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In this study, wavelet analysis and traditional cross-correlation analysis (TCA) have been employed to explore the temporal characteristics of the Air Quality Index (AQI) (PM2.5) and its relationships with meteorological factors, air temperature, and rainfall in the capital city of Nepal, Kathmandu, during 2017 - 2020. The temporal variation of monthly averaged (AQI) (PM2.5) revealed that the air quality was unhealthy in winter, improved in summer, and subsequently became unhealthy again in autumn and spring. We also noticed that the lowest AQI (PM2.5) was recorded in 2020, which is due to the COVID-19 pandemic lockdown. By analyzing the time-frequency relationship of (AQI) (PM2.5) with air temperature and rainfall, using Cross Wavelet Transform (XWT), we observed the interannual, seasonal, and monthly common periodicity between them. The coherency of XWT is then tested by using Wavelet Transform Coherence (WTC), which showed a negative correlation of AQI (PM2.5) with rainfall and air temperature, while an anomaly was seen among AQI (PM2.5) and temperature as they were positively associated for a few months in 2017, 2018, and 2020. Moreover, the results of cross-correlation and multiresolution analysis (MRA) are consistent with wavelet analysis, indicating the driving effect of air temperature and rainfall on (AQI) (PM2.5). [ABSTRACT FROM AUTHOR]

Low adoption of improved agricultural practices is one of the major challenges to improve food security. A case study was carried out to assist the farmer's fertilizer application gap in rice cultivation in Nepal. To collect data a household survey was conducted in 2017 by selecting 90 households randomly from rice growing pocket area of Banke district of Nepal. The rates of fertilizers use were assessed in relation to farm size, crop variety, irrigation etc. The applications of both organic and mineral fertilizers vary highly by farmer type. Small and medium farmers applied twice the amount of organic manure compared to large farmers. For inorganic fertilizer use, large farmers applied higher amounts of nitrogen (N) fertilizer compared to medium and small farmers. Across farmer types, a higher amount of N and P fertilizers was used for hybrid varieties than inbred varieties and in irrigated fields than in rainfed fields. The use of potassium (K) fertilizer was low and not affected by farmer type or variety. Overall, farmers used a lower amount of N and K and a higher amount of P than the recommendation. The imbalanced use of fertilizers was associated with poor access to agricultural extension services. Variations of fertilizer use among farmers and the role of extension in the adoption of improved practices are still under-researched, and hence this study exposes the need to investigate in-depth knowledge, determinants of fertilizer use and role of extension education. Results from this study could be important to develop an innovative extension program using multiple channels to increase farmers' access to and awareness regarding balanced use of fertilizers to increase soil fertility and crop productivity. [ABSTRACT FROM AUTHOR]

Large carnivores such as leopards (Panthera pardus) experience continuing threats from habitat loss and fragmentation, depletion of prey populations, and retaliatory killing following conflicts with humans. We aimed to identify factors affecting leopard occupancy and temporal overlap between leopards and tigers (P. tigris), their major prey, and human activities in the Parsa‐Koshi Complex (PKC), Nepal. We deployed 154 cameras for 21 days each along wildlife trails throughout PKC during December 2022–March 2023. We found low leopard occupancy (0.17 ± 0.04) in PKC, with greater occupancy rates within protected areas, particularly in Parsa National Park and its buffer zone. Human (63.10 ± 23) and livestock (36.46 ± 102) detections were higher across the PKC. Leopard occupancy was positively associated with the presence of tigers and prey. Temporal overlap was moderately high between leopards and tigers, as well as between leopards and their prey. Our research suggests that coexistence between leopards and tigers is likely largely facilitated by higher prey availability, which may reduce competition. Further, we demonstrate that maintaining forest cohesion can improve habitat for leopards. Intensifying use of agricultural areas could reduce forest fragmentation and increase leopard habitat overall, in turn reducing leopard depredation of livestock and improving leopard‐human co‐existence and conservation. [ABSTRACT FROM AUTHOR]

Prostate-specific membrane antigen (PSMA) is a transmembrane glycoprotein known to be overexpressed in prostate cancer and certain types of salivary gland cancer (SGC). Extracellular vesicles (EVs) are membrane-bound vesicles released from cells that are emerging as a promising blood biomarker for disease monitoring. The purpose of this exploratory analysis is to determine if circulating PSMA EVs can be detected in patients with recurrent or metastatic (R/M) SGC and to explore whether the direction of PSMA EV change correlates with tumor volume change. Research blood samples were collected prospectively from patients with R/M SGC being treated on a clinical trial. Blood samples and controls were incubated with fluorescent antibody-matched isotypes or antibodies against PSMA and analyzed by nanoscale flow cytometry. Positive counts in the controls were subtracted from the counts observed in corresponding samples to correct for the level of non-specific binding. Total tumor volume was approximated using two-dimensional measurements on cross-sectional imaging and converted to volume using a validated formula. 19 individual patients had 27 blood samples available for analysis (57.9% male, median age 60 years, range 43-79) with the following histologies: 6 adenoid cystic, 5 acinic cell, 4 salivary duct, 1 high grade mucoepidermoid (MEC), 2 adenocarcinoma, 1 poorly differentiated carcinoma NOS. Number of prior lines of cancer therapy (1 missing value): 1 line in 12 patients (66.7%), 2 lines in 5 patients (27.8%), and 3+ lines in 1 patient (5.6%). 8 patients had paired samples at baseline (BL) and 3-month post-treatment. All patients had detectable circulating PSMA EVs across all histologies. The median concentration of PSMA EVs for all 27 samples was 1.73E+06 (historical comparison 1.64E+06 for oligometastatic hormone sensitive prostate cancer). Baseline PSMA EVs/mL, total EV particles/mL, and relative fluorescence intensity of PSMA by histology are listed in Table 1. In patients with paired samples, the direction of the change was concordant between volume change and EV change in 6 out of 8 patients (75%). Circulating PSMA EVs appear to represent a possible novel biomarker of disease across salivary cancer histologies. Further prospective data collection is warranted. [ABSTRACT FROM AUTHOR]

