction of tumor burden. Disclosures Göhring: Celgene Corp.:. Schlegelberger:Celgene Corp.:.
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Grafinger, Christine Maria. "nr="313"Daniela Mondini, Carola Jäggi und Peter Cornelius Claussen, Die Kirchen der Stadt Rom im Mittelalter 1050-1300, Bd. 4: M-O. SS. Marcellino e Pietro bis S. Omobono, mit Beiträgen von Peter Cornelius Claussen, Carola Jäggi, Almuth Klein, Giorgia Pollio, Alexander Racz, Michael Schmitz, Darko Senekovic und Angela Yorck von Wartenburg. Corpus Cosmatorum II, 4. Forschungen zur Kunstgeschichte und christlichen Archäologie. 23. Stuttgart: Franz Steiner Verlag, 2020, S. 709, 492 Abb., 51 Farbtafeln." Mediaevistik 33, no. 1 (January 1, 2020): 313–14. http://dx.doi.org/10.3726/med.2020.01.45.
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McIntyre, Matthew, Barry Cheaney, Jesse Jia-Xin Liu, Aclan Dogan, and Olabisi Sanusi. "709 Establishment of an Early ICU De-escalation Pathway Using the Modified Frailty Index Among Angiogram-Negative Subarachnoid Hemorrhage Patients." Neurosurgery 70, Supplement_1 (April 2024): 164. http://dx.doi.org/10.1227/neu.0000000000002809_709.
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INTRODUCTION: Angiogram-negative subarachnoid hemorrhage (ANSAH) may have a benign clinical course. Our standard practice is to observe ANSAH patients for a prolonged period in the ICU. Previous work has established frailty as a strong predictor of ANSAH outcomes. METHODS: A retrospective cohort analysis was performed among patients admitted between 2011 and 2022 with non-traumatic subarachnoid hemorrhage and initial angiogram (DCA) negative for source. Primary endpoints were in-hospital complications, discharge home, and length-of-stay (LOS). Cost analysis was performed using hospital charges. RESULTS: 101 patients were included with an average age of 59.7 ±1.2 years, Hunt and Hess score of 2.0 ± 0.1, and 51 (50.5%) with a perimesencephalic hemorrhage distribution. 2 patients had a subsequent DCA showing aneurysmal etiology, both of whom would have been considered high risk. 38 (37.6%) were frail, 38 (37.6%) required an EVD, and 68 (67.3%) were intact on arrival. Multivariate analysis showed that frailty but not age or perimesencephalic distribution predicted the 3 primary endpoints (p < 0.039) while lack of EVD predicted LOS (p = 0.004) and intact neurologic exam predicted discharge home (p = 0.043). Low-risk patients (40/101, 39.6%) had no deaths, significantly reduced odds of any complication (OR 0.14, 95%CI: 0.04-0.44, p < 0.001), increased odds of discharge home (OR 9.98; 95%CI: 2.19-45.46, p < 0.001), and shorter LOS (7.8 ± 0.4 v. 14.7 ± 1.1 days, p < 0.001). Assuming a 6-day ward stay after 1-day of ICU observation, early de-escalation of low-risk ANSAH patients would, on average, save $20,177.70 per patient. CONCLUSIONS: Non-frail ANSAH patients who are neurologically intact and without an EVD are likely to have a benign clinical course and may benefit from early ICU de-escalation.
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Ансарін Алі Акбар and Джаваді Шалал. "Маскований семантичний/ асоціативний та перекладний праймінг у різних мовах." East European Journal of Psycholinguistics 5, no. 1 (June 30, 2018): 7–15. http://dx.doi.org/10.29038/eejpl.2018.5.1.ans.
Full textAbstract:
Статтю присвячено спробі дослідити двомовний ментальний лексикон. Головне питання дослідження – встановити, чи персько-англійські білінгви можуть досягнути ефекту семантичного / асоціативного або перекладацького праймінгу. Для відповіді на це питання було застосовано масковану праймінгову парадигму як техніку, що відображає автоматичні когнітивні процеси, що тривають під час семантичної обробки, а не стратегічного використання прайму. Із метою вирішення лексичного завдання було сформовано чотири типи цільових пар праймінгу (перекладацькі еквіваленти, семантично подібні, асоціативно та семантично пов’язані пари). Загалом у дослідженні взяло участь 85 персько-англійських білінгвів. Хоча ефекту праймінгу не було виявлено для перших трьох груп, респонденти із семантично пов’язаних пар (найміцніше пов’язаних слів) відповіли приблизно на 29 мс швидше. Результати засвідчили, що білінгви мають спільні уявлення для асоціативних семантично пов’язаних слів. Отже, навчання новим словам другої мови, шляхом поєднання їх із асоціативно пов’язаними словами першої мови, може привести до кращих результатів.
Література
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Specchia, Giorgina, Patrizia Pregno, Maura Nicolosi, Fausto Castagnetti, Bruno Martino, Massimo Breccia, Massimiliano Bonifacio, et al. "Chronic Myeloid Leukemia Italian Multicenter Observational Study (CML-IT-MOS): Clinical Characteristics of Chronic Myeloid Leukemia (CML) Patients Treated in Real-Life between 2012 and 2016 in 66 Italian Hematology Centers of the Gimema Study Group." Blood 132, Supplement 1 (November 29, 2018): 45. http://dx.doi.org/10.1182/blood-2018-99-116648.
