Towards a Reconfigurable Sense-and-Stimulate Neural Interface Generating Biphasic Interleaved Stimulus

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The Evaluation of Total Antioxidant Capacity and Related Markers in Patients with Chronic Peritoneal Dialysis

Abstract: Introduction: Oxidative stress due to overproduction of reactive oxygen species and impairment in antioxidant defense mechanisms have been suggested as possible factors contributing to the pathogenesis of atherosclerosis in patients with end- stage renal disease. The aim of this study was to evaluate antioxidant markers of oxidative stress including glutathione and glutathione related enzymes [i.e. glutathione peroxidase (GPx) and glutathione reductase (GR)] as well as total antioxidant capacity in peritoneal dialysis (PD) patients. Methods: Twelve PD patients and 17 healthy controls (age range: 25-60 and 22-53 years respectively) were selected. Erythrocyte glutathione levels and plasma activities of GPx, GR and total antioxidant capacity were determined spectrophtometrically. Results: Glutathione levels and GPx activity were significantly lower in the patients group than in controls (1.17± 0.28 vs. 1.42± 0.25 µmol/ml and 57.1± 21.8 vs. 142.5± 31.7 U/L; p<0.05, respectively). Higher levels of GR activity and total antioxidant capacity were noted in patient group (57.5± 16.4 U/L and 0.60± 0.09 µmol/ml; respectively) in comparison to control group (32± 9.4 U/L and 0.47± 0.11 µmol/ml; p<0.05, respectively). Conclusion: Decreased glutathione levels and alteration in the activities of its related enzymes imply increased oxidative stress and disturbances of antioxidant defense systems in peritoneal dialysis patients. This condition may contribute to the development of accelerated cardiovascular disease and its morbidity and mortality in these patients. Keywords: Peritoneal dialysis, Oxidative stress, Glutathione, Glutathione peroxidase, Glutathione reductase, Total antioxidant capacit

A Programmable Neural Interface for Investigating Arbitrary Stimulation Strategies

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Confession Session: Learning from Others Mistakes

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Total hip replacement. Results of a postal survey of current practice on the cement fixation of the acetabular cup in the UK

Previous finite element studies and laboratory investigations on reconstructed acetabulum joints show that long-term fixation of the acetabular cup in total hip replacements (THRs) is influenced by surgical fixation techniques. The aim of this study is to determine and understand the reasons of current practice in the cement fixation of the acetabular cup in THRs in the UK. Following a pilot study, a postal survey was carried out among 1350 orthopaedic consultants. Response rate was 40% and data obtained from the returned questionnaires provided information about the current practice of 431 consultants with an average of 16.5 years of experience and who perform an average of 55 cemented THR operations annually. The survey showed wide variations in the fixation methods of the acetabular component. 95% of the respondents use cement to fix the acetabular cup, 46% maintain the subchondral bone and 63 % use a flanged acetabular cup. The numbers of anchorage holes drilled vary from zero to thirty-six and drill diameters vary from 2 to 15 mm. Anchorage hole depths vary from 3 to 20 mm. Given the variability of surgical fixation methods, further studies need to be carried out to determine how fixation techniques could be improved to increase the longevity of the acetabular component in THRs. Further investigations could lead to a better understanding of the factors that contribute to the stability of THRs

Genetically Engineered Alginate Lyase-PEG Conjugates Exhibit Enhanced Catalytic Function and Reduced Immunoreactivity

Alginate lyase enzymes represent prospective biotherapeutic agents for treating bacterial infections, particularly in the cystic fibrosis airway. To effectively deimmunize one therapeutic candidate while maintaining high level catalytic proficiency, a combined genetic engineering-PEGylation strategy was implemented. Rationally designed, site-specific PEGylation variants were constructed by orthogonal maleimide-thiol coupling chemistry. In contrast to random PEGylation of the enzyme by NHS-ester mediated chemistry, controlled mono-PEGylation of A1-III alginate lyase produced a conjugate that maintained wild type levels of activity towards a model substrate. Significantly, the PEGylated variant exhibited enhanced solution phase kinetics with bacterial alginate, the ultimate therapeutic target. The immunoreactivity of the PEGylated enzyme was compared to a wild type control using in vitro binding studies with both enzyme-specific antibodies, from immunized New Zealand white rabbits, and a single chain antibody library, derived from a human volunteer. In both cases, the PEGylated enzyme was found to be substantially less immunoreactive. Underscoring the enzyme's potential for practical utility, >90% of adherent, mucoid, Pseudomonas aeruginosa biofilms were removed from abiotic surfaces following a one hour treatment with the PEGylated variant, whereas the wild type enzyme removed only 75% of biofilms in parallel studies. In aggregate, these results demonstrate that site-specific mono-PEGylation of genetically engineered A1-III alginate lyase yielded an enzyme with enhanced performance relative to therapeutically relevant metrics.Cystic Fibrosis Foundation (Research Development Program)National Center for Research Resources (U.S.) (P20RR018787-06

Effects of melatonin administration on mental health parameters, metabolic and genetic profiles in women with polycystic ovary syndrome: A randomized, double-blind, placebo-controlled trial

