Urban to rural COVID-19 progression in India: The role of massive migration and the challenge to India's traditional labour force policies.

The coronavirus disease-2019 (COVID-19) has emerged as a deadliest disease in the 21st century. Initially in India, this disease was concentrated in major urban cities like Mumbai, Delhi, Gujarat, and Chennai, which were the national hotspots for the COVID-19 pandemic. However, in subsequent months, returning migrants (mainly day labour) brought the disease back to their home; this vector triggered significant spread to semi-urban and rural areas. This highlighted serious concerns in rural India, where access to sophisticated healthcare and mitigation strategies were lacking. There is little data on this new pattern of disease spread. This article provides a short review for tracking the spread of COVID-19 into major rural states in India based on understanding urban-rural workforce migration relative to the growing proportion of the nation's COVID-19 caseload between May-September 2020.

Source and background threshold values of potentially toxic elements in soils by multivariate statistics and GIS-based mapping: a high density sampling survey in the Parauapebas basin, Brazilian Amazon.

A high-density regional-scale soil geochemical survey comprising 727 samples (one sample per each 5 × 5 km grid) was carried out in the Parauapebas sub-basin of the Brazilian Amazonia, under the Itacaiúnas Basin Geochemical Mapping and Background Project. Samples were taken from two depths at each site: surface soil, 0-20 cm and deep soil, 30-50 cm. The ground and sieved (< 75 µm) fraction was digested using aqua regia and analyzed for 51 elements by inductively coupled plasma mass spectrometry (ICPMS). All data were used here, but the principal focus was on the potential toxic elements (PTEs) and Fe and Mn to evaluate the spatial distribution patterns and to establish their geochemical background concentrations in soils. Geochemical maps as well as principal component analysis (PCA) show that the distribution patterns of the elements are very similar between surface and deep soils. The PCA, applied on clr-transformed data, identified four major associations: Fe-Ti-V-Sc-Cu-Cr-Ni (Gp-1); Zr-Hf-U-Nb-Th-Al-P-Mo-Ga (Gp-2); K-Na-Ca-Mg-Ba-Rb-Sr (Gp-3); and La-Ce-Co-Mn-Y-Zn-Cd (Gp-4). Moreover, the distribution patterns of elements varied significantly among the three major geological domains. The whole data indicate a strong imprint of local geological setting in the geochemical associations and point to a dominant geogenic origin for the analyzed elements. Copper and Fe in Gp-1 were enriched in the Carajás basin and are associated with metavolcanic rocks and banded-iron formations, respectively. However, the spatial distribution of Cu is also highly influenced by two hydrothermal mineralized copper belts. Ni-Cr in Gp-1 are highly correlated and spatially associated with mafic and ultramafic units. The Gp-2 is partially composed of high field strength elements (Zr, Hf, Nb, U, Th) that could be linked to occurrences of A-type Neoarchean granites. The Gp-3 elements are mobile elements which are commonly found in feldspars and other rock-forming minerals being liberated by chemical weathering. The background threshold values (BTV) were estimated separately for surface and deep soils using different methods. The '75th percentile', which commonly used for the estimation of the quality reference values (QRVs) following the Brazilian regulation, gave more restrictive or conservative (low) BTVs, while the 'MMAD' was more realistic to define high BTVs that can better represent the so-called mineralized/normal background. Compared with CONAMA Resolution (No. 420/2009), the conservative BTVs of most of the toxic elements were below the prevention limits (PV), except Cu, but when the high BTVs are considered, Cu, Co, Cr and Ni exceeded the PV limits. The degree of contamination (Cdeg), based on the conservative BTVs, indicates low contamination, except in the Carajás basin, which shows many anomalies and had high contamination mainly from Cu, Cr and Ni, but this is similar between surface and deep soils indicating that the observed high anomalies are strictly related to geogenic control. This is supported when the Cdeg is calculated using the high BTVs, which indicates low contamination. This suggests that the use of only conservative BTVs for the entire region might overestimate the significance of anthropogenic contamination; thus, we suggest the use of high BTVs for effective assessment of soil contamination in this region. The methodology and results of this study may help developing strategies for geochemical mapping in other Carajás soils or in other Amazonian soils with similar characteristics.

Generative network modeling reveals quantitative definitions of bilateral symmetry exhibited by a whole insect brain connectome.