Membrane proteins play a vital role in various cellular functions and are important targets for drug interactions. However, determining their local secondary structure is challenging due to their hydrophobic nature and limited experimental techniques. This study focuses on the use of electron spin echo envelope modulation (ESEEM) spectroscopy, in combination with site-directed spin labeling (SDSL) and 2 H-labeled amino acid side chain (d 10 -Leu), to study the local secondary structure of a recently discovered phage-encoded lytic protein, gp28. gp28 is a membrane protein with three predicted helices that plays a crucial role in the lysis process of bacteriophages that lack spanins. gp28 is an antimicrobial protein specifically involved in disrupting the outer membrane of the host cell. Through the synthesis of nine constructs of gp28 peptides, we systematically probed the three predicted helices. The local secondary structure of the gp28 protein in POPC/POPG vesicles was investigated using ESEEM spectroscopy. Additionally, the global secondary structure was verified using CD spectroscopy. Subsequently, the ESEEM technique allowed us to determine the local secondary structure within the three predicted alpha helices of gp28 in a membrane. This study revealed the presence of alpha helical structural components in all three predicted helices of gp28. These results not only enhance our comprehension of the local secondary structure of gp28 but also showcase the effectiveness of the ESEEM spectroscopic technique in studying membrane protein systems encoded by bacteriophages.

Background: Acute kidney Injury associated with Coronavirus disease COVID-19 appeared to negatively influence clinical outcomes and is found to be associated with significant risk of death. This retrospective study aimed to describe the incidence of Acute Kidney Injury, its associations with clinical characteristics and outcomes among COVID-19 patients in Sukraraj Tropical and Infectious Disease Hospital, a tertiary infectious disease hospital in Nepal., Methods: A cross-sectional study was done where. Medical and lab records of reverse transcriptase Polymerase chain reaction positive COVID-19 inpatients, admitted between April 2021 to July 2021 were reviewed. It represented the second wave of wave of coronavirus pandemic caused by the delta strain. Patients aged less than 18 years, pregnant females and patients with known chronic kidney disease were excluded Results: Of 393 admissions, 83 (21.1%) patients developed Acute Kidney Injury. Characteristics found to have significant association with development of AKI was age (p <0.001), multiple co morbidities (2 or more) (p <0.001), use of mechanical ventilation (p <0.001), lymphopenia (p<0.001), Neutrophil to Lymphocyte Ratio (p =0.001) and d-dimer levels (p <0.001). Mortality was found to be significantly higher in COVID-19 patients with AKI compared to COVID-19 patients without AKI ((36.14% vs 15.8%, p value <0.01)). The median duration of hospital stay for patients with AKI was higher than for patients without AKI (10 days vs 6 days,p <0.01)., Conclusions: AKI develops in a sizeable percentage of patients with COVID-19 and is significantly associated with increasing age, multiple comorbidities, increased biomarkers, use of mechanical ventilation and is associated with poor outcome in terms of mortality and morbidity.

Timely diagnosis and surgical intervention are crucial in managing hydrocele of the canal of Nuck. A systematic approach, including thorough examination and appropriate imaging, followed by meticulous surgical technique, ensures successful treatment and favorable long-term outcomes for patients., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Author(s). Clinical Case Reports published by John Wiley & Sons Ltd.)

Early recognition and prompt intervention are crucial in managing aconite poisoning. Rapid treatment with intravenous magnesium sulfate and amiodarone can stabilize severe cardiac arrhythmias. Vigilant monitoring and tailored therapeutic strategies enhance recovery and improve patient outcomes in acute poisoning cases., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Author(s). Clinical Case Reports published by John Wiley & Sons Ltd.)

Background: Cannabis and its derivatives show encouraging therapeutic effects in the treatment of various diseases. However, further studies are needed to better assess their efficacy and safety. A promising base for research in the field of medicine and additional pharmacovigilance is social networks, in which experience and knowledge are exchanged between researchers, doctors, and patients, as well as information about the potential risks and benefits of using drugs for medical purposes is disseminated. The aim of this study was to investigate the reported efficiency and safety of medical use of cannabinoids in patients using posts on the social media Instagram and analyze the observed trends., Methods: Social media listening platform Apify was used to collect data with hashtags as of June 4, 2024, including posts from 2023 and 2024, with some data extending into later periods, in compliance with a systematic approach to data collection. The analysis of the data obtained from the research was conducted using the RStudio platform., Results: The analysis covered 1,466 posts containing hashtags related to cannabinoids. The posts studied were categorized as follows: 33.08% focused on advertising and commercialization, 25.58% on personal experience, 21.35% on other topics, and 19.99% contained educational content. An analysis of overall content relevance found that the majority of Instagram posts (81.79%) related to cannabis and cannabinoid hashtags are relevant. Most of the Instagram posts studied were posters, followed by personal photos and videos. The analysis shows that English dominates the studied category (70.74% of posts), while German, French, Spanish, and other languages also occupy a significant place, emphasizing the importance of a multilingual approach in content analysis. It has been revealed that organizations publish a larger percentage of posts under this study, with a higher percentage of relevance. Personal experience stories receive a significant number of "likes" indicating a strong emotional connection between audience and content. Instagram discussions about cannabinoid treatment support evidence from scientific studies about their effectiveness in treating a range of diseases, such as epilepsy with Lennox-Gastaut and Dravet syndromes, multiple sclerosis, cancer, and HIV-cachexia, nausea and vomiting caused by chemotherapy. At the same time, they emphasize the need for further clinical studies to better assess safety, side effects, and optimal dosages. Advertising and commercial posts can contribute to increased cannabis use, highlighting the need to raise awareness of risks and strengthen preventive measures., Conclusion: Analysis of content on the social media Instagram can complement traditional scientific research by providing information on the real use of cannabis and its derivatives, contributing to the development of safe and effective recommendations for its use., 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. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Litvinova, Baral, Wochele-Thoma, Matin, Tzvetkov, Adamska, Kamińska, Łapiński, Stolarczyk and Atanasov.)

