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We present high-cadence UV, optical, and near-infrared data on the luminous Type II-P supernova SN 2017gmr from hours after discovery through the first 180 days. SN 2017gmr does not show signs of narrow, high-ionization emission lines in the early optical spectra, yet the optical light-curve evolution suggests that an extra energy source from circumstellar medium (CSM) interaction must be present for at least 2 days after explosion. Modeling of the early light curve indicates a ∼500 R o progenitor radius, consistent with a rather compact red supergiant, and late-time luminosities indicate that up to 0.130 ± 0.026 M o of 56Ni are present, if the light curve is solely powered by radioactive decay, although the 56Ni mass may be lower if CSM interaction contributes to the post-plateau luminosity. Prominent multipeaked emission lines of Hα and [O i] emerge after day 154, as a result of either an asymmetric explosion or asymmetries in the CSM. The lack of narrow lines within the first 2 days of explosion in the likely presence of CSM interaction may be an example of close, dense, asymmetric CSM that is quickly enveloped by the spherical supernova ejecta.

We present high-cadence photometric and spectroscopic observations of SN 2020jfo in ultraviolet and optical/near-infrared bands starting from ∼3 to ∼434 d after the explosion, including the earliest data with the 10.4-m GTC. SN 2020jfo is a hydrogen-rich Type II SN with a relatively short plateau duration (67.0 ± 0.6 d). When compared to other Type II supernovae (SNe) of similar or shorter plateau lengths, SN 2020jfo exhibits a fainter peak absolute V -band magnitude (M V = −16.90 ± 0.34 mag). SN 2020jfo shows significant Hα absorption in the plateau phase similar to that of typical SNe II. The emission line of stable [Ni  ii ] λ7378, mostly seen in low-luminosity SNe II, is very prominent in the nebular-phase spectra of SN 2020jfo. Using the relative strengths of [Ni  ii ] λ7378 and [Fe  ii ] λ7155, we derive the Ni/Fe production (abundance) ratio of 0.08–0.10, which is ∼1.5 times the solar value. The progenitor mass of SN 2020jfo from nebular-phase spectral modelling and semi-analytical modelling falls in the range of 12–15 M⊙. Furthermore, semi-analytical modelling suggests a massive H envelope in the progenitor of SN 2020jfo, which is unlikely for SNe II having short plateaus. [ABSTRACT FROM AUTHOR]