Objective: The aim of this study was to evaluate the effect of melatonin supplementation on mental health parameters, metabolic and genetic parameters in women suffering from polycystic ovary syndrome (PCOS). Methods: This randomized, double-blinded, placebo-controlled clinical trial was performed on 58 subjects, aged 18�40 years old. Subjects were randomly allocated to take either 10 mg melatonin (2 melatonin capsules, 5 mg each) (n = 29) or placebo (n = 29) once a day 1 h before bedtime for 12 weeks. Glycemic control and lipid profiles were measured at baseline and after the 12-week intervention. Using RT-PCR method, gene expression related to insulin and lipid metabolism was conducted on peripheral blood mononuclear cells (PBMCs) of PCOS women. Results: Melatonin supplementation significantly decreased Pittsburgh Sleep Quality Index (β �2.15; 95 CI, �3.62, �0.68; P = 0.005), Beck Depression Inventory index (β �3.62; 95 CI, �5.53, �1.78; P<0.001) and Beck Anxiety Inventory index (β �1.95; 95 CI, �3.41, �0.48; P = 0.01) compared with the placebo. In addition, melatonin administration, compared with the placebo, significantly reduced serum insulin (β �1.20 µIU/mL; 95 CI, �2.14, �0.26; P = 0.01), homeostasis model of assessment-insulin resistance (HOMA-IR) (β �0.28; 95 CI, �0.50, �0.05; P = 0.01), serum total- (β �7.96 mg/dL; 95 CI, �13.75, �2.17; P = 0.008) and LDL-cholesterol levels (β �5.88 mg/dL; 95 CI, �11.42, �0.33; P = 0.03), and significantly increased the quantitative insulin sensitivity check index (QUICKI) (β 0.008; 95 CI, 0.002, 0.014; P = 0.007). Moreover, melatonin supplementation upregulated gene expression of peroxisome proliferator-activated receptor gamma (PPAR-γ) (P = 0.004) and low-density lipoprotein receptor (LDLR) (P = 0.01) compared with the placebo. Conclusions: Overall, melatonin administration for 12 weeks had beneficial effects on mental health parameters, insulin levels, HOMA-IR, QUICKI, total- and LDL-cholesterol levels, and gene expression of PPAR-γ and LDLR among women with PCOS. © 2019 Elsevier B.V

Is generative AI reshaping academic practices worldwide? A survey of adoption, benefits, and concerns

Although generative AI is transforming academic research and education, little is known about the role, gender, international, and disciplinary variations in uptake and use. This 20-country survey of publishing academics shows the widespread awareness and adoption of generative AI tools in academia, but with substantial international and disciplinary differences, and some role and gender differences. In particular, females were 10 % less likely to use Gen AI frequently (daily or weekly) for research, which may exacerbate gender inequalities. Perhaps surprisingly, the highest adoption rates occurred in some non-Western nations, possibly because of a greater need for translation services. The highest awareness is in the social sciences, perhaps because of the greater need for text analysis. Across all groups, these tools were mainly used for academic writing rather than data analysis and support for critical thinking. Despite this, personalized instruction and problem-solving are among generative AI's most generally claimed benefits. However, participants in all groups were skeptical about the creativity, accuracy, and consistency of AI-generated content in academic contexts. The most significant concerns about using generative AI in academia were inaccuracy, plagiarism, discouraging critical thinking, a lack of transparency and explainability, intellectual property rights violations, and data privacy risks. For policymakers, the findings point to fields and countries that may need action to prevent falling behind, as well as the ongoing need to investigate and monitor the impacts of generative AI on research practices

Effects of melatonin supplementation on hormonal, inflammatory, genetic, and oxidative stress parameters in women with polycystic ovary syndrome

Purpose: The aim of the current study was to evaluate the effect of melatonin administration on clinical, hormonal, inflammatory, and genetic parameters in women with polycystic ovarian syndrome (PCOS). Methods: The present randomized, double-blinded, placebo-controlled clinical trial was conducted among 56 patients with PCOS, aged 18�40 years old. Subjects were randomly allocated to take either 5 mg melatonin supplements (n = 28) or placebo (n = 28) twice a day for 12 weeks. Results: Melatonin administration significantly reduced hirsutism (β �0.47; 95 CI, �0.86, �0.09; P = 0.01), serum total testosterone (β �0.11 ng/mL; 95 CI, �0.21, �0.02; P = 0.01), high-sensitivity C-reactive protein (hs-CRP) (β �0.61 mg/L; 95 CI, �0.95, �0.26; P = 0.001), and plasma malondialdehyde (MDA) levels (β �0.25 μmol/L; 95 CI, �0.38, �0.11; P < 0.001), and significantly increased plasma total antioxidant capacity (TAC) levels (β 106.07 mmol/L; 95 CI, 62.87, 149.28; P < 0.001) and total glutathione (GSH) (β 81.05 μmol/L; 95 CI, 36.08, 126.03; P = 0.001) compared with the placebo. Moreover, melatonin supplementation downregulated gene expression of interleukin-1 (IL-1) (P = 0.03) and tumor necrosis factor alpha (TNF-α) (P = 0.01) compared with the placebo. Conclusions: Overall, melatonin administration for 12 weeks to women with PCOS significantly reduced hirsutism, total testosterone, hs-CRP, and MDA, while increasing TAC and GSH levels. In addition, melatonin administration reduced gene expression of IL-1 and TNF-α. Copyright © 2019 Jamilian, Foroozanfard, Mirhosseini, Kavossian, Aghadavod, Bahmani, Ostadmohammadi, Kia, Eftekhar, Ayati, Mahdavinia and Asemi