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SARS-CoV-2 causes profound changes in the sense of smell, including total smell loss. Although these alterations are often transient, many patients with COVID-19 exhibit olfactory dysfunction that lasts months to years. Although animal and human autopsy studies have suggested mechanisms driving acute anosmia, it remains unclear how SARS-CoV-2 causes persistent smell loss in a subset of patients. To address this question, we analyzed olfactory epithelial samples collected from 24 biopsies, including from nine patients with objectively quantified long-term smell loss after COVID-19. This biopsy-based approach revealed a diffuse infiltrate of T cells expressing interferon-γ and a shift in myeloid cell population composition, including enrichment of CD207+ dendritic cells and depletion of anti-inflammatory M2 macrophages. Despite the absence of detectable SARS-CoV-2 RNA or protein, gene expression in the barrier supporting cells of the olfactory epithelium, termed sustentacular cells, appeared to reflect a response to ongoing inflammatory signaling, which was accompanied by a reduction in the number of olfactory sensory neurons relative to olfactory epithelial sustentacular cells. These findings indicate that T cell-mediated inflammation persists in the olfactory epithelium long after SARS-CoV-2 has been eliminated from the tissue, suggesting a mechanism for long-term post-COVID-19 smell loss.

Salicylic acid (SA) is an important phytohormone, well‐known for its regulatory role in shaping plant immune responses. In recent years, significant progress has been made in unravelling the molecular mechanisms underlying SA biosynthesis, perception, and downstream signalling cascades. Through the concerted efforts employing genetic, biochemical, and omics approaches, our understanding of SA‐mediated defence responses has undergone remarkable expansion. In general, following SA biosynthesis through Avr effectors of the pathogens, newly synthesized SA undergoes various biochemical changes to achieve its active/inactive forms (e.g. methyl salicylate). The activated SA subsequently triggers signalling pathways associated with the perception of pathogen‐derived signals, expression of defence genes, and induction of systemic acquired resistance (SAR) to tailor the intricate regulatory networks that coordinate plant immune responses. Nonetheless, the mechanistic understanding of SA‐mediated plant immune regulation is currently limited because of its crosstalk with other signalling networks, which makes understanding this hormone signalling more challenging. This comprehensive review aims to provide an integrated overview of SA‐mediated plant immunity, deriving current knowledge from diverse research outcomes. Through the integration of case studies, experimental evidence, and emerging trends, this review offers insights into the regulatory mechanisms governing SA‐mediated immunity and signalling. Additionally, this review discusses the potential applications of SA‐mediated defence strategies in crop improvement, disease management, and sustainable agricultural practices. [ABSTRACT FROM AUTHOR]

Plants constantly perceive and process environmental signals and balance between the energetic demands of growth and defense. Growth arrest upon pathogen attack was previously suggested to result from a redirection of the plants' metabolic resources towards the activation of plant defense. The energy sensor Target of Rapamycin (TOR) kinase is a conserved master coordinator of growth and development in all eukaryotes. Although TOR is positioned at the interface between development and defense, little is known about the mechanisms by which TOR may potentially regulate the relationship between these two modalities. The plant hormones cytokinin (CK) and gibberellin (GA) execute various aspects of plant development and defense. The ratio between CK and GA was reported to determine the outcome of developmental programmes. Here, investigating the interplay between TOR‐mediated development and TOR‐mediated defense in tomato, we found that TOR silencing resulted in rescue of several different aberrant developmental phenotypes, demonstrating that TOR is required for the execution of developmental cues. In parallel, TOR inhibition enhanced immunity in genotypes with a low CK/GA ratio but not in genotypes with a high CK/GA ratio. TOR‐inhibition mediated disease resistance was found to depend on developmental status, and was abolished in strongly morphogenetic leaves, while being strongest in mature, differentiated leaves. CK repressed TOR activity, suggesting that CK‐mediated immunity may rely on TOR downregulation. At the same time, TOR activity was promoted by GA, and TOR silencing reduced GA sensitivity, indicating that GA signalling requires normal TOR activity. Our results demonstrate that TOR likely acts in concert with CK and GA signalling, executing signalling cues in both defense and development. Thus, differential regulation of TOR or TOR‐mediated processes could regulate the required outcome of development‐defense prioritisation. Summary Statement: Target of Rapamycin (TOR) is positioned at the interface between development and defense, but little is known about the mechanisms by which TOR may regulate shifts between them. Here, we demonstrate that TOR likely acts in concert with cytokinin and gibberellin to execute signalling cues in both defense and development. [ABSTRACT FROM AUTHOR]