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Abstract Background: The advent of Tyrosine Kinase Inhibitors (TKI) totally changed the outcome of patients affected by Chronic Myeloid Leukemia (CML). Most of informations about the clinical characteristics of CML patients are based on data derived from clinical trials, that often exclude patients not fitting with strict inclusion criteria. In real life may be important to know the characteristics of the entire CML patients' population and this is better reflected by registries studies including all consecutive patients. Aim: To provide a robust and updated information on clinical, hematologic characteristics and treatment response in non-selected Italian patients with CML in each phase of the disease. Methods:We retrospectively and prospectively recorder in a web-based database clinical, hematological, cytogenetic and biological informations about all new diagnosis of CML patients referred to Italian Hematology Centers of the GIMEMA Study Group from January 2012 to June 2016. Results:Our study covered 1051 patients newly diagnosed with CML and treated between January 2012 and June 2016 in 66 Italian centers. Median age at diagnosis was 59 years (range 47-71) and 60.8% were males. At diagnosis among 908 patients 899 (99%) patients were in chronic phase, 7 (0.8%) patients in accelerate phase and 2 (0.2%) in blastic crisis. Among 1051 patients, 148 (14%), 351 (33%), 318 (30.3%) were high, intermediate and low risk by Sokal with 234 (22.2%) missing; 54 (5%), 418 (40%), 342 (32.5%) high, intermediate and low risk by EURO with 237 (22.6%) missing; 55 (5%) and 797 (76%) high and low risk by EUTOS with 199 (18.9%) missing; 96 (9%), 208 (20%), 533 (51%) high, intermediate and low risk by ELTS with 214 (20.4%) missing, respectively. The median follow-up was 36 months and 36 patients died (10 CML related). At cytogenetic analysis, there were 887 available informations: 809 (77%) without additional cytogenetic aberrations (ACA), 49 (5%) with major route and 29 (2.8%) with minor route ACA respectively. BCR-ABL transcripts among 873 data available were: b2a2 in 303 (34.7%), b3a2 in 493 (56.5%), b2a2+b3a2 in 61 (7%), e1a2 in 12 (1.4%), e19a2 in 2 (0.2%) b3a2+e1a2 in 2 (0.2%) patients respectively. ECOG performance status among 801 patients was 0, 1, or ≥ 2 in 585 (73%), 181 (22.6%) and 35 (4.4%) cases respectively. According to co-morbidity and excluding CML diagnosis as parameter, among 995 cases the Charlson comorbidity index, was 0, 1, 2 or ≥3 in 771 (73.4%), 115 (11%), 60 (5.7%) and 49 (4.7%) patients respectively; among 556 patients cardiovascular, lung, metabolic and oncologic diseases were observed in 283 (24%), 108 (10.3%), 77 (7.3%) and 88 (8.4%) patients respectively. Five hundred-ten (48.5%) and 541 (51.4%) patients were treated in first-line with imatinib (IMA) and with II generation TKI (IIGen-TKI) respectively. Three hundred twenty-one (30%) cases were pretreated with hydroxyurea. Molecular responses data at 3th month were available in 728 patients and of these 102 (14.01%) obtained at least Major Molecular Response IS (MR) MR3, 29 (3.98%) MR4, 27 (3.71%) MR4.5, 13 (1.79%) MR5 and 11 (1.5%) undetectable BCR-ABL1transcript, respectively. At 6thmonth, among 731 data available, at least 292 patients (39,57%) obtained MR3, 90 (12,19%) MR4, 75(10.16%) MR4.5, 35 (4.74%) MR5 and 29 (3.97%) undetectable BCR-ABL1transcript, respectively. At 12thmonth among 709 molecular responses available, 425 patients (59.94%) achieved at least MR3, 203 (28,63%) MR4, 171 (24.12%) MR4.5, 90 (12.69%) MR5 and 78 (11%) undetectable BCR-ABL1transcript, respectively. As showed in table 1, the IIGen-TKI were able to obtain a higher, earlier and deeper molecular response at 3th, 6thand 12thmonth than IMA. Data analysis about responses at 24thmonth are ongoing. Overall survival at 5 years was 93.4% (95% IC 90.1-95.6). Conclusions:Our preliminary results of this observational epidemiologic study suggest that collection of clinical data of CML patients treated out of strictly clinical trials represent an essential tool for long/term treatment, able to observe setting strategies based on the clinical characteristics, the degree of response obtained, and the toxicity related to the therapy in overall CML population. We are planning to continue to analyze all these endpoints to estimate the response and toxicity according to ELN guidelines, and feasibility of treatment sequence in a cohort of patients treated in real-life. Disclosures Castagnetti: Pfizer: Consultancy, Honoraria; Bristol Meyers Squibb: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Incyte: Consultancy, Honoraria. Breccia:BMS: Honoraria; Incyte: Honoraria; Pfizer: Honoraria; Novartis: Honoraria. Pane:AMGEN: Speakers Bureau; Novartis: Research Funding, Speakers Bureau; BMS: Speakers Bureau.
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Jang, Jun Ho, Ji-Hyun Kim, Kyungah Lee, Eugene Kim, Hyojin Kim, and Fangyuan Wang. "Red Blood Cell Transfusion Dependence Is Associated with Greater Healthcare Resource Utilization, Higher Medical Cost, and Poorer Prognosis in Patients with Lower-Risk Myelodysplastic Syndromes: A 28-Year Retrospective Observation Study Result." Blood 142, Supplement 1 (November 28, 2023): 1869. http://dx.doi.org/10.1182/blood-2023-173351.
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Myelodysplastic syndromes (MDS) encompass a heterogeneous group of myeloid neoplasms characterized by cytopenia due to inefficient hematopoiesis, with a considerable risk of progression to acute myeloid leukemia (AML) or early mortality. In lower-risk MDS (LR-MDS) patients, anemia and its associated complications have been the focus of clinical attention. A significant portion of these patients eventually develop red blood cell transfusion dependence (RBC TD), which has been linked to a poorer prognosis. Given the limited efficacy of available treatments in reducing RBC TD, most patients face increased risks of chronic anemia and various complications. Moreover, RBC TD is known to be associated with reduced overall survival (OS) and leukemia-free survival (LFS). This study aimed to assess the impact of RBC TD on the socioeconomic burden and clinical prognosis of LR-MDS patients, utilizing an electronic medical records (EMR) database spanning nearly 30 years of MDS patient data. This retrospective observational study examined adult MDS patients (≥ 18 years of age) treated at Samsung Medical Center in the Republic of Korea. Eligible patients were diagnosed with MDS between Sep 1, 1994, to Apr 1, 2022 (index period), with the observation period spanning from Sep 1, 1994, to Sep 1, 2022. Baseline assessments included estimation of revised international prognostic scoring system (IPSS-R) scores, categorizing patients with very low, low or intermediate risks as lower-risk MDS (LR-MDS). TD was defined as the occurrence of any 16-week period with RBC transfusion of ≥ 2 units per 8 weeks, without consecutive 56-day period without transfusion. Healthcare resource utilization (HCRU), medical costs, and prognosis indicators including overall survival (OS) and AML-free survival (AFS) were analyzed and compared between patients who experiencing TD and those not (non-TD). Out of 831 MDS patients, 349 (42.0%) were classified as lower-risk at baseline. Among LR-MDS patients, 29.5% (103/349) experienced TD while 23.3% (194/831) experienced TD in the entire study population. The median age at diagnosis of MDS was 63 (ranging from 18 to 89), and 65.3% (543/831) were male. In LR-MDS patients, there were no significant differences in either baseline age (61 vs 63, P=0.16) or gender (71.8% vs 61.0% males, P=0.053) between TD and non-TD groups. However, TD group exhibited significantly higher median erythropoietin (EPO) level than non-TD group (290.5U/L vs. 112U/L, P<0.001) among LR-MDS patients with available baseline serum EPO levels (76 TD and 178 non-TD). Among the 76 TD LR-MDS patients with baseline serum EPO levels, 51 (67.1%) exhibited > 200U/L, which is considered a clinical threshold for erythropoiesis-stimulating agent (ESA) treatment. As shown in Table 1, RBC TD was consistently associated with greater HCRU and higher medical costs, especially in LR-MDS patients. TD LR-MDS patients had higher rates of outpatient department and emergency room visits (15676 vs. 8303 visits and 587 vs. 328 visits per 1000 person-years [PY], respectively), and increased hospitalizations (709 vs. 456 per 1000 PY), with longer hospital stays (13343 vs. 8272 days per 1000 PY). Furthermore, TD LR-MDS patients required over four-times of packed RBC units than non-TD patients (31107 vs. 7073 units per 1000 PY). Consequently, TD LR-MDS patients incurred higher total medical cost than their non-TD counterpart (13.5 million vs. 6.1 million USD per 1000 PY). Median OS (58.4 months vs. 103.1 months) and AFS (52.7 months vs. 102.7 months) were both significantly shorter in the TD group compared to the non-TD group among LR-MDS patients, while the differences in OS and AFS did not reach the level of significance in the entire study population (Table 1 and Figure 1). Notably, median OS after the first documented RBC TD event was 33.8 months (95% confidence interval: 24.7-58.5 months) in LR-MDS patients. The findings of this study indicate that RBC TD can be a strong predictor of increased HCRU and medical costs, as well as decreased OS and AFS over a 20-year period following the initial diagnosis of LR-MDS. Given that a majority of LR-MDS patients experiencing TD may not be eligible for ESA treatment due to elevated EPO levels exceeding 200U/L, and the use of cytotoxic agents is not usually recommended for these patients, these results highlight a substantial unmet need for alternative treatment options to address RBC TD in LR-MDS patients.
