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The increasing interest in postbiotics, a term gaining recognition alongside probiotics and prebiotics, aligns with a growing number of clinical trials demonstrating positive outcomes for specific conditions. Postbiotics present several advantages, including safety, extended shelf life, ease of administration, absence of risk, and patentability, making them more appealing than probiotics alone. This review covers various aspects, starting with an introduction, terminology, classification of postbiotics, and brief mechanisms of action. It emphasizes microbial metabolomics as the initial step in discovering novel postbiotics. Commonly employed techniques such as NMR, GC-MS, and LC-MS are briefly outlined, along with their application principles and limitations in microbial metabolomics. The review also examines existing research where these techniques were used to identify, isolate, and characterize postbiotics derived from different microbial sources. The discovery section concludes by highlighting challenges and future directions to enhance postbiotic discovery. In the second half of the review, we delve deeper into numerous published postbiotic clinical trials to date. We provide brief overviews of system-specific trial applications, their objectives, the postbiotics tested, and their outcomes. The review concludes by highlighting ongoing applications of postbiotics in extended clinical trials, offering a comprehensive overview of the current landscape in this evolving field.

Bifidobacterium bifidum strain BB1 causes a strain-specific enhancement in intestinal epithelial tight junction (TJ) barrier. Tumor necrosis factor (TNF)-α induces an increase in intestinal epithelial TJ permeability and promotes intestinal inflammation. The major purpose of this study was to delineate the protective effect of BB1 against the TNF-α-induced increase in intestinal TJ permeability and to unravel the intracellular mechanisms involved. TNF-α produces an increase in intestinal epithelial TJ permeability in Caco-2 monolayers and in mice. Herein, the addition of BB1 inhibited the TNF-α increase in Caco-2 intestinal TJ permeability and mouse intestinal permeability in a strain-specific manner. BB1 inhibited the TNF-α-induced increase in intestinal TJ permeability by interfering with TNF-α-induced enterocyte NF-κB p50/p65 and myosin light chain kinase (MLCK) gene activation. The BB1 protective effect against the TNF-α-induced increase in intestinal permeability was mediated by toll-like receptor-2/toll-like receptor-6 heterodimer complex activation of peroxisome proliferator-activated receptor γ (PPAR-γ) and PPAR-γ pathway inhibition of TNF-α-induced inhibitory kappa B kinase α (IKK-α) activation, which, in turn, resulted in a step-wise inhibition of NF-κB p50/p65, MLCK gene, MLCK kinase activity, and MLCK-induced opening of the TJ barrier. In conclusion, these studies unraveled novel intracellular mechanisms of BB1 protection against the TNF-α-induced increase in intestinal TJ permeability. The current data show that BB1 protects against the TNF-α-induced increase in intestinal epithelial TJ permeability via a PPAR-γ-dependent inhibition of NF-κB p50/p65 and MLCK gene activation., Competing Interests: Disclosure Statement None declared., (Copyright © 2024 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Background: Defective intestinal epithelial tight junction (TJ), characterized by an increase in intestinal TJ permeability, has been shown to play a critical role in the pathogenesis of inflammatory bowel disease (IBD). Tumor necrosis factor-α (TNF-α) is a key pro-inflammatory cytokine involved in the immunopathology of IBD and has been shown to cause an increase in intestinal epithelial TJ permeability. Although TNF-α antibodies and other biologics have been advanced for use in IBD treatment, these therapies are associated with severe side effects and have limited efficacy, and there is an urgent need for therapies with benign profiles and high therapeutic efficacy. Probiotic bacteria have beneficial effects and are generally safe and represent an important class of potential therapeutic agents in IBD. Lactobacillus acidophilus (LA) is one of the most used probiotics for wide-ranging health benefits, including in gastrointestinal, metabolic, and inflammatory disorders. A specific strain of LA, LA1, was recently demonstrated to have protective and therapeutic effects on the intestinal epithelial TJ barrier. However, the mechanisms of actions of LA1 remain largely unknown., Methods: The primary aim of this study was to investigate microbial-epithelial interactions and novel signaling pathways that regulate the effect of LA1 on TNF-α-induced increase in intestinal epithelial TJ permeability, using cell culture and animal model systems., Results and Conclusion: Pre-treatment of filter-grown Caco-2 monolayers with LA1 prevented the TNF-α-induced increase in intestinal epithelial TJ permeability by inhibiting TNF-α-induced activation of NF-κB p50/p65 and myosin light chain kinase (MLCK) gene and kinase activity in a TLR-2-dependent manner. LA1 produced a TLR-2- and MyD88-dependent activation of NF-κB p50/p65 in immune cells; however, LA1, in intestinal cells, inhibited the NF-κB p50/p65 activation in a TLR-2-dependent but MyD88-independent manner. In addition, LA1 inhibition of NF-κB p50/p65 and MLCK gene was mediated by TLR-2 pathway activation of phosphatidylinositol 3-kinase (PI3K) and IKK-α phosphorylation. Our results demonstrated novel intracellular signaling pathways by which LA1/TLR-2 suppresses the TNF-α pathway activation of NF-κB p50/p65 in intestinal epithelial cells and protects against the TNF-α-induced increase in intestinal epithelial TJ permeability., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Haque, Kaminsky, Abdulqadir, Engers, Kovtunov, Rawat, Al-Sadi and Ma.)

High-altitude (HA) environment presents immense physiological adversities for humans that have been overcome by supplementing bio-active phytochemicals from functional foods that support and accelerate acclimatization under these extreme environmental conditions. Several agricultural interventions have been investigated to enhance the phytochemical content in vegetables however; these studies have been limited to low-altitude (LA) regions only. In view of an existing knowledge gap, current work is designed to compare the phytochemical compositions of HA and LA-grown Brassicaceae vegetables (cabbage, cauliflower, knol-khol, and radish) using organic treatments via farm yard manure (FYM) and Azotobacter. The open field study was conducted as a two-factorial randomized block design. The first factor was treatment (T 1 -FYM, T 2 -Azotobacter, T 3 -FYM + Azotobacter, and T 4 -control) while the second was locations (HA and LA). Among all these treatments, the application of treatment T 3 in HA-grown cabbage showed the highest total phenolic content (TPC; 9.56 μg/mg), total flavonoids content (TFC; 14.48 μg/mg), and antioxidant potential using 2,2-diphenyl-1-picrylhydrazyl (DPPH; 85.97%) and ferric reducing antioxidant power (FRAP; 30.77 μg/mg) compared to LA grown samples. Reverse Phase high performance liquid chromatography (RP-HPLC) analysis showed that treatment T 3 at HA led to significantly high kaempferol (0.92 μg/mg) and sulforaphane (8.94 μg/mg) contents in cabbage whereas, indole-3-carbinol (1.31 μg/mg) was higher in HA grown cauliflower. The present study provides scientific evidence for the enrichment of health-promoting phytochemical compounds in Brassicaceae vegetables grown with T 3 treatment specifically at HA., (© 2024. The Author(s).)

