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Yaish, Hassan M., Maria Sol Cruz, Kay Decker, Eva M. K. Zetterberg, Sylvia Werner, Mariko Hashimoto, Sigurd Knaub, and George M. Rodgers. "Final Results from a Non-Interventional Safety and Efficacy Study of a VWF/FVIII Concentrate (wilate®) in Patients with Von Willebrand Disease." Blood 132, Supplement 1 (November 29, 2018): 1182. http://dx.doi.org/10.1182/blood-2018-99-118069.
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Abstract Introduction: Post-marketing studies provide important insight into the consistency of data from clinical studies and routine clinical use. This non-interventional, prospective, multicentre study (WIL-20) collected real-life data on the use of a human VWF/FVIII concentrate with the native VWF/FVIII complex in a physiological 1:1 ratio (wilate®; pdVWF/FVIII) in routine clinical practice. Here, we report the final results from this study. Methods: The primary objective was to document the safety and tolerability of pdVWF/FVIII in routine clinical practice, with a planned observation period per patient of 2 years. Secondary objectives were to document the efficacy in on-demand treatment of acute bleeding, long-term prophylaxis, and surgical prophylaxis. Male and female patients of any age and with any type of VWD who were prescribed pdVWF/FVIII were eligible for the study. pdVWF/FVIII was administered at the investigator's discretion. Data recorded included patient demographics, laboratory parameters, treatment details, and occurrence of adverse drug reactions (ADRs), including immunogenicity and thrombogenicity. Tolerability was assessed using a verbal rating scale; efficacy of on-demand treatment and surgical prophylaxis using a haemostatic scale; and prophylactic efficacy based on the frequency of spontaneous breakthrough bleeds. Results: The study enrolled 120 patients from 11 countries. Within the safety population (111 patients who received at least one dose of pdVWF/FVIII), 45% of patients had type 1 VWD, 29% type 2 and 18% type 3; disease type was unavailable for 8 patients, and 1 patient was diagnosed with haemophilia A during the study. Of the 111 patients, 33% were previously untreated with a FVIII/VWF product. A total of 7024 infusions were administered to the safety population over a median observation time of 2 years; median dose was 320.5 IU/kg. A total of 26 ADRs were reported in 8 patients; 4 were mild, 3 moderate and 1 severe. Three patients discontinued treatment and 1 stopped treatment temporarily due to adverse events. Using an experimental assay, 3 cases of VWF inhibitors were identified, with no impact on clinical outcome. No thromboembolic events were reported. Tolerability was rated for 6497 infusions, with 96.2% rated 'excellent', 3.7% 'satisfactory', and 0.1% 'unsatisfactory'. Of the 29 patients treated on-demand, 150 bleeding events (BEs), excluding menstrual bleeds, were reported in 25 patients; 18% of BEs were mild, 71.3% were moderate, and 10% were severe. 94% of treated bleeds (130/138) resolved with 1 or 2 infusions, with a median dose per BE of 33 IU/kg. The efficacy of treatment was rated as 'excellent' or 'good' for 100% of BEs. Of the 25 patients treated with pdVWF/FVIII for prophylaxis, 18 patients had a total of 233 breakthrough BEs; 37% mild, 44% moderate, and 9% severe (severity information was unavailable for 11% of bleeds). Of the breakthrough BEs that required treatment, 85% (149/175) were treated with 1 or 2 infusions of pdVWF/FVIII, with a median dose per BE of 55.4 IU/kg. Efficacy of pdVWF/FVIII was rated as 'excellent' or 'good' by investigators for 99% of 139 evaluable breakthrough BEs. For patients on prophylaxis (n = 25), the median annualised bleeding rate for spontaneous BEs was 1.5 (range 0.0-19.7). The efficacy of prophylaxis for prevention of spontaneous breakthrough bleeds was rated as 'excellent' or 'good' in 96% (24/25) of these patients. A total of 99 surgical procedures were performed in 62 patients; 56% with type 1 VWD, 29% type 2 and 13% type 3 (2% were type unknown). Of the procedures, 46 were major and 53 minor. All but one of the surgeries were managed with pdVWF/FVIII prophylaxis, and the efficacy was rated as 'excellent' or 'good' in 99% (96/97) of surgeries with assessments available. Conclusions: The final results of this non-interventional study indicate that pdVWF/FVIII is well tolerated and effective for on-demand treatment, prophylaxis, and surgical prophylaxis in patients with all types of VWD treated as part of routine clinical practice. The data are consistent with those from previous clinical studies and provide real-life evidence from around the world on the use of pdVWF/FVIIIfor management of VWD in all clinical settings. Disclosures Werner: Octapharma USA Inc.: Employment. Hashimoto:Octapharma USA Inc.: Employment. Knaub:Octapharma AG: Employment. Rodgers:Octapharma: Membership on an entity's Board of Directors or advisory committees, Research Funding.
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Jones, Jane H., Bohumil Štíbr, John D. Kennedy, and Mark Thornton-Pett. "Ten-Vertex Polyhedral Monocarbaborane Chemistry. The Novel High-Yield Formation of the Ten-Vertex closo Compound [6-(PMe2Ph)-closo-1-CB9H9] from the Thermolysis of [8,8-(PMe2Ph)2-nido-8,7-PtCB9H11]." Collection of Czechoslovak Chemical Communications 58, no. 12 (1993): 2924–35. http://dx.doi.org/10.1135/cccc19932924.
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Thermolysis of [8,8-(PMe2Ph)2-nido-8,7-PtCB9H11] in boiling toluene solution results in an elimination of the platinum centre and cluster closure to give the ten-vertex closo species [6-(PMe2Ph)-closo-1-CB9H9] in 85% yield as a colourles air stable solid. The product is characterized by NMR spectroscopy and single-crystal X-ray diffraction analysis. Crystals (from hexane-dichloromethane) are monoclinic, space group P21/c, with a = 903.20(9), b = 1 481.86(11), c = 2 320.0(2) pm, β = 97.860(7)° and Z = 8, and the structure has been refined to R(Rw) = 0.045(0.051) for 3 281 observed reflections with Fo > 2.0σ(Fo). The clean high-yield elimination of a metal centre from a polyhedral metallaborane or metallaheteroborane species is very rare.
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Baillif, Stéphanie, Pascal Staccini, Michel Weber, Marie-Noëlle Delyfer, Yannick Le Mer, Vincent Gualino, Laurence Collot, et al. "Management of Patients with Diabetic Macular Edema Switched from Dexamethasone Intravitreal Implant to Fluocinolone Acetonide Intravitreal Implant." Pharmaceutics 14, no. 11 (November 5, 2022): 2391. http://dx.doi.org/10.3390/pharmaceutics14112391.
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To assess anatomical and functional outcomes after switching from dexamethasone implant (DEXi) to fluocinolone acetonide implant (FAci) in 113 diabetic macular edema eyes, a multicentric retrospective observational study was conducted. Seventy-five eyes (73.5%) were switched 1–8 weeks after their last DEXi. The mean best-corrected visual acuity improved to 59.8 letters at month 4 and remained stable during the follow-up. The mean central macular thickness (CMT) significantly decreased during the follow-up, with a minimum of 320.9 μm at month 3. The baseline CMT was higher in eyes that received the last DEXi >8 weeks versus <8 weeks before the first FAci (p < 0.021). After FAci injection, additional treatments were needed in 37 (32.7%) eyes. A longer diabetes duration (p = 0.009), a longer time between the last DEXi and the first FAci (p = 0.035), and a high baseline CMT (p = 0.003) were risk factors for additional treatments. The mean intraocular pressure was <19 mmHg at all timepoints, with no difference between eyes receiving the last DEXi ≤8 weeks or >8 weeks before the switch. Switching from DEXi to FAci in DME is effective and safe. A short time between the last DEXi and the first FAci reduced CMT fluctuations and the need for early additional treatments.
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Xu, Ping. "Comparison of cytotoxicity evaluation of chlorogenic acid extract between Real-time cell analysis and CCK-8 method." Ukrainian Journal of Veterinary and Agricultural Sciences 4, no. 2 (June 21, 2021): 58–61. http://dx.doi.org/10.32718/ujvas4-2.10.
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Critical cytotoxicity evaluation of pharmaceuticals is necessary for the clinical practice of chemotherapy. To quantitatively evaluate cell viability, currently there are two main types of sensitive methods including real-time cell analysis (RTCA) and CCK-8 assay, in which RTCA records electrochemical signal changes around an incubated cell, whereas CCK-8 is based on the colorimetric method. Despite the different detection principles adopted for the cytotoxicity assessment, the comparison of the two methods in terms of the application scope is lacking. In order to compare and determine the best experimental method for the study of the toxicity of chlorogenic acid extract from taraxacum officinale on dairy cow mammary epithelial cells. The real time cell analysis (RTCA) and CCK-8 method were used to analyze the cytotoxicity of chlorogenic acid extract to BMEC and calculate its IC50. The results of the real time cell analysis method and the CCK-8 method showed that different concentrations of chlorogenic acid extract reduced the viability of dairy cow mammary epithelial cells, and the decrease was most obvious at 400 ug/mL. The IC50 of the two analysis methods were 326.8 and 320.4 ug/mL, respectively. In contrast, the CCK-8 method had limitations in fixed-point determination. However, the real time cell analysis method can monitor the dynamic biological response process of cell growth and proliferation in real time. Therefore, the real time cell analysis method can observe cell growth more intuitively and accurately, compensate for the shortcomings of the CCK-8 method, and it is a new experimental method for studying cytotoxicity.
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FLEISCHMANN, ROY M., ANNE-MARIE HALLAND, MAREK BRZOSKO, RUBEN BURGOS-VARGAS, CHRISTOPHER MELA, EMMA VERNON, and JOEL M. KREMER. "Tocilizumab Inhibits Structural Joint Damage and Improves Physical Function in Patients with Rheumatoid Arthritis and Inadequate Responses to Methotrexate: LITHE Study 2-year Results." Journal of Rheumatology 40, no. 2 (January 15, 2013): 113–26. http://dx.doi.org/10.3899/jrheum.120447.
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Objective.To assess radiographic progression, physical function, clinical disease activity, and safety in patients with rheumatoid arthritis (RA) who had inadequate response to methotrexate (MTX) and who were treated with tocilizumab-MTX or MTX during Year 2 of a 2-year study.Methods.During Year 1, patients were randomized to placebo-MTX, 4 mg/kg tocilizumab-MTX, or 8 mg/kg tocilizumab-MTX. During Year 2, patients continued the initial double-blind treatment or switched to open-label 8 mg/kg tocilizumab-MTX. Co-primary endpoints at Week 104 were mean change from baseline in Genant-modified Total Sharp Score (GmTSS) and adjusted mean area under the curve (AUC) for change from baseline in the Health Assessment Questionnaire–Disability Index (HAQ-DI). Signs and symptoms of RA and safety were also evaluated.Results.At Week 104, mean change from baseline in GmTSS was significantly lower for patients initially randomized to tocilizumab-MTX 4 mg/kg (0.58; p = 0.0025) or 8 mg/kg (0.37; p < 0.0001) than for patients initially randomized to placebo-MTX (1.96). Adjusted mean AUC of change from baseline in HAQ-DI was also significantly lower in patients initially randomized to tocilizumab-MTX 4 mg/kg (–287.5; p < 0.0001) or 8 mg/kg (–320.8; p < 0.0001) than in patients initially randomized to placebo-MTX (–139.4). Signs and symptoms of RA were maintained or showed improvement. No new safety signals were noted.Conclusion.Compared with placebo-MTX, tocilizumab-MTX significantly inhibited structural joint damage and improved physical function in patients with RA who previously had inadequate response to MTX. An extension of this study is continuing and will provide additional longterm efficacy and safety data. National Clinical Trials registry NCT00106535.
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Kersten, Sebastian, Robert Prill, Hassan Tarek Hakam, Hannes Hofmann, Mahmut Enes Kayaalp, Jan Reichmann, and Roland Becker. "Postoperative Activity and Knee Function of Patients after Total Knee Arthroplasty: A Sensor-Based Monitoring Study." Journal of Personalized Medicine 13, no. 12 (November 21, 2023): 1628. http://dx.doi.org/10.3390/jpm13121628.
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Inertial measurement units (IMUs) are increasingly being used to assess knee function. The aim of the study was to record patients’ activity levels and to detect new parameters for knee function in the early postoperative phase after TKA. Twenty patients (n = 20) were prospectively enrolled. Two sensors were attached to the affected leg. The data were recorded from the first day after TKA until discharge. Algorithms were developed for detecting steps, range of motion, horizontal, sitting and standing postures, as well as physical therapy. The mean number of steps increased from day 1 to discharge from 117.4 (SD ± 110.5) to 858.7 (SD ± 320.1), respectively. Patients’ percentage of immobilization during daytime (6 a.m. to 8 p.m.) was 91.2% on day one and still 69.9% on the last day. Patients received daily continuous passive motion therapy (CPM) for a mean of 36.4 min (SD ± 8.2). The mean angular velocity at day 1 was 12.2 degrees per second (SD ± 4.4) and increased to 28.7 (SD ± 16.4) at discharge. This study shows that IMUs monitor patients’ activity postoperatively well, and a wide range of interindividual motion patterns was observed. These sensors may allow the adjustment of physical exercise programs according to the patient’s individual needs.
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Tomita, K., H. Nonoguchi, Y. Terada, and F. Marumo. "Effects of ET-1 on water and chloride transport in cortical collecting ducts of the rat." American Journal of Physiology-Renal Physiology 264, no. 4 (April 1, 1993): F690—F696. http://dx.doi.org/10.1152/ajprenal.1993.264.4.f690.
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Endothelin-1 (ET-1) is known as a vasoconstrictor peptide. However, recent reports suggested the effects on the transport of renal tubule. We previously reported that ET-1 inhibited arginine vasopressin (AVP)-dependent adenosine 3',5'-cyclic monophosphate in rat collecting ducts. Physiologically, ET-1 reversibly and significantly inhibited AVP-stimulated water permeability in inner medullary collecting duct (IMCD). We therefore investigated the effects on water and electrolyte transport in rat cortical collecting ducts (CCD), where Na and Cl are actively reabsorbed more than in IMCD. Pathogen-free male Sprague-Dawley rats weighing 80-120 g were used after treatment with deoxycorticosterone pivalate for 1-2 wk. Isolated CCD were microperfused in vitro. The Cl concentration was measured by a continuous-flow ultra-microcolorimeter, and the raffinose concentration was measured as a volume marker by a continuous-flow ultra-microfluorometer. In the presence of 10(-9) M AVP, 10(-8) M ET-1 significantly inhibited fluid absorption (nl.mm-1 x min-1) from 0.25 +/- 0.02 to 0.15 +/- 0.05 (mean +/- SE, n = 6, P < 0.01), Cl absorption (pmol.mm-1 x min-1) from 30. 6 +/- 2.8 to 14.9 +/- 4.0 (P < 0.01), and potential difference (mV) from -5.4 +/- 1.3 to -4.0 +/- 1.2 (P < 0.01). Similar results were obtained in the lower concentration of 10(-10) M AVP and 10(-10) M ET-1. As for the osmotic water permeability (microns/s), 10(-8) M ET-1 significantly inhibited this from 320.1 +/- 50.9 to 202.1 +/- 42.2 (n = 7, P < 0.01) in the presence of 10(-9) M AVP.(ABSTRACT TRUNCATED AT 250 WORDS)
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Abbasi, S., and A. Honaramooz. "305 OPTIMIZING DONOR AND RECIPIENT FACTORS IN XENOGRAFTING OF TESTIS TISSUE." Reproduction, Fertility and Development 22, no. 1 (2010): 308. http://dx.doi.org/10.1071/rdv22n1ab305.
