Influence of activator ratios and concentration on the physio-mechanical and microstructural characteristics of the geopolymers derived from sandstone processing waste.

Natural stones have been utilized to meet various needs of human civilization since ancient times. The exploitation of any resource is associated with the production of redundant materials called wastes. Sandstone waste (SW) is one such waste obtained during the industrial processing of sandstones. Due to its siliceous composition, extensive yield, and disorganized dumping, noxious conditions related to land and human health are promoted. However, the lack of comprehensive engineering studies, mineralogical analysis, and design methodologies associated with the utilization of sandstone processing wastes restricted their applicability only to fillers or partial substitutes with pozzolans and traditional cement in meager volumes. In the past, limited efforts have been made to utilize SW as a construction entity, particularly for binding purposes. Thus, to enhance the scope of its utilization, a comprehensive investigation has been performed in this research to transform sandstone waste into a novel construction material by geopolymerization. Mix design tailoring and laboratory tests were implemented to understand the effects of sodium hydroxide concentration and sodium silicate to sodium hydroxide ratio on the dissolution and physio-mechanical characteristics of SW-based geopolymers. The activator-to-binder ratio was restricted to 0.4 to obtain pastes with sufficient workability without hindering the properties of the matrix. Besides, a high temperature-curing regime was selected based on SW's crystallographic and reactivity analysis. Subsequently, a total of 48 samples were prepared and tested at the curing age of 28 days. Detailed characterization of SW and SW-based geopolymer samples was performed using optical, X-ray, and infrared spectroscopies aided by electron imaging and thermogravimetric techniques. SW-based geopolymer samples showed compressive strengths in the range of 6-12 MPa, ~2 to 3 times higher than those obtained in previous experimentations. Phase analysis and microstructural examinations confirmed SW's participation in geopolymerization. Overall, it could be advocated that geopolymerization is an innovative approach for solving issues related to the disposal and re-utilization of SW, extending its possible application to the fields of cement mixes, wall tiles, mortars, and masonry as per the commendations of ASTM and ACI committee.

Hypertension: A National Cross-Sectional Study in India.

OBJECTIVE: Hypertension is a global public health problem. This article aimed to estimate the national prevalence of hypertension in India for both women and men. The study had also examined the demographic and socioeconomic status of hypertensive women and men. METHODS: The study used the National Family Health Survey 4 from all over India. Hypertension of 661 771 women (15-49 years) and 104 357 men (15-54 years) and their demographic and socioeconomic variables were assessed. Crosstabulation, chi-square tests, and multivariate logistic regression were used. RESULTS: The prevalence of hypertension in women and men were 11.40% and 18.10%, respec- tively. State-wise, Sikkim had shown the maximum prevalence. Older women (45-49 years) and men (50-54 years) had the highest hypertension prevalence among all age groups. Urban people had shown proportionately more hypertension than rural people. Education, working status, and richer economic status emerged as significant risk factors. Women with lower edu- cational status and men with higher educational status were more likely to be hypertensive. Working people were more hypertensive than their non-working peers. Economically, sound men were more hypertensive than poor people. Hypertensive people accessed medical care more. CONCLUSION: There are various modifiable risk socioeconomic factors associated with hyperten- sion. Policymakers can consider the current findings for better preventive planning. The risk factors identified in the study should be considered with appropriate weightage.

Violence against physicians and nurses: a systematic literature review.

Background: Violence against physicians and nurses is a global public health problem. This study explored violence against physicians and nurses using a systematic literature review. Methods: Pubmed and Scopus were searched using search words 'violence' OR 'aggression' 'against' 'physicians' AND 'nurses'. Articles published between 2010 and 2020 in the English language, excluding review/systemic review articles, were included in the study. We used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for literature search and reporting and assessed the quality of the article based on the JBI checklist for analytical cross sectional studies. Results: A total of 22 studies were included. The majority of the studies showed that there was a significant violent incident within every setting, often directly involving patients or their relatives. Workers of emergency departments were more likely to be exposed to violence. Verbal abuses were the highest among all settings. Physicians were more likely to face physical violence, while nurses were more prone to sexual harassment. Lack of communication plays a significant role. Fewer reports of violence were noted due to lack of action taken previously. Conclusion: Adequate policy making and implementation and operational research are required to further mitigate the episodes of violence.

A phase 2 single center open label randomised control trial for convalescent plasma therapy in patients with severe COVID-19.