Staphylococcus aureus is a major human pathogen that can cause infections that range from superficial skin and mucosal infections to life threatening disseminated infections. S. aureus can attach to medical devices and host tissues and form biofilms that allow the bacteria to evade the host immune system and provide protection from antimicrobial agents. To counter host-generated oxidative and nitrosative stress mechanisms that are part of the normal host responses to invading pathogens, S. aureus utilizes low molecular weight (LMW) thiols, such as bacillithiol (BSH). Additionally, S. aureus synthesizes its own nitric oxide (NO), which combined with its downstream metabolites may also protect the bacteria against specific host responses. We have previously shown that LMW thiols are required for biofilm formation in Mycobacterium smegmatis and Pseudomonas aeruginosa. Here, we show that the S. aureus bshC mutant strain, which is defective in the last step of the BSH pathway and lacks BSH, is impaired in biofilm formation. We also identify a possible S-nitrosobacillithiol reductase (BSNOR), similar in sequence to an S-nitrosomycothiol reductase found in M. smegmatis and show that the putative S. aureus bsnoR mutant strain has reduced levels of BSH and decreased biofilm formation. Our studies also show that NO plays an important role in biofilm formation and that acidified sodium nitrite severely reduces biofilm thickness. These studies provide insight into the roles of oxidative and nitrosative stress mechanisms on biofilm formation and indicate that BSH and NO are key players in normal biofilm formation in S. aureus., Competing Interests: Declaration of competing interest Clarissa J. Nobile is an associate editor for Microbial Pathogenesis. Clarissa J. Nobile is a cofounder of BioSynesis, Inc., a company developing diagnostics and therapeutics for biofilm infections. Megha Gulati was a consultant for BioSynesis, Inc. The confocal scanning laser microscopy images in this work were taken using a confocal microscope acquired through the National Science Foundation (NSF) MRI award DMR-1625733. This work was supported by the National Institutes of Health (NIH) National Institute of General Medical Sciences (NIGMS) award R35GM124594 to CJN, by the NIH NIGMS award SC3GM100855 and National Science Foundation (NSF) award MCB1244611 to MR, and by the NIH National Institutes of Allergy and Infectious Diseases (NIAID) award R15AI137975 to ADH. CLE was supported by fellowship F31DE028488 from the NIH National Institute of Dental and Craniofacial Research (NIDCR). The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The placenta is a selective maternal-fetal barrier that provides nourishment and protection from infections. However, certain pathogens can attach to and even cross the placenta, causing pregnancy complications with potential lifelong impacts on the child's health. Here, we profiled at the single-cell level the placental responses to three pathogens associated with intrauterine complications-Plasmodium falciparum, Listeria monocytogenes, and Toxoplasma gondii. We found that upon exposure to the pathogens, all placental lineages trigger inflammatory responses that may compromise placental function. Additionally, we characterized the responses of fetal macrophages known as Hofbauer cells (HBCs) to each pathogen and propose that they are the probable niche for T. gondii. Finally, we revealed how P. falciparum adapts to the placental microenvironment by modulating protein export into the host erythrocyte and nutrient uptake pathways. Altogether, we have defined the cellular networks and signaling pathways mediating acute placental inflammatory responses that could contribute to pregnancy complications., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Climate change jeopardizes human health, global biodiversity, and sustainability of the biosphere. To make reliable predictions about climate change, scientists use Earth system models (ESMs) that integrate physical, chemical, and biological processes occurring on land, the oceans, and the atmosphere. Although critical for catalyzing coupled biogeochemical processes, microorganisms have traditionally been left out of ESMs. Here, we generate a "top 10" list of priorities, opportunities, and challenges for the explicit integration of microorganisms into ESMs. We discuss the need for coarse-graining microbial information into functionally relevant categories, as well as the capacity for microorganisms to rapidly evolve in response to climate-change drivers. Microbiologists are uniquely positioned to collect novel and valuable information necessary for next-generation ESMs, but this requires data harmonization and transdisciplinary collaboration to effectively guide adaptation strategies and mitigation policy., Competing Interests: The authors declare no conflict of interest.

Microbial life is not restricted to any particular setting. Over the past several decades, it has been evident that microbial populations can exist in a wide range of environments, including those with extremes in temperature, pressure, salinity, and pH. Bacteria and Archaea are the two most reported types of microbes that can sustain in extreme environments, such as hot springs, ice caves, acid drainage, and salt marshes. Some can even grow in toxic waste, organic solvents, and heavy metals. These microbes are called extremophiles. There exist certain microorganisms that are found capable of thriving in two or more extreme physiological conditions simultaneously, and are regarded as polyextremophiles. Extremophiles possess several physiological and molecular adaptations including production of extremolytes, ice nucleating proteins, pigments, extremozymes and exopolysaccharides. These metabolites are used in many biotechnological industries for making biofuels, developing new medicines, food additives, cryoprotective agents etc. Further, the study of extremophiles holds great significance in astrobiology. The current review summarizes the diversity of microorganisms inhabiting challenging environments and the biotechnological and therapeutic applications of the active metabolites obtained as a response to stress conditions. Bioprospection of extremophiles provides a progressive direction with significant enhancement in economy. Moreover, the introduction to omics approach including whole genome sequencing, single cell genomics, proteomics, metagenomics etc., has made it possible to find many unique microbial communities that could be otherwise difficult to cultivate using traditional methods. These findings might be capable enough to state that discovery of extremophiles can bring evolution to biotechnology., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: Our objective was to evaluate the trend and to assess the impact of maternal region of residence in Western New York (WNY), on severe neonatal opioid withdrawal syndrome (NOWS)., Study Design: Term infants' born at gestational age greater than or equal to 37 weeks with severe NOWS, defined as withdrawal resulting in the receipt of pharmacologic therapy from WNY admitted to our neonatal intensive care unit (NICU) from January 1, 2008 to December 31, 2016, were included. Severe NOWS admissions to our NICU from the following five regions were controlled with birth and insurance data: (1) Urban North, (2) Erie Coastal, (3) Niagara Frontier, (4) Southern Tier, and (5) Urban South., Results: "Urban South" residence was associated with an increased risk of severe NOWS (adjusted odds ratio = 1.8, 97.5% confidence interval: 1.1-2.9). The trend in admission for severe NOWS doubled between 2008 to 2010 and 2014 to 2016 ( p  = 0.01). More infants born to maternal nonprescribed opioid users were placed in foster care at discharge (36.5 vs. 1.9%, p  < 0.001)., Conclusion: In WNY, neonates born to mothers from the "Urban South" were twice at risk of being admitted for severe NOWS. One-third of infants with severe NOWS after nonprescribed opioid use were placed in foster care. Implementing targeted strategies at the community level may help improve outcomes in NOWS., Key Points: · Maternal region of residence is a risk factor for severe neonatal opioid withdrawal.. · Admissions for severe neonatal opioid withdrawal trended up from 2008 to 2010 to 2014 to 2016.. · One-third of the infants born to mothers on nonprescribed opioids were discharged to foster care.., Competing Interests: None declared., (Thieme. All rights reserved.)

Recognizing the real emotion of humans is considered the most essential task for any customer feedback or medical applications. There are many methods available to recognize the type of emotion from speech signal by extracting frequency, pitch, and other dominant features. These features are used to train various models to auto-detect various human emotions. We cannot completely rely on the features of speech signals to detect the emotion, for instance, a customer is angry but still, he is speaking at a low voice (frequency components) which will eventually lead to wrong predictions. Even a video-based emotion detection system can be fooled by false facial expressions for various emotions. To rectify this issue, we need to make a parallel model that will train on textual data and make predictions based on the words present in the text. The model will then classify the type of emotions using more comprehensive information, thus making it a more robust model. To address this issue, we have tested four text-based classification models to classify the emotions of a customer. We examined the text-based models and compared their results which showed that the modified Encoder decoder model with attention mechanism trained on textual data achieved an accuracy of 93.5%. This research highlights the pressing need for more robust emotion recognition systems and underscores the potential of transfer models with attention mechanisms to significantly improve feedback management processes and the medical applications., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Roshan 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.)

We present the complete genome sequence of the probiotic strain Lactobacillus acidophilus ATCC 9224. The genome sequence provides a valuable resource for investigating the phylogenetic evolution of this lineage and conducting comparative genomics with other Lactobacillus strains and species., Competing Interests: The authors declare no conflict of interest.

The tropical and subtropical regions of the world support the growth of the Indian plant Moringa oleifera . It usually goes by the name drumstick tree or horseradish tree and thrives in warm climates. The leaves of the M. oleifera tree are now frequently used as nutrients and nutraceuticals due to their availability of various minerals. While having only very minor antinutritional effects, the leaves are abundant in many beneficial compounds. A recent review of the bioactive components and activity of moringa leaves has focused on both in vivo and in vitro studies. Drumstick leaves have antidiabetic qualities, anti-inflammatory, anticancer, and antibacterial qualities among other health benefits. Phytochemicals, in addition to minerals and vitamins, are abundant in this vegetable. The majority of these effects, according to a review in the literature, are mostly brought on by the presence of carotenoids, glucosinolates, and phytochemicals. As a value-added component in the production of wholesome meals, moringa is becoming more popular. Despite extensive research into locating and quantifying these advantageous elements in drumstick leaves, bioavailability and bioaccessibility studies were carried out. Beneficial photochemicals are absorbed and digested through incredibly intricate processes that involve several physicochemical and physiological interactions. Therefore, the biological impact of food may be attributed to its various metabolites that can access particular areas of action rather than its original substances. This body of literature offers the most recent findings in scientific research on the bioavailability, health advantages, nutritional profiles, and bioactive activities of moringa leaves as they relate to their use in a range of food products. Drumsticks are frequently used as a food element that promotes health because of their potent protection against a variety of ailments and the presence of environmental pollutants., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Authors. Food Science & Nutrition published by Wiley Periodicals LLC.)

Background and Aims: Multiple sources of medical oxygen, namely liquid medical oxygen (LMO) tanks, pressure swing adsorption (PSA) plants, concentrators, and gaseous cylinders, are available at different healthcare facilities. These sources of oxygen have varying installation and operational costs. In low-resource settings, it is imperative to utilise these assets optimally. This study investigated the operational costs of multiple oxygen sources available at a healthcare facility., Methods: A Microsoft (MS) Excel-based model was developed to analyse and compare the oxygen manufacturing costs (in ₹/m 3 ) using PSA plants and procurement costs (in ₹/m 3 ) of LMO and third-party vendor-refilled cylinders., Results: The oxygen manufacturing costs for PSA plants of different capacities and running times on electricity and diesel generators (DGs) as a power source were calculated. This study highlights the cost-benefit of using PSA plants over LMO and third-party vendor-refilled cylinders as a source of oxygen. PSA plants are most economical when they are of higher capacity and used to their maximum capacity on electricity as the power source. On the contrary, they are most expensive when used on a DG set as a power source. Furthermore, this study provides evidence of PSA plants being more cost-effective for refilling cylinders using a booster compressor unit when compared to third-party vendor-cylinder refilling., Conclusion: Given their cost-effectiveness and low third-party dependence, they should be utilised to their maximum capacity as medical oxygen sources at healthcare facilities., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Indian Journal of Anaesthesia.)

