Unraveling gene regulation mechanisms in fish: insights into multistress responses and mitigation through iron nanoparticles.

The recent trend of global warming poses a significant threat to ecosystems worldwide. This global climate change has also impacted the pollution levels in aquatic ecosystems, subsequently affecting human health. To address these issues, an experiment was conducted to investigate the mitigating effects of iron nanoparticles (Fe-NPs) on arsenic and ammonia toxicity as well as high temperature stress (As+NH3+T). Fe-NPs were biologically synthesized using fish waste and incorporated into feed formulations at 10, 15, and 20 mg kg-1 diet. A total of 12 treatments were designed in triplicate following a completely randomized design involving 540 fish. Fe-NPs at 15 mg kg-1 diet notably reduced the cortisol levels in fish exposed to multiple stressors. The gene expressions of HSP 70, DNA damage-inducible protein (DDIP), and DNA damage were upregulated by stressors (As+NH3+T) and downregulated by Fe-NPs. Apoptotic genes (Cas 3a and 3b) and detoxifying genes (CYP 450), metallothionein (MT), and inducible nitric oxide synthase (iNOS) were downregulated by Fe-NPs at 15 mg kg-1 diet in fish subjected to As+NH3+T stress. Immune-related genes such as tumor necrosis factor (TNFα), immunoglobulin (Ig), and interleukin (IL) were upregulated by Fe-NPs, indicating enhanced immunity in fish under As+NH3+T stress. Conversely, Toll-like receptor (TLR) expression was notably downregulated by Fe-NPs at 15 mg kg-1 diet in fish under As+NH3+T stress. Immunological attributes such as nitro blue tetrazolium chloride, total protein, albumin, globulin, A:G ratio, and myeloperoxidase (MPO) were improved by dietary Fe-NPs at 15 mg kg-1 diet in fish, regardless of stressors. The antioxidant genes (CAT, SOD, and GPx) were also strengthened by Fe-NPs in fish. Genes associated with growth performance, such as growth hormone regulator (GHR1 and GHRß), growth hormone (GH), and insulin-like growth factor (IGF 1X and IGF 2X), were upregulated, enhancing fish growth under stress, while SMT and MYST were downregulated by Fe-NPs in the diet. Various growth performance indicators were improved by dietary Fe-NPs at 15 mg kg-1 diet. Notably, Fe-NPs also enhanced arsenic detoxification and reduced the cumulative mortality after a bacterial infection. In conclusion, this study highlights that dietary Fe-NPs can effectively mitigate arsenic and ammonia toxicity as well as high temperature stress by modulating gene expression in fish.

The ACROBAT 2022 challenge: Automatic registration of breast cancer tissue.

The alignment of tissue between histopathological whole-slide-images (WSI) is crucial for research and clinical applications. Advances in computing, deep learning, and availability of large WSI datasets have revolutionised WSI analysis. Therefore, the current state-of-the-art in WSI registration is unclear. To address this, we conducted the ACROBAT challenge, based on the largest WSI registration dataset to date, including 4,212 WSIs from 1,152 breast cancer patients. The challenge objective was to align WSIs of tissue that was stained with routine diagnostic immunohistochemistry to its H&E-stained counterpart. We compare the performance of eight WSI registration algorithms, including an investigation of the impact of different WSI properties and clinical covariates. We find that conceptually distinct WSI registration methods can lead to highly accurate registration performances and identify covariates that impact performances across methods. These results provide a comparison of the performance of current WSI registration methods and guide researchers in selecting and developing methods.

Speciation-specific chromium bioaccumulation and detoxification in fish using hydrogel microencapsulated biogenic nanosilver and zeolite synergizing with biomarkers.

Grass carp intestinal waste-mediated biosynthesized nanosilver (AgNPs) was valorized using guaran and zeolite matrices, resulting in AgNPs-guaran, AgNPs-zeolite, and AgNPs-guaran -zeolite composites. The valorized products were examined using Environmental Scanning Electron Microscopy, Energy Dispersive X-ray analysis and X-ray Diffraction analysis to confirm uniform dispersion and entrapment of AgNPs within the matrixes. These valorized products were evaluated for their efficacy in detoxifying the ubiquitous and toxic hexavalent chromium (Cr6+) in aquatic environments, with Anabas testudineus exposed to 2 mg l-1 of Cr6+ for 60 days. Remarkable reduction of Cr6+ concentration to 0.86 ± 0.007 mg l-1 was achieved with AgNPs-guaran-zeolite composite, indicating successful reclamation of contaminated water and food safety assurance. Consistency in results was further corroborated by minimal stress-related alterations in fish physiological parameters and integrated biomarker response within the experimental group treated with the AgNPs-guaran-zeolite composite. Despite observed chromium accumulation in fish tissues, evidence of physiological stability was apparent, potentially attributable to trivalent chromium accumulation, serving as an essential nutrient for the fish. Additionally, the challenge study involving Anabas testudineus exposed to Aeromonas hydrophila exhibited the lowest cumulative mortality (11.11%) and highest survival rate (87.5%) within the same experimental group. The current study presents a novel approach encompassing the valorization of AgNPs for Cr6+ detoxification