Physiological and genomic insights into a psychrotrophic drought-tolerant bacterial consortium for crop improvement in cold, semiarid regions.

The agricultural land in the Indian Himalayan region (IHR) is susceptible to various spells of snowfall, which can cause nutrient leaching, low temperatures, and drought conditions. The current study, therefore, sought an indigenous psychrotrophic plant growth-promoting (PGP) bacterial inoculant with the potential to alleviate crop productivity under cold and drought stress. Psychrotrophic bacteria preisolated from the night-soil compost of the Lahaul Valley of northwestern Himalaya were screened for phosphate (P) and potash (K) solubilization, nitrogen fixation, indole acetic acid (IAA) production, siderophore and HCN production) in addition to their tolerance to drought conditions for consortia development. Furthermore, the effects of the selected consortium on the growth and development of wheat (Triticum aestivum L.) and maize (Zea mays L.) were assessed in pot experiments under cold semiarid conditions (50 % field capacity). Among 57 bacteria with P and K solubilization, nitrogen fixation, IAA production, siderophore and HCN production, Pseudomonas protegens LPH60, Pseudomonas atacamensis LSH24, Psychrobacter faecalis LUR13, Serratia proteamaculans LUR44, Pseudomonas mucidolens LUR70, and Glutamicibacter bergerei LUR77 exhibited tolerance to drought stress (-0.73 MPa). The colonization of wheat and maize seeds with these drought-tolerant PGP strains resulted in a germination index >150, indicating no phytotoxicity under drought stress. Remarkably, a particular strain, Pseudomonas sp. LPH60 demonstrated antagonistic activity against three phytopathogens Ustilago maydis, Fusarium oxysporum, and Fusarium graminearum. Treatment with the consortium significantly increased the foliage (100 % and 160 %) and root (200 % and 133 %) biomasses of the wheat and maize plants, respectively. Furthermore, whole-genome sequence comparisons of LPH60 and LUR13 with closely related strains revealed genes associated with plant nutrient uptake, phytohormone synthesis, siderophore production, hydrogen cyanide (HCN) synthesis, volatile organic compound production, trehalose and glycine betaine transport, cold shock response, superoxide dismutase activity, and gene clusters for nonribosomal peptide synthases and polyketide synthetases. With their PGP qualities, biocontrol activity, and ability to withstand environmental challenges, the developed consortium represents a promising cold- and drought-active PGP bioinoculant for cereal crops grown in cold semiarid regions.

Longitudinally extensive transverse myelitis as an initial manifestation of sarcoidosis: A rare case and its management.

Key Clinical Message: Sarcoidosis-induced LETM represents a rare but life-threatening neurological manifestation of sarcoidosis, characterized by spinal cord inflammation, and associated neurological deficits. Sarcoidosis should be included in the differential diagnosis of LETM, particularly in patients with no lung involvement. Prompt recognition and management are obligatory to optimize outcomes and prevent long-term disability. Abstract: Sarcoidosis is a multisystem inflammatory granulomatous disorder characterized by the formation of noncaseating granulomas. Although sarcoidosis commonly affects the skin, lymph nodes, and lungs, neurological involvement of sarcoidosis has also been reported. Longitudinally extensive transverse myelitis (LETM) is a rare but well-documented serious manifestation of neuroscoidosis. We report a case of LETM caused by sarcoidosis in a 53-year-old male who presented with progressive bilateral lower extremity weakness, urinary retention, and paresthesia. Laboratory evaluations revealed elevated inflammatory markers. Magnetic resonance imaging of the spine showed hyperintense signals consistent with transverse myelitis. Cerebrospinal fluid analysis revealed lymphocytic pleocytosis and elevated protein levels. Chest computed tomography showed hilar lymphadenopathy. A biopsy of the intrathoracic lymph node showed noncaseating granulomas consistent with sarcoidosis. A diagnosis of sarcoidosis-induced LETM was made after ruling out all other possible etiologies. His condition improved gradually after starting high-dose prednisone, mycophenolate, and rehabilitation strategies. Our case underscores the importance of prompt diagnosis and management of sarcoidosis-induced LETM and highlights that sarcoidosis must be included among differential diagnoses of LETM, especially in cases with no lung involvement.