SUMMARY: Bacterial fruit blotch, caused by Acidovorax citrulli, is a serious disease of melon and watermelon. The strains of the pathogen belong to two major genetic groups: group I strains are strongly associated with melon, while group II strains are more aggressive on watermelon. A. citrulli secretes many protein effectors to the host cell via the type III secretion system. Here we characterized AopW1, an effector that shares similarity to the actin cytoskeleton‐disrupting effector HopW1 of Pseudomonas syringae and with effectors from other plant‐pathogenic bacterial species. AopW1 has a highly variable region (HVR) within amino acid positions 147 to 192, showing 14 amino acid differences between group I and II variants. We show that group I AopW1 is more toxic to yeast and Nicotiana benthamiana cells than group II AopW1, having stronger actin filament disruption activity, and increased ability to induce cell death and reduce callose deposition. We further demonstrated the importance of some amino acid positions within the HVR for AopW1 cytotoxicity. Cellular analyses revealed that AopW1 also localizes to the endoplasmic reticulum, chloroplasts, and plant endosomes. We also show that overexpression of the endosome‐associated protein EHD1 attenuates AopW1‐induced cell death and increases defense responses. Finally, we show that sequence variation in AopW1 plays a significant role in the adaptation of group I and II strains to their preferred hosts, melon and watermelon, respectively. This study provides new insights into the HopW1 family of bacterial effectors and provides first evidence on the involvement of EHD1 in response to biotic stress. [ABSTRACT FROM AUTHOR]

Background: Menstruation is one of the most significant social, and psychological changes that a female experiences. A mixture of incomplete and erroneous information about the safe and hygienic menstrual practices, as well as improper menstrual management at home or school can be a significant barrier to girls' school attendance and educational experience quality. Menstrual hygiene being a multi-sectoral public health issue needs to be dealt in integration with education, health, women and child development and water sanitation hygiene (WASH). Objective: To assess the knowledge and practices towards menstruation and menstrual hygiene among adolescent girls and its association with the school environment. Method: This study was an analytical cross sectional study, conducted among the 850 adolescent girls of government and private schools in Haldwani. Data was analyzed using SPSS (version 16). Results: More than half of the participants from government and private school showed average knowledge and practices regarding menstruation and menstrual hygiene. Facilities in school related to menstrual hygiene management was found to be associated with menstrual hygiene practices among the study participants. (p<0.05) Conclusion: These findings indicate the need for education about safe and correct menstrual hygiene practices. School environment related to menstrual hygiene management should be improved and strengthened as per the need of adolescent population. [ABSTRACT FROM AUTHOR]

BACKGROUND. Presbyosmia, or aging-related olfactory loss, occurs in a majority of humans over age 65 years, yet remains poorly understood, with no specific treatment options. The olfactory epithelium (OE) is the peripheral organ for olfaction and is subject to acquired damage, suggesting a likely site of pathology in aging. Adult stem cells reconstitute the neuroepithelium in response to cell loss under normal conditions. In aged OE, patches of respiratory-like metaplasia have been observed histologically, consistent with a failure in normal neuroepithelial homeostasis. METHODS. Accordingly, we have focused on identifying cellular and molecular changes in presbyosmic OE. The study combined psychophysical testing with olfactory mucosa biopsy analysis, single-cell RNA-Sequencing (scRNA-Seq), and culture studies. RESULTS. We identified evidence for inflammation-associated changes in the OE stem cells of presbyosmic patients. The presbyosmic basal stem cells exhibited increased expression of genes involved in response to cytokines or stress or the regulation of proliferation and differentiation. Using a culture model, we found that cytokine exposure drove increased TP63, a transcription factor acting to prevent OE stem cell differentiation. CONCLUSIONS. Our data suggest aging-related inflammatory changes in OE stem cells may contribute to presbyosmia via the disruption of normal epithelial homeostasis. OE stem cells may represent a therapeutic target for restoration of olfaction. FUNDING. NIH grants DC018371, NS121067, DC016224; Office of Physician-Scientist Development, Burroughs-Wellcome Fund Research Fellowship for Medical Students Award, Duke University School of Medicine., Introduction The olfactory system detects volatile odors, providing chemosensory input via the first cranial nerve. Olfaction contributes to daily social interactions and quality of life, is important in the detection [...]

