3,420 research outputs found

    Peptides as Promising Non-Viral Vectors for Gene Therapy

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    Particle creation rate for dynamical black holes

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    We present the particle creation probability rate around a general black hole as an outcome of quantum fluctuations. Using the uncertainty principle for these fluctuation, we derive a new ultraviolet frequency cutoff for the radiation spectrum of a dynamical black hole. Using this frequency cutoff, we define the probability creation rate function for such black holes. We consider a dynamical Vaidya model, and calculate the probability creation rate for this case when its horizon is in a slowly evolving phase. Our results show that one can expect the usual Hawking radiation emission process in the case of a dynamical black hole when it has a slowly evolving horizon. Moreover, calculating the probability rate for a dynamical black hole gives a measure of when Hawking radiation can be killed off by an incoming flux of matter or radiation. Our result strictly suggests that we have to revise the Hawking radiation expectation for primordial black holes that have grown substantially since they were created in the early universe. We also infer that this frequency cut off can be a parameter that shows the primordial black hole growth at the emission moment.Comment: 10 pages, 1 figure. The paper was rewritten in more clear presentation and one more appendix is adde

    Decreased total antioxidant levels and increased oxidative stress in South African type 2 diabetes mellitus patients

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    Background: Chronic hyperglycaemia in diabetes mellitus leads to increased lipid peroxidation in the body, followed by the development of chronic complications due to oxidative stress. Objective: The aim of this study was to compare total antioxidant (TAO) levels and oxidative stress in type 2 diabetes mellitus (T2DM) patients with that of healthy controls without diabetes.Methods: A total of 98 participants (57 T2DM and 41 healthy people) gave their consent and participated in the study. Routine biochemical methods were used for fasting plasma glucose (FPG), glycosylated haemoglobin (HbA1c) and lipid profile measurements. Serum TAO levels, malondialdehyde (MDA), oxidised low-density lipoprotein (ox-LDL) levels and superoxide dismutase (SOD) activity were analysed using standard commercial reagent kits.Results: A significant rise in FPG, HbA1c, triglycerides, MDA and ox-LDL, and a significant reduction in TAO and high-density lipoprotein cholesterol (HDL-C) was observed in T2DM patients compared with controls. A significant negative relationship was observed between TAO levels and MDA levels in the T2DM group. Increased lipid peroxidation and reduced antioxidant levels were observed in T2DM patients.Conclusion: Early management through an antioxidant-rich diet and lifestyle changes in T2DM patients would help to avert the debilitating complications of diabetes.Keywords: diabetes mellitus, oxidative stress, total antioxidant statu

    Patient-reported outcomes measures and patient preferences for minimally invasive glaucoma surgical devices.

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    BackgroundMany therapeutic options are available to glaucoma patients. One recent therapeutic option is minimally invasive glaucoma surgical (MIGS) devices. It is unclear how patients view different treatments and which patient-reported outcomes would be most relevant in patients with mild to moderate glaucoma. We developed a questionnaire for patients eligible for MIGS devices and a patient preference study to examine the value patients place on certain outcomes associated with glaucoma and its therapies.ObjectivesTo summarize the progress to date.MethodsQuestionnaire development: We drafted the questionnaire items based on input from one physician and four patient focus groups, and a review of the literature. We tested item clarity with six cognitive interviews. These items were further refined. Patient preference study: We identified important benefit and risk outcomes qualitatively using semi-structured, one-on-one interviews with patients who were eligible for MIGS devices. We then prioritized these outcomes quantitatively using best-worst scaling methods.ResultsQuestionnaire testing: Three concepts were deemed relevant for the questionnaire: functional limitations, symptoms, and psychosocial factors. We will evaluate the reliability and validity of the 52-item draft questionnaire in an upcoming field test. Patient preference study: We identified 13 outcomes that participants perceived as important. Outcomes with the largest relative importance weights were "adequate IOP control" and "drive a car during the day."ConclusionsPatients have the potential to steer clinical research towards outcomes that are important to them. Incorporating patients' perspectives into the MIGS device development and evaluation process may expedite innovation and availability of these devices

    Transcription profiling reveals potential mechanisms of dysbiosis in the oral microbiome of rhesus macaques with chronic untreated SIV infection.

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    A majority of individuals infected with human immunodeficiency virus (HIV) have inadequate access to antiretroviral therapy and ultimately develop debilitating oral infections that often correlate with disease progression. Due to the impracticalities of conducting host-microbe systems-based studies in HIV infected patients, we have evaluated the potential of simian immunodeficiency virus (SIV) infected rhesus macaques to serve as a non-human primate model for oral manifestations of HIV disease. We present the first description of the rhesus macaque oral microbiota and show that a mixture of human commensal bacteria and "macaque versions" of human commensals colonize the tongue dorsum and dental plaque. Our findings indicate that SIV infection results in chronic activation of antiviral and inflammatory responses in the tongue mucosa that may collectively lead to repression of epithelial development and impact the microbiome. In addition, we show that dysbiosis of the lingual microbiome in SIV infection is characterized by outgrowth of Gemella morbillorum that may result from impaired macrophage function. Finally, we provide evidence that the increased capacity of opportunistic pathogens (e.g. E. coli) to colonize the microbiome is associated with reduced production of antimicrobial peptides

    Empagliflozin and Cardiovascular and Kidney Outcomes across KDIGO Risk Categories: Post Hoc Analysis of a Randomized, Double-Blind, Placebo-Controlled, Multinational Trial

