Comparative Analysis of Stress Levels Among Undergraduate Students at St. John's College, Agra.

Background Stress is prevalent among college students, impacting their mental health and academic performance. Understanding the distribution and determinants of stress levels in students is crucial for developing effective interventions. This study aims to assess the prevalence of stress and its association with sociodemographic factors among undergraduate students at St. John's College, Agra, India. Materials and methods A descriptive cross-sectional study was conducted between August 1, 2023, and December 31, 2023, involving 160 undergraduate students from B.A., B. Com., and B.Sc. programs. Students were selected using a stratified random sampling technique. Stress levels were measured using the Perceived Stress Scale (PSS), which classifies low, moderate, and high levels. Data were collected through a validated, semi-structured questionnaire administered via Google Forms. Statistical analysis was performed using IBM SPSS Statistics for Windows, Version 29 (Released 2023; IBM Corp., Armonk, New York), with descriptive statistics and chi-square tests used to examine associations between stress levels and sociodemographic variables. Results The study found that 103 (64.4%) of students experienced moderate stress, 34 (21.3%) reported high perceived stress, and 23 (14.4%) had low stress. A significant association was observed between stress levels and gender (p = 0.022), with female students more likely to experience high stress. Additionally, urban students reported higher stress levels than their rural counterparts (p = 0.012). However, no significant differences in stress levels were found across different courses. Conclusion The study reveals a substantial prevalence of moderate to high stress among college students, particularly among females and those from urban areas. These findings suggest the need for targeted stress management interventions to support student well-being. Further research is recommended to explore the underlying causes of stress and develop comprehensive stress reduction strategies in the student population.

Correlation of glycosylated hemoglobin (HbA1c) with retinal nerve fiber layer (RNFL) thickness and central macular thickness (CMT) in the diabetic population in North India.

PURPOSE: The current study was aimed to find correlation of glycosylated hemoglobin with retinal nerve fiber layer thickness (RNFLT) and central macular thickness (CMT) in the diabetic population in North India. METHODS: This was a cross-sectional observational study of 300 diabetic patients divided equally in two groups with and without retinopathy, and 150 people were included as control. The study was conducted from October 2020 to August 2022. All patients underwent slitlamp fundoscopy with a +78 D lens, and spectral-domain (SD) optical coherence tomography was performed to measure the RNFLT and CMT, and the staging of retinopathy was done as per the ETDRS classification. Along with that, blood investigations were ordered, including fasting (FBS) and post-prandial (PPBS) blood sugar and glycosylated hemoglobin (HbA1c). Quantitative variables were compared using one-way analysis of variance, or Kruskal-Wallis test was applied for inter-group comparison, followed by a Student Newman Keuls Test. RESULTS: The mean age of the patients in the diabetic group with retinopathy was 52.62 ± 9.38 years. The overall male: female ratio was 3:2. The mean FBS in the diabetic group with retinopathy was 146.54 ± 45.40mg/dl; the PPBS and HbA1c in the same were 210.39 ± 63.71mg/dl and 7.85 ± 1.33%, respectively. RNFL thinning was found in all four quadrants in diabetics irrespective of the status of retinopathy (P-value = 0.000) with a significant weak negative (r<0.4) correlation of glycosylated hemoglobin values with RNFLT in the inferior (r value = -0.300, P-value = 0.000) and superior (r value = -0.236, P-value = 0.004) quadrants of right eyes and in inferior (r value = -0.176, p- value = 0.031), superior (r value = -0.222, P value = 0.006), and nasal quadrants (r value = -0.166, p- value = 0.043) of left eyes in diabetics with retinopathy. However, in diabetics without retinopathy, no correlation was found. On correlating HbA1c with CMT, a weak positive (r<0.3) association existed in both eyes in the diabetic group without retinopathy (r = 0.020 and 0.048 for OD and OS, respectively) and diabetics with retinopathy (r = 0.152 and 0.127 for OD and OS, respectively). However, the association was not found to be significant in either of the groups (P-value > 0.05). CONCLUSION: The study concluded that neurodegeneration occurs in diabetic retinopathy as evident with nerve fiber layer thinning, and it is negatively correlated with glycosylated hemoglobin (HbA1c).

Synergistic action of lactoferrin and its derived functional fragments as a promising therapeutic agent in combating mucormycosis.