Background/introduction: Leprosy control remains a challenge in Nepal. Single-dose rifampicin post-exposure prophylaxis (SDR-PEP) shows promise in reducing leprosy incidence among contacts of index cases, contributing to reducing the transmission of Mycobacterium (M.) leprae. This study evaluates the effectiveness of routine SDR-PEP implementation in Nepal in addition to contact screening, focusing on its impact on reducing leprosy risk among contacts and potential population-level effects., Methodology: We conducted a retrospective cohort study to compare leprosy case notification rates and leprosy risk among close contacts. We compared two districts implementing SDR-PEP (the intervention group) and two without (the comparator group). Data from 2015 onwards included demographics, index case types, and contact relationships. Statistical analyses, including Cox regression and Kaplan-Meier survival curves, assessed the impact of SDR-PEP implementation., Findings: All four districts showed a decrease in case notification rates since 2015, with the steepest decline in the intervention districts. The risk of developing leprosy among contacts was significantly lower in the intervention districts (HR 0.28, 95% CI 0.18-0.44). SDR-PEP offered 72% protection, consistent over time, as shown in Kaplan-Meier plots. The protective effect was equally strong in blood-related contacts (HR 0.29 versus 0.27 in others, p = 0.32), and the proportion of MB cases among incident cases was not significantly different post-PEP (51.4% vs. 53.6%, p = 0.82)., Conclusions: This study demonstrates the substantial protective effect of integrating SDR-PEP in routine leprosy control programs with contact screening, significantly lowering leprosy risk among contacts. SDR-PEP is equally effective for blood-related contacts and does not preferentially prevent PB cases. While suggesting potential population-level impact, the study design does not allow for firm conclusions at this level. Further research is needed to fully assess SDR-PEP's effectiveness in diverse contexts and optimize its implementation. Integrating SDR-PEP within well-organized contact screening programs is effective and is expected to reduce leprosy transmission when applied as a rolling intervention., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Banstola 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.)

Helicobacter pylori is a pathogenic bacterium that causes gastritis and gastric carcinoma. Besides gastric complications its potential link with gut-brain axis disruption and neurological disorders has also been reported. The current study investigated the plausible role and its associated molecular mechanism underlying H. pylori mediated gut-brain axis disruption and neuroinflammation leading to neurological modalities like Alzheimer's disease (AD). We have chosen the antimicrobial resistant and susceptible H. pylori strains on the basis of broth dilution method. We have observed the increased inflammatory response exerted by H. pylori strains in the gastric as well as in the neuronal compartment after treatment with Helicobacter pylori derived condition media (HPCM). Further, elevated expression of STAT1, STAT3, and AD-associated proteins- APP and APOE4 was monitored in HPCM-treated neuronal and neuron-astrocyte co-cultured cells. Excessive ROS generation has been found in these cells. The HPCM treatment to LN229 causes astrogliosis, evidenced by increased glial fibrillary acidic protein. Our results indicate the association of STAT3 as an important regulator in the H. pylori- mediated pathogenesis in neuronal cells. Notably, the inhibition of STAT3 by its specific inhibitor, BP-1-102, reduced the expression of pSTAT3 and AD markers in neuronal compartment induced by HPCM. Thus, our study demonstrates that H. pylori infection exacerbates inflammation in AGS cells and modulates the activity of STAT3 regulatory molecules. H. pylori secretome could affect neurological compartments by promoting STAT3 activation and inducing the expression of AD-associated signature markers. Further, pSTAT-3 inhibition mitigates the H. pylori associated neuroinflammation and amyloid pathology.

The Watson-Crick base pairing property of DNA is widely used for fabricating DNA nanostructures with well-defined geometry. Moreover, DNA nanostructures can be easily modified in terms of shape, size and function at the nanoscale level. Therefore, investigation on smaller and stable branched DNA (bDNA) is of critical significance for biomedical applications. In the present communication, we report smaller and stable branched DNA (bDNA) which is of critical significance for biomedical applications. In this study, a novel strategy has been used in identifying stable bDNA nanostructures with a minimum number of Watson-Crick base pairings. The importance of hybridizing regions and helical twists between multiple oligonucleotides has been explored using various biophysical techniques. The electrophoretic analysis demonstrated that hybridizing regions with ≥12 nt nucleotides can form stable bDNA structures. Substantial negative enthalpic contributions determine the significance of base stacking and the length of oligonucleotides in the hybridization process. Finally, thermal melting investigations confirmed the creation of bDNA nanostructures with ≥12 nt long hybridizing regions. In general, our findings indicate that bDNA oligonucleotides do not undergo hybridization if the number of base pairs is lesser for a single helical turn. Furthermore, the yield and stability of smaller bDNA nanostructures in physiological conditions are comparable with the earlier reported higher-order structures. Hence, smaller bDNAs are more stable which may be preferred over conventional bDNA nanostructures for advanced biomedical applications., 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 © 2024 Elsevier B.V. All rights reserved.)

Competing Interests: Conflict of interest statement. None declared.