Detecting and monitoring concerns against HPV vaccination on social media using large language models.

Health risks due to preventable infections such as human papillomavirus (HPV) are exacerbated by persistent vaccine hesitancy. Due to limited sample sizes and the time needed to roll out, traditional methodologies like surveys and interviews offer restricted insights into quickly evolving vaccine concerns. Social media platforms can serve as fertile ground for monitoring vaccine-related conversations and detecting emerging concerns in a scalable and dynamic manner. Using state-of-the-art large language models, we propose a minimally supervised end-to-end approach to identify concerns against HPV vaccination from social media posts. We detect and characterize the concerns against HPV vaccination pre- and post-2020 to understand the evolution of HPV vaccine discourse. Upon analyzing 653 k HPV-related post-2020 tweets, adverse effects, personal anecdotes, and vaccine mandates emerged as the dominant themes. Compared to pre-2020, there is a shift towards personal anecdotes of vaccine injury with a growing call for parental consent and transparency. The proposed approach provides an end-to-end system, i.e. given a collection of tweets, a list of prevalent concerns is returned, providing critical insights for crafting targeted interventions, debunking messages, and informing public health campaigns.

Sorption and mobility assessment of tembotrione in soils of upper, trans and middle Gangetic plain zones of India.

The presence of undesired agrochemicals residues in soil and water poses risks to both human health and the environment. The behavior of pesticides in soil depends both on the physico-chemical properties of pesticides and soil type. This study examined the adsorption-desorption and leaching behavior of the maize herbicide tembotrione in soils of the upper (UGPZ), trans (TGPZ) and middle Gangetic plain zones of India. Soil samples were extracted using acetone followed by partitioning with dichloromethane, whereas liquid-liquid extraction using dichloromethane was used for aqueous samples. Residues of tembotrione and its metabolite TCMBA, {2-chloro-4-(methylsulfonyl)-3-[(2,2,2-trifluoroethoxy) methyl] benzoic acid}, were quantified using liquid chromatography-tandem mass spectrometry. The data revealed that tembotrione adsorption decreased with increasing pH and dissolved organic matter but increased with salinity. The maximum adsorption occurred at pH 4, 0.01 m sodium citrate and 4 g/L NaCl, with corresponding Freundlich constants of 1.83, 2.28 and 3.32, respectively. The hysteresis index <1 indicated faster adsorption than desorption. Leaching studies under different flow conditions revealed least mobility in UGPZ soil and high mobility in TGPZ soil, consistent with groundwater ubiquity scores of 4.27 and 4.81, respectively. Soil amendments decreased tembotrione mobility in the order: unamended > wheat straw ash > wheat straw > farm yard manure > compost. The transformation of tembotrione to TCMBA and its mobility in soil columns were also assessed.

Prediction of axial capacity of corrosion-affected RC columns strengthened with inclusive FRP.