Global mental health [GMH] scholarship and practice has typically focused on the unmet needs and barriers to mental health in communities, developing biomedical and psychosocial interventions for integration into formal health care platforms in response. In this article, we analyse four diverse settings to disrupt the emphasises on health system weaknesses, treatment gaps and barriers which can perpetuate harmful hierarchies and colonial and medical assumptions, or a 'deficit model'. We draw on the experiential knowledge of community mental health practitioners and researchers working in Ghana, India, the Occupied Palestinian Territory and South Africa to describe key assets existing in 'informal' community mental health care systems and how these are shaped by socio-political contexts. These qualitative case studies emerged from an online mutual learning process convened between 39 academic and community-based collaborators working in 24 countries who interrogated key tenets to inform a social paradigm for global mental health. Bringing together diverse expertise gained from professional practice and research, our sub-group explored the role of Community Mental Health Systems in GMH through comparative country case studies describing the features of community care beyond the health and social care system. We found that the socio-political health determinants of global economic structures in all four countries exert significant influence on local community health systems. We identified that key assets across sites included: family and community care, and support from non-profit organisations and religious and faith-based organisations. Strengthening community assets may promote reciprocal relationships between the formal and informal sectors, providing resources for support and training for communities while communities collaborate in the design and delivery of interventions rooted in localised expertise. This paper highlights the value of informal care, the unique social structures of each local context, and resources within local communities as key existing assets for mental health., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Mathias 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.)

Background & Aims: Diarrhea occurs in up to 50% of cases of COVID-19. Nonetheless, the pathophysiologic mechanism(s) have not been determined., Methods: This was examined using normal human enteroid monolayers exposed apically to live SARS-CoV-2 or non-replicating virus-like particles (VLPs) bearing the 4 SARS-CoV-2 structural proteins or irradiated virus, all of which bound and entered enterocytes., Results: Live virus and VLPs incrieased secretion of multiple cytokines and reduced mRNAs of ACE2, NHE3, and DRA. Interleukin (IL)-6 plus IL-8 alone reduced NHE3 mRNA and protein and DRA mRNA and protein. Neither VLPs nor IL-6 plus IL-8 alone altered Cl - secretion, but together they caused Cl - secretion, which was Ca 2+ -dependent, CFTR-independent, blocked partially by a specific TMEM16A inhibitor, and entirely by a general TMEM16 family inhibitor. VLPs and irradiated virus, but not IL-6 plus IL-8, produced Ca 2+ waves that began within minutes of VLP exposure, lasted for at least 60 minutes, and were prevented by pretreatment with apyrase, a P2Y1 receptor antagonist, and general TMEM16 family inhibitor but not by the specific TMEM16A inhibitor., Conclusions: The pathophysiology of COVID-19 diarrhea appears to be a unique example of a calcium-dependent inflammatory diarrhea that is caused by direct viral effects plus the virus-induced intestinal epithelial cytokine secretion., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Small round cell tumors (SRCTs) are a group of malignant neoplasms with minimal or no differentiation, characterized by the presence of round cells with high nuclear-cytoplasmic ratio. Although SRCTs can occur in any part of the body, involvement of central nervous system (CNS) is uncommon., Aim: We aimed to study the clinicopathological spectrum of cranial SRCT diagnosed in our institute over a period of four years (2016-2019)., Material and Methods: A retrospective review of medical records (2016-2019) with a morphological diagnosis of cranial SRCT was made. Both intra-axial and extra-axial tumors were included. A total of 60 cases were retrieved, and the clinical and histopathological features were studied. Special cytochemical staining and immunohistochemistry were performed, where needed., Results: The mean age at presentation was 18.4 years (range, 1-60 years), with a male-to-female ratio of 2.5:1. The most common site was posterior fossa of brain (n = 28, 47%), followed by dorso-lumbar spine (n = 9, 15%). The most common type of tumor was medulloblastoma (n = 29, 48.3%), followed by Ewing sarcoma (ES)/peripheral primitive neuroectodermal tumor (pPNET) (n = 11, 18.3%), non-Hodgkin lymphoma (NHL) (n = 9, 15%), neuroblastoma (n = 3, 5%), and CNS embryonal tumor, NOS (n = 2, 3.3%). One case each of atypical teratoid rhabdoid tumor (ATRT), rhabdomyosarcoma, pineoblastoma, melanoma, rhabdomyosarcoma, and undifferentiated pleomorphic sarcoma was also documented., Conclusions: SRCTs have a variable age of presentation. Their incidence in CNS is low as compared to other organ systems. On light microscopy, the histopathology of these lesions is overlapping, posing a great diagnostic dilemma for the pathologist. The use of ancillary techniques like immunohistochemistry helps in arriving at the correct diagnosis. Treatment strategy and tumor prognosis also vary along the entire spectrum of SRCT, thus making exact characterization essential for proper management., (Copyright © 2023 Copyright: © 2023 Journal of Cancer Research and Therapeutics.)

The standard of care in treating respiratory distress syndrome in preterm infants is respiratory support with nasal continuous positive airway pressure or a combination of continuous positive airway pressure and exogenous surfactant replacement. Endotracheal intubation, the conventional method for surfactant administration, is an invasive procedure associated with procedural and mechanical ventilation complications. The INSURE (intubation, surfactant administration, and extubation soon after) technique is an accepted method aimed at reducing the short-term complications and long-term morbidities related to mechanical ventilation but does not eliminate risks associated with endotracheal intubation and mechanical ventilation. Alternative methods of surfactant delivery that can overcome the problems associated with the INSURE technique are surfactant through a laryngeal mask, surfactant through a thin intratracheal catheter, and aerosolized surfactant delivered using nebulizers. The three alternative methods of surfactant delivery studied in the last two decades have advantages and limitations. More than a dozen randomized controlled trials have aimed to study the benefits of the three alternative techniques of surfactant delivery compared with INSURE as the control arm, with promising results in terms of reduction in mortality, need for mechanical ventilation, and bronchopulmonary dysplasia. The need to find a less invasive surfactant administration technique is a clinically relevant problem. Before broader adoption in routine clinical practice, the most beneficial technique among the three alternative strategies should be identified. This review aims to summarize the current evidence for using the three alternative techniques of surfactant administration in neonates, compare the three techniques, highlight the knowledge gaps, and suggest future directions. KEY POINTS: · The need to find a less invasive alternative method of surfactant delivery is a clinically relevant problem.. · Clinical trials that have studied alternative surfactant delivery methods have shown promising results but are inconclusive for broader adoption into clinical practice.. · Future studies should explore novel clinical trial methodologies and select clinically significant long term outcomes for comparison.., Competing Interests: None declared., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Low-molecular weight (LMW) thiols, encompassing peptides and small proteins with active cysteine residue(s), are important to bacteria as they are involved in a wide range of redox reactions. They include the tripeptide glutathione (GSH) and the small redox proteins, thioredoxins and glutaredoxins. We review the low MW thiols and related molecules in Francisella species and what role they may play in growth and virulence. Genes for GSH biosynthesis, metabolism and thioredoxins are present in all strains of Francisella , including the fully human-virulent strains. GSH and cysteine (CSH) are the major LMW thiols in Francisella extracts. We explore the potential role of the LMW thiols to overcome the nutritional challenges of intracellular growth (high GSH conditions) as well as the nutritional challenges of planktonic growth (low GSH conditions), and their contribution to Francisella' s sensing its environmental location. Francisella may also use GSH as a source of CSH, for which it is auxotrophic. "Glutathione stealing" from the host may be an important part of Francisella 's success strategy as a facultative intracellular pathogen both to detect its location and obtain CSH. An understanding of GSH metabolism in Francisella provides insights into the interaction of this pathogen with its host and may reveal additional targets for therapeutic intervention for tularemia infections., 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., (© 2023 The Author(s).)

