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The rapid spread of SARS-CoV-2 variants in the global population is indicative of the development of selective advantages in emerging virus strains. Here, we performed a case-control investigation of the clinical and demographic characteristics, clinical history, and virological markers to predict disease progression in hospitalized adults for COVID-19 between December 2021 and January 2022 in Chennai, India. COVID-19 diagnosis was made by a commercial TaqPath COVID-19 RT-PCR, and WGS was performed with the Ion Torrent Next Generation Sequencing System. High-quality (

The dynamics of host-virus interactions, and impairment of the host’s immune surveillance by dengue virus (DENV) serotypes largely remain ambiguous. Several experimental and preclinical studies have demonstrated how the virus brings about severe disease by activating immune cells and other key elements of the inflammatory cascade. Plasmablasts are activated during primary and secondary infections, and play a determinative role in severe dengue. The cross-reactivity of DENV immune responses with other flaviviruses can have implications both for cross-protection and severity of disease. The consequences of a cross-reactivity between DENV and anti-SARS-CoV-2 responses are highly relevant in endemic areas. Here, we review the latest progress in the understanding of dengue immunopathogenesis and provide suggestions to the development of target strategies against dengue.

It is rare for young, healthy patients to have retinal venous or arterial occlusions and even rarer for both to occur in concert. Such an occurrence should prompt a rapid and extensive workup to prevent further complications. We present our patient, a 37-year-old Lebanese male, who reported a 3-day history of blurring of vision in his left eye. He had no medical or ocular history and is a nonsmoker. Examination of the left fundus revealed inferior macular edema and retinal whitening associated with tortuous retinal veins. He was diagnosed with a combined central retinal vein and cilioretinal artery occlusion. Emergency treatment was done for an acute arterial occlusion. Embolic and thrombotic causes were excluded with investigations. The only positive result was homozygosity for 677C>T mutation of the 5,10 methylenetetrahydrofolate reductase (MTHFR) enzyme gene. MTHFR enzyme breaks down homocysteine, which is atherogenic and prothrombotic. This mutation can lead to a prothrombotic state, precipitating this occurrence. In fact, the Lebanese population is known to have the highest incidence of such mutations, but there are surprisingly few reports on retinal vascular occlusions attributed to this. He was promptly treated with antiplatelet therapy, possibly preventing a full-blown central retinal vein occlusion. After 4 weeks, his vision improved to 6/6 bilaterally. Examination showed less tortuous veins, no more retinal whitening, resolution of macula edema and visual field defect. Hyperhomocysteinemia can be significant in patients without ischemic risk factors. It is vital to manage these patients promptly, preventing future sight and life-threatening events.

Summary: Neuroinflammation exacerbates the progression of SOD1-driven amyotrophic lateral sclerosis (ALS), although the underlying mechanisms remain largely unknown. Herein, we demonstrate that misfolded SOD1 (SOD1Mut)-causing ALS results in mitochondrial damage, thus triggering the release of mtDNA and an RNA:DNA hybrid into the cytosol in an mPTP-independent manner to activate IRF3- and IFNAR-dependent type I interferon (IFN-I) and interferon-stimulating genes. The neuronal hyper-IFN-I and pro-inflammatory responses triggered in ALS-SOD1Mut were sufficiently robust to cause a strong physiological outcome in vitro and in vivo. cGAS/DDX41-STING-signaling is amplified in bystander cells through inter-neuronal gap junctions. Our results highlight the importance of a common DNA-sensing pathway between SOD1 and TDP-43 in influencing the progression of ALS.

BackgroundThe magnitude of protection conferred following recovery from COVID-19 or by vaccine administration, and the duration of protective immunity developed, remains ambiguous.MethodsWe investigated the factors associated with anti-SARS-CoV-2 S1 IgG decay in 519 individuals who recovered from COVID-19 illness or received COVID-19 vaccination with two commercial vaccines, viz., an adenoviral vector-based (AZD1222) and a whole-virion-based inactivated (BBV152) vaccine in Chennai, India from March to December 2021. Blood samples collected during regular follow-up post-infection/-vaccination were examined for anti-SARS-CoV-2 S1 IgG by a commercial automated chemiluminescent immunoassay (CLIA).ResultsAge and underlying comorbidities were the two variables that were independently associated with the development of a breakthrough infection. Individuals who were >60 years of age with underlying comorbid conditions (viz., hypertension, diabetes mellitus and cardiovascular disease) had a ~15 times and ~10 times greater odds for developing a breakthrough infection and hospitalization, respectively. The time elapsed since the first booster dose was associated with attrition in anti-SARS-CoV-2 IgG, where each month passed was associated with an ebb in the anti-SARS-CoV-2 IgG antibody levels by a coefficient of −6 units.ConclusionsOur findings advocate that the elderly with underlying comorbidities be administered with appropriate number of booster doses with AZD1222 and BBV152 against COVID-19.

