Epidemiological Predictors of Financial Toxicity in Surgical Burn Injuries: A Multicenter, Longitudinal, Cohort Study.

BACKGROUND: Burns constitute a major global health challenge, causing over 11 million injuries and 300,000 deaths annually and surpassing the economic burden of cervical cancer and HIV combined. Despite this, patient-level financial consequences of burn injuries remain poorly quantified, with a significant gap in data from low- and middle-income countries. In this study, we evaluate financial toxicity in burn patients. METHODS: A prospective, multicenter cohort study was conducted across two tertiary care hospitals in India, assessing 123 adult surgical in-patients undergoing operative interventions for burn injuries. Patient sociodemographic, clinical, and financial data were collected through surveys and electronic records during hospitalization and at 1, 3, and 6 months postoperatively. Out-of-pocket costs (OOPCs) for surgical burn treatment were evaluated during hospitalization. Longitudinal changes in income, employment status, and affordability of basic subsistence needs were assessed at the 1-, 3-, and 6-month postoperative time point. Degree of financial toxicity was calculated using a combination of the metrics catastrophic health expenditure and financial hardship. Development of financial toxicity was compared by sociodemographic and clinical characteristics using logistic regression models. RESULTS: Of the cohort, 60% experienced financial toxicity. Median OOPCs was US$555.32 with the majority of OOPCs stemming from direct nonmedical costs (US$318.45). Cost of initial hospitalization exceeded monthly annual income by 80%. Following surgical burn care, income decreased by US$318.18 within 6 months, accompanied by a 53% increase in unemployment rates. At least 40% of the cohort consistently reported inability to afford basic subsistence needs within the 6-month perioperative period. Significant predictors of developing financial toxicity included male gender (odds ratio, 4.17; 95% confidence interval, 1.25-14.29; P = 0.02) and hospital stays exceeding 20 days (odds ratio, 11.17; 95% confidence interval, 2.11-59.22; P ≤ 0.01). CONCLUSIONS: Surgical treatment for burn injuries is associated with substantial financial toxicity. National and local policies must expand their scope beyond direct medical costs to address direct nonmedical and indirect costs. These include burn care insurance, teleconsultation follow-ups, hospital-affiliated subsidized lodging, and resources for occupational support and rehabilitation. These measures are crucial to alleviate the financial burden of burn care, particularly during the perioperative period.

Significance of dietary quinoa husk (Chenopodium quinoa) in gene regulation for stress mitigation in fish.

The persistent challenges posed by pollution and climate change are significant factors disrupting ecosystems, particularly aquatic environments. Numerous contaminants found in aquatic systems, such as ammonia and metal toxicity, play a crucial role in adversely affecting aquaculture production. Against this backdrop, fish feed was developed using quinoa husk (the byproduct of quinoa) as a substitute for fish meal. Six isonitrogenous diets (30%) and isocaloric diets were formulated by replacing fish meal with quinoa husk at varying percentages: 0% quinoa (control), 15, 20, 25, 30 and 35%. An experiment was conducted to explore the potential of quinoa husk in replacing fish meal and assess its ability to mitigate ammonia and arsenic toxicity as well as high-temperature stress in Pangasianodon hypophthalmus. The formulated feed was also examined for gene regulation related to antioxidative status, immunity, stress proteins, growth regulation, and stress markers. The gene regulation of sod, cat, and gpx in the liver was notably upregulated under concurrent exposure to ammonia, arsenic, and high-temperature (NH3 + As + T) stress. However, quinoa husk at 25% downregulated sod, cat, and gpx expression compared to the control group. Furthermore, genes associated with stress proteins HSP70 and DNA damage-inducible protein (DDIP) were significantly upregulated in response to stressors (NH3 + As + T), but quinoa husk at 25% considerably downregulated HSP70 and DDIP to mitigate the impact of stressors. Growth-responsive genes such as myostatin (MYST) and somatostatin (SMT) were remarkably downregulated, whereas growth hormone receptor (GHR1 and GHRß), insulin-like growth factors (IGF1X, IGF2X), and growth hormone gene were significantly upregulated with quinoa husk at 25%. The gene expression of apoptosis (Caspase 3a and Caspase 3b) and nitric oxide synthase (iNOS) were also noticeably downregulated with quinoa husk (25%) reared under stressful conditions. Immune-related gene expression, including immunoglobulin (Ig), toll-like receptor (TLR), tumor necrosis factor (TNFα), and interleukin (IL), strengthened fish immunity with quinoa husk feed. The results revealed that replacing 25% of fish meal with quinoa husk could improve the gene regulation of P. hypophthalmus involved in mitigating ammonia, arsenic, and high-temperature stress in fish.

