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Yunita, D., E. Indarti, R. Rafiqah, D. Darurrachmi, and R. A. Lahmer. "Physical, thermal and functional groups’ characteristics of biofoam cup made from coconut fibre waste, soy flour and Rhizopus oligosporus." IOP Conference Series: Earth and Environmental Science 1183, no. 1 (May 1, 2023): 012057. http://dx.doi.org/10.1088/1755-1315/1183/1/012057.
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Abstract Biofoam is a replacement packaging for Styrofoam made from natural fibres that are naturally biodegradable and food-safe. Many studies use chemicals and starch as a matrix adhesive in the manufacture of biofoam. In previous studies, biofoam cups have been developed using the mold Rhizopus oligosporus which is found in coconut fibre. The objective of this study was to analyse the physical, thermal and functional groups’ characteristics in order to determine the most durable biofoam cup. The mixtures of fibre, tempeh mold, and soy flour were fermented for 3 days at 35°C in two stacked plastic cups and were dried for 46 hours at 50°C to stop the fermentation process. The biofoam cups were then analysed for the physical, thermal and functional groups’ characteristics. The most favourable characteristics of the biofoam cup is not easily destroyed and resistant to heat. The results showed that it had 0.08 g/cm3 ± 0.1 g/cm3 of density and 320.54°C of thermal gravimetry analysis. It also had a hydroxyl functional group (O-H) at wave number 3273.20 cm−1, an alkyl group (C-H) at wave number 2937.59 cm−1, a carbonyl group (C=O) at wave number 1654.92 cm−1, 1535.34 cm−1, and 1259.52 cm−1, and the C-O functional group at the wave number 1060.85 cm−1.
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Alcón, Pablo, Guillermo Montoya, and Stefano Stella. "Assembly ofFrancisella novicidaCpf1 endonuclease in complex with guide RNA and target DNA." Acta Crystallographica Section F Structural Biology Communications 73, no. 7 (June 20, 2017): 409–15. http://dx.doi.org/10.1107/s2053230x1700838x.
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Bacteria and archaea use the CRISPR–Cas system as an adaptive response against infection by foreign nucleic acids. Owing to its remarkable flexibility, this mechanism has been harnessed and adopted as a powerful tool for genome editing. The CRISPR–Cas system includes two classes that are subdivided into six types and 19 subtypes according to conservation of thecasgene and loci organization. Recently, a new protein with endonuclease activity belonging to class 2 type V has been identified. This endonuclease, termed Cpf1, in complex with a single CRISPR RNA (crRNA) is able to recognize and cleave a target DNA preceded by a 5′-TTN-3′ protospacer-adjacent motif (PAM) complementary to the RNA guide. To obtain structural insight into the inner workings of Cpf1, the crystallization of an active complex containing the full extent of the crRNA and a 31-nucleotide dsDNA target was attempted. The gene encoding Cpf1 fromFrancisella novicidawas cloned, overexpressed and purified. The crRNA was transcribed and purifiedin vitro. Finally, the ternary FnCpf1–crRNA–DNA complex was assembled and purified by preparative electrophoresis before crystallization. Crystals belonging to space groupC2221, with unit-cell parametersa= 85.2,b= 137.6,c= 320.5 Å, were obtained and subjected to preliminary diffraction experiments.
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Tunçbilek, Zehra, Bedriye Nur Ayrancıoğlu, and Ayşe Feyza Önder. "Efficacy of Ranibizumab in the Treatment of Macular Edema Secondary to Retinal Vein Occlusion." Medical Science and Discovery 11, no. 5 (May 20, 2024): 157–62. http://dx.doi.org/10.36472/msd.v11i5.1153.
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Objective: Branch retinal vein occlusion (BRVO), a major cause of vision loss, is a significant ocular health concern. The frequency of macular edema due to BRVO is a critical area of study because of its profound impact on patient quality of life. This study investigated the effectiveness of ranibizumab, a monoclonal antibody fragment and VEGF inhibitor, in the treatment of macular edema in patients with BRVO. Material and Methods: Twelve patients (12 eyes) diagnosed with macular edema secondary to BRVO were included in this study. Patients were selected on the basis of specific visual acuity and macular thickness criteria, excluding those with other ocular conditions or systemic diseases. 0.05 milligrams of ranibizumab was administered intravitreally to each patient. Ophthalmological assessments were conducted both before and after the injection and at 1, 2, 3, and 6-month intervals following medication administration. Results: The average follow-up duration was 5.5±1.16 months (ranging from 2 to 6 months). The average central macular thickness before the injection was 542.66±191.44 µm, which decreased to 320.50±101.44 µm at 1-month post-injection, 283.66±125.01 µm at 2 months, 299.40±91.52 µm at 3 months, and 260.90±144.97 µm at 6 months. The reduction in central macular thickness at all time points was statistically significant (p<0.01). The mean Early Treatment Diabetic Retinopathy Study (ETDRS) letter score was 55.83±23.91 before the injection and improved to 71.25±17.07 at 1 month, 74.33±15.97 at 2 months, 66.7±21.60 at 3 months, and 71.2±17.38 at 6 months post-injection. The increase in visual acuity at 1, 2, 3, and 6 months after the injection was statistically significant compared to the pre-injection ETDRS letter scores (p<0.05). An improvement of two or more lines in visual acuity was observed in 58.3% of cases at 1 month, 58.3% at 2 months, 50% at 3 months, and 80% at 6 months (one line equivalent to five letters). Conclusion: Intravitreal Ranibizumab injections have been found to be effective and reliable in the early stages of treating macular edema due to branch retinal vein occlusion.
