Sexually dimorphic mechanisms of VGLUT-mediated protection from dopaminergic neurodegeneration.

Parkinson's disease (PD) targets some dopamine (DA) neurons more than others. Sex differences offer insights, with females more protected from DA neurodegeneration. The mammalian vesicular glutamate transporter VGLUT2 and Drosophila ortholog dVGLUT have been implicated as modulators of DA neuron resilience. However, the mechanisms by which VGLUT2/dVGLUT protects DA neurons remain unknown. We discovered DA neuron dVGLUT knockdown increased mitochondrial reactive oxygen species in a sexually dimorphic manner in response to depolarization or paraquat-induced stress, males being especially affected. DA neuron dVGLUT also reduced ATP biosynthetic burden during depolarization. RNA sequencing of VGLUT+ DA neurons in mice and flies identified candidate genes that we functionally screened to further dissect VGLUT-mediated DA neuron resilience across PD models. We discovered transcription factors modulating dVGLUT-dependent DA neuroprotection and identified dj-1ß as a regulator of sex-specific DA neuron dVGLUT expression. Overall, VGLUT protects DA neurons from PD-associated degeneration by maintaining mitochondrial health.

Outcomes of COVID-19 Among High-Risk Individuals: A Study Comparing Febrile and Afebrile Presentation.

Background: Fever is one of the most frequent symptoms of coronavirus disease 2019 (COVID-19) and clinicians are faced with a practice question on whether fever is a risk for progression of disease especially in persons with risk factors for severe illness. We studied if a difference exists in the clinical course and outcome between febrile and afebrile (symptomatic) presentation. Methods: Patients aged > 18 years with confirmed COVID-19 with at least one risk factor for severe illness were studied. Enrolment was done from a home COVID-19 care cohort between May 2020 and March 2022. Participants were divided into febrile and afebrile groups and further divided into six sub-groups based on their comorbidities (diabetes mellitus, hypertension, chronic lung disease, chronic kidney disease, liver disease and others) using a pre-specified inclusion method. Severity of illness was classified as non-hypoxic or hypoxic and clinical course was monitored. Results: A total of 3,752 patients were studied, of whom 965 (25.7%) had severe illness and 117 (3.1%) died. Persons with obesity (P < 0.001), chronic kidney disease (P = 0.003) and chronic liver disease (P = 0.02) more frequently had presentation without fever. No significant difference in hypoxia (P = 0.35) or mortality (P = 0.50) was observed between febrile (n = 1,240) and afebrile (n = 2,512) presentation. Conclusion: Fever in COVID-19 was not associated with severe illness or mortality. The overall and risk factor specific mortality observed in our study is substantially low, probably due to lesser bias in selection of study participants or due to ethnicity of study population.

FlatNet: Towards Photorealistic Scene Reconstruction From Lensless Measurements.

Lensless imaging has emerged as a potential solution towards realizing ultra-miniature cameras by eschewing the bulky lens in a traditional camera. Without a focusing lens, the lensless cameras rely on computational algorithms to recover the scenes from multiplexed measurements. However, the current iterative-optimization-based reconstruction algorithms produce noisier and perceptually poorer images. In this work, we propose a non-iterative deep learning-based reconstruction approach that results in orders of magnitude improvement in image quality for lensless reconstructions. Our approach, called FlatNet, lays down a framework for reconstructing high-quality photorealistic images from mask-based lensless cameras, where the camera's forward model formulation is known. FlatNet consists of two stages: (1) an inversion stage that maps the measurement into a space of intermediate reconstruction by learning parameters within the forward model formulation, and (2) a perceptual enhancement stage that improves the perceptual quality of this intermediate reconstruction. These stages are trained together in an end-to-end manner. We show high-quality reconstructions by performing extensive experiments on real and challenging scenes using two different types of lensless prototypes: one which uses a separable forward model and another, which uses a more general non-separable cropped-convolution model. Our end-to-end approach is fast, produces photorealistic reconstructions, and is easy to adopt for other mask-based lensless cameras.

Low secondary transmission rates of SARS-CoV-2 infection among contacts of construction laborers at open air environment.