As a part of the Himalayan mountains, the North East Hill (NEH) region of India is geophysically dynamic and seismotectonically active since its formation about 55 million years ago with a head-on collision of the Indian plate and the Eurasian plate. The region still has been underthrusting at a rate of 4.5-5 cm/year causing the reshaping and changing of its geophysical characteristics (geology, geomorphology, relief, slope gradient, drainage system, etc.), whereas anthropogenic activities, particularly shifting cultivation and technological intervention, have caused changes or degradation of the ecological environment (air, land, water, vegetation, crop pattern, climate, wildlife, etc.). Addressing this burning geoecological problem, a geospatial technology-based case study from the Kohima district of Nagaland in the North East Hill region of India is presented here. Through the development and integration of multiple GIS modules, this reconnaissance study suggests that continuous seismic activities (about 27 seismic events/year) along tectonic faults, thrusts, and lithological shear zones have been reshaping and changing the geophysical environment, whereas the ecological environment has been changing or degrading due to decreasing natural landscape and habitats (forest area, water bodies, and shrubs) at an annual rate of 5.91 km 2 (0.60%), increasing built-up area, agricultural land, and wasteland at an annual rate of 2.73 km 2 (0.28%), 2.69 km 2 (0.27%), and 0.49 km 2 (0.05%) respectively. Results also suggest that environmental degradation results in accelerated trends of climate change (rising temperature at the rate of 0.13 °C/year, decreasing annual rainy days at the rate of 2 days/year, decreasing annual rainfall at the rate of 9.55 cm/year, mounting climatic zones at the rate of 175 m/year) and its adverse impacts (increasing extreme rainfall events at the rate of 3 events/year and causing cloud burst, erosion, landslides, and floods) in the region., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

The anaerobic region of the gastrointestinal (GI) tract has been replicated in the anaerobic chamber of a microbial fuel cell (MFC). Electroactive biomolecules released by the facultative anaerobes (Providencia rettgeri) under anoxic conditions have been studied for their potential role for redox balance. MALDI study reveals the presence of vitamin B9 (folate), 6-methylpterin, para-aminobenzoic acid (PABA) and pteroic acid called pterin pool. ATR-FTIR studies further confirm the presence of the aromatic ring and side chains of folate, 6-methylpterin and PABA groups. The photoluminescence spectra of the pool exhibit the maximum emission at 420, 425, 440, and 445 nm when excited by 310, 325, 350, and 365 nm wavelengths (day 20 sample) highlighting the presence of tunable bands. The cyclic voltammetric studies indicate the active participation of pterin pool molecules in the transfer of electrons with redox potentials at - 0.2 V and - 0.4 V for p-aminobenzoate and pterin groups, respectively. In addition, it is observed that under prolonged conditions of continuous oxidative stress (> 20 days), quinonoid tetrahydrofolate is formed, leading to temporary storage of charge. The results of the present study may potentially be useful in designing effective therapeutic strategies for the management of various GI diseases by promoting or blocking folate receptors., (© 2023. The Author(s).)

Environmentally benign synthesis of nanocomposite, a pivotal facet of nanotechnology, and gaining prominence due to the increasing demand for facile, sustainable, and safe synthesis methods. The present research reports an facile/cost-effective method for the preparation of carbon dots (CDs) and carbon dot silver nanocomposites ( CD@AgNCs) via a hydrothermal treatment of peanut shells. The well-dispersed and spherical CDs with an average diameter of 5-6 nm were obtained and further employed for the preparation of CD@AgNCs. The formation of CD@AgNCs. was confirmed by optical and microscopic studies and ared shift in the λ max from 277 nm (CDs) to 450 nm (CD@AgNCs) with a size range of 30-40 nm was observed. The synthesized CD@AgNCs exhibit excellent catalytic potency for the reduction of 4-nitrophenol to 4-aminophenol, and also displaying a unique interaction and sensing ability towards heavy metal ions (Hg 2+ ), causing a pronounced change in color from reddish-brown to transparent with limit of detection (LOD) of 23.47 ppm. Also, the prepared composite exhibit efficient antimicrobial potential against gram-negative (Escherichia coli) bacteria. Consequently, this study delves into a unified effective remediation platform with the integration of catalysis, sensing, and antimicrobial potentials., Competing Interests: Declaration of competing interest 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., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: The goal of chest compressions during neonatal resuscitation is to increase cerebral and coronary blood flow leading to the return of spontaneous circulation (ROSC). During chest compressions, bilateral femoral occlusion may increase afterload and promote carotid and coronary flow, an effect similar to epinephrine. Our objectives were to determine the impact of bilateral femoral occlusion during chest compressions on the incidence and timing of ROSC and hemodynamics., Methodology: In this randomized study, 19 term fetal lambs in cardiac arrest were resuscitated based on the Neonatal Resuscitation Program guidelines and randomized into two groups: femoral occlusion or controls. Bilateral femoral arteries were occluded by applying pressure using two fingers during chest compressions., Results: Seventy percent (7/10) of the lambs in the femoral occlusion group achieved ROSC in 5 ± 2 min and three lambs (30%) did not receive epinephrine. ROSC was achieved in 44% (4/9) of the controls in 13 ± 6 min and all lambs received epinephrine. The femoral occlusion group had higher diastolic blood pressures, carotid and coronary blood flow., Conclusion: Femoral occlusion resulted in faster and higher incidence of ROSC, most likely due to attaining increased diastolic pressures, coronary and carotid flow. This is a low-tech intervention that can be easily adapted in resource limited settings, with the potential to improve survival and neurodevelopmental outcomes.

Vancomycin, is widely used against methicillin-resistant bacterial infections. However, Vancomycin accumulation causes nephrotoxicity which leads to an impairment in the filtration mechanisms of kidney. Traditional herbal medicines hold potential for treatment of drug-induced nephrotoxicity. Herein, we investigated protective properties of plant-based medicine Renogrit against Vancomycin-induced kidney injury. Phytometabolite analysis of Renogrit was performed by UHPLC. Spheroids formed from human proximal tubular cell (HK-2) were used for in vitro evaluation of Vancomycin-induced alterations in cell viability, P-gp functionality, NAG, KIM-1 levels, and mRNA expression of NGAL and MMP-7. The in vivo efficacy of Renogrit against Vancomycin-induced nephrotoxicity was further evaluated in Sprague-Dawley (SD) rats by measurement of BUN, serum creatinine, and their respective clearances. Moreover, eGFR, kidney-to-body weight ratio, GSH/GSSG ratio, KIM-1, NAG levels and mRNA expression of KIM-1 and osteopontin were also analyzed. Changes in histopathology of kidney and hematological parameters were also observed. Renogrit treatment led to an increase in cell viability, normalization of P-gp functionality, decrease in levels of NAG, KIM-1, and reduction in mRNA expression of NGAL and MMP-7. In Vancomycin-challenged SD rats, Renogrit treatment normalized altered kidney functions, histological, and hematological parameters. Our findings revealed that Renogrit holds a clinico-therapeutic potential for alleviating Vancomycin-associated nephrotoxicity., Competing Interests: The authors have read the journal’s policy and have the following competing interests: The test formulation (Renogrit) was provided by Divya Pharmacy, Haridwar, Uttarakhand, India. Renogrit is a marketed medicinal product of Divya Pharmacy, Haridwar, India. AB is an honorary trustee in Divya Yog Mandir Trust, which governs Divya Pharmacy, Haridwar. In addition, he holds an honorary managerial position in Patanjali Ayurved Ltd, Haridwar, India. Divya Pharmacy, Haridwar and Patanjali Ayurved Ltd. Haridwar manufacture and sell many herbal medicinal products. Other than providing the test formulation (Renogrit), Divya Pharmacy was not involved in any aspect of the research reported in this study. This does not alter our adherence to PLOS ONE policies on sharing data and materials. All other authors have declared no competing interests., (Copyright: © 2023 Balkrishna 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.)

Coronavirus disease 2019 (COVID-19) has affected a broad demographics, eliciting a more significant effect on specific groups such as males, African Americans, and Hispanic minorities. Treatment of COVID-19 often requires antiviral drugs or monoclonal antibodies. However, immunotherapies such as mesenchymal stem cells and mesenchymal stem cells-derived exosomal vesicles should be evaluated as treatment options for COVID-19. Mesenchymal stem cell therapy offers regenerative, anti-inflammatory, and immunomodulatory properties that can speed up the recovery from COVID-19. Mesenchymal stem cell therapy can also benefit COVID-19 patients who suffer from strokes, as COVID-19 increases the risk of strokes due to increased cytokines and clotting factors. Most stroke cases that occur in COVID-19 patients are ischemic strokes. Therefore, with the help of mesenchymal stem cell therapy and mesenchymal stem cells-derived exosomes, COVID-19-induced stroke patients might benefit from dual-ended treatment. The objective of this review was to discuss COVID-19 and stroke incidence and the available treatment options., Competing Interests: None

Pig pasteurellosis, caused by Pasteurella multocida, is an acute infection that also has economic implications for pig farmers. We report the complete genome sequence of a P. multocida, serovar B:2 'Soron' strain isolated from the blood of a pig that had died of pasteurellosis in India. The isolate was not found to be haemorrhagic septicaemia (HS) specific B:2 by the PCR assay. The genome of 'Soron' strain is a single circular chromosome of 2,272,124 base pairs in length and contains 2014 predicted coding regions, 4 ribosomal RNA operons, and 52 tRNAs. It has 1812 protein-coding genes that were also found in reference sequence PmP52Vac. Phylogenetic analysis revealed that Pm&#95;P52VAc and P. multocida 'Soron' serovar B:2 were clustered in different clades. Pasteurella multocida 'Soron' serovar B:2 was found to cluster with the same ancestor of Pm70, which is of avian origin. The genome was found to contain regions that encode proteins which may confer resistance to various antibiotics including cephalosporin, which is used to treat pasteurellosis. The isolate was also found to harbour a phage region. This strain represents a novel multi-locus sequence type (MLST) that has not been previously identified, as all of the alleles used for MLST were found, but did not match any of the alleles in the database with 100% nucleotide identity. The most closely related ST was ST221. This is the first whole-genome sequence from P. multocida serovar B:2 of pig origin., (© 2023. The Author(s) under exclusive licence to Sociedade Brasileira de Microbiologia.)