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Nath, Kapil Deb, C. Nickhil, Debasish Borah, R. Pandiselvam, and Sankar Chandra Deka. "Preparation, Characterization, and Nutritional Analysis of Napham: An Indian Traditional Smoke-Dried-Fermented Fish Paste." Journal of Food Biochemistry 2024 (January 25, 2024): 1–11. http://dx.doi.org/10.1155/2024/7410065.
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Napham, a unique smoked-dried-fermented fish paste, is a traditional delicacy prepared by the Assamese Bodo people. This research focuses on the process of Napham preparation and explores its nutritional benefits. To make Napham, sundried and smoked trash fishes, along with Alocasia macrorrhiza stems, are ground and stuffed into immature bamboo tubes, where they ferment for 2-3 months. Although Napham possesses a distinct taste and texture that may not appeal to everyone, the fermentation process significantly enhances its nutritional value by increasing its vitamin content, improving fatty acid profiles, and enhancing amino acid profiles. The study reveals that Napham is a remarkable source of protein (63.65 ± 0.83 g/100 g), potassium (667.87 ± 3.48 mg/kg), sodium (531.48 ± 3.43 mg/kg), and magnesium (56.23 ± 1.53 mg/kg). Napham contains both omega-3 and omega-6 fatty acids, including linoleic acid (10.10 ± 0.002%), α-linolenic acid (6.47 ± 0.062%), arachidonic acid (4.65 ± 0.031%), eicosapentaenoic acid (1.08 ± 0.007%), and docosahexaenoic acid (3.44 ± 0.036%). Furthermore, Napham is rich in essential amino acids such as methionine (227.407 µmol/L), isoleucine (478.525 µmol/L), leucine (797.944 µmol/L), valine (640.867 µmol/L), phenylalanine (320.573 µmol/L), lysine (1066.557 µmol/L), and histidine (104.525 µmol/L), complementing its nutritional profile.
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Paiva, Lisete, Elisabete Lima, Madalena Motta, Massimo Marcone, and José Baptista. "Influence of Seasonal and Yearly Variation on Phenolic Profiles, Caffeine, and Antioxidant Activities of Green Tea (Camellia sinensis (L.) Kuntze) from Azores." Applied Sciences 11, no. 16 (August 13, 2021): 7439. http://dx.doi.org/10.3390/app11167439.
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This study compares the antioxidant properties (RSADPPH–DPPH radical scavenging activity, FRAP–ferric reducing activity power, and FIC–ferrous ion-chelating activity), the total phenolics (TP), total flavonoids (TF), and catechin profiles, as well as the caffeine content of Azorean Camellia sinensis green tea collected in seasons of two different years. The RSADPPH showed some variation between 2019 and 2020, and presented, in general, better results in 2020 as well as during the summer seasons. The FRAP was also noted to be at its highest in July and August of the two investigated years (6.64 and 6.40 µg/mL in 2019 and 5.85 and 5.46 µg/mL in 2020). According to FIC activity, the August 2019 sample exhibited the highest value (76.18%). The TP varied between 291.14 and 326.93 mg gallic acid equivalents (GAE)/g of dried extract (DE) in 2019 and between 300.25 and 320.58 mg GAE/g DE in 2020. Concerning the TF, the values varied between 51.85 and 67.93 mg rutin equivalents (RE)/g DE in 2019 and between 50.27 and 69.57 mg RE/g DE in 2020. Epicatechins derivatives, determined by HPLC, presented higher values in all samples from 2020 compared to 2019, and the same was observed for esterified catechins. The epigallocatechin-3-gallate content was also higher in all samples from 2020 (214.52–240.16 mg/g DE) compared to 2019 (140.91–210.83 mg/g DE). Regarding caffeine content (12.86–20.45 mg/g DE in 2019 and 13.19–29.35 mg/g DE in 2020), the samples from April and June exhibited similar values in both years. In general, green tea samples exhibited better results in 2020 than in 2019, with the exception of FIC activity, while the varied TP and TF contents in certain months reflect the impact of climatic variation on tea quality.
