The outcome of Descemet membrane endothelial keratoplasty (DMEK) with different tamponade material.

OBJECTIVE: To compare the outcome of different tamponade material in Descemet membrane endothelial keratoplasty (DMEK). METHODS: Retrospective, interventional case series that includes 8 patients underwent DMEK performed by a single surgeon within Covid-19 pandemic period. All donor tissues were stripped by the operating surgeon with endothelial cell density of > 2400 cells/mm2. The tamponade material used were air in 2 patients, 20% sulfur hexafluoride (SF6) gas in 3 patients and 12% perfluoropropane (C3F8) gas in 3 patients. The main outcomes were graft detachment rate, rebubbling rate and graft survival rate. RESULTS: The overall graft detachment rate was 25% (2 patients). The graft detachment rate was 0% in 20% SF6 gas group compared to 50% (1 patient) from air tamponade group and 33.3% (1 patient) from 12% C3F8 gas group (p<0.05). The patient from air group underwent rebubbling twice while another patient from 12% C3F8 gas group underwent once. The overall survival rate was 75% (6 patients). All of them did not have graft detachment. CONCLUSION: 20% SF6 gas provides superior tamponade effect compared to both air and 12% C3F8 gas. The detachment rate influenced graft survival. Air tamponade showed higher rebubbling rate

A Spatial Analysis of Rift Valley Fever Virus Seropositivity in Domestic Ruminants in Tanzania

Rift Valley fever (RVF) is an acute arthropod-borne viral zoonotic disease primarily occurring in Africa. Since RVF-like disease was reported in Tanzania in 1930, outbreaks of the disease have been reported mainly from the eastern ecosystem of the Great Rift Valley. This cross-sectional study was carried out to describe the variation in RVF virus (RVFV) seropositivity in domestic ruminants between selected villages in the eastern and western Rift Valley ecosystems in Tanzania, and identify potential risk factors. Three study villages were purposively selected from each of the two Rift Valley ecosystems. Serum samples from randomly selected domestic ruminants (n = 1,435) were tested for the presence of specific immunoglobulin G (IgG) and M (IgM), using RVF enzyme-linked immunosorbent assay methods. Mixed effects logistic regression modelling was used to investigate the association between potential risk factors and RVFV seropositivity. The overall RVFV seroprevalence (n = 1,435) in domestic ruminants was 25.8% and species specific seroprevalence was 29.7%, 27.7% and 22.0% in sheep (n = 148), cattle (n = 756) and goats (n = 531), respectively. The odds of seropositivity were significantly higher in animals sampled from the villages in the eastern than those in the western Rift Valley ecosystem (OR = 1.88, CI: 1.41, 2.51; p<0.001), in animals sampled from villages with soils of good than those with soils of poor water holding capacity (OR = 1.97; 95% CI: 1.58, 3.02; p< 0.001), and in animals which had been introduced than in animals born within the herd (OR = 5.08, CI: 2.74, 9.44; p< 0.001). Compared with animals aged 1-2 years, those aged 3 and 4-5 years had 3.40 (CI: 2.49, 4.64; p< 0.001) and 3.31 (CI: 2.27, 4.82, p< 0.001) times the odds of seropositivity. The findings confirm exposure to RVFV in all the study villages, but with a higher prevalence in the study villages from the eastern Rift Valley ecosystem

Effects of beta-alanine supplementation on brain homocarnosine/carnosine signal and cognitive function: an exploratory study

Objectives: Two independent studies were conducted to examine the effects of 28 d of beta-alanine supplementation at 6.4 g d-1 on brain homocarnosine/carnosine signal in omnivores and vegetarians (Study 1) and on cognitive function before and after exercise in trained cyclists (Study 2). Methods: In Study 1, seven healthy vegetarians (3 women and 4 men) and seven age- and sex-matched omnivores undertook a brain 1H-MRS exam at baseline and after beta-alanine supplementation. In study 2, nineteen trained male cyclists completed four 20-Km cycling time trials (two pre supplementation and two post supplementation), with a battery of cognitive function tests (Stroop test, Sternberg paradigm, Rapid Visual Information Processing task) being performed before and after exercise on each occasion. Results: In Study 1, there were no within-group effects of beta-alanine supplementation on brain homocarnosine/carnosine signal in either vegetarians (p = 0.99) or omnivores (p = 0.27); nor was there any effect when data from both groups were pooled (p = 0.19). Similarly, there was no group by time interaction for brain homocarnosine/carnosine signal (p = 0.27). In study 2, exercise improved cognitive function across all tests (P0.05) of beta-alanine supplementation on response times or accuracy for the Stroop test, Sternberg paradigm or RVIP task at rest or after exercise. Conclusion: 28 d of beta-alanine supplementation at 6.4g d-1 appeared not to influence brain homocarnosine/ carnosine signal in either omnivores or vegetarians; nor did it influence cognitive function before or after exercise in trained cyclists

Aurora kinase A drives the evolution of resistance to third-generation EGFR inhibitors in lung cancer.

