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Abstract Background Avahan, the India AIDS initiative began HIV prevention interventions in 2003 in Andhra Pradesh (AP) among high-risk groups including female sex workers (FSWs), to help contain the HIV epidemic. This manuscript describes an assessment of this intervention using the published Avahan evaluation framework and assesses the coverage, outcomes and changes in STI and HIV prevalence among FSWs. Methodology Multiple data sources were utilized including Avahan routine program monitoring data, two rounds of cross-sectional survey data (in 2006 and 2009) and STI clinical quality monitoring assessments. Bi-variate and multivariate analyses, Wald Chi-square tests and multivariate logistic regressions were used to measure changes in behavioural and biological outcomes over time and their association. Results Avahan scaled up in conjunction with the Government program to operate in all districts in AP by March 2009. By March 2009, 80% of the FSWs were being contacted monthly and 21% were coming to STI services monthly. Survey data confirmed an increase in peer educator contacts with the mean number increasing from 2.9 in 2006 to 5.3 in 2009. By 2008 free and Avahan-supported socially marketed condoms were adequate to cover the estimated number of commercial sex acts, at 45 condoms/FSW/month. Consistent condom use was reported to increase with regular (63.6% to 83.4%; AOR=2.98; p Conclusions The absence of control groups is a limitation of this study and does not allow attribution of changes in outcomes and declines in HIV and STI to the Avahan program. However, the large scale implementation, high coverage, intermediate outcomes and association of these outcomes to the Avahan program provide plausible evidence that the declines were likely associated with Avahan. Declining HIV prevalence among the general population in Andhra Pradesh points towards a combined impact of Avahan and government interventions.

Skin cancer is common and deadly, hence a correct diagnosis at an early age is essential. Effective therapy depends on precise classification of the several skin cancer forms, each with special traits. Because dermoscopy and other sophisticated imaging methods produce detailed lesion images, early detection has been enhanced. It's still difficult to analyze the images to differentiate benign from malignant tumors, though. Better predictive modeling methods are needed since the diagnostic procedures used now frequently produce inaccurate and inconsistent results. In dermatology, Machine learning (ML) models are becoming essential for the automatic detection and classification of skin cancer lesions from image data. With the ensemble model, which mix several ML approaches to take use of their advantages and lessen their disadvantages, this work seeks to improve skin cancer predictions. We introduce a new method, the Max Voting method, for optimization of skin cancer classification. On the HAM10000 and ISIC 2018 datasets, we trained and assessed three distinct ML models: Random Forest (RF), Multi-layer Perceptron Neural Network (MLPN), and Support Vector Machine (SVM). Overall performance was increased by the combined predictions made with the Max Voting technique. Moreover, feature vectors that were optimally produced from image data by a Genetic Algorithm (GA) were given to the ML models. We demonstrate that the Max Voting method greatly improves predictive performance, reaching an accuracy of 94.70% and producing the best results for F1-measure, recall, and precision. The most dependable and robust approach turned out to be Max Voting, which combines the benefits of numerous pre-trained ML models to provide a new and efficient method for classifying skin cancer lesions., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Aims: The aim of this study is the evaluation of an Azomethine derivative, BCS2, for its antioxidant and anti-tumor activities against mammary carcinoma through the Nrf2- Keap1-HO-1 pathway., Background: The global prevalence of breast cancer is rising at an alarming rate. The facilitation of abnormal cell proliferation in mammary carcinoma occurs due to the disruption of signaling pathways that balance pro- and antioxidant status, thereby producing oxidative stress that disrupts genomic stability. Therefore, introducing a potent antioxidant molecule with antitumor activity is of paramount importance for treating breast cancer., Objective: Synthesis, characterization, and in-vitro, in-vivo, and in-silico evaluation of an Azomethine derivative, BCS2, for its antioxidant and anti-tumor activities against chemical carcinogen- induced mammary carcinogenesis in Sprague-Dawley rats., Methods: An azomethine derivative, 1-(4-nitrophenyl)-N-phenylmethanimine (BCS2), was synthesized and characterized based on its spectral data. The cytotoxic potential was observed on breast cancer cells, MCF-7, MDA-MB-231, and MDA-MB-468. The in vivo chemotherapeutic potential of BCS2 was established on 7,12-dimethylbenz(a)anthracene (DMBA) induced breast cancer in Sprague-Dawley (SD) rats. The effect of BCS2 on kelch-like ECH-associated protein- 1 (Keap1), Nrf2, heme oxygenase-1 (HO-1), mitogen-activated protein kinase (MAPK), and nuclear factor kappa-light-chain-enhancer of activated-B (NF-κB) was evaluated through ELISA and qPCR techniques. Furthermore, the binding potential and stability of BCS2 with Keap-1, HO-1, and MAPK were predicted using in silico molecular docking and dynamics studies. Additionally, drug-likeness properties of BCS2 were evaluated using in silico ADMET tools., Results: BCS2 showed remarkable cytotoxic activity on MCF-7 cells followed by MDA-MB- 231 and MDA-MB-468 cells having an IC50 of 2.368μM, 4.843μM and 6.472μM respectively, without affecting normal breast cells, MCF-10A. In the DMBA-induced animal model, BCS2 showed potent antitumor potential and showed protective action on endogenous-enzymatic and non-enzymatic antioxidants in cancer-bearing animals. Marked improvement in cellular architecture and ultrastructure of breast/tumor tissues excised from experimental animals was noted through histopathological and field emission scanning electron microscopy (FESEM) analyses. Significant upregulation of antioxidant proteins, Keap1 and HO-1, and downregulation of inflammatory proteins, MAPK, and NF-κB was observed after BCS2 treatment. The in silico computational studies predicted the potent binding of BCS2 with the active pockets of Keap1, HO-1, and MAPK proteins that validated the biological findings., Conclusion: The study revealed BCS2's potent antioxidant and antitumor potential against mammary carcinoma through the Nrf2-Keap1-HO-1 signaling pathway., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Zinc oxide NPs (ZnO NPs) are notable in nanomedicine for their exceptional physicochemical and biological properties. This study synthesizes and characterizes beta-carotene-coated ZnO NPs (BT-ZnO NPs) for potential anti-cancer and antimicrobial applications, demonstrating significant efficacy against dental pathogens and oral cancer cells. Scanning Electron Microscopy, EDAX, UV, FTIR, XRD, and Zeta potential analysis of prepared BT-ZnO NPs revealed uniform flower-like crystalline structures with intricate morphology and an average particle size of 38.06 nm. FTIR spectra identified various functional groups, suggesting a complex organic compound coated with ZnO NPs. Zeta potential measurements showed pH-dependent surface charge variations, which are crucial for understanding colloidal stability. The antimicrobial activity was potent against dental pathogens, with minimum inhibitory concentration (MIC) values of 50 µg/mL highlighting significant inhibition. Molecular docking studies demonstrated strong binding affinities of BT to key receptor proteins of dental pathogens. BT-ZnO NPs exhibited notable antioxidant activity of 68%, comparable to ascorbic acid, and significant anti-inflammatory effects of 75.1% at 100 µg/mL. Cytotoxicity assays indicated a concentration-dependent suppression of KB cell proliferation, decreasing cell viability to 37.19%, and gene expression studies showed elevated P53 expression, suggesting a strong apoptotic response. These multifaceted properties underscore the potential of BT-ZnO NPs as an integrated therapeutic approach for dental healthcare and oncology.

Articular cartilage and osteochondral defect repair and regeneration presents significant challenges to the field of tissue engineering (TE). TE and regenerative medicine strategies utilizing natural and synthetic-based engineered scaffolds have shown potential for repair, however, they face limitations in replicating the intricate native microenvironment and structure to achieve optimal regenerative capacity and functional recovery. Herein, we report the development of a cartilage extracellular matrix (ECM) as a printable biomaterial for tissue regeneration. The biomaterial was prepared through decellularization and solubilization of articular cartilage. The effects of two different viscoelastic modifiers, xanthan gum and Laponite®, and the introduction of a secondary photo-crosslinkable component on the rheological behavior and stability were studied. The rheological evaluation of the bioinks demonstrated the tunability of the bioinks in terms of their viscosity and degree of shear thinning, allowing the formulations to be readily extruded during 3D printing. dcECM-Laponite® bioink formulations demonstrated rheological property G' ranging from 750 to 4000 Pa, which is three orders of magnitude higher than that for the dcECM-XG bioink formulations. Furthermore, this was further increased to G' ranging from 2400 to 5700Pa post-crosslinking. Herein, a spreadable ink composition was identified to form a uniform cartilage layer post-printing. The choice of viscosity modifier along with UV cross-linking warrants shape fidelity of the structure post-printing, along with improvements in the storage and loss moduli. The modified ECM-based bioink also significantly improved the stability and allowed for prolonged and sustained release of loaded growth factors through the addition of Laponite®. The ECM-based bioink supported human bone-marrow derived stromal cell and chondrocyte viability and increased chondrogenic differentiation in vitro. By forming decellularized cartilage ECM biomaterials in a printable and stable bioink form, we develop a "Cartilage Ink" that can support cartilaginous tissue formation by closely resembling the native cartilage extracellular matrix in structure and function., (Creative Commons Attribution license.)

