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Arsenic contamination of groundwater in different parts of the world is an outcome of natural and/or anthropogenic sources, leading to adverse effects on human health and ecosystem. Millions of people from different countries are heavily dependent on groundwater containing elevated level of As for drinking purposes. As contamination of groundwater, poses a serious risk to human health. Excessive and prolonged exposure of inorganic As with drinking water is causing arsenicosis, a deteriorating and disabling disease characterized by skin lesions and pigmentation of the skin, patches on palm of the hands and soles of the feet. Arsenic poisoning culminates into potentially fatal diseases like skin and internal cancers. This paper reviews sources, speciation, and mobility of As and global overview of groundwater As contamination. The paper also critically reviews the As led human health risks, its uptake, metabolism, and toxicity mechanisms. The paper provides an overview of the state-of-the-art knowledge on the alternative As free drinking water and various technologies (oxidation, coagulation flocculation, adsorption, and microbial) for mitigation of the problem of As contamination of groundwater.

Selenium (Se) is an essential micronutrient for humans and animals, but lead to toxicity when taken in excessive amounts. Plants are the main source of dietary Se, but essentiality of Se for plants is still controversial. However, Se at low doses protects the plants from variety of abiotic stresses such as cold, drought, desiccation, and metal stress. In animals, Se acts as an antioxidant and helps in reproduction, immune responses, thyroid hormone metabolism. Selenium is chemically similar to sulfur, hence taken up inside the plants via sulfur transporters present inside root plasma membrane, metabolized via sulfur assimilatory pathway, and volatilized into atmosphere. Selenium induced oxidative stress, distorted protein structure and function, are the main causes of Se toxicity in plants at high doses. Plants can play vital role in overcoming Se deficiency and Se toxicity in different regions of the world, hence, detailed mechanism of Se metabolism inside the plants is necessary for designing effective Se phytoremediation and biofortification strategies.

Abstract Background Translocation renal cell carcinoma (tRCC) is an aggressive subtype of RCC driven by a gene fusion involving a transcription factor in the MiT/TFE gene family, most commonly TFE3. There are currently no approved therapeutic agents specific to tRCC and this subtype of kidney cancer represents a major unmet medical need. Methods We utilized integrative genomic approaches associated with activation of the cyclin- dependent kinase 4/6 (CDK4/6) and mammalian target of rapamycin complex 1 (mTORC1) signaling in tRCC. We tested the activity of CDK4/6 inhibitors (CDK4/6i), alone or in combination with mTORC1-selective inhibition, using in vitro and in vivo models of tRCC. Results Our work shows that tRCC tumors harbor multiple genomic and transcriptional features associated with activation of the CDK4/6 and mTORC1 signaling pathways. Pharmacological inhibition of CDK4/6 activity using palbociclib or abemaciclib, causes cell cycle arrest which was also recapitulated upon genetic knockout of CDK4/6 using CRISPR-Cas9. This was further accompanied by impaired cell growth in long-term culture in presence of palbociclib with a rapid cell regrowth observed upon drug withdrawal. CDK4/6 proteins regulate G1-S cell cycle progression by combining with CyclinD1, the expression of which is significantly reduced upon treatment with mTORC1-selective inhibitor, RMC-5552. Combined treatment with the CDK4/6 inhibitor, palbociclib, and RMC-5552 resulted in synergistic suppression of tRCC cell viability and increased markers of apoptosis in vitro. The combination of palbociclib and RMC-5552 in a tRCC xenograft model showed greater efficacy than either single agent while also being well-tolerated. Conclusions Our work suggests that combined inhibition of CDK4/6 and mTORC1 activity has therapeutic potential in tRCC. This work may offer rationale for molecularly directed therapies in tRCC, which currently lacks any standard of care.