A single center open label phase 2 randomised control trial (Clinical Trial Registry of India No. CTRI/2020/05/025209) was done to assess clinical and immunological benefits of passive immunization using convalescent plasma therapy. At the Infectious Diseases and Beleghata General Hospital in Kolkata, India, 80 patients hospitalized with severe COVID-19 disease and fulfilling the inclusion criteria (aged more than 18 years, with either mild ARDS having PaO2/FiO2 200-300 or moderate ARDS having PaO2/FiO2 100-200, not on mechanical ventilation) were recruited and randomized into either standard of care (SOC) arm (N = 40) or the convalescent plasma therapy (CPT) arm (N = 40). Primary outcomes were all-cause mortality by day 30 of enrolment and immunological correlates of response to therapy if any, for which plasma abundance of a large panel of cytokines was quantitated before and after intervention to assess the effect of CPT on the systemic hyper-inflammation encountered in these patients. The secondary outcomes were recovery from ARDS and time taken to negative viral RNA PCR as well as to report any adverse reaction to plasma therapy. Transfused convalescent plasma was characterized in terms of its neutralizing antibody content as well as proteome. The trial was completed and it was found that primary outcome of all-cause mortality was not significantly different among severe COVID-19 patients with ARDS randomized to two treatment arms (Mantel-Haenszel Hazard Ratio 0.6731, 95% confidence interval 0.3010-1.505, with a P value of 0.3424 on Mantel-Cox Log-rank test). No adverse effect was reported with CPT. In severe COVID-19 patients with mild or moderate ARDS no significant clinical benefit was registered in this clinical trial with convalescent plasma therapy in terms of prespecified outcomes.

ApoE ε4 and IL-6-174G/C Polymorphism may Lead to Early Onset of Alzheimer's Disease with Atypical Presentation.

BACKGROUND: Alzheimer's disease (AD) is the most common cause of dementia. Although genetic mutations are known in rare familial form, exact cause of neurodegeneration in sporadic AD is still unknown. While ApoE ε4 and IL-6 C-174G/C patterns have been found to increase the risk of AD in Caucasians, the results are inconsistent in other ethnic groups. OBJECTIVE: The aim of this study was to evaluate the effect of ApoE and IL-6-174G/C polymorphisms among patients of AD in the Eastern part of India. MATERIALS AND METHODS: Consecutive patients of probable AD diagnosed as per National Institute on Aging-Alzheimer's Association (NIA-AA) criteria with age, gender, and education-matched healthy controls were recruited between December 2015 and September 2018. Patients were clinically evaluated and along with controls were genotyped for ApoE and IL-6-174G/C polymorphisms by the polymerase chain reaction method. RESULTS: A total 115 patients and 162 controls showed a similar pattern of ApoE and IL-6-174G/C polymorphism pattern. While ε3ε3 and GG patterns were the commonest, followed by ε3ε4 and GC pattern in ApoE and IL-6 respectively, the effect of ApoE ε4 and IL-6-174 C allele on AD symptoms could not be established. However, patients with onset before 50 years were found to have significantly higher proportion of ApoE ε4 and C allele of IL-6-174 in comparison to patients with onset above 50. These young patients were also having more atypical presentation than their older counterpart. CONCLUSION: Our study revealed a novel role of both ApoE ε4 and C allele of IL-6-174 together in developing early onset AD with more atypical clinical features.

Midbrain infarction in inherited protein S deficiency: a rare association.

Inherited thrombophilic disorders are well-established predisposing factors for venous thromboembolism, but their role in arterial ischaemic stroke is uncertain. The exact mechanism of arterial thrombosis in thrombophilias remains elusive. Herein, we report a case of a 30-year-old woman who was admitted to our facility with sudden-onset right-sided ptosis and ophthalmoplegia. Detailed clinical features, neuroimaging and laboratory evaluation clinched the diagnosis of ischaemic stroke in midbrain due to microvascular obstruction associated with isolated protein S deficiency. She was treated with oral anticoagulant (warfarin) and physiotherapy; without any improvement of her symptoms at 2 months of follow-up. A high index of clinical suspicion is needed in any case of young ischaemic stroke in absence of common cardiac and vascular risk factors, to recognise the presence of inherited thrombophilia.

Hedgehog dysregulation contributes to tissue-specific inflammaging of resident macrophages.