Herein, we report the precise control of molecular to supramolecular chirality induction at the single-molecule level just upon subtle modification in an achiral 'nano-size' trizinc(II) porphyrin trimer. A slight variation in the projection of the substituent at the periphery of the central porphyrin unit in a porphyrin trimer (host) resulted in pronounced changes in the interchromophoric arrangement, leading to distinct 'open' and 'closed' conformations. While 'open' form generates 'monomeric' complex with low CD amplitude, 'closed' form produces exclusive 'polymer' with large, amplified CD signal with opposite sign due to stronger intermolecular excitonic coupling. Also, the sign of the CD couplets is just opposite between R and S substrates for both polymer and monomer which suggest that the chirality is predominantly governed by the stereogenic projection of the chiral center. X-ray structures of the host and polymer have been reported here. Crystallographic characterization offers a detailed perspective on the structural and geometrical transformations in the polymer, enabling a systematic understanding of its optical properties. DFT and TD-DFT calculations strongly corroborate with the experimental findings., (© 2025 Wiley‐VCH GmbH.)

Rationale: Early mortality in intracerebral hemorrhage (ICH) is due to hematoma volume (HV) expansion, and there are no effective treatments available other than reduction in blood pressure. Tranexamic acid (TXA) a hemostatic drug that is widely available and safe can be a cost-effective treatment for ICH, if proven efficacious., Hypothesis: Administration of TXA in ICH patients when given within 4.5 h of symptom onset will reduce early mortality at 30 days., Design: Indian Trial of Tranexamic acid in Spontaneous Intracerebral Haemorrhage (INTRINSIC trial) is a multicenter, randomized, open-label, trial enrolling patients aged more than 18 years presenting with non-traumatic ICH within 4.5 h of symptom onset or when last seen well. Study participants received 2 g of TXA administered within 45 min while control group received standard of care. Intensive blood pressure reduction as per INTERACT 2 protocol is followed is done in both groups. Study plans to recruit 3400 patients. Primary outcome is mortality at day 30. Secondary outcomes are radiological reduction in HV at 24 h from baseline, neurological impairment at day 7 or earlier (if discharged), and assessments of dependency and quality of life at day 90., Summary: If proven to be beneficial, TXA will have a major impact on medical management of ICH., Trial Registration: Clinical Trial Registry India (CTRI/2023/03/050224) and Clinical Trials.gov (NCT05836831)., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

A niche in the context of microorganisms defines the specific ecological role or habitat inhabited by microbial species within an ecosystem. For the human commensal Malassezia, the skin surface is considered its primary niche, where it adapts to the skin environment by utilising lipids as its main carbon and energy source. However pathogenic characteristics of Malassezia include the production of allergens, immune modulation and excessive lipid utilisation, which result in several diseases such as pityriasis versicolor, seborrheic dermatitis, Malassezia folliculitis and atopic dermatitis. Recent studies have revealed Malassezia colonisation in internal organs, including the lungs, gut, genitourinary tract, eyes, ears and breast milk. In these organs, Malassezia is associated with diseases linked to respiratory conditions, neurological disorders, gastrointestinal diseases and genital infections. The immune system plays a critical role in shaping Malassezia prevalence, with factors like, immune suppressive drugs and underlying health conditions influencing susceptibility. Accurate diagnosis of Malassezia-related skin disorders is challenging due to its unique growth requirements, but molecular fingerprinting assays and sequencing methods, particularly ITS sequencing, offer precise identification. Treatment involves antifungal drugs, corticosteroids and phytocompounds, yet recurrent infections highlight the need for more targeted therapeutic strategies addressing Malassezia's pathogenic characteristics. Understanding the complex interactions between Malassezia and the host organs is crucial for diagnosis, treatment and prevention and exploring its potentially beneficial roles in health and disease. This review highlights the current findings on the intricate interactions between Malassezia and the diverse ecosystem of the human body, underscoring the complexity of these associations and emphasising their multifaceted role in health and disease., (© 2025 Wiley‐VCH GmbH. Published by John Wiley & Sons Ltd.)

The human mycobiome encompasses diverse communities of fungal organisms residing within the body and has emerged as a critical player in shaping health and disease. While extensive research has focused on the skin and gut mycobiome, recent investigations have pointed toward the potential role of fungal organisms in neurological disorders. Among those fungal organisms, the presence of the commensal fungus Malassezia in the brain has created curiosity because of its commensal nature and primary association with the human skin and gut. This budding yeast is responsible for several diseases, such as Seborrheic dermatitis, Atopic dermatitis, Pityriasis versicolor, Malassezia folliculitis, dandruff, and others. However recent findings surprisingly show the presence of Malassezia DNA in the brain and have been linked to diseases like Alzheimer's disease, Parkinson's disease, Multiple sclerosis, and Amyotrophic lateral sclerosis. The exact role of Malassezia in these disorders is unknown, but its ability to infect human cells, travel through the bloodstream, cross the blood-brain barrier, and reside along with the lipid-rich neuronal cells are potential mechanisms responsible for pathogenesis. This also includes the induction of pro-inflammatory cytokines, disruption of the blood-brain barrier, gut-microbe interaction, and accumulation of metabolic changes in the brain environment. In this review, we discuss these key findings from studies linking Malassezia to neurological disorders, emphasizing the complex and multifaceted nature of these cases. Furthermore, we discuss potential mechanisms through which Malassezia might contribute to the development of neurological conditions. Future investigations will open up new avenues for our understanding of the fungal gut-brain axis and how it influences human behavior. Collaborative research efforts among microbiologists, neuroscientists, immunologists, and clinicians hold promise for unraveling the enigmatic connections between human commensal Malassezia and neurological disorders., Competing Interests: Declarations. Ethical Approval: Not applicable Consent to Participate: Not applicable Consent for Publication: Not applicable Conflict of Interest: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Uncaria tomentosa is a traditional medicinal herb renowned for its anti-inflammatory, antioxidant, and immune-enhancing properties. In the realm of neurodegenerative diseases (NDDS), CLASP proteins, responsible for regulating microtubule dynamics in neurons, have emerged as critical players. Dysregulation of CLASP proteins is associated with NDDS, such as Alzheimer's, Parkinson's, and Huntington's diseases. Consequently, comprehending the role of CLASP proteins in NDDS holds promise for the development of innovative therapeutic interventions., Objectives: The objectives of the research were to identify phytoconstituents in the hydroalcoholic extract of Uncaria tomentosa (HEUT), to evaluate its antioxidant potential through in vitro free radical scavenging assays and to explore its potential interaction with CLASP using in silico molecular docking studies., Methods: HPLC and LC-MS techniques were used to identify and quantify phytochemicals in HEUT. The antioxidant potential was assessed through DPPH, ferric reducing antioxidant power (FRAP), nitric oxide (NO) and superoxide (SO) free radical scavenging methods. Interactions between conventional quinovic acid, chlorogenic acid, epicatechin, corynoxeine, rhynchophylline and syringic acid and CLASP were studied through in silico molecular docking using Auto Dock 4.2., Results: The HEUT extract demonstrated the highest concentration of quinovic acid derivatives. HEUT exhibited strong free radical-scavenging activity with IC 50 values of 0.113 μg/ml (DPPH) and 9.51 μM (FRAP). It also suppressed NO production by 47.1 ± 0.37% at 40 μg/ml and inhibited 77.3 ± 0.69% of SO generation. Additionally, molecular docking revealed the potential interaction of quinovic acid with CLASP for NDDS., Conclusion: The strong antioxidant potential of HEUT and the interaction of quinovic acid with CLASP protein suggest a promising role in treating NDDS linked to CLASP protein dysregulation., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The gut microbiome plays a key role in the pathogenesis and disease activity of inflammatory bowel disease (IBD). While research has focused on the bacterial microbiome, recent studies have shifted towards host genetics and host-fungal interactions. The mycobiota is a vital component of the gastrointestinal microbial community and plays a significant role in immune regulation. Among fungi, Candida species, particularly Candida albicans ( C. albicans ), have been extensively studied due to their dual role as gut commensals and invasive pathogens. Recent findings indicate that various strains of C. albicans exhibit considerable differences in virulence factors, impacting IBD's pathophysiology. Intestinal fungal dysbiosis and antifungal mucosal immunity may be associated to IBD, especially Crohn's disease (CD). This article discusses intestinal fungal dysbiosis and antifungal immunity in healthy individuals and CD patients. It discusses factors influencing the mycobiome's role in IBD pathogenesis and highlights significant contributions from the scientific community aimed at enhancing understanding of the mycobiome and encouraging further research and targeted intervention studies on specific fungal populations. Our article also provided insights into a recent study by Wu et al in the World Journal of Gastroenterology regarding the role of the gut microbiota in the pathogenesis of CD., Competing Interests: Conflict-of-interest statement: The authors declare no conflicts of interest relevant to the content of this manuscript., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

The identification of recyclable resources are extremely important to balance the growing demand for polymer composite 3D printing and sustainable manufacturing. In the present study, SS 316L powder particle infused PLA filaments are fabricated by deriving PLA from discarded bi-material extrudates, adopting solvent mixing methodology. The matrix reclaimability, composite feedstock fabrication, extrudability and printability are investigated by increasing the solid loading from 10 - 40 wt%. Outcomes of the FTIR for 'PLA gel' and 'extrudate dissolved gel' are identical and confirms the matrix reclaimability. Essential characterization studies like XRD, TGA, and DSC are carried out for composite feedstock. The reinforcement dispersion in composites is quantified with the help of microscopy results. The melt rheological studies reveal that all the extruded filaments exhibit shear thinning over a shear rate of 50 s -1 and are compatible with 3D printing. The tensile strength is improved by 22.4% after adding 10 wt% reinforcement to the recycled PLA. The economical benefits are evaluated by comparing the composite filament fabrication with the pure PLA matrix. The study concludes recommending viscous modifiers to improve filament processability and increase loading capacity beyond 40 wt% for indirect metal additive manufacturing., 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 Ltd. All rights reserved.)