Comparative evaluation of tocilizumab and itolizumab for treatment of severe COVID-19 in India: a retrospective cohort study.

Background: Itolizumab downregulates the synthesis of proinflammatory cytokines and adhesion molecules by inhibiting CD6 leading to lower levels of interferon-γ, interleukin-6, and tumor necrotic factor-α and reduced T-cell infiltration at inflammatory sites. This study aims to compare the effects of tocilizumab and itolizumab in the management of severe coronavirus disease 2019 (COVID-19). Methods: The study population was adults (>18 years) with severe COVID-19 pneumonia admitted to the intensive care unit receiving either tocilizumab or itolizumab during their stay. The primary outcome was clinical improvement (CI), defined as a two-point reduction on a seven-point ordinal scale in the status of the patient from initiating the drug or live discharge. The secondary outcomes were time until CI, improvement in PO2/FiO2 ratio, best PO2/FiO2 ratio, need for mechanical ventilation after administration of study drugs, time to discharge, and survival days. Results: Of the 126 patients included in the study, 92 received tocilizumab and 34 received itolizumab. CI was seen in 46.7% and 61.7% of the patients in the tocilizumab and itolizumab groups, respectively and was not statistically significant (P=0.134). The PO2/FiO2 ratio was significantly better with itolizumab compared to tocilizumab (median [interquartile range]: 315 [200-380] vs. 250 [150-350], P=0.043). The incidence of serious adverse events due to the study drugs was significantly higher with itolizumab compared to tocilizumab (14.7% vs. 3.3%, P=0.032). Conclusions: The CI with itolizumab is similar to tocilizumab. Better oxygenation can be achieved with itolizumab and it can be a substitute for tocilizumab in managing severe COVID-19.

Unraveling the genetics of heat tolerance in chickpea landraces (Cicer arietinum L.) using genome-wide association studies.

Chickpea, being an important grain legume crop, is often confronted with the adverse effects of high temperatures at the reproductive stage of crop growth, drastically affecting yield and overall productivity. The current study deals with an extensive evaluation of chickpea genotypes, focusing on the traits associated with yield and their response to heat stress. Notably, we observed significant variations for these traits under both normal and high-temperature conditions, forming a robust basis for genetic research and breeding initiatives. Furthermore, the study revealed that yield-related traits exhibited high heritability, suggesting their potential suitability for marker-assisted selection. We carried out single-nucleotide polymorphism (SNP) genotyping using the genotyping-by-sequencing (GBS) method for a genome-wide association study (GWAS). Overall, 27 marker-trait associations (MTAs) linked to yield-related traits, among which we identified five common MTAs displaying pleiotropic effects after applying a stringent Bonferroni-corrected p-value threshold of <0.05 [-log10(p) > 4.95] using the BLINK (Bayesian-information and linkage-disequilibrium iteratively nested keyway) model. Through an in-depth in silico analysis of these markers against the CDC Frontier v1 reference genome, we discovered that the majority of the SNPs were located at or in proximity to gene-coding regions. We further explored candidate genes situated near these MTAs, shedding light on the molecular mechanisms governing heat stress tolerance and yield enhancement in chickpeas such as indole-3-acetic acid-amido synthetase GH3.1 with GH3 auxin-responsive promoter and pentatricopeptide repeat-containing protein, etc. The harvest index (HI) trait was associated with marker Ca3:37444451 encoding aspartic proteinase ortholog sequence of Oryza sativa subsp. japonica and Medicago truncatula, which is known for contributing to heat stress tolerance. These identified MTAs and associated candidate genes may serve as valuable assets for breeding programs dedicated to tailoring chickpea varieties resilient to heat stress and climate change.

Can glycated haemoglobin (HbA1c) be used as a predictor of left ventricular diastolic dysfunction in non-hypertensive patients with newly diagnosed type 2 diabetes mellitus: a cross-sectional study at a tertiary care centre in Eastern India.