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Terpos, Evangelos, Dimitrios Christoulas, Maria Gkotzamanidou, Cornelia Bratengeier, Maria Gavriatopoulou, Magdalini Migkou, Athanasios Papatheodorou, Efstathios Kastritis, Wolfgang Woloszczuk, and Meletios A. Dimopoulos. "Circulating Levels of the Wnt Inhibitors Dickkopf-1 and Sclerostin In Different Phases of Multiple Myeloma: Alterations Post-Therapy with Lenalidomide and Dexamethasone with or without Bortezomib." Blood 116, no. 21 (November 19, 2010): 2963. http://dx.doi.org/10.1182/blood.v116.21.2963.2963.
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Abstract Abstract 2963 Dickkopf-1 (Dkk-1) and sclerostin are inhibitors of the Wingless-type and integrase 1 (Wnt) signaling and they are implicated in the pathogenesis of multiple myeloma (MM) bone disease through inhibition of osteoblast function. There is very limited information for the circulating levels of Dkk-1 and sclerostin in different phases of MM and their alterations post therapies with novel agents. Therefore, we studied 284 MM patients (153M/131F, median age 66 years): 167 consecutive patients were newly-diagnosed (20 had asymptomatic MM and 147 symptomatic MM), 29 patients were at the plateau phase of MM and 88 patients had relapsed/refractory MM and received therapy with the combination of lenalidomide plus dexamethasone with or without bortezomib (VRD or RD; Dimopoulos et al, Leukemia 2010). For newly diagnosed patients, serum was stored at the time of diagnosis, while for patients at the plateau phase serum was collected at the time of confirmation of the plateau (at least 6 months with stable M-protein without criteria confirming progression) and for relapsed/refractory patients on day 1 of cycles 1, 4 and 7 of VRD or RD administration. Circulating levels of Dkk-1 and sclerostin were measured using ELISA methodology (R&D Systems, Minneapolis, MN, USA and Biomedica Medizinprodukte, Vienna, Austria, respectively) in all patients and in 20 gender- and age- matched healthy controls. Circulating Dkk-1 and sclerostin concentrations of newly diagnosed symptomatic patients (median: 1383 pg/mL, range:274-32, 862 pg/mL and 415 pg/mL, 0–3,340 pg/mL respectively) were increased compared to controls (1069 pg/mL, 540-2, 709 pg/mL; p<0.001 and 250 pg/mL, 0–720 pg/mL; p=0.03, respectively) and to asymptomatic patients at diagnosis (1044 pg/mL, 480-2, 335 pg/mL; p<0.001 and 140 pg/mL, 0–1,100 pg/mL; p=0.001, respectively). Patients at plateau phase had increased circulating levels of sclerostin (704 pg/mL, 68–2000 pg/mL; p <0.001) compared to controls (p=0.002) as well as to MM patients at diagnosis (p=0.02). In contrast, they had lower serum levels of Dkk-1 (1013 pg/mL, 414–1729 pg/mL) compared to MM patients at diagnosis (p<0.001) and no difference compared to controls. Patients with ISS-3 myeloma at diagnosis had higher values of Dkk-1 and sclerostin than ISS-1 and ISS-2 patients [median Dkk-1 values for ISS-1, ISS-2 and ISS-3 were: 1059 pg/mL, 1290 pg/mL and 2649 pg/mL, respectively; p(ANOVA)=0.031; median sclerostin values for ISS-1, ISS-2 and ISS-3 were: 394 pg/mL, 392 pg/mL and 714 pg/mL, respectively; p(ANOVA)=0.001]. Patients with lytic disease at diagnosis (n=116) had increased levels of Dkk-1 compared with patients with no lytic disease (n=51): 1475 pg/mL, 327-32, 862 pg/mL vs. 840 pg/mL, 274–1112 pg/mL; p=0.002. There was no difference in sclerostin levels between these patients; however, patients with advanced bone disease (>3 lytic lesions and/or a fracture) had a borderline increase in their circulating sclerostin compared to all others (p=0.072). Dkk-1 circulating levels correlated weakly with sclerostin (r=0.201, p=0.05). Relapsed patients had increased Dkk-1 (1218 pg/mL, 161-19, 325 pg/mL) and sclerostin (886 pg/mL, 90-6, 272 pg/mL) levels compared to controls and to asymptomatic patients at diagnosis (p<0.001 for all comparisons). In patients who received RD, Dkk-1 was increased and sclerostin was decreased after 6 cycles of therapy. Responders to RD had a median increase of 9% in Dkk-1 serum levels after 6 cycles of therapy, while non-responders had a median increase of 91% compared to baseline values (p<0.01). Patients who did not respond to RD showed an increase in bone resorption marker CTX (p=0.021) after 6 cycles of therapy. VRD administration resulted in a significant reduction of sRANKL (p=0.024) and increase of bone formation marker, osteocalcin (p=0.01) after 6 cycles, but showed only minimal reduction of Dkk-1 (p=0.08) and no alterations on sclerostin. In conclusion our study suggests that Dkk-1 is elevated in active myeloma, while sclerostin is elevated even in the plateau phase of the disease. Both correlated with adverse disease features. The increase of Dkk-1 by RD seems to be balanced by a reduction effect of bortezomib on Dkk-1 in VRD. Furthermore, the reduction of sclerostin in RD patients may represent a modulatory effect of lenalidomide on marrow microenvironment. These results further support the rationale for the use of drugs targeting Dkk-1 and sclerostin in MM. Disclosures: No relevant conflicts of interest to declare.
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Kubica, Claudia, Sascha Ketelhut, and Claudio R. Nigg. "Effects of a training intervention tailored to the menstrual cycle on endurance performance, recovery and well-being in female recreational runners – A randomized-controlled pilot study." Current Issues in Sport Science (CISS) 8, no. 2 (February 14, 2023): 026. http://dx.doi.org/10.36950/2023.2ciss026.