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Grafting of donor mammalian testis tissue into recipient mice allows completion of spermatogenesis in the grafted tissue and therefore can serve as a new option for preservation of male germ line. For testis tissue xenografting, castrated male nude mice typically serve as recipients, each receiving 8 testis tissue fragments; however, no study has comprehensively investigated donor and recipient factors. The objective of this study was to determine the effects of strain of immunodeficient recipient mouse (nude v. SCID), gonadal status (intact v. gonadectomized), and gender (male v. female) on the outcome of testis tissue xenografting. A secondary objective was to determine the optimal number of testis tissue fragments per mouse most suitable for xenografting. Testis parenchyma from newborn piglets were cut into small fragments (5 mg each) and grafted under the back skin of different groups of immunodeficient mice. In Experiment 1, 8 groups of mice (n = 7/group) served as recipients: castrated male nude, intact male nude, ovariectomized female nude, intact female nude, castrated male SCID, intact male SCID, ovariectomized female SCID, and intact female SCID. In Experiment 2, 4 groups of mice (n = 10/group) served as recipients of 2, 4, 8, or 16 testis tissue fragments per mouse. Recipient mice were sacrificed 8 months after grafting and the weight of the grafts and vesicular glands (male mice) were compared among groups by analysis of variance. In Experiment 1, mouse gonadal status (intact v. gonadectomized) did not affect the total graft weight (P > 0.05), but both the recipient mouse strain (nude v. SCID) and gender (male v. female) affected the total graft weight (2460 ± 320.9, 1420 ± 290.0, 758 ± 156.7, and 2780 ± 297.4, mean ± SEM, P < 0.0001 for SCID, nude, female, and male mice, respectively). In Experiment 2, the total graft weight was highest in the group of mice receiving 8 testis tissue fragments (192 ± 76.1, 695 ± 96.5, 2443 ± 338.8, and 1458 ± 305.4, mean ± SEM, P < 0.0001 for 2, 4, 8, or 16 fragment groups, respectively). These results collectively indicate that male SCID mice receiving 8 testis tissue fragments provide optimized conditions for the recovery of largest grafts. Research was supported by grants from the Natural Sciences and Engineering Research Council of Canada (NSERC) and the Saskatchewan Health Research Foundation (SHRF) to A. Honaramooz and scholarships from the Western College of Veterinary Medicine and the International Peace Scholarship to S. Abbasi.
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Singh, Akanksha, and Ram Pal Singh. "Study of Interrelationship among Economically Important Production Traits and Season of Calving on Milk Production in Jersindh Crosses." Current Journal of Applied Science and Technology 42, no. 44 (November 25, 2023): 13–18. http://dx.doi.org/10.9734/cjast/2023/v42i444279.
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Study was conducted on productive traits in Jersindh crosses. The data were collected from the records of history sheets maintained in Department of Animal Husbandry and Dairying, SHUATS for the period from 1924 to 1973. The productive traits selected from history sheets were first, second and third lactation milk yield and lactation length and dry period. The mean of 1/4J X3/4RS crosses for 1st ,2nd and 3rd LMY (Kg) were 2259.95, 1963.59 and 1832.74 and for lactation length (days) 378.71, 357.78 and 352 and for Dry period (days) 65.94, 98.23 and 98.26, respectively. The mean of 1/2J X 1/2RS crosses for 1st ,2nd and 3rd LMY (Kg) were 1892.14, 1680.14 and 1789.25 and for lactation length (days) 366.06, 338.75 and 359.43 for Dry period (days) 76.81,61 and 59.93 respectively. The mean of 3/8J X 5/8RS crosses for 1st ,2nd and 3rd LMY (Kg) were 1754, 1843.39 and 3682.36 and for lactation length (days) 320.1, 357.15 and 3 and for Dry period (days) 71.2, 70.7 and 72.35 respectively. The mean of 1/8J X 7/8RS crosses for 1st ,2nd and 3rd LMY (Kg) were 1966.35, 1906.51 and 1837.68 and for lactation length (days) 425.6, 371.75 and 446.4, and for Dry period (days) 71.35, 58.75 and 111.2 respectively. Significant effects of season of calving were observed on 3rd LMY of 1/2J X 1/2RS crosses as well as 3/8J X 5/8RS and 2nd LMY of1/4J X 3/4RS crosses , Second and third lactation length of 1/8 X 7/8 crosses has significant influence on lactation milk yield. Second and third lactation length of 1/4 X 3/4 crosses has significant correlation with lactation milk yield and also the regression of milk yield on lactation length was recorded. Third lactation length of 3/8 X 5/8 crosses has significant correlation with lactation milk yield and also the regression of milk yield on lactation length was recorded. Second lactation length of 1/8 X 7/8 crosses has significant correlation with lactation milk yield and also the regression of milk yield on lactation length was recorded. Out of these crosses (1/4Jx3/4RS,1/2JX1/2RS,3/8 JX5/8RS,1/8JX7/8RS) 3/8JX5/8RS has highest lactation length 652.76 and lactation milk yield is 3682.36.
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Ialongo, I., V. Buchard, C. Brogniez, G. R. Casale, and A. M. Siani. "Aerosol Single Scattering Albedo retrieval in the UV range: an application to OMI satellite validation." Atmospheric Chemistry and Physics Discussions 9, no. 5 (September 14, 2009): 19009–33. http://dx.doi.org/10.5194/acpd-9-19009-2009.
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Abstract. The aerosol Single Scattering Albedo (SSA) and Absorbing Aerosol Optical Depth (AAOD) at 320.1 nm are derived at Rome site by the comparison between Brewer and modelled spectra. The UVSPEC radiative transfer model is used to calculate the UV irradiances for different SSA values, taking into account as input data total ozone and Aerosol Optical Depth (AOD) obtained from Brewer spectral measurements. The accuracy in determining SSA depends on the aerosol amount and on Solar Zenith Angle (SZA) value: SSA uncertainty increases when AOD and SZA decrease. The monthly mean values of SSA and AAOD during the period January 2005–June 2008 are analysed, showing a monthly and seasonal variability. It is found that the SSA and AAOD averages are 0.80±0.08 and 0.056±0.028, respectively. AAOD retrievals are also used to quantify the error in the Ozone Monitoring Instrument (OMI) surface UV products due to absorbing aerosols, not included in the current OMI UV algorithm. OMI and Brewer UV irradiances at 324.1 nm and Erythemal Dose Rates (EDRs) under clear sky conditions, are compared as a function of AAOD. Three methods are considered to investigate on the applicability of an absorbing aerosol correction on OMI UV data at Rome site. Depending on the correction methodology, the bias value decreases from 18% to 2% for spectral irradiance at 324.1 nm and from 25% to 8% for EDR.
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Ialongo, I., V. Buchard, C. Brogniez, G. R. Casale, and A. M. Siani. "Aerosol Single Scattering Albedo retrieval in the UV range: an application to OMI satellite validation." Atmospheric Chemistry and Physics 10, no. 2 (January 18, 2010): 331–40. http://dx.doi.org/10.5194/acp-10-331-2010.
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Abstract. The aerosol Single Scattering Albedo (SSA) and Absorbing Aerosol Optical Depth (AAOD) at 320.1 nm are derived at Rome site by the comparison between Brewer and modelled spectra. The UVSPEC radiative transfer model is used to calculate the UV irradiances for different SSA values, taking into account as input data total ozone and Aerosol Optical Depth (AOD) obtained from Brewer spectral measurements. The accuracy in determining SSA depends on the aerosol amount and on Solar Zenith Angle (SZA) value: SSA uncertainty increases when AOD and SZA decrease. The monthly mean values of SSA and AAOD during the period January 2005–June 2008 are analysed, showing a monthly and seasonal variability. It is found that the SSA and AAOD averages are 0.80±0.08 and 0.056±0.028, respectively. AAOD retrievals are also used to quantify the error in the Ozone Monitoring Instrument (OMI) surface UV products due to absorbing aerosols, not included in the current OMI UV algorithm. OMI and Brewer UV irradiances at 324.1 nm and Erythemal Dose Rates (EDRs) under clear sky conditions, are compared as a function of AAOD. Three methods are considered to investigate on the applicability of an absorbing aerosol correction on OMI UV data at Rome site. Depending on the correction methodology, the bias value decreases from 18% to 2% for spectral irradiance at 324.1 nm and from 25% to 8% for EDR.
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Delamere, C., C. Jakins, and E. Lewars. "On the generation of oxirene and dimethyloxirene by retro-DielsAlder reactions, and reactions of dimethyloxirene: a computational study." Canadian Journal of Chemistry 80, no. 1 (January 1, 2002): 94–105. http://dx.doi.org/10.1139/v01-194.
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The isomerization of oxirene (oxacyclopropene) (1) to ketene, dimethyloxirene (7) to dimethylketene via the oxo carbene ("ketocarbene"), and the retro-DielsAlder extrusion of oxirene and dimethyloxirene from their formal adducts (9 and 24, respectively) with benzene were studied computationally. All species were optimized at the MP2(fc)/631G(df,p) level; the species involving 1 were also subjected to MP2(fc)/631G(df,p) frequency and single-point CCSD(T)/631G(df,p) calculations. At the CCSD(T)/631G(df,p)//MP2(fc)/631G(df,p) level 1 isomerized to ketene in one step with a barrier of 2.8 kJ mol1 and a reaction energy of 320.6 kJ mol1. The extrusion of 1 from 9 had a late transition state and activation and reaction energies of 264.2 and 214.2 kJ mol1, respectively, cf. cyclopropene extrusion from its adduct (192.3 and 95.9 kJ mol1), indicating an antiaromatic destabilization energy of 214.2 95.9 = 118 kJ mol1 for 1. The carbene 8 from ring-opening of 7 lay 10.9 kJ mol1 above 7 (CCSD(T)/631G(df,p)//MP2(fc)/631G(df,p)), but the transition state could not be found; 8 isomerized to dimethylketene (252.7 kJ mol1 below 7) with a barrier of 16.4 kJ mol1, and to s-(Z)- and s-(E)-butenone with barriers of 28.5 and 35.4 kJ mol1, respectively. The UV (TDDFT, B3P86/6311++G**//MP2(fc)/631G(df,p)) spectra of 1 and 7 were calculated. Discrepancies were seen between the calculated IR spectra of 7 (bis(trifluoromethyl)oxirene) and perfluoro ethyl methyloxirene, and those attributed to these species in earlier matrix-isolation work. Key words: oxirene, dimethyloxirene, ab initio, retro-DielsAlder, DielsAlder.
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Feng, Yadong, Yan Liang, Bin Yao, Jiajia Xu, Juncai Zang, Youyu Zhang, Jiong Zhang, et al. "A Rapid Cytological Screening as pre-Endoscopy Screening for Early Esophageal Squamous Cell Lesions: A Prospective Pilot Study from a Chinese Academic Center." Technology in Cancer Research & Treatment 21 (January 2022): 153303382110662. http://dx.doi.org/10.1177/15330338211066200.
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Background: Cytological detection of early esophageal squamous cell carcinoma (ESCC) remains challenging. Therefore, we introduced a rapid cytological screening method and evaluated its efficacy as a pre-endoscopy screening for early ESCC and precursor lesions. Methods: This method consisted of a sponge sample retrieval, automatic liquid-based cytological treatment and slides preparation, computer-assisted screening and manual diagnosis. Efficacy for detection of early ESCC and precursor lesions was evaluated. Also, diagnostic efficiency was compared with manual diagnosis. Results: Eighty-three patients with early ESCC and precursor lesions and 2,090 asymptomatic participants with high risks of ESCC were enrolled. Whole procedure was accomplished within two working days. Abnormal cells were detected in all 83 patients, and in 272 (13.01%) subjects among 2,090 asymptomatic participants. Early ESCC, high-grade intraepithelial neoplasia, low-grade intraepithelial neoplasia and reflux esophagitis and normal endoscopic findings were detected in 8, 13, 11, 187 and 53 participants with abnormal cells, respectively. The calculated sensitivity, specificity, positive predictive value and negative predictive value for detection of early ESCC and precursor lesions were 100%, 88.34%, 11.76%, and 100%, respectively. Compared with manual diagnosis, this method was accomplished in a shorter time duration (5.4 ± 0.45 min vs 320.2 ± 132.4 min, p < 0.001), a higher diagnostic accuracy (96.7% vs74.4%, p = 0.015) and a better inter-observer agreement (93.3% vs66.7%, K = 0.286, p < 0.001). Conclusions: Our study provides a promising methodology as pre-endoscopy screening for early ESCC and precursor lesions.
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Němčanský, Jan, Alexandr Stěpanov, Miroslav Veith, Michal Koubek, Adam Kopecký, Sabina Němčanská, David Beran, and Jan Studnička. "Effect of baseline central retinal thickness on the results of treatment of diabetic macular edema with aflibercept: Real-Life Evidence in the Czech Republic." Czech and Slovak Ophthalmology 78, no. 2 (March 21, 2022): 64–70. http://dx.doi.org/10.31348/2022/9.
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Aim: Presentation of the 1-year results of aflibercept treatment in patients suffering from diabetic macular edema (DME) and comparison of the response to treatment of patients with different baseline central retinal thickness (CRT). Methods: This was a multicentre, retrospective observational study of a series of cases. Patients with DME were treated in a fixed regimen (5 injections at 1-monthly intervals and then injections at 2-monthly intervals). The period of follow-up was 12 months. The development of best corrected visual acuity (BCVA) and CRT was evaluated. Measurements were performed prior to the commencement of treatment and then after 4, 6, 8, 10, and 12 months. Results: The therapeutically naive group consisted of 82 eyes of 79 patients. The total cohort of patients was divided into 3 groups according to the baseline values of CRT. The first group was composed of 28 eyes with baseline CRT < 450 μm (34.1%), the second included 25 eyes with CRT in the range of 450–550 μm (30.5%), and the third group consisted of 29 eyes with baseline CRT > 550 μm (35.4%). The average baseline BCVA and SD in the first group was 66 ±7.1 letters ETDRS optotypes, and then 70 ±7 letters, 69.6 ±7.3 letters, and 71.3 ±7 letters at the follow-ups after 4, 8, and 12 months. The average baseline value of CRT and SD in the first group was 379 ±48.6 μm, and then 337.1 ±76.5 μm, 320.2 ±74.1 μm, and 315.1 ±62.2 μm after 4, 8, and 12 months. The average baseline BCVA and SD in the second group was 64.1 ±9.7 ETDRS letters, and then 66.9 ±10 letters, 70 ±9.9 letters, and 70.5 ±11.5 letters after 4, 8, and 12 months. The average baseline value of CRT and SD in the second group was 497.4 ±76.4 μm, and then 376.5 ±106.1 μm, 360.8 ±70 μm, and 351.3 ±91.3 μm after 4, 8, and 12 months. In the third group, the average baseline value of BCVA and SD was 59.7 ±10.4 ETDRS letters, and then 65 ±10.6 letters, 64.8 ±9.6 letters, and 67 ±10 letters after 4, 8, and 12 months. The average baseline value of CRT and SD in the third group was 639.4 ±79.6 μm, and then 396.7 ±147.1 μm, 416.9 ±139.8 μm, and 368.5 ±109.9 μm after 4, 8, and 12 months. All these changes were statistically significant (p < 0.05). Conclusion: Aflibercept treatment in a fixed regimen in patients suffering from DME results in a statistically significant improvement in BCVA and a decrease in CRT in the first year of treatment. Patients with a higher baseline CRT showed the best anatomical and functional results of the 1-year treatment with aflibercept.
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Guseinova, B. M., and R. T. Musaeva. "Content of mineral substances and sugar acid complex of introduced and local breeding varieties of cherries grown in Dagestan." Rossiiskaia selskokhoziaistvennaia nauka, no. 2 (April 15, 2023): 45–51. http://dx.doi.org/10.31857/s2500262723020102.