Aim: Currently, we have limited armamentarium of antifungal agents against Mucorales. There is an urgent need to discover novel antifungal agents that are effective, safe and affordable. Materials & methods: In this study, the anti-Mucorale action of native lactoferrin (LF) and its functional fragments CLF, RR6 and LFcin against three common Mucorale species are reported. The synergistic action of LF with antifungal agents like amphotericin B, isavuconazole and posaconazole was analyzed using checkerboard technique. Results: All the three mucor species showed inhibition when treated with fragments. The checkerboard assay confirmed that native LF showed the best synergistic action against Mucorales in combination with Amphotericin B. Conclusion: These results highlight the potential therapeutic value of native LF against Mucorales.

Black fungus, or 'mucormycosis', is a dangerous fungal infection. Normally, it affects people with a weakened immune system. It is only treatable when diagnosed early. It spreads by breathing the fungus in, eating contaminated food or direct contact with an infected wound. There are not many medicines that can treat this type of fungus, so it is important to find new ones. In this study, we tested a natural protein called lactoferrin and some of its building blocks, called peptides, to see if they could stop the fungus from growing. Lactoferrin and its peptides could stop the fungus from growing, especially when used with a medicine called amphotericin B. This means that lactoferrin could potentially be a helpful treatment for this fungal infection.

Exploring the global landscape of work-life balance research: A bibliometric and thematic analysis.

The research on work-life balance (WLB) published in journals with a Scopus index between 2011 and 2022 is carefully examined in this work. Our research attempts to clarify the evolution and trends in WLB research and the importance of publications that Scopus indexes. After analyzing 2717 research articles, we found that WLB publications have a significant annual growth rate of 14.71 %, which suggests that the trend continues to grow. Significant changes are seen, with 1888 papers produced between 2017 and 2022 highlighting a notable increase in interest in the field. With 1608 papers, social sciences account for the majority of WLB research. With 54 publications, Griffith University (Australia) is the most affiliated institution. With 30 papers, the "Economic and Social Research Council of the United Kingdom" became the primary source of financing. The most prolific author, with nine publications, is Lingard H. At the same time, co-citation analysis reveals 168 co-cited authors. The United States (USA), the United Kingdom (U.K.), and Australia (A.U.) are the top three producing nations. A thematic analysis reveals ten major WLB themes, from work stress to difficulties with human resource management. This study provides crucial insights for policymakers and leaders to address work-life balance issues effectively. Using tools like Gephi or CiteSpace, we could deepen our understanding through advanced analysis methods such as page rank and network visualization.

Assessing the Brainstem Auditory Evoked Potentials in Subjects with Family History of Hypertension.

Background: Hypertension (HTN) has a genetic predisposition and it also impairs microcirculation, thereby, affecting the well vascularized structures like the brainstem and causing changes in Brainstem Auditory Evoked Potentials (BAEPs). Purpose: To find out the usefulness of BAEPs as a screening tool in apparently healthy individuals with a family history of HTN. Methods: One hundred and ten volunteers, aged 17 to 23 years, were enrolled in the study as participants with proper consent. After excluding the subjects with existing diseases or co-morbidities (e.g. diabetes, HTN, schizophrenia, neuropathy, etc.), those on ototoxic or neurotoxic drugs, a preliminary physical examination was performed, following which BAEPs were recorded with a proper device. Statistical analysis is done with SPSS 2016 software using the chi-square test. Results: A consistent distortion in the inter-peak latency of III-V waves is noted when a family history of HTN is present in either parent or maternal grandparents. Other statistically significant findings are present in V/I% (HTN in mother), wave I (HTN in paternal grandfather), wave III (HTN in maternal grandfather), and inter-peak latency I-V (HTN in maternal grandmother). Conclusion: BAEP may be used as a screening tool in individuals with a family history of HTN with supportive evidence from further studies in the near future.

Comprehensive Review on the Virulence Factors and Therapeutic Strategies with the Aid of Artificial Intelligence against Mucormycosis.