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Introduction Female endurance athletes, such as runners, show a high prevalence of menstrual cycle (MC) related symptoms and diseases (Dusek, 2001). Almost one in four runners and 65% of long-distance runners are suffering from secondary amenorrhea (Dusek, 2001) and consecutive symptoms, such as an increased risk of injury, reduced bone mass, and a higher risk for cardiovascular diseases (Ihalainen et al., 2021). Causes for MC-related symptoms or diseases are multifactorial but in sports, a relationship to the training load, recovery, and sufficient energy availability exists (Redman & Loucks, 2005). Evidence is growing that the MC phases affect endurance performance development, training response, and recovery in eumenorrheic women (with normal or regular menstruation), and adaptions of the training program to the MC could reduce risk factors for MC-related symptoms and diseases (Ihalainen et al., 2021; McNulty et al., 2020; Oosthuye & Bosch, 2010). This assumption is based on the changes in steroid hormone concentrations of estrogen and progesterone and their interactions (Pitchers & Elliott-Sale, 2019) during the MC. Five phases usually describe the MC: the early follicular phase, beginning with the onset of menses; the late follicular phase; ovulation; early-, mid-, and late luteal phase (Janse de Jonge et al., 2019). High estrogen levels characterize the late follicular phase and ovulation. In comparison, during the mid-luteal phase, progesterone is the dominating hormone (Janse de Jonge et al., 2019). Current findings in resistance training support the idea that responses to follicular phase-based training are superior to luteal-phase-based or regular training (Thompson et al., 2020). Adaptions of a traditional training program, such as polarized training (Kenneally et al., 2018), to the individual MC phases may impact training response, adaptation, and recovery in female runners (Ihalainen et al., 2021). To our knowledge, no study has investigated the impact of a polarized training intervention tailored to the MC on performance, recovery, and well-being in eumenorrheic women. Therefore, this study aimed to assess the effectiveness of polarized training in female runners and polarized training adaption to the MC phases on endurance performance development, recovery, and MC-related symptoms, as a part of well-being. Methods Fourteen eumenorrheic, moderately trained female runners (age: 24 ±2.8 years; BMI: 22.3 ±2.6 kg/cm2; 240 ±152 min of moderate to vigorous physical activity/week) took part in an 8-week running training intervention consisting of three weekly training sessions. The participants were randomly assigned to a control and an intervention group. Menstrual cycles and time points of menstruation and ovulation were determined by calendar-based counting. The control group (CG) followed a general polarized training program (Muñoz et al., 2014) consisting of two 4-week mesocycles. The mesocycles included three weeks of progressive training load and one week with a reduced load, not adjusted to the MC. The intervention group (IG) followed the same training. However, the single training sessions were adapted to their MC with a higher training load within the follicular phase, medium training load within the luteal phase, and regeneration during the premenstrual and menstrual phases. Both interventions were load-matched and controlled by the training impulse (TRIMP) of all training sessions. At baseline and following the intervention period, anthropometrics (weight, height, BMI), performance (countermovement jump performance [CMJ] [OptoGait, MicroGait, Italy], and maximum oxygen uptake [VO2peak {treadmill: Quasar, h/p/cosmos, Germany; respiratory gas analyzer: MetaMax 3B, Cortex, Germany}]) were assessed. The TRIMP and rate of perceived exertion (RPE) were collected to determine training loads for each training session. Furthermore, recovery and well-being were monitored using the short version of the Recovery and Stress Questionnaire (SRSS; recovery subscale: rSRSS; stress subscale: sSRSS) in the baseline assessment and at the end of the training intervention. The premenstrual assessment form (PAF) was used to determine MC-related symptoms at the same time points. Results Seven females were each randomly assigned to the IG (age: 22.4 ±1.2; BMI: 22.7 ±2.9 kg/cm2; VO2peak: 41.1 ±4.4 ml/min/kg; CMJ: 26.7 ±6.2; PAF: 23.1 ±8,4; rSRSS: 16.6 ±2.3) and to the CG (age: 24.1 ±3.0; BMI: 21.8 ±2.1 kg/cm2; VO2peak: 43.6 ±6.1 ml/min/kg; CMJ: 27.1 ±5.9 cm; PAF: 25.6 ±5.8; rSRSS: 14.1 ±2.7). No significant group differences were revealed in the baseline assessment for anthropometrics, performance, recovery, and well-being (p < .05). A repeated measures ANOVA with a Greenhouse-Geisser correction determined no statistically significant time x group interaction effects in mean performance levels (VO2peak: F(1, 6) = 0.21 p = .890 η² = .003; CMJ: F(1,6) = .691 p = .690 η² = .028). Also no significant time x group interactions effects were found for PAF (F[1,6] = .293 p = .608 η² = .047); rSRSS (F[1,6] = .153 p = .709 η² = .0.25) and sSRSS (F[1,6] = .004 p = .952 η² = .0.001). A significant time effect was found for VO2peak (F[1,6] = 17.93 p = .005 partial η² = .75), but not for the other parameters (p < .05). No group effect was found for any of the parameters (p < .05). Discussion, conclusion, and research perspective An 8-week polarized running training, block-periodized or individually adapted to the MC, is efficacious in improving VO2peak in eumenorrheic female runners. These results are in line with previous findings (Muñoz et al., 2014; Stöggl & Sperlich, 2014). Running training adapted to the menstrual cycle seems to impact performance development in an 8-week training intervention to the same extent as traditional block-periodized training. Our results implicate no further benefits of an MC adapted training on recovery and premenstrual symptoms in recreational runners. However, a post-analysis revealed that in 57% of participants in the CG, training recovery phases of the block-periodized training protocol randomly matched with current recommendations for the late-luteal and early-follicular phase of their MC (Pitchers & Elliott-Sale, 2019).Therefore, the structure of the training protocols between the IG and CG did not really differ. Additionally, the less reliable calendar-based determination of the menstrual cycle (Thompson & Han, 2019) limits the generalization of the results and comparability of the IG and CG. Therefore, we are currently conducting a study with a lager sample size and enhanced study design, including determining the menstrual cycle via changes in basal body temperature and luteinizing hormone occurrence. The control group’s training program will be adapted contrary to the current menstrual cycle training recommendations (Pitchers & Elliott-Sale, 2019) to avoid random matches for the recovery phase. Furthermore, questionnaire-based data assessing recovery, well-being, and (pre-)menstrual symptoms using ecologic-momentary assessment and daily heart rate variability measurements will be included to get an in-depth insight into the well-being of the eumenorrheic women. The follow-up study results will be presented at the conference. References Dušek, T. (2001). Influence of high intensity training on menstrual cycle disorders in athletes. Croatian Medical Journal, 42(1), 79-82. Ihalainen, J. K., Kettunen, O., McGawley, K., Solli, G. S., Hackney, A. C., Mero, A. A., & Kyröläinen, H. (2021). Body composition, energy availability, training, and