Background and Objective: Dilated cardiomyopathy (DCM) is a prevalent form of heart failure results in dilation and disruption of heart. Most strikingly a majority of the DCM cases do not have any identified etiology, hence known as idiopathic DCM (IDCM). Our study aimed to investigate the cross-talk between leukocytes and cardiomyocytes in terms of cardiac inflammation and stress response in IDCM., Methods: 60 IDCM patients and 60 age and sex matched healthy volunteers were recruited in this study based on the New York Heart Association (NYHA) guidelines. Their echocardiographic and biochemical markers were assessed and PBMCs were analyzed for leukocyte migration and inflammation. Also C2C12 myocyte cells were cultured with LPS-activated RAW264.7 monocytes to investigate the cross-talk between them., Results: Left ventricular (LV) dysfunction was evident in the IDCM patients which were correlated with their physical discomfort level according to NYHA classification. Their serum levels of IL-1β and TNF-α (≈ 20 pg/ml) were found to be very high along with hs-CRP and IL-2. Elevated levels of ROCK, SMA and ICAM-1 proteins indicated activation and migration of the leukocytes. During monocyte-myocyte co-culture, robust diapedesis was observed in the cultured macrophage cells towards myocytes through the transwell pores (8 µM) in presence of IL-1β and TNF-α causing ER stress and cell death in the myocytes. Inhibition of this migration or by alleviating ER stress inhibits leukocyte recruitment and ensures protection to the myocytes., Conclusion: The present study showed that alleviating cellular stress and managing leukocyte migration promotes protection to the heart., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Highly pathogenic Burkholderia pseudomallei is the causative agent of melioidosis, a neglected tropical disease endemic in Southeast Asian tropical region. This bacterium encompasses diverse virulence factors which further undergo dynamic gene-expression flux as it transits through distinct environmental niches within the host which may lead to manifestation of differential clinical symptoms. B. pseudomallei, is classified as a Tier 1 select agent in the United States and regarded as a risk group 3 organism in India with the potential to be used as bioweapon. Considering these facts, it is vital to uncover both physiological and genetic heterogeneity of B. pseudomallei, particularly to identify any novel virulence factors that may contribute to pathogenicity. B. pseudomallei strain CM000113 was isolated from a clinical case in India, characterized it for its physiological, biochemical, and prominently genetic traits through WGS. It has a type 2 morphotype with faster doubling time and high biofilm producing capacity as compared to Pseudomonas aeruginosa. The genome size is 7.3 Mbp and it is phylogenetically close to B. pseudomallei strain Mahidol 1106a and Burkholderia mallei Turkey 2. We observed genetic heterogeneity, as key virulence factors that were identified shows sequence dissimilarity with reference strains. Additionally, presence of genomic islands, harbouring two virulence factors, GmhA and GmhB2, associated with pathogenesis indicates possibility of horizontal gene transfer. These results emphasize the need for an extensive study focusing the genome of B. pseudomallei and its associated heterogeneity, to identify molecular biomarkers aiding to develop point-of-care diagnostic kits for early diagnosis of melioidosis., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The concept of the vitamin D response index was developed based on vitamin D intervention studies conducted with Finnish cohorts. In this study, we challenged the concept by performing a single vitamin D 3 bolus (80,000 IU) intervention with a cohort of 100 native Saudis. The change of serum levels of the proinflammatory cytokines interleukin 6, interleukin 8 and tumor necrosis factor measured directly before intervention in comparison to samples taken one and thirty days after vitamin D 3 supplementation were used as biomarkers for distinguishing low, mid and high responders. Interestingly, we identified 39 % of the study participants as low responders. In contrast, when we used in a subset of 37 study participants whole blood expression changes of seven well-known vitamin D target genes one and thirty days after supplementation as alternative biomarkers, only 9 persons (24 %) were identified as low responders. In conclusion, in Saudi Arabia the rate of low vitamin D responders is equal or even higher than that in Finland. Therefore, similar to Nordic countries also in Saudi Arabia appropriate vitamin D 3 supplementation is essential, in order to fulfill the needs of low responders., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

Vitamin D modulates innate and adaptive immunity, the molecular mechanisms of which we aim to understand under human in vivo conditions. Therefore, we designed the study VitDHiD (NCT03537027) as a human investigation, in which 25 healthy individuals were supplemented with a single vitamin D 3 bolus (80,000 IU). Transcriptome-wide differential gene expression analysis of peripheral blood mononuclear cells (PBMCs), which were isolated directly before and 24 h after supplementation, identified 452 genes significantly (FDR < 0.05) responding to vitamin D. In vitro studies using PBMCs from the same individuals confirmed 138 of these genes as targets of 1α,25-dihydroxyvitamin D 3 . A subset of the 91 most regulated in vivo vitamin D target genes indicated focal adhesion as the major pathway being upregulated by vitamin D 3 supplementation of healthy individuals. Differences in the individual-specific responsiveness of in vivo vitamin D target genes in relation to the increase of the person's vitamin D status allowed a segregation of the VitDHiD participants into 9 high, 12 mid and 4 low responders. The expression profile of nearly 600 genes elucidate the difference between high and low vitamin D responders, the most prominent of which is the HLA-C (major histocompatibility complex, class I, C) gene., (© 2024. The Author(s).)