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In sweet cherry varieties cultivated in foothill Dagestan, to establish their selection and technological priorities, the mineral composition was studied, the content of sugars and acids was determined by generally accepted analysis methods. The subjects of the study were fruits of 8 introduced and 12 local breeding varieties of sweet cherries, which, depending on the variety, contained: potassium 80.6- 312.5; calcium 10.0-35.6; sodium 9.4-48.9; magnesium 7.7-21.2; phosphorus 25.6-55.1; iron 0.19-1.02; copper 0.08-0.63; manganese 0.11-0.68 and zinc 0.31-0.94 mg%. The best in terms of the total supply of macroelements in fruits were varieties: Gudzon - 427.7; Valeriy Chkalov - 335.2; Vinka - 320.8; Lezginka- 294.6; Durona de Vinola (sek.) - 284.3; Dagestanskaya chernaya - 271.4 and Pozdnyaya Lermontova - 271.0 mg%. A large amount of microelements (2.18-1.79 mg%) were found in the fruits of the varieties Valeriy Chkalov, Gudzon, Durona de Vinola (sek.), Krupnoplodnaya, Bigarro Krainskogo, Dagestanskaya rannyaya, Dagestanskaya chernaya and Pozdnyaya Lermontova. Most varieties of sweet cherries: Polyanka, Gudzon, Vinka, Romantika, Bigarro Krainskogo, Buynakskaya chernaya, Lezginka, Leningradskaya gvardeyskaya and Pozdnyaya Lermontova, the total amount of sugars ranged from 11.2-12.8 %, and the concentration of acids was 0.63-1.10 %. The most promising for the optimization of the industrial variety of sweet cherries in the conditions of Dagestan, the use in selection work and the design of new specialized food products, were the varieties Valeriy Chkalov, Vinka, Durona de Vinola (sek.), Gudzon, Krupnoplodnaya, Bigarro Krainskogo, Dagestanskaya chernaya, Lezginka and Pozdnyaya Lermontova, distinguished by the greatest ability formation of mineral substances, sugars and acids in fruits.
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Qiu, Hongxia, Hanxin Wu, Songwen Ju, Wei Xu, Ji Xu, Xin Lv, Jinzhang Shao, and Ri Zhang. "Analysis of Clinical Features and Survival in 42 Cases of Acute Monocytic Leukemia." Blood 112, no. 11 (November 16, 2008): 3992. http://dx.doi.org/10.1182/blood.v112.11.3992.3992.
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Abstract Background: Acute monocytic leukemia (M5) is a distinct subtype of acute myeloid leukemia (AML) with characteristic biologic and clinical features. This study was designed to analyze the clinical and laboratory features, and management and survival of newly diagnosed patients at with M5. Methods: The white blood counts, immunophenotype and karyotypes were retrospectively analyzed in 42 patients (pts) with M5. The overall survival(OS)was estimated by Kaplan-Meier analysis, and the different groups were compared using log-rank test. Results: Of the 42 pts, 7 had M5a and 35 had M5b. The incidence rates of M5 in newly diagnosed patients with acute leukemia and acute myelocytic leukemia were 13.7% and 22%, respectively. 28(66.7%) pts with M5 had a higher white blood counts more than 25×109/L. 36 pts obtained the outcomes of karyotype, 14(39%) pts with an abnormal cytogenetic clone, seven (19.4%) of these patients had trisomy 8 as the sole or accompanied complex cytogenetic aberration, 5(13.8%) had a translocation involving 11q23. An immunophenotype consistent with acute monocytic leukemia (CD14) was seen in 24(57.1%) of 42 pts. 16 pts (38.1%) gave up the chemotherapy at diagnosis and the complete remission rate was 73.1% for 26 pts who received induction chemotherapy. The OS for all M5 pts was 90 days (95%CI, 51.3~128.7) and the median survival for all M5 pts was 137.5 days. The median OS for the 19 CR pts was 273 days (95% CI, 226~320.1) and 85 days (95% CI, 72.2~97.8) for the 16 NR pts (95% CI, 72.2~97.8). For 16 pts who didn’t receive chemotherapy, the median OS was 35 days (95% CI, 33~37)(P<0.0001). M5 presents hyperleukocytosis, 86.1% pts of M5 has a normal clone or trisomy 8 or a translocation involving 11q23. The overall survival of M5 pts with currently available therapy is poor.
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Rincón-Catalán, Néstor Isidro, Abumalé Cruz-Salomón, P. J. Sebastian, Sergio Pérez-Fabiel, Maritza del Carmen Hernández-Cruz, Rocío Magdalena Sánchez-Albores, Jesús Mauricio Ernesto Hernández-Méndez, et al. "Banana Waste-to-Energy Valorization by Microbial Fuel Cell Coupled with Anaerobic Digestion." Processes 10, no. 8 (August 9, 2022): 1552. http://dx.doi.org/10.3390/pr10081552.
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Banana is the most cultivated fruit plant in the world. It is produced in Latin America, Asia and Africa. India and China are the world’s largest banana producers, with almost 41% of the world’s production. This fruit reaches a total world production of 158.3 million tons per year. However, during their production cycle, the banana agroindustry produces large volumes of solid waste derived from overripe fruit. It contributes between 8–20 percent of the waste (around 100 kg of banana waste for every ton of banana produced). Therefore, the use of overripe banana waste represents a huge opportunity for bioenergy production. This work demonstrates that banana waste can be further used for power generation using a microbial fuel cell (MFC) coupled with anaerobic digestion (AD). First, the maximum methane production (MMP), methane production rate (MPR) and biochemical methane potential (BMP) were measured using an anaerobic batch bioreactor for 64 days of monitoring. Finally, the digestate generated from AD was used in the MFC to determine the polarization curve, maximum voltage, maximum power density (MPD), resistance and current. As a result, the AD generated an MMP of 320.3 mL, BMP of 373.3 mLCH4/gVS and MPR of 18.6 mLCH4/Lb⋅day. The MFC generated 286 mV (maximum voltage), 41.3 mW/m2 (MPD), 580.99 Ω (resistance) and 0.0002867 A (current). Both processes together produced a total bioenergy of 13.38 kJ/gVS. This coupled system showed a suitable and promising use of banana waste for ecofriendly bioenergy generation. Therefore, this feedstock could be taken advantage of for generating sustainable processes and developing a circular economy in the banana agroindustry.
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Wang, Minghao, Praveen V. Mummaneni, Zhuo Xi, Chih-Chang Chang, Joshua Rivera, Jeremy Guinn, Rory Mayer, and Dean Chou. "Lower Hounsfield units on CT are associated with cage subsidence after anterior cervical discectomy and fusion." Journal of Neurosurgery: Spine 33, no. 4 (October 2020): 425–32. http://dx.doi.org/10.3171/2020.3.spine2035.
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OBJECTIVEA consequence of anterior cervical discectomy and fusion (ACDF) is graft subsidence, potentially leading to kyphosis, nonunion, foraminal stenosis, and recurrent pain. Bone density, as measured in Hounsfield units (HUs) on CT, may be associated with subsidence. The authors evaluated the association between HUs and subsidence rates after ACDF.METHODSA retrospective study of patients treated with single-level ACDF at the University of California, San Francisco, from 2008 to 2017 was performed. HU values were measured according to previously published methods. Only patients with preoperative CT, minimum 1-year follow-up, and single-level ACDF were included. Patients with posterior surgery, tumor, infection, trauma, deformity, or osteoporosis treatment were excluded. Changes in segmental height were measured at 1-year follow-up compared with immediate postoperative radiographs. Subsidence was defined as segmental height loss of more than 2 mm.RESULTSA total of 91 patients met inclusion criteria. There was no significant difference in age or sex between the subsidence and nonsubsidence groups. Mean HU values in the subsidence group (320.8 ± 23.9, n = 8) were significantly lower than those of the nonsubsidence group (389.1 ± 53.7, n = 83, p < 0.01, t-test). There was a negative correlation between the HU values and segmental height loss (Pearson’s coefficient −0.735, p = 0.01). Using receiver operating characteristic curves, the area under the curve was 0.89, and the most appropriate threshold of HU value was 343.7 (sensitivity 77.1%, specificity 87.5%). A preoperative lower HU is a risk factor for postoperative subsidence (binary logistic regression, p < 0.05). The subsidence rate and distance between allograft and polyetheretherketone (PEEK) materials were not significantly different (PEEK 0.9 ± 0.7 mm, allograft 1.0 ± 0.7 mm; p > 0.05).CONCLUSIONSLower preoperative CT HU values are associated with cage subsidence in single-level ACDF. Preoperative measurement of HUs may be useful in predicting outcomes after ACDF.
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Saud, Shirjana, Duc Ba Nguyen, Seung-Geon Kim, Ho Won Lee, Seong Bong Kim, and Young Sun Mok. "Improvement of Ethylene Removal Performance by Adsorption/Oxidation in a Pin-Type Corona Discharge Coupled with Pd/ZSM-5 Catalyst." Catalysts 10, no. 1 (January 17, 2020): 133. http://dx.doi.org/10.3390/catal10010133.
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The adsorption and plasma-catalytic oxidation of dilute ethylene were performed in a pin-type corona discharge-coupled Pd/ZSM-5 catalyst. The catalyst has an adsorption capacity of 320.6 μ mol g cat − 1 . The catalyst was found to have two different active sites activated at around 340 and 470 °C for ethylene oxidation. The removal of ethylene in the plasma catalyst was carried out by cyclic operation consisting of repetitive steps: (1) adsorption (60 min) followed by (2) plasma-catalytic oxidation (30 min). For the purpose of comparison, the removal of ethylene in the continuous plasma-catalytic oxidation mode was also examined. The ethylene adsorption performance of the catalyst was improved by the cyclic plasma-catalytic oxidation. With at least 80% of C2H4 in the feed being adsorbed, the cyclic plasma-catalytic oxidation was carried out for the total adsorption time of 8 h, whereas it occurred within 2 h of early adsorption in the case of catalyst alone. There was a slight decrease in catalyst adsorption capability with an increased number of adsorption cycles due to the incomplete release of CO2 during the plasma-catalytic oxidation step. However, the decreased rate of adsorption capacity was negligible, which is less than one percent per cycle. Since the activation temperature of all active sites of Pd/ZSM-5 for ethylene oxidation is 470 °C, the specific input energy requirement by heating the feed gas in order to activate the catalyst is estimated to be 544 J/L. This value is higher than that of the continuous plasma-catalytic oxidation (450 J/L) for at least 86% ethylene conversion. Interestingly, the cyclic adsorption and plasma-catalytic oxidation of ethylene is not only a low-temperature oxidation process but also reduces energy consumption. Specifically, the input energy requirement was 225 J/L, which is half that of the continuous plasma-catalytic oxidation; however, the adsorption efficiency and conversion rate were maintained. To summarize, cyclic plasma treatment is an effective ethylene removal technique in terms of low-temperature oxidation and energy consumption.
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Mirlashari, Mohammad Reza, Ingrid Randen, and Jens Kjeldsen-Kragh. "Glycogen Synthase Kinase-3β (GSK-3β) Inhibition Induces Apoptosis In Leukemic Cells through Mitochondria-Dependent Pathway." Blood 116, no. 21 (November 19, 2010): 2889. http://dx.doi.org/10.1182/blood.v116.21.2889.2889.
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Abstract Abstract 2889 GSK-3β is a multifunctional kinase that plays a role in several signaling pathways. Due to the contradictory roles of GSK-3β as a mediator of both cell survival and apoptosis, we have examined the role of GSK-3β for proliferation and apoptosis in leukemic cell lines KG1a, K562 and CMK. GSK-3β was selectively inhibited by the small-molecule SB-415286. Treatment of leukemia cells with SB-415286 (40 μM) for 72 hr approximately halved cell growth in all three cell lines. SB-415286 also showed a concentration-dependent stabilization of intracellular β-catenin: In KG1a cells the mean fluorescence intensity (MFI) [± 95% CI] was 3.1 [± 1.7] in untreated cells vs. 423 [± 24] in treated cell. The figures for the K562 and CMK cell lines were: 2.8 [± 1.6] vs. 353.2 [± 11.1], and 6.8 [± 4.0] vs. 320.2 [± 23.7], respectively. Cell cycle analysis was carried out to examine if the growth inhibition was caused by arrest in cell cycle and/or induction of apoptosis. We found that SB-415286 caused cell cycle arrest in the G2/M phase and accumulation of events corresponding to the subG1 phase, indicative of DNA fragmentation. The subG1 population was 45%, 34% and 17% in KG1a, K562 and CMK cells, respectively. To confirm that the increase of the subG1 fraction represented an apoptotic effect of the GSK-3β inhibition, we analyzed phosphatidylserine (PS) externalization and plasma membrane integrity. We found that SB-415286 caused a considerable increase of the proportion of early apoptotic cells, i.e. cells that were annexin V-positive and 7-AAD-negative: Mean [± 95% CI] in KG1a cells increased from 6.2% [± 1.2%] in untreated cells to 38% [± 3.1%] in treated cells. The figures for the K562 and CMK cell lines were: 3.0% [± 1.2%] vs. 29% [± 3.3%], and 3.9% [± 1.0%] vs. 16.0% [± 1.1%], respectively. Apoptosis signaling can be initiated by extracellular (death receptor) and/or intracellular (mitochondrial) signals. Flow cytometric analysis of cells stained by a dual-fluorescent mitochondrial dye JC-1 showed that 5–11% of untreated leukemic cells had low mitochondrial membrane potential. After 72 hr exposure to SB-415286 the mean [±95% CI] loss of the mitochondrial potential was found in 23% [± 2.0%], 33% [± 3.5%] and 42% [± 3.8%], in CMK, K562 and KG1a cells, respectively. Since drug treatment in some cell types may result in activation of both the intrinsic or extrinsic cell-death pathway in a parallel manner, we investigated if the external pathway is involved in SB-415286-induced apoptosis. For this purpose we assessed caspase-8 activation by flow cytometry. After 72 hr of treatment of CMK, K562 and KG1a cells the caspase-8 activities compared, to untreated cells, had increased 3.7-fold, 3.9-fold, and 4.4-fold, respectively. In some cell types, the extrinsic cell-death pathway leads to the cleavage of Bid (pro-apoptotic member of the Bcl-2 family) by caspase-8, generating a truncated version of the protein (tBid) which in turn activates the mitochondrial apoptotic pathway. Therefore, we determined whether depolarization of the mitochondrial membrane in the leukemic cell lines was an effect of activated caspase-8 or a direct effect of SB-415286. For this purpose Z-IETD-FMK (25 μM), a specific inhibitor of caspase-8, was applied to the cells for 2 hr. We found that inhibition of caspase-8 did not prevent SB-415286-induced apoptosis assessed by PS externalization. This indicates that activation of caspase-8 is part of the intrinsic apoptotic pathway and occurs downstream of mitochondria membrane potential depolarization mediated by other caspases. Taken together, our observations suggest that inhibition of GSK-3β induces apoptosis of leukemic cells by depolarizing the mitochondria membrane. Thus, inhibition of GSK-3β could be an attractive target for treatment of leukemia. Disclosures: No relevant conflicts of interest to declare.
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Reinthaller, A., P. Sevelda, and L. A. Hefler. "Preoperative serum vascular endothelial growth factor as a prognostic parameter in ovarian cancer." Journal of Clinical Oncology 24, no. 18_suppl (June 20, 2006): 10093. http://dx.doi.org/10.1200/jco.2006.24.18_suppl.10093.
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10093 Objective: Serum vascular endothelial growth factor (VEGF) levels have been shown to be associated with an adverse outcome in patients with ovarian cancer. We studied the clinical value of serum VEGF as an independent prognostic parameter. Methods: In the present study, we ascertained preoperative serum VEGF in a series of 314 patients with ovarian cancer. VEGF serum were evaluated in 45 new cases. Serum VEGF was evaluated prior to primary surgery in all patients. The re-analysis of previously published data comprised a total of 269 cases. Patients were treated between 1990 and 2003. Mean duration of follow-up was 38.9 (32.4) months. Patients with epithelial ovarian cancer were included into the present study, patients with other malignant ovarian tumors, borderline tumors, and benign adnexal masses were excluded. Serum VEGF was evaluated prior to primary surgery using an enzyme linked immunosorbent assay (Quantikine Human VEGF Immunoassay; R&D Systems, Minneapolis, MN) in all studies. Results were correlated with clinical data. Results: Median serum VEGF was 407 (238–746) pg/mL. Serum VEGF was associated with serum CA 125 (p=0.003) and residual tumor mass (p=0.02; residual tumor mass < 1cm: 375.5 [209.5–608.9] pg/mL vs. residual tumor mass ≥ 1cm: 625.2 [320.7–1046.7] pg/mL). Serum VEGF was not associated with FIGO stage (p=0.5), lymph node involvement (p=0.2), tumor grade (p=0.2), and patients’ age (p=0.08). In a univariate Kaplan-Meier analysis, FIGO stage, residual tumor mass, tumor grade, patients’ age, serum CA 125, and preoperative serum VEGF were associated with overall survival. In a multivariate Cox regression model, higher FIGO stage, presence of residual tumor mass after primary surgery, and higher serum VEGF were independently associated with a shortened overall survival. Planned subgroup analysis was performed for patients with ovarian cancer FIGO stage I. In a multivariate Cox regression model, higher tumor grade and higher serum VEGF were the only independent prognosticators for overall survival. Patients with FIGO stage I ovarian cancer and a serum VEGF ≥ 380 pg/mL had a 8-fold increased risk for experiencing cancer related death. Conclusion: Serum VEGF is an independent prognostic parameter in patients with all stages of ovarian cancer. No significant financial relationships to disclose.