The high mountain ecosystem of the Indian Himalayas has frequently been experiencing primary hazards (like earthquakes, avalanches, and landslides). Often, these events are followed by the triggering of secondary hazards (like landslide dams, debris flows, and flooding), thereby posing massive risks to infrastructure and residents in the region. This study was taken up to understand the dynamics of an extraordinary debris flood disaster in the Rishiganga River valley, Chamoli district of Uttarakhand on 7th February 2021. Rapid mass movements (RAMMS)-debris flow software was employed to recreate the entire sequence of the hazard consisting of a rock-ice slide, mass deposition and erosion along the channel, and subsequent debris flood. Forty-nine scenarios were analyzed for accurate calibration of dry-Coulomb type friction coefficient (µ) and viscous-turbulent friction coefficient (ξ). Consequently, the geomorphologic characteristics of the debris flow were validated using high-resolution satellite image interpretation and field photographs. The volume of detached rock-ice mass was estimated to be 26.42 × 10 6 m 3 . At the same time, the RAMMS-derived model outputs for velocity, flow depth, and momentum were found in good agreement with the extent and height of actual debris on the ground. The study highlights an urgent need to identify the glaciers with a high risk of ice avalanches in the Indian Himalayas. The presented modeling approach may be applied in dynamic mountain ecosystems to simulate potential flash floods due to avalanches. Moreover, the information reported in this study can be vital input for improving the district-level disaster management plan., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Antimalarial drug discovery has until recently been driven by high-throughput phenotypic cellular screening, allowing millions of compounds to be assayed and delivering clinical drug candidates. In this review, we will focus on target-based approaches, describing recent advances in our understanding of druggable targets in the malaria parasite. Targeting multiple stages of the Plasmodium lifecycle, rather than just the clinically symptomatic asexual blood stage, has become a requirement for new antimalarial medicines, and we link pharmacological data clearly to the parasite stages to which it applies. Finally, we highlight the IUPHAR/MMV Guide to MALARIA PHARMACOLOGY, a web resource developed for the malaria research community that provides open and optimized access to published data on malaria pharmacology., (© 2023 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Knowledge co-production can improve the quality and accessibility of health, and also benefit service users, allowing them to be recognised as skilled and capable. Yet despite these clear benefits, there are inherent challenges in the power relations of co-production, particularly when experts by experience (EBE) are structurally disadvantaged in communication skills or literacy. The processes of how knowledge is co-produced and negotiated are seldom described. This paper aims to describe processes of co-production building on the experiences of EBE (people with lived experience of psychosocial or physical disability), practitioners and researchers working together with a non-profit community mental health programme in North India. We describe processes of group formation, relationship building, reflexive discussion and negotiation over a 7-year period with six diverse EBE groups. Through a process of discussion and review, we propose these five questions which may optimise co-production processes in communities: (1) Who is included in co-production? (2) How can we optimise participation by people with diverse sociodemographic identities? (3) How do we build relationships of trust within EBE groups? (4) How can we combine psychosocial support and knowledge co-production agendas in groups? and (5) How is the expertise of experts by experience acknowledged?, Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Introduction: Ultrasonography allows high-resolution visualisation of the peripheral nerves for quantitative and qualitative analyses. We report cross-sectional area values (quantitative measure) and echo intensity values (qualitative measure) for 46 peripheral nerve sites in upper and lower extremities in cadaveric specimens., Objective: To determine cross-sectional area values and echo intensity values of peripheral nerves of upper and lower extremities at 46 nerve sites., Methods: Nerve measurements were obtained using electronic callipers and ultrasonography for linear dimension and cross-sectional area measurements, respectively, in six cadaveric specimens for 46 peripheral nerve sites. Ultrasound images were further analysed to estimate echo intensity percentage values for 46 nerves., Results: We present normal cross-sectional area values of various nerves of upper and lower extremities with their respective echo intensity values. Calculated cross-sectional area values from linear dimensions did not match the measured cross-sectional area values via trace method., Conclusion: Cross-sectional area values (quantitative measure) and echo intensity values (qualitative measure) for 46 peripheral nerve sites in upper and lower extremities in cadaveric specimens are presented. The estimation of cross-sectional area via linear measurement is not a good approximation of the cross-sectional area (cross-sectional area measured by trace method on ultrasound image)., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article., (© The Author(s) 2022.)

Background: Studies have proven that lack of access to menstruation products negatively affects school attendance, academic performance, and individual health. Implementing "period policies," or programs offering free menstruation products, are becoming popular in schools, businesses, and communities in high-income countries. U.S.-based Purdue University announced in February 2020 that free pads and tampons would be stocked in all women's and gender-neutral restrooms in campus buildings. This study aimed to capture the experiences of menstruators about free menstrual products and the impact of a university-wide free menstruation management product policy and program. A second purpose was to understand how access to menstrual management products is intertwined with broader socio-cultural experiences of a menstruator., Methods: As part of a larger study, virtual focus group discussions (n = 32 across 5 focus groups) were conducted in February 2021. Eligible participants were student-menstruators attending Purdue University. We used thematic analysis techniques for data analysis, allowing for a constant comparative approach to data contextualization and theme identification., Results: Focus group discussions revealed vivid menarche and menstruation experiences, shifting period culture, recollections of shame and stigma, and use of various technologies to manage menstruation. Recommendations for community-based programs offering free products included maintaining stock, making informed product choices, and broadly distributing program information to increase awareness of free product placements., Conclusions: Findings offer practical recommendations that will contribute to menstruation management and period poverty solutions for university communities., (© 2023. The Author(s).)

Uterine fibroids (UF), most prevalent gynecological disorder, require surgery when symptomatic. It is estimated that between 25 and 35 percent of women wait until the symptoms have worsened like extended heavy menstrual bleeding and severe pelvic pain. These UF may be reduced in size through various methods such as medical or surgical intervention. Progesterone (prog) is a crucial hormone that restores the endometrium and controls uterine function. In the current study, 28 plant-based molecules are identified from previous literature and docked onto the prog receptors with 1E3K and 2OVH. Tanshinone-I has shown the best docking score against both proteins. The synthetic prog inhibitor Norethindrone Acetate is used as a standard to evaluate the docking outcomes. The best compound, tanshinone-I, was analyzed using molecular modeling and DFT. The RMSD for the 1E3K protein-ligand complex ranged from 0.10 to 0.42 Å, with an average of 0.21 Å and a standard deviation (SD) of 0.06, while the RMSD for the 2OVH protein-ligand complex ranged from 0.08 to 0.42 Å, with an average of 0.20 Å and a SD of 0.06 showing stable interaction. In principal component analysis, the observed eigen values of HPR-Tanshinone-I fluctuate between -1.11 to 1.48 and -1.07 to 1.25 for PC1 and PC2, respectively (1E3K), and the prog-tanshinone-I complex shows eigen values of -38.88 to -31.32 and -31.32 to 35.87 for PC1 and PC2, respectively (2OVH), which shows Tanshinone-I forms a stable protein-ligand complex with 1E3K in comparison to 2OVH. The Free Energy Landscape (FEL) analysis shows the Gibbs free energy in the range of 0 to 8 kJ/mol for Tanshinone-I with 1E3K and 0 to 14 kJ/mol for Tanshinone-I with the 2OVH complex. The DFT calculation reveals ΔE value of 2.8070 eV shows tanshinone-I as a stable compound. 1E3K modulates the prog pathway, it may have either an agonistic or antagonistic effect on hPRs. Tanshinone-I can cause ROS, apoptosis, autophagy (p62 accumulation), up-regulation of inositol requiring protein-1, enhancer-binding protein homologous protein, p-c-Jun N-terminal kinase (p-JNK), and suppression of MMPs. Bcl-2 expression can change LC3I to LC3II and cause apoptosis through Beclin-1 expression., 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., (© 2023 The Author(s).)