The vitamin D3 metabolite 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), its nuclear receptor VDR (vitamin D receptor) and hundreds of their target genes are not only key regulators of calcium homeostasis, but also important modulators of the immune system. Innate immune cells like monocytes use VDR for efficient differentiation and are very responsive to vitamin D. So far, most information on the gene regulatory function of vitamin D and its physiological impact had been obtained from in vitro studies using supraphysiological doses of 1,25(OH)2D3. Therefore, medical experiments like the study VitDHiD (NCT03537027), where 25 healthy individuals were supplemented once with a vitamin D3 bolus (80,000 IU), provide important insight into the response to vitamin D under in vivo conditions. In this study, we inspected 452 in vivo vitamin D target genes from peripheral blood mononuclear cells (PBMCs) detected in VitDHiD and found 61 of them involved in eight major KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways of innate immunity. Under in vivo conditions in healthy individuals vitamin D either silences five pathways of innate immunity, stabilizes two and increases one, so that acute inflammation is suppressed and the release of cytokines is kept under control. A ranking of the 61 target genes by inducibility, basal expression and multiple involvements in the pathways highlighted the genes NFKBIA (NFκB inhibitor alpha), NFKBIZ, FOSL2 (FOS like 2, AP1 transcription factor subunit), JDP2 (Jun dimerization protein 2), PIK3R1 (phosphoinositide-3-kinase regulatory subunit 1), CLEC7A (C-type lectin domain containing 7A), DUSP6 (dual specificity phosphatase 6), NCF2 (neutrophil cytosolic factor 2), PLCB1 (phospholipase C beta 1), PLCG2 and TNFAIP3 (TNF alpha induced protein 3). In conclusion, vitamin D's in vivo effect on innate immunity in healthy adults is mediated by the interconnection of the pathways of neutrophil extracellular trap formation, Toll-like receptor, chemokine and phagosome signaling, NOD-like receptor, C-type lectin receptor, apoptosis and interleukin 17 through a limited set of proteins encoded by key target genes., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Jaroslawska et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Chronic kidney disease (CKD) is one of the leading causes of mortality across the globe. Early diagnosis of the disease is important in order to prevent the adverse outcome related to CKD. Many laboratories adopt creatinine-based e-GFR equations which yields imprecise results leading to misdiagnosis of CKD. Emerging studies indicated cystatin C as a better renal marker than creatinine. The aim of the study is to compare the efficacy of CKD epidemiology collaboration (CKD-EPI) creatinine e-GFR equations with (CKD EPI) cystatin-based e-GFR equations alone and in combination with creatinine for early detection of CKD. A cross-sectional study employing 473 patients was conducted. Three estimating GFR equations were calculated based on creatinine and cystatin C. Pearson Correlation study was done to assess the correlation of creatinine and cystatin C with their respective GFRs. A predictive model was developed, and ROC curve was constructed to compare efficacy, sensitivity and specificity of the creatinine and cystatin C based equations. Cystatin C exhibited better negative correlation with GFR than creatinine in correlation study performed with three commonly employed eGFR equations including  CKD EPI Creatine cystatin C combined  equation (2021), cys C alone and CKD EPI  creatinine (2021)  equations respectively[r=(-) 0.801 vs. r=(-)0.786 vs. r=(-)0.773]. Predictive model demonstrated highest efficiency, sensitivity and specificity for creatinine-cystatin C combined equation (88%, 81% and 93%) followed by cystatin C alone equation (73%,63% and 82%) and creatinine-based equation  (61%, 56% and 66% respectively). The study showed better performance of cystatin C based equations for early detection of advance stages in chronic kidney disease as compared to creatinine-based e-GFR equation., Competing Interests: Conflict of interestThe authors declare no conflict of interest for this study., (© The Author(s), under exclusive licence to Association of Clinical Biochemists of India 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

AFG3L2 is a zinc metalloprotease and an ATPase localized in an inner mitochondrial membrane involved in mitochondrial quality control of several nuclear- and mitochondrial-encoded proteins. Mutations in AFG3L2 lead to diseases like slow progressive ataxia, which is a neurological disorder. This review delineates the cellular functions of AFG3L2 and its dysfunction that leads to major clinical outcomes, which include spinocerebellar ataxia type 28, spastic ataxia type 5, and optic atrophy type 12. It summarizes all relevant AFG3L2 mutations associated with the clinical outcomes to understand the detailed mechanisms attributable to its structure-related multifaceted roles in proteostasis and quality control. We face early diagnostic challenges of ataxia and optic neuropathy due to asymptomatic parents and variable clinical manifestations due to heterozygosity/homozygosity of AFG3L2 mutations. This review intends to promote AFG3L2 as a putative prognostic or diagnostic marker., (© 2023. The Author(s).)