Comparing connectomes can help explain how neural connectivity is related to genetics, disease, development, learning, and behavior. However, making statistical inferences about the significance and nature of differences between two networks is an open problem, and such analysis has not been extensively applied to nanoscale connectomes. Here, we investigate this problem via a case study on the bilateral symmetry of a larval Drosophila brain connectome. We translate notions of 'bilateral symmetry' to generative models of the network structure of the left and right hemispheres, allowing us to test and refine our understanding of symmetry. We find significant differences in connection probabilities both across the entire left and right networks and between specific cell types. By rescaling connection probabilities or removing certain edges based on weight, we also present adjusted definitions of bilateral symmetry exhibited by this connectome. This work shows how statistical inferences from networks can inform the study of connectomes, facilitating future comparisons of neural structures.

Exploration of Residual Confounding in Analyses of Associations of Metformin Use and Outcomes in Adults With Type 2 Diabetes.

Importance: Metformin is often used as a first-line therapy for type 2 diabetes; however, frequent discontinuation with reduced kidney function and increased disease severity indicates that a comparison with any other group (eg, nonusers or insulin users) must address significant residual confounding concerns. Objectives: To examine the potential for residual confounding in a commonly used observational study design applied to metformin and to propose a more robust study design for future observational studies of metformin. Design, Setting, and Participants: This retrospective cohort study with a prevalent user design was conducted using an administrative claims database for Medicare Advantage beneficiaries in the US. Participants were categorized into 2 distinct cohorts: 404 458 individuals with type 2 diabetes and 81 791 individuals with prediabetes. Clinical history was observed in 2018, and end points were observed in 2019. Statistical analyses were conducted between May and December 2021. Exposures: Prevalent use (recent prescription and history of use on at least 90 of the preceding 365 days) of metformin or insulin but not both at the start of the observation period. Main Outcomes and Measures: Total inpatient admission days in 2019 and total medical spending (excluding prescription drugs) in 2019. Each of these measures was treated as a binary outcome (0 vs >0 inpatient days and top 10% vs bottom 90% of medical spending). Results: The study included 404 458 adults with type 2 diabetes (mean [SD] age, 74.5 [7.5] years; 52.7% female). A strong metformin effect estimate was associated with reduced inpatient admissions (odds ratio, 0.60; 95% CI, 0.58-0.62) and reduced medical expenditures (odds ratio, 0.57; 95% CI, 0.55-0.60). However, implementation of additional robust design features (negative control outcomes and a complementary cohort) revealed that the estimated beneficial effect was attributable to residual confounding associated with individuals' overall health, not metformin itself. Conclusions and Relevance: These findings suggest that common observational study designs for studies of metformin in a type 2 diabetes population are at risk for consequential residual confounding. By performing 2 additional validation checks, the study design proposed here exposes residual confounding that nullifies the initially favorable claim derived from a common study design.

Meta-analysis of uranium contamination in groundwater of the alluvial plains of Punjab, northwest India: Status, health risk, and hydrogeochemical processes.

Despite numerous studies, there are many knowledge gaps in our understanding of uranium (U) contamination in the alluvial aquifers of Punjab, India. In this study, a large hydrogeochemical dataset was compiled to better understand the major factors controlling the mobility and enrichment of uranium (U) in this groundwater system. The results showed that shallow groundwaters (<60 m) are more contaminated with U than from deeper depths (>60 m). This effect was predominant in the Southwest districts of the Malwa, facing significant risk due to chemical toxicity of U. Groundwaters are mostly oxidizing and alkaline (median pH: 7.25 to 7.33) in nature. Spearman correlation analysis showed that U concentrations are more closely related to total dissolved solids (TDS), salinity, Na, K, HCO3-, NO3- Cl-, and F- in shallow water than deep water, but TDS and salinity remained highly correlated (U-TDS: ρ = 0.5 to 0.6; U-salinity: ρ = 0.5). This correlation suggests that the salt effect due to high competition between ions is the principal cause of U mobilization. This effect is evident when the U level increased with increasing mixed water species (Na-Cl, Mg-Cl, and Na-HCO3). Speciation data showed that the most dominant U species are Ca2UO2(CO3)2- and CaUO2(CO3)3-, which are responsible for the U mobility. Based on the field parameters, TDS along with pH and oxidation-reduction potential (ORP) were better fitted to U concentration above the WHO guideline value (30 µg.L-1), thus this combination could be used as a quick indicator of U contamination. The strong positive correlation of U with F- (ρ = 0.5) in shallow waters indicates that their primary source is geogenic, while anthropogenic factors such as canal irrigation, groundwater table decline, and use of agrochemicals (mainly nitrate fertilizers) as well as climate-related factors i.e., high evaporation under arid/semi-arid climatic conditions, which result in higher redox and TDS/salinity levels, may greatly affect enrichment of U. The geochemical rationale of this study will provide Science-based-policy implications for U health risk assessment in this region and further extrapolate these findings to other arid/semi-arid areas worldwide.