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Sasaki, T., H. Yasuda, K. Nakayama, S. Okinaga, T. Suzuki, M. Asada, A. Kanda, T. Shindo, Y. Ohuchi, and M. Yamaya. "A randomized phase II trial comparing carboplatin pleurodesis with cisplatin pleurodesis in patients with stage IIIB/IV non-small cell lung cancer (NSCLC) with malignant pleural effusions (MPE)." Journal of Clinical Oncology 24, no. 18_suppl (June 20, 2006): 17012. http://dx.doi.org/10.1200/jco.2006.24.18_suppl.17012.
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17012 Background: We previously reported that carboplatin pleurodesis in patients with advanced lung adenocarcinoma with MPE, renal insufficiency, and poor performance status (PS) was an effective palliative therapy. However, the efficacy and toxicity profile of carboplatin pleurodesis in patients with NSCLC with MPE in comparison with those of cisplatin pleurodesis have not been reported. Methods: Thirty patients with stage IIIB/IV NSCLC accompanied with MPE who did not have an indication for systemic chemotherapy because of poor PS more than 2 were randomized to carboplatin pleurodesis (target area under the curve as 5 μg-min/ml using Calvert’s formula) and cisplatin pleurodesis (80 mg/m2) in a single-blind and controlled trial. Enrollment took place between Oct 2004 and Dec 2005. Primary efficacy endpoints were the best confirmed response rate, time to progression (TTP) in controlling MPE and adverse effects. Results: Fifteen of 30 patients were treated by carboplatin pleurodesis, and resting 15 of 30 patients were treated by cisplatin pleurodesis to control MPE. The response rate in carboplatin pleurodesis was not statistically different from that for patients in cisplatin pleurodesis (P = .226). The use of anticancer drugs for pleurodesis was not significantly associated with response rate in logistic regression analysis (relative risk = 14.2, 95% CI: 0.6–320.5, P = .095). Median TTP in carboplatin pleurodesis was not different from that in cisplatin pleurodesis (96 days vs 83 days). The use of carboplatin for pleurodesis (P = .016) and gender (P = .005) were associated with prolongation of TTP in the Cox regression method. Kaplan-Meier analysis showed that the progression free probability curve in carboplatin pleurodesis was not different from that in cisplatin pleurodesis (P = .275). The rate of Grade 3 thrombocytopenia in carboplatin pleurodesis (25%) was higher than that in cisplatin pleurodesis (0%), but there was no statistical significance (P = .096). Conclusions: Carboplatin pleurodesis and cisplatin pleurodesis may be feasible and acceptable toxicity profiles. No significant financial relationships to disclose.
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Honstettre, S., G. Julien, E. Allado, I. Chary Valckenaere, and D. Loeuille. "POS0502 ULTRASOUND THRESHOLDS FOR INFLAMMATORY AND STRUCTURAL LESIONS TODISTINGUISH OSTEOARTHRITIC FROM RHEUMATOID ARTHRITIS PATIENTS." Annals of the Rheumatic Diseases 81, Suppl 1 (May 23, 2022): 505.2–505. http://dx.doi.org/10.1136/annrheumdis-2022-eular.293.
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BackgroundRheumatoid arthritis (RA) is the most common chronic inflammatory rheumatic disease affecting small and medium-sized joints symmetrically, leading to poor functional outcomes and structural damages with time. The RA elementary inflammatory lesions, synovitis and tenosynovitis, have been associated with the development and worsening of bone erosions leading to loss of joint function and pain. The median age at diagnosis of RA patients, ranged between 50-60 years old, age at which degenerative and inflammation lesions relative to osteoarthritis (OA) damages may be present and interfere to establish a diagnosis of inflamed and/or structural RA disease.ObjectivesTo assess prevalence, topography and severity of inflammation and erosion on ultrasound (US) in RA and OA patients and to propose US thresholds to classify RA patients.MethodsPatients fulfilling ACR 1987 and/or ACR/EULAR 2010 criteria for RA or ACR criteria for hand OA were reprospectively included. Synovitis and tenosynovitis (TS) in B and Power Doppler (PD) modes on seven bilateral joints (carpus, MCP2, 3, 5, MTP2, 3, 5) were scored according to a four-grade scale of severity. Erosive disease was defined by the presence of at least one erosion >2 mm confirmed in 2 perpendicular plans on 30 targeted facet joints. Sensitivity, specificity and OR for the diagnosis of RA were calculated for each elementary (inflammatory and erosive) US lesion.Results153 patients were included: 107 (31 early <2 years) RA and 46 OA patients. Synovitis (B and PD modes) was observed in 92 (85.9%) RA and 12 (26%) OA patients, respectively (p <0.0001). TS (B and PD modes) was depicted in 61(57%) RA and 4 (8.7%) OA patients, respectively (p <0.0001). 