Helicobacter pylori and Epstein Barr virus (EBV) are group1 carcinogens and their role in Gastric cancer (GC) is well established. Previously we have shown that H. pylori and EBV appears to support aggressive gastric oncogenesis through the upregulation of oncoprotein Gankyrin. Natural plant active molecules have the potential to interrupt oncogenesis. Herein, we investigated the potential of Withania somnifera root extract (WSE) as a possible chemotherapeutic agent against host oncoprotein Gankyrin whose expression was altered by H. pylori and EBV-associated modified cellular milieu. The results show that WSE does not have any inhibitory effect on H. pylori and EBV-associated gene transcripts except for the lmps ( lmp1 , lmp2a, and lmp2B ). Moreover, the WSE exert their anticancer activity via host cellular response and decreased the expression of cell-migratory ( mmp3 and mmp7 ); cell-cycle regulator ( pcna ); antiapoptotic gene ( bcl2 ); increased the expression of the proapoptotic gene ( apaf1 and bax ); and tumor suppressor ( p53 , prb, and pten ). Knockdown of Gankyrin followed by the treatment of WSE also decreases the expression of TNF-ɑ, Akt, and elevated the expression of NFkB, PARP, Casp3, and Casp9. WSE also reduces cell migration, and genomic instability and forced the cells to commit programmed cell death. Moreover, molecular simulation studies revealed that out of eight active compounds of WSE, only four compounds such as withaferin A (WFA), withanoside IV (WA4), withanolide B (WNB), and withanolide D (WND) showed direct stable interaction with Gankyrin. This article reports for the first time that treatment of WSE decreased the cancerous properties through host cellular response modulation in gastric epithelial cells coinfected with H. pylori and EBV.Communicated by Ramaswamy H. Sarma.

The intermittent nature of solar energy presents a significant challenge to its reliability, particularly in applications that require a consistent energy supply, such as cooking. This issue is especially critical in emerging economies with abundant solar resources, where sustainable energy solutions are needed to reduce reliance on traditional fuels. To address this challenge, this study introduces a novel solar thermal storage (STS), utilizing a metal-based material to accumulate and retain heat for off-sunshine hour cooking. The research focuses on optimizing aluminium as the STS material, evaluating its temperature suitability, efficiency, and heat retention capabilities for household solar cooking applications. Numerical simulations using the OpenFOAM framework were conducted to analyze heat transfer within the cooker, determining the optimal size of the aluminium block based on existing literature and predefined parameters. Practical experiments, including solar-induced heating-cooling cycles and controlled cooking tests, were carried out to validate the findings. Experimental results demonstrate STS's ability to efficiently absorb and retain heat, reaching a maximum of 235 °C during a 5.5-h heating session. The water boiling experiment further confirmed STS's practical utility, effectively transferring stored heat to cooking tasks and sustaining temperatures up to 160 °C even after the test. Additionally, experiments with black lentils and chicken stew highlighted aluminium's suitability for practical cooking applications, showcasing its ability to sustain high temperatures and efficiently transfer stored heat despite longer cooking times. The study's novelty lies in integrating numerical modeling with experimental analysis to optimize STS systems, providing practical guidelines for efficient thermal storage in cooking applications. This research advances beyond previous efforts by providing a validated methodology for the design and optimization of thermal storage systems. It improves the reliability and adaptability of solar energy for cooking applications., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background: Recurrent squamous cell carcinoma (SCC) of the head and neck (SCCHN) remains a formidable clinical challenge despite available treatments. The phosphatidylinositol 3-kinase (PI3K) pathway has been identified as a potential therapeutic target, and alpelisib, a selective PI3Kα inhibitor, has demonstrated efficacy in certain malignancies. Combining this targeted therapy with immunotherapy has been suggested in previous studies as a promising strategy to bolster the immune response against cancer., Cases: A 69-year-old woman with locoregional recurrence of PIK3CA-mutated SCC of the left maxilla and cervical nodal metastases. Several chemotherapeutic regimens, including cisplatin, docetaxel, 5FU, chemoradiotherapy, and mono-immunotherapy, resulted in disease progression. Alpelisib combined with pembrolizumab led to a sustained response for 9 months. A 58-year-old man with recurrent metastatic PIK3CA-mutated SCC of the oropharynx, involving the left lung, hilar, and mediastinal lymph nodes. Despite prior palliative radiation and platinum-based chemotherapy with pembrolizumab and cetuximab, treatment with alpelisib and nivolumab resulted in a partial response. Severe hyperglycemia and rash led to treatment discontinuation., Conclusion: Our findings highlight the potential of this innovative therapeutic combination, suggesting a need for further investigations in this setting., (© 2024 The Author(s). Cancer Reports published by Wiley Periodicals LLC.)

Background: Head and neck cancers (HNC) present diagnostic challenges due to multifocal disease manifestations, posing difficulties in distinguishing between metastatic disease and second primary malignancies (SPM). This complexity underscores the need for advanced diagnostic approaches. Emerging technologies, such as next-generation sequencing (NGS) and molecular classifier assays, show promise in providing precise insights into the diverse etiologies of HNC., Method: In this article, we employed NGS and molecular classifier assays to delve into three distinct clinical cases. The objective was to showcase the instrumental role of these technologies in facilitating accurate diagnoses and differentiating between metastatic disease and SPM in HNC cases., Results: The results of this series highlight the effectiveness of NGS and molecular classifier assays in enhancing diagnostic accuracy for HNC and contributing to the precise differentiation of disease etiologies. The utilization of these advanced technologies proved instrumental in avoiding unnecessary interventions and paved the way for more targeted and effective treatment strategies., Conclusion: Our findings underscore the necessity of incorporating advanced molecular testing technologies into the diagnostic and therapeutic approaches for HNC, thereby championing a more nuanced and effective approach to managing these complex cases., (© 2024 Wiley Periodicals LLC.)