Soil-sediment linkage and trace element contamination in forested/deforested areas of the Itacaiúnas River Watershed, Brazil: To what extent land-use change plays a role?

Trace elements (TE) contamination in forested areas of the Itacaiúnas River Watershed (IRW), Brazilian Amazon, arouses growing interest owing to the rapid deforestation and mining activities. In this study, soils (surface, SS; bottom, BS) and stream sediments (SD) from forested/deforested areas of IRW were analyzed with the aim of (1) evaluating the major sources of TE (mainly As, Ba, Cd, Cu, Co, Cr, Hg, Mo, Mn, Ni, Pb, V, and Zn), and (2) examining the soil-sediment TE link related to land-use change and/or geologic factors. Compositional data analysis (CoDA) was used to eliminate data closure issues and the centred log-ratio (clr) transformation yielded better results in Principal Component Analysis (PCA). The TE distribution pattern was significantly different (p < 0.05) between forested and deforested areas, but in both areas the TE distribution pattern is significantly correlated between SS, BS, and SD, indicating a strong lithogenic control. PCA (clr-transformed) identified the major geochemical bedrock signature as Fe-Ti-V-Cu-Cr-Ni, which is nearly similar in soil and sediments. The more accentuated enrichment and the maximum number of anomalies of these elements were found in the Carajás Basin and are highly coincident with mineral deposits/local lithologies without clear indication of anthropogenic contamination from point sources. Besides geogenic factors, deforestation is also affecting TE distribution in the basin. In deforested areas, Mn was significantly enriched in the surface horizon. Furthermore, linear regression analysis shows stronger TE relationships between soils and sediments in deforested areas than in forested ones, reflecting higher erosion in the former. This could be the reason for the relatively higher enrichment of TE (e.g., Fe, Mn, Cu, Cr, Ni) in deforested sediments. The TE contamination using regional background values provides more accurate results than worldwide reference values. Thus, the former should be considered for a more realistic environmental risk assessment in IRW and other forest ecosystems in the Brazilian Amazon.

A decrease in cellular energy status stimulates PERK-dependent eIF2alpha phosphorylation and regulates protein synthesis in pancreatic beta-cells.

In the present study, we demonstrate that, in pancreatic beta-cells, eIF2alpha (eukaryotic initiation factor 2alpha) phosphorylation in response to a decrease in glucose concentration is primarily mediated by the activation of PERK [PKR (protein kinase RNA activated)-like endoplasmic reticulum kinase]. We provide evidence that this increase in PERK activity is evoked by a decrease in the energy status of the cell via a potentially novel mechanism that is independent of IRE1 (inositol requiring enzyme 1) activation and the accumulation of unfolded nascent proteins within the endoplasmic reticulum. The inhibition of eIF2alpha phosphorylation in glucose-deprived cells by the overexpression of dominant-negative PERK or an N-terminal truncation mutant of GADD34 (growth-arrest and DNA-damage-inducible protein 34) leads to a 53% increase in the rate of total protein synthesis. Polysome analysis revealed that this coincides with an increase in the amplitude but not the number of ribosomes per mRNA, indicating that eIF2alpha dephosphorylation mobilizes hitherto untranslated mRNAs on to polysomes. In summary, we show that PERK is activated at low glucose concentrations in response to a decrease in energy status and that this plays an important role in glucose-regulated protein synthesis in pancreatic beta-cells.

Matrix Signaling Subsequent to a Myocardial Infarction: A Proteomic Profile of Tissue Factor Microparticles.

This study investigated the release and proteomic profile of tissue factor microparticles (TFMPs) prospectively (up to 6 months) following a myocardial infarction (MI) in a chronic porcine model to establish their utility in tracking cellular level activities that predict physiologic outcomes. Our animal groups (n = 6 to 8 each) consisted of control, noninfarcted (negative control); infarcted only (positive control); and infarcted animals treated with cardiac resynchronization therapy (CRT) and a ß-blocker (BB) (metoprolol succinate). The authors found different protein profiles in TFMPs between the control, infarcted only group, and the CRT + BB treated group with predictive impact on the outward phenotype of pathological remodeling after an MI within and between groups. This novel approach of monitoring cellular level activities by profiling the content of TFMPs has the potential of addressing a shortfall of the current crop of cardiac biomarkers, which is the inability to capture composite molecular changes associated with chronic maladaptive signaling in a spatial and temporal manner.