OBJECTIVES: This study was conducted to establish the association between glycated haemoglobin (HbA1c) and left ventricular diastolic dysfunction (LVDD) in non-hypertensive patients with newly diagnosed type 2 diabetes mellitus (DM) and determine the cut-off value of HbA1c for detecting LVDD. DESIGN: Cross-sectional study. SETTING: This study was conducted in General Medicine Department in collaboration with the Cardiology Department at All India Institute of Medical Sciences, Patna. PARTICIPANTS: The study population comprised patients with newly diagnosed type 2 DM within the past 3 months, aged between 18 years and 80 years, who were not hypertensive and without any systemic diseases and who presented to the General Medicine Department. PRIMARY AND SECONDARY OUTCOME MEASURES: The presence of LVDD was the primary outcome measure. RESULTS: Among the total of 60 participants, it was observed that age (adjusted odds ratio (AOR): 1.169, 95% CI: 1.066 to 1.283) and HbA1c (AOR: 2.625, 95% CI: 1.264 to 5.450) were found to be independent predictors for the presence of LVDD. Receiver operating characteristic analysis identified a cut-off value of HbA1c at 9.5% (80 mmol/mol) for detecting LVDD, with a specificity of 96.43%, a sensitivity of 37.5% and a positive predictive value (PPV) of 91.62%. CONCLUSIONS: This study demonstrated that age and HbA1c levels are independent predictors of LVDD in patients with newly diagnosed type 2 DM without hypertension. A cut-off value of 9.5% for HbA1c was identified with a high specificity and PPV for predicting LVDD in patients with newly diagnosed type 2 diabetes. This underscores the importance of conducting echocardiography in patients with newly diagnosed asymptomatic type 2 diabetes with HbA1c 9.5% or more to assess LVDD, allowing for prompt interventions if necessary and to decelerate the progression towards heart failure.

Clinical features, pathogenesis, pathology, neuroimaging, clinical course and outcome of measles inclusion-body encephalitis: a systematic review of published case reports and case series.

Measles inclusion-body encephalitis (MIBE) is rare, with insights largely from case studies. We systematically analyzed subacute Sclerosing Panencephalitis (SSPE) cases in immunocompromised patients, identifying distinctive clinical and neuroimaging features. These findings could facilitate MIBE diagnosis without the need for brain biopsies. Our systematic review on MIBE and HIV-related SSPE adhered to PRISMA guidelines and was registered with PROSPERO. We searched multiple databases and followed a detailed inclusion process with independent reviews and quality assessment. Data on patient demographics, clinical features, and outcomes were compiled. A review of 39 studies on 49 MIBE patients and 8 reports on HIV-positive SSPE patients was conducted. Acute lymphoblastic leukemia, HIV, organ transplants, and malignancies were common precursors to MIBE. Perinatal HIV was prevalent among SSPE cases. Seizures were the primary symptom in MIBE, often drug-resistant and progressing to status epilepticus or epilepsia partialis continua, whereas periodic myoclonus was universal in SSPE. Neuroimaging showed distinct patterns for each group, and histopathology confirmed measles virus presence in 39% of MIBE cases. MIBE patients typically progressed to coma and death. In conclusion, MIBE and SSPE in HIV-infected patients present with distinct clinical pictures but identical brain pathological abnormalities.

Treatment Outcome in Patients with Disseminated Cysticercosis: A Systematic Review of Case Reports and Case Series.

Disseminated cysticercosis is defined by multiple brain lesions and involvement of other body sites. Cysticidal treatment in disseminated cysticercosis is considered life-threatening. We conducted a systematic review of all published cases and case series to assess the safety and efficacy of cysticidal treatment. We conducted a systematic review in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (PROSPERO CRD42022331895) to assess the safety and efficacy of cysticidal treatment. Using the search term "disseminated neurocysticercosis OR disseminated cysticercosis," databases like PubMed, Scopus, Embase, and Google Scholar were searched. Outcomes included death and secondary measures like clinical improvement and lesion reduction. We calculated the predictors of primary outcome (death) using the binary logistic regression analysis. We reviewed 222 published cases from 101 publications. Approximately 87% cases were reported from India. Of 222 cases, 134 (60%) received cysticidal treatment. Follow-up information was available from 180 patients, 11 of them died, and 169 showed clinical improvement. The death rate was 4% (5 out of 114) in patients treated with cysticidal drugs plus corticosteroids, in comparison with 13% (5 out of 38) in patients who were treated with corticosteroids alone. All patients using only praziquantel faced fatality. Death predictors identified were altered sensorium and lack of treatment with albendazole. We noted that the risk of death after cysticidal treatment is not as we expected, and a multicentric randomized controlled trial is needed to resolve this issue.