Rhabdomyolysis is a rare but serious complication of hypothyroidism, typically associated with precipitating factors such as medication interactions, strenuous exercise, and illicit drug use. We present a unique case of rhabdomyolysis in an 89-year-old female due to severe hypothyroidism without identifiable precipitating factors. Laboratory results revealed markedly elevated creatine kinase (CK) levels and acute kidney injury (AKI). The diagnosis was confirmed by critically elevated thyroid-stimulating hormone (TSH) and low free thyroxine (FT4) levels. Prompt initiation of levothyroxine supplementation and fluid resuscitation led to clinical improvement and downward trend in creatinine and CK levels. This case highlights the importance of considering hypothyroidism in the differential diagnosis of rhabdomyolysis and the need for timely T4 supplementation and supportive care to prevent severe complications., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Baral et al.)

Coinfection of pathogenic bacteria and viruses is associated with multiple diseases. During the COVID-19 pandemic, the co-infection of other pathogens with SARS-CoV-2 was one of the important determinants of the severity. Although primarily a respiratory virus gastric manifestation of the SARS-CoV-2 infection was widely reported. This study highlights the possible consequences of SARS-CoV-2 - Helicobacter pylori coinfection in the gastrointestinal cells. We utilized the transfection and infection model for SARS-CoV-2 spike Delta (δ) and H. pylori respectively in colon carcinoma cell line HT-29 to develop the coinfection model to study inflammation, mitochondrial function, and cell death. The results demonstrate increased transcript levels of inflammatory markers like TLR2 (p < 0.01), IL10 (p < 0.05), TNFα (p < 0.05) and CXCL1 (p < 0.05) in pre- H. pylori infected cells as compared to the control. The protein levels of the β-Catenin (p < 0.01) and c-Myc (p < 0.01) were also significantly elevated in pre- H. pylori infected group in case of co-infection. Further investigation of apoptotic and necrotic markers (Caspase-3, Caspase-8, and RIP-1) reveals a necroptotic cell death in the coinfected cells. The infection and coinfection also damage the mitochondria in HT-29 cells, further implicating mitochondrial dysfunction in the necrotic cell death process. Our study also highlights the detrimental effect of pre- H. pylori exposure in the coinfection model compared to post-exposure and lone infection of H. pylori and SARS-CoV-2. This knowledge could aid in developing targeted interventions and therapeutic strategies to mitigate the severity of COVID-19 and improve patient outcomes., Competing Interests: Authors have no conflict of interest to declare., (© 2024 The Authors.)

DNA has been employed as building blocks for the construction of nanomaterials due to their programmability and wide range applications. The functional branched DNA (bDNA) nanostructure is largely dependent on the sequence and structural symmetry. Despite the discovery of different structures, the synthesis of bDNA nanostructures from optimal number of oligonucleotides is yet to be explored. In the current study, for the first time we demonstrate the designing of stable monomeric bDNA structures using two or three oligonucleotides. Furthermore, the stability of bDNA nanostructures was thoroughly investigated in presence of different pH, cations, fetal bovine serum and DNase I. The thermodynamic parameters indicated that hydrogen bonding and van der Waals interactions played a major role during self-assembly of bDNA nanostructures. From the gel retardation assay, we confirmed the binding of complementary oligonucleotides to the bDNA nanostructures, thus can be explored for target specific transcript regulation. In conclusion, the self-assembled DNA nanostructures developed from optimal oligonucleotides are stable in physiological environment and can be used for biomedical applications., Competing Interests: Declaration of competing interest The authors declare no competing financial interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

This literature review offers an extensive exploration of Chaga mushrooms ( Inonotus obliquus ), focusing on their phytochemical composition, health-promoting attributes, and mechanisms of action. The aim was to provide an up-to-date overview of Chaga's significance in the medicinal sector, emphasizing its potential role in diverse health benefits. The review highlights Chaga's remarkable anticancer, antioxidant, anti-diabetic, anti-inflammatory, antimicrobial, and immunomodulating properties. By synthesizing recent findings, this work underscores Chaga's importance in the medicinal industries and provides valuable insights into its pharmacological potential., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

High mortality has been reported in severe cases of COVID-19. Emerging reports suggested that the severity is not only due to SARS-CoV-2 infection, but also due to coinfections by other pathogens exhibiting symptoms like COVID-19. During the COVID-19 pandemic, simultaneous respiratory coinfections with various viral (Retroviridae, Flaviviridae, Orthomyxoviridae, and Picoviridae) and bacterial (Mycobacteriaceae, Mycoplasmataceae, Enterobacteriaceae and Helicobacteraceae) families have been observed. These pathogens intensify disease severity by potentially augmenting SARSCoV-2 replication, inflammation, and modulation of signaling pathways. Coinfection emerges as a critical determinant of COVID-19 severity, principally instigated by heightened pro-inflammatory cytokine levels, as cytokine storm. Thereby, in co-infection scenario, the severity is also driven by the modulation of inflammatory signaling pathways by both pathogens possibly associated with interleukin, interferon, and cell death exacerbating the severity. In the current review, we attempt to understand the role of co- infections by other pathogens and their involvement in the severity of COVID-19., Competing Interests: Declaration of Competing Interest None., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Over the past several years, a significant increase in the expanding field of biomaterial sciences has been observed due to the development of biocompatible materials based on peptide derivatives that have intrinsic therapeutic potential. In this report, we synthesized nucleobase functionalized peptide derivatives (NPs). Hydrogelation in the synthesized NPs was induced by increasing their hydrophobicity with an aromatic moiety. The aggregation behavior of the NPs was analyzed by performing molecular dynamics simulations and DOSY NMR experiments. We performed circular dichroism (CD), thioflavin-T binding and PXRD to characterize the supramolecular aggregation in the NP1 hydrogel. The mechanical strength of the NP1 hydrogel was tested by performing rheological experiments. TEM and SEM experiments were performed to investigate the morphology of the NP1 hydrogel. The biocompatibility of the newly synthesized NP1 hydrogel was investigated using McCoy and A549 cell lines. The hemolytic activity of the NP1 hydrogel was examined in human blood cells. The stability of the newly formed NP1 hydrogel was examined using proteinase K and α-chymotrypsin. The NP1 hydrogel was used for in vitro wound healing. Western blotting, qRT-PCR and DCFDA assay were performed to determine the anti-inflammatory activity of the NP1 hydrogel. The synthesized NP1 hydrogel also exhibits antibacterial efficacy.