Mucormycosis, a rare but deadly fungal infection, was an epidemic during the COVID-19 pandemic. The rise in cases (COVID-19-associated mucormycosis, CAM) is attributed to excessive steroid and antibiotic use, poor hospital hygiene, and crowded settings. Major contributing factors include diabetes and weakened immune systems. The main manifesting forms of CAM─cutaneous, pulmonary, and the deadliest, rhinocerebral─and disseminated infections elevated mortality rates to 85%. Recent focus lies on small-molecule inhibitors due to their advantages over standard treatments like surgery and liposomal amphotericin B (which carry several long-term adverse effects), offering potential central nervous system penetration, diverse targets, and simpler dosing owing to their small size, rendering the ability to traverse the blood-brain barrier via passive diffusion facilitated by the phospholipid membrane. Adaptation and versatility in mucormycosis are facilitated by a multitude of virulence factors, enabling the pathogen to dynamically respond to various environmental stressors. A comprehensive understanding of these virulence mechanisms is imperative for devising effective therapeutic interventions against this highly opportunistic pathogen that thrives in immunocompromised individuals through its angio-invasive nature. Hence, this Review delineates the principal virulence factors of mucormycosis, the mechanisms it employs to persist in challenging host environments, and the current progress in developing small-molecule inhibitors against them.

Silt erosion and cavitation impact on hydraulic turbines performance: An in-depth analysis and preventative strategies.

The primary issues in the Himalayan Rivers are sediment and cavitation degradation of the hydroelectric power turbine components. During the monsoon season, heavy material is transported by streams in hilly areas like the Himalayas through regular rainfalls, glacial and sub-glacial hydrological activity, and other factors. The severe erosion of hydraulic turbines caused by silt abrasion in these areas requires hydropower facilities to be regularly shut down for maintenance, affecting the plant's overall efficiency. This article provides an in-depth examination of the challenges that can lead to cavitation, silt erosion, and a decrease in the efficiency of various hydroelectric turbines, and it demands attention on the design, manufacture, operation, and maintenance of the turbines. This study's main objective is to critically evaluate earlier theoretical, experimental, and numerical evaluation-based studies (on cavitation and silt erosion) that are provided and addressed throughout the study. As a part of this study, various strategies for mitigating the effects of these problems and elongating the time that turbine may be utilized before they must be replaced have been provided.

Pollution indices and correlation of heavy metals contamination in the groundwater around brick kilns in Jammu and Kashmir, India.

The present investigation focuses on assessing the water quality of groundwater surrounding brick kilns in the Jammu district of Jammu and Kashmir (J&K). At 43 different brick kiln sites in both north and south regions of Jammu, concentrations of heavy metals were measured using established techniques. The elements zinc, copper, iron, lead, cadmium, nickel, and manganese were analyzed utilizing an Atomic Absorption Spectrophotometer (AAS). The pollution load index value was consistently below unity across all sites, suggesting an absence of pollution and making the water suitable for consumption. The average concentrations, listed in ascending order, were found to be 0.38 mg/L for copper, 0.31 mg/L for zinc, 0.01 mg/L for iron, and 0.09 mg/L for manganese. Notably, concentrations of lead, cadmium, and nickel were found below the detectable levels. Evaluation of contamination factors revealed the sequence Cu > Fe > Zn > Mn, while the geo accumulation index followed the sequence Cu > Fe > Mn > Zn. Comparison of these findings with the established standards of World Health Organization and Bureau of Indian Standards indicated that the recorded ranges were within permissible limits. The study's outcomes suggest that heavy metal emissions from brick kilns may not significantly impact the quality of groundwater. Elevated copper levels found near brick kilns were likely to result from plumbing materials in the study area. Iron and manganese in groundwater seems to have geo-genic origin and not emission-related. This research represents a foundational step in examining groundwater contamination by heavy metals specifically in the neighborhood of brick kilns in Jammu district. It contributes to the establishment of a comprehensive database and serves as a reference point for future studies. Additionally, the study recommends regular monitoring of groundwater to ensure the maintenance of drinking water quality.

Structure of a novel form of phosphopantetheine adenylyltransferase from Klebsiella pneumoniae at 2.59 Å resolution.

Phosphopantetheine adenylyltransferase (EC. 2.7.7.3, PPAT) catalyzes the penultimate step of the multistep reaction in the coenzyme A (CoA) biosynthesis pathway. In this step, an adenylyl group from adenosine triphosphate (ATP) is transferred to 4'-phosphopantetheine (PNS) yielding 3'-dephospho-coenzyme A (dpCoA) and pyrophosphate (PPi). PPAT from strain C3 of Klebsiella pneumoniae (KpPPAT) was cloned, expressed and purified. It was crystallized using 0.1 M HEPES buffer and PEG10000 at pH 7.5. The crystals belonged to tetragonal space group P41212 with cell dimensions of a = b = 72.82 Å and c = 200.37 Å. The structure was determined using the molecular replacement method and refined to values of 0.208 and 0.255 for Rcryst and Rfree factors, respectively. The structure determination showed the presence of three crystallographically independent molecules A, B and C in the asymmetric unit. The molecules A and B are observed in the form of a dimer in the asymmetric unit while molecule C belongs to the second dimer whose partner is related by crystallographic twofold symmetry. The polypeptide chain of KpPPAT folds into a ß/α structure. The conformations of the side chains of several residues in the substrate binding site in KpPPAT are significantly different from those reported in other PPATs. As a result, the modes of binding of substrates, phosphopantetheine (PNS) and adenosine triphosphate (ATP) differ considerably. The binding studies using fluorescence spectroscopy indicated a KD value of 3.45 × 10-4 M for ATP which is significantly lower than the corresponding values reported for PPAT from other species.