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Csapó, János, and Szidónia Salamon. "A kanca kolosztrumának és tejének összetétele – Irodalmi összefoglaló." Tejgazdaság - Hungarian Dairy Journal 75, no. 1 (July 9, 2018): 29–42. http://dx.doi.org/10.34100/tejgazdasagvol75iss1pp29-42.
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Manapság Nyugat Európában, mind emberi táplálék, jelentősen megnőtt az érdeklődés a kancatej iránt. Sokan úgy gondolják, hogy a kancatej különféle anyagcsere betegségek esetében gyógyhatással rendelkezik, az ára is jelentősen megnőtt a piacon, ezért szükség volt a kancatejet, mint emberi táplálékot értékelni. Mivel kevés adat állt rendelkezésre az összetételről, a szerzők meghatározták a kancatej összetételét. A kísérlet célja volt az is, hogy elemezzék a változásokat az elléstől a laktáció 45. napjáig. Írásukban összegzik kísérleteik eredményeit, és azokat hasonlítva az irodalmi adatokhoz, áttekintést adnak a kanca kolosztrumának és tejének összetételéről.Megállapították, hogy közvetlenül az ellés után a kolosztrum összesfehérje-, savófehérje-, kazein- és NPN tartalma 16.41, 13.46, 2.95 és 0.052%, mely a laktáció 2. és 5. napja között 4.13, 2.11, 2.02 és 0.043%-ra, a 8. és 45. nap között pedig 2.31, 1.11, 1.20 és 0.031%-ra csökken. A valódi fehérje és a savófehérje aránya ebben a periódusban csökken, míg a kazein és az NPN aránya nő. A kolosztrum és a tej aminosav tartalma csökken a laktáció 45. napjáig, míg a tejfehérje legtöbb esszenciális aminosava (treonin, valin, cisztin, tirozin és lizin) csökken, a glutaminsav- és a prolin-tartalom pedig nő az ellés után. A tejfehérje biológiai értéke az ellés után közvetlenül a legmagasabb (132.3), köszönhetően igen magas treonin- és lizintartalmának. Ez az érték a laktáció 5. napjáig 119.7-re, a 45. napjáig pedig 107.9-re csökken.A kolosztrum és a tej szárazanyag- és zsírtartalma közvetlenül az ellés után 24.25 és 26.28%, valamint 2.85 és 2.93%, a 2. és 5. nap között 12.15 és 12.78%, valamint 2.05 és 2.17% között, a laktáció 8. és 45. napja között pedig 10.37 és 10.61%, valamint 1.04 és 1.32% között változott. A tejzsír kaprinsav-, a kaprilsav-, a laurinsav-, a mirisztinsav- és a palmitinsav-tartalma nőtt, míg a sztearinsav-, az olajsav-, a linolsav- és a linolénsav-tartalma csökkent a laktáció folyamán. A kancatej zsírja több kaprilsavat, kaprinsavat, laurinsavat, linolsavat és linolénsavat, és kevesebb sztearinsavat, mirisztinsavat és palmitinsavat tartalmazott, mint a tehéntejé. A kancatej esszenciális zsírsavtartalma magasabb volt, mint a tehéntejé.A kolosztrum A-, D-, K- és C-vitamin-tartalma (0.88, 0.0054, 0.043, 23.8 mg/kg) 1.4 és 2.6-szorosa volt a normál tejének (0.34, 0.0032, 0.029, 17.2 mg/kg). Nem volt szignifikáns különbség a kolosztrum és a tej E-vitamin-tartalmában.A kolosztrum hamutartalma szignifikánsan nagyobb (0.592%), mint a normál tejé (0.405%). Az ellés után közvetlenül volt a legalacsonyabb a kolosztrum kalcium-tartalma (747.7 mg/kg), mely az 5. napon érte el maximumát (953.7 mg/kg). A cink- és réztartalom az 5. napon mutatott maximum után csökkent, míg a mangán koncentrációja az 5. napi maximum után változatlan maradt. A kolosztrum és a tej makro- és mikroelem-tartalmára az alábbiakat határozták meg: kálium, 928.6 és 517.2; nátrium, 320.0 és 166.6; kalcium, 747.7 és 822.9; foszfor, 741.7 és 498.8; magnézium, 139.7 és 65.87; cink, 2.95 és 1.99; vas, 0.996 és 1.209; réz, 0.606 és 0.249 és mangán, 0.0447 és 0.0544 mg/kg. A kancatej alacsony nátrium-tartalma előnyös lehet a szív érrendszeri panaszokkal, ill. magas vérnyomással küzdő emberek számára.
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Sartori, R., G. M. Machado, M. M. Guardieiro, M. R. Bastos, L. Leme, E. Siqueira Filho, R. Rumpf, and M. A. N. Dode. "135 IN VITRO DEVELOPMENT OF IN VIVO PRODUCED EMBRYOS FROZEN AT MORULA OR BLASTOCYST STAGES." Reproduction, Fertility and Development 20, no. 1 (2008): 148. http://dx.doi.org/10.1071/rdv20n1ab135.
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This study was designed to compare cryotolerance between morulae and blastocysts collected from superovulated heifers. Twenty pubertal beef heifers (10 Nelore and 10 crossbred Nelore � Simmental) were superovulated with 100 mg of FSHp (Folltropin-V, Bioniche, Ontario, Canada), and embryos were collected and evaluated 7 days after estrus. Grades 1 and 2 embryos (IETS) were divided into four groups: morulae cryopreserved (MC) in liquid nitrogen (n = 24); blastocysts cryopreserved (BC; n = 19); morulae fresh (MF; n = 23); and blastocysts fresh (BF; n = 18). For freezing, embryos were immersed in ethylene glycol (Ethylene Glycol Freeze Plus with 0.1 m sucrose, Bioniche, Pullman, WA, USA), and a standard protocol (cooling rate of –0.5�C/min) was used. Prior to in vitro culture, embryos were removed from nitrogen, kept at room temperature for 5 s, and put in a water bath at 30�C for 20 s. Within 5 h after recovery, thawed and fresh embryos were washed five times in holding solution (Holding Plus, Bioniche), transferred to synthetic oviduct fluid medium (SOF, Nutricell, Campinas, SP, Brazil), and cultured for 72 h. Embryos were evaluated at 48 and 72 h of culture. After the last evaluation, degenerate and non-hatched embryos were removed from culture, and the remaining embryos were measured by a graduated ocular coupled to the Motic Images Plus 2.0 program. Hatched blastocysts were kept in culture for an additional 48 h for post-hatching development assessment. For post-hatching culture PHD medium (Brand�o DO et al. 2005 Biol. Reprod. 71, 2048–2055) was added into each well, to have a final composition of 50% SOF and 50% SOF PHD. At 120 h of culture (48 h of PHD culture) only morphologically normal blastocysts were measured. Comparison among groups was performed by ANOVA or chi-square test. Data are presented as mean � SEM. After 48 h of culture, hatching rate (%) was significantly lower in cryopreserved (MC = 8.3 and BC = 21.5) than in fresh (MF = 56.5 and BF = 77.8) embryos (P < 0.05). However at 72 h, hatching rate was similar among BC (75.9), MF (78.3), and BF (88.9), being MC (41.7) still lower (P < 0.05). The diameter (µm) of hatched embryos after 72 h of culture was 272.8 � 27.1a (n = 8), 320.6 � 18.6ab (n = 14), 385.3 � 14.2c (n = 17), and 378.0 � 22.0bc (n = 16) for MC, BC, MF, and BF, respectively (a–cP < 0.05). After 120 h of culture, the diameter of MC (379.0 � 39.9; n = 8), although similar to BC (495.4 � 59.6; n = 10), was smaller than MF (509.1 � 36.5; n = 11) and BF (511.8 � 41.2; n = 14). The results of this study with zebu cattle suggest that morulae are less resistant to cryopreservation in liquid nitrogen than blastocysts. Moreover, frozen/thawed embryos, when put in culture, present a slower development compared with fresh embryos. Financial support from CNPq and FAPESP from Brazil.
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Myniv, R. M. "Modern tendencies of development of meat cattle breeding in Ukraine in conditions of European integration." Scientific Messenger of LNU of Veterinary Medicine and Biotechnologies 21, no. 92 (May 11, 2019): 3–8. http://dx.doi.org/10.32718/nvlvet-e9201.
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European integration processes have become an indispensable feature and direction of development of meat cattle breeding in Ukraine. At the same time, the interrelated activity of the state and agricultural enterprises, aimed at ensuring food security of the state, was of paramount importance. Sales volumes for slaughter of cattle and poultry by all categories of farms increased in 2018, compared to 2017, by 34.3 thousand tons, including agricultural enterprises increased by 49.9 thousand tons, and households decreased by 15.6 thousand. The volume of sales of cattle and poultry on slaughter in all categories of farms has increased 11 regions, in agricultural enterprises – 11, in farms of the population – 8 oblasts. In January-November 2018, the overall indicator for livestock and poultry farming in agricultural enterprises increased by 65.5 thousand tons compared to the corresponding period of last year due to an increase in poultry production by 81.9 thousand tons. The stock of cattle on January 1, 2019 in all categories of farms decreased, against the corresponding period of 2018, by 152.0 thousand heads, including 27.7 thousand in agricultural enterprises, and in the farms of the population – by 124.3 thousand goals. In 2018, in all categories of farms, the number of pigs, as compared to 2017, decreased by 123.4 thousand heads, including 124.3 thousand heads in the households, and by 70 per cent in agricultural enterprises, 5 thousand heads. The bovine population in all categories of farms as of January 1, 2019 increased by 5957.5 thousand heads compared to the corresponding period of last year, including 5474.3 thousand in agricultural enterprises, and 483.2 thousand in households , while the realization of slaughter of cattle and poultry increased by 34.3 thousand tons in live weight (1.0%). According to customs authorities in 2018: exports of meat and meat products in terms of meat in January-November 2018 amounted to 368.2 thousand tons, which is January-November 2017 (320.3 thousand tons). t) more by 47.9 thousand tons, or by 15.0%. At the same time, in monetary terms, exports increased by $ 118.2 million. The United States, or 24.1%, amounted to $ 608.6 million. USA; imports of meat and meat products in terms of meat in January-November 2018 amounted to 239.1 thousand tons, which is more compared to 2017 (190.3 thousand tons) by 48.8 thousand tons, or 25.6%. At the same time, in monetary terms, imports were at the level of 170.0 million USD. US $ 55.6 million The United States (or 48.6%) more than last year ($ 114.4 million).
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De Bock, V., H. De Backer, R. Van Malderen, A. Mangold, and A. Delcloo. "Relations between erythemal UV dose, global solar radiation, total ozone column and aerosol optical depth at Uccle, Belgium." Atmospheric Chemistry and Physics 14, no. 22 (November 20, 2014): 12251–70. http://dx.doi.org/10.5194/acp-14-12251-2014.
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Abstract. At Uccle, Belgium, a long time series (1991–2013) of simultaneous measurements of erythemal ultraviolet (UV) dose (Sery), global solar radiation (Sg), total ozone column (Q_{O3}$) and aerosol optical depth (τaer) (at 320.1 nm) is available, which allows for an extensive study of the changes in the variables over time. Linear trends were determined for the different monthly anomalies time series. Sery, Sg and QO3 all increase by respectively 7, 4 and 3% per decade. τaer shows an insignificant negative trend of −8% per decade. These trends agree with results found in the literature for sites with comparable latitudes. A change-point analysis, which determines whether there is a significant change in the mean of the time series, is applied to the monthly anomalies time series of the variables. Only for Sery and QO3, was a significant change point present in the time series around February 1998 and March 1998, respectively. The change point in QO3 corresponds with results found in the literature, where the change in ozone levels around 1997 is attributed to the recovery of ozone. A multiple linear regression (MLR) analysis is applied to the data in order to study the influence of Sg, QO3 and τaer on Sery. Together these parameters are able to explain 94% of the variation in Sery. Most of the variation (56%) in Sery is explained by Sg. The regression model performs well, with a slight tendency to underestimate the measured Sery values and with a mean absolute bias error (MABE) of 18%. However, in winter, negative Sery are modeled. Applying the MLR to the individual seasons solves this issue. The seasonal models have an adjusted R2 value higher than 0.8 and the correlation between modeled and measured Sery values is higher than 0.9 for each season. The summer model gives the best performance, with an absolute mean error of only 6%. However, the seasonal regression models do not always represent reality, where an increase in Sery is accompanied with an increase in QO3 and a decrease in τaer. In all seasonal models, Sg is the factor that contributes the most to the variation in Sery, so there is no doubt about the necessity to include this factor in the regression models. The individual contribution of τaer to Sery is very low, and for this reason it seems unnecessary to include τaer in the MLR analysis. Including QO3, however, is justified to increase the adjusted R2 and to decrease the MABE of the model.
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van Oosterhout, J. J., F. K. Dzinjalamala, A. Dimba, D. Waterhouse, G. Davies, E. E. Zijlstra, M. E. Molyneux, E. M. Molyneux, and S. Ward. "Pharmacokinetics of Antituberculosis Drugs in HIV-Positive and HIV-Negative Adults in Malawi." Antimicrobial Agents and Chemotherapy 59, no. 10 (July 27, 2015): 6175–80. http://dx.doi.org/10.1128/aac.01193-15.
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ABSTRACTLimited data address the impact of HIV coinfection on the pharmacokinetics (PK) of antituberculosis drugs in sub-Saharan Africa. A total of 47 Malawian adults underwent rich pharmacokinetic sampling at 0, 0.5, 1, 2, 3, 4, 6, 8, and 24 h postdose. Of the subjects, 51% were male, their mean age was 34 years, and 65% were HIV-positive with a mean CD4 count of 268 cells/μl. Antituberculosis drugs were administered as fixed-dose combinations (150 mg rifampin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol) according to recommended weight bands. Plasma drug concentrations were determined by high-performance liquid chromatography (rifampin and pyrazinamide) or liquid chromatography-mass spectrometry (isoniazid and ethambutol). Data were analyzed by noncompartmental methods and analysis of variance of log-transformed summary parameters. The pharmacokinetic parameters were as follows (median [interquartile range]): for rifampin, maximum concentration of drug in plasma (Cmax) of 4.129 μg/ml (2.474 to 5.596 μg/ml), area under the curve from 0 to 24 h (AUC0–∞) of 21.32 μg/ml · h (13.57 to 28.60 μg/ml · h), and half-life of 2.45 h (1.86 to 3.08 h); for isoniazid,Cmaxof 3.97 μg/ml (2.979 to 4.544 μg/ml), AUC0–24of 22.5 (14.75 to 34.59 μg/ml · h), and half-life of 3.93 h (3.18 to 4.73 h); for pyrazinamide,Cmaxof 34.21 μg/ml (30.00 to 41.60 μg/ml), AUC0–24of 386.6 μg/ml · h (320.0 to 463.7 μg/ml · h), and half-life of 6.821 h (5.71 to 8.042 h); and for ethambutol,Cmaxof 2.278 μg/ml (1.694 to 3.098 μg/ml), AUC0–24of 20.41 μg/ml · h (16.18 to 26.27 μg/ml · h), and half-life of 7.507 (6.517 to 8.696 h). The isoniazid PK data analysis suggested that around two-thirds of the participants were slow acetylators. Dose, weight, and weight-adjusted dose were not significant predictors of PK exposure, probably due to weight-banded dosing. In this first pharmacokinetic study of antituberculosis drugs in Malawian adults, measures of pharmacokinetic exposure were comparable with those of other studies for all first-line drugs except for rifampin, for which theCmaxand AUC0–24values were notably lower. Contrary to some earlier observations, HIV status did not significantly affect the AUC of any of the drugs. Increasing the dose of rifampin might be beneficial in African adults, irrespective of HIV status. Current co-trimoxazole prophylaxis was associated with an increase in the half-life of isoniazid of 41% (P= 0.022). Possible competitive interactions between isoniazid and sulfamethoxazole mediated by theN-acetyltransferase pathway should therefore be explored further.