Hypophysitis is a rare pituitary gland disease primarily seen in females of reproductive age. Patients can present with various non-specific symptoms, which makes diagnosis challenging. Appropriate endocrine workup supplemented with magnetic resonance imaging (MRI) helps establish a diagnosis. We present a case of a 22-year-old postpartum female who came with nausea, vomiting, and abdominal pain. Global endocrine insufficiency was seen in the laboratory workup, and an MRI confirmed the diagnosis of hypophysitis. She was treated with steroid and thyroid hormone supplementation., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Baral et al.)

This literature review provides an up-to-date exploration of the multifaceted attributes of maitake mushrooms ( Grifola frondosa ), elucidating their bioactive phytochemicals and diverse health advantages, including their substantial role in supporting human health and potential incorporation into the medicinal industry. Carbohydrates and protein are the major constituents contributing to the dry weight of G. frondosa , taking up around 70-80 % and 13-21 %, respectively, with emerging research linking these constituents to various health benefits. By synthesising current research findings, this review emphasises the substantial role of maitake mushrooms in supporting human health and underscores their potential incorporation into the medicinal industry. To further advance our understanding, future research should delve into the mechanisms underlying their health-promoting effects, with a focus on conducting quantitative studies to elucidate physiological pathways and potential drug interactions. Additionally, exploring their integration into functional foods or nutraceuticals through quantitative assessments of bioavailability and efficacy will be crucial for maximising their therapeutic benefits. This review aims to provide comprehensive insights, catalysing further research and innovation in utilising maitake mushrooms for improved well-being and industry advancement., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

DNA is widely used as building block material for the construction of polyhedral nanostructures. DNA polyhedrons (DNA prism, cube, and square pyramid) are small 3D wireframed nanostructures with tunable shapes and sizes. Despite substantial progress in synthesis, the study regarding cellular responses to DNA polyhedrons is limited. Herein, the molecular interaction between DNA polyhedrons and the antioxidant enzyme, catalase has been explored. The enzymatic activity of bovine liver catalase (BLC) remains unaltered in the presence of DNA polyhedrons after 1 h of incubation. However, the activity of BLC was protected after 24 h of incubation in the presence of DNA polyhedrons as compared to the natural unfolding. The kinetics study confirmed the protective role of DNA polyhedrons on BLC with lower K M and higher catalytic efficiency. Furthermore, no profound conformational changes of BLC occur in the presence of DNA polyhedrons as observed in spectroscopic studies. From fluorescence quenching data we confirmed the binding between DNA polyhedrons and BLC. The thermodynamic parameters indicate that non-covalent bonds played a major role during the interaction of BLC with DNA polyhedrons. Moreover, the hepatic catalase activity remains unaltered in the presence of DNA polyhedrons. The cytotoxicity assay revealed that DNA polyhedrons were biocompatible in the cellular environment. The protective role of DNA polyhedrons on enzyme activity and the unaltered conformational change of protein ensures the biocompatibility of DNA polyhedrons in the cellular environment., 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 © 2024 Elsevier B.V. All rights reserved.)

Multi-walled Carbon Nanotubes (MWCNTs) are inert structures with high aspect ratios that are widely used as vehicles for targeted drug delivery in cancer and many other diseases. They are largely non-toxic in nature however, when cells are exposed to these nanotubes for prolonged durations or at high concentrations, they show certain adverse effects. These include cytotoxicity, inflammation, generation of oxidative stress, and genotoxicity among others. To combat such adverse effects, various moieties can be attached to the surface of these nanotubes. Curcumin is a known anti-inflammatory, antioxidant and cytoprotective compound derived from a medicinal plant called Curcuma longa. In this study, we have synthesized and characterized Curcumin coated-lysine functionalized MWCNTs and further evaluated the cytoprotective, anti-inflammatory, antioxidant and antiapoptotic effect of Curcumin coating on the surface of MWCNTs. The results show a significant decrease in the level of inflammatory molecules like IL-6, IL-8, IL-1β, TNFα and NFκB in cells exposed to Curcumin-coated MWCNTs as compared to the uncoated ones at both transcript and protein levels. Further, compared to the uncoated samples, there is a reduction in ROS production and upregulation of antioxidant enzyme-Catalase in the cells treated with Curcumin-coated MWCNTs. Curcumin coating also helped in recovery of mitochondrial membrane potential in the cells exposed to MWCNTs. Lastly, cells exposed to Curcumin-coated MWCNTs showed reduced cell death as compared to the ones exposed to uncoated MWCNTs. Our findings suggest that coating of Curcumin on the surface of MWCNTs reduces its ability to cause inflammation, oxidative stress, and cell death., (© 2024. The Author(s).)