Native Mass Spectrometry Dissects the Structural Dynamics of an Allosteric Heterodimer of SARS-CoV-2 Nonstructural Proteins.

Structure-based drug design, which relies on precise understanding of the target protein and its interaction with the drug candidate, is dramatically expedited by advances in computational methods for candidate prediction. Yet, the accuracy needs to be improved with more structural data from high throughput experiments, which are challenging to generate, especially for dynamic and weak associations. Herein, we applied native mass spectrometry (native MS) to rapidly characterize ligand binding of an allosteric heterodimeric complex of SARS-CoV-2 nonstructural proteins (nsp) nsp10 and nsp16 (nsp10/16), a complex essential for virus survival in the host and thus a desirable drug target. Native MS showed that the dimer is in equilibrium with monomeric states in solution. Consistent with the literature, well characterized small cosubstrate, RNA substrate, and product bind with high specificity and affinity to the dimer but not the free monomers. Unsuccessfully designed ligands bind indiscriminately to all forms. Using neutral gas collision, the nsp16 monomer with bound cosubstrate can be released from the holo dimer complex, confirming the binding to nsp16 as revealed by the crystal structure. However, we observed an unusual migration of the endogenous zinc ions bound to nsp10 to nsp16 after collisional dissociation. The metal migration can be suppressed by using surface collision with reduced precursor charge states, which presumably resulted in minimal gas-phase structural rearrangement and highlighted the importance of complementary techniques. With minimal sample input (∼µg), native MS can rapidly detect ligand binding affinities and locations in dynamic multisubunit protein complexes, demonstrating the potential of an "all-in-one" native MS assay for rapid structural profiling of protein-to-AI-based compound systems to expedite drug discovery.

Immunomodulatory Effect of Phytoactive Compounds on Human Health: A Narrative Review Integrated with Bioinformatics Approach.

BACKGROUND: Immunomodulation is the modification of immune responses to control disease progression. While the synthetic immunomodulators have proven efficacy, they are coupled with toxicity and other adverse effects, and hence, the efforts were to identify natural phytochemicals with immunomodulatory potential. OBJECTIVE: The objective of this study is to understand the immunomodulatory properties of various phytochemicals and investigate them in Echinacea species extracts using an in silico approach. METHODOLOGY: Several scientific database repositories were searched using different keywords: "Phytochemicals," "Alkaloids," "Polyphenols," "Flavonoids," "Lectins," "Glycosides," "Tannins," "Terpenoids," "Sterols," "Immunomodulators," and "Human Immune System" without any language restriction. Additionally, the study specifically investigated the immunomodulatory properties of Echinacea species extracts using gene expression analysis of GSE12259 from NCBI-GEO through the Bioconductor package GEOquery and limma. RESULTS: A total of 182 studies were comprehensively analyzed to understand immunomodulatory phytochemicals. The in silico analysis highlighted key biological processes (positive regulation of cytokine production, response to tumor necrosis factor) and molecular functions (cytokine receptor binding, receptor-ligand activity, and cytokine activity) among Echinacea species extracts contributing to immune responses. Further, it also indicated the association of various metabolic pathways, i.e., pathways in cancer, cytokine-cytokine receptor interaction, NF-kappa B, PI3K-Akt, TNF, MAPK, and NOD-like receptor signaling pathways, with immune responses. The study revealed various hub targets, including CCL20, CCL4, GCH1, SLC7A11, SOD2, EPB41L3, TNFAIP6, GCLM, EGR1, and FOS. CONCLUSION: The present study presents a cumulative picture of phytochemicals with therapeutic benefits. Additionally, the study also reported a few novel genes and pathways in Echinacea extracts by re-analyzing GSE 12259, indicating its anti-inflammatory, anti-viral, and immunomodulatory properties.

Computer-aided drug discovery of c-Abl kinase inhibitors from plant compounds against chronic myeloid leukemia.