The retention and mobility of arsenic (As) in soil depend on various physical and chemical factors. The knowledge of the sorption-desorption chemistry of As in soil is necessary for predicting the fate and behavior of As in soil environments. Therefore, this study assessed different organic (sugarcane bagasse and vermicompost) and inorganic amendments (steel slag and fly ash) for their impact on sorption-desorption of As in texturally different contaminated soils (of sandy clay (SC) and sandy clay loam (SCL) texture) to understand the effect of amendments on As retention and mobility. The results showed that the sorption data fitted well with both Langmuir and Freundlich isotherm equations. The As sorption capacity was significantly enhanced with the application of all amendments. At 30 °C, the adsorption maxima (q max ) of SC soils enhanced to a greater extent following the order: steel slag (278 mg kg -1 ) > sugarcane bagasse (264 mg kg -1 ) > vermicompost (246 mg kg -1 ) > fly ash (242 mg kg -1 ). Whereas, in SCL, the order of q max was steel slag (145 mg kg -1 ) > sugarcane bagasse (132 mg kg -1 ) > fly ash (120 mg kg -1 ) > vermicompost (118 mg kg -1 ). Desorption index (DI) was invariably to > 1 at both temperatures with the application of amendments indicating hysteretic desorption of As. The free energy change (ΔG°) was negative in all treatments and soils (indicating a favorable sorption process) with positive entropy change (ΔS°) values. The study recommends steel slag as the most effective amendment for enhancing As (V) retention in contaminated soils, due to its higher sorption capacity compared to other amendments like sugarcane bagasse, vermicompost, and fly ash. The amendments generally improved As sorption in both soils, reducing As mobility and potentially limiting its environmental spread., Competing Interests: Declarations. Ethics approval: All authors have read, understood, and have complied as applicable with the statement on “Ethical responsibilities of Authors” as found in the Instructions for Authors. Consent to participate: NA. Consent for publication: The paper is submitted with the consent of all authors. Conflict of interest: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background and Objective: Boswellia serrata Roxb. ex Colebr. (Family: Burseraceae; Genus: Boswellia) gum resin (Salai guggul) has profound therapeutic value in Ayurvedic and Unani medicines in alleviating several chronic inflammatory illnesses, including arthritis, asthma, skin and blood diseases, fever, etc. SN13108F (Aflapin ® ) is a proprietary, standardized Boswellia serrata gum resin extract. This 180-day randomized, placebo-controlled clinical study aimed to evaluate cartilage morphology using magnetic resonance imaging (MRI), pain and joint function and long-term safety in the SN13108F-supplemented volunteers with knee osteoarthritis (KOA)., Materials and Methods: Eighty adult male and female subjects with the Kellgren-Lawrence grade II - III KOA were supplemented with SN13108F (100 mg/day) or a matched placebo for 180 consecutive days., Results: SN13108F reduced ( p  < 0.001; vs. baseline and placebo) Western Ontario and McMaster Universities Osteoarthritis Index, Visual Analogue Scale, Lequesne's Functional Index scores, improved six-minute walk test, and stair climb test. Post-trial MRI assessments of the tibiofemoral joints revealed that the cartilage volume, thickness, and joint space width were increased ( p  < 0.001; vs. placebo), and levels of high-sensitivity C-reactive protein, matrix metalloproteinase-3, Fibulin-3, type II collagen degradation peptide in serum, and cross-linked C-terminal telopeptide of type II collagen in urine were significantly reduced ( p  < 0.001; vs. baseline and placebo) in the SN13108F-supplemented subjects. Hematology, complete serum biochemistry, urine analysis, and the participants' vital signs did not alter between the groups., Conclusion: SN13108F supplementation is safe, and it mitigates joint pain and improves musculoskeletal function and cartilage morphology in KOA.

The disposal of waste glass is an environmental concern to municipal solid waste management authorities. An effective approach for reducing the environmental burdened and disposal problems with waste glass is its reuse in the construction industry. Hence, the feasible utilization of glass powder (GP) was assessed by studying the strength properties of the slag-GP binary geopolymers cured at different curing regimens. It includes ambient (30 °C), low (- 15 °C, 0 °C, and 15 °C) and high temperatures (45 °C, 60 °C, 75 °C, and 90 °C) under dry and humid conditions. In addition, the impact of submerged and autoclave curing conditions was assessed. The workability, setting period, and bulk density of the slag-GP mixes were reduced with increased GP content. As per the experimental data, the optimum GP dose was 10% at ambient temperature. However, a higher dose of GP is beneficial for specimens cured at elevated temperatures. No improvement in strength with the curing period was noticed for specimens cured at low temperatures. Under humid curing, slag-GP geopolymers attained dense microstructure, whereas intense micro-cracks were observed in dry environments. Submerged curing conditions achieved better strength gain under alkali conditions compared to normal and saline conditions. Autoclave-curing conditions established rapid strength gain due to geopolymer mechanism advancements. Moreover, the proposed analytical models predict well the CS at different GP contents, curing temperatures, and curing durations., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The future of next-generation electronics relies on low-cost organic semiconductors that are tailored to simultaneously provide all requisite optoelectronic properties, focusing greatly on ambipolar charge-transport and solution processability. In this regard, room-temperature discotic liquid crystals (DLCs) are potential candidates, where quasi-1D self-assembly affords a charge-transport channel along their columnar axis. This work shows a molecular design strategy by utilizing anthraquinone as the primary motif, surrounded by ester functionalized tri-alkoxy phenyl units to develop room-temperature DLCs (1.1-1.3). Here, the polar ester functionality stabilizes the columnar mesophase over a wide range through the involvement of dipole-dipole interaction along with the π-π stacking. Throughout the entire mesophase transition, reported compounds 1.1-1.3 exhibit a highly ordered 2D columnar oblique (Col ob ) self-assembly. Space charge limited current (SCLC) experiments reveal balanced ambipolar charge transport, with the maximum hole and electron mobilities of 5.04 and 4.93 cm 2 V -1 s -1 , respectively. From the conoscopic results, their propensity to align in a highly homeotropic fashion is demonstrated. It is further justified by the azimuthal plot corresponding to the (11) peak of grazing incidence small angle X-ray scattering (GISAXS), denoting the crucial role of the design and alignment for efficient movement of charge carriers in the material., (© 2024 Wiley‐VCH GmbH.)

For the first time, explicit stabilization of all the three conformers, viz. (cis,cis), (cis,trans) and (trans,trans), of a 'nano-sized' highly-flexible urea-bridged Zn(II)porphyrin dimer have been achieved via careful manipulations of external stimuli such as solvent dielectrics, temperature, anionic interactions, axial ligation and surface-induced stabilization. The conformers differ widely in their structures, chemical and photophysical properties and thus have vast potential applicability. X-ray structural characterizations have been reported for the (cis,cis) and (cis,trans)-conformers. While (cis,cis) conformer stabilized exclusively in dichloromethane, more polar solvents resulted in the stabilization of (cis,trans) and (trans,trans)-conformers. Low temperature promotes the stabilization of (cis,trans)-conformer while rise in temperature facilitates flipping to the (cis,cis) one. Significantly, exclusive stabilization of the (trans,trans)-isomer has been illustrated using acetate anion which facilitates H-bonding with the two amide linkages of the urea spacer. Remarkably, HOPG surface facilitates stabilization of the energetically challenging (trans,trans)-conformer via CH⋅⋅⋅π and π⋅⋅⋅π interactions with the solid surface to the porphyrinic cores. DFT calculations demonstrate that the relative stability of the conformers can be modulated upon slight external perturbations as also observed in the experiment. Several factors contributing towards the conformational landscape for the highly flexible urea-bridged porphyrin dimers have been mapped., (© 2024 Wiley-VCH GmbH.)

Designing smart autonomous healing soft materials is crucial to attaining cost-efficiency and optimal performance in organic semiconductors. In this context, we design an unsymmetrical thiophene-fused phenazine (TFP)-based discotic liquid crystal (DLC) with the goal of creating an active organic semiconductor that encompasses favorable attributes, such as polarizability, mobility, and processability. Aligned with our objective, we successfully synthesized two unsymmetrical TFP core-based DLCs by linking alkyl chains of variable lengths at the periphery through a coupling reaction. These DLCs show room temperature columnar oblique (Col ob ) mesophase as evident from temperature-dependent studies employing polarized optical microscopy (POM) and small-angle X-ray scattering (SAXS). We performed space charge-limited current (SCLC) techniques to evaluate the hole mobility of TFP-based DLCs and found that they have high hole mobility (∼10 -3 cm 2 /V s). Additionally, the film morphology and its self-healing nature have been examined using atomic force microscopy (AFM) and stress relaxation test. One of the unsymmetrical DLCs exhibited an ability to relax stress over time while maintaining a constant strain (up to 1-3%). The rational design of these unsymmetrical discotics, exhibiting reduced threshold voltage (as confirmed by conductivity studies) highlights their possible potential in various organic semiconductor devices.