Introduction and Importance: Cytarabine, a pyrimidine analogue, is commonly used to treat multiple haematological conditions, such as acute leukaemias and lymphomas. One of the rare and less reported complications of cytarabine is peripheral neuropathy, in which peripheral nerves are damaged, often causing weakness, numbness, and pain, usually in the hands and feet., Case Presentation: The authors report the case of a 17-year-old male who developed a gradual onset of weakness and sensory loss in all four limbs during treatment with a conventional dose of cytarabine for acute myeloid leukaemia. Cytarabine was discontinued after the development of symptoms, and his motor and sensory functions gradually improved over the course of 3 months., Clinical Discussion: Alongside some well-known side effects of cytarabine, including bone marrow suppression, cerebellar syndrome, and cardiotoxicity, peripheral neuropathy is one of the uncommon side effects of cytarabine. Diagnosis includes identifying and grading the severity of chemotherapy-induced peripheral neuropathy (CIPN) through clinical assessment and nerve conduction studies. Management includes withdrawing the chemotherapeutic agent and supportive treatment with drugs such as duloxetine. Recent studies also favour the use of acupuncture and sensorimotor-based exercise intervention for the management of CIPN., Methods: This case report has been prepared in line with the SCARE 2023 criteria., Conclusion: Although rare, even a conventional dosage of cytarabine can cause peripheral neuropathy, and routine neuromuscular examinations can help in the early diagnosis and intervention to limit further progression and reverse the course of the disease., Competing Interests: None to declare.Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Sialidosis is a rare variety of lysosomal storage disease that results in intracellular accumulation of sialic acid containing compounds. The authors report the first case of type II sialidosis, juvenile subtype in a 30-month-old male child from Nepal., Case Presentation: Progressive hearing loss with coarse facies, hepatomegaly, kyphoscoliosis, dysostosis multiplex were the major features in a 30-month-old child born to healthy non-consanguineous parents. With the suspicion of lysosomal storage disease, urinary oligosaccharides were tested and were positive. Whole-exome sequencing revealed a mutation in the neuraminidase gene (NEU1) and established the diagnosis of sialidosis., Clinical Discussion: Sialidosis is a rare autosomal recessive type of lysosomal storage disease resulting due to mutation of the neuraminidase gene leading to intracellular accumulation of sialic acid compounds. Based on the presence of visual symptoms, sialidosis is classified into type I and II varieties. Our case is of type II juvenile sialidosis., Conclusion: Despite rare, sialidosis is a life-threatening, and disabling disease. Exploring targeted therapy is the utmost to treat this condition., Competing Interests: Not applicable.Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Though direct greenhouse gas emissions cannot be observed in health care sectors, there can exist indirect emissions contributing to global climate change. This study addresses the concept of the carbon footprint and its significance in understanding the environmental impact of human activities, with a specific emphasis on the healthcare sector through gate-to-gate (GtoG) life cycle assessment. Transportation, energy consumption, and solid waste generated by hospitals are the primary sources of carbon emissions., Methods: Different standards, guidelines and parameters were used to estimate emissions from both the primary and secondary data. All steps and sub-steps involved in GtoG were accessed and analyzed within the standard ISO 14040:44 guideline. An extensive review of existing literature was carried out for the evaluation and verification of secondary data., Results: The total carbon footprint of generators, electricity consumption, transportation activities, LPG cylinders, PV systems was found to be 58,780 kg-CO2-eq/yr, 519,794 kg-CO2-eq/yr, 272,375 kg-CO2-eq/yr, 44,494 kg-CO2-eq/yr, 35,283 kg-CO2-eq/yr respectively and the emissions from non-biodegradable solid waste was found to be 489,835 kg-CO2/yr. Local air pollutants such as PM 10 , CO, SO 2 , NO X , and VOCs generated by generators and transportation were also estimated. The CH 4 emissions from liquid waste were 1177.344 kg CH 4 /BOD yr, and those from biodegradables were 3821.6954 kg CH4/yr., Conclusions: Healthcare professionals and policymakers can take action to reduce the sector's carbon footprint by implementing best practices and encouraging sustainable behavior. This study can be taken as foundation for further exploration of indirect emissions from healthcare sectors not only in Nepal but also in south Asian scenario., Competing Interests: No competing interests were disclosed., (Copyright: © 2024 Adhikari B et al.)

The asymmetrical distribution of the cellular organelles inside the cell is maintained by a group of cell polarity proteins. The maintenance of polarity is one of the vital host defense mechanisms against pathogens, and the loss of it contributes to infection facilitation and cancer progression. Studies have suggested that infection of viruses and bacteria alters cell polarity. Helicobacter pylori and Epstein-Barr virus are group I carcinogens involved in the progression of multiple clinical conditions besides gastric cancer (GC) and Burkitt's lymphoma, respectively. Moreover, the coinfection of both these pathogens contributes to a highly aggressive form of GC. H. pylori and EBV target the host cell polarity complexes for their pathogenesis. H. pylori-associated proteins like CagA, VacA OipA, and urease were shown to imbalance the cellular homeostasis by altering the cell polarity. Similarly, EBV-associated genes LMP1, LMP2A, LMP2B, EBNA3C, and EBNA1 also contribute to altered cell asymmetry. This review summarized all the possible mechanisms involved in cell polarity deformation in H. pylori and EBV-infected epithelial cells. We have also discussed deregulated molecular pathways like NF-κB, TGF-β/SMAD, and β-catenin in H. pylori, EBV, and their coinfection that further modulate PAR, SCRIB, or CRB polarity complexes in epithelial cells., (© 2023. Institute of Microbiology, Academy of Sciences of the Czech Republic, v.v.i.)

Synovial sarcoma is a mesenchymal tumour with partial epithelial differentiation. About 85-90% of SS occur in the extremities. We present a case of a 44-year-old woman diagnosed with recurrent synovial sarcoma with breast and pulmonary nodules. The primary treatment for synovial sarcoma is wide surgical excision, while chemotherapy is reserved for metastatic cases. In the first-line metastatic setting, combination treatment with adriamycin and ifosfamide is administered. Despite the unfavourable prognosis, the patient's extended survival is fortunately not the typical outcome., Keywords: case reports; chemotherapy; immunohistochemistry; synovial sarcoma.