Introduction: Endometrial cancer is the seventh most common cancer in women worldwide with Age Standardised Incidence Rate (ASIR) of 8.4 per lac. In Indian subcontinent, the incidence is lesser and the ASIR is 2.1/100,000 women. However, its incidence is on the steady rise in developing part of the world including India. Surgery is the primary treatment and adjuvant radiotherapy is given in patients with high-risk of recurrence and significant change has happened in the management in the last 20 years. From India limited literature is available for management practices for endometrial cancer. Aim: To assess the referral patterns, demography, staging, surgical practices, adjuvant treatment and follow-up policies for endometrial cancer in a tertiary care hospital in northern India. Materials and Methods: A retrospective cross-sectional study was done for patients having endometrial cancer treated between January 2000-December 2015 in a tertiary care hospital in northern India in January 2022. A total of 93 patients having endometrial cancer were referred for radiotherapy. For these patients, their referral patterns, demography, staging, surgical practices, adjuvant treatment and follow-up policies were analysed, retrospectively. Disease Free Survival (DFS) and Overall Survival (OS) were computed by Kaplan-Meier method. Results: The median age at presentation was 55 years. Postmenopausal vaginal bleeding was the commonest symptom 78 (83.87%). Ultrasonography 23 (24.73%) was the preferred first imaging modality. Type 1 endometroid carcinoma was 75 (80.64%) and total abdominal hysterectomy with bilateral salpingo-oophrectomy was done in 82 (88.17%). Adjuvant External Beam Radiotherapy (EBRT) with Brachytherapy (BT) was given in 61 (65.59%), EBRT alone in 7(7.52%) and BT alone given in 11 (11.83%). Median EBRT dose was 50.4 Gy. Vaginal cylinder applicator was used in 69 (95.83%) out of 72 patients receiving BT. A 6.0 Gy/# to a total of 2 fractions were given in 57 (79.16%). Median treated length of vagina was 3 cm (range 2-8 cm). Five year DFS and OS was 25% and 25% and 64% and 62% respectively in worst and best case scenario. Ten (10.75%) patients, all having high-risk had multiple visceral and local recurrence. Conclusion: In patients with endometrial cancer, total abdominal hysterectomy with bilateral salpingo-oophrectomy is commonest surgical practice with adjuvant radiotherapygiven in patients with high risk of recurrence. In a developing country like India, assuring uniformity of treatment protocols is a challenging task. [ABSTRACT FROM AUTHOR]

Background: Malnutrition in children is global issue that may have both short- and long-term irreversible negative health consequences. Objectives: To determine the prevalence of under-nutrition among the under-five children inrural area of Haldwani. Material and methods: Community-based cross-sectional study. Results: Four-hundred children were examined. The prevalence of undernutrition among children was depicted as underweight, stunting and wasting was 7.75%, 9.25% and 4% respectively. [ABSTRACT FROM AUTHOR]

Botrytis cinerea is the causative agent of gray mold disease, and infects more than 1400 plant species, including important crop plants. In tomato, B. cinerea causes severe damage in greenhouses and post-harvest storage and transport. Plant viruses of the Tobamovirus genus cause significant damage to various crop species. In recent years, the tobamovirus tomato brown rugose fruit virus (ToBRFV) has significantly affected the global tomato industry. Most studies of plant-microbe interactions focus on the interaction between the plant host and a single pathogen, however, in agricultural or natural environments, plants are routinely exposed to multiple pathogens. Here, we examined how preceding tobamovirus infection affects the response of tomato to subsequent infection by B. cinerea. We found that infection with the tobamoviruses tomato mosaic virus (ToMV) or ToBRFV resulted in increased susceptibility to B. cinerea. Analysis of the immune response of tobamovirus-infected plants revealed hyperaccumulation of endogenous salicylic acid (SA), upregulation of SA-responsive transcripts, and activation of SA-mediated immunity. Deficiency in SA biosynthesis decreased tobamovirus-mediated susceptibility to B. cinerea, while exogenous application of SA enhanced B. cinerea symptoms. These results suggest that tobamovirus-mediated accumulation of SA increases the plants' susceptibility to B. cinerea, and provide evidence for a new risk caused by tobamovirus infection in agriculture. [ABSTRACT FROM AUTHOR]