Vitamin D intervention studies are designed to evaluate the impact of the micronutrient vitamin D 3 on health and disease. The appropriate design of studies is essential for their quality, successful execution, and interpretation. Randomized controlled trials (RCTs) are considered the "gold standard" for intervention studies. However, the most recent large-scale (up to 25,000 participants), long-term RCTs involving vitamin D 3 did not provide any statistically significant primary results. This may be because they are designed similarly to RCTs of a therapeutic drug but not of a nutritional compound and that only a limited set of parameters per individual were determined. We propose an alternative concept using the segregation of study participants into different groups of responsiveness to vitamin D 3 supplementation and in parallel measuring a larger set of genome-wide parameters over multiple time points. This is in accordance with recently developed mechanistic modeling approaches that do not require a large number of study participants, as in the case of statistical modeling of the results of a RCT. Our experience is based on the vitamin D intervention trials VitDmet, VitDbol, and VitDHiD, which allowed us to distinguish the study participants into high, mid, and low vitamin D responders. In particular, investigating the vulnerable group of low vitamin D responders will provide future studies with more conclusive results both on the clinical and molecular benefits of vitamin D 3 supplementation. In conclusion, our approach suggests a paradigm shift towards detailed investigations of transcriptome and epigenome-wide parameters of a limited set of individuals, who, due to a longitudinal design, can act as their own controls.

Objective: Measurement of total vitamin B12 (vit B12) concentration raised concerns over early detection of vit B12 deficiency due to its clinical unreliability. In this present article we aimed to assess the efficacy of holo-transcobolamin (active vit B12) for true evaluation of vit B12 deficiency., Methods: This retrospective study included 100 participants referred for vit B12 assay. Serum total vit B12, active vit B12 and homocysteine were estimated., Results: Our study showed 59% of the total participants with vit B12 deficiency (185 ± 64.62 pg/ml) and 18% with hyper-cobalaminemia (1666.9 ± 367.13 pg/ml) based on their total vit B12 concentrations. A comparative study on total vit B12 and active vit B12 was done which reflected a striking disparity in results. Active vit B12 reported 28.8% patients with vit B12 deficiency (19.8 ± 17.48 pg/ml) and only 16.6% patients with hyper-cobalaminemia (224.14 ± 10 pg/ml). Active vit B12 appeared to be more sensitive (82.35% vs 65%) and specific (46.6% vs. 43.8%) diagnostic marker compared to total vit B12. Pearson Correlation study indicated a strong positive correlation (r = 0.695 at p < 0.01) hence justified use of the two methods., Conclusion: We claim that active vit B12 is a much more reliable biomarker than total vit B12 for early diagnosis of vit B12 deficiency., (© 2022. The Author(s).)

Background: Mask wearing can restrict the spread of respiratory viral transmission during the third wave of the COVID-19 pandemic. Globally, governments have emphasized its use in workplaces and public areas to prevent the transmission routes of corona virus. In spite of the current awareness in the general population, the stringency of wearing the mask lies as an individual's choices. Subject and Methods . This research work discusses available studies on the types and comparison of masks in the market for use. It includes a short survey conducted with 1,173 anonymized healthy participants primarily devoid of comorbidities. The survey includes the effects of mask wearing, while outdoor with minimal activities like walking and with mild activities like jogging and stretching. Our research further discusses various health effects of wearing a mask, including cardiac output, hypoxemia, hypoxia, and dyspnoea, and how such situations that pose a threat can be consciously avoided., Results: It was found that the majority of people use cloth/fabric reusable mask. There remains scope for better-designed masks and improving health in the mass population by inculcating healthy breathing habits and other relevant exercises that can help people cope up better in this fight against the deadly virus at a larger scale., Conclusion: For most of the survey questions, there was significant correlation between gender and the related responses as there was no significantly observable difference in the nonparametric, unpaired analyses of responses. The main objective of this research work is to initiate more discussions and enhance awareness in natural ways of staying healthy during the pandemic emphasizing mask use. Further progress in this aspect remains a whole new area for future exploration., Competing Interests: The authors declare they have no financial or nonfinancial conflicts to disclose., (Copyright © 2022 Revati Amin et al.)