71 (66%) RA and 5 (11%) OA patients responded to the definition of erosive disease (p<0.001). The combination of US erosion and PD+ synovitis provided the best compromise to classify RA patients: sensitivity 49.1% (39.7-58.4)), specificity 97.8% (87.4-99.5) and OR= 43.8 (CI95: 8.2-230.2). For early RA, PD+ TS provided the best compromise: sensitivity 54.8% (37.8-58.4), specificity 97.8% (87.4 -100) and OR= 54.6 (CI95: 9.3- 320.5).ConclusionThe combination of PD+ synovitis and erosion in RA and PD+ tenosynovitis alone in early RA offered the best compromise to classify RA versus OA patients.References[1]Scott DL et al. Rheumatoid arthritis. The Lancet.[2]Funck-Brentano et al. Prediction of Radiographic Damage in Early Arthritis by Sonographic Erosions and Power Doppler Signal: A Longitudinal Observational Study. Arthritis Care & Research.[3]Vlychou et al. Ultrasonographic evidence of inflammation is frequent in hands of patients with erosive osteoarthritis. Osteoarthritis and Cartilage.[4]Roux et al. Ultrasonographic criteria for the diagnosis of erosive rheumatoid arthritis using osteoarthritic patients as controls compared to validated radiographic criteria. Joint Bone Spine.[5]Sahbudin et al. The role of ultrasound-defined tenosynovitis and synovitis in the prediction of rheumatoid arthritis development.Disclosure of InterestsNone declared.
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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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Manana, Pholani, Eric C. Hosten, and Richard Betz. "The crystal structure of 4-chloro-thiophenol, C6H5ClS." Zeitschrift für Kristallographie - New Crystal Structures, July 13, 2021. http://dx.doi.org/10.1515/ncrs-2021-0225.
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Jiang, Xu, Zhen Wang, Jing Feng, Ziyi Du, Zhongjun Zhang, Yibin Zhang, Mingzhe Che, Junda Ren, Haiguang Wang, and Wei Quan. "Mapping and validation of a novel major QTL for resistance to stripe rust in four wheat populations derived from landrace Qishanmai." Frontiers in Plant Science 14 (June 16, 2023). http://dx.doi.org/10.3389/fpls.2023.1207764.
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Wheat yield has been constrained by stripe rust disease globally. A wheat landrace (Qishanmai, QSM) consistently showed lower stripe rust severities in multiple year studies than susceptible check varieties including Suwon11 (SW) at the adult plant stage. To detect QTL for reducing the severity in QSM, 1218 recombinant inbred lines (RILs) were developed from SW × QSM. QTL detection was conducted firstly using 112 RILs selected for similarity in pheno-morphological characters. The 112 RILs were assessed for stripe rust severity at the 2nd leaf, 6th leaf and flag leaf stages under field and greenhouse conditions, and genotyping was done primarily with a single nucleotide polymorphism (SNP) array. On the basis of these phenotypic and genotypic data, a major QTL (QYr.cau-1DL) was detected on chromosome 1D at the 6th leaf and flag leaf stages. Further mapping was conducted by genotyping 1218 RILs using new simple sequence repeat (SSR) markers, which were developed by referring to the sequences of the wheat line Chinese Spring (IWGSC RefSeq v1.0). QYr.cau-1DL was mapped within a 0.5 cM (5.2 Mb) interval delimited by the SSR markers 1D-320.58 and 1D-325.79. These markers were applied to select for QYr.cau-1DL by screening F2 or BC4F2 plants of the wheat crosses RL6058 × QSM, Lantian10 × QSM and Yannong21 × QSM. F2:3 or BC4F2:3 families derived from the selected plants were assessed for stripe rust resistance in the fields of two locations and in a greenhouse. Wheat plants carrying the resistant marker haplotype in homozygous state for QYr.cau-1DL showed lower stripe rust severities (by 44% to 48%) than plants lacking this QTL. The trial of RL6058 (a carrier of Yr18) × QSM also indicated that QYr.cau-1DL had larger effect than Yr18 on reducing severity; they acted synergistically, yielding an elevated level of stripe rust resistance.
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Eyo, Victor Oscar. "Effects of Weevil Infested Feed on the Fecundity and Gonadal Development of the African Catfish Clarias gariepinus (BURCHELL 1822)." Journal of Agricultural Science and Agrotechnology, May 13, 2022, 1–13. http://dx.doi.org/10.56391/jasa.2022.1003.