This paper suggests the Chebyshev pseudo-spectral approach to solve the variable-order fractional Lane–Emden differential equations (VOFLEDE). The variable-order fractional derivative (VOFD) is defined in the Caputo sense. The proposed method transforms the problem into a set of algebraic equations that can be solved for unknowns. Few examples are discussed to exhibit the viability and effectiveness of the approach. The present study indicates the accuracy, efficiency, and powerfulness of the Chebyshev collocation method in solving the VOFD Lane–Emden equation. Error bound and convergence analysis of the method is also discussed. It is worth noticing that using lesser collocation nodes in computation is another advantage of the technique, which eventually reduces the computational cost. [ABSTRACT FROM AUTHOR]

Background: According to the WHO, antimicrobial resistance (AMR) occurs when bacteria, viruses, fungi, and parasites change over time and no longer respond to medicines making infections harder to treat and increasing the risk of disease spread, severe illness, and death and is a global issue and measures to halt this is the need of the hour. Aims and Objectives: This study aims at identifying awareness as well as knowledge, attitude, perception, and practice regarding AMR and antibiotic use among medical undergraduate students, so to get insight and take appropriate actions to enhance their knowledge that will help in reducing AMR as they are the future prescribers. Materials and Methods: A descriptive cross-sectional study was conducted among 483 undergraduate medical students enrolled in government medical college, Haldwani. A pretested, semi structured questionnaire was designed to collect data from participants through Google forms regarding sociodemographic profile, and behavior of the participants regarding antibiotic use which comprises: Attitude, perceptions, and practice. Results: Majority of study participants have heard about AMR before (97%) of which most of them got information about antibiotic resistance by web/internet (35%). Majority of study participants were aware (>90%) of phenomenon of antibiotic resistance, 98.9% of them were correctly able to identify Amoxicillin and Penicillin as antibiotics, most of them had correct knowledge about role of antibiotics. Majority (83.6%) of participants take antibiotic only after the prescription of doctor, 78.9% of them reported use of antibiotics in the last year. Conclusion: A fair good amount of awareness, knowledge, attitude, perception, and practice regarding AMR and its use was found among study participants. Still, there is scope of improvement in it that can be addressed through giving more emphasis on this in undergraduate teaching curriculum. [ABSTRACT FROM AUTHOR]

Background: The foundation of any nation is children. Malnutrition in children is global issue that may have both short- and long-term irreversible negative health consequences and thus associated with morbidity and mortality. Aims and Objectives: The study aims to determine the prevalence and associated risk factors of under-nutrition among under-five children in rural area of Haldwani. Materials and Methods: A community-based cross-sectional study conducted on Four hundred children residing in the rural field practice area of the Department of Community Medicine, Government Medical College, Haldwani. Results: The prevalence of underweight, stunting, and wasting was 7.75%, 9.25%, and 4%, respectively among under five children. The risk factors found significantly associated with undernutrition and sociodemographic profile were family size, parent's education, mother's occupation, and the socioeconomic class. The maternal factors found significantly associated with undernutrition were intake of iron folic acid tablets during antenatal care and postnatal care period, duration of pregnancy, site of delivery. Prelacteal, colostrum given, exclusive breastfeeding, and age of introducing complementary feeding and occurrence of recurrent diarrhea, recurrent acute respiratory infection, and worm infestation were child characteristics and medical illness found significantly associated with undernutrition. Conclusion: In this study, 17.5% of children were found undernourished. Factors determining undernourishment were parents literacy, social class, type and size of family, iron folic acid taken during pregnancy, feeding practices, immunization status, history of recurrent diarrhea, and other infections in the past 1 year. [ABSTRACT FROM AUTHOR]