Approved drug products may be subject to change(s) for a variety of reasons. The changes may include, but are not limited to, increase in batch size, alteration of the drug product constituent(s), improvement in the manufacturing process, and shift in manufacturing sites. The extent of pharmaceutical testing and the regulatory pathway for timely implementation of any change in the approved product and/or process depends upon the nature and extent of change. The U.S. Food and Drug Administration (FDA) has published guidelines that outline its expectations for the Scale-Up and Postapproval Changes (SUPAC) in the solid oral immediate and modified release (MR) products, and semisolid formulations. However, to date, no such guidelines have been issued to address SUPAC in the orally inhaled drug products (OIDPs), and this article represents a seminal contribution in this direction. It is hoped that it will inspire contributions from the relevant multidisciplinary experts from the pharmaceutical industry and the agency in accomplishing formal regulatory guidelines relevant to the OIDP SUPAC. The OIDPs are complex drug-device combination products. Therefore, a conceptualization of SUPAC guidelines for these products warrants consideration of contributions of effect of change(s) in individual components (drug substance, formulation, device) as well as a compound effect that a single or multiple changes may have on product performance, and its safety and efficacy. This article provides a discussion of scientific aspects and regulatory bases relevant to the development of SUPAC for OIDPs, and it attempts to outline considerations that may be applicable in addressing issues related to the OIDP SUPAC in the context of human drugs. The authors' statements should not be viewed as recommendations from any regulatory agency, as the applicable guidelines would be determined on case-by-case evaluation by the relevant authorities.

Background : Breast cancer influences more than 2 million women worldwide annually. Since apoptotic dysregulation is a cancer hallmark, targeting apoptotic regulators encompasses strategic drug development for cancer therapy. One such class of apoptotic regulators is inhibitors of apoptosis proteins (IAP) which are a class of E3 ubiquitin ligases that actively function to support cancer growth and survival. Methods : The current study reports design, synthesis, docking analysis (based on binding to IAP-BIR3 domains), anti-proliferative and anti-tumor potential of the azomethine derivative, 1-(4-chlorophenyl)-N-(4-ethoxyphenyl)methanimine ( BCS3 ) on breast cancer (in vitro and in vivo) and its possible mechanisms of action. Results : Strong selective cytotoxic activity was observed in MDA-MB-231, MCF-7, and MDA-MB-468 breast cancer cell lines that exhibited IC50 values, 1.554 µM, 5.979 µM, and 6.462 µM, respectively, without affecting normal breast cells, MCF-10A. For the evaluation of the cytotoxic potential of BCS3 , immunofluorescence, immunoblotting, and FACS (apoptosis and cell cycle) analyses were conducted. BCS3 antagonized IAPs, thereby causing MDM2-p53 and Bcl-2-Caspase-mediated intrinsic and extrinsic apoptosis. It also modulated p53 expression causing p21-CDK1/cyclin B1-mediated cell cycle arrest at S and G2/M phases. The in vitro findings were consistent with in vivo findings as observed by reduced tumor volume and apoptosis initiation (TUNEL assay) by IAP downregulation. BCS3 also produced potent synergistic effects with doxorubicin on tumor inhibition. Conclusions : Having witnessed the profound anti-proliferative potential of BCS3 , the possible adverse effects related to anti-cancer therapy were examined following OECD 407 guidelines which confirmed its systemic safety profile and well tolerability. The results indicate the promising effect of BCS3 as an IAP antagonist for breast cancer therapy with fewer adverse effects.

Thiazolidinedione derivatives have shown significant potential as targeted cancer therapies by leveraging their various mechanisms of action. These include suppressing cell proliferation, triggering apoptosis, and influencing signaling pathways associated with tumor development. Their multifaceted effects make them promising candidates for advancing cancer treatment strategies. They have shown significant promise as anti-cancer agents, particularly through their ability to inhibit lipogenesis pathways and apoptosis essential for cancer cell survival and proliferation. This review comprehensively examines the anti-cancer potential of thiazolidinedione derivatives by targeting key aspects of lipid metabolism, apoptosis, and various mechanistic pathways. This review provides an in-depth examination of the anti-cancer potential of TZD derivatives, focusing on their mechanisms of action, therapeutic applications, and future directions in oncology. The anti-tumor effects of TZDs primarily involve the stimulation of peroxisome proliferator-activated receptor gamma (PPAR-γ), suppressing cell proliferation, induction of apoptosis, and inhibition of angiogenesis. Moreover, recent evidence highlights their ability to modulate non-PPAR-γ pathways, such as PI3K/Akt, NF-κB, and MAPK, further expanding their role in overcoming drug resistance and enhancing therapeutic outcomes. This review explores the preclinical (in vitro and in vivo) and clinical research investigating TZD derivatives efficacy in various cancer types. The insights underscore the significance of targeting lipogenesis as a novel anti-cancer strategy, positioning thiazolidinedione derivatives as potent candidates for future cancer therapeutics. As the oncology landscape evolves, TZD derivatives (rosiglitazone, pioglitazone, inolitazone, troglitazone, and 2,4-thiazolidinedione derivatives) represent a promising class of agents with the potential to contribute meaningfully to cancer treatment. By integrating existing knowledge with recent advancements, this study provides valuable insights into the role of thiazolidinedione derivatives in cancer treatment, paving the way for further research and clinical applications., Competing Interests: Declarations. Ethics approval: Not applicable. Consent to participate: Not applicable Consent to publish: Not applicable Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Filamentous Fungal Human Pathogens (FFHPs) such as Aspergillus fumigatus, are growing resistant to currently available antifungal drugs. One possible target, the Nucleoside diphosphate kinase (Ndk) is significant for nucleotide biosynthesis and crucial for fungal metabolism. Violacein, a natural food colorant, was examined for its antifungal effects against Aspergillus fumigatus via computational approach against the Ndk protein. Known and predicted interactions of Ndk with proteins was performed using the STRING application. Molecular docking was performed using Schrodinger Maestro software (V.14.1) under enhanced precision docking, with OPLS4 forcefield. MDS was performed for 500ns under OPLS4 forcefield and the TIP3P solvent system. The geometry optimization for DFT was performed using the Becke 3-parameter exchange functional (B3LYP) method. The Molecular Docking Studies revealed significant interactions with good binding energy between Violacein and Ndk. Subsequent MD Simulations confirmed the stability of Violacein-Ndk complex, compared to the reference ligand-complex, indicating a stable interaction between the protein and violacein. The energy band gap of violacein was found to be 0.072567 eV suggesting its softness with lower kinetic stability and higher chemical reactivity. The results suggest Violacein could potentially disrupt nucleotide metabolism by targeting Ndk, thus demonstrating antifungal activity. However, further experimental validation is required to confirm these computational findings and explore the practical use of Violacein in antifungal treatments., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

There is a molecular coupling between neurodegenerative diseases, including glaucomatous neurodegeneration (GN), Alzheimer's disease (AD), and Parkinson's disease (PD). Many cells in the eye and the brain have the right amount of 14-3-3 proteins (14-3-3 s) and their isoforms, such as β, ε, γ, η, θ, π, and γ. These cells include keratocytes, endothelial cells, corneal epithelial cells, and primary conjunctival epithelial cells. 14-3-3 s regulate autophagy and mitophagy, help break down built-up proteins, and connect to other proteins to safeguard against neurodegeneration in AD, PD, GN, and glioblastoma. By interacting with these proteins, 14-3-3 s stop Bad and Bax proteins from entering mitochondria and make them less effective. These interactions inhibit neuronal apoptosis. They play many important roles in managing the breakdown of lysosomal proteins, tau, and Aβ, which is why the 14-3-3 s could be used as therapeutic targets in AD. Furthermore, researchers have discovered 14-3-3 s in Lewy bodies, which are associated with various proteins like LRRK2, ASN, and Parkin, all of which play a role in developing Parkinson's disease (PD). The 14-3-3 s influence the premature aging and natural wrinkles of human skin. Studies have shown that lowering 14-3-3 s in the brain can lead to an increase in cell-death proteins like BAX and ERK, which in turn causes excitotoxicity-induced neurodegeneration. This review aimed to clarify the role of 14-3-3 s in the neuropathology of AD, PD, and GN, as well as potential diagnostic markers for improving neuronal survival and repair., Competing Interests: Declaration of Competing Interest None, (Copyright © 2024 Elsevier B.V. All rights reserved.)

Campylobacter fetus is a zoonotic pathogen. Although the precise virulence mechanisms have not yet been fully elucidated, cytolethal distending toxin (CDT) is considered as one of the well-characterized virulence factors in Campylobacter. In silico analysis of the genome of C. fetus type strain ATCC27374 T indicates that there are three cdt gene clusters, Cfcdt-I, Cfcdt-II and Cfcdt-III. However, it is not clear whether these clusters are ubiquitously present in C. fetus and their association with diseases in humans and animals. In this study, we have analyzed the distribution and nucleotide sequences of these cdt gene clusters in 137 C. fetus strains isolated from human patients and healthy cattle. MLST and PFGE were also applied to determine clonal relationship between C. fetus strains isolated from patients and cattle. We found all C. fetus strains carry three Cfcdt gene clusters by colony hybridization assay and the strains belonged to 38 different pulsotypes. Whole genome sequencing of 38 C. fetus strains was carried out to determine the entire cdt gene cluster sequences and their sequence type (ST). Among 38 strains, six STs were identified, and each cdt gene cluster showed high similarity (>99%). Interestingly, some of these Cfcdt genes are more similar to the cdt genes of other Campylobacter species than other Cfcdt gene types. Altogether, the results suggest that three Cfcdt gene clusters are highly conserved in C. fetus and the strains belonging to ST-6 may be more pathogenic to human.