An overview of techniques for monitoring and compensating tool wear in micro-electrical discharge machining.

Micro-electrical discharge machining (µEDM) is severely affected by tool wear and its process variants, which can lead to compromised precision and dimensional disruptions in micro-part production. Several attempts have been made to address this problem by suggesting offline and online (real-time) tool wear compensation strategies. Research efforts in this area have intensified over the last 20 years. However, most methods proposed were applicable only for a few work-tool combinations and in limited input process parametric settings. Instead of tool wear compensation, several research articles have focused on strategies to reduce the negative impact of tool wear on the quality of fabricated parts. The present study systematically reviews various investigations conducted in this area and aims to add cutting-edge compensation for tool wear to future inquiries. The articles reviewed here are explored in detail. Critical findings/innovations are classified into four categories: tool wear in µEDM, tool wear compensation techniques, and offline and online compensation methods.

An integrated multicriteria decision making framework for the selection of waste cement dust filled automotive brake friction composites.

This work discusses selecting optimal brake friction composite alternatives based on an integrated MABAC (multi-attributive border approximation area comparison) and AHP (analytic hierarchy process) approach. Therefore, non-asbestos automotive brake friction composites containing varying proportions of cement dust (50 to 0 wt%) and barium sulfate (0 to 50 wt%) were developed and tribo-evaluated on a Krauss machine following European regulations. Composite made up of 30 wt% cement dust and 20 wt% barium sulfate had the highest friction coefficient (0.361), lowest variability coefficient (0.598), and maximum recovery (123.27%). The composite with the least fading (15.36%) included 50 wt% cement dust, whereas the composite with the lowest wear (9.10 g) and the least frictional fluctuations (0.271) contained 50 wt% barium sulfate. By AHP, the friction coefficient (0.1989), fade (0.1696), recovery (0.1551), and wear (0.1412) were selected as the essential criteria in the performance assessment. Based on the MABAC ranking evaluation, the composite comprises 20 wt% barium sulfate and 30 wt% cement dust has the best tribological profile, whereas the composites of solely cement dust or barium sulfate have the poorest tribological profile. The acquired ranking results were confirmed using other decision-making models and subjected to sensitivity analysis to demonstrate their robustness.

A historical review and analysis on MOORA and its fuzzy extensions for different applications.

Multi-criteria decision-making (MCDM) methods have been widely used among researchers to provide a trade-off solution between best and worst, considering conflicting criteria and sets of preferences. An efficient and systematic literature review of these methods is needed to maintain their application in distinctive domains. To this end, this paper presents a comprehensive and systematic literature survey on "multi-objective optimization by ratio analysis" (MOORA) method and its fuzzy extensions developed and discussed in recent years. This review includes articles categorized based on the publication name, publishing year, journal name, type of applications, and type of fuzzy extensions. In addition, this review will enhance the understanding of practitioners and decision-makers on the MOORA method, its development, fuzzy hybridization, different application areas, and future work. The study revealed that the MOORA technique was predominantly used with the TOPSIS approach, followed by the AHP and COPRAS methods. Furthermore, 76.28 % use single and hybridization approaches among all MOORA studies, while 23.72 % use MOORA in a fuzzy environment.

Performance analysis and modelling of circular jets aeration in an open channel using soft computing techniques.