Chronic myeloid leukemia (CML) is a hematological malignancy characterized by the neoplastic transformation of hematopoietic stem cells, driven by the Philadelphia (Ph) chromosome resulting from a translocation between chromosomes 9 and 22. This Ph chromosome harbors the breakpoint cluster region (BCR) and the Abelson (ABL) oncogene (BCR-ABL1) which have a constitutive tyrosine kinase activity. However, the tyrosine kinase activity of BCR-ABL1 have been identified as a key player in CML initiation and maintenance through c-Abl kinase. Despite advancements in tyrosine kinase inhibitors, challenges such as efficacy, safety concerns, and recurring drug resistance persist. This study aims to discover potential c-Abl kinase inhibitors from plant compounds with anti-leukemic properties, employing drug-likeness assessment, molecular docking, in silico pharmacokinetics (ADMET) screening, density function theory (DFT), and molecular dynamics simulations (MDS). Out of 58 screened compounds for drug-likeness, 44 were docked against c-Abl kinase. The top hit compound (isovitexin) and nilotinib (control drug) were subjected to rigorous analyses, including ADMET profiling, DFT evaluation, and MDS for 100 ns. Isovitexin demonstrated a notable binding affinity (-15.492 kcal/mol), closely comparable to nilotinib (-16.826 kcal/mol), showcasing a similar binding pose and superior structural stability and reactivity. While these findings suggest isovitexin as a potential c-Abl kinase inhibitor, further validation through urgent in vitro and in vivo experiments is imperative. This research holds promise for providing an alternative avenue to address existing CML treatment and management challenges.Communicated by Ramaswamy H. Sarma.

Antidiabetic Evaluation of Kigelia pinnata Root Bark Extract in Streptozotocin-Induced Type-2 Diabetes Model of Rats.

Diabetes mellitus (DM) is the most common endocrine disorder characterized by increased blood glucose levels resulting from defective insulin secretion, resistance to insulin action, or both. DM is often associated with severe complications, and there is an increasing appreciation that cognitive function declines in DM. The aim of this research work was to evaluate Kigelia pinnata root bark extract in Streptozotocin (STZ)-induced type-2 diabetes. Experimental diabetes was induced by a single administration of STZ (60 mg/kg, intraperitoneal [i.p.]), immediately after the STZ administration, and all animals were fed with normal food and water. Nicotinamide was administered (120 mg/kg, i.p.) 15 min before STZ. The development of hyperglycemia was confirmed by the elevated blood glucose levels determined at fixed intervals, which was confirmed by measuring fasting blood glucose levels in rats' blood taken from the tail vein. Supplementation with ethanolic extract of K. pinnata root bark (EEKP) significantly reduced the elevated blood glucose in STZ-induced hyperglycemia in rats. EEKP significantly restored the biochemical and antioxidant defense system. On the final day of the protocol, the extract also reduced inflammatory cytokines in the blood serum.

Neuroimaging Abnormalities in Patients with Subacute Sclerosing Panencephalitis : Prospective Follow-up Study.

OBJECTIVE: This study aimed to assess the neuroimaging abnormalities and their progression in patients with Subacute sclerosing panencephalitis (SSPE) and identify clinical predictors of these imaging findings. METHODS: This prospective observational study evaluated clinical and neuroimaging features in patients with SSPE. Patients were categorized using Dyken's criteria, Jabbour's staging system, and the definition of fulminant SSPE. They underwent comprehensive clinical assessments, cerebrospinal fluid examination, Electroencephalogram (EEG), and Magnetic Resonance Imaging (MRI) scans. Treatment involved intrathecal interferon­α and antiepileptic medications. Functional disability was assessed using the modified Barthel index. Follow-ups were performed at 6 months, including reassessment of Modified Barthel Index (MBI) and Jabbour's staging and EEG and MRI scans. RESULTS: The mean age was 13.9 ± 6.7 years, with males comprising 81.5% (44/54) of the cohort. Fulminant SSPE was noted in 33% (18/54) of cases. Disease duration before presentation varied significantly between fulminant and non-fulminant forms (p = 0.001). Neuroimaging abnormalities were more prevalent in JS III stage patients, with diffuse cerebral atrophy being a significant finding (p = 0.011). Basal ganglia involvement correlated with movement disorders. The 6­month follow-up showed increased cerebral atrophy (p = 0.004). Increasing disease duration was an independent predictor of cerebral atrophy. An Intercomplex interval (ICI) of more than 10 minutes correlated with normal neuroimaging, 10 patients died within the study period, 8 of whom had fulminant SSPE. CONCLUSION: Parieto-occipital White matter hyperintensity (WMH) is the most prevalent and sensitive neuroimaging finding for the diagnosis of SSPE. Despite interferon treatment, cerebral atrophy progressed in both aggressive and fulminant SSPE. Increasing disease duration is an independent predictor of cerebral atrophy.