Aims: The purpose of this review is to highlight the therapeutic effectiveness of phenolic acids in slowing the progression of diabetic retinopathy (DR)-linked dementia by addressing the nuclear factor kappa B (NFκB)/matrix metalloproteinase-9 (MMP9)/vascular endothelial growth factor (VEGF) interconnected pathway., Materials and Methods: We searched 80 papers published in the last 20 years using terms like DR, dementia, phenolic acids, NFkB/VEFG/MMP9 signaling, and microRNAs (miRs) in databases including Pub-Med, WOS, and Google Scholar. By encasing phenolic acid in nanoparticles and then controlling its release into the targeted tissues, nanotherapeutics can increase their effectiveness. Results were summarized, and compared, and research gaps were identified throughout the data collection and interpretation., Key Findings: Amyloid beta (Aβ) deposition in neuronal cells and drusen sites of the eye leads to the activation of NFkB/VEGF/MMP9 signaling and microRNAs (miR146a and miR155), which in turn energizes the accumulation of pro-inflammatory and pro-angiogenic microenvironments in the brain and retina leading to DR-linked dementia. This study demonstrates the potential of phenolic acid-enabled nanotherapeutics as a functional food or supplement for preventing and treating DR-linked dementia, and oxidative stress-related diseases., Significance: The retina has mechanisms to clear metabolic waste including Aβ, but the activation of NFkB/ MMP9/ VEGF signaling leads to fatal pathological consequences. Understanding the role of miR146a and miR155 provides potential therapeutic avenues for managing the complex pathology shared between DR and dementia. In particular, phenolic acid nanotherapeutics offer a dual benefit in retinal regeneration and dementia management., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Malassezia species are commensal fungi residing on the skin and in the gut of humans and animals. Yet, under certain conditions, they become opportunistic pathogens leading to various clinical conditions including dermatological disorders. The emergence of drug resistance and adverse effects associated with conventional antifungal agents has propelled the search for alternative treatments, among which phytomedicine stands out prominently. Phytochemicals, including phenolic acids, flavonoids, and terpenoids, demonstrate potential antifungal activity against Malassezia by inhibiting its growth, adhesion, and biofilm formation. Furthermore, the multifaceted therapeutic properties of phytomedicine (including anti-fungal and, antioxidant properties) contribute to its efficacy in alleviating symptoms associated with Malassezia infections. Despite these promising prospects, several challenges hinder the widespread adoption of phytomedicine in clinical practice mostly since the mechanistic studies and controlled experiments to prove efficacy have not been done. Issues include standardization of herbal extracts, variable bioavailability, and limited clinical evidence. Hence, proper regulatory constraints necessitate comprehensive research endeavors and regulatory frameworks to harness the full therapeutic potential of phytomedicine. In conclusion, while phytomedicine holds immense promise as an alternative or adjunctive therapy against Malassezia, addressing these challenges is imperative to optimize its efficacy and ensure its integration into mainstream medical care. In this review we provide an update on the potential phytomedicines in combating Malassezia-related ailments, emphasizing its diverse chemical constituents and mechanisms of action., Competing Interests: Declaration of competing interest The authors do hereby declare that they have no affiliations with or involvement in any organization or entity with any financial interest., (Copyright © 2024. Published by Elsevier B.V.)

Purpose: This study investigates the influence of gantry and collimator angles on the dosimetric leaf gap (DLG) and leaf transmission factor (LTF) in a Varian LINAC equipped with rounded-end multi-leaf collimators (MLCs). While Varian guidelines recommend DLG measurements at zero degrees for both gantry and collimator, this research aims to address the knowledge gap by assessing DLG and LTF variations at different gantry and collimator angles., Methods: Measurements were conducted using a Varian TrueBeam LINAC with a Millennium 120-leaf MLC and Eclipse TPS version 16.1. The beams utilized in this study had energies of 6 MV, 10 MV, 6 FFF, and 10 FFF. LTF and DLG were determined using ionization chambers in solid water phantoms at various gantry angles (0°, 45°, 90°, 135°, 180°, 225°, 270°, and 315°). For each gantry angle, measurements were also taken at various collimator angles (0°, 45°, 90°, and 315°). Dosimetric impacts were evaluated through VMAT Picket Fence tests and patient-specific verification using portal dosimetry for 10 clinical VMAT plans., Results: LTF values showed no significant variation across gantry and collimator angles. However, DLG values exhibited notable differences depending on the gantry angle and were independent of the collimator angle. The highest DLG value was observed at a gantry angle of 270 degrees, while the lowest was at 90 degrees. The AXB DLG Average (averaging seven measurements of DLGs at different gantry angles) model demonstrated the best agreement between measured and calculated dose distributions, indicating the importance of considering averaged DLG values across multiple gantry angles for accurate dose calculations., Conclusion: Our study highlights the variability of DLG with gantry angle alterations, contrary to Varian guidelines recommending DLG measurements at zero gantry angle only. We advocate for utilizing an averaged DLG value from measurements across multiple gantry angles, as outlined in our methodology., (© 2024 The Author(s). Journal of Applied Clinical Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

MCM10 plays a vital role in genome duplication and is crucial for DNA replication initiation, elongation, and termination. It coordinates several proteins to assemble at the fork, form a functional replisome, trigger origin unwinding, and stabilize the replication bubble. MCM10 overexpression is associated with increased aggressiveness in breast, cervical, and several other cancers. Disruption of MCM10 leads to altered replication timing associated with initiation site gains and losses accompanied by genome instability. Knockdown of MCM10 affects the proliferation and migration of cancer cells, manifested by DNA damage and replication fork arrest, and has recently been shown to be associated with clinical conditions like CNKD and RCM. Loss of MCM10 function is associated with impaired telomerase activity, leading to the accumulation of abnormal replication forks and compromised telomere length. MCM10 interacts with histones, aids in nucleosome assembly, binds BRCA2 to maintain genome integrity during DNA damage, prevents lesion skipping, and inhibits PRIMPOL-mediated repriming. It also interacts with the fork reversal enzyme SMARCAL1 and inhibits fork regression. Additionally, MCM10 undergoes several post-translational modifications and contributes to transcriptional silencing by interacting with the SIR proteins. This review explores the mechanism associated with MCM10's multifaceted role in DNA replication initiation, chromatin organization, transcriptional silencing, replication stress, fork stability, telomere length maintenance, and DNA damage response. Finally, we discuss the role of MCM10 in the early detection of cancer, its prognostic significance, and its potential use in therapeutics for cancer treatment., Competing Interests: Declarations Ethical approval Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Skin concerns are frequent among urban-living Aboriginal children, yet specialist dermatology consultations are limited with studies highlighting the need for improved cultural security. Through newly established paediatric dermatology clinics at two urban Aboriginal Community Controlled Health Organisations (ACCHOs), we aimed to describe clinic and patient data, including disease frequencies and associations, to inform dermatology service provision and advocacy., Methods: A prospective cohort study of Aboriginal children and young people (CYP, 0-18 years) attending Aboriginal Health Practitioner (AHP) co-ordinated paediatric dermatology clinics at two urban ACCHOs., Results: Data were collected from 32 clinics over 19 months, with 335 episodes of care and a mean attendance rate of 74%. From 78 new patients, 72 (92%) were recruited into the study, only one of whom had previously received dermatologist assessment. Eczema, tinea or acne accounted for 47% (34/72) of referrals, and 60% of patients received their first appointment within 4 weeks of referral. In 47/72 (65%) consultations, the GP referral and dermatologist diagnosis concurred. The most frequent diagnoses (primary or secondary) at first consultation were atopic dermatitis (26%, 19/72), dermatophyte infections (25%, 18/72), acne (21%, 15/72), bacterial skin infections (18%, 13/72) and post-inflammatory dyspigmentation (18%, 13/72). Three categories of the 2022 Australasian College of Dermatologists curriculum (infections, eczema/dermatitis, pigmentary disorders) accounted for 59% of all diagnoses., Conclusions: This study highlights the specialist dermatology needs of urban-living Aboriginal CYP. ACCHO-embedded dermatology clinics co-ordinated by AHPs demonstrated benefits for Aboriginal CYP in accessing care. Opportunities to embed dermatology practice within ACCHOs should be prioritised., (© 2024 The Author(s). Australasian Journal of Dermatology published by John Wiley & Sons Australia, Ltd on behalf of Australasian College of Dermatologists.)

Background: In suspected Ankle Instability, the parameters that can be defined in the X-ray have their limitation owing to their variability in positioning and rotation of the tibiofibular joint. This inaccuracy further increases due to variability in morphometric parameters of distal tibiofibular syndesmosis among different populations based on race and sex. This research aims to study morphometry of normal distal tibiofibular syndesmosis based on computed tomography imaging in the Indian population., Methods: An Prospective observational study was performed from December 2020 to October 2022 on normal ankle CT scans of 100 Indian population using axial, sagittal, and coronal CT images. Anterior and posterior tibiofibular distance, Morphology of the incisura fibularis based on depth, Tibiofibular clear space (TFCS) and tibiofibular overlap (TFO), Transverse and longitudinal length of the fibula, and Relationship between the center of the talus and the center of a line joining the outer aspect of malleoli in the coronal plane were measured and analyzed by two different observers., Results: Out of the 100 participants, 77 (77 %) were male, and 23 (23 %) were female. The overall mean age of participants was 34.69 ± 9.7 years. The incisura fibularis was concave in 54 %, and shallow in 46 %. Anterior tibiofibular distance, Posterior tibiofibular distance, and Tibiofibular overlap were significantly different in comparison to the male with female populations (p-value < 0.05)., Conclusion: This study gives the indices that describe normal variations in the anatomical relationship between the fibula and fibular incisure in the Indian population, which will be helpful for improving the diagnostic accuracy of distal tibiofibular syndesmoses and providing optimal treatment in order to improve functional outcomes and reduce the risk of complications., Level of Evidence: III., Competing Interests: Conflict of interest statement The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2024 European Foot and Ankle Society. Published by Elsevier Ltd. All rights reserved.)