menstrual status in female runners. International Journal of Sports Physiology and Performance, 16(7), 1043-1048. https://doi.org/10.1123/ijspp.2020-0276 Janse de Jonge, X., Thompson, B., & Han, A. (2019). Methodological recommendations for menstrual cycle research in sports and exercise. Medicine and Science in Sports and Exercise, 51(12), 2610–2617. https://doi.org/10.1249/MSS.0000000000002073 Kenneally, M., Casado, A., & Santos-Concejero, J. (2018). The effect of periodization and training intensity distribution on middle-and long-distance running performance: A systematic review. International Journal of Sports Physiology and Performance, 13(9), 1114-1121. https://doi.org/10.1123/ijspp.2017-0327 McNulty, K. L., Elliott-Sale, K. J., Dolan, E., Swinton, P. A., Ansdell, P., Goodall, S., Thomas, K., & Hicks, K. M. (2020). The effects of menstrual cycle phase on exercise performance in eumenorrheic women: A systematic review and meta-analysis. Sports Medicine, 50(10), 1813-1827. https://doi.org/10.1007/s40279-020-01319-3 Muñoz, I., Seiler, S., Bautista, J., España, J., Larumbe, E., & Esteve-Lanao, J. (2014). Does polarized training improve performance in recreational runners? International Journal of Sports Physiology and Performance, 9(2), 265-272. https://doi.org/10.1123/ijspp.2012-0350 Oosthuyse, T., & Bosch, A. N. (2010). The effect of the menstrual cycle on exercise metabolism. Sports Medicine, 40(3), 207-227. https://doi.org/10.2165/11317090-000000000-00000 Pitchers, G., & Elliott-Sale, K. (2019). Considerations for coaches training female athletes. Professional Strength & Conditioning, 55, 19-30. Redman, L. M., & Loucks, A. B. (2005). Menstrual disorders in athletes. Sports Medicine, 35(9), 747-755. https://doi.org/10.2165/00007256-200535090-00002 Stöggl, T., & Sperlich, B. (2014). Polarized training has greater impact on key endurance variables than threshold, high intensity, or high volume training. Frontiers in Physiology, 5, Article 33. Thompson, B., Almarjawi, A., Sculley, D., & Janse de Jonge, X. (2020). The effect of the menstrual cycle and oral contraceptives on acute responses and chronic adaptations to resistance training: A systematic review of the literature. Sports Medicine, 50(1), 171-185. https://doi.org/10.1007/s40279-019-01219-1 Thompson, B., & Han, A. (2019). Methodological recommendations for menstrual cycle research in sports and exercise. Medicine & Science in Sports & Exercise, 51(12), 2610-2617. https://doi.org/10.1249/MSS.0000000000002073
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Maritza, Erra Khanza, and Berliana Widi Scarvanovi. "The Effect of “Si Andi” Flashcard Games on Improving Personal Safety Skills." JPUD - Jurnal Pendidikan Usia Dini 18, no. 1 (April 30, 2024): 112–28. http://dx.doi.org/10.21009/jpud.181.08.
Full textAbstract:
One of the highest and continually increasing phenomena of violence in Indonesia is sexual abuse. The most frequent victims of this phenomenon are early childhood. The purpose of this study is to determine the influence of the "SI ANDI - Siap Amankan Diri” (Ready to Protect Yourself) flashcard games on improving personal safety skills in early childhood. This study involved 40 subjects aged 4-6 years, divided into control and experimental groups (n=20 for each group). This research is a quasi-experimental study with a non-equivalent control group design. Assessment of personal safety skills employed the WIST-III instrument. The hypothesis was analyzed using independent sample t-tests. The "SI ANDI" flashcard games program was effective on improving personal safety skills among participants in the experimental group, as evidenced by a statistically significant p-value of sig. 0.000 < 0.005. This finding suggests that the "SI ANDI" flashcard games can be used as an alternative tool for teaching personal safety skills in early childhood. Further observation is necessary to ascertain the long-term effects of using the "SI ANDI - Siap Amankan Diri" flashcards on the personal safety skills of young children. This is essential for identifying changes that occur over an extended period, providing insight into the sustained impact of the intervention. Keywords: personal safety skills; sexual abuse; early childhood; sex education References: Agudo, J. E., Rico, M., & Sánchez, H. (2016). Design and Assessment of Adaptive Hypermedia Games for English Acquisition in Preschool. Journal of Universal Computer Science, 22(2), 161–179. Agustina, L. S. S., Kusumawati, R. N., & Hardjono. (2022). Edukasi Seks Berbasis Permainan Puzzle untuk Meningkatkan Keterampilan Perlindungan Diri Anak. 14(2), 49–61. https://doi.org/10.15294/intuisi.v14i2.29575 Akbar, Z., & Mudzdaliffah, F. (2012). 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Abderrahmane, Fatimetou, Gerald Raverot, Herve Lefebvre, CARDOT Catherine, Marie-Christine Vantyghem, Jérôme Bertherat, and Stéphanie Espiard. "SUN-714 Phenotype of Patients Carrying the c.709(-7-2)del PRKAR1A Mutation in a Large Cohort of 41 Patients." Journal of the Endocrine Society 4, Supplement_1 (April 2020). http://dx.doi.org/10.1210/jendso/bvaa046.1395.
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Abstract Objective: The Carney Complex (CNC) is a multiple endocrine and non endocrine neoplasia, mostly due to PRKAR1A mutations. The PRKAR1A mutation c.709(-7-2)del located in the intron 7 is one of the three known hot spot. The objective of this study is to described the CNC manifestations presented by patients harboring the c.709(-7-2)del. Methods: This study is a multicenter retrospective longitudinal study. Patients data have been collected from medical files. Multicenter retrospective study. Age at the diagnosis or at the screening of the different CNC manifestations is described by mean +/- standard deviation or median (interquartile) according to the distribution. Results: 41 patients [14 index cases and 37 relatives, 29 females, 43.6 ±14.3 years old (yo)] from 15 families have been included. 58% of the cohort including the 14 index cases presented with a primary pigmented adrenal disease (PPNAD) at 24-yo (18-40). For the remaining 17 patients, only 3 patients had normal glucocorticoid biological evaluation while others presented with subclinical hypercortisolism diagnosed at 35-yo (22-50). 7% of the cohort had an abnormal IGF1 and/or GH after oral glucose tolerance test while other patients had normal evaluation with a last test performed at 41 ±15yo. 22% of patients presented with lentigines diagnosed at 43yo (24-51) while others had no dermatological lesions at the last examination performed at 37 ±14yo. 13% of patients had thyroid nodules or papillary carcinoma diagnosed at 46 ±15yo (normal ultrasound for others at 37 ±15yo). At the last cardiac ultrasound, pituitary magnetic resonance imaging (MRI), spine MRI, testicular ultrasound, mammography performed at 40±15yo, 37.9±14.3yo, 46±12yo, 35±13yo and 48±12yo, no patient had cardiac myxoma, pituitary adenoma, schwannoma, testicular calcifying tumor or breast myxoma. Overall, 52% of the relatives did not have any manifestations of the disease. Penetrance of the disease is 65%. Conclusion: The phenotype of patients carrying the c.709(-7-2)del PRKAR1A mutation is restricted to PPNAD, lentigines, fluctuating somatotroph anomalies and thyroid tumors. Follow-up of these patients should also be individualized from other CNC patients. Imaging, especially repeated cardiac ultrasound may not be needed to follow these patients The results of this real life study will be useful to elaborate further recommendation for follow-up of CNC patients.