The primary cause behind the degradation of reinforced concrete (RC) structures is the propagation of corrosion in the steel-RC structures. Nowadays, numerous retrofitting techniques are available in the construction sector. Fiber-reinforced polymer (FRP) is one of the efficient rehabilitation measures that can be implemented on corroded structures to enhance structural capacities. However, the estimation of axial strength of FRP-strengthened columns affected by corrosion has been a challenging and tedious task in the laboratory as well as on the site. Considering such shortcomings, the prediction of axial capacity can be done using various analytical methods and artificial intelligence (AI) techniques. In this study, a comprehensive dataset of circular columns was extracted from the literature to predict the axial strength of FRP-wrapped and unstrengthened RC corroded columns. The laboratory results from the assembled dataset were compared to corresponding values estimated using relevant design codes provided by American Concrete Institute (ACI 440.2R-17 and ACI 318-19), and Bureau of Indian Standard (IS 456:2000). Five machine learning models were employed on columns to predict the axial load carrying capacity of FRP-strengthened and un-strengthened RC corroded columns. The results discovered that the extreme gradient boosting (XGBoost) model achieves superior accuracy with the least errors and could be used by the scientific community and FRP applicators to forecast the axial performance of corroded columns strengthened with and without FRP. The findings from the design codes revealed that prediction errors were available in high margins. Furthermore, feature importance analysis was conducted using the Shapley Additive exPlanation algorithm to know the contribution and influence of each input parameter on axial capacity. The feature analysis found that unconfined compressive strength of concrete plays an important role in deciding the axial capacity of columns. Moreover, to enhance the precision of axial capacity computation and improving the overall efficacy in engineering practice, a web-based user-friendly interface was developed for FRP applicators and engineers to simplify the process.

Comparison of bone health among pre-menopausal and post-menopausal females in rural Eastern India: A pilot study.

PURPOSE: The aim of this study was to identify the at-risk female population (pre- and post-menopausal), identify the risk factors for low bone mineral density (BMD) and assess the knowledge of the subjects regarding osteoporosis by Osteoporosis Knowledge Assessment Tool (OKAT) in both the groups and to determine areas for early intervention in a predominantly rural and tribal area of Eastern India. STUDY DESIGN: This was a cross-sectional hospital-based study conducted in a predominant tribal and rural area of Eastern India. Females who were pre- and post-menopausal without a prior diagnosis of osteoporosis were included in the study. MAIN OUTCOME MEASURES: Factors affecting osteoporosis and quantified knowledge regarding the disease. RESULTS: A total of 388 females were included in the study (pre-menopausal = 190 and post-menopausal = 198). Although no significant difference was noted in the age at menarche between both the groups, a gradual significant shift in the age at menarche was noted in the younger females (p = .031). The mean OKAT score in the pre-menopausal and post-menopausal group was 9.5 ± 3.4 and 9.2 ± 3.5, respectively. 80% of females in the pre-menopausal group had normal T-scores whereas only 25% of the females in the post-menopausal group had normal T-scores. CONCLUSION: Targeted educational programs which influence the preventive health behaviour in general and osteoporosis knowledge in particular would bridge this gap. Peer-led community intervention programs which focus on behaviour change with respect to lifestyle and diet modification in the younger population should be the step ahead to reduce the prevalence of the disease.

MXene/biochar composites for enhanced wastewater reclamation and bioenergy production: A kinetics and thermodynamics study.

The study explores the synthesis and utilization of biochar (BC) and multi-layer MXene to MXene/biochar (MB) composites for wastewater treatment. Simultaneously, it also investigates their energy generation potential through biomass and soil property assessments. The integrated column and batch treatments have shown significant results, elevating total dissolved solids from 63.7 to 125.5 mg L-1 with column treatment, while reducing them to 6.37 % and 1.35 % with BC and MB treatment, respectively. BC with high carbon content, demonstrated increased hydrophobicity, which was amplified by the integration of MXene, thereby enhancing its potential for advanced wastewater treatment. Treated wastewater exhibited elevated nutrient concentrations (Ca, Cu, Fe, K, Na, and NH4+), promoting the growth of Pennisetum purpureum. WW_B shows promising energy potential, with a higher heating value of 25.03 MJ kg-1 and a lower heating value of 23.57 MJ kg-1. They demonstrated high volatile matter exceeding 70.9 wt %, and a fixed carbon from 10.02 to 27.53 wt %, signifying their potential for efficient conversion and bio-oil yield during pyrolysis. The ultimate analysis emphasized significant carbon, with oxygen content ranging from 43.42 to 47.78 wt %., influencing combustion characteristics. MT_B exhibited its suitability for energy production through thermochemical conversion, underlined by its high flammability and low volatile ignition values. In the absence of BC, the Ea ranged from 24.77 to 77.88 kJ mol-1 in wastewater and from 21.67 to 69.6 kJ mol-1 in MB treated wastewater. Meanwhile, when soil contained BC and was irrigated with wastewater, the Ea varied from 24.66 to 80.91 kJ mol-1. In the case of MB treated wastewater, it ranged from 25.01 to 75.79 kJ mol-1. The research thereby affirms the potential of MB composites to advance water and energy sustainability setting us for broader nexus-based applications.