Introduction: Patients with chronic kidney disease (CKD) are at increased risk of developing tuberculosis (TB). These patients may also be at higher risk of developing antitubercular treatment (ATT)-associated adverse drug reactions (ADRs). Although dose modification has been recommended, data regarding the impact of impaired kidney function on ATT-associated ADRs is sparse. We studied the incidence and profile of ATT-associated ADRs in patients with CKD and compared them with those with normal kidney function., Methodology: This retrospective study analyzed all patients initiated on ATT from January 2016 to August 2019. Patients were grouped into CKD and normal kidney function based on their eGFR. Data on ATT-associated ADRs were collected from medical records. Predictors of ADRs were assessed using univariable and multivariable logistic regression. Additionally, Propensity score matching and analysis were done for CKD and normal kidney function in 1:3 ratio., Results: Of 1815 patients on ATT, 75 (4.1%) had CKD. ADRs were more frequent [36/75 (48.0%) vs. 239/1740 (13.7%), p  ≤ 0.0001] and more severe [15/46 (32.6%) vs. 43/283 (15.1%), p  = 0.010] in CKD than those with normal kidney function. The most common ADRs were hepatobiliary [23/75 (30.6%) vs. 156/1740 (8.9%), p  ≤ 0.0001], neuropsychiatric [8/75(10.6%) vs. 21/1740(1.2%), p  ≤ 0.0001], renal [4/75(5.3%) vs. 8/1740(0.4%), p  = 0.001], and gastrointestinal [5/75(6.6%) vs. 34/1740 (1.9%), p  = 0.020]. CKD was an independent predictor for ADRs (OR -4.96, 95% CI: 2.79-8.82; p  ≤ 0.0001). The matched cohort showed similar results., Conclusion: ATT-associated ADRs were more common and severe in patients with CKD, despite drug dose modifications. Optimal dosing of ATT in CKD needs to be further evaluated.

Competing Interests: Conflicts of interest None.

Previous meta-analyses have documented the association of immune-inflammatory pathways with the pathophysiology of Major Depressive Episode (MDE), as reflected by alterations in peripheral blood immune cell counts. However, it remains unclear whether these immunological changes are distinct in individuals experiencing suicidal ideation (SI) or suicidal behavior (SB), beyond the context of an MDE. This systematic review and meta-analysis aimed to examine peripheral immune cell profiles across samples with SI/SB and compare them to healthy controls or patients with MDE. A systematic literature search was conducted in MEDLINE, Embase, and PsycINFO for articles published from inception until June 12, 2023. Two independent reviewers screened the articles for inclusion, extracted data, and assessed the risk of bias using the Newcastle-Ottawa scale. Meta-analyses were performed using a random-effects model to calculate standardized mean differences (SMDs) and 95% confidence intervals (CIs) for immune cell counts or ratios between groups with and without SI/SB. Heterogeneity across studies was assessed using the restricted maximum-likelihood estimator for tau statistic and I 2 -statistic and tested by the Q test. Publication bias was evaluated using the Egger´s test and funnel plots. Meta-regression analyses were conducted to explore the potential moderating effects of age, gender, current or lifetime SI/SB, and the type of self-harming behavior (SI or SB). The study was registered with PROSPERO (CRD42023433089). The systematic review included 30 studies, with data from 19 studies included in the meta-analyses comprising 139 unique comparisons. Eleven different cell populations or ratios were included, comprising 1973 individuals with SI/SB and 5537 comparison subjects. White blood cell (WBC) and neutrophil counts were higher in individuals with SI/SB than in controls (WBC: SMD = 0.458; 95% CI = 0.367-0.548; p value ≤ 0.001; I 2  = 0.002% and; Neutrophils: SMD = 0.581; 95% CI = 0.408-0.753; p < 0.001), indicating an inflammatory process. The neutrophil-to-lymphocyte ratio (NLR) emerged as a potential marker, demonstrating a notable elevation in individuals with SI/SB (SMD = 0.695; 95% CI = 0.054-1.335; p value = 0.033; I 2  = 94.281%; Q test p value ≤ 0.001). The elevated NLR appears to be primarily driven by the increase in neutrophil counts, as no significant differences were found in lymphocyte counts between groups. Comparisons among participants with and without SI/SB and depression revealed similar trends with increased NLR, monocyte-to-lymphocyte ratio (MLR), and platelet-to-lymphocyte ratio (PLR) observed in depressed individuals with SI/SB compared to those without SI/SB. Broad alteration in the peripheral immune cell populations and their ratios were observed in individuals with SI/SB, indicating an immune activation or dysfunction. Notably, these immunological changes were also evident when comparing MDE individuals with and without SI/SB, suggesting that such immune dysfunction associated with suicidality cannot be solely attributed to or explained by depressive symptoms. The NLR, MLR, and PLR ratios, in combination with novel immune cellular and protein biomarkers, open new avenues in understanding the immunological underpinnings of SI/SB. These findings highlight the potential utility of immune markers as part of a multi-modal approach for risk stratification and therapeutic monitoring in SI/SB., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Introduction: We report on post stillbirth and newborn death socio-cultural experience of women from a population-based representative sample in the Indian state of Bihar., Methods: A state-representative sample of 7,270 births between July 2020 and June 2021 was sampled, including 582 stillbirths and 831 newborn deaths. Detailed confidential interviews were conducted with the consenting women with stillbirth and newborn death to understand their post-birth experience., Results: A total of 501 (86.1% participation) women with stillbirth and 717 (86.3% participation) with neonatal death provided interview. Able to talk to someone about their baby and receiving support to cope with their loss were reported by 369 (74.2%) and 398 (80.2%) women with stillbirth; these proportions were 76.7% and 77.3% for women with newborn deaths, respectively. More than 80% of these women reported spouses as their main source of support. At least one negative experience was reported by 150 (30.9%) and 233 (32.5%) women with stillbirth and newborn death, respectively. The most commonly reported negative experience was receiving insensitive/hurtful comments about the baby (18.6% for stillbirth and 20.4% for newborn deaths), followed by being blamed for the baby's death (14.3% for stillbirths and 15.0% for newborn deaths). The majority of women reported being verbally abused by the mother-in-law for both stillbirth (24, 63.2%) and newborn death (49, 64.5%); while 48 (67.6%) and 66 (61.7%) women were blamed by the mother-in-law for stillbirth and neonatal death, respectively. Most women with stillbirth (72.7%) and with neonatal death (77.1%) were asked to forget about their babies as a means to cope with their loss. Naming, seeing, and holding the stillborn were reported by 56 (11.2%), 229 (45.9%), and 64 (12.8%) women with a stillborn., Conclusion: With one-third women with adverse birth outcome reporting negative experience, this translates into a significant number of women in India as it accounts for high numbers of stillbirths and newborn deaths globally. These population-based data can facilitate in designing interventions to improve post-partum experience for women with adverse birth outcomes in India., Competing Interests: Declarations. Ethics approval and consent to participate: ENHANCE 2020 was approved by the Institutional Ethics Committee of the Public Health Foundation of India. All participants provided written informed consent, and for those who could not read or write, the participant information sheet and consent form were explained by the trained interviewer, and a thumb impression was obtained. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

The dual-target inhibitors (ZINC000008876351 and ZINC000253403245) were identified by utilizing an advanced computational drug discovery method by targeting two critical enzymes such as FeSODA (Iron superoxide dismutase) and TryR (Trypanothione reductase) within the antioxidant defense system of Leishmania donovani (Ld). In vitro enzyme inhibition kinetics reveals that both the compound's ability to inhibit the function of enzyme LdFeSODA and LdTryR with inhibition constant (Ki) value in the low μM range. Flow cytometry analysis, specifically at IC 50 and 2X IC 50 doses of both the compounds, the intracellular ROS was significantly increased as compared to the untreated control. The compounds ZINC000253403245 and ZINC000008876351 exhibited strong anti-leishmanial activity in a dose-dependent manner against both the promastigote and amastigote stages of the parasite. The data indicate that these molecules hold promise as potential anti-leishmanial agents for developing new treatments against visceral leishmaniasis, specifically targeting the LdFeSODA and LdTryR enzymes. Additionally, the in vitro MTT assay shows that combining these compounds with miltefosine produces a synergistic effect compared to miltefosine alone. This suggests that the compounds can boost miltefosine's effectiveness by synergistically inhibiting the growth of L. donovani promastigotes. Given the emergence of miltefosine resistance in some Leishmania strains, these findings are particularly significant., 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 Inc. All rights reserved.)