Age-associated low-grade sterile inflammation, commonly referred to as inflammaging, is a recognized hallmark of aging, which contributes to many age-related diseases. While tissue-resident macrophages are innate immune cells that secrete many types of inflammatory cytokines in response to various stimuli, it is not clear whether they have a role in driving inflammaging. Here we characterized the transcriptional changes associated with physiological aging in mouse resident macrophage populations across different tissues and sexes. Although the age-related transcriptomic signatures of resident macrophages were strikingly tissue-specific, the differentially expressed genes were collectively enriched for those with important innate immune functions such as antigen presentation, cytokine production, and cell adhesion. The brain-resident microglia had the most wide-ranging age-related alterations, with compromised expression of tissue-specific genes and relatively exaggerated responses to endotoxin stimulation. Despite the tissue-specific patterns of aging transcriptomes, components of the hedgehog (Hh) signaling pathway were decreased in aged macrophages across multiple tissues. In vivo suppression of Hh signaling in young animals increased the expression of pro-inflammatory cytokines, while in vitro activation of Hh signaling in old macrophages, in turn, suppressed the expression of these inflammatory cytokines. This suggests that hedgehog signaling could be a potential intervention axis for mitigating age-associated inflammation and related diseases. Overall, our data represent a resourceful catalog of tissue-specific and sex-specific transcriptomic changes in resident macrophages of peritoneum, liver, and brain, during physiological aging.

Assaying Homodimers of NF-κB in Live Single Cells.

NF-κB is a family of heterodimers and homodimers which are generated from subunits encoded by five genes. The predominant classical dimer RelA:p50 is presumed to operate as "NF-κB" in many contexts. However, there are several other dimer species which exist and may even be more functionally relevant in specific cell types. Accurate characterization of stimulus-specific and tissue-specific dimer repertoires is fundamentally important for understanding the downstream gene regulation by NF-κB proteins. In vitro assays such as immunoprecipitation have been widely used to analyze subunit composition, but these methods do not provide information about dimerization status within the natural intracellular environment of intact live cells. Here we apply a live single cell microscopy technique termed Number and Brightness to examine dimers translocating to the nucleus in fibroblasts after pro-inflammatory stimulation. This quantitative assay suggests that RelA:RelA homodimers are more prevalent than might be expected. We also found that the relative proportion of RelA:RelA homodimers can be perturbed by small molecule inhibitors known to disrupt the NF-κB pathway. Our findings show that Number and Brightness is a useful method for investigating NF-κB dimer species in live cells. This approach may help identify the relevant targets in pathophysiological contexts where the dimer specificity of NF-κB intervention is desired.

Ezh2 Regulates Activation-Induced CD8+ T Cell Cycle Progression via Repressing Cdkn2a and Cdkn1c Expression.

Transition from resting to cell cycle in response to antigenic stimulation is an essential step for naïve CD8+ T cells to differentiate to effector and memory cells. Leaving the resting state requires dramatic changes of chromatin status in the key cell cycle inhibitors but the details of these concerted events are not fully elucidated. Here, we showed that Ezh2, an enzymatic component of polycomb repressive complex 2 (PRC2) catalyzing the trimethylation of lysine 27 on histone 3 (H3K27me3), regulates activation induced naïve CD8+ T cells proliferation and apoptosis. Upon deletion of Ezh2 during thymocyte development (Ezh2fl/flCd4Cre+ mice), naive CD8+ T cells displayed impaired proliferation and increased apoptosis in response to antigen stimulation. However, naive CD8+ T cells only had impaired proliferation but no increase in apoptosis when Ezh2 was deleted after activation (Ezh2fl/flGzmBCre+ mice), suggesting cell cycle and apoptosis are temporally separable events controlled by Ezh2. We then showed that deletion of Ezh2 resulted in the increase in expression of cyclin-dependent kinase inhibitors Cdkn2a (p16 and Arf) and Cdkn1c (p57) in activated naïve CD8+ T cells as the consequence of reduced levels of H3K27me3 at these two gene loci. Finally, with real time imaging, we observed prolonged cell division times of naïve CD8+ T cells in the absence of Ezh2 post in vitro stimulation. Together, these findings reveal that repression of Cdkn1c and Cdkn2a by Ezh2 plays a critical role in execution of activation-induced CD8+ T cell proliferation.

Engulfment pathways promote programmed cell death by enhancing the unequal segregation of apoptotic potential.

Components of the conserved engulfment pathways promote programmed cell death in Caenorhabditis elegans (C. elegans) through an unknown mechanism. Here we report that the phagocytic receptor CED-1 mEGF10 is required for the formation of a dorsal-ventral gradient of CED-3 caspase activity within the mother of a cell programmed to die and an increase in the level of CED-3 protein within its dying daughter. Furthermore, CED-1 becomes enriched on plasma membrane regions of neighbouring cells that appose the dorsal side of the mother, which later forms the dying daughter. Therefore, we propose that components of the engulfment pathways promote programmed cell death by enhancing the polar localization of apoptotic factors in mothers of cells programmed to die and the unequal segregation of apoptotic potential into dying and surviving daughters. Our findings reveal a novel function of the engulfment pathways and provide a better understanding of how apoptosis is initiated during C. elegans development.