Insight into physico-chemical properties and microbial community structure of biogas slurry from household biogas plants of sub-Himalaya for its implications in improved biogas production.

Numerous metagenomics studies, conducted in both full-scale anaerobic digesters and household biogas plants, have shed light on the composition and activity of microbial flora essential for optimizing the performance of biogas reactors, underscoring the significance of microbial community composition in biogas plant efficiency. Although the efficiency of household biogas plants in the sub-Himalayan region has been reported, there is no literature evidence on the microbial community structure of such household biogas plants in the sub-Himalayan region. The current study evaluated the physico-chemical properties and bacterial community structure from the slurry samples of household biogas plants prevalent in the sub-Himalayan region. The slurry samples were observed to be rich in nutrients; however, their carbon and nitrogen contents were higher than the recommended standard values of liquid-fermented organic manure. The species richness and diversity indices (Chao1, Shannon, and Simpson) of household biogas plants were quite similar to the advanced biogas reactors operating at mesophilic conditions. 16S rRNA gene amplicon sequencing reveals microbial diversity, showing a higher abundance of Firmicutes (70.9%) and Euryarchaeota (9.52%) in advanced biogas reactors compared to household biogas plants. Microbial analysis shows a lack of beneficial microbes for anaerobic digestion, which might be the reason for inefficient biogas production in household biogas plants of the sub-Himalayan region. The lack of efficient bacterial biomass may also be attributed to the digester design, feedstock, and ambient temperatures. This study emphasized the establishment of efficient microbial consortia for enhanced degradation rates that may increase the methane yield in biogas plants.

Identification of circulatory microRNA based biomarkers for early pregnancy diagnosis in buffalo.

Introduction: The most crucial factor in improving animal reproduction efficiency is early pregnancy diagnosis. Early diagnosis not only reduces the time interval between two calvings but also aids farmers in identifying open animals, thereby preventing significant milk production losses. Therefore, the objective of this study was to discover circulatory miRNAs that would be useful for early pregnancy diagnosis in buffalo. Material and methods: Blood samples were taken on 0, 6th, 12th, and 18th day after artificial insemination from pregnant animals (n = 30) and non-pregnant animals (n = 20). During these stages of pregnancy, total RNA was extracted, and a small RNA library was subsequently generated and sequenced on the Illumina platform. Subsequently, Real-time PCR was used to validate the findings. Results and discussion: There were 4,022 miRNAs found during the pregnancy, with 15 of those lacking sequences and 4,007 having sequences already in the database. From the beginning of pregnancy until the 18th day, 25 of these miRNAs showed a substantial shift in expression levels in the maternal blood, with a change more than two logs. Furthermore, based on qPCR results, 19 miRNAs were found to be more abundant in pregnant animals than in non-pregnant animals. We used target prediction analysis to learn how maternally expressed miRNAs relate to fetal-maternal communication. In conclusion, miRNA based biomarkers that could be associated with the diagnosis of pregnancy were identified including miR-181a and miR-486 highly upregulated on the 18th day of pregnancy. This study also provides a comprehensive profile of the entire miRNA population in maternal buffalo blood during the early stages of pregnancy.

Diffusion-Weighted MRI in Perianal Abscess: Role and Comparison With Contrast-Enhanced MRI.