Hexavalent chromium (Cr(vi)) is a prominent carcinogen. In environmental engineering, the elimination of hexavalent chromium from aqueous media is a noteworthy field of study. In this regard, nanoparticle science and technology have contributed significantly to the photocatalytic reduction of Cr(vi). In this review, a methodical search was undertaken to discover the most recent advancements in the field of photocatalytic reduction of Cr(vi) utilizing g-C 3 N 4 and composites derived from it. This paper deals with the advancements and applications of g-C 3 N 4 and its composites in the Cr(vi) remediation of water-borne pollutants. Different intriguing systems, suggested by various researcher groups, have been discussed. Different characterization techniques often conducted on photocatalysts based on g-C 3 N 4 have also been highlighted so as to gain an understanding of the Cr(vi) removal process. Lastly, the future scope of the g-C 3 N 4 -derived photocatalysts, present challenges, and the viability of employing these photocatalysts in an extensive treatment plant have been discussed., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Tumor-associated macrophages (TAMs) drive the protumorigenic responses and facilitate tumor progression via matrix remodeling, angiogenesis, and immunosuppression by interacting with extracellular matrix proteins via integrins. However, the expression dynamics of integrin and its correlation with TAM functional programming in the tumors remain unexplored. In this study, we examined surface integrins' role in TAM recruitment and phenotypic programming in a 4T1-induced murine breast tumor model. Our findings show that integrin α5β1 is upregulated in CD11b+Ly6Chi monocytes in the bone marrow and blood by day 10 after tumor induction. Subsequent analysis revealed elevated integrin α5β1 expression on tumor-infiltrating monocytes (Ly6ChiMHC class II [MHCII]low) and M1 TAMs (F4/80+Ly6ClowMHCIIhi), whereas integrin αvβ3 was predominantly expressed on M2 TAMs (F4/80+Ly6ClowMHCIIlow), correlating with higher CD206 and MERTK expression. Gene profiling of cells sorted from murine tumors showed that CD11b+Ly6G-F4/80+α5+ TAMs had elevated inflammatory genes (IL-6, TNF-α, and STAT1/2), whereas CD11b+Ly6G-F4/80+αv+ TAMs exhibited a protumorigenic phenotype (IL-10, Arg1, TGF-β, and STAT3/6). In vitro studies demonstrated that blocking integrin α5 and αv during macrophage differentiation from human peripheral blood monocytes reduced cell spreading and expression of CD206 and CD163 in the presence of specific matrix proteins, fibronectin, and vitronectin. Furthermore, RNA sequencing data analysis (GEO dataset: GSE195857) from bone marrow-derived monocytes and TAMs in 4T1 mammary tumors revealed differential integrin α5 and αv expression and their association with FAK and SRC kinase. In line with this, FAK inhibition during TAM polarization reduced SRC, STAT1, and STAT6 phosphorylation. In conclusion, these findings underscore the crucial role of integrins in TAM recruitment, polarization, and reprogramming in tumors., (Copyright © 2024 by The American Association of Immunologists, Inc.)

Background: Wound healing relies on a controlled inflammatory process vital for tissue regeneration. Chronic wounds, characterized by persistent inflammation and high infection risk, pose significant challenges in healthcare. Hydrogel dressings offer promise in wound care; however, the understanding of their role in managing inflammation and infection remains unclear. This study aimed to elucidate these processes and assess the efficacy of Asiatic acid (AA)-infused hydrogels in reducing inflammation and preventing infection. The unique properties of AA suggest its potential to modulate inflammation, promote tissue regeneration, and inhibit microbial colonization, thereby paving the way for specialized dressings that optimize healing outcomes., Methods: The investigation encompassed the antibacterial, anti-biofilm, antioxidant activity, and biocompatibility of AA using a fibroblast cell line. A hydrogel incorporating AA was developed and characterized through scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FTIR), contact angle analysis, tensile testing, swelling capacity, and thermal stability assessments. Biodegradability was evaluated via enzymatic degradation, alongside controlled drug release and antibacterial efficacy against MRSA. In vivo studies using a zebrafish model examined wound healing and immune response., Results: Results confirmed AA's potent antibacterial activity against MRSA and its effectiveness in disrupting mature biofilms. Additionally, AA exhibited strong antioxidant activity and biocompatibility. Morphological analysis revealed a pore structure conducive to wound healing, and the hydrogel demonstrated enhanced tensile strength, swelling properties, and thermal stability. In vivo, the AA-infused hydrogel accelerated wound closure, re-epithelialization, and immune response, supporting its potential for advanced wound care applications. In conclusion, the AA-infused chitosan hydrogel emerges as a promising candidate for advanced wound care therapies., 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.)

Conventional pre-genomics breeding methodologies have significantly improved crop yields since the mid-twentieth century. Genomics provides breeders with advanced tools for whole-genome study, enabling a direct genotype-phenotype analysis. This shift has led to precise and efficient crop development through genomics-based approaches, including molecular markers, genomic selection, and genome editing. Molecular markers, such as SNPs, are crucial for identifying genomic regions linked to important traits, enhancing breeding accuracy and efficiency. Genomic resources viz. genetic markers, reference genomes, sequence and protein databases, transcriptomes, and gene expression profiles, are vital in plant breeding and aid in the identification of key traits, understanding genetic diversity, assist in genomic mapping, support marker-assisted selection and speeding up breeding programs. Advanced techniques like CRISPR/Cas9 allow precise gene modification, accelerating breeding processes. Key techniques like Genome-Wide Association study (GWAS), Marker-Assisted Selection (MAS), and Genomic Selection (GS) enable precise trait selection and prediction of breeding outcomes, improving crop yield, disease resistance, and stress tolerance. These tools are handy for complex traits influenced by multiple genes and environmental factors. This paper explores new genomic technologies like molecular markers, genomic selection, and genome editing for plant breeding showcasing their impact on developing new plant varieties., (© 2024. The Author(s).)

Enzymes, especially amylases, have been an economic boon to the industrial sector, their bioprospective and biotechnological use is an added advantage. Our primary focus of the study was to isolate the most potent amylase producer and to optimize its production parameters through One Factor At A Time (OFAT), Central Composite Rotatable Design Response Surface Methodology (CCRD RSM) and Artificial Neural Network (ANN). Based on the qualitative and quantitative analysis, SLAB1 was selected as the most potent amylase producer out of the potential isolates. Further SLAB1 was identified as Priestia flexa via 16SrRNA identification protocol. Optimization of the production parameters showed the best carbon, nitrogen sources, temperature and pH to be fructose, peptone, 20 °C and pH 8.0 respectively. Further, the enzyme was purified using ammonium sulphate precipitation followed by dialysis. Later, DEAE Sepharose (Sigma) resin was used for ion exchange chromatography and the protein was eluted using NaCl gradients from 0.1 M - 0.6 M. Enzyme kinetics assessment of the purified amylase with the Lineweaver Burk plot showed values of maximum rate; Vmax (10.869 μmoL/min), and Michaelis-Menten constant Km to be around (14.91 mg/mL). To determine its potential application, analysis of this purified amylase in cleaning the tomato and chocolate stained cotton fabrics after comparing its compatibility with different detergents were executed. Further analysis of the washed stained fabrics via Scanning Electron Microscopy was carried out., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

Background and Objectives: Despite increasing urbanisation, little is known about skin health for urban-living Aboriginal children and young people (CYP, aged <18 years). This study aimed to investigate the primary care burden and clinical characteristics of skin conditions in this cohort., Method: A one-year retrospective cohort study of urban-living Aboriginal CYP presenting for general practitioner (GP) consultation at an Aboriginal Community Controlled Health Organisation (ACCHO) was conducted., Results: At least one dermatological diagnosis was made in 27% (253/939) of GP face-to-face consultations for the 585 urban-living Aboriginal CYP included. Infections and dermatitis accounted for 54% (152/284) and 18% (50/284) of all dermatological diagnoses, respectively. Bacterial skin infection (BSI) cumulative incidence was 13% (74/585; 95% CI 10-16%), with recurrent BSI affecting <1% (5/585; 95% CI 0.3-2%) and hospitalisation required in 1% (1/82; 95% CI 0.06-7%) of incident BSI cases., Discussion: We present a culturally secure, multidisciplinary skin health assessment model within an urban ACCHO, where dermatological conditions account for a significant proportion of GP workload.

Human hosts possess a complex network of immune responses against microbial pathogens. The production of antimicrobial peptides (AMPs), which target the pathogen cell membranes and inhibit them from inhabiting the hosts, is one such mechanism. However, pathogens have evolved systems that encounter these host-produced AMPs. The Sap (sensitivity to antimicrobial peptides) transporter uptakes AMPs inside the microbial cell and proteolytically degrades them. The Sap transporters comprise five subunits encoded by genes in an operon. Despite its ubiquitous nature, its subunits are not found to be in tandem with many organisms. In this study, a total of 421 Sap transporters were analyzed for their operonic arrangement. Out of 421, a total of 352 operons were found to be in consensus arrangement, while the remaining 69 show a varying arrangement of genes. The analysis of the intergenic distance between the subunits of the sap operon suggests a signature pattern with sapAB (-4), sapBC (-14), sapCD (-1), and sapDF (-4 to 1). An evolutionary analysis of these operons favors the consensus arrangement of the Sap transporter systems, substantiating its prevalence in most of the Gram-negative pathogens. Overall, this study provides insight into bacterial evolution, favoring the maintenance of the genetic organization of essential pathogenicity factors., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.)