Cold agglutinin disease (CAD) is a rare autoimmune disease caused by high titres of cold-reacting autoantibodies that cause red blood cell agglutination and subsequent hemolysis at low temperatures. Trauma, surgery, and infection/inflammation exacerbate CAD. The present report describes the successful perioperative management of a patient with CAD who underwent outpatient total knee arthroplasty (TKA). A 70-yr-old female was diagnosed with CAD in 2016 with symptoms of pain and pallor in her fingertips, numbness and bluish discoloration of her tongue, and shortness of breath. She was treated with folic acid, rituximab, and bendamustine. After remaining symptom-free for 4 yrs and following consultation with hematology, she was scheduled to undergo TKA. She received a spinal anesthetic with chloroprocaine, intravenous sedation, antiemetic prophylaxis, and an adductor canal catheter for continuous perineural analgesia. Warming measures, including a warm (20 °C) operating room, warm intravenous fluids, warm irrigating fluids, warm surgical prepping solution, forced-air warming blankets, and avoidance of a thigh tourniquet, helped prevent hypothermia in the patient. The patient's perioperative course was uneventful, and she was discharged on the same day. She was followed up via a patient monitoring mobile application and advised to monitor herself for signs of CAD relapse. She had no concerns up to three months after surgery. The perioperative management of patients with CAD is challenging, and multidisciplinary collaboration and coordination between the anesthesiologist, surgeon, hematologist, and nurses, as well as adequate intraoperative precautions and postoperative instructions and monitoring, are essential to ensuring safe surgery and optimal patient outcomes.

Purpose Cold agglutinin disease (CAD) is a rare autoimmune disease caused by high titres of cold-reacting autoantibodies that cause red blood cell agglutination and subsequent hemolysis at low temperatures. Trauma, surgery, and infection/inflammation exacerbate CAD. The present report describes the successful perioperative management of a patient with CAD who underwent outpatient total knee arthroplasty (TKA). Clinical features A 70-yr-old female was diagnosed with CAD in 2016 with symptoms of pain and pallor in her fingertips, numbness and bluish discoloration of her tongue, and shortness of breath. She was treated with folic acid, rituximab, and bendamustine. After remaining symptom-free for 4 yrs and following consultation with hematology, she was scheduled to undergo TKA. She received a spinal anesthetic with chloroprocaine, intravenous sedation, antiemetic prophylaxis, and an adductor canal catheter for continuous perineural analgesia. Warming measures, including a warm (20 °C) operating room, warm intravenous fluids, warm irrigating fluids, warm surgical prepping solution, forced-air warming blankets, and avoidance of a thigh tourniquet, helped prevent hypothermia in the patient. The patient’s perioperative course was uneventful, and she was discharged on the same day. She was followed up via a patient monitoring mobile application and advised to monitor herself for signs of CAD relapse. She had no concerns up to three months after surgery. Conclusion The perioperative management of patients with CAD is challenging, and multidisciplinary collaboration and coordination between the anesthesiologist, surgeon, hematologist, and nurses, as well as adequate intraoperative precautions and postoperative instructions and monitoring, are essential to ensuring safe surgery and optimal patient outcomes.

Hydrogels and ferrogels are greatly emerged biomimetic cross-linked polymeric networks with three-dimensional structures having applications in the fields of joint replacements, catalysts, wound healing, biosensing, contact lenses, and drug delivery. Here, preparations, types, and applications of hydrogels/ferrogels have been assembled. The different types of classes of hydrogels based on the interaction mechanism between the metallic nanoparticles and polymeric network are covered in the review. Recent progress of mechanical, tribological, and magnetic aspects of hydrogels/ferrogels are critically investigated. The clinical perspectives of hydrogels/ferrogels are confirmed by cell migration and proliferation studies. Additionally, this report demonstrates that the addition of different nanoparticles (carbon nanotubes or silicon) within hydrogels/ferrogels can alter the properties of the ferrogels due to the synergistic effect and strong mechanical bonding. Therefore, polymeric candidate hydrogels/ferrogels are precisely illuminated in this review, and can be a potential highlight for future research related to biomedical engineering.