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Brédart, Anne, Jean-Luc Kop, Anja Tüchler, Antoine De Pauw, Alejandra Cano, Julia Dick, Kerstin Rhiem, et al. "Assessment of psychosocial difficulties by genetic clinicians and distress in women at high risk of breast cancer: a prospective study." European Journal of Human Genetics, April 11, 2022. http://dx.doi.org/10.1038/s41431-022-01096-9.
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AbstractWe examined how often genetic clinicians correctly identify psychosocial difficulties in women at high breast cancer risk and explored effects of this assessment and the genetic test result on counselees’ distress. A prospective observational study of counselee–clinician dyads was performed in three French, German and Spanish genetic clinics, involving 709 counselees (participation rate, 83.4%) and 31 clinicians (participation rate, 100%). Counselee–clinician agreement in perceived psychosocial difficulties was measured after the pre-test genetic consultation. Multivariate mixed linear models accounting for clinicians were tested. Predicted distress levels were assessed after the pre- (T1) and post-test result disclosure consultations (T2). Depending on the difficulty domain, clinicians adequately assessed the presence or absence of difficulties in 51% (“familial issues”) to 59% (“emotions”) of counselees. When counselees’ and clinicians’ perceptions disagreed, difficulties were generally underestimated by clinicians. Counselees’ distress levels remained stable from T1 to T2, irrespective of clinicians’ appraisal adequacy, and the genetic test result disclosure. Psychological referral need were found in 20–42% of counselees, more frequently observed for difficulties in the “emotions” domain. Our findings suggest that the genetic test result is a suboptimal indicator for psychological referral. Instead, clinicians should focus on emotions expressed by counselees to appraise their needs for psychological support.
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SETHI, BIPIN, RAKESH K. SAHAY, MANGESH H. TIWASKAR, RAJNISH DHEDIYA, KUMAR GAURAV, RAHUL T. RATHOD, BHAVESH P. KOTAK, GAURI D. DHANAKI, and SNEHAL SHAH. "889-P: Effectiveness of Dapagliflozin as Add-on to Metformin Alone or Metformin with Other Oral Antidiabetic Drug Classes in Type 2 Diabetes Mellitus—A Multicentre, Retrospective, Real-World Evidence Study." Diabetes 72, Supplement_1 (June 20, 2023). http://dx.doi.org/10.2337/db23-889-p.
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Background: Present real-world study evaluated the effectiveness of dapagliflozin as an add-on modality, in adult patients with T2DM. Method: We conducted an EMR-based retrospective, multicentre study in adult T2DM patients inadequately controlled on existing antidiabetic therapy and receiving dapagliflozin as add-on therapy. Baseline characteristics (visit 1) and treatment-related outcomes (visit 2 considered between 60 days-140 days after adding dapagliflozin) which included HbA1C, BMI, SBP & DBP were analyzed. Results: 3616 patients were included from 478 centres, of which 55.7% were males. Mean age was 51 years (range: 40-64 years). Most patients had received dapagliflozin + metformin + at least one other OAD [D+M+OAD, n=2907 (80.4%), 408 followed-up], while 709 patients (19.6%, 138 followed-up) received dapagliflozin + metformin (D+M). For D+M group, significant mean change was noted for all parameters at follow-up except SBP and DBP (non-significant reductions for HbA1c ≥ 8% subgroup). For D+M+OAD group, significant change was noted for all parameters at follow-up except BMI (non-significant reduction). (Table 1) Conclusion: Dapagliflozin showed significant improvement in glycemic parameter, BMI and BP when added to metformin, with or without other OADs in real-world. Disclosure B.Sethi: None. R.K.Sahay: Advisory Panel; Torrent Pharmaceuticals Ltd, Speaker's Bureau; Novo Nordisk A/S, USV Private Limited, Intas Pharmaceuticals Ltd., Eris Lifesciences Ltd. M.H.Tiwaskar: None. R.Dhediya: None. K.Gaurav: None. R.T.Rathod: None. B.P.Kotak: Employee; Dr. Reddy's Laboratories Ltd. G.D.Dhanaki: None. S.Shah: None. Funding Dr. Reddy’s Laboratories, Ltd.
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Ojo, Oluwadamilola Omolara, Sara Bandres‐Ciga, Mary B. Makarious, Peter Wild Crea, Dena G. Hernandez, Henry Houlden, Mie Rizig, et al. "GBA1 rs3115534 Is Associated with REM Sleep Behavior Disorder in Parkinson's Disease in Nigerians." Movement Disorders, February 23, 2024. http://dx.doi.org/10.1002/mds.29753.
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AbstractBackgroundRapid eye movement (REM) sleep behavior disorder (RBD) is an early feature of Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Damaging coding variants in Glucocerebrosidase (GBA1) are a genetic risk factor for RBD. Recently, a population‐specific non‐coding risk variant (rs3115534) was found to be associated with PD risk and earlier onset in individuals of African ancestry.ObjectivesWe aimed to investigate whether the GBA1 rs3115534 PD risk variant is associated with RBD in persons with PD.MethodsWe studied 709 persons with PD and 776 neurologically healthy controls from Nigeria. All DNA samples were genotyped and imputed, and the GBA1 rs3115534 risk variant was extracted. The RBD screening questionnaire (RBDSQ) was used to assess symptoms of possible RBD.ResultsRBD was present in 200 PD (28.2%) and 51 (6.6%) controls. We identified that the non‐coding GBA1 rs3115534 risk variant is associated with possible RBD in individuals of Nigerian origin (β, 0.3640; standard error [SE], 0.103, P = 4.093e−04), as well as in all samples after adjusting for PD status (β, 0.2542; SE, 0.108; P = 0.019) suggesting that although non‐coding, this variant may have the same downstream consequences as GBA1 coding variants.ConclusionsOur results indicate that the non‐coding GBA1 rs3115534 risk variant is associated with an increasing number of RBD symptoms in persons with PD of Nigerian origin. Further research is needed to assess if this variant is also associated with polysomnography‐defined RBD and with RBD symptoms in DLB. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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Groenendijk, Eva A., Maritta N. van Stigt, Anita A. G. A. van de Munckhof, Johannes H. T. M. Koelman, Miou S. Koopman, Henk A. Marquering, Wouter V. Potters, and Jonathan M. Coutinho. "Subhairline Electroencephalography for the Detection of Large Vessel Occlusion Stroke." Journal of the American Heart Association 12, no. 22 (November 21, 2023). http://dx.doi.org/10.1161/jaha.123.031929.