Abstract Background Chronic obstructive pulmonary disease (COPD) is an incurable and debilitating chronic disease characterized by progressive airflow limitation associated with abnormal levels of tissue inflammation. Therefore, stem cell-based approaches to tackle the condition are currently a focus of regenerative therapies for COPD. Extracellular vesicles (EVs) released by all cell types are crucially involved in paracrine, extracellular communication. Recent advances in the field suggest that stem cell-derived EVs possess a therapeutic potential which is comparable to the cells of their origin. Methods In this study, we assessed the potential anti-inflammatory effects of human umbilical cord mesenchymal stem cell (hUC-MSC)-derived EVs in a rat model of COPD. EVs were isolated from hUC-MSCs and characterized by the transmission electron microscope, western blotting, and nanoparticle tracking analysis. As a model of COPD, male Sprague-Dawley rats were exposed to cigarette smoke for up to 12 weeks, followed by transplantation of hUC-MSCs or application of hUC-MSC-derived EVs. Lung tissue was subjected to histological analysis using haematoxylin and eosin staining, Alcian blue-periodic acid-Schiff (AB-PAS) staining, and immunofluorescence staining. Gene expression in the lung tissue was assessed using microarray analysis. Statistical analyses were performed using GraphPad Prism 7 version 7.0 (GraphPad Software, USA). Student’s t test was used to compare between 2 groups. Comparison among more than 2 groups was done using one-way analysis of variance (ANOVA). Data presented as median ± standard deviation (SD). Results Both transplantation of hUC-MSCs and application of EVs resulted in a reduction of peribronchial and perivascular inflammation, alveolar septal thickening associated with mononuclear inflammation, and a decreased number of goblet cells. Moreover, hUC-MSCs and EVs ameliorated the loss of alveolar septa in the emphysematous lung of COPD rats and reduced the levels of NF-κB subunit p65 in the tissue. Subsequent microarray analysis revealed that both hUC-MSCs and EVs significantly regulate multiple pathways known to be associated with COPD. Conclusions In conclusion, we show that hUC-MSC-derived EVs effectively ameliorate by COPD-induced inflammation. Thus, EVs could serve as a new cell-free-based therapy for the treatment of COPD.

Geophysical flows impacting a flexible barrier can create complex flows and solid-fluid-structure interactions, which are challenging to quantify and characterize towards a unified description. Here, we examine the common physical laws of multiphase, multiway interactions during debris flows, debris avalanches and rock avalanches against a flexible barrier system using a coupled computational fluid dynamics and discrete element (CFD-DEM) method. This model captures essential physics observed in experiments and fields. The bi-linear, positive correlations are found between peak impact load and Fr or maximum barrier deflection, with inflection points due to the transitions from trapezoid- to triangle-shaped dead zones. Our findings quantitatively elucidate how flow materials (wet versus dry) and impact dynamics (slow versus fast) control the patterns of the identified bi-linear correlations. This work offers a physics-based reference and insights for improving widely-used impact solutions for geophysical flows against flexible barriers.

The lethal combination involving TB and HIV, known as “syndemic” diseases, synergistically act upon one another to magnify the disease burden. Individuals on anti-retroviral therapy (ART) are at risk of developing TB-associated immune reconstitution inflammatory syndrome (TB-IRIS). The underlying inflammatory complication includes the rapid restoration of immune responses following ART, eventually leading to exaggerated inflammatory responses to MTB antigens. TB-IRIS continues to be a cause of morbidity and mortality among HIV/TB coinfected patients initiating ART, and although a significant quantum of knowledge has been acquired on the pathogenesis of IRIS, the underlying pathomechanisms and identification of a sensitive and specific diagnostic marker still remain a grey area of investigation. Here, we reviewed the latest research developments into IRIS immunopathogenesis, and outlined the modalities to prevent and manage strategies for better clinical and diagnostic outcomes for IRIS.

Quantitative understanding of the load–deflection mechanisms of a flexible barrier in intercepting debris flows is critical for barrier design, but remains practically challenging due to the difficulties involved in capturing multi-phase, multi-way interactions. This study employs a physics-based coupled computational fluid dynamics and discrete-element method (CFD–DEM) to simulate a flexible ring-net barrier as a permeable, deformable multi-component system by DEM and model a debris flow as a mixture of discrete particles and a continuous slurry by DEM and CFD, respectively. The CFD–DEM coupling framework offers a unified treatment of in-flow solid–fluid interaction, flow–barrier interaction and interactions among barrier components. Numerical predictions of key flow–barrier interactions and cable forces show reasonable consistency with large-scale experiments. Systematic simulations with varying flow–barrier height ratios ε and flow dynamics are performed to examine the evolving mechanisms of load sharing and transmission and quantify the ε-dependent load–deflection modes. The ratio ε is found to bear a strong, positive correlation with the key barrier response in three typical modes. The post-peak barrier deformations experience shrinkages with ε ≤ 0·6 and expansions when ε > 0·6. This study helps to improve understanding of the load–deflection mechanisms for practical design of flexible barriers in mitigating debris flows. [ABSTRACT FROM AUTHOR]