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Bettiol, A., F. Fagni, I. Mattioli, G. Bagni, G. Vitiello, A. Grassi, C. Della Bella, et al. "AB0164 SERUM LEVELS OF INTERLEUKIN-36 Α TO DISTINGUISH BEHÇET’S SYNDROME AND PSORIATIC ARTHRITIS." Annals of the Rheumatic Diseases 82, Suppl 1 (May 30, 2023): 1262–63. http://dx.doi.org/10.1136/annrheumdis-2023-eular.1545.
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BackgroundBehçet’s syndrome (BS) is a rare systemic vasculitis hallmarked by oral, genital and ocular involvement, often accompanied by articular, cutaneous, vascular, neurological, and gastrointestinal manifestations [1, 2]. Articular involvement is present in up to 80% of BS patients [3], and, from a clinical point of view, it may resemble seronegative arthritis, particularly psoriatic arthritis (PsA), with which an overlap has also been described [4-6]. To this date, no specific instrumental or laboratory biomarker is available to help the differential diagnosis between BS and PsA, which currently relies only on clinical assessment and might be particularly challenging. On these bases, there is a growing interest on the identification of new laboratory biomarkers which might assist in the diagnostic process. Among them, interleukin (IL)-36 belongs to the IL-1 family and is involved in skin and joint-related inflammatory conditions [7, 8]. Increased serum levels of IL-36, especially IL-36α, have been described in PsA at synovial level [9], while no study investigated its levels in BS.ObjectivesThis study aimed to assess the ability of serum IL-36α to differentiate BS from PsA patients.MethodsA cross-sectional study was performed on a cohort of 90 adult patients with BS followed at two referral centres for BS (Behçet Center of the Careggi University Hospital of Florence, and University Hospital of Siena, Italy), 80 patients with PsA from the University Hospital Erlangen (Germany), and 80 healthy controls (HCs). Serum IL-36α concentrations were measured in blood samples using human IL-36α enzyme-linked immunosorbent assay (ELISA) kits (MyBioSource, San Diego, Ca), and compared in the three groups.ResultsSerum IL-36α concentrations were significantly higher among BS patients [median level of 201.7 (112.7 – 320.2) pg/mL] as compared to HC [16.9 (13.7-22.2); p<0.001]. Conversely, BS patients displayed significantly lower IL-36α levels as compared to the PsA group (544 (296-759); p<0.001) (Figure 1). When we investigated the ability of IL-36α to discriminate BS patients from PsA patients, an empirical optimal cut-off of 420.6 pg/ml displayed a specificity of 0.93, with a sensitivity of 0.70 (AUC 0.82) in discriminating PsA from BS.This cut-off displayed a good diagnostic performance also in BS patients with mucosal and ocular manifestations, i.e., the two BS involvement associated with the highest IL-36α levels, as well as in those lacking major organ involvement, who represent a challenging group from a diagnostic point of view.ConclusionSerum IL-36α is remarkably increased in patients with PsA as well as in BS, although to a lesser extent. Serum IL-36α could be a candidate biomarker for the differential diagnosis between these two conditions.References[1] Bettiol A, Front Immunol. 2019.[2] Bettiol A, Rheumatology (Oxford). 2020[3] Tursen U, Int J Dermatol. 2003[4] International Team for the Revision of the International Criteria for Behcet’s Disease, J Eur Acad Dermatol Venereol. 2014;28(3):338-47.[5] Di Scala G, J Autoimmun. 2019[6] Fagni F, Ann Rheum Dis. 2020[7] Magne D, Arthritis Res Ther. 2006.[8] Boutet MA, Clin Exp Immunol. 2016.[9] Boutet MA, Rheumatology (Oxford). 2020.Figure 1.IL-36α levels in patients with Behçet’s syndrome (BS), with psoriatic arthritis (PsA), and in healthy controls (HC).Acknowledgements:NIL.Disclosure of InterestsNone Declared.
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De Bock, V., H. De Backer, R. Van Malderen, A. Mangold, and A. Delcloo. "Relations between erythemal UV dose, global solar radiation, total ozone column and aerosol optical depth at Uccle, Belgium." Atmospheric Chemistry and Physics Discussions 14, no. 11 (June 24, 2014): 16529–89. http://dx.doi.org/10.5194/acpd-14-16529-2014.
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Abstract. At Uccle, a long time series (1991–2013) of simultaneous measurements of erythemal ultraviolet (UV) dose, global solar radiation, total ozone column (TOC) and Aerosol Optical Depth (AOD) (at 320.1 nm) is available which allows for an extensive study of the changes in the variables over time. A change-point analysis, which determines whether there is a significant change in the mean of the time series, is applied to the monthly anomalies time series of the variables. Only for erythemal UV dose and TOC, a significant change point (without any known instrumental cause) was present in the time series around February 1998 and March 1998 respectively. The change point in TOC corresponds with results found in literature, where the change in ozone levels (around 1997) is attributed to the recovery of ozone. Linear trends were determined for the different (monthly anomalies) time series. Erythemal UV dose, global solar radiation and TOC all increase with respectively 7, 4 and 3% per decade. AOD shows an (insignificant) negative trend of −8% per decade. These trends agree with results found in literature for sites with comparable latitudes. A multiple linear regression (MLR) analysis is applied to the data in order to study the influence of global solar radiation, TOC and AOD on the erythemal UV dose. Together these parameters are able to explain 94% of the variation in erythemal UV dose. Most of the variation (56%) in erythemal UV dose is explained by global solar radiation. The regression model performs well with a slight tendency to underestimate the measured erythemal UV doses and with a Mean Absolute Bias Error (MABE) of 18%. However, in winter, negative erythemal UV dose values are modeled. Applying the MLR to the individual seasons solves this issue. The seasonal models have an adjusted R2 value higher than 0.8 and the correlation between modeled and measured erythemal UV dose values is higher than 0.9 for each season. The summer model gives the best performance, with an absolute mean error of only 6%. Again, global solar radiation is the factor that contributes the most to the variation in erythemal UV dose, so there is no doubt about the necessity to include this factor in the regression models. A large part of the influence of AOD is already represented by the global solar radiation parameter. Therefore the individual contribution of AOD to erythemal UV dose is so low. For this reason, it seems unnecessary to include AOD in the MLR analysis. Including TOC however, is justified as the adjusted R2 increases and the MABE of the model decreases compared to a model where only global solar radiation is used as explanatory variable.
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Badros, Ashraf, A. Rapoport, O. Goloubeva, K. Ruehle, S. Westphal, S. Hefner, and B. Meisenberg. "Phase I Trial of Bortezomib (V) in Combination with “DT-PACE”: Toxicity, Stem Cell Collection and Engraftment in Newly Diagnosed Multiple Myeloma (MM) Patients (Pts)." Blood 106, no. 11 (November 16, 2005): 2747. http://dx.doi.org/10.1182/blood.v106.11.2747.2747.
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Abstract Several studies have established the safety and efficacy of V in various regimens before stem cell mobilization and transplant (SCT). The primary objective of our study was to determine the MTD of V (3 dose levels: 0.7, 1.0, 1.3 mg/m2 days 1, 4, and 8) in combination with DT-PACE (dexamethasone 40 mg/day and thalidomide 200–400 mg/day orally x 4 days, Cisplatinum 10 mg/m2, Adriamycin 10 mg/m2, cyclophosphamide 400 mg/m2 and Etoposide 40 mg/m2 all given by IVCI for 4 days) in newly diagnosed MM. Pts received 2 cycles (C) of VDT-PACE; stem cells were collected after C 1. G-CSF 10-ug/kg/day was given from day 5 until stem cell collection (GCSF was held on day 8 of V). The secondary endpoint was to evaluate the effects of V during mobilization on engraftment. Eleven Pts enrolled, six on dose level I; 3 on dose level II and 2 on dose level III. Median age was 58 yrs (42–70), 9 were males. Four had no prior therapy and 7 had one prior cycle including DT (n=4) and DT-PACE (n=3). Median B2M was 2.9 mg/L (range: 1.9–8.5) and BM plasma cells was 45% (range: 10–80). No DLT was observed. Pts, mostly with cycle 2, had G- 3/4 hematological toxicity requiring transfusiona and neutropenic fever requiring hospitalization. G-3 toxicity included diarrhea (n= 2), (DVT= 3) despite enoxaparin, hypotension (n=3) including syncope (n=2). G-2 included bradycardia (n= 3) and peripheral neuropathy (n= 3). Stem cells were collected at a median of 13 days (range: 12–15). Pts had a median of 20.57 (range: 7.85 – 33.3) x 106 CD 34+/kg in 1 (n=4), 2 (n=6) and 3 days (n=1). Two pts collected additional cells after C 2, both received prior DT-PACE. All 11 Pts responded; CR (n=1), near CR (n=1) and PR (n=9); to date, all pts had received SCT; conditioning regimens were melphalan 200 mg/m2 (n=9) and 140 (n=2), 2 pts had tandem SCTs. Median CFU-C of the infused CD-34 cells was 320.2 (range: 57–1000) x 104/kg. Median time to ANC > 1000/mcl was 14 days (range: 13–25), plt > 20, 000/mcl was 16 days (range: 10–50) and > 50,000 was 25 days (range: 15–57). CMV antigenemia with fever and delayed engraftment was seen in one pt and autologous GVHD (skin and gut), biopsy proven, was seen in one pt. After SCT, pts achieved CR (n=3), nCR (n=4) and PR (n=4). At a median follow up of 252 days (range: 23–467), 1 pt had relapsed at 8 m with high-risk MM, hypodiploid clone. The results were compared to a control group (pts mobilized with DT-PACE; n=14). They had a median of 14.5 days to first day of phoresis (range: 11– 22) with a median 17.8 x 106 CD 34+/kg (range: 9- 35) collected in 1 (n=6), 2 (n=5) and 3 days (n=3). Median CFU-C was 540 (range: 153–1388) x 104/kg. For the control group; ANC > 1000 was reached at a median of 12 days (range: 11–20) and plt > 20000 at 18 days (range: 13–25) and > 50,000 at 19 (range: 15–38). There was no statistically significant correlation between total CD34 count and times to engraftment between both groups. There was a tendency for pts treated with V to have lower CFU-C (p=0.0565), the clinical significance is unclear. In conclusion: the VDT-PACE regimen was associated with expected and acceptable toxicities. There was a rapid response in all pts treated. Adequate numbers of stem cells were collected with prompt engraftment after SCT. VDT-PACE regimen has the advantage of short induction time prior to SCT and should be evaluated in a randomized fashion before SCT against other regimens like DT and VDT with regards to quality of life and long-term toxicities.
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Basset, Marco, Irene Defrancesco, Paolo Milani, Sara Rattotti, Andrea Foli, Marzia Varettoni, Alessandro Corso, et al. "Light Chain Amyloidosis and Non-Hodgkin's Lymphomas: A Peculiar Association with Distinct Clinical Features and Outcome." Blood 132, Supplement 1 (November 29, 2018): 2026. http://dx.doi.org/10.1182/blood-2018-99-118161.
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Abstract Bakground. The association of light chain (AL) amyloidosis with lymphoplasmacytic lymphoma/Waldenström's Macroglobulinemia is well established. However, both localized and systemic AL amyloidosis have been also reported in other types of lymphoma, but a detailed description of these cases is still lacking. Methods. We systematically searched the database of 1,415 newly diagnosed consecutive patients (pts) with AL amyloidosis of the Pavia Amyloidosis Research and Treatment Center for pts with non-lymphoplasmacytic lymphoma and AL amyloidosis, and identified 34 pts diagnosed between 2004 and 2018. Results. Seventeen pts (50%) had a diagnosis of marginal zone lymphoma (MZL), mainly extranodal MZL (EMZL). Median age at the time of lymphoma diagnosis was 65 years (45-81) and 23 pts (68%) were males. An autoimmune disease was documented in 8 pts (24%), with Sjögren Syndrome as the commonest type. Clinical characteristics of pts according to type of lymphoma (MZL vs non-MZL) and type of AL (systemic vs localized) are presented in Tables 1 and 2. The amyloid deposits were characterized as AL-type by immunoelectron microscopy or mass spectrometry in all cases. Twelve pts (35%) had a concomitant diagnosis of AL (within 12 months before or after the diagnosis of lymphoma). In 2 cases the diagnosis of lymphoma occurred after 16 and 45 months from diagnosis of AL, respectively. In 20 pts (10 MZLs), the lymphoma was diagnosed a median time of 58.6 months (range: 13.6-320.8 months) before AL diagnosis: all but 1 of these cases were treated for the underlying lymphoma and 16 of them had a complete remission at the time of AL diagnosis. Twenty-nine pts (85%) had positive serum and/or urine immunofixation and/or an abnormal free light chains ratio (FLCR), while 5 pts had no detectable monoclonal component (MC) and normal FLCR: these pts developed only localized AL amyloidosis. Localized AL was documented in 10 pts (29%), 7 of them had a MZL. Involved organs were represented by MALT sites (6 nodular pulmonary, 1 tracheobronchial, 2 skin, 1 bladder). Eleven pts with systemic AL amyloidosis died for progression of amyloidosis and 1 because of gastric cancer, while no patient with localized AL died during follow-up. The median overall survival (OS) from the diagnosis of AL amyloidosis was 42.5 months (Fig.1). Conclusions. In our series collected in a referral center, MZL is the most common non-lymphoplasmacytic lymphoma that associates with AL amyloidosis. Hematologists should be aware that MZL is associated not only with localized light chain deposition at the lymphoma site, but also with systemic AL amyloidosis. Systemic AL amyloidosis could be itself an indication to start a specific treatment for the lymphoproliferative disease, even in otherwise asymptomatic lymphomas. The presence of a MC and elevated FLC are clues for systemic AL amyloidosis. Figure 1. Figure 1. Disclosures Merlini: Prothena: Consultancy; Janssen: Consultancy; Ionis: Consultancy; Millenium: Consultancy; Akcea: Consultancy; Pfizer: Consultancy. Palladini:Janssen: Membership on an entity's Board of Directors or advisory committees; Celgene: Other: Travel support; Prothena: Honoraria.
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KRISTINA, NATALINI NOVA, and SITTI FATIMAH SYAHID. "PENGARUH AIR KELAPA TERHADAP MULTIPLIKASI TUNAS IN VITRO, PRODUKSI RIMPANG, DAN KANDUNGAN XANTHORRHIZOL TEMULAWAK DI LAPANGAN." Jurnal Penelitian Tanaman Industri 18, no. 3 (June 19, 2020): 125. http://dx.doi.org/10.21082/jlittri.v18n3.2012.125-134.