Purpose: The present study was intended to investigate whether monocyte immune activation shapes plasma positive to negative acute phase reactants (APRs) ratio and predicts disease severity in dengue infection., Methods: Serum level of ferritin, ceruloplasmin and transferrin was measured by means of electrochemiluminescence and immunoturbidimetry, respectively. Gene expression and plasma level for TNF-α, IL-6 and IL1-β was measured by means of RT-qPCR and ELISA., Results: A significant increased serum ferritin to transferrin [6.6 (3-11.7) vs 3.4 (1.9-6.1)] and ceruloplasmin to transferrin ratio [0.48 (0.21-0.87) vs 0.22 (0.13-0.43)] has been detected among the subjects with secondary dengue infection (SDENI) compared to primarily infected (PDENI) subjects (P < 0.001). Significant increased expression for CD14 + monocyte TNF-α, IL-6 and IL-1β has been detected in SDENI patients (vs PDENI and control, P < 0.001). Plasma ferritin to transferrin ratio was found in a significant association with high level of plasma TNF-α [ρ = 0.6522, 95% CI (0.4714-0.7805)], IL-6 [ρ = 0.6181, 95% CI (0.4257-0.7571)] and IL- 1β [ρ = 0.4119, 95% CI (0.1689-0.6077)] level among SDENI patients at 5th day time point after progression of the disease, with significantly low platelet [P < 0.001] and prolonging prothrombin time [P < 0.001] compared to control and PDENI subjects, respectively., Conclusion: Acute proinflammatory cytokine response is significantly associated with increased positive to negative APRs ratio in SDENI patients, which predicts intense immune activation, and renders SDENI patients extremely susceptible to hemostatic derangement., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objectives: To study any possible correlation between arsenic toxicity and the development of oral carcinoma in West Bengal population., Material and Methods: Ethical clearance for this study was obtained from the Vivekananda Institute of Medical Sciences. Out of 30 785 patients attending our hospital from November 2012 to July 2015, 107 cases and 50 control individuals were selected. The hair and buccal smear samples were obtained upon their consent for the purpose of the analysis of arsenic count and cytogenetic damage, respectively., Results: Ninety-six percent of cases came from the highly arsenic affected districts and 81.3% showed their arsenic count above the safe limit (0.8 μg/g) whereas 96% of the controls' arsenic count was within the safe limit. The study showed a significant difference of the micronuclei and apoptosis frequency between the cases and controls., Conclusions: The difference of micronuclei and apoptosis frequency between cases and controls was significant. The maximum number of cases came from highly arsenic affected areas and a higher percentage of cases showed elevated arsenic count, as compared to controls, which may indicate a possible link between arsenic toxicity and this disease. However, a larger sample size is required for a proper correlation. Int J Occup Med Environ Health 2017;30(2):271-279., (This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.)

This article reports the incidence of hemoglobin H (HbH) disease among the nontribe Bengali population living in South 24-Parganas of West Bengal. Among 105 patients with unexplained anemia with moderate hematological parameters referred to our laboratory over a period of 2 years, 17 cases (16.19%) were found to have HbH disease identified by hemoglobin electrophoresis. Molecular investigation for two common mutations of α-thalassemia (-3.7α, -4.2α) was carried out in these 17 cases using DNA extraction followed by multiplex polymerase chain reaction. Presence of these common mutations were identified in 10 of the 17 cases. Of them, -3.7α homozygotes (-3.7α/-3.7α), -3.7α/-4.2α double heterozygotes, and -4.2α homozygotes (-4.2α/-4.2α) were found in three, five, and one patient, respectively. The South East Asian (- -SEA) mutation was searched for in one Chinese patient because this mutation is very common among the Chinese population, and he showed the presence of this mutation. Seven patients with HbH disease did not show any of these mutations. These patients may have other α mutations, which need to be studied further. The need to screen for α-thalassemia at the molecular level in patients with unexplained anemia and its implication in the future generation of our society have been discussed in this article.