Although targeted therapies often elicit profound initial patient responses, these effects are transient due to residual disease leading to acquired resistance. How tumors transition between drug responsiveness, tolerance and resistance, especially in the absence of preexisting subclones, remains unclear. In epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma cells, we demonstrate that residual disease and acquired resistance in response to EGFR inhibitors requires Aurora kinase A (AURKA) activity. Nongenetic resistance through the activation of AURKA by its coactivator TPX2 emerges in response to chronic EGFR inhibition where it mitigates drug-induced apoptosis. Aurora kinase inhibitors suppress this adaptive survival program, increasing the magnitude and duration of EGFR inhibitor response in preclinical models. Treatment-induced activation of AURKA is associated with resistance to EGFR inhibitors in vitro, in vivo and in most individuals with EGFR-mutant lung adenocarcinoma. These findings delineate a molecular path whereby drug resistance emerges from drug-tolerant cells and unveils a synthetic lethal strategy for enhancing responses to EGFR inhibitors by suppressing AURKA-driven residual disease and acquired resistance

Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015

SummaryBackground The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. Methods We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defined criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors—the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specific DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI). Findings Between 1990 and 2015, global exposure to unsafe sanitation, household air pollution, childhood underweight, childhood stunting, and smoking each decreased by more than 25%. Global exposure for several occupational risks, high body-mass index (BMI), and drug use increased by more than 25% over the same period. All risks jointly evaluated in 2015 accounted for 57·8% (95% CI 56·6–58·8) of global deaths and 41·2% (39·8–42·8) of DALYs. In 2015, the ten largest contributors to global DALYs among Level 3 risks were high systolic blood pressure (211·8 million [192·7 million to 231·1 million] global DALYs), smoking (148·6 million [134·2 million to 163·1 million]), high fasting plasma glucose (143·1 million [125·1 million to 163·5 million]), high BMI (120·1 million [83·8 million to 158·4 million]), childhood undernutrition (113·3 million [103·9 million to 123·4 million]), ambient particulate matter (103·1 million [90·8 million to 115·1 million]), high total cholesterol (88·7 million [74·6 million to 105·7 million]), household air pollution (85·6 million [66·7 million to 106·1 million]), alcohol use (85·0 million [77·2 million to 93·0 million]), and diets high in sodium (83·0 million [49·3 million to 127·5 million]). From 1990 to 2015, attributable DALYs declined for micronutrient deficiencies, childhood undernutrition, unsafe sanitation and water, and household air pollution; reductions in risk-deleted DALY rates rather than reductions in exposure drove these declines. Rising exposure contributed to notable increases in attributable DALYs from high BMI, high fasting plasma glucose, occupational carcinogens, and drug use. Environmental risks and childhood undernutrition declined steadily with SDI; low physical activity, high BMI, and high fasting plasma glucose increased with SDI. In 119 countries, metabolic risks, such as high BMI and fasting plasma glucose, contributed the most attributable DALYs in 2015. Regionally, smoking still ranked among the leading five risk factors for attributable DALYs in 109 countries; childhood underweight and unsafe sex remained primary drivers of early death and disability in much of sub-Saharan Africa. Interpretation Declines in some key environmental risks have contributed to declines in critical infectious diseases. Some risks appear to be invariant to SDI. Increasing risks, including high BMI, high fasting plasma glucose, drug use, and some occupational exposures, contribute to rising burden from some conditions, but also provide opportunities for intervention. Some highly preventable risks, such as smoking, remain major causes of attributable DALYs, even as exposure is declining. Public policy makers need to pay attention to the risks that are increasingly major contributors to global burden. Funding Bill & Melinda Gates Foundation

Prevalence and demographics of anxiety disorders: a snapshot from a community health centre in Pakistan

<p>Abstract</p> <p>Background</p> <p>The developing world is faced with a high burden of anxiety disorders. The exact prevalence of anxiety disorders in Pakistan is not known. There is a need to develop an evidence base to aid policy development on tackling anxiety and depressive disorders in the country. This is the first pilot study to address the prevalence of anxiety disorders and their association with sociodemographic factors in Pakistan.</p> <p>Methods</p> <p>A cross-sectional study was conducted among people visiting Aga Khan University Hospital (AKUH), a tertiary care facility in Karachi, Pakistan. The point prevalence of anxiety amongst the sample population, which comprised of patients and their attendants, excluding all health care personnel, was assessed using the validated Urdu version of the Hospital Anxiety and Depression Scale (HADS). The questionnaire was administered to 423 people. Descriptive statistics were performed for mean scores and proportions.</p> <p>Results</p> <p>The mean anxiety score of the population was 5.7 ± 3.86. About 28.3% had borderline or pathological anxiety. The factors found to be independently predicted with anxiety were, female sex (odds ratio (OR) = 2.14, 95% CI 1.36–3.36, p = 0.01); physical illness (OR = 1.67, 95% CI 1.06–2.64, p = 0.026); and psychiatric illness (OR = 1.176, 95% CI 1.0–3.1, p = 0.048). In the final multivariate model, female sex (adjusted odds ratio (AOR) = 2, 95% CI 1.28–3.22) and physical illness (AOR = 1.56, 95% CI 0.97–2.48) were found to be significant.</p> <p>Conclusion</p> <p>Further studies via nationally representative surveys need to be undertaken to fully grasp the scope of this emerging public health issue in Pakistan.</p