BACKGROUND: Perianal abscess is a clinical infective and/or inflammatory collection in the perianal region, one entity of a large group of anal and perianal disorders. Perianal abscesses are often seen as a complication of grade 2 and grade 4 perianal fistulas from St. James's University Hospital classification. Several imaging modalities have been tried in the past for adequate assessment of perianal abscess with contrast-enhanced magnetic resonance imaging (CE-MRI) providing the most accurate results. Diffusion-weighted imaging (DWI) is an emerging sequence that can provide comparable results to CE-MRI in diagnosing and characterizing perianal abscess. The main objective of this study is to assess the role of DWI in adequate identification and assessment of perianal abscess and compare the final results with contrast-enhanced images. METHODS: Twenty patients with complicated perianal fistula with clinically suspected perianal abscess were evaluated with DWI and CE-MRI. This study was a comparative cross-sectional study conducted in the Department of Radiodiagnosis and Imaging, All India Institute of Medical Sciences, Bhopal, India. Chi-square test was done to find the association between categorical variables. Kappa test was used to find the agreement between two different tests. Receiver operating characteristics (ROC) analysis was done to estimate the area under the curve in predicting the outcome. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy were used to measure the validity of the tests. RESULTS: DWI is a very sensitive MRI sequence and is equivalent to CE-MRI to detect the location and analyzing the loco-regional extent of abscess in complicated perianal fistula cases. DWI is also very sensitive and superior to T2 short tau inversion recovery (STIR) in differentiating perianal abscess from perianal inflammation without abscess. CONCLUSION: DWI can be used as an alternative to post-contrast fat-suppressed MRI in precisely defining the location and extent of anal and perianal abscesses and disease activity in complicated fistula cases.

Impact of Implementing Paris System on Diagnostic Precision and Management of Urinary Bladder Neoplasms.

The diagnosis of atypia has always been under question both by the pathologist and the clinician. It was one of the main aims of the Paris system (TPS) to reduce the number of cases under the AUC (Atypical urothelial cells) category. With the strict criteria laid down by the Paris system, the rate of diagnosis of this category has reduced markedly. This study was done to test the impact of implementing TPS categories and criteria in comparison to our previously used system. TPS is one of the important deciding factors for the management of the patient. The management of patients with AUC diagnosis often varies depending on the treating physician (urologist/nonurologist). For further categorization of the diagnosis of AUC, markers like p53 and Ki67 can be used. One hundred urinary cytology specimens received for the period of 6 months were included in the study. The presentation of the categorical variables was done in the form of numbers and percentages (%). Interrater kappa agreement was used to find out the strength of the agreement between the Paris system and the traditional system. Using histopathological diagnosis as the gold standard, sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic accuracy were calculated. Immunohistochemistry was performed on the cell block for Ki67 and p53, and their values were correlated with histopathological examination, using Spearman's rank correlation. The interrater kappa agreement analyzed between the traditional reporting system and the Paris system was 0.522. Around 32% (6/19) of cases that were reported as AUC by the traditional system were recategorized under negative for high-grade urothelial carcinoma (NHGUC) by the Paris system. Thus, obliviating the need for further management and decreasing the unnecessary cost of the health care system with a decrease in patient anxiety. Histopathology was available in 28 cases and diagnostic accuracy of urine cytology classified by TPS was 89.2% with a sensitivity of 94.4%, specificity of 80%, positive likelihood ratio of 89.4, and negative likelihood ratio of 88.6. The correlation coefficient of p53 with grading of carcinoma was found to be strong at 0.864. The correlation coefficient of Ki67 with grading of carcinoma was also as strong as 0.885. TPS along with immunohistochemistry improves the performance of urine cytology by reclassifying the AUC category into other groups and increases the sensitivity for detecting HGUC.

Advancing nanobubble technology for carbon-neutral water treatment and enhanced environmental sustainability.