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Background Endovascular thrombectomy is standard treatment for patients with anterior circulation large vessel occlusion stroke (LVO‐a). Prehospital identification of these patients would enable direct routing to an endovascular thrombectomy‐capable hospital and consequently reduce time‐to‐endovascular thrombectomy. Electroencephalography (EEG) has previously proven to be promising for LVO‐a stroke detection. Fast and reliable electrode application, however, can remain a challenge. A potential alternative is subhairline EEG. We evaluated the diagnostic accuracy of subhairline EEG for LVO‐a stroke detection. Methods and Results We included adult patients with a suspected stroke or known LVO‐a stroke and symptom onset time <24 hours. A single 3‐minute EEG recording was performed at the emergency department, before endovascular thrombectomy, using 9 self‐adhesive electrodes placed on the forehead and behind the ears. We evaluated the diagnostic accuracies of EEG features quantifying frequency band power and brain symmetry (pairwise derived Brain Symmetry Index) for LVO‐a stroke detection using receiver operating characteristic analysis. EEG data were of sufficient quality for analysis in 51/52 (98%) included patients. Of these patients, 16 (31%) had an LVO‐a stroke, 16 (31%) a non‐LVO‐a ischemic stroke, 5 (10%) a transient ischemic attack, and 14 (27%) a stroke mimic. Median symptom‐onset‐to‐EEG‐time was 266 (interquartile range 130–709) minutes. The highest diagnostic accuracy for LVO‐a stroke detection was reached by the pairwise derived Brain Symmetry Index in the theta frequency band (area under the receiver operating characteristic curve 0.90; sensitivity 86%; specificity 83%). Conclusions Subhairline EEG could detect LVO‐a stroke with high diagnostic accuracy and had high data reliability. These data suggest that subhairline EEG is potentially suitable as a prehospital stroke triage instrument.
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Jia, Judy, Michael Abboud, William Pajerowski, Michelle Guo, Guy David, Steven R. Messe, Roger Band, Brendan G. Carr, and Michael T. Mullen. "Abstract 86: Accuracy of Emergency Medical Services Dispatcher and Provider Recognition of Stroke in Clinical Practice." Stroke 46, suppl_1 (February 2015). http://dx.doi.org/10.1161/str.46.suppl_1.86.
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Objective: It is imperative that prehospital providers accurately recognize stroke. We assessed the sensitivity of stroke recognition by emergency medical services (EMS) in clinical practice in a major US city, and assessed variables associated with failure to recognize stroke. Methods: Data from the Philadelphia EMS system was linked with data from a single comprehensive stroke center to identify patients diagnosed with transient ischemic attack, ischemic stroke, or intracerebral hemorrhage by EMS dispatchers, EMS providers, or at hospital discharge between September 2009 and October 2012. Sensitivity and positive predictive value (PPV) were calculated. Multivariable logistic regression was used to identify variables associated with EMS recognition of stroke. Results: There were a total of 709 cases, 400 of which were cerebrovascular events (38% infarct, 10% ICH, and 8% TIA). Of these cases, 80 (20%) were not recognized by EMS dispatcher or EMS provider, 90 (23%) were recognized by dispatcher alone, 87 (22%) by EMS provider alone, and 143 (36%) by both. EMS providers recognized stroke with a sensitivity of 58%, PPV 69%. Dispatchers or EMS providers recognized stroke with a sensitivity of 80%, PPV 51%. In a multivariable model, EMS providers were more likely to miss a stroke when NIHSS was low (compared to NIHSS 10+, NIHSS 5-9 OR=1.6, 95% CI 0.9-3.0 & NIHSS<5 OR=4.6, 95% CI 2.7-7.9), when motor signs were absent (OR=2.4, 95% CI 1.5-3.9), and when symptom duration was > 270 minutes (OR=2.4, 95% CI 1.5-3.8). Medics correctly recognized 81% of stroke patients with NIHSS>4 and symptom duration <270 minutes, and dispatcher or EMS providers correctly recognized 90% of these patients. Conclusions: EMS recognized stroke with limited sensitivity, resulting in a high proportion of missed stroke cases. When added to the EMS provider impression, dispatcher impression meaningfully improves the sensitivity for recognizing stroke. Maximizing sensitivity is critical to prehospital interventions which may improve overall stroke care, such as transportation to designated stroke centers or EMS prenotification of receiving hospitals.
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HOUSNI, ASMAA, ALEXANDRA KATZ, JESSICA C. KICHLER, MERANDA NAKHLA, and ANNE-SOPHIE BRAZEAU. "624-P: Portrayal of Perceived Stigma across Ages in Type 1 Diabetes—A BETTER Registry Analysis." Diabetes 72, Supplement_1 (June 20, 2023). http://dx.doi.org/10.2337/db23-624-p.
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Background: People with type 1 diabetes (PWT1D) perceiving high diabetes-related stigma are less likely to report in-target A1c levels. We hypothesized that people with higher levels of stigma have suboptimal psychosocial outcomes and that stigma would be perceived differently across age groups. Methods: Cross-sectional analysis of 709 PWT1D aged ≥14 years in the BETTER T1D registry (Quebec, Canada) who completed the T1D Stigma Assessment Scale (DSAS-1). The DSAS-1 (/95) includes 3 subscales; Blame & Judgment (6 items), Identity Concern (7 items), and Treated Differently (6 items). Individuals who perceived more stigma compared to the total cohort (DSAS-1 mean score +1 standard deviation), were stratified into groups by age to determine associations with diabetes self-management behaviours and outcomes. Results: Across groups, youth (n=105; 14-24 years) had the highest stigma perception (20%), followed by 18% in middle-aged adults (n=401; 35-64 years), then 15% for both young adults (n=130; 25-34 years) and seniors (n=73; 65+ years). The majority of youth, young and middle-aged adults, and seniors perceived stigma as Blame & Judgment (51%, 44%, 33%, and 19%, respectively). Stigma related to Identity Concern was highest among seniors (15%). In an age- and diabetes duration-adjusted models, 40% of adjusted variance in stigma score was explained by increased diabetes distress (p<0.001), depression (p=0.005), hyperglycemia avoidance behaviours (p<0.001), fear of hypoglycemia (p<0.001) and decreased social support (p<0.001). Conclusion: Interventions targeting diabetes-related stigma need to be tailored for different age groups to target suboptimal diabetes self-management behaviours and improve psychosocial outcomes. Disclosure A.Housni: None. A.Katz: None. J.C.Kichler: None. M.Nakhla: None. A.Brazeau: Other Relationship; Dexcom, Inc., Diabète québec, Ordre des diététistes nutritionnistes du Québec, Research Support; Canadian Institutes of Health Research, Fonds de recherche du Québec en Santé. Funding JDRF (4-SRA-2018-651-Q-R); Canadian Institutes of Health Research (JT1-157204)
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Jozwiak, Mathieu, Denis Doyen, Pierre Denormandie, Antoine Goury, Jonathan Marey, Frédéric Pène, Alain Cariou, Jean-Paul Mira, Jean Dellamonica, and Lee S. Nguyen. "Impact of sex differences on cardiac injury in critically ill patients with COVID-19." Respiratory Research 24, no. 1 (November 20, 2023). http://dx.doi.org/10.1186/s12931-023-02581-5.