Dissolved oxygen (DO) is an important parameter in assessing water quality. The reduction in DO concentration is the result of eutrophication, which degrades the quality of water. Aeration is the best way to enhance the DO concentration. In the current study, the aeration efficiency (E20) of various numbers of circular jets in an open channel was experimentally investigated for different channel angle of inclination (θ), discharge (Q), number of jets (Jn), Froude number (Fr), and hydraulic radius of each jet (HRJn). The statistical results show that jets from 8 to 64 significantly provide aeration in the open channel. The aeration efficiency and input parameters are modelled into a linear relationship. Additionally, utilizing WEKA software, three soft computing models for predicting aeration efficiency were created with Artificial Neural Network (ANN), M5P, and Random Forest (RF). Performance evaluation results and box plot have shown that ANN is the outperforming model with correlation coefficient (CC) = 0.9823, mean absolute error (MAE) = 0.0098, and root mean square error (RMSE) = 0.0123 during the testing stage. In order to assess the influence of different input factors on the E20 of jets, a sensitivity analysis was conducted using the most effective model, i.e., ANN. The sensitivity analysis results indicate that the angle of inclination is the most influential input variable in predicting E20, followed by discharge and the number of jets.

Thermal, thermomechanical and structural properties of recycled polyethylene terephthalate (rPET)/waste marble dust composites.

The main objective of this work is to review the capability of using waste marble dust (MD) particles as reinforcing materials in recycled polymeric composites to achieve environmentally friendly materials. In the present study, polymer composites were fabricated from recycled polyethylene terephthalate (rPET) and MD and then analyzed for their structural and thermal properties. Preparation of rPET-based composites containing 0-20 wt% MD was carried out through extrusion and injection molding. For their characterization Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and dynamic mechanical analysis (DMA) were applied. The DSC analysis revealed a nucleating effect of MD on rPET, which was manifested in a higher crystallization temperature (196.7 °C ⇒ 204.4 °C); however, the marble particles were also found to hamper chain mobility, thereby decreasing the crystallinity ratio (23.7 % ⇒ 19.2 %) of rPET and altering its crystalline structure. According to the TGA measurements, a slight increase occurred in the thermal stability of rPET, its major decomposition temperature increased from 446 °C to 451 °C when 20 wt% MD was incorporated into it. DMA showed an improved stiffness in the entire investigated temperature range for MD-filled composites versus neat rPET. Additionally, several factors were derived from the DMA data, including the effectiveness factor, degree of entanglement, and reinforcing efficiency factor which all suggested a decent interaction between the components indicating a proper reinforcing ability of marble powder. However, above 5 wt% MD content the reinforcing efficiency deteriorated due to the agglomeration of filler particles, which was also supported by scanning electron microscopic images.

UV index-based model for predicting synthesis of (pre-)vitamin D3 in the mediterranean basin.

The importance of solar radiation for the body's ability to synthesize Vitamin D3 is well documented, yet the precise amount of sun exposure required to avoid Vitamin D insufficiency is less clear. To address this knowledge gap, this study sought to utilize the sun in a suitable period at the optimum dose by utilizing numerical simulations to determine the amount of Vitamin D3 synthesis in the skin according to season, time of day, and geographical location in Turkey. The study was carried out in three stages; in the first stage, daily, monthly, and annual values were determined in cases where the solar zenith angle has the active UV-B wavelength. The second stage determined the level of Vitamin D that can be synthesized in all skin types at 25% solar radiation exposure. In the third stage, the sun exposure time required for 1000 International Units (IU) for all skin types was calculated. According to the analysis, the yearly period of active synthesis of D3 on Earth lasts from the beginning of March to the third week of October. During the day, it is between 10:00 and 16:00. For 1000 IU/day, the average annual estimated times (minutes) are 5.05 for Type I, 6.3 for Type II, 7.6 for Type III, 11.35 for Type IV, 15.15 for Type V, and 25.25 for Type VI. The results of this paper will impact awareness for academic-medical users.

Ataxia-telangiectasia and combined hepatocellular-cholangiocarcinoma: A case report.

Ataxia-telangiectasia (A-T) is a rare autosomal recessive disease characterized by ataxia, cutaneous and ocular telangiectasia, impaired immunity with susceptibility to sino-pulmonary infections, radiation sensitivity, and cancers particularly of hemato-lymphoid origin. Liver function tests abnormalities and elevated alfa feto-protein have been reported in A-T; however, there is no reported case of combined hepatocellular-cholangiocarcinoma (cHCC-CC) in literature. These tumors should be treated in similar fashion as in general population; however, reduction of chemotherapy dose might be helpful in decreasing chemo-toxicity.

Effectiveness of the WHO Protocol for the Management of Shock in Children With Severe Acute Malnutrition.