Gaseous nanobubbles (NBs) with dimensions ranging from 1 to 1000 nm in the liquid phase have garnered significant interest due to their unique physicochemical characteristics, including specific surface area, low internal gas pressure, long-term stability, efficient mass transfer, interface potential, and free radical production. These remarkable properties have sparked considerable attention in the scientific community and industries alike. These hold immense promise for environmental applications, especially for carbon-neutral water remediation. Their long-lasting stability in aqueous systems and efficient mass transfer properties make them highly suitable for delivering gases in the vicinity of pollutants. This potential has prompted research into the use of NBs for targeted delivery of gases in contaminated water bodies, facilitating the degradation of harmful substances and advancing sustainable remediation practices. However, despite significant progress in understanding NBs physicochemical properties and potential applications, several challenges and knowledge gaps persist. This review thereby aims to summarize the current state of research on NBs environmental applications and potential for remediation. By discussing the generation processes, mechanisms, principles, and characterization techniques, it sheds light on the promising future of NBs in advancing environmental sustainability. It explores their role in improving oxygenation, aeration, and pollutant degradation in water systems. Finally, the review addresses future research perspectives, emphasizing the need to bridge knowledge gaps and overcome challenges to unlock the full potential of this frontier technology for enhanced environmental sustainability.

Leucaena leucocephala succinate based polyelectrolyte complexes for colon delivery of synbiotic in management of inflammatory bowel disease.

Polyelectrolyte complexes (PECs) formed by the interaction between oppositely charged polymers have emerged as promising carriers for accomplishing colon-specific release. In this study, we have explored the potential of polyelectrolyte complexes between a succinate derivative of Leucaena leucocephala galactomannan and cationic guar gum for colon delivery of synbiotic. The PECs were prepared using a polyelectrolyte complexation method and characterized. The PECs exhibited excellent stability, with high encapsulation efficiency for both probiotics (95.53 %) and prebiotics (83.33 %). In vitro studies demonstrated enhanced survivability and proliferation of the encapsulated probiotics in the presence of prebiotics (93.29 %). The SEM images revealed a smooth and firm structure with reduced number of pores when both prebiotic and probiotic were encapsulated together. The treatment with synbiotic PECs in acetic acid induced IBD rats significantly relieves colitis symptoms as was evident from colon/body ratio, DAI score and histopathology studies. An increase in the protein and reduced glutathione levels and reduction in superoxide dismutase activity was observed in colitic rats that received synbiotic treatment as compared to colitic rats. Overall, this study highlights the potential of Leucaena leucocephala succinate-cationic guar gum PECs as a promising system for colon-specific synbiotic delivery, with implications for improved gut health and the treatment of various gastrointestinal disorders.

Physio-biochemical responses and crop performance analysis in chickpea upon botanical priming.

Chickpea is a highly nutritious protein-rich source and one of the major crops to alleviate global malnutrition, but poor seed quality affects its productivity. Seed quality is essential for better crop establishment and higher yields, particularly in the uncertain climate change. The present study investigated the impact of botanical priming versus hydropriming and bavistin seed treatment on chickpea seeds. A detailed physiological (germination percentage, root and shoot length, vigour index) and biochemical (amylase, protease, dehydrogenase, phytase, and lipid peroxidation) analysis was carried out in order to assess the effect of priming treatments. Turmeric-primed seeds showed better germination rate (94.5%), seedling length, enzyme activity, and lower malondialdehyde (MDA) content. Sodium dodecyl-sulfate polyacrylamide gel electrophoresis (SDS-PAGE) analysis revealed the expression of minor polypeptides of albumin and globulin in the primed seeds. Moreover, field experiments indicated increased crop growth, vigour, days to 50% flowering, yield and its attributing traits in turmeric-primed seeds. Botanical priming can increase chickpea yield by up to 16% over the control group. This low-cost and eco-friendly technique enhances seed and crop performance, making it a powerful tool for augmenting chickpea growth. Therefore, chickpea growers must adopt botanical priming techniques to enhance the quality of seed and crop performance. Moreover, this approach is environmentally sustainable and can help conserve natural resources in the long term. Therefore, this new approach must be widely adopted across the agricultural industry to ensure sustainable and profitable farming practices.