Background and Objectives: Oxygen (O 2 ) use during neonatal cardiopulmonary resuscitation (CPR) remains a subject of controversy. The inspired O 2 concentration during neonatal CPR, that hastens return of spontaneous circulation (ROSC), allows adequate cerebral and myocardial O 2 delivery, and enhances survival to discharge, is not known. The optimal FiO 2 during CPR should decrease incidence of hypoxia but also avoid hyperoxia, and ultimately lead to improved neurodevelopmental outcomes. Due to infrequent need for extensive resuscitation, and emergent circumstances surrounding neonatal CPR, conducting randomized clinical trials continues to be a challenge. The goal of this study was to review the evolution of oxygen use during neonatal CPR, the evidence from animal and clinical studies on oxygen use during neonatal CPR and after ROSC, the pertinent physiology including myocardial oxygen consumption and cerebral oxygen delivery during CPR, and outcomes following CPR in the DR and in the neonatal intensive care unit., Methods: This narrative review is based on recent and historic English literature in PubMed and Google scholar over the past 35 years (January 1, 1985 - May 1, 2021)., Key Content and Findings: Several studies in animal models have compared ventilation with different inspired O 2 concentrations (mostly 21% and 100%) during chest compressions and after ROSC. These studies reported no difference in short-term outcomes, even with as low as 18% O 2 . However, in lamb models of cardiac arrest and CPR, 100% O 2 during chest compressions is associated with better oxygen delivery to the brain compared to 21% O 2 . Abrupt weaning to 21% O 2 following ROSC followed by titration to achieve preductal SpO 2 of 85-95% minimizes systemic hyperoxia and oxidative stress compared to slow weaning from 100% O 2 following ROSC., Conclusions: Clinical research is needed to arrive at the best strategy for assessment of oxygenation and choice of FiO 2 during neonatal CPR that lead to improved survival and outcomes. In this article, we have reviewed the literature on evidence behind O 2 use during neonatal advanced CPR and after ROSC.

In vitro evolution of drug resistance is a powerful approach for identifying antimalarial targets, however, key obstacles to eliciting resistance are the parasite inoculum size and mutation rate. Here we sought to increase parasite genetic diversity to potentiate resistance selections by editing catalytic residues of Plasmodium falciparum DNA polymerase δ. Mutation accumulation assays reveal a ~5-8 fold elevation in the mutation rate, with an increase of 13-28 fold in drug-pressured lines. Upon challenge with the spiroindolone PfATP4-inhibitor KAE609, high-level resistance is obtained more rapidly and at lower inocula than wild-type parasites. Selections also yield mutants with resistance to an "irresistible" compound, MMV665794 that failed to yield resistance with other strains. We validate mutations in a previously uncharacterised gene, PF3D7&#95;1359900, which we term quinoxaline resistance protein (QRP1), as causal for resistance to MMV665794 and a panel of quinoxaline analogues. The increased genetic repertoire available to this "mutator" parasite can be leveraged to drive P. falciparum resistome discovery., (© 2023. The Author(s).)

Phenology, an important ecological attribute, deals with the development of vegetative and reproductive parts of trees called "phenophases", which are important determinants of primary productivity and sensitive to climate change. The present study recorded various phenophases of major tree species (i.e., Quercus leucotrichophora , Rhododendron arboreum, and Myrica esculenta ) as per the two-digit numerical system of Biologische Bundesanstalt, Bundessortenamt, Chemische Industrie (BBCH) scale. A total of 72 individual trees, twenty-four from each species, distributed between 1400 and 1980 m. a.s.l elevations were tagged and measured fortnightly for two consecutive years (2019-2021) in the moist temperate forest of Western Himalaya and compared with earlier existing records. Various phenophases were correlated with climatic factors along with duration and thermal time for each phenological growth stage. We found 24 growth stages for Q . leucotrichophora and M . esculenta and 28 for R . arboreum distributed across seven principal growth stages (e.g. bud development, 0; leaf development, 1; shoot development, 3; inflorescence development, 5; flower development, 6; fruit development, 7; and fruit maturation, 8) of trees as per BBCH scale. Maximum growing degree was 748.87 and 627.95 days recorded for R . arboreum and M . esculenta during leaf development, and 796.17 days for Q . leucotrichophora during fruit development. Flower emergence was observed pre, during, and post-emergence of new leaves for R . arboreum , M . esculenta, and Q . leucotrichophora , respectively, which varied at spatial scale with previous findings. Longevity of fruit development to ripening took 17, 4, and 2 months, respectively in Q . leucotrichophora , R . arboreum and M . esculenta . Duration of leaf initiation and flowering was positively correlated with climatic variables, whereas, the reverse was observed for fruiting in the studied tree species. The study concludes that the variations in phenophases of the three species were strongly influenced by climatic variations, especially minimum temperature. The result of the present study would be important in enabling us to formulate efficient forest management strategies by understanding the short-term adaptation of the climate-sensitive important tree species in the western Himalaya., 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, (© 2023 The Authors. Published by Elsevier Ltd.)

The role of pesticides in enhancing global agricultural production is magnificent. However, their unmanaged use threatens water resources and individual health. A significant pesticide concentration leaches to groundwater or reaches surface waters through runoff. Water contaminated with pesticides may cause acute or chronic toxicity to impacted populations and exert adverse environmental effects. It necessitates the monitoring and removing pesticides from water resources as prime global concerns. This work reviewed the global occurrences of pesticides in potable water and discussed the conventional and advanced technologies for the removal of pesticides. The concentration of pesticides highly varies in freshwater resources across the globe. The highest concentration of α-HCH (6.538 μg/L, at Yucatan, Mexico), lindane (6.08 μg/L at Chilka lake, Odisha, India), 2,4, DDT (0.90 μg/L, at Akkar, Lebanon), chlorpyrifos (9.1 μg/L, at Kota, Rajasthan, India), malathion (5.3 μg/L, at Kota, Rajasthan, India), atrazine (28.0 μg/L, at Venado Tuerto City, Argentina), endosulfan (0.78 μg/L, at Yavtmal, Maharashtra, India), parathion (4.17 μg/L, at Akkar, Lebanon), endrin (3.48 μg/L, at KwaZuln-Natl Province, South Africa) and imidacloprid (1.53 μg/L, at Son-La province, Vietnam) are reported. Pesticides can be significantly removed through physical, chemical, and biological treatment. Mycoremediation technology has the potential for up to 90% pesticide removal from water resources. Complete removal of the pesticides through a single biological treatment approach such as mycoremediation, phytoremediation, bioremediation, and microbial fuel cells is still a challenging task, however, the integration of two or more biological treatment approaches can attain complete removal of pesticides from water resources. Physical methods along with oxidation methods can be employed for complete removal of pesticides from drinking water., Competing Interests: Declaration of competing interest 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., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Dysmotility and postoperative ileus (POI) are frequent major clinical problems post-abdominal surgery. Erythropoietin (EPO) is a multifunctional tissue-protective cytokine that promotes recovery of the intestine in various injury models. While EPO receptors (EPOR) are present in vagal Schwann cells, the role of EPOR in POI recovery is unknown because of the lack of EPOR antagonists or Schwann-cell specific EPOR knockout animals. This study was designed to explore the effect of EPO via EPOR in vagal nerve Schwann cells in a mouse model of POI., Results: The structural features of EPOR and its activation by EPO-mediated dimerization were understood using structural analysis. Later, using the Cre-loxP system, we developed a myelin protein zero (Mpz) promoter-driven knockout mouse model of Schwann cell EPOR (MpzCre-EPOR flox/flox / Mpz-EPOR-KO) confirmed using PCR and qRT-PCR techniques. We then measured the intestinal transit time (ITT) at baseline and after induction of POI with and without EPO treatment. Although we have previously shown that EPO accelerates functional recovery in POI in wild type mice, EPO treatment did not improve functional recovery of ITT in POI of Mpz-EPOR-KO mice., Conclusions: To the best of our knowledge, this is the first pre-clinical study to demonstrate a novel mouse model of EPOR specific knock out on Schwan cells with an effect in the gut. We also showed novel beneficial effects of EPO through vagus nerve Schwann cell-EPOR in intestinal dysmotility. Our findings suggest that EPO-EPOR signaling in the vagus nerve after POI is important for the functional recovery of ITT., (© 2023. The Author(s).)

This study was aimed to isolate and characterize bacteriophage against drug-resistant, shigatoxigenic Escherichia coli (STEC), one of the zoonotic, food-borne organisms associated with ruminants, mainly cattle. STEC were isolated (n = 35) from neonatal calves, dairy workers, and the surrounding environment and their antimicrobial resistance pattern was studied. Out of the 35 isolates tested, 17 isolates were found to be multidrug resistant to important antibiotics like ampicillin, amoxicillin-clavulanate, ciprofloxacin, streptomycin, and tetracycline. Bacteriophage namely Ib&#95;pec2 was isolated against one of the STEC isolates and its morphology, genetic and proteomic characterization was done. Morphological analysis by TEM revealed bacteriophages belonging to myoviridae family. The genetic characterization of g23 gene revealed that the bacteriophage belonged to Tequatrovirus of myoviridae family. Proteomic analysis was able to identify five proteins identical to Tequatrovirus of myoviridae family. One-step growth curve experiment revealed a latency period of 40 min and a burst size of 893 pfu/bacteria. Temperature and pH ranging from 40°C to 50°C, pH 6-8, respectively. Phage could able to lyse majority of the STEC isolates. STEC are commensal organisms in the gastrointestinal tract of ruminants but are pathogenic in humans. Bacteriophages can be used as alternatives to antibiotics to control bacterial growth in ruminants and prevent its further spillage in the environment., (© 2022 Wiley-VCH GmbH.)