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This study was carried out for 126 days to evaluate the effects of weevil infested feed on the fecundity and gonadal development of the African Catfish Clariasgariepinus. Six (6) tarpaulin tanks (100 by 80 by 100 cm3) were stocked randomly with twenty (20) healthy post fingerlings of C. gariepinus with a mean initial bulk body weight 320.58 ± 1.24 g and total length 11.62 ± 0.36 cm. Coppens feed (42% crude protein) was divided into two groups including group A (control feed) and group B (weevil infested feed) and fed to the experimental fishes in triplicate group twice daily at 8.00 am and 4.00 pm at 3% of their body weight. Results showed a significant deterioration (P<0.05) in the proximate composition of weevil infested feed compared to the control feed. Mean fecundity of fish fed the control diet (27,440 ± 670.03 eggs) was significantly higher (P<0.05) than fish fed weevil infested feed (19,100 ± 650.00 eggs).A linear relationship and positive significant correlation (P>0.05) was obtained between fecundity of C. gariepinus fed the two diets and body parameters (total length, body weight, ovary weight, and mean egg diameter) except total length and total weight of fish fed weevil infested feed which showed a negative significant (P<0.05) relationship. Mean female gonad weight, female GSI and male gonad weight of fish fed the control was significantly better (P < 0.05) than fish fed weevil infested feed whereas male GSI showed no significant (P > 0.05) variation. Histological examination showed that the interstitial cells of the testes and oocytes were fully matured and normally distributed. Based on these findings, infestation of weevil in fish feed may lead to loss or deterioration of feed condition, quality, palatability, odor and taste which may affect feed acceptability. It is concluded that to obtain high fecundity and a better gonad development, weevil infested feed should be avoided. Feed should be stored in a good hygienic and sanitary conditions and infested feed should be destroyed with a serious implementation of sanitation and prevention practices to prevent the infestation from recurrence.
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Schönfeld, Tobias, Patrick Seitz, Christian Krieghoff, Slavica Ponorac, Alexander Wötzel, Stefan Olthoff, Sebastian Schaudt, Jonas Steglich, Matthias Gutberlet, and Robin F. Gohmann. "High-pitch CT pulmonary angiography (CTPA) with ultra-low contrast medium volume for the detection of pulmonary embolism: a comparison with standard CTPA." European Radiology, September 1, 2023. http://dx.doi.org/10.1007/s00330-023-10101-8.
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Abstract Objective To investigate the feasibility and image quality of high-pitch CT pulmonary angiography (CTPA) with reduced iodine volume in normal weight patients. Methods In total, 81 normal weight patients undergoing CTPA for suspected pulmonary arterial embolism were retrospectively included: 41 in high-pitch mode with 20 mL of contrast medium (CM); and 40 with normal pitch and 50 mL of CM. Subjective image quality was assessed and rated on a 3-point scale. For objective image quality, attenuation and noise values were measured in all pulmonary arteries from the trunk to segmental level. Contrast-to-noise ratio (CNR) was calculated. Radiation dose estimations were recorded. Results There were no statistically significant differences in patient and scan demographics between high-pitch and standard CTPA. Subjective image quality was rated good to excellent in over 90% of all exams with no significant group differences (p = 0.32). Median contrast opacification was lower in high-pitch CTPA (283.18 [216.06–368.67] HU, 386.81 [320.57–526.12] HU; p = 0.0001). CNR reached a minimum of eight in all segmented arteries, but was lower in high-pitch CTPA (8.79 [5.82–12.42], 11.01 [9.19–17.90]; p = 0.005). Median effective dose of high-pitch CTPA was lower (1.04 [0.72–1.27] mSv/mGy·cm; 1.49 [1.07–2.05] mSv/mGy·cm; p < 0.0001). Conclusion High-pitch CTPA using ultra-low contrast volume (20 mL) rendered diagnostic images for the detection of pulmonary arterial embolism in most instances. Compared to standard CTPA, the high-pitch CTPA exams with drastically reduced contrast medium volume had also concomitantly reduced radiation exposure. However, objective image quality of high-pitch CTPA was worse, though likely still within acceptable limits for confident diagnosis. Clinical relevance This study provides valuable insights on the performance of a high-pitch dual-source CTPA protocol, offering potential benefits in reducing contrast medium and radiation dose while maintaining sufficient image quality for accurate diagnosis in patients suspected of pulmonary embolism. Key Points • High-pitch CT pulmonary angiography (CTPA) with ultra-low volume of contrast medium and reduced radiation dose renders diagnostic examinations with comparable subjective image quality to standard CTPA in most patients. • Objective image quality of high-pitch CTPA is reduced compared to standard CTPA, but contrast opacification and contrast-to-noise ratio remain above diagnostic thresholds. • Challenges of high-pitch CTPA may potentially be encountered in patients with severe heart failure or when performing a Valsalva maneuver during the examination.
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Runco, Daniel V., Linda A. DiMeglio, Charles P. Vanderpool, Yan Han, Joanne Daggy, Mary M. Kelley, Raya Mikesell, and Teresa A. Zimmers. "Growth differentiation factor 15 (GDF15) elevation in children with newly diagnosed cancer." Frontiers in Oncology 13 (December 11, 2023). http://dx.doi.org/10.3389/fonc.2023.1295228.