Diagnostic criteria for diabetes revisited: making use of combined criteria

BACKGROUND: Existing cut-offs for fasting plasma glucose (FPG) and post-load glucose (2hPG) criteria are not equivalent in the diagnosis of diabetes and glucose intolerance. Adjusting cut-offs of single measurements have not helped so we undertook this project to see if they could be complementary. METHODS: We performed oral glucose tolerance tests and mean levels of hemoglobin A1c (HbA1c) measurements on 43 patients referred to a diabetes clinic for possible diabetes. Results of single and combined use of the FPG and 2hPG criteria were evaluated against the levels of HbA1c and results re-interpreted in the light of existing reports in the literature. RESULTS: Our results confirm that the FPG and the 2hPG, being specific and sensitive respectively for the presence of glucose intolerance or diabetes, are not equivalent. They are shown to be indeed complementary and a re-definition of diagnostic criteria based on their combined use is proposed. CONCLUSIONS: We conclude that altering single measurement cut-offs for the diagnosis of diabetes and altered glucose tolerance will not result in better outcomes. We present the case for a combined criteria in the diagnosis and definition of diabetes with a FPG≥7 mmol/L AND 2-hour glucose ≥7.8 mmol/L being used to define diabetes while a FPG<7 mmol/L AND 2-hour glucose <7.8 mmol/L being used to define normality. Discordant values will define impaired glucose tolerance (IGT). This proposal requires prospective evaluation in a large cohort

Influence of reaction time and synthesis temperature on the physical properties of ZnO nanoparticles synthesized by the hydrothermal method

Influence of synthesis temperature and reaction time on the structural and optical properties of ZnO nanoparticles synthesized by the hydrothermal method was investigated using X-ray diffraction (XRD), high resolution transmission electron microscopy (HR-TEM), energy-dispersive X-ray, Fourier transform infra-red spectroscopy, and UV–visible and fluorescence spectroscopy. The XRD pattern and HR-TEM images confirmed the presence of crystalline hexagonal wurtzite ZnO nanoparticles with average crystallite size in the range 30–40 nm. Their energy gap determined by fluorescence was found to depend on the synthesis temperature and reaction time with values in the range 2.90–3.78 eV. Thermal analysis, thermogravimetric and the differential scanning calorimetry were used to study the thermal reactions and weight loss with heat of the prepared ZnO nanoparticles

The Evolution of the Major Hepatitis C Genotypes Correlates with Clinical Response to Interferon Therapy

Patients chronically infected with hepatitis C virus (HCV) require significantly different durations of therapy and achieve substantially different sustained virologic response rates to interferon-based therapies, depending on the HCV genotype with which they are infected. There currently exists no systematic framework that explains these genotype-specific response rates. Since humans are the only known natural hosts for HCV-a virus that is at least hundreds of years old-one possibility is that over the time frame of this relationship, HCV accumulated adaptive mutations that confer increasing resistance to the human immune system. Given that interferon therapy functions by triggering an immune response, we hypothesized that clinical response rates are a reflection of viral evolutionary adaptations to the immune system.We have performed the first phylogenetic analysis to include all available full-length HCV genomic sequences (n = 345). This resulted in a new cladogram of HCV. This tree establishes for the first time the relative evolutionary ages of the major HCV genotypes. The outcome data from prospective clinical trials that studied interferon and ribavirin therapy was then mapped onto this new tree. This mapping revealed a correlation between genotype-specific responses to therapy and respective genotype age. This correlation allows us to predict that genotypes 5 and 6, for which there currently are no published prospective trials, will likely have intermediate response rates, similar to genotype 3. Ancestral protein sequence reconstruction was also performed, which identified the HCV proteins E2 and NS5A as potential determinants of genotype-specific clinical outcome. Biochemical studies have independently identified these same two proteins as having genotype-specific abilities to inhibit the innate immune factor double-stranded RNA-dependent protein kinase (PKR).An evolutionary analysis of all available HCV genomes supports the hypothesis that immune selection was a significant driving force in the divergence of the major HCV genotypes and that viral factors that acquired the ability to inhibit the immune response may play a role in determining genotype-specific response rates to interferon therapy