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    BACKGROUND AND OBJECTIVES: In the Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients (EMPA-REG Outcome), empagliflozin, in addition to standard of care, significantly reduced risk of cardiovascular death by 38%, hospitalization for heart failure by 35%, and incident or worsening nephropathy by 39% compared with placebo in patients with type 2 diabetes and established cardiovascular disease. Using EMPA-REG Outcome data, we assessed whether the Kidney Disease Improving Global Outcomes (KDIGO) CKD classification had an influence on the treatment effect of empagliflozin. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Patients with type 2 diabetes, established atherosclerotic cardiovascular disease, and eGFR≥30 ml/min per 1.73 m2 at screening were randomized to receive empagliflozin 10 mg, empagliflozin 25 mg, or placebo once daily in addition to standard of care. Post hoc, we analyzed cardiovascular and kidney outcomes, and safety, using the two-dimensional KDIGO classification framework. RESULTS: Of 6952 patients with baseline eGFR and urinary albumin-creatinine ratio values, 47%, 29%, 15%, and 8% were classified into low, moderately increased, high, and very high KDIGO risk categories, respectively. Empagliflozin showed consistent risk reductions across KDIGO categories for cardiovascular outcomes (P values for treatment by subgroup interactions ranged from 0.26 to 0.85) and kidney outcomes (P values for treatment by subgroup interactions ranged from 0.16 to 0.60). In all KDIGO risk categories, placebo and empagliflozin had similar adverse event rates, the notable exception being genital infection events, which were more common with empagliflozin for each category. CONCLUSIONS: The observed effects of empagliflozin versus placebo on cardiovascular and kidney outcomes were consistent across the KDIGO risk categories, indicating that the effect of treatment benefit of empagliflozin was unaffected by baseline CKD status. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: EMPA-REG OUTCOME, NCT01131676

    Psychometric properties of a prostate cancer radiation late toxicity questionnaire

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    <p>Abstract</p> <p>Background</p> <p>To construct a short prostate cancer radiation late toxicity (PCRT) questionnaire with health-related quality-of-life (HRQoL) domains.</p> <p>Methods</p> <p>The PCRT was developed by item generation, questionnaire construction (n = 7 experts, n = 8 focus group patients), pilot testing (n = 37), item reduction (n = 100), reliability testing (n = 237), and validity testing (n = 274).</p> <p>Results</p> <p>Reliability of the three item-reduced subscales demonstrated intraclass correlation coefficients (CC) of 0.811 (GU), 0.842 (GI), and 0.740 (sexual). Discriminant validity demonstrated Pearson CC of 0.449 (GU-GI), 0.200 (sexual-GU), and 0.09 (sexual-GI). Content validity correlations between PCRT-PCQoL were 0.35–0.78, PCRT-FACT-G<sup>© </sup>were 0.19–0.39, and PCRT-SF-36<sup>® </sup>were 0.03–0.34.</p> <p>Conclusion</p> <p>We successfully generated a PCRT HRQoL questionnaire including subscales with very good psychometric properties.</p

    Selective Breeding for a Behavioral Trait Changes Digit Ratio

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    The ratio of the length of the second digit (index finger) divided by the fourth digit (ring finger) tends to be lower in men than in women. This 2D∶4D digit ratio is often used as a proxy for prenatal androgen exposure in studies of human health and behavior. For example, 2D∶4D ratio is lower (i.e. more “masculinized”) in both men and women of greater physical fitness and/or sporting ability. Lab mice have also shown variation in 2D∶4D as a function of uterine environment, and mouse digit ratios seem also to correlate with behavioral traits, including daily activity levels. Selective breeding for increased rates of voluntary exercise (wheel running) in four lines of mice has caused correlated increases in aerobic exercise capacity, circulating corticosterone level, and predatory aggression. Here, we show that this selection regime has also increased 2D∶4D. This apparent “feminization” in mice is opposite to the relationship seen between 2D∶4D and physical fitness in human beings. The present results are difficult to reconcile with the notion that 2D∶4D is an effective proxy for prenatal androgen exposure; instead, it may more accurately reflect effects of glucocorticoids, or other factors that regulate any of many genes

    Management approach for recurrent spontaneous pneumothorax in consecutive pregnancies based on clinical and radiographic findings

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    OBJECTIVE: To describe management and clinical features observed in a patient's seven spontaneous pneumothoraces that developed during two consecutive pregnancies involving both hemithoraces. MATERIALS AND METHODS: A 21 year old former smoker developed three spontaneous left pneumothoraces in the index pregnancy, having already experienced four right pneumothorax events in a prior pregnancy at age 19. RESULTS: Chest tubes were required in several (but not all) hospitalizations during these two pregnancies. Following her fourth right pneumothorax, thoracoscopic excision of right apical lung blebs and mechanical pleurodesis was performed. The series of left pneumothoraces culminated in mini-thoracotomy and thoracoscopically directed mechanical pleurodesis. For both pregnancies unassisted vaginal delivery was performed with no adverse perinatal sequelae. With the exception of multiple pneumothoraces, there were no additional pregnancy complications. CONCLUSION: Spontaneous pneumothorax in pregnancy is believed to be a rare phenomenon, yet the exact incidence is unknown. Here we present the first known case of multiple spontaneous pneumothoraces in two consecutive pregnancies involving both hemithoraces. Clinical management coordinated with obstetrics and surgical teams facilitated a satisfactory outcome for both pregnancies. The diagnosis of pneumothorax should be contemplated in any pregnant patient with dyspnea and chest pain, followed by radiographic confirmation
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