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<p>ABSTRAK<br />Langkah antisipatif pemenuhan kebutuhan massal benih temulawak<br />dilakukan dengan perbanyakan secara in vitro menggunakan medium<br />tumbuh yang murah mengandung air kelapa. Penelitian bertujuan untuk<br />menganalisis kandungan kimia air kelapa dan peranannya dalam multi-<br />plikasi tunas temulawak in vitro, serta pengaruhnya terhadap produksi<br />rimpang dan kandungan xanthorrizol. Penelitian dilakukan mulai Mei<br />2009 sampai Agustus 2010 di Laboratorium dan Kebun Percobaan Balai<br />Penelitian Tanaman Rempah dan Obat; serta Balai Besar Penelitian dan<br />Pengembangan Pascapanen Pertanian. Air kelapa yang digunakan berasal<br />dari kelapa muda (7-8 bulan) dan kelapa tua berumur (10-12 bulan).<br />Penelitian dilakukan secara bertahap, terdiri atas 4 kegiatan. Pertama,<br />analisis zat pengatur tumbuh, vitamin dan mineral dalam air kelapa<br />menggunakan metode HPLC. Kedua, pengaruh konsentrasi air kelapa (0,<br />5, 10, 15, 20, dan 25%) terhadap multiplikasi tunas temulawak in vitro.<br />Kegiatan dirancang secara acak kelompok, 3 ulangan. Pengamatan<br />meliputi parameter pertumbuhan. Ketiga, aklimatisasi dan kandungan<br />klorofil tanaman hasil in vitro. Keempat, pertumbuhan dan produksi<br />rimpang benih temulawak in vitro dalam pot berisi media tanah + pasir dan<br />analisis kandungan xanthorrizolnya. Rancangan penelitian acak kelompok,<br />3 ulangan, dan parameter pengamatan karakter pertumbuhan, produksi<br />rimpang, dan kandungan xanthorrizol. Hasil penelitian menunjukkan<br />bahwa air kelapa mengandung kinetin, zeatin, auksin, vitamin, mineral dan<br />sumber karbon yang berguna untuk multiplikasi tunas in vitro. Kandungan<br />kimia air kelapa muda lebih tinggi dibanding air kelapa tua. Medium<br />tumbuh mengandung air kelapa 15% terbaik dalam merangsang pertum-<br />buhan tunas in vitro (rata-rata 4,6 jumlah tunas per botol selama periode<br />awal pertumbuhan (8 minggu) sehingga dijadikan sebagai standar perba-<br />nyakan. Bibit temulawak hasil perbanyakan in vitro tumbuh baik (72%)<br />pada masa aklimatisasi, walaupun sebagian kecil ada yang menguning.<br />Kandungan klorofil a, b, dan total klorofil temulawak asal kultur in vitro<br />lebih tinggi dibandingkan dengan yang konvensional, dan bentuk<br />rimpangnya normal. Poduksi rimpang generasi awal (Vo) mencapai rata-<br />rata 320,2g, lebih rendah dibandingkan dengan rimpang konvensional<br />(800,5g). Kandungan xanthorrhizol temulawak hasil kultur in vitro lebih<br />rendah dibandingkan rimpang konvensional. Hasil penelitian mengindi-<br />kasikan potensi air kelapa sebagai zat pengatur tumbuh alami pada<br />temulawak in vitro.<br />Kata kunci: air kelapa, Curcuma xanthorrhiza, in vitro, xanthorrhizol,<br />hasil</p><p>ABSTRACT<br />Anticipated step for Java turmeric seed massal fulfillment was<br />conducted by in vitro using cheap growth medium enriched with coconut<br />water. The aim of the research was to analyse the chemical content of<br />coconut water and its role on java turmeric micropropagation in vitro and<br />their effect on yield and xanthorrhizol content. The experiement was<br />conducted from May 2009 to August 2009 at Indonesian Spices and<br />Medicinal Research Institute and Indonsian Center for Agricultural Post<br />Harvest Research and Development. The coconut water used comes from<br />young coconut (7-8 months) and old coconut (10-12 months). The research<br />consisted of four steps. First, analysis of growth regulator, vitamin and<br />sucrose from coconut water using HPLC method. Second, the effect of<br />several concentration od water coconut: 0, 5, 10, 15, 20, and 25% on in<br />vitro multiplication. The experiment was arranged in completely block<br />design with three replicates. The parameters observed were growth of<br />culture during in vitro. Third, acclimatization and chlorophyll content of<br />plant derived from in vitro and fourth, growth, and yield of java turmeric<br />seed on pot containing soil + sand as growth medium and xanthorrhizol<br />analysis. The experiment was arranged in completely block design with<br />three replicates. The parameters observed were growth characters, yield<br />and xnthorrhizol content. Result showed that coconut water contain<br />kinetin, zeatin, auksin, vitamin, mineral and carbon source which used for<br />in vitro shoots multiplication. The chemical of young coconut water was<br />higher than old coconut. The growth medium enriched with 15 % coconut<br />water gave the best result on inducing shoots in vitro (average 4.6<br />shoots/bottle during 8 weeks culture), so it’s used as multiplication<br />standard. Java turmeric seed from in vitro culture grew well (72%) on<br />acclimatization. Although, some of them were greenish.The content of a,<br />b, and total chlorophyll of java ginger from in vitro culture was higher than<br />conventional rhizome and have a normal rhizome. The production on Vo<br />(plantlet generation) around 320.2 g/plant, is lower than conventional<br />rhyzome (800.5 g). Xanthorhizol and essential oil content of Java turmeric<br />from in vitro seed were lower than conventional rhyzome. Result research<br />indicated potency of the coconut water as a nature growth regulator in<br />vitro.<br />Key words: coconut water, Curcuma xanthorrhiza, in vitro, growth,<br />xanthorrhizol, yield</p>
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Papassotiriou, Gerasimos-Petros, Evangelos Terpos, Efstathios Kastritis, Maria Gkotzamanidou, Filia Apostolakou, Evangelos Eleutherakis-Papaiakovou, and Meletios Athanasios Dimopoulos. "High Circulating Vascular Endothelial Growth Factor Receptor-1 Correlates with Increased Microvessel Density and Inferior Survival in Newly-Diagnosed Patients with Multiple Myeloma Who Receive Frontline Therapy with Novel Agent-Based Regimens." Blood 118, no. 21 (November 18, 2011): 5082. http://dx.doi.org/10.1182/blood.v118.21.5082.5082.
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Abstract Abstract 5082 Vascular Endothelial Growth Factor Receptor-1 (VEGF-R1) is a receptor tyrosine kinase specific for the angiogenic factors VEGF-A, VEGF-B and placenta growth factor (PlGF), which is also a member of the VEGF family. In contrast to VEGF, the role of PlGF and VEGFR-1 in neovascularization is less clear. Angiogenesis is increased in patients with multiple myeloma (MM) and correlated with inferior outcome in several studies. The role of PlGF and VEGFR-1 has not been evaluated in MM. Therefore, we measured the circulating levels of PlGF and VEGFR-1: i) in 64 patients with newly diagnosed myeloma: 16 with asymptomatic disease (7M/9F; median age 59 years, range 37–82 years) and 48 with symptomatic myeloma (30M/18F; median age 70 years, range 45–89 years; ii) in 8 patients with MGUS (4M/4F; median age 72 years, range 39–84 years); and iii) in 20 healthy, gender and age-matched controls. PlGF and sVEGFR-1 were measured in serum samples using an electrochemiluminescence immunoassays (ECLIA) on a cobas e411 immunology analyzer (Roche Diagnostics, Mannheim, Germany). We also explored possible correlations between PlGF and VEGFR-1 circulating levels with clinical and laboratory values of the patients including microvessel density (MVD) of the bone marrow trephine biopsies and survival. Immunohistochemical identification of microvascular endothelial cells was performed in the trephine biopsies of MGUS and MM patients using a human monoclonal antibody against CD34 (DAKO A/S, Glostrup, Denmark). In each biopsy sample, microvessels were counted in at least 3 independent hot spots per section and the MVD of a bone marrow specimen was calculated as the mean value of all independent readings and recorded as the number of microvessels per ×400 field. When the microvessel count was 1–2, angiogenesis was characterized as low grade, while intermediate grade angiogenesis was defined by the presence of a microvessel count of 3–6 and high grade angiogenesis by the presence of microvessel count ≥7. Compared to controls, patients with symptomatic MM had elevated circulating PlGF (median: 19.5 pg/ml, range: 6.7–91.3 pg/ml vs. 16.1 pg/ml, 10.9–25.0 pg/ml of control group; p<0.01) and elevated VEGFR-1 levels (88.6 pg/ml, 51.5–320 pg/ml vs. 73.3 pg/ml, 62.9–100.8 pg/ml; p<0.001). Patients with MGUS and asymptomatic MM had no differences compared to controls for PlGF and VEGFR-1. In myeloma patients there was a strong correlation between circulating PlGF and VEGFR-1 levels (r=0.62, p=0.009 for asymptomatic patients and r=0.36, p=0.01 for symptomatic MM). PlGF also correlated with IL-6 (r=0.68, p<0.01) and high sensitivity CRP (r=0.5031, p<0.01) in MM patients. Of 16 patients with asymptomatic myeloma, 11 (68%) had low grade angiogenesis in the trephine biopsies and 5 (31%) intermediate grade angiogenesis; no one had high grade angiogenesis. There was no difference for PlGF levels between patients with low and intermediate grade angiogenesis in asymptomatic myeloma. However, patients with asymptomatic myeloma and intermediate grade angiogenesis had elevated VEGFR-1 (98.3 pg/ml, 87.1–148.9 pg/ml) compared to patients with low grade angiogenesis (72.3 pg/ml, 63.7–95.8 pg/ml). Similar results were obtained for patients with symptomatic myeloma. Of those, 18 (37%) had low grade angiogenesis in the trephine biopsies, while 20 (41%) had intermediate grade and 10 (20%) high grade angiogenesis. The median values and ranges of VEGFR-1 for low, intermediate and high grade angiogenesis were: 75.1 pg/ml (51.5–109.1 pg/ml), 94.2 pg/ml (61.2–143.8 pg/ml) and 151.8 pg/ml (103.7–320.0 pg/ml), respectively (p-ANOVA<0.0001). All patients with symptomatic myeloma received frontline therapy with novel agent-based regimens: 25 with lenalidomide-based regimens, 16 with thalidomide-based regimens and 7 with bortezomib-based regimens. The median follow-up period was 18.8 months and 8/47 patients have died. The probability of survival was 86% at 1 year and 78% at 2 years. In the univariate analysis the VEGFR-1 as a continuous variable correlated with higher risk of death (HR: 1.011, 95% CI: 1.004–1.018, p=0.003). In conclusion our study suggests that myeloma patients have increased circulating PlGF and VEGFR-1. High levels of VEGFR-1 correlated with increased angiogenesis and inferior survival, supporting a significant role of VEGFR-1 in the biology of angiogenesis in MM. Disclosures: No relevant conflicts of interest to declare.
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Wright, G. C., E. Mysler, Y. H. Chen, C. Kinch, A. Yndestad, K. Kwok, M. J. Cadatal, R. Germino, and A. Ogdie. "POS0671 IMPACT OF RACE ON THE EFFICACY AND SAFETY OF TOFACITINIB IN PATIENTS WITH RHEUMATOID ARTHRITIS: A POST HOC ANALYSIS OF PHASE 2, 3 AND 3B/4 CLINICAL TRIALS." Annals of the Rheumatic Diseases 81, Suppl 1 (May 23, 2022): 609. http://dx.doi.org/10.1136/annrheumdis-2022-eular.716.
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BackgroundWhile racial disparities in clinical outcomes for rheumatoid arthritis (RA) patients (pts) have been described,1 there is a paucity of data on racial differences in response to advanced therapies.ObjectivesTo evaluate impact of self-reported race on tofacitinib efficacy/safety in RA pts.MethodsThis post hoc analysis used pooled data from 8 Phase (P)2, 6 P3 and 1 P3b/4 randomised controlled trials (RCTs) of RA pts treated with tofacitinib 5 or 10 mg twice daily (BID), adalimumab (ADA; 40 mg once every 2 weeks) or placebo (PBO), stratified by self-reported pt race (White, Black, Asian, Other) at baseline (BL). Efficacy outcomes (Month [M]3): ACR20/50/70 and CDAI/DAS28-4(ESR) low disease activity (LDA; scores ≤10 and ≤3.2, respectively) rates, and least squares (LS) mean change from BL (Δ) in DAS28-4(ESR) and HAQ-DI. Incidence rates (IRs; unique pts with events/100 pt-yrs) were estimated for adverse events (AEs) and serious AEs.Results6355 pts were included (White, n=4145; Black, n=213; Asian, n=1348; Other, n=649). BL characteristics were generally similar across treatment/racial groups, excepting higher prior bDMARD exposure rates in White/Black vs Asian/Other pts. Across treatments, White, Black, Asian and Other pts most commonly enrolled from Europe (40.9%), North America (68.1%), East/South Asia (97.9%) and Latin America (80.6%), respectively; most Other pts self-reported as Hispanic and/or Latino (52.4%), followed by mixed race (36.8%) and unspecified (4.6%). At M3, ACR50 rates were higher in Other vs White pts with tofacitinib, similar across racial groups with ADA, and numerically higher in Black vs White/Asian/Other pts with PBO (Figure 1); broadly similar trends were seen with ACR20/70 and CDAI LDA rates (data not shown [DNS]). DAS28-4(ESR) LDA rates, and LS mean ΔDAS28-4(ESR) and ΔHAQ-DI were generally comparable across racial groups with active treatment, and numerically higher in Black vs White/Asian/Other pts with PBO (DNS). Across efficacy outcomes, PBO-adjusted response rates and improvements generally supported the trends observed with active treatments (Figure 1; DNS). Safety outcomes were broadly similar across treatment arms, with some higher IRs for AEs observed with Black/Other vs White/Asian pts (Table 1). Results should be interpreted with caution due to low pt numbers in some groups and the heterogenous nature of the Other pts group.Table 1.AEs and SAEs, stratified by raceWhiteBlackAsianOthernIR (95% CI)nIR (95% CI)nIR (95% CI)nIR (95% CI)Tofacitinib 5 mg BIDN=1699; PY=1588.3N=93; PY=81.8N=560; PY=548.8N=257; PY=245.9AE1150141.976244.1382150.0205227.1(133.8, 150.3)(192.4, 305.6)(135.4, 165.9)(197.1, 260.4)SAE1469.11519.16111.3176.7(7.7, 10.7)(10.7, 31.4)(8.6, 14.5)(3.9, 10.8)Tofacitinib 10 mg BIDN=1264; PY=1175.4N=60; PY=49.8N=462; PY=487.2N=238; PY=239.8AE919188.548434.3338178.4190234.3(176.5, 201.1)(320.2, 575.8)(159.9, 198.5)(202.2, 270.1)SAE1038.923.9479.7156.2(7.3, 10.8)(0.5, 14.3)(7.1, 12.9)(3.5, 10.2)ADAN=484; PY=390.4N=22; PY=18.6N=73; PY=60.1N=64; PY=49.5AE318140.416162.251157.044161.6(125.4, 156.7)(92.7, 263.4)(116.9, 206.5)(117.4, 216.9)SAE317.6210.3914.511.9(5.2, 10.8)(1.3, 37.4)(6.6, 27.5)(0.1, 10.4)PBON=698; PY=177.3N=38; PY=10.0N=253; PY=72.3N=90; PY=24.5AE369311.623424.9122251.548271.4(280.6, 345.1)(269.4, 637.6)(208.9, 300.3)(200.1, 359.8)SAE2312.519.4810.9311.5(7.9, 18.7)(0.2, 52.2)(4.7, 21.4)(2.4, 33.6)n, number of pts with events; PY, pt-yrs; SAE, serious AEConclusionAcross racial groups, tofacitinib efficacy/safety was consistent with previous tofacitinib RA clinical programme findings. Some racial differences in clinical outcomes were observed, which may reflect regional practice norms or demographic differences. Future analyses should focus on the impact of socioeconomic, cultural, genetic or practice-based differences that may underpin these results.References[1]Greenberg et al. Am J Med 2013; 126: 1089-1098.AcknowledgementsStudy sponsored by Pfizer Inc. Medical writing support was provided by Kirsten Woollcott, CMC Connect, and funded by Pfizer Inc.Disclosure of InterestsGrace C. Wright Speakers bureau: AbbVie, Amgen, Bristol-Myers Squibb, Eli Lilly, Myriad Autoimmune, Novartis and UCB, Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Eli Lilly, Janssen, Myriad Autoimmune, Novartis, Pfizer Inc and UCB, Employee of: Association of Women in Rheumatology, United Rheumatology, Eduardo Mysler Speakers bureau: AbbVie, Bristol-Myers Squibb, Eli Lilly, Janssen, Pfizer Inc, Roche and Sanofi, Grant/research support from: Eli Lilly, Pfizer Inc and Roche, Yi-Hsing Chen Grant/research support from: Bristol-Myers Squibb, GSK and Pfizer Inc, Cassandra Kinch Shareholder of: Pfizer Inc, Employee of: Pfizer Canada ULC, Arne Yndestad Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Kenneth Kwok Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Mary Jane Cadatal Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Rebecca Germino Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Alexis Ogdie Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, CorEvitas, Eli Lilly, Gilead Sciences, GSK, Janssen, Novartis, Pfizer Inc and UCB, Grant/research support from: AbbVie, Amgen, Novartis and Pfizer Inc
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Nouruzi, Ellahe, Seyed Mostafa Hosseini, Babak Asghari, Reza Mahjoub, Ehsan Nazarzadeh Zare, Mohammad-Ali Shahbazi, Fereshte Kalhori, and Mohammad Reza Arabestani. "Effect of poly (lactic-co-glycolic acid) polymer nanoparticles loaded with vancomycin against Staphylococcus aureus biofilm." BMC Biotechnology 23, no. 1 (September 18, 2023). http://dx.doi.org/10.1186/s12896-023-00811-8.