Therapeutic targeting of telomerase ameliorates experimental choroidal neovascularization.

Choroidal neovascularization (CNV) is the principal driver of blindness in neovascular age-related macular degeneration (nvAMD). Increased activity of telomerase, has been associated with endothelial cell proliferation, survival, migration, and invasion in the context of tumor angiogenesis. Expanding on this knowledge, we investigated the role of telomerase in the development of CNV in mouse model. We observed increased gene expression and activity of telomerase in mouse CNV. Genetic deficiency of the telomerase components, telomerase reverse transcriptase (Tert) and telomerase RNA component (Terc) suppressed laser-induced CNV in mice. Similarly, a small molecule inhibitor of TERT (BIBR 1532), and antisense oligonucleotides (ASOs) targeting Tert and Terc reduced CNV growth. Bone marrow chimera studies suggested that telomerase activity in non-bone marrow-derived cells is crucial for the development of CNV. Comparison of BIBR 1532 with VEGF neutralizing therapeutic strategy in mouse revealed a comparable level of angiosuppressive activity. However, when BIBR and anti-VEGF antibodies were administered as a combination at sub-therapeutic doses, a statistically significant suppression of CNV was observed. These findings underscore the potential benefits of combining sub-therapeutic doses of BIBR and anti-VEGF antibodies for developing newer therapeutic strategies for NV-AMD. Telomerase inhibition with BIBR 1532 suppressed induction of multiple cytokines and growth factors critical for neovascularization. In conclusion, our study identifies telomerase as a promising therapeutic target for treating neovascular disease of the eye and thus provides a proof of principle for further exploration of telomerase inhibition as a novel treatment strategy for nvAMD.

Efficacy of Inclisiran in Patients Having Familial Hypercholesterolemia: Heterozygous Compared to Homozygous Trait, a Systematic Review and Meta-analysis.

OBJECTIVE: To find out whether inclisiran sodium has different efficacy in heterozygous familial hypercholesterolemia (HeFH) and homozygous familial hypercholesterolemia (HoFH) patient groups. METHODS: We conducted the systematic review and meta-analysis of ORION clinical trials. PubMed, Embase, and Clinicaltrials.gov databases were searched for the relevant studies. Atheroscalerotic parameters considered for our objective were low-density lipoprotein cholesterol, total cholesterol, proprotein convertase subtilisin/kexin type 9 (PCSK9), apolipoprotein B, and nonhigh-density lipoprotein cholesterol. Primary outcomes were the percentage difference in atheroscalerotic parameters at follow-up relative to baseline values. Our study examined these primary outcomes to determine whether there is a statistically significant difference between the HeFH and HoFH groups. Risk of bias was assessed by the Cochrane risk of bias tool. Meta-analysis was performed when at least 2 studies reported on the same variable. RESULTS: Four ORION clinical trials provided the data related to the mean difference in the atheroscalerotic parameters at follow-up relative to baseline, of HeFH and HoFH patient populations, after administration of 300 mg inclisiran subcutaneously. We pooled together these mean differences for each group and applied a statistical test to analyze if the values were significantly different between the groups. The results of our study unveiled the significant difference in pooled mean differences in low-density lipoprotein cholesterol (HeFH: -48.62%; HoFH: -9.12%; P < 0.05), total cholesterol (HeFH: -30.31%; HoFH: -11.50%; P < 0.05), apolipoprotein (HeFH: -39.97%; HoFH: -14.68%; P < 0.05), and nonhigh-density lipoprotein (HeFH: -44.51%; HoFH: -12.22%; P < 0.05) between HeFH and HoFH groups. However, the difference in pooled mean difference in PCSK9 values (HeFH: -68.41%; HoFH: -56.25%; P = 0.2) between HeFH and HoFH groups was statistically insignificant. Studies were of high quality. CONCLUSIONS: There was a significant difference in the reductions in atherosclerotic lipid parameters in heterozygous and homozygous populations after the administration of inclisiran except for PCSK9 parameter. Further studies are needed to support this conclusion.