A 3-substituted isocoumarin scaffold has captivated extensive interest in synthetic and medicinal chemistry due to its presence in various natural products with diverse biological activities. Herein, we report a mesoporous CuO@MgO nanocomposite that was prepared via the sugar-blowing induced confined method with an E -factor of 12.2 and its catalytic potential in the facile synthesis of 3-substituted isocoumarin from 2-iodobenzoic acids and terminal alkynes. Powder X-ray diffraction, scanning electron microscopy, high-resolution transmission electron microscopy, energy-dispersive X-ray analysis, X-ray photoelectron spectroscopy, and Brunauer-Emmett-Teller techniques were utilized for the characterization of the as-prepared nanocomposite. A broad substrate scope, mild reaction conditions, excellent yield in short reaction time, no usage of additives, and better green chemistry metrices such as a low E -factor (0.71), high reaction mass efficiency (58.28%), low process mass efficiency (1.71), and high turnover number (629) are the various advantages of the present synthetic route. The nanocatalyst was recycled and reused up to five runs without significant loss in its catalytic activity and a very low leaching of copper (3.20 ppm) and magnesium ions (0.72 ppm). Powder X-ray diffraction and high-resolution transmission electron microscopy techniques confirmed the structural integrity of the recycled CuO@MgO nanocomposite., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

In Himalayas, new glacial lake formation and expansion of existing glacial lakes have occurred as a consequence of the increasing temperature and glacier recession. These lakes have the potential to release catastrophic volumes of water and trigger a glacial lake outburst flood (GLOF). GLOFs can cause devastating downstream impacts including loss of lives, damage to infrastructure, and economic loss. The risk associated with GLOFs is evident in the case of the Mochowar and the Shisper glaciers of the Hunza valley in the Karakoram ranges. The present study is divided in two parts: 1) investigation of the recent GLOF event from the Shisper glacier ice-dammed lake on 7th May 2022. 2) identification of an overdeepening site for future lake formation at the Mochowar glacier and its future GLOF susceptibility; We used the Himalayan Glacier Thickness Mapper (HIGTHIM) to calculate the thickness of Mochowar glacier and identify an overdeepening site at its terminus. This site could host a glacial lake of area 0.22 km 2 and a mean depth of 58.97 m that can release a potential flood volume leading to cascading effects with the Shisper ice-dammed lake that further increases the GLOF susceptibility. The GLOF susceptibility of this future lake was determined to be high based on a multi-criterion decision analysis. The recent GLOF event of 7th May 2022 occurred from the Shisper glacier ice-dammed lake. We applied a 2D hydrodynamic model for investigating this GLOF episode and estimated a release volume of 6.23 × 10 6 m 3 , with a modelled peak discharge of approximately 1505 m 3 s -1 ., Competing Interests: Declaration of competing interest 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., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Communication about menstrual health continues to be influenced by institutional and social practices which deem it to be unclean and impure. In a country such as India, several customs and traditions reinforce secrecy and shame about menstruation. As such, scholars advocate the need to generate knowledge that can open opportunities to converse on the topic of menstruation and understand issues related to bodily changes. Using a culture-centered approach, this study examined how college-going adult women from two cities in Northern India made sense of menstrual health. Data collection included 20 focus groups with 180 college-going women and interviews with 16 female family members. Participants discussed communication patterns surrounding menstrual health and how they uphold, challenge, and change social practices. Specifically, participants reflected on how they were communicated to about their menstrual health with underpinnings of secrecy and shame and how the influence of current opportunities for openness encourage them to anticipate positive change. Theoretical and practical implications for studying communication around menstruation in diverse cultural contexts are discussed.

Atherosclerosis is the main pathological process of several cardiovascular diseases. It may begin early in life and stay latent and asymptomatic for an extended period before its clinical manifestation. The formation of foamy macrophages due to dysregulated lipid metabolism is a key event in the development and progression of atherosclerotic plaque. The current pharmacotherapy for atherosclerosis is not able to address multiple aetiologies associated with the disease. Lipidom, an herbal prescription medicine, has anti-oxidant, lipid lowering and anti-inflammatory properties that lead to multifaceted treatment benefits against chronic inflammation, dyslipidaemia, and oxidative stress. The present study aimed to characterize the pharmacological effects of Lipidom using various experimental models. The phytochemical analysis of Lipidom was performed on ultra-high performance liquid chromatography (UHPLC) platform. Lipidom was evaluated for cytosafety, IL-1β and MCP-1 release, modulation of NLRP3 pathway, NFκB activity, ROS generation, lipid accumulation and gene expression in THP1 macrophages. Furthermore, Lipidom evaluation was also performed in the N2, CF1553, and TJ356 strains of Caenorhabditis elegans (C. elegans). The evaluation of brood size, adult (%), lipid accumulation, triglyceride levels, SOD-3 GFP signal, MDA formation, DAF-16 nuclear translocation, and gene expression was performed in C. elegans. Lipidom treatment significantly reduced the inflammatory mediators, lipid accumulation, oxidative stress, and normalized genes involved in the development of foamy macrophages. Lipidom treated C. elegans showed a significant decline in lipid accumulation and oxidative stress. Taken together, Lipidom treatment showed a multifaceted approach in the modulation of several mediators responsible for the development and progression of atherosclerotic plaque., Competing Interests: Conflicts of interest statement The test article was provided by Divya Pharmacy, Haridwar, Uttarakhand, India. Acharya Balkrishna is an honorary trustee in Divya Yog Mandir Trust, which governs Divya Pharmacy, Haridwar. In addition, he holds an honorary managerial position in Patanjali Ayurved Ltd, Haridwar, India. Other than providing the test formulation (Lipidom), Divya Pharmacy was not involved in any aspect of the research reported in this study. All other authors have declared no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Glacier-associated hazards are becoming a common and serious challenge to the high mountainous regions of the world. Glacial lake outburst floods (GLOFs) are one of the most serious unanticipated glacier hazards, with the potential to release a huge amount of water and debris in a short span of time, resulting in the loss of lives, property, and severe damage to downstream valleys. The present study used multi-temporal Landsat and Google earth imageries to analyze the spatio-temporal dynamism of the selected glacial lake (moraine-dammed) in the Satluj basin of Western Himalayas. Furthermore, GLOF susceptibility of the lake was assessed using a multi-criteria decision-based method. The results show that the lake area has increased from 0.11 to 0.26 km 2 over the past 28 years from 1990 to 2018. The susceptibility index value for the lake was calculated as 0.75, which indicates that the lake is highly susceptible to the GLOF. The depth and volume of the lake were estimated to be 16 m and 57 × 10 5 m 3 , respectively, using an empirical formula. HEC-RAS, HECGeo-RAS, and Arc-GIS software were utilized in this study to perform unsteady flow analysis and to determine the GLOF impact on the downstream area. The worst-case GLOF scenario (breach width of 75 m) was revealed during an overtopping failure of the moraine dam, resulted in a peak discharge of 4060 m 3 /s and releasing a total water volume of 57 × 10 5 m 3 . The breach hydrograph has been routed to calculate the spatial and temporal distribution of peak flood, inundation depth, velocity, water surface elevation, and flood peak arrival time along the river channel. The analysis further reveals that the routed flood waves reach the nearest settlement, i.e., Rajpur town, situated at a distance of 102 km in the downstream valley of the lake at 6 h after the beginning of the lake breach event with a peak discharge/flood of 1757 m 3 /s and maximum flow velocity of 1.5 m/s. With the ongoing climate warming and glacier retreat, moraine-dammed lakes are becoming more hazardous and thus increasing the total threat. Therefore, it is mandatory to monitor and assess such lakes at regular intervals of time to lessen the disastrous impacts of GLOFs on the livelihood and infrastructure in the downstream valleys. The findings of this study will aid in the creation of risk management plans, preparatory tactics, and risk reduction techniques for GLOF hazards in the region., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Current neonatal resuscitation guidelines recommend the use of epinephrine for bradycardia/arrest not responding to ventilation and chest compressions. Vasopressin is a systemic vasoconstrictor and is more effective than epinephrine in postnatal piglets with cardiac arrest. There are no studies comparing vasopressin with epinephrine in newly born animal models with cardiac arrest induced by umbilical cord occlusion. Objective: To compare the effect of epinephrine and vasopressin on the incidence and time to return of spontaneous circulation (ROSC), hemodynamics, plasma drug levels, and vasoreactivity in perinatal cardiac arrest. Design/Methods: Twenty-seven term fetal lambs in cardiac arrest induced by cord occlusion were instrumented and resuscitated following randomization to epinephrine or vasopressin through a low umbilical venous catheter. Results: Eight lambs achieved ROSC prior to medication. Epinephrine achieved ROSC in 7/10 lambs by 8 ± 2 min. Vasopressin achieved ROSC in 3/9 lambs by 13 ± 6 min. Plasma vasopressin levels in nonresponders were much lower than responders after the first dose. Vasopressin caused in vivo increased pulmonary blood flow and in vitro coronary vasoconstriction. Conclusions: Vasopressin resulted in lower incidence and longer time to ROSC compared to epinephrine in a perinatal model of cardiac arrest supporting the current recommendations for exclusive use of epinephrine in neonatal resuscitation.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes lethal coronavirus disease (COVID-19). SARS-CoV-2 has been the chief source of threat to public health and safety from 2019 to the present. SARS-CoV-2 caused a sudden and significant rise in hospitalization due to respiratory issues and pneumonia. We are consistently uncovering new information about SARS-CoV-2, and yet so much is to explore to implement efficient interventions to combat the emergent variants and spread of the ongoing pandemic. Information regarding the existing COVID-19 pandemic is streamlining continuously. However, clinical symptoms of SARS-CoV-2 infections spanning from asymptomatic infection to severe death-instigating disease remain consistent with preliminary reports. In this review, we have briefly introduced highlights of the COVID-19 pandemic and features of SARS-CoV-2. We have focused on current knowledge of innate and adaptive immune responses during SARS-CoV-2 infections and persisting clinical features of recovered patients. Furthermore, we have discussed how these immune responses are not tightly regulated and imbalance can direct the latter phases of COVID-19, long-COVID symptoms, and cause detrimental immunopathogenesis. COVID-19 vaccines are also discussed in detail to describe the efforts going around the world to control and prevent the infection. Overall, we have summarized the current knowledge on the immunology of SARS-CoV-2 infection and the utilization of that knowledge in the development of a suitable COVID-19 therapeutics and vaccines., (© The Author(s) 2023. Published by Oxford University Press.)