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BackgroundGrowth differentiation factor 15 (GDF15), an inflammatory marker and mediator of adult cancer cachexia, remains largely unexplored in children. GDF15 increases nausea, vomiting, and anorexia in cancer and contributes to malnutrition, with the potential to be a cachexia therapeutic target. No studies have examined GDF15 in children with newly diagnosed cancer. Our pilot study compares GDF15 in children with newly diagnosed cancer to age- and sex-matched controls and correlates levels with anthropometric measurements and quality of life (QOL).MethodsChildren with newly diagnosed cancer aged 2-21 years were enrolled with serum GDF15 ELISA, anthropometric measures [height, weight, and mid-upper arm circumference (MUAC)], and QOL assessments (using PedsQL™ Core and Gastrointestinal Modules), which were collected at baseline and repeated 3 months later. Serum GDF15 levels were obtained from age- and sex-matched controls for comparison.ResultsA total of 57 participants enrolled (N=30, cancer group; N=27, control group) with a median age of 8.8 years (IQR 5.6-15.9 years). The participants were primarily male (54.4%), white (82.5%), and non-Hispanic (82.5%). Cancer diagnoses included acute lymphoblastic leukemia (N=8), lymphoma (N=8), neuroblastoma (N=5), soft tissue tumors (N=4), acute myeloid leukemia (N=2), and single participants with brain, kidney, and bone tumors. Baseline GDF15 was higher in the cancer cohort compared to the control cohort (median=614.6pg/mL and 320.5pg/mL, respectively; p<0.001). When examining participants with evaluable baseline and 3-month follow-up GDF15 levels (N=18), GDF15 was not statistically different (median=657.1pg/mL and 675.3pg/mL, respectively; p=0.702). A total of 13 of the 30 participants and 21 caregivers completed the PedsQL™ Core and Gastrointestinal symptom modules. QOL scores did not differ significantly at 3-month follow-up compared to baseline, but diarrhea worsened (p=0.017). Median participant response for diarrhea at baseline was 92.9 (IQR=92.9-96.4; N=13), which was significantly better than the follow-up (median=78.6; IQR= 71.4-92.9; p=0.017). There were no correlations between change in height, weight, or MUAC and change in GDF15 levels (p=0.351, 0.920, and 0.269 respectively).ConclusionGDF15 was elevated in children with cancer at diagnosis compared to controls but did not correlate with anthropometric measurements or QOL. This pilot study will inform future prospective studies to better describe the natural history of GDF15 and its role in cachexia and as a potential therapeutic target.
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JANUSZEWSKI, ANDRZEJ S., LUKE CARROLL, YIK W. LOH, DAVID N. O'NEAL, and ALICIA JENKINS. "403-P: Reduced Mitochondrial DNA Copy Number in Type 1 Diabetes and Nephropathy and Correlates Thereof." Diabetes 71, Supplement_1 (June 1, 2022). http://dx.doi.org/10.2337/db22-403-p.
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Background: Mitochondrial DNA (Mt-DNA) copy number (mtDNA-CN) has been proposed as a marker of diabetic kidney disease (DKD) . Most studies are in type 2 diabetes. We determined mtDNA-CN in adults with type 1 diabetes vs. non-diabetic subjects, including associations with complications and risk factors. Methods: Cross-sectional study: 178 T1D adults (mean (SD) age: 38 (14) yrs, 21 (14) yrs T1D, HbA1c: 8.0 (1.5) %, 36% with complications (CX+)) ; 132 non-diabetic adults (CON) (age: 37 (14) yrs, HbA1c: 5.1 (0.4) %) . mtDNA-CN by RT-PCR (ScienCell, Carlsbad, CA) in DNA from whole blood samples. Results: T1D vs. CON: Median (LQ, UQ) mtDNA-CN in T1D vs. CON: 270.8 (189.4, 348.1) vs. 320.5 (264.4, 410.5) ; p<0.0001. mtDNA-CN was lower in T1D with vs. without DKD (238.2 (179.6, 309.1) vs. 293.7 (197.6, 364.4) ; p=0.02, but did not differ by retinopathy or macrovascular disease. T1D mtDNA-CN tertiles: The highest tertile had lowest CX rate (25% (tertile 3) vs. 41% (tertiles 1+2) , p=0.03. Detectable C-peptide rates increased with higher mtDNA-CN tertiles (55%, 69%, 79%, p=0.02) . There were no differences by sex, smoking, BMI status, metabolic syndrome, HbA1c, exercise, statins or ACE/ARB. Correlates of mtDNA-CN: In T1D: FBG (r=-0.19, p=0.02) , HDL-C (r=0.17, p=0.03) , WCC (r=-0.16, p=0.04) , sVCAM-1 (r=-0.17, p=0.03) and sICAM-1 (r=-0.20, p=0.02) . In CON: WHR (r=-0.22, p=0.03) ; WCC (r=-0.24, p=0.007) . Independent determinants of mtDNA-CN: In T1D: age (-0.25±0.10; p=0.02) , HDL-C (0.27±0.10; p=0.007) , sICAM-1 (-0.42±0.12; p=0.001) . Area under ROC curve 0.72. In CON: pulse pressure (0.25±013; p=0.047) , WCC (-0.41±0.15; p=0.005) , smoking status (never) (0.22±0.13; p=0.09) ; sex (female) (0.35±0.12; p=0.005) . Area under ROC curve 0.74. Conclusion: T1D per se is associated with lower mtDNA-CN than CON, particularly with DKD. Higher mtDNA-CN in T1D is associated with detectable C-peptide. Age and inflammation related factors are associated with mtDNA-CN. Longitudinal and intervention studies are merited. Disclosure A.S.Januszewski: None. L.Carroll: None. Y.W.Loh: None. D.N.O'neal: None. A.Jenkins: Advisory Panel; Abbott Diabetes, Amgen Inc., Board Member; Insulin for Life , International Diabetes Federation Western Pacific Region, Research Support; JDRF, Medtronic, Mylan N.V., NHMRC Australia.