Background: Prior vaccination is often studied for its impact on individuals' post-infection prognosis. Ayurveda, Yoga, Unani, Siddha and Homeopathy (AYUSH) medicines, advised by the Government of India as prophylaxis during the first wave of the coronavirus disease 2019 (COVID-19) pandemic, were consumed by the masses in 2020. A study was therefore undertaken to observe any association between the prior usage of AYUSH prophylactic medicines and post-infection severity as reported by recovered COVID-19 individuals., Methods: This was a retrospective, multi-centre, cohort study conducted in 21 cities of India from 5th August to 30th November 2020. Data from recovered COVID-19 patients, of either sex or any age, captured information about AYUSH prophylactic medicines intake prior to infection, disease severity, symptomatology, duration of complaints, etc. The study participants were grouped into AYUSH intake and non-intake. Primary composite outcome was the disease clinical course. Secondary clinical outcomes were the rate of and time to clinical recovery., Results: Data of 5,023 persons were analysed. Ayurveda or homeopathic prophylactic medicines were consumed by more than half of the study participants: that is, 56.85% ( n  = 1,556) and 56.81% ( n  = 1,555) respectively. The overall adjusted protective effect (PE) of AYUSH prophylactic intake against moderate/severe forms of COVID-19 disease was 56.7% (95% confidence interval [CI], 48.7 to 63.50; p  < 0.001). Adjusted PE for homeopathy and Siddha was 52.9% (95% CI, 42.30 to 61.50; p  < 0.001) and 59.8% (95% CI, 37.80 to 74.10; p  < 0.001), respectively. A statistically significant association was found between AYUSH prophylactic medicine intake and clinical recovery more frequently by the 3rd day of illness (χ 2  = 9.01; p  = 0.002). Time to resolution of symptoms in the AYUSH intake group was on average 0.3 days earlier than in the non-intake group ( p  = 0.002)., Conclusion: AYUSH prophylactics were associated with statistically significant levels of protection against COVID-19 disease severity. Amongst these, previous intake of homeopathy or Siddha medicines was associated with some protection against moderate/severe illness and with a somewhat quicker clinical recovery. Prospective studies with experimental research design are needed to validate the findings of this study., Study Registration: Clinical Trials Registry-India (CTRI/2020/08/027000)., Competing Interests: None declared., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Cervical cancer remains a significant health burden worldwide, emphasizing the need for early detection and intervention. DNA replication is perturbed in cancer cells, and the minichromosome maintenance protein 10 plays an important role in origin firing. By analyzing the MCM10 mRNA expression in healthy controls, precancerous lesions, and cervical cancer using qRT-PCR, we can infer if it can be considered a biomarker. We collected cervical smear samples from patients and performed MCM10 expression analysis to set up thresholds for risk stratification. We also investigated the HPV status among the patient samples with precancerous lesions and cervical cancer and found 70 % of them to be positive. Our results demonstrated a significant upregulation of MCM10 mRNA expression in tumor samples (n = 40, 7.83 ± 1.2) and precancerous lesions (n = 54, 5.69 ± 1.4) compared to normal (n = 50, 4.27 ± 0.80) with a R 2 value of 0.59, confirming its role in the progression and development of cervical cancer. In conclusion, this study emphasizes the potential role of MCM10 as a biomarker. Our study would improve early detection rates, and we propose MCM10-based community screening for risk stratification, prevention, and prognosis., 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.)

Background: Anatomic single-bundle ACL reconstruction (ACLR) produces good results when the graft and tunnel are positioned in the anatomic footprint on the femoral and tibial insertion sites in a more oblique orientation. The Anterolateral Complex of the knee and its biomechanical role in controlling rotational laxity, internal rotation, and pivot shift has led to adding adjunctive procedures like extra-articular augmentation and lateral extra-articular tenodesis (LET) to decrease rotational laxity. We prospectively analyzed young adults with rotational instability and generalized laxity undergoing an arthroscopic single bundle ACLR with an additional LET procedure., Methods: 42 patients, aged between 20 and 50, undergoing all-inside ACLR augmented with concomitant lateral extra-articular tenodesis between November 2020 and October 2021 were included. All patients were followed up for one year and functional assessment comprised of the International Knee Documentation Committee [IKDC] score, visual analogue score [VAS], and Lysholm Knee Scoring Scale at 6 months and 1 year. Return to activity was assessed using the Tegner Activity Score., Results: The Lysholm score, IKDC score, and VAS showed significant improvements at 6 months after ACLR + LET ( p  < 0.0001) and further improved significantly at 1 year. The patients had a significant decline in the Tegner Activity Scale at 6 months but returned to the near pre-injury level (5.98 ± 0.924) at 1 year (5.67 ± 0.816) which was insignificant ( p  = 0.1067). Three patients sustained mild complications. 93% were satisfied with the surgery, 66% returned to sports and no patient underwent re-operation., Conclusions: Combination of LET with ACLR produces good functional outcomes, high rates of return to sports activities, and no graft failure in young patients at high risk of failure., Competing Interests: Conflict of InterestDebashish Mishra declares that he has no conflict of interest. Suhas Sondur declares that he has no conflict of interest. Anwesit Mohanty declares that he has no conflict of interest. Swatantra Mohanty declares that he has no conflict of interest. Ankit Gulia declares that he has no conflict of interest. Shakti Prasad Das declares that he has no conflict of interest., (© Indian Orthopaedics Association 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Background: Tyrosine kinase inhibitors improve chronic myeloid leukemia (CML) outcomes. Dasatinib inhibits breakpoint cluster region-Abelson 1 proto-oncogene tyrosine kinase better than imatinib in CML. T-regulatory cells prevent autoimmune diseases and aberrant immune responses by reducing oncoprotein antigen reactivity. They also reduce self-antigen-induced immune responses to maintain peripheral tolerance. In this study, T-regulatory cells in peripheral blood of chronic myeloid leukemia-chronic phase patients were measured, together with serum levels of cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) and transforming growth factor (TGF)-β1 at diagnosis and 3 months postdasatinib therapy., Materials and Methods: The Pathology and Clinical Haematology Departments at King George's Medical University, Lucknow, India, conducted this prospective analytical study. Forty CML-chronic patients and 10 healthy controls were analyzed. Flow cytometry was used to determine T-regulatory cell percentage in peripheral blood mononuclear cells of newly diagnosed CML patients before and after 3 months of dasatinib treatment; ELISA was used to measure serum levels of CTLA-4 and TGF-β1., Results: T-regulatory cells, CTLA-4, and TGF-β1 significantly decreased in CML-chronic phase patients after 3 months of dasatinib therapy compared to the initial diagnosis. No significant change in T-regulatory cell, CTLA-4, or TGF-β1 percentages were seen between responders and poor responders. However, responders had a lower percentage of T-regulatory cells than suboptimal responders., Conclusions: The study concluded that dasatinib treatment improved response in CML patients with decreased Treg cells. Dasatinib reduces Treg-mediated immunological suppression, reducing CTLA-4 and TGF-β1 levels., (Copyright © 2024 Copyright: © 2024 Annals of African Medicine.)

Background: Acute encephalitis (AE) is associated with a high burden of mortality and permanent disability and has a spectrum of underlying etiologies. The prognosis of encephalitis is difficult and almost all the patients seem to be at a high risk of poor outcomes. A number of physiological changes take place during encephalitis and have been evaluated for their prognostic value. Platelet count, which has been recognized as a surrogate prognostic marker in various viral illnesses, has recently been recognized to have a prognostic value in AE too. In the present study, we attempted to study the role of thrombocytopenia in the prognosis of AE., Methods: Total of 98 cases based on clinical, cerebrospinal fluid, and radiological profiles consistent with the diagnosis of AE were enrolled in the study. A clinical profile was noted, and platelet count was assessed. Thrombocytopenia was defined as platelet count <150,000/mm3. Platelet count 100,000-150,000, 50,000-99,999, and <50,000/mm3 were considered mild, moderate, and severe thrombocytopenia. The underlying etiology was explored, and patients were followed till discharge/outcome. The outcome was noted in terms of the Modified Rankin score (MRS). MRS 0-2 was considered good, 3-4 fair, and 5-6 as poor outcome., Results: The mean age of patients was 34.06 ± 18.76 years. Majority of patients were women (54.1%). Prevalence of thrombocytopenia was 75.5%. A total of 34 (45.9%) had mild, 30 (40.5%) had moderate, and 10 (13.5%) had severe thrombocytopenia. Acute viral encephalitis (unclassified) was the most common etiology (33.7%), followed by scrub meningoencephalitis (24.5%) and Japanese encephalitis (12.2%), respectively. Good, fair, and poor outcomes were noted in 48 (49%), 21 (21.4%), and 29 (29.6%) cases. On univariate analysis, no significant association of poor outcome was seen with age, sex, duration of fever, and mechanical ventilation need (P > 0.05). Low Glasgow Coma Scale (GCS), splenomegaly, low platelet count, and Japanese encephalitis virus/scrub typhus etiologies were found to be significantly associated with poor outcomes (P < 0.05). Thrombocytopenia compared to normal platelet count and severe thrombocytopenia compared to mild and moderate thrombocytopenia were significantly associated with poor outcomes (P < 0.05). On multivariate analysis, GCS <8 (odds ratio [OR] =4.52; 95% confidence interval [CI] =1.56-13.20) and thrombocytopenia (OR = 11.92; 95% CI = 1.38-103.32) emerged as independent predictors of poor outcome., Conclusions: The findings of the study showed that low GCS and thrombocytopenia could be used as predictors of poor outcomes in AE cases., (Copyright © 2024 Copyright: © 2024 Annals of African Medicine.)