Background: Stigma and poor mental health are important factors influencing the quality of life (QOL) of people with neglected tropical diseases (NTDs). This study examines the relationship between stigma, depression and QOL among people affected by leprosy and lymphatic filariasis (LF) in Nepal., Methods: A cross-sectional community-based survey was conducted among 102 NTD-affected persons (70 leprosy and 32 LF) using interview-administered questionnaires measuring the level of stigma (5-QSI-AP), symptoms of depression (PHQ-9) and QOL (WHOQOL-8). Three different regression models were developed, each using the ordinary least squares and Poisson regression to evaluate the association between stigma and QOL, depression and QOL, and stigma and depression., Results: The mean scores were 21.8±4.4 for QOL, 6.6±5.6 for depression and 3.0±2.8 for stigma. Almost 17% reported the prevalence of depression symptoms. Both stigma (β=-0.65, p<0.001) and depression (β=-0.32, p<0.001) were associated with lower scores for QOL, while there was a significant positive relationship between stigma and depression (β=0.92, p<0.001). Similar results were obtained from the Poisson regression models., Conclusions: The study showed a considerable burden of depression, stigma and poor QOL among study participants with leprosy and LF in Nepal. A holistic package of care that addresses the physical, mental and psychological well-being of people with NTD is required., Contexte: La stigmatisation et la mauvaise santé mentale sont des facteurs importants qui influencent la qualité de vie des personnes atteintes de maladies tropicales négligées (MTN). Cette étude examine la relation entre la stigmatisation, la dépression et la qualité de vie chez les personnes atteintes de lèpre et de filariose lymphatique au Népal., Méthodes Utilisées: Une enquête communautaire transversale a été menée auprès de 102 personnes atteintes de MTN (70 de la lèpre et 32 de la filariose lymphatique) à l'aide de questionnaires administrés par entretien mesurant le niveau de stigmatisation (5-QSI-AP), les symptômes de dépression (PHQ-9) et la qualité de vie (WHOQOL-8). Trois modèles de régression différents ont été développés, chacun utilisant les moindres carrés ordinaires et la régression de Poisson pour évaluer l'association entre : (i) la stigmatisation et la QV; (ii) la dépression et la QV; et (iii) la stigmatisation et la dépression., Résultats: Les scores moyens étaient de 21,8±4,4 pour la QV, 6,6±5,6 pour la dépression, et 3,0±2,8 pour la stigmatisation. Près de 17% des personnes interrogées ont signalé la prévalence de symptômes dépressifs. La stigmatisation (β = -0,65, p<0 001) et la dépression (β = -0,32, p<0 001) ont été associées à des scores plus faibles pour la qualité de vie, tandis qu'il existait une relation positive significative entre la stigmatisation et la dépression (β = 0,92, p<0 001). Des résultats similaires ont été obtenus à partir des modèles de régression de Poisson., Conclusions: L'étude a montré une incidence importante de dépression, de stigmatisation et d'une mauvaise qualité de vie parmi les participants atteints de lèpre et de FL au Népal. Il convient donc de mettre en place un ensemble de soins holistiques pour ces patients qui prendrait en compte le bien-être physique, mental et psychologique des personnes atteintes de MTN., Antecedentes: La estigmatización y la mala salud mental son factores importantes que influyen en la calidad de vida de las personas con enfermedades tropicales desatendidas. las personas con enfermedades tropicales desatendidas (ETD). Este estudio examina la relación entre el estigma, la depresión y la CdV entre las personas afectadas por lepra y lepra y la filariasis linfática en Nepal., Métodos: Se realizó una encuesta comunitaria transversal entre 102 personas afectadas por ETD (70 de lepra y 32 de filariasis linfática) utilizando cuestionarios entrevistas para medir el nivel de estigma (5-QSI-AP), los síntomas de depresión (PHQ- 9) y la CdV (OMS- 9). 9) y la calidad de vida (WHOQOL-8). Se desarrollaron tres modelos de regresión diferentes regresión de Poisson para evaluar la asociación entre: (i) el estigma y (ii) la depresión. entre: (i) estigma y CdV; (ii) depresión y CdV; y (iii) estigma y depresión., Resultados: Las puntuaciones medias fueron 21,8±4,4 para la CdV, 6,6±5,6 para la depresión y 3,0±2,8 para el estigma. Casi el 17% informó de la prevalencia de síntomas de depresión. Tanto el estigma (β = -0,65, p<0 001), como la depresión (β = -0,32, p<0 001) se asociaron con puntuaciones más bajas para la CdV, mientras que hubo una relación positiva significativa entre el estigma y la depresión (β = 0,92, p<0 001). Se obtuvieron resultados similares en los modelos de regresión de Poisson., Conclusiones: El estudio mostró una carga considerable de depresión, estigma y mala CdV entre los participantes del estudio con lepra y FL en Nepal. Se requiere un paquete holístico de atención que aborde el bienestar físico, mental y psicológico de las personas con ETD., (© The Author(s) 2023. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

SARS-CoV-2 Envelope protein (E) is one of the crucial components in virus assembly and pathogenesis. The current study investigated its role in the SARS-CoV-2-mediated cell death and inflammation in lung and gastrointestinal epithelium and its effect on the gastrointestinal-lung axis. We observed that transfection of E protein increases the lysosomal pH and induces inflammation in the cell. The study utilizing Ethidium bromide/Acridine orange and Hoechst/Propidium iodide staining demonstrated necrotic cell death in E protein transfected cells. Our study revealed the role of the necroptotic marker RIPK1 in cell death. Additionally, inhibition of RIPK1 by its specific inhibitor Nec-1s exhibits recovery from cell death and inflammation manifested by reduced phosphorylation of NFκB. The E-transfected cells' conditioned media induced inflammation with differential expression of inflammatory markers compared to direct transfection in the gastrointestinal-lung axis. In conclusion, SARS-CoV-2 E mediates inflammation and necroptosis through RIPK1, and the E-expressing cells' secretion can modulate the gastrointestinal-lung axis. Based on the data of the present study, we believe that during severe COVID-19, necroptosis is an alternate mechanism of cell death besides ferroptosis, especially when the disease is not associated with drastic increase in serum ferritin., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)