Identification of pleiotropic loci mediating structural and non-structural carbohydrate accumulation within the sorghum bioenergy association panel using high-throughput markers.

Molecular characterization of diverse germplasm can contribute to breeding programs by increasing genetic gain for sorghum [Sorghum bicolor (L.) Moench] improvement. Identifying novel marker-trait associations and candidate genes enriches the existing genomic resources and can improve bioenergy-related traits using genomic-assisted breeding. In the current scenario, identifying the genetic loci underlying biomass and carbon partitioning is vital for ongoing efforts to maximize each carbon sink's yield for bioenergy production. Here, we have processed a high-density genomic marker (22 466 550) data based on whole-genome sequencing (WGS) using a set of 365 accessions from the bioenergy association panel (BAP), which includes ~19.7 million (19 744 726) single nucleotide polymorphism (SNPs) and 2.7 million (~2 721 824) insertion deletions (indels). A set of high-quality filtered SNP (~5.48 million) derived markers facilitated the assessment of population structure, genetic diversity, and genome-wide association studies (GWAS) for various traits related to biomass and its composition using the BAP. The phenotypic traits for GWAS included seed color (SC), plant height (PH), days to harvest (DTH), fresh weight (FW), dry weight (DW), brix content % (BRX), neutral detergent fiber (NDF), acid detergent fiber (ADF), non-fibrous carbohydrate (NFC), and lignin content. Several novel loci and candidate genes were identified for bioenergy-related traits, and some well-characterized genes for plant height (Dw1 and Dw2) and the YELLOW SEED1 locus (Y1) were validated. We further performed a multi-variate adaptive shrinkage analysis to identify pleiotropic QTL, which resulted in several shared marker-trait associations among bioenergy and compositional traits. Significant marker-trait associations with pleiotropic effects can be used to develop molecular markers for trait improvement using a marker-assisted breeding approach. Significant nucleotide diversity and heterozygosity were observed between photoperiod-sensitive and insensitive individuals of the panel. This diverse bioenergy panel with genomic resources will provide an excellent opportunity for further genetic studies, including selecting parental lines for superior hybrid development to improve biomass-related traits in sorghum.

Optimization, In Vitro and Ex Vivo Assessment of Nanotransferosome Gels Infused with a Methanolic Extract of Solanum xanthocarpum for the Topical Treatment of Psoriasis.

The goal of this investigation is to improve the topical delivery of medicine by preparing and maximizing the potential of a nanotransferosome gel infused with Solanum xanthocarpum methanolic extract (SXE) to provide localized and regulated distribution. Thin-film hydration was used to create SXE-infused nanotransferosomes (SXE-NTFs), and a Box-Behnken design was used to improve them. Phospholipon 90G (X1), cholesterol (X2) and sodium cholate (X3) were chosen as the independent variables, and their effects on vesicle size (Y1), polydispersity index (PDI) (Y2) and the percentage of entrapment efficiency (EE) (Y3) were observed both individually and in combination. For the SXE-NTFs, the vesicle size was 146.3 nm, the PDI was 0.2594, the EE was 82.24 ± 2.64%, the drug-loading capacity was 8.367 ± 0.07% and the drug release rate was 78.86 ± 5.24%. Comparing the antioxidant activity to conventional ascorbic acid, it was determined to be 83.51 ± 3.27%. Ex vivo permeation tests revealed that the SXE-NTF gel (82.86 ± 2.38%) considerably outperformed the SXE gel (35.28 ± 1.62%) in terms of permeation. In addition, it seemed from the confocal laser scanning microscopy (CLSM) picture of the Wistar rat's skin that the rhodamine-B-loaded SXE-NTF gel had a higher penetration capability than the control. Dermatokinetic studies showed that the SXE-NTF gel had a better retention capability than the SXE gel. According to the experimental results, the SXE-NTF gel is a promising and successful topical delivery formulation.