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Cristina Martins, Ana, Diogo Francisco, Gonçalo Pimenta, Margarida Gonçalves, Célia Gil, Ivo Laranjinha, and Augusta Gaspar. "MO147: Fat Check: Lipid Abnormalities in Nephrotic Primary Glomerulopathies." Nephrology Dialysis Transplantation 37, Supplement_3 (May 2022). http://dx.doi.org/10.1093/ndt/gfac066.049.
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Abstract BACKGROUND AND AIMS Lipid abnormalities are a defining feature of nephrotic syndrome. In nephrotic patients, changes such as increased total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG) and decreased high-density lipoprotein cholesterol (HDL-C) as well as decreased HDL-C: TC ratio are more frequently found than in healthy subjects. The aims of this study were to evaluate the differences in the serum lipidic profile at baseline (diagnosis) among each primary glomerulopathies (PG) presenting with nephrotic syndrome (NS) and its association with several clinical parameters such as serum albumin (SAbl) and proteinuria. METHOD We conducted a retrospective cohort study with patients older than 18 years who presented with nephrotic syndrome and diagnosed with a PG by kidney biopsy in the last 10 years in a tertiary-level hospital. RESULTS The study included 60 patients: 38 were male (63.3%), with median age of 52 (IQR 27) years, 43.3% had hypertension, median serum creatinine (SCr) was 1.11 mg/dL (IQR 0.86), median protein-creatinine ratio was 7443 (IQR 5033.5) mg/g and median SAlb of 2.0 (IQR 1.03) mg/dL. At baseline, the median TC was 320.5 mg/dL (IQR 184.5), HDL-C 55 (IQR 25.5) mg/dL, LDL-C 225mg/dL (IQR 174), TG 176 (IQR 122.6) mg/dL and HDL: TC ratio 0.19 (IQR 0.13). Median follow-up time was 24 (IQR 51) months. Patients were grouped in four categories regarding the PG subtype: membranous nephropathy (MN, 38.3%), minimal change disease (MCD, 38.3%), IgA nephropathy (IgAN, 11.7%) and focal segmental glomerulosclerosis (FSGS, 11.7%). Evaluating all the patients enrolled, we found a strong negative correlation between SAlb and TC (r = –0.511, P < .001), LDL-C (r = –0.529, P < .001) and a weaker negative correlation with TG (r = –0.282, P = .030), but not with HDL-C. We did not find a statistically significant correlation between proteinuria and each cholesterol subtype or TG levels. A Kruskal–Wallis test showed that different subtypes of PG were associated with different median HDL-C (H(3) = 12.073, P = .007) and TG serum levels (H(3) = 10.128, P = .018). No statistically significant differences in the TC, LDL-C or HDL-C: TC ratio were found. Comparing all pairs of groups, we found that HDL-C levels were statistically different between MN and MCD (45.5 versus 67 mg/dL, P < .001), but not in the other pairs. The same analysis found that TG serum levels were only significantly different between IgAN and MN (114 versus 187 mg/dL, P = .008) and between IgAN and FSGS (114 versus 200 mg/dL, P = .012). MN patients that progressed to CKD stage 5D had lower median HDL-C levels at diagnosis, when compared to the patients who did not progress (41 versus 49 mg/dL, P = .037). This difference was not observed in IgA, FSGS or MCD. CONCLUSION Each GP subtype presents a different lipid profile, particularly differing on HDL and TG. Patients with MCD presented with the highest levels of HDL-C, while MN with the lowest. Regarding TG levels, FSGS presented with the highest levels while IgAN presented with the lowest. In the membranous nephropathy group, patients that progressed to ESRD had statistically significantly lower serum levels of HDL-C. As expected, SAlb is significantly associated with TC, LDL-C and TG levels, in nephrotic patients. This could be due to different levels of lecithin–cholesterol acyltransferase (an enzyme responsible for the maturation of HDL), which is increasingly lost through urine in nephrotic syndromes. The differences found in the lipidic profile between PG subtypes could have screening, therapeutic and prognosis implications in the management of cardiovascular risk in these patients. More studies are needed to understand the pathophysiology and the prognosis significance of each lipid profile.