OBJECTIVES To evaluate the predictive value of fasting plasma glucose (FPG) for in-hospital mortality in patients with acute myocardial infarction (AMI) with different glucose metabolism status. METHODS We selected 5,308 participants with AMI from the prospective, nationwide, multicenter CAMI registry, of which 2,081 were diabetic and 3,227 were nondiabetic. Patients were divided into high FPG and low FPG groups according to the optimal cutoff values of FPG to predict in-hospital mortality for diabetic and nondiabetic cohorts, respectively. The primary endpoint was in-hospital mortality. RESULTS Overall, 94 diabetic patients (4.5%) and 131 nondiabetic patients (4.1%) died during hospitalization, and the optimal FPG thresholds for predicting in-hospital death of the two cohorts were 13.2 mmol/L and 6.4 mmol/L, respectively. Compared with individuals who had low FPG, those with high FPG were significantly associated with higher in-hospital mortality in diabetic cohort (10.1% vs. 2.8%; odds ratio [OR] = 3.862, 95% confidence interval [CI]: 2.542–5.869) and nondiabetic cohort (7.4% vs. 1.7%; HR = 4.542, 95%CI: 3.041–6.782). After adjusting the potential confounders, this significant association was not changed. Furthermore, FPG as a continuous variable was positively associated with in-hospital mortality in single-variable and multivariable models regardless of diabetic status. Adding FPG to the original model showed a significant improvement in C-statistic and net reclassification in diabetic and nondiabetic cohorts. CONCLUSIONS This large-scale registry indicated that there is a strong positive association between FPG and in-hospital mortality in AMI patients with and without diabetes. FPG might be useful to stratify patients with AMI. [ABSTRACT FROM AUTHOR]

This study sought to investigate the vertical distribution pattern of the soil faunal community in a low-altitude mountain area. On 8 July 2022, a low hill was selected as the study area, and soil arthropods were collected through traps. The leaf litter, vegetation type, and distribution quantity of each sampling site were investigated while the soil faunae were collected. In addition, the soil's physical and chemical parameters were measured. The results of a one-way ANOVA showed that there were significant differences (p < 0.05) in the soil properties, leaf litter, and plant quantities at different altitudes within the research area. A total of 1086 soil arthropods, belonging to five classes and ten orders, were collected during the study period. The dominant species of soil arthropods at different altitudes were significantly different. The dominant species in low-altitude areas were Armadillidium sp. and Aethus nigritus. However, Eupolyphaga sinensis and Philodromidae were the dominant species in high-altitude areas. The results of a non-metric multidimensional scaling (NMDS) analysis showed that the soil faunae at different altitudes were clustered into two communities: a high-altitude community and a low-altitude community. With the increase in altitude, the species richness of the soil arthropods gradually decreased, and their abundance showed a decreasing trend. A redundancy analysis (RDA) of the soil arthropods and environmental factors showed that soil moisture (p < 0.01), pH (p < 0.01) and defoliation (p < 0.05) had significant effects on the distribution of the soil fauna. The results of a Pearson correlation analysis indicated that different environmental factors had interactive effects on the distribution of the soil arthropods. The quantity and species richness of the soil arthropods in different sample lines were tested using a variance analysis. The results showed that there were significantly smaller quantities of soil arthropods in the sampling line closer to the trekking ladder. This indicates that human tourism, namely mountaineering activities, had a direct impact on the soil fauna. This study can provide a reference for and data support in the development of biodiversity conservation measures for forest parks in low mountain areas. [ABSTRACT FROM AUTHOR]

Radiation-induced optic neuropathy (RION) is a severely disabling complication of radiotherapy, without any known effective treatment. Three patients, one female and two males, aged 60, 34, and 45 years, respectively, developed progressive deterioration in visual acuity over 1 month, 8 years, and 2 months, starting 3, 12, and 9 years after radiotherapy for nasopharyngeal carcinoma. They received 70.15, 60.89, and 56.11 Gy over a period of 6–7 weeks, with fractionated doses of 2, 1.79, and 1.81 Gy, respectively. Ophthalmological examination revealed a relative afferent pupillary defect in the latter 2 patients, best-corrected visual acuity was 6/12 or better in all. Visual field charting showed a superior altitudinal field defect in the first two, and generalised visual loss in the third patient in the symptomatic eyes. Anticoagulation with heparin bridging and oral warfarin with an INR target of 2.0–3.0 was commenced within 2 months of symptom onset. All showed improvement in visual fields within 2 weeks, and remained stable for at least 2 years while on warfarin. Our encouraging findings will need to be confirmed in a randomised controlled clinical trial.

Ethnicity, native and/or foreign language knowledge, as well as the learned writing systems potentially influence the development of an individual's handwriting. The unique education system consisting of National schools, Chinese-medium vernacular schools, Tamil-medium vernacular schools, and Islamic religious schools in Malaysia may have established specific characteristic handwritten allographic features that deserve investigation within the intelligence context. This study was aimed to explore handwritten allographic features of handwriting samples from 120 subjects (30 writers from four different educational backgrounds mentioned above). Characteristic features which could be attributed to the study groups were statistically analyzed and identified. In this study, thirteen allographic features, including letters "A", "B", "D", "H", "p", "T", "t", "w", "X" and "x", were found to be discriminative. Such information could serve to indicate the primary education system undergone by a writer; enabling the comparison of different handwriting profiles and allowing characterization of writers to a specific group of people.