Uncommon Presentation: A Case Report on a Rare Vulvar Fibroadenoma.

Vulval fibroadenoma is an uncommon, benign tumor that originates from ectopic breast tissue or mammary-like glands in the anogenital region. Only a limited number of cases have been documented in medical literature. Typically occurring in young and middle-aged women, this condition, when surgically removed, generally exhibits a favorable prognosis with a low recurrence rate. We report a case of vulvar fibroadenoma wherein the patient exhibited a groin region mass. The mass was then excised and examined histologically. Histological examination of the polypoidal tissue section unveiled a clearly defined lesion comprising both epithelial and stromal components.

Molecular and Structural Insights into Buffalo Interleukin-17A.

Interleukin-17A is a pro-inflammatory cytokine that plays a key role in the immune response to many pathogens and implicated in autoimmune diseases. This molecule is also involved in providing protection to many bacterial and fungal infections of gastro-intestinal tract and respiratory mucosa. Although molecular aspect of IL-17A has been studied in few species, no data are available for buffalo, which is one of the major sources of milk production in India. Therefore, in the present study, IL-17A gene of Indian Murrah Buffalo origin was cloned, expressed, and analyzed using bioinformatic tools. The coding sequence of buffalo IL-17A gene was cloned in prokaryotic expression vector (pET-28a) followed by its expression, purification, and characterization. A computational analysis was performed to understand the sequence, structure, and evolutionary relationship of buIL-17A. It revealed that the length of buIL-17A sequence without signal peptide is 132 amino acids as in cattle. However, sequence identity is found to be 99% due to one amino substitution difference between buffalo and cattle. After analysis, it can be concluded that buIL-17A recombinant protein can be used as a potential immunobiological reagent for diagnostic and therapeutic purpose.

Acaricide resistance status of deltamethrin and coumaphos in Hyalomma anatolicum ticks collected from different districts of Haryana.

To study the acaricide resistance status and possible mechanisms of action in conferring resistance to commonly used acaricides (deltamethrin and coumaphos), Hyalomma anatolicum ticks were collected from 6 dairy farms of Hisar and Charkhi Dadri districts of Haryana. By using standard larval packet test, H. anatolicum tick larvae of Charkhi Dadri isolates were found to be susceptible (100% mortality) to both the acaricides. Level-I resistance against coumaphos was recorded from four isolates, whereas, level-II was observed in only one isolate, collected from Hisar. One isolates (Kaimri) from Hisar also showed level-I resistance against deltamethrin. Biochemically, the ticks having higher values of resistance factor (RF) against coumaphos were found to possess increased enzymatic activity of α-esterase, ß-esterase, glutathione-S-transferase (GST) and mono-oxygenase enzymes, whereas, the monoamine oxidase did not show any constant trend. However, the RF showed a statistical significant correlation with GST only. Native PAGE analysis of H. anatolicum ticks revealed the presence of nine types of esterases (EST-1 h to EST-9 h) by using napthyl acetate as substrate. In the inhibitory assay, esterases were found to be inhibited by PMSF, indicating the presence of serine residue at catalytic triad. The partial cds of carboxylesterase and domain II of sodium channel genes were sequenced to determine any proposed mutations in resistant isolates of H. anatolicum ticks, however, no mutations were observed in either gene, indicating that increased expression of detoxification enzymes as a possible mechanism for resistance development, in the current study.