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Venturella, R., A. Lukes, R. McLean, D. Zhai, and A. Al-Hendy. "O-191 Effects of relugolix combination therapy (Relugolix-CT) on uterine fibroid (UF) and uterine volume through 52 weeks: post hoc analysis of the LIBERTY Long-Term Extension study." Human Reproduction 38, Supplement_1 (June 1, 2023). http://dx.doi.org/10.1093/humrep/dead093.232.
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Abstract Study question How does baseline UF and uterine volume impact the proportion of women achieving meaningful UF and uterine volume reductions with Relugolix-CT through 52 weeks? Summary answer Women with larger UF and uterine volumes at baseline may be more likely to experience clinically meaningful reductions of UF and uterine volume with Relugolix-CT. What is known already In the randomised, Phase 3 LIBERTY 1 and 2 pivotal studies, the efficacy and safety of once-daily Relugolix-CT (relugolix 40 mg, estradiol 1 mg, norethisterone acetate 0.5 mg) were demonstrated in premenopausal women (aged 18–50 years), with a significant reduction in UF-associated heavy menstrual bleeding (HMB) vs placebo, and preserved bone mineral density (BMD) through 24 weeks. The open-label, 28-week LIBERTY Long-Term Extension (LTE) study continued to demonstrate sustained menstrual blood loss reductions and preservation of BMD, alongside reductions in UF and uterine volume. Study design, size, duration The LIBERTY 1 and 2 studies of Relugolix-CT were conducted in 770 premenopausal women with UF-associated HMB. Women were randomised 1:1:1 to receive Relugolix-CT or placebo for 24 weeks, or delayed Relugolix-CT (relugolix 40 mg alone for 12 weeks, then Relugolix-CT for 12 weeks). Women who completed the pivotal trials were eligible to participate in the LIBERTY LTE study, receiving open-label Relugolix-CT for an additional 28 weeks. Participants/materials, setting, methods Endpoints of the LTE included change from baseline to Week 52 in UF and uterine volume. This post hoc analysis assessed the proportion of women who experienced a clinically meaningful reduction in UF or uterine volume of > 25% or > 50% through 52 weeks of Relugolix-CT. Subgroup analyses were performed to descriptively summarise the impact of UF and uterine volume at baseline (<25cm3 or ≥ 25cm3; <300cm3 or ≥ 300cm3, respectively) on change in UF and uterine volume. Main results and the role of chance In total, 477 women enrolled in the LTE, 363 completed 52 weeks of treatment, and 163 received Relugolix-CT continuously up to 52 weeks. At baseline, the mean (standard deviation) volume of the largest UF was 80.0 (145.1) cm3; mean (SD) uterine volume was 386.7 (320.5) cm3 in the Relugolix-CT group. At Week 24, 52.6% and 30.3% of women in the Relugolix-CT group experienced >25% and >50% reduction in UF volume, respectively. These proportions increased to 61.1% and 36.6%, respectively, at Week 52. For uterine volume, 36.1% and 4.5% experienced a > 25% and >50% reduction at Week 24, increasing to 41.2% and 9.6% at Week 52. At Week 52, of 81 women with a baseline UF volume of < 25cm3, 52.4% and 27.0% experienced a > 25% and >50% reduction in UF volume, respectively; 69.1% and 45.6% of 81 women with a baseline UF volume of ≥ 25cm3 experienced >25% and >50% reductions in UF volume, respectively. At Week 52, of 96 women with a baseline uterine volume of < 300cm3, 38.5% and 6.4% experienced a > 25% and >50% reduction in uterine volume; 44.8% and 13.8% of 67 women with a baseline uterine volume of ≥ 300cm3 experienced >25% and >50% reductions in uterine volume. Limitations, reasons for caution The study was conducted as an open-label study without a control group over the 28 weeks of the extension period. The present data are from a post hoc analysis of LIBERTY data without predefined criteria. Wider implications of the findings Treatment with Relugolix-CT led to a substantial reduction of UF and uterine volume in a large proportion of women with UF-associated HMB. Women with larger UF and uterine volume at baseline may be more likely to experience substantial reductions of UF and uterine volume. Trial registration number NCT03049735, NCT03103087, NCT03412890