Copper (Cu) and selenium (Se) are antioxidants and essential trace elements that have mutual interaction and are reported to have beneficial effects at supranutritional levels. The experiment was executed to evaluate the individual impact of supranutritional levels of targeted elements with the effect of their interactions in buffalo calves. Twenty male Murrah buffalo calves of about 8-9 months (bodyweight 112.1 ± 7.69 kg) were distributed into four groups of five calves in each group and fed either a control (C) diet or supplemented with supranutritional levels of Cu (T 1 ), Se (T 2 ), or combination of both (T 3 ) for 120 days. Higher (P = 0.015) values of packed cell volume were observed in group T 2 at day 120; otherwise, all other hematological parameters remained comparable among groups. Over the period (day 120 vs. day 0), an enhancement in the percentage of lymphocytes (P = 0.006) with a reduction in neutrophils (P = 0.028) and hemoglobin (P = 0.024) values was observed in the control group. An enhancement in the percentage of monocytes (P = 0.031), with a reduced percentage of neutrophils (P = 0.022), was reported in groups T 2 and T 3 , respectively. Interaction of Cu and Se at supranutritional level (T3) dramatically reduced plasma Cu (P = 0.008) level against the control values, with an improvement in Se markers (i.e., plasma Se, P = 0.041 and enzyme glutathione peroxidase, P = 0.057) over the values in calves fed supplemental Se alone (T 2 ). Additionally, Cu (T 1 and T 3 ) was forced to decline (P < 0.05) Zn level in the plasma of buffalo calves. Cu (T 1 , P < 0.05) and Se (T 2 and T 3 , P ≤ 0.01) supplementation was able to improve their respective plasma levels. The interaction of two trace elements at the supranutritional level further helped in reducing the lipid peroxidation (P = 0.01) values as well. Though antioxidant vitamins and cell-mediated immunity remained unaffected, humoral immunity against antigen P. multocida was high (P = 0.005) in the group T 2 . The conclusion may be drawn that supranutritional Cu and Se were capable to influence certain blood parameters with an additional interaction effect due to simultaneous supplementation in buffalo calves., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The prevalence of diabetes has considerably increased in recent years. In the long run, use of dual therapy of anti-diabetic agents becomes mandatory to attain euglycemia. Also, the incidences of diabetes-related co-morbidities have warranted the search for new therapeutic approaches for the management of the disease. Traditional herbo-mineral, anti-diabetic agents like Madhugrit are often prescribed to mitigate diabetes and related complications. The present study aimed to thoroughly characterize the pharmacological applications of Madhugrit., Methods: Phytometabolite characterization of Madhugrit was performed by ultra-high performance liquid chromatography. Evaluation of cell viability, α-amylase inhibition, glucose uptake, inflammation, and wound healing was performed by in vitro model systems using AR42J, L6, THP1, HaCaT cells, and reporter cell lines namely NF-κB, TNF-α, and IL-1β. The formation of advanced glycation end products was determined by cell-free assay. In addition, the therapeutic potential of Madhugrit was also analyzed in the in vivo Caenorhabditis elegans model system. Parameters like brood size, % curling, glucose and triglyceride accumulation, lipid deposition, ROS generation, and lipid peroxidation were determined under hyperglycemic conditions induced by the addition of supraphysiological glucose levels., Results: Madhugrit treatment significantly reduced the α-amylase release, enhanced glucose uptake, decreased AGEs formation, reduced differentiation of monocyte to macrophage, lowered the pro-inflammatory cytokine release, and enhanced wound healing in the in vitro hyperglycemic (glucose; 25 mM) conditions. In C. elegans stimulated with 100 mM glucose, Madhugrit (30 µg/ml) treatment normalized brood size, reduced curling behavior, decreased accumulation of glucose, triglycerides, and lowered oxidative stress., Conclusions: Madhugrit showed multimodal approaches in combating hyperglycemia and related complications due to the presence of anti-diabetic, anti-inflammatory, anti-oxidant, wound healing, and lipid-lowering phytoconstituents in its arsenal. The study warrants the translational use of Madhugrit as an effective medicine for diabetes and associated co-morbidities., Competing Interests: The test article was provided by Divya Pharmacy, Haridwar, Uttarakhand, India. AB is an honorary trustee in Divya Yog Mandir Trust, which governs Divya Pharmacy, Haridwar. In addition, he holds an honorary managerial position in Patanjali Ayurved Ltd., Haridwar, India. Other than providing the test formulation (Madhugrit), Divya Pharmacy was not involved in any aspect of the research reported in this study. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Balkrishna, Gohel, Pathak, Tomer, Rawat, Dev and Varshney.)

Background: Currently, 21−30% supplemental oxygen is recommended during resuscitation of preterm neonates. Recent studies have shown that 58% of infants < 32 week gestation age are born with a heart rate (HR) < 100 bpm. Prolonged bradycardia with the inability to achieve a preductal saturation (SpO2) of 80% by 5 min is associated with mortality and morbidity in preterm infants. The optimal oxygen concentration that enables the achievement of a HR ≥ 100 bpm and SpO2 of ≥80% by 5 min in preterm lambs is not known. Methods: Preterm ovine model (125−127 d, gestation equivalent to human neonates < 28 weeks) was instrumented, and asphyxia was induced by umbilical cord occlusion until bradycardia. Ventilation was initiated with 30% (OX30), 60% (OX60), and 100% (OX100) for the first 2 min and titrated proportionately to the difference from the recommended preductal SpO2. Our primary outcome was the incidence of the composite of HR ≥ 100 bpm and SpO2 ≥ 80%, by 5 min. Secondary outcomes were to evaluate the time taken to achieve the primary outcome, gas exchange, pulmonary/systemic hemodynamics, and the oxidative injury. Results: Eighteen lambs (OX30-6, OX60-5. OX100-7) had an average HR < 91 bpm with a pH of <6.92 before resuscitation. Sixty seven percent achieved the primary outcome in OX100, 40% in OX60, and none in OX30. The time taken to achieve the primary outcome was significantly shorter with OX100 (6 ± 2 min) than with OX30 (10 ± 3 min) (* p = 0.04). The preductal SpO2 was highest with OX100, while the peak pulmonary blood flow was lowest with OX30, with no difference in O2 delivery to the brain or oxidative injury by 10 min. Conclusions: The use of 30%, 60%, and 100% supplemental O2 in a bradycardic preterm ovine model did not demonstrate a significant difference in the composite primary outcome. The current recommendation to use 30% oxygen did not achieve a preductal SpO2 of 80% by 5 min in any preterm lambs. Clinical studies to optimize supplemental O2 in depressed preterm neonates not requiring chest compressions are warranted.