Australia is a multicultural and linguistically diverse country. Despite the vital role of religion/spirituality in the mental health of people from culturally and linguistically diverse (CALD) backgrounds, it is not commonly included in their mental health care. A rapid review was conducted to critically evaluate the studies that identified relevant religious/spiritual aspects regarding mental health care for CALD communities. After a systematic search and screening, sixteen empirical studies were included. The findings of the review suggest that people from CALD backgrounds draw strength and comfort from their religion to support mental health. Religious/spiritual practices were identified as effective mental health strategies by CALD people. Religious leaders were noted to be important sources of mental health support and guidance for individuals from some CALD communities. Collaboration of religious leaders in the mental health care, and integration of religious/spiritual practices into mainstream mental health interventions, may improve mental health care for people with CALD backgrounds.

In this work, a comprehensive analysis was performed on the perovskite solar cells (PSCs) considering MoS 2 as the electron transport layer. For the initial calculations, numerical simulations obtained through SCAPS-1D were matched with experimental results. Further, multi-faceted exploration of material parameters was performed to obtain better performing PSC device. Electron affinity values of MoS 2 layer were varied to obtain an optimum value to quantify its n-type behaviour. Furthermore, the impact of charge density and thickness of MoS 2 , Spiro-OMeTAD, thickness of perovskite layer, interface engineering of perovskite/charge transport layers and temperature were investigated in detail. Incorporation of optimized parameters has resulted in an improved device with J sc , V oc , FF and η values as 23.7 mA cm −2 , 1.15 V, 83.04 and 22.76%, respectively. To ensure higher stability, MoTe 2 and WSe 2 as hole transport layers were also investigated in this work. The obtained results point to the applicability of these HTLs as an optimum replacement for the commonly employed transport layers. Analysis conducted in this work provides a pathway to explore prospective options for improving the efficiency and sustainability of PSCs for commercial applications.

The incidence of anaesthetic complications in children is much more than in adults and sometimes with a severe outcome. Patients under one year of age, those with co-morbidities and posted for emergency surgery are at increased risk for morbidities. Sources of information on the risk involved come from institutional audit, closed claim analysis, and large-scale studies of cardiac arrest. A strategy for preventing postoperative nausea and vomiting (PONV), emergence delirium (ED) and postoperative pain should be a part of every anaesthetic plan. A planned multimodal approach should be opted consisting of nonpharmacologic and pharmacologic prophylaxis along with interventions to reduce the baseline risks. The literature in this subject is reviewed extensively to give comprehensive information to postgraduate students about the current understanding of postoperative anaesthetic concerns. Relevant articles from Pub med, review articles, meta-analysis, and editorials were the primary source of information for this article.

Mitochondrial ribosomes (mitoribosomes) are essential, and their function of synthesising mitochondrial proteins is universal. The core of almost all mitoribosomes is formed from a small number of long and self-folding rRNA molecules. In contrast, the mitoribosome of the apicomplexan parasite Toxoplasma gondii assembles from over 50 extremely short rRNA molecules. Here, we use cryo-EM to discover the features that enable this unusual mitoribosome to perform its function. We reveal that poly-A tails added to rRNA molecules are integrated into the ribosome, and we demonstrate their essentiality for mitoribosome formation and for parasite survival. This is a distinct function for poly-A tails, which are otherwise known primarily as stabilisers of messenger RNAs. Furthermore, while ribosomes typically consist of unique rRNA sequences, here nine sequences are used twice, each copy integrated in a different mitoribosome domain, revealing one of the mechanisms enabling the extreme mitochondrial genome reduction characteristic to Apicomplexa and to a large group of related microbial eukaryotes. Finally, several transcription factor-like proteins are repurposed to compensate for reduced or lost critical ribosomal domains, including members of the ApiAP2 family thus far considered to be DNA-binding transcription factors. Structure of the Toxoplasma mitoribosome made of >50 short rRNA molecules reveals evolutionary solutions to rRNA fragmentation: addition of poly A tails to rRNAs, reused rRNA sequences, and repurposing of proteins with transcription factor domains.