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AbstractStaphylococcus aureus is a unique challenge for the healthcare system because it can form biofilms, is resistant to the host's immune system, and is resistant to numerous antimicrobial therapies. The aim of this study was to investigate the effect of poly (lactic-co-glycolic acid) (PLGA) polymer nanoparticles loaded with vancomycin and conjugated with lysostaphin (PLGA-VAN-LYS) on inhibiting S. aureus biofilm formation. Nano drug carriers were produced using the double emulsion evaporation process. we examined the physicochemical characteristics of the nanoparticles, including particle size, polydispersity index (PDI), zeta potential, drug loading (DL), entrapment efficiency (EE), Lysostaphin conjugation efficiency (LCE), and shape. The effect of the nano drug carriers on S. aureus strains was evaluated by determining the minimum inhibitory concentration (MIC), conducting biofilm formation inhibition studies, and performing agar well diffusion tests. The average size, PDI, zeta potential, DL, EE, and LCE of PLGA-VAN-LYS were 320.5 ± 35 nm, 0.270 ± 0.012, -19.5 ± 1.3 mV, 16.75 ± 2.5%, 94.62 ± 2.6%, and 37% respectively. Both the agar well diffusion and MIC tests did not show a distinction between vancomycin and the nano drug carriers after 72 h. However, the results of the biofilm analysis demonstrated that the nano drug carrier had a stronger inhibitory effect on biofilm formation compared to the free drug. The use of this technology for treating hospital infections caused by the Staphylococcus bacteria may have favorable effects on staphylococcal infections, considering the efficacy of the nano medicine carrier developed in this study.
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Sarker, Ayesha, Yangjin Jung, and Rafat Siddiqui. "Yoghurt Fortification with Green Papaya Powder and Banana Resistant Starch: Effects on the Physicochemical and Bioactive Properties." International Journal of Food Science & Technology, August 24, 2023. http://dx.doi.org/10.1111/ijfs.16672.
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SummaryFor enhanced nutritional and health benefits, yoghurts have been fortified with plant‐based ingredients. In this study, functional yoghurts were formulated by incorporating banana resistant starch (BRS) and green papaya powder (GPP) into partially skimmed milk (2%). These yoghurts were analyzed for various parameters over a 21‐day storage period at 5 °C, including pH, titratable acidity (TA), firmness, viscosity, water activity (aw), water holding capacity (WHC), colour, probiotic viability, protein and dietary fibre content, antioxidant activity (AA), and total phenolic content (TPC). The results demonstrated that the optimal addition of BRS and GPP significantly enhanced the WHC, nutritional, antioxidative, and TPC properties of the yoghurts (p < 0.05). Total dietary fibre was 73% higher, and TPC and AA were increased by 320.6% and 274%, respectively, in yoghurt containing a higher proportion of GPP than the control. During the storage period, the viable total lactic acid bacteria (LAB) counts in yoghurts were above 8 log CFU/mL. However, the formulated yoghurts exhibited decreased firmness and viscosity, as well as a darker colour (reduced L*) compared to the control, which significantly affected consumer preference (p < 0.05). Overall, the incorporation of plant‐based ingredients like BRS and GPP can effectively enhance the nutritional and functional values of yoghurts.
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Miodonski, Gregory, Jessica Bruning, Derrick Simet, Haley Ruiter, Christian Johnson, Mingjun Gu, Zhiying Shan, and Qinghui Chen. "Exercise augments small conductance Ca2+ -activated potassium channel (SK) function in the paraventricular nucleus (PVN) of Sprague Dawley rats to reduce sympathetic outflow." Physiology 38, S1 (May 2023). http://dx.doi.org/10.1152/physiol.2023.38.s1.5735231.
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Elevated sympathetic outflow is a key feature of cardiovascular disease (CVD) that worsens disease progression. Our lab has shown that SK channels expressed in the PVN play a crucial role in regulating neuronal activity and sympathetic outflow, and that SK channels become dysfunctional in rats fed a high salt diet. Exercise has been shown to be an effective treatment for reducing sympathoexcitation in CVD including hypertension and heart failure, but the underlying mechanisms are not fully understood. We hypothesized that aerobic exercise would upregulate SK channel function in the PVN to reduce sympathetic nerve activity (SNA). To test this, 5–6 week old Sprague Dawley rats were randomly divided into sedentary (SED) and exercise (EXT) two groups and fed a 0.4% NaCl normal salt diet. Following acclimation, EXT groups ran on a motorized treadmill 5 days/week for 8-10 weeks. Conscious blood pressure was measured weekly via tail plethysmography. After 8-10 weeks, animals were anesthetized and underwent in vivo surgery to record the renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) following PVN microinjection of the SK channel blocker, apamin (0.25mM, 60nL/side). The data showed that the RSNA response to PVN apamin was significantly enhanced in EXT rats compared with SED rats (320.8 ± 174.6 % baseline, n=9 vs 184.8 ± 143.1 % baseline, n=9; p = 0.02). The corresponding ABP response to apamin was not significantly different in EXT rats compared with SED rats (20.40 ± 9.98 mmHg, n=9 vs 25.27 ± 9.97 mmHg, n=8; p = 0.1658). Our data indicates exercise enhances PVN SK channel function to reduce sympathetic outflow. This improvement of SK channel function may be one mechanism by which exercise reduces SNA in CVD including hypertension and heart failure. Support: 1R15HL145655 (Chen); 1R15 HL150703 (Shan); MTU Health Research Institute. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
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Saha, Piu, Beng San Yeoh, Mrunmayee Kandalgaonkar, Bina Joe, and Matam Vijay-Kumar. "Abstract 003: Aberrant Host Immune Responses Specific To Microbial-derived Ligands Are Linked To Hypertension In BPH/2J Mice." Hypertension 80, Suppl_1 (September 2023). http://dx.doi.org/10.1161/hyp.80.suppl_1.003.
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It has been established that derangements in host-microbiota homeostasis leads to hypertension. However, the precise mechanisms remain largely unknown. Microbial-derived ligands released into the host circulation are sensed and eliminated by various host innate and adaptive immune mechanisms. Herein, we focused on such microbial-derived ligands and hypothesized that defect in host innate and adaptive immune response to counter microbial-derived ligands is linked to hypertension. To test this hypothesis, both in vitro and in vivo studies were conducted. First, bone marrow-derived macrophages from Blood Pressure Normal (BPN/3J, systolic blood pressure: 113.2±2.20 mm Hg) and Blood Pressure Hypertensive (BPH/2J, systolic blood pressure: 143.9±4.10 mm Hg) mice (male, 8 weeks) were challenged with various Toll-like receptor (TLR) ligands of microbial origin. Unstimulated macrophages from BPH mice displayed reduced levels of the co-stimulatory activation markers CD40, CD80 and CD86 (~2 fold) compared to macrophages from BPN/3J mice. Such differences, however, was normalized upon stimulation with ligands for TLR3 (poly-I:C), TLR4 (LPS), TLR5 (flagellin), TLR7/8 (R848) and TLR9 (CpG-DNA). Despite so, BPH-macrophages displayed blunted IL-6 and lipocalin-2 (~2 fold) levels in response to all the aforementioned TLR ligands when compared to macrophages from BPN mice. To confirm these findings in vivo , we challenged BPN and BPH mice with the microbial-derived ligand, flagellin. Interestingly, even though BPH mice had reduced cytokine responses to flagellin as monitored by levels of Lcn2 (BPN 320.9 ± 22.20 vs BPH 230.8 ± 12.40, p<0.05) and CXCL1 (BPN 40.9 ± 4.6 vs BPH 23.8 ± 2.4, p<0.05), they displayed higher levels of flagellin-specific IgG (BPN vs BPH O.D 450 , 0.51 ± 0.10 vs 0.93 ± 0.07, p<0.05) and substantially lower levels of flagellin-specific IgA (BPN vs BPH O.D 450 , 0.44 ± 0.13 v s 0.13 ± 0.03, p<0.05). Collectively, both in vitro and in vivo studies demonstrate that both innate and adaptive immune responses specifically against microbial ligands is substantially deranged in the hypertensive state.
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Yoshimoto, Hisashi, Kyoko Kawaida, Shohei Dobashi, Go Saito, and Yukiko Owaki. "Effect of provision of non-alcoholic beverages on alcohol consumption: a randomized controlled study." BMC Medicine 21, no. 1 (October 2, 2023). http://dx.doi.org/10.1186/s12916-023-03085-1.
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Abstract Background The use of alcohol-flavored beverages not containing alcohol (hereinafter referred to as non-alcoholic beverages) is recommended to reduce alcohol consumption. However, it is unclear if this reduces excessive drinking. Objective To verify whether non-alcoholic beverages impact the alcohol consumption of excessive drinkers. Study design Single-center, open-label, randomized, parallel-group study. Methods Participants aged 20 years or older who were not diagnosed with alcoholism, who drank at least four times a week, and whose alcohol consumption on those days was at least 40 g in males and 20 g in females, were recruited. Participants were randomized into the intervention or control group by simple randomization using a random number table. In the intervention group, free non-alcoholic beverages were provided once every 4 weeks for 12 weeks (three times in total), and thereafter, the number of alcoholic and non-alcoholic beverages consumed were recorded for up to 20 weeks. The consumption of alcoholic and non-alcoholic beverages was calculated based on a drinking diary submitted with the previous 4 weeks of data. The primary endpoint was the change from baseline in total alcohol consumption during past 4 weeks at week 12. The participants were not blinded to group allocations. Results Fifty-four participants (43.9%) were allocated to the intervention group and 69 (56.1%) to the control group. None of the participants in the intervention group dropped out, compared to two (1.6%) in the control group. The change in alcohol consumption was − 320.8 g (standard deviation [SD], 283.6) in the intervention group and − 76.9 g (SD, 272.6) in the control group at Week 12, indicating a significant difference (p < 0.001). Even at Week 20 (8 weeks after the completion of the intervention), the change was − 276.9 g (SD, 39.1) in the intervention group, which was significantly greater than − 126.1 g (SD, 41.3) in the control group (p < 0.001). The Spearman rank correlation coefficient between the change in non-alcoholic beverage consumption and alcohol consumption at Week 12 was significantly negative only in the intervention group (ρ = − 0.500, p < 0.001). There were no reports of adverse events during the study. Conclusions Providing non-alcoholic beverages significantly reduced alcohol consumption, an effect that persisted for 8 weeks after the intervention. Trial registration UMIN UMIN000047949. Registered 4 June 2022.
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Su, Jin, Weihong Guo, Zhian Chen, Lingzhi Wang, Hao Liu, Liying Zhao, Tian Lin, et al. "Safety and short-term outcomes of laparoscopic surgery for advanced gastric cancer after neoadjuvant immunotherapy: A retrospective cohort study." Frontiers in Immunology 13 (December 8, 2022). http://dx.doi.org/10.3389/fimmu.2022.1078196.
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BackgroundImmune checkpoint inhibitors (ICIs) have been increasingly used for the treatment of advanced gastric cancer (AGC). However, the safety and the short-term outcomes of laparoscopic gastrectomy for patients with AGC after neoadjuvant immunotherapy (NAI) remain unknown.MethodsWe retrospectively analyzed the patients with AGC who underwent laparoscopic surgery after neoadjuvant therapy between 1 January 2019 and 31 October 2021. We further compared the differences in postoperative complications, overall response rate, adverse events, surgical parameters, and postoperative recovery between two cohorts: the NAI group (NAI plus chemotherapy) and the neoadjuvant chemotherapy (NAC) group. Multivariable regression analyses were used to determine the risk factors for the overall response rate.ResultsOverall, 80 patients were enrolled, of whom 30 cases were included in the NAI cohort and 50 were included in the NAC cohort. The overall rate of postoperative complications was 30.0% in both groups (p = 1.000). The overall response rate was 70.0% in the NAI cohort and 40% in the NAC cohort (p = 0.012). The adverse effects were found in 16 cases (53.3%) of the NAI cohort and 23 cases (46.0%) of the NAC cohort (p = 0.645). There was no statistical difference in intraoperative bleeding (50 ml vs. 50 ml, p = 0.983), operation time (320.9 min vs. 303.5 min, p = 0.382), dissected lymph node count (43.5 vs. 40.0, p = 0.364), first postoperative anal aerofluxus (3 days vs. 3 days, p = 0.091), first liquid diet (4 days vs. 5 days, p = 0.213), and postoperative length of stay in the hospital (8 days vs. 7 days, p = 0.508) between the two groups. NAI was estimated to be the independent protective factor [odds ratio (OR) 4.931, 95% confidence interval (CI) (1.385–17.559), p = 0.014] for odds to overall response rate, whereas vessel invasion was found to be the significant risk factor [OR 0.113, 95% CI (0.027–0.475), p = 0.003].ConclusionsLaparoscopic surgery after NAI combined with chemotherapy is a safe therapeutic choice for AGC and may bring better short-term outcomes due to a higher overall response rate.
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Oliveira, Tales L., Caroline G. Shimoura, Gisele S. Lincevicius, Michelle L. Garcia, Mirian A. Boim, Guiomar N. Gomes, Cassia T. Bergamaschi, and Ruy R. Campos. "PREFERENTIAL RENAL SYMPATHETIC HYPERACTIVITY IN EXPERIMENTAL DIABETES MELLITUS." FASEB Journal 31, S1 (April 2017). http://dx.doi.org/10.1096/fasebj.31.1_supplement.1039.3.
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Autonomic, cardiovascular and renal dysfunction has been observed in diabetic patients and animal models of diabetes mellitus (DM), including the streptozotocin‐induced type 1 diabetes model. The aim of this study was to evaluate the effects of the experimental DM on efferent post‐ganglionic sympathetic nerve activity, arterial baroreceptor reflex sensitivity to heart rate (HR), renal (rSNA) and lumbar (lSNA) sympathetic nerves in DM rats. The DM was induced by Streptozotocin (60 mg/kg, ip) 4 weeks before experimental analysis. Male Wistar rats (n=6–8 per group), 8 weeks of age, 230–250 g of body weight were used. The animals were separated into control (CTR) and diabetic (DM) groups. Protocol CEUA/UNIFESP 1787250714. The results were expressed as mean ± SEM and compared with t‐Student test (p<0.05). DM was confirmed by the reduction in body weight (CTR: 320.1±6.3; DM: 242.1±6.7 g, p<0.05) and significantly increased in blood glucose (CTR: 100.3±3.7; DM: 509.1±14.4 mg/dL, p<0.05) in the DM group. A significant increase in feed intake (CTR: 75.8±3; DM: 158.3±6.4 g/kg), water intake (CTR: 98±4.3; DM: 608±31,3 ml/kg), and urinary flow in the DM rats evaluated for 24h (CTR: 40±3.1; DM: 562±25,1 ml/kg) was found. Sodium urinary excretion (CTR: 5.1±0.5; DM: 17.4±1.2 mmol/kg), potassium (CTR: 16±0.9; DM: 36.4±1 mEq/kg), glucose (CTR: 12±1.4; DM: 2719±192 mg/kg), and albumin urinary excretion (CTR: 82.3±8; DM: 394.3±42.7 mg/kg) were significantly increased in DM group. In addition, sodium (CTR: 123±1.7; DM: 141.4±1.6 mmol/L) and potassium plasma concentration (CTR: 4.4±0.1; DM: 5.2±0.1 mEq/L) were significantly increased in DM rats compared to control group. The creatinine clearance was reduced in the DM rats (CTR: 1.4±0.1; DM: 1±0.1 mL/min). DM reduced heart rate (HR) (CTR: 352.6±013.5; DM: 292.2±11 bpm, p<0.05), but did not change basal values of blood pressure (BP) compared to control group. rSNA was significantly increased (CTR: 85.5±3.1; DM: 133.5±2.5 pps) but lSNA did not change in DM rats. The arterial baroceptor function was significantly decreased to rSNA, (CTR: 1.3±0.1; DM: 0.9±0.1 pps/mmHg), lSNA (CTR: 1.4±0.1, DM: 0.8±0.1 pps/mmHg) and HR control (tachycardic response = CTR: −1.4 ± 0.1; DM: 0.8 ± 0.05 and bradycardic response = CTR: 1.3 ± 0.05; DM: 0.7 ± 0.03 bpm/mmHg, respectively) in the DM group compared to control rats. Taken altogether, the results suggest that autonomic dysfunction, characterized by impaired baroreceptor function, preferential increasein renal sympathetic nerve activity associated with impaired renal function are involved in the development and/or maintenance of experimental DM. Whether the renal sympathoexcitation in DM is a cause or a consequence of renal dysfunction remains to be determined.Support or Funding InformationCAPES and FAPESP.