Background The WHO protocol for the management of shock in children with severe acute malnutrition (SAM) is not supported by physiological evidence. In this study, we aimed to assess the effectiveness of the WHO treatment protocol in the management of shock in children with SAM. Methodology This cohort study included children aged 2-60 months with WHO-defined SAM and fulfilling the WHO criteria for identification of shock. The exclusion criteria included severe anemia (hemoglobin <4 g/dL), congenital anomalies, congenital heart defects, and chronic diseases. The WHO treatment protocol for the management of shock was used, and features of resolution of shock were assessed at eight and 24 hours. Oliguria was recorded at eight and 24 hours along with in-hospital mortality. Multiple logistic regression was used to determine predictors of mortality. Results Of 53 children, 40 (75.4%) were discharged and 13 (24.5%) expired. We observed significant resolution of features of shock at 24 hours compared to eight hours (35 (71.4%) vs. 10 (18.8%), p < 0.0001). Further analysis revealed a significant resolution of features of shock (p = 0.03) at 24 hours in both fluid-responsive (24 vs. 10) and fluid-refractory children (11 vs. 27) compared to eight hours. Multivariate analysis revealed that mechanical ventilation was positively related to death (odds ratio (OR) = 85, 95% confidence interval (CI) = 8.49, 860, p < 0.0001), and inotrope scores <20 (OR = 0.053, 95% CI = 0.004, 0.64, p = 0.021) and blood transfusion (OR = 0.025, 95% CI = 0.001, 0.61, p = 0.024) had favorable outcomes. Conclusions The WHO protocol for the management of shock in children with SAM is effective in fluid-responsive shock whereas evidence was inconclusive in fluid-refractory shock.

Regulatory T cells control Staphylococcus aureus and disease severity of cutaneous leishmaniasis.

Cutaneous leishmaniasis causes alterations in the skin microbiota, leading to pathologic immune responses and delayed healing. However, it is not known how these microbiota-driven immune responses are regulated. Here, we report that depletion of Foxp3+ regulatory T cells (Tregs) in Staphylococcus aureus-colonized mice resulted in less IL-17 and an IFN-γ-dependent skin inflammation with impaired S. aureus immunity. Similarly, reducing Tregs in S. aureus-colonized and Leishmania braziliensis-infected mice increased IFN-γ, S. aureus, and disease severity. Importantly, analysis of lesions from L. braziliensis patients revealed that low FOXP3 gene expression is associated with high IFNG expression, S. aureus burden, and delayed lesion resolution compared to patients with high FOXP3 expression. Thus, we found a critical role for Tregs in regulating the balance between IL-17 and IFN-γ in the skin, which influences both bacterial burden and disease. These results have clinical ramifications for cutaneous leishmaniasis and other skin diseases associated with a dysregulated microbiome when Tregs are limited or dysfunctional.

SWATH-MS analysis of plasma proteins among Indian HIV-1 infected patients.

The identification and characterization of plasma proteins in drug resistant and drug sensitive in HIV-1 infected/AIDS patients were carried out using the SWATH-MS protocol. In total, 204 proteins were identified and quantified, 57 proteins were differentially expressed, out of which 25 proteins were down regulated and 32 proteins were up regulated in drug resistant patients. Six proteins such as complement C4-A, immunoglobulin heavy variable 1-2, carboxylic ester hydrolase, fibulin-1, immunoglobulin lambda constant7, secreted phosphoprotein 24 were differentially expressed in individuals with drug resistant HIV as compared to individuals with drug sensitive HIV. Gene ontology of 57 differentially expressed proteins was analysed and documented.

Multiomic profiling of cutaneous leishmaniasis infections reveals microbiota-driven mechanisms underlying disease severity.

Leishmania braziliensis is a parasitic infection that can result in inflammation and skin injury with highly variable and unpredictable clinical outcomes. Here, we investigated the potential impact of microbiota on infection-induced inflammatory responses and disease resolution by conducting an integrated analysis of the skin microbiome and host transcriptome on a cohort of 62 patients infected with L. braziliensis. We found that overall bacterial burden and microbiome configurations dominated with Staphylococcus spp. were associated with delayed healing and enhanced inflammatory responses, especially by IL-1 family members. Quantification of host and bacterial transcripts on human lesions revealed that high lesional S. aureus transcript abundance was associated with delayed healing and increased expression of IL-1ß. This cytokine was critical for modulating disease outcomes in L. braziliensis-infected mice colonized with S. aureus, given that its neutralization reduced pathology and inflammation. These results highlight how the human microbiome can shape disease outcomes in cutaneous leishmaniasis and suggest pathways toward host-directed therapies to mitigate the inflammatory consequences.