Leveraging Artificial Intelligence to Expedite Antibody Design and Enhance Antibody-Antigen Interactions.

This perspective sheds light on the transformative impact of recent computational advancements in the field of protein therapeutics, with a particular focus on the design and development of antibodies. Cutting-edge computational methods have revolutionized our understanding of protein-protein interactions (PPIs), enhancing the efficacy of protein therapeutics in preclinical and clinical settings. Central to these advancements is the application of machine learning and deep learning, which offers unprecedented insights into the intricate mechanisms of PPIs and facilitates precise control over protein functions. Despite these advancements, the complex structural nuances of antibodies pose ongoing challenges in their design and optimization. Our review provides a comprehensive exploration of the latest deep learning approaches, including language models and diffusion techniques, and their role in surmounting these challenges. We also present a critical analysis of these methods, offering insights to drive further progress in this rapidly evolving field. The paper includes practical recommendations for the application of these computational techniques, supplemented with independent benchmark studies. These studies focus on key performance metrics such as accuracy and the ease of program execution, providing a valuable resource for researchers engaged in antibody design and development. Through this detailed perspective, we aim to contribute to the advancement of antibody design, equipping researchers with the tools and knowledge to navigate the complexities of this field.

Understanding the molecular mechanism of arsenic and ammonia toxicity and high-temperature stress in Pangasianodon hypophthalmus.

The current investigation explores the mechanisms of ammonia and arsenic toxicity, along with high-temperature stress, which other researchers rarely addressed. Pangasianodon hypophthalmus was exposed to low doses of ammonia and arsenic (1/10th of LC50, 2.0 and 2.68 mg L-1, respectively) and high temperature (34 °C) for 105 days. The following treatments were applied: control (unexposed), arsenic (As), ammonia (NH3), ammonia + arsenic (NH3 + As), ammonia + temperature (NH3 + T), and NH3 + As + T. Cortisol levels significantly increased with exposure to ammonia (NH3), arsenic (As), and high temperature (34 °C) compared to the unexposed group. Heat shock protein (HSP 70), inducible nitric oxide synthase (iNOS), and metallothionein (MT) gene expressions were notably upregulated by 122-210%, 98-122%, and 64-238%, respectively, compared to the control. Neurotransmitter enzymes (acetylcholine esterase, AChE) were significantly inhibited by NH3 + As + T, followed by other stressor groups. The apoptotic (caspase, Cas 3a and 3b) and detoxifying (cytochrome P450, CYP P450) pathways were substantially affected by the NH3 + As + T group. Immune (total immunoglobulin, Ig; tumor necrosis factor TNFα; and interleukin IL) and growth-related genes (growth hormone, GH; growth hormone regulator, GHR1 and GHRß; myostatin, MYST and somatostatin, SMT) were noticeably upregulated by NH3 + As + T, followed by other stress groups, compared to the control group. Weight gain %, protein efficiency ratio, feed efficiency ratio, specific growth rate, and other growth attributes were significantly affected by low doses of ammonia, arsenic, and high-temperature stress. Albumin, total protein, globulin, A:G ratio, and myeloperoxidase (MPO) were highly affected by the As + NH3 + T group. Blood profiling, including red blood cells (RBC), white blood count (WBC), and hemoglobin (Hb), were also impacted by stressor groups compared to the control group. Genotoxicity, as DNA damage, was significantly higher in groups exposed to NH3 + As + T (89%), NH3 + T (78%), NH3 (73), NH3 + As (71), and As (68%). The bioaccumulation of arsenic was substantially higher in liver and kidney tissues. The present study contributes to understanding the toxicity mechanisms of ammonia and arsenic, as well as high-temperature stress, through different gene expressions, biochemical attributes, genotoxicity, immunological status, and growth performance of P. hypophthalmus.

The spectrum of psychiatric manifestations in subacute sclerosing panencephalitis: A systematic review of published case reports and case series.