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Kajal, Dev Raj Sharma, Vinay Pandit, and M. S. Ashawat. "Formulation and Evaluation of Niosomal Loaded Transdermal Patches for the Treatment of Osteoarthritis." Drug Delivery Letters 14 (July 2, 2024). http://dx.doi.org/10.2174/0122103031283166240619043041.
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Introduction: Osteoarthritis (OA) is a degenerative joint disease resulting from the breakdown of joint cartilage and underlying bone. The most common symptoms of osteoarthritis are joint pain and stiffness. The major hurdle in its treatment is that the oral administration of NSAIDs (Lornoxicam) causes side effects like GI side effects, cardiovascular problems, liver issues, or renal problems. Thus, there is a need to develop a Transdermal drug delivery system for the transport of drugs, which reduces side effects and has several benefits over oral delivery, and a Novel drug delivery system to enhance the permeation of drugs and give relief from symptoms of OA. Objectives: This work deals with the formulation and evaluation of niosomal-loaded Transdermal Patches for the treatment of Osteoarthritis. Method: The Niosomes were prepared using the thin film hydration method, and Niosomalloaded Transdermal patches were prepared using the Solvent Casting method. The preliminary evaluation and characterization studies were conducted to find the optimized formulation. The invitro release and ex-vivo permeation studies were investigated. Stability studies were also assessed. Result: The prepared Niosomes suspension (F2) was found to have particle size 320.2 nm, Zeta potential 23.9 mV, and Drug entrapment 79 ± 0.32%. The in-vitro drug release studies of optimized formulation show 96.44 ± 0.34 % drug release for 24 hours. Then, the optimized Niosome formulation (F2) was loaded into the transdermal patches. The in-vitro permeation studies of Niosomal-loaded transdermal patch F1 (NLXTP) were performed, which showed a higher permeability than plain drug-loaded transdermal patch. F1 (NLXTP) followed Zero order release kinetic model, which shows a non-fickian controlled release diffusion mechanism. The ex-vivo drug release studies of optimized formulation F1 (NLXTP) show 2.79 ± 0.76 (µg/ml) drug permeated for 8 hours with a flux value of 0.35 ± 0.55, and the percentage of drug retention was found to be 5.67%. The stability studies showed that patches were stable over 90 days in different atmospheric conditions. Conclusion: The Lornoxicam-loaded Niosomal transdermal patch was found to be a promising nano-drug-delivery alternative that showed better entrapment and release with a permeation profile for the daily management of osteoarthritis.
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Matousek, M., C. Carati, B. Gannon, and M. Brannstrom. "Novel method for intrafollicular pressure measurements in the rat ovary: increased intrafollicular pressure after hCG stimulation." Reproduction, February 1, 2001, 307–14. http://dx.doi.org/10.1530/rep.0.1210307.
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The ovulatory process in the rat comprises a period of about 12-15 h, from the time of the preovulatory LH surge to follicular rupture and extrusion of the oocyte. Follicular rupture is most likely caused, at least in part, by decreased tensile strength at the follicular apex due to degradation of collagen fibres of the extracellular matrix. It has been debated whether changes in intrafollicular pressure occur during the ovulatory process and whether such changes facilitate rupture of the follicle. In the present study, rats were primed with equine chorionic gonadotrophin (eCG, 10 iu) followed by hCG (10 iu) 48 h later. The intrafollicular pressure in the preovulatory follicle was recorded during 1 h at distinct time phases of the ovulatory process by use of an active servo-null pressure system based on the proportionality between electrical resistance and pressure within the tip of an inserted micropipette. The basal intrafollicular pressure was 16.6 +/- 1.0 mm Hg at the preovulatory phase (48 h after eCG) and increased gradually throughout the ovulatory process to 21.4 +/- 2.4 mm Hg at 4-7 h after hCG (mid-ovulatory phase) and 23.9 +/- 1.9 mm Hg at 8-12 h after hCG (late ovulatory phase; significantly higher (P < 0.01) than the preovulatory phase). Short-term peaks of increased pressure, possibly representing contractility, were not detected in follicles of the preovulatory phase, but were seen in most follicles of the mid- and late ovulatory phases. The mean amplitude of the short-term pressure increases was 12.3 +/- 3.2 mm Hg and the increases occurred at intervals of 24.7 +/- 3.6 s. These short-term increments in intrafollicular pressure were still present after hysterectomy had been performed. The wall tension index was calculated by measuring the follicular size and estimating the thickness of the follicle wall. The index increased from 93.9 +/- 13.3 at the preovulatory phase to 207.3 +/- 47.7 (mid-ovulatory phase) and to significantly higher values at the late ovulatory phase (320.9 +/- 33.5). In conclusion, this study shows that there is an increase in intrafollicular pressure in the ovulating follicle of the rat ovary during the late stages of the ovulatory process, and that short-term increases in intrafollicular pressure occur during the late phase of the ovulatory process. These changes in pressure may be essential for follicular rupture to proceed normally.
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Lutsenko, M. M., and O. Yu Galay. "Resource-saving milk production technologies with use of easy-assembled premises and high-performance milking plants." Scientific Messenger of LNU of Veterinary Medicine and Biotechnologies 20, no. 84 (March 28, 2018). http://dx.doi.org/10.15421/nvlvet8430.
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High productivity of dairy cows in the conditions of new innovative technologies can not be obtained without providing comfortable conditions for their functioning.In this connection, the conditions for maintaining high-yielding cows in various types of livestock buildings are investigated: the traditional, 24.0 m wide and new unassembled, 32.5 m wide and 36.0 m in extreme periods of the year. The different width of the premises is due to the need to use different types of milking plants: MilkProud, Parallel, Carousel and robotic milking systems.Studies have established that volumetric-planning and technological solutions for easy-assembled premises increase the volume of space per head from 45.6 m3 to 96.3 m3 and 129.6 m3. It positively affects the conditions for the maintenance of highly productive cows. The presence in their design of side curtains and light-aeration ridge increases the speed of air in 3 times. This provides a reduction in the concentration of ammonia in 8 times, and bacterial pollution at 18.7 times compared with traditional barn.Increasing the volume of the room up to 129.6m³ per head reduces the bacterial air pollution in the winter period to a minimum value of 2.8 thousand/m³. New elements in the design of easy-assembled spaces provide resource-saving and organizing their lighting.According to the existing standards in Ukraine, the lighting in the feeding area should be at 52 lux. In traditional rooms, this level is achieved only by installing additional energy sources, which provide an increase in lighting from 31 lux to 52 lux. In new types of premises the required level of lighting is provided naturally, which leads to significant energy savings. It was established that technological solutions of easy-assembled premises provide comfortable conditions for recreation of high-yielding cows.In these types of rooms, the animals rest 12.4% and 20.0% more time compared to traditional rooms. Feeding of cows in easy-assembled premises from the stern table provides quick feeding of animals with feed. At the same time the time consumed for feed consumption in new types of barns is significantly less and is 252.0–246.0 min a day compared to 320.2 min in traditional premises where feeding is carried out from traditional feeding troughs.It is positive that in the new types of premises in animals there is a new important element of behavior – the movement, which they spend 8.6% and 9.9% of the time. New types of premises with resource-saving milk production technologies have a positive effect on the conditions for the maintenance of highly productive cows and can be widely implemented in Ukraine.
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Magill, Stephen T., Minh P. Nguyen, Manish K. Aghi, Philip V. Theodosopoulos, Javier E. Villanueva-Meyer, and Michael W. McDermott. "Postoperative diffusion-weighted imaging and neurological outcome after convexity meningioma resection." Journal of Neurosurgery, January 2021, 1–8. http://dx.doi.org/10.3171/2020.8.jns193537.
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OBJECTIVEConvexity meningiomas are commonly managed with resection. Motor outcomes and predictors of new deficits after surgery are poorly studied. The objective of this study was to determine whether postoperative diffusion-weighted imaging (DWI) was associated with neurological deficits after convexity meningioma resection and to identify the risk factors for postoperative DWI restriction.METHODSA retrospective review of patients who had undergone convexity meningioma resection from 2014 to 2018 was performed. Univariate and multivariate logistic regressions were performed to identify variables associated with postoperative neurological deficits and a DWI signal. The amount of postoperative DWI signal was measured and was correlated with low apparent diffusion coefficient maps to confirm ischemic injury.RESULTSThe authors identified 122 patients who had undergone a total of 125 operations for convexity meningiomas. The median age at surgery was 57 years, and 70% of the patients were female. The median follow-up was 26 months. The WHO grade was I in 62% of cases, II in 36%, and III in 2%. The most common preoperative deficits were seizures (24%), extremity weakness/paralysis (16%), cognitive/language/memory impairment (16%), and focal neurological deficit (16%). Following resection, 89% of cases had no residual deficit. Postoperative DWI showed punctate or no diffusion restriction in 78% of cases and restriction > 1 cm in 22% of cases. An immediate postoperative neurological deficit was present in 14 patients (11%), but only 8 patients (7%) had a deficit at 3 months postoperatively. Univariate analysis identified DWI signal > 1 cm (p < 0.0001), tumor diameter (p < 0.0001), preoperative motor deficit (p = 0.0043), older age (p = 0.0113), and preoperative embolization (p = 0.0171) as risk factors for an immediate postoperative deficit, whereas DWI signal > 1 cm (p < 0.0001), tumor size (p < 0.0001), and older age (p = 0.0181) were risk factors for deficits lasting more than 3 months postoperatively. Multivariate analysis revealed a DWI signal > 1 cm to be the only significant risk factor for deficits at 3 months postoperatively (OR 32.42, 95% CI 3.3–320.1, p = 0.0002). Further, estimated blood loss (OR 1.4 per 100 ml increase, 95% CI 1.1–1.7, p < 0.0001), older age (OR 1.1 per year older, 95% CI 1.0–1.1, p = 0.0009), middle third location in the sagittal plane (OR 16.9, 95% CI 1.3–216.9, p = 0.0026), and preoperative peritumoral edema (OR 4.6, 95% CI 1.2–17.7, p = 0.0249) were significantly associated with a postoperative DWI signal > 1 cm.CONCLUSIONSA DWI signal > 1 cm is significantly associated with postoperative neurological deficits, both immediate and long-lasting. Greater estimated blood loss, older age, tumor location over the motor strip, and preoperative peritumoral edema increase the risk of having a postoperative DWI signal > 1 cm, reflective of perilesional ischemia. Most immediate postoperative deficits will improve over time. These data are valuable when preoperatively communicating with patients about the risks of surgery and when postoperatively discussing prognosis after a deficit occurs.
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Yu, Xueqing, Zhiming Ye, Yiqing Wu, Cuihua Huang, and Shuting Pan. "#437 A multicenter, single-arm study of roxadustat in Chinese patients with chronic kidney disease-associated anemia receiving peritoneal dialysis." Nephrology Dialysis Transplantation 39, Supplement_1 (May 2024). http://dx.doi.org/10.1093/ndt/gfae069.1473.
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Abstract Background and Aims Anemia increases morbidity and mortality in patients with chronic kidney disease (CKD). Phase 3 studies have demonstrated the efficacy of roxadustat for anemia treatment in patients with CKD undergoing dialysis; however, data from Chinese patients undergoing peritoneal dialysis (PD) are limited. We evaluated the efficacy and safety of roxadustat in Chinese patients with CKD-anemia undergoing PD. Method In this phase 4, single-arm, multicenter study, we planned to enroll at least 150 Chinese patients with CKD-anemia undergoing PD (either erythropoiesis-stimulating agent [ESA]-treated or ESA-naïve at enrollment), including at least 50 patients with type 2 diabetes mellitus (T2DM) and 50 patients without diabetes mellitus (DM). Study visits occurred every 2 weeks until Week 8 and then every 4 weeks. All patients received oral roxadustat treatment three times per week for 24 weeks according to the approved product package insert. The primary efficacy endpoint was the proportion of patients with a mean hemoglobin (Hb) ≥100 g/L at Weeks 20–24. The secondary efficacy endpoints were subgroup analyses (T2DM vs. non-DM). The exploratory endpoints were the dose required to maintain Hb at ≥100 g/L over Weeks 20–24, the proportion of time when Hb was 100–130 g/L, changes in residual renal function (RRF), urea clearance index (Kt/V), and creatinine clearance (Ccr), amongst others. For the safety analyses, adverse events (AEs) were assessed during treatment and at 4 weeks after completion. Results Overall, 195 patients (116 male [59.5%]) with a mean (standard deviation [SD]) age of 46.3 (12.3) years were enrolled from 22 centers, and 172 (88.2%) completed the study (main reasons for discontinuation: withdrawal, 7 [3.6%]; AE, 5 [2.6%]; switched from PD to hemodialysis, 5 [2.6%]). Overall, 189 patients (96.9%) were ESA-treated and 43 (22.1%) had T2DM. The median (interquartile range) dialysis duration was 16.1 (5.2–43.2) months. The mean (SD) baseline Hb was 98.1 (10.7) g/L, and the ferritin level and transferrin saturation were 320.9 (287.5) μg/L and 35.5% (17.0%), respectively. The mean (SD) treatment duration was 154.3 (35.6) days, and the mean (SD) weekly dose was 244.9 (88.7) mg. The intention-to-treat (ITT) set and safety analysis set (SAF) included all 195 patients. In the ITT set, 85.1% (95% confidence interval [CI] 79.8%–90.5%) of patients had Hb ≥100 g/L over Weeks 20–24. According to the subgroup analysis, 89.2% (95% CI 78.5%–99.9%) of T2DM patients and 84.0% (95% CI 77.8%–90.1%) of non-DM patients had Hb ≥100 g/L over Weeks 20–24 (Fig. 1). The mean (SD) weekly dose required to maintain Hb at ≥100 g/L at Weeks 20–24 was 215.9 (100.0) mg, and the proportion of time that Hb was 100–130 g/L was 76.4% (23.2%). There was a slight decrease in RRF and Ccr. Table 1 shows the RRF, Kt/V, and Ccr results. Of the 195 SAF patients, 158 (81.0%) had ≥1 treatment-emergent AE (TEAE), 20 (10.3%) had drug-related TEAEs, 40 (20.5%) had treatment-emergent serious AEs, and 1 (0.5%) had a TEAE that led to death. The top three TEAEs were upper respiratory tract infection (25 [12.8%]), hypokalemia (17 [8.7%]), and hypoalbuminemia (15 [7.7%]). Conclusion Treatment with roxadustat for 24 weeks effectively corrected anemia in Chinese CKD patients undergoing PD and maintained Hb at ≥100 g/L in the majority of patients, irrespective of baseline T2DM. The AEs were consistent with the characteristics of patients with CKD undergoing PD and with the known safety profile of roxadustat.