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Abstract Background COVID-19 infections are associated with accrued inflammatory responses which may result in cardiac injury. Immune response to infection appears different between men and women, suggesting that COVID-19 patients’ outcomes may differ according to biological sex. However, the impact of biological sex on the occurrence of cardiac injury during intensive care unit (ICU) stay in COVID-19 patients remain unclear. Methods In this multicenter and prospective study, we included consecutive patients admitted to ICU for severe COVID-19 pneumonia, during the first two pandemic waves. Biological, electrocardiogram (ECG) and echocardiographic variables were collected on ICU admission. Cardiac injury was defined by increased troponin above 99th percentile of upper norm value and newly diagnosed ECG and/or echocardiographic abnormalities. The primary endpoint was the proportion of patients with cardiac injury during ICU stay according to biological sex. The impact of biological sex on other subsequent clinical outcomes was also evaluated. Results We included 198 patients with a median age of 66 (56–73) years, 147 (74%) patients were men and 51 (26%) were women. Overall, 119 (60%) patients had cardiac injury during ICU stay and the proportion of patients with cardiac injury during ICU stay was not different between men and women (60% vs. 61%, p = 1.00). Patients with cardiac injury during ICU stay showed more cardiovascular risk factors and chronic cardiac disease and had a higher ICU mortality rate. On ICU admission, they had a more marked lymphopenia (0.70 (0.40–0.80) vs. 0.80 (0.50–1.10) × 109/L, p < 0.01) and inflammation (C-Reactive Protein (155 (88–246) vs. 111 (62–192) mg/L, p = 0.03); D-Dimers (1293 (709–2523) vs. 900 (560–1813) µg/L, p = 0.03)). Plasmatic levels of inflammatory biomarkers on ICU admission correlated with SAPS-2 and SOFA scores but not with the different echocardiographic variables. Multivariate analysis confirmed cardiovascular risk factors (OR = 2.31; 95%CI (1.06–5.02), p = 0.03) and chronic cardiac disease (OR = 8.58; 95%CI (1.01–73.17), p = 0.04) were independently associated with the occurrence of cardiac injury during ICU stay, whereas biological sex (OR = 0.88; 95%CI (0.42–1.84), p = 0.73) was not. Biological sex had no impact on the occurrence during ICU stay of other clinical outcomes. Conclusions Most critically ill patients with COVID-19 were men and experienced cardiac injury during ICU stay. Nevertheless, biological sex had no impact on the occurrence of cardiac injury during ICU stay or on other clinical outcomes. Clinical trial registration NCT04335162
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Aguiar Neves, A. I., M. Leite, R. Teixeira, F. Nunes, M. Ribeiro Silva, M. Almeida, A. Lobo, et al. "Opportunistic coronary calcium screening in patients undergoing procedural planning for catheter ablation of atrial fibrillation." European Heart Journal - Cardiovascular Imaging 25, Supplement_1 (June 27, 2024). http://dx.doi.org/10.1093/ehjci/jeae142.028.
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Abstract Introduction Coronary artery calcium score (CACS) may be a useful tool for opportunistic cardiovascular risk stratification in patients with atrial fibrillation undergoing cardiac computed tomography (CCT) for catheter ablation planning. Methods This cohort retrospectively included all consecutive patients who underwent CCT for ablation procedure planning between 2017 and 2021. CACS was assessed using the Agatston method. Cardiovascular risk was assessed using the SCORE algorithm for patients aged less than 70 years and the SCORE-OP algorithm for patients 70 years and older. Patients with known CAD were excluded. Clinical, analytical and procedural characteristics were collected during the follow-up period. Results In this cohort, a total of 709 patients (37% female; mean age 58±8 years; 13% aged ≥70 years; mean CHA2DS2VASc score 1.4±1.2; 76% paroxysmal AF) underwent CCT planning for AF catheter ablation. The mean SCORE value was 1±1.5 points, while the mean SCORE-OP value in patients aged ≥70 years was 10.9±6.1 points. Median follow-up after catheter ablation was 30 months. In this population, 232 patients (33%) were prescribed statins, of whom 174 patients (28%) were prescribed a moderate intensity statin and 31 patients (5%) were prescribed a high intensity statin. When considering CACS, 400 patients (56%) had a CACS greater than zero, of whom 163 patients (41%) presented CACS ≥100 and 79 patients (20%) presented CACS ≥300. Compared to patients without coronary calcification, patients with CACS greater than 0 were older (62±6.0 vs. 52±8.5 years, p<0.001), had higher body mass index (27.7 vs. 26.4 kg/m2, p<0.001), higher triglyceride levels (101 vs. 93 mg/dl, p=0.013), hypertension (59% vs. 33%, p<0.001), dyslipidaemia (55% vs. 34%, p<0.001), type 2 diabetes mellitus (18% vs. 6%, p<0.001), heart failure (10% vs. 5%, p=0.006) and obstructive sleep apnoea (12% vs. 5%, p=0.003). Patients with CACS greater than zero were more likely to be prescribed statins (51% vs. 21%, p<0.001). Considering a CACS of 100 or greater as a threshold for initiating statin therapy in low to moderate risk patients, an additional 86 patients could be identified as candidates for statin therapy. Furthermore, when considering a threshold of CACS ≥300 for intensification of statin therapy, a change in statin therapy from a low or moderate-intensity statin to a high-intensity statin could be recommended in 33 patients. Conclusions Patients with incidental coronary calcification have an increased cardiovascular risk profile compared to those without coronary calcification, even in the absence of known coronary disease. Patients undergoing CCT for procedural planning may benefit from opportunistic calcium scoring in order to better stratify their risk profile and determine the need for intensification of medical therapy.
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Thompson, N., and I. Street. "709 A Prospective Analysis of Post-Tonsillectomy Haemorrhage and Hospital Reamission Rates in A Tertiary Pediatric Centre." British Journal of Surgery 108, Supplement_6 (September 1, 2021). http://dx.doi.org/10.1093/bjs/znab259.554.
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Abstract Introduction Tonsillectomies are one of the most commonly performed procedures., with one particular leading tertiary paediatric centre performing 1,067 tonsillectomies within the last year. Post-tonsillectomy haemorrhage is a considerable complication leading to further primary care costs, readmission, and surgical intervention. Previous national audits have suggested that post-tonsillectomy haemorrhage rates are between 3.0-3.5%1 and readmission rates are approximately 8.8%2. Aim Assess post-tonsillectomy haemorrhage and readmission rates at a leading tertiary paediatric centre. Method A prospective phone survey was completed for every patient receiving a tonsillectomy 6 weeks post-operatively, using a 2-month inclusion period. Results Of the 51 patients included, 51 responded to phone survey. The total post-tonsillectomy haemorrhage rate was 23.5%. Of the 51 respondents, 10 (19.6%) were readmitted through A&E, all of which had extracapsular tonsillectomies. 1 (10%) of those readmitted had further surgical intervention whilst the remaining 9 (90%) were treated conservatively. A further 4 (7.8%) attended their GP, with 3 (75%) of those requiring antibiotics. Conclusions This data shows that both the post-tonsillectomy haemorrhage and readmission rates at the tertiary paediatric centre were higher than the national average. We suggest that previous national data audits describing bleeding rates lack the granularity to reveal true post-operative complication rates. Our prospective cohort has demonstrated that there may be a large proportion of patients with morbidity that never reach the attention of the ENT surgeon and additionally that subgroups in particular may benefit from interventions designed to minimise patients’ post-operative risks, including specific perioperative management and advice.