Data related to psychiatric manifestations in subacute sclerosing panencephalitis (SSPE) is currently available only in the form of isolated case reports. In this systematic review, we evaluated the spectrum of psychiatric manifestations and their impact on the course and outcome of SSPE. Data were obtained from 4 databases (PubMed, Embase, Scopus, and Google Scholar), with the most recent search conducted on March 27, 2023. The PRISMA guidelines were followed, and the PROSPERO registration number for the protocol is CRD42023408227. SSPE was diagnosed using Dyken's criteria. Extracted data were recorded in an Excel spreadsheet. To evaluate the quality of the data, the Joanna Briggs Institute Critical Appraisal tool was employed. Our search resulted in 30 published reports of 32 patients. The mean age was 17.9 years. Schizophrenia, catatonia, and poorly characterized psychotic illnesses were the 3 most common psychiatric presentations that were seen in 63% (20/32) of cases. Catatonia was seen in 4 patients. Affective disorders, mania, and depression were reported among 22% (7/32) cases. In approximately 81% (26/32) cases, the course of SSPE was acute fulminant. Treatment with antipsychotic drugs had poor or no response. Out of 17 patients, who received antipsychotic drugs, 6 patients noted severe extrapyramidal adverse effects. SSPE often masquerades as a psychiatric disorder. Unresponsive psychiatric symptoms, early extrapyramidal signs, and progressive encephalopathy indicate SSPE.

Occurrence and determinants of seizures and their impact on tuberculous meningitis: a prospective evaluation.

OBJECTIVE: To assess the incidence of seizures and the factors contributing to poor outcomes in patients with tuberculous meningitis (TBM). METHODS: In this prospective observational study, 129 patients with TBM were enrolled at the Department of Neurology, King George's Medical University, Uttar Pradesh, India, from April 2021 to April 2023. Detailed clinical history, neurological examinations, baseline laboratory tests, contrast-enhanced Magnetic resonance imaging (MRI) and electroencephalography (EEG) were obtained for all patients. Patients received anti-tuberculous therapy and, if necessary, anti-epileptic treatment. Patients were followed for 6 months, with outcomes evaluated using the Modified Rankin Scale (MRS). RESULTS: Of the 129 patients, 48 (37.2%) reported seizures. Advanced TBM stage (p = 0.040, OR = 2.50 95% CI:1.02-6.07), cortical involvement (p = .0.013, OR = 2.58 95% CI:1.20-5.51) and spike-wave discharges in the EEG (p = 0.001) were significantly associated with seizure occurrence. After multivariate analysis, only cortical involvement (p = 0.031, OR = 2.34, 95% CI:1.08-5.08) emerged as independent predictor of for seizures. Focal to bilateral seizures (p = 0.008, OR = 9.41, 95% CI: 1.76-74.04), status epilepticus (p = 0.002, OR = 8.00, 95% CI: 1.86-34.32), and rifampicin resistance (p = 0.022, OR = 9.25, 95% CI: 1.43-59.50) were significantly associated with poor outcomes at the 6-month mark. CONCLUSION: Seizures were significantly associated with advanced stage of the disease, cortical involvement on neuro-imaging and epileptiform pattern on EEG. Additionally, focal to bilateral seizures and status epilepticus adversely affected the outcome.

Xanthone Derivatives Enhance the Therapeutic Potential of Neomycin against Polymicrobial Gram-Negative Bacterial Infections.

Gram-negative bacterial infections are difficult to manage as many antibiotics are ineffective owing to the presence of impermeable bacterial membranes. Polymicrobial infections pose a serious threat due to the inadequate efficacy of available antibiotics, thereby necessitating the administration of antibiotics at higher doses. Antibiotic adjuvants have emerged as a boon as they can augment the therapeutic potential of available antibiotics. However, the toxicity profile of antibiotic adjuvants is a major hurdle in clinical translation. Here, we report the design, synthesis, and biological activities of xanthone-derived molecules as potential antibiotic adjuvants. Our SAR studies witnessed that the p-dimethylamino pyridine-derivative of xanthone (X8) enhances the efficacy of neomycin (NEO) against Escherichia coli and Pseudomonas aeruginosa and causes a synergistic antimicrobial effect without any toxicity against mammalian cells. Biochemical studies suggest that the combination of X8 and NEO, apart from inhibiting protein synthesis, enhances the membrane permeability by binding to lipopolysaccharide. Notably, the combination of X8 and NEO can disrupt the monomicrobial and polymicrobial biofilms and show promising therapeutic potential against a murine wound infection model. Collectively, our results unveil the combination of X8 and NEO as a suitable adjuvant therapy for the inhibition of the Gram-negative bacterial infections.