INTRODUCTION: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection spreads through droplet and aerosols. Household contacts have a high risk of infection and transmission outside the home can occur at closed and open locations. We studied the transmission risk at open environment among contacts of construction laborers. METHODS: Close contacts of 18 SARS-CoV-2 infected construction laborers were assessed for symptomatic or asymptomatic infection. Contacts were classified as: a) persons at residence of index case b) persons at workplace (open and closed environment), and c) persons outside the index case residence or workplace who are traceable. Relative risk of infection among contacts at different locations and observed parameters were compared between them. RESULTS: Four hundred and ninety-six contacts were assessed. The secondary transmission rate was maximum among household contacts (n=28, 43.7%) followed by contacts at closed environment at workplace (n=44, 26%), traceable other contacts (n=8, 15.7%) and contacts at open environment at workplace (n=3, 1.4%). Relative risk of SARS-CoV-2 infection among household contacts was 30.9 (CI 9.7-98.3, p<0.001) compared to open environmental work contacts and 1.68 (CI 1.15-2.44, p=0.006) compared to closed environmental work contacts. Relative risk was 18.3 (CI 5.8-58.2, P<0.001) among closed environmental work contacts compared to open environmental work contacts. One index and one secondary case died. CONCLUSIONS: The low secondary transmission rate of SARS-CoV-2 infection among open environmental contacts emphasizes the fact that free air flow has the ability to dilute or probably blow away the virus particles and lowers the transmission risk substantially.

Effect of Platelet Transfusion on Clot Strength in Dengue Fever with Thrombocytopenia Related Bleeding: A Thromboelastography-Based Study.

Platelet transfusions are often administered in dengue illness complicated by thrombocytopenia-related bleeding. However, whether this practice results in an improvement of clot strength is not clear. This study assessed the impact of platelet transfusion on the control of bleeding and improvement in clot strength as assessed by thromboelastography among 74 patients with dengue. The effect of either weight-based random donor platelets or 1 unit of single donor aphaeresis units was studied. Transfusion of weight-based random donor platelets resulted in a mean platelet count increase of 10,210 cells per mm3 at 24 h from pretransfusion values, which reached marginal statistical significance (p = 0.031). Patients who received single donor platelets achieved a mean platelet increment of 22,874 cells per mm3 at 24 h, and the difference observed had a high statistical significance (p < 0.001). However, no significant improvement in clot strength was observed in thromboelastography. The mean increment in maximum amplitude value at 24 h was only 2 mm in the random donor platelet group and 5 mm in the single donor group, both of which did not reach statistical significance. Furthermore, the majority of patients had ongoing bleeding despite the administration of platelets. This study observed that platelet transfusion in dengue patients with bleeding complication improved the absolute platelet count with no improvement in clot strength.

Estimation of Upper Limit of Normal for Serum Alanine Transaminase in Healthy South Indian Population.

Alanine aminotransferase (ALT) is the most common and cost effective screening test for asymptomatic liver disease. There is paucity of data on normal ALT among healthy individuals in India. An observational cross sectional study was conducted from January to July 2013 to estimate the upper limit of normal for ALT in healthy south Indian population. Adults undergoing voluntary or pre-employment health screening were included. Those with current and past alcoholism or smoking, acute illness or hospitalization during preceding 12 months, non-steroidal anti-inflammatory or over the counter medication use within a month, current or past intake of herbal medications, any chronic medical illness, abnormal body mass index (BMI), fatty liver in ultrasound, abnormality in haemoglobin, platelet count, blood sugar, creatinine, lipid profile and thyroid function test and positive serology (Hepatitis B, C or HIV) were excluded. A total of 2600 subjects were screened. 344 were included for analysis. Mean age was 35 years in men and 34.83 years in women, with a mean BMI of 22.2 kg/m2 in men and 21.8 kg/m2 in women. The mean ALT in men and women were 21.87 ± 2.9 (97.5th percentile 28 U/L) and 19.35 ± 3.3 (97.5th percentile 24 U/L) respectively. In conclusion, mean and upper limit of ALT (97.5th percentile) in south Indian men was 21.87 and 28 IU/L and women were 19.35 and 24 IU/L respectively. There is a need to re-consider ALT levels in our population for better detection of individuals at risk for liver disease.

Prevalence, patterns, and factors associated with bleeding tendencies in dengue.

INTRODUCTION: The pattern of bleeding tendencies in dengue and its corellation with platelet count and other factors requires clarification. METHODOLOGY: A retrospective study on bleeding tendencies in adults with dengue and platelet counts of less than 100,000 per mm(3) was conducted. Factors associated with bleeding were analyzed. The study cohort were grouped as dengue with severe thrombocytopenia when platelet count was < 50,000/mm(3) and as dengue with moderate thrombocytopenia if platelet count was 50,000-100,000/mm(3) RESULTS: A total of 638 patients formed the study cohort. A 24.1% prevalence of bleeding tendencies was observed. Prior anti-platelet drug intake, platelet count of < 70,000/mm(3), international normalized ratio > 2.0, and partial thromboplastin time > 60 seconds were associated with bleeding. Esophagogastroduodenoscopy was found to identify structural gastroduodenal lesions when dengue was complicated by hematemesis or melena. CONCLUSIONS: The results of this study suggest that bleeding complications in dengue can occur at platelet counts of up to 70,000/mm(3), and that prior anti-platelet drug intake increases bleeding risk. Evaluation of hematemesis or melena in dengue with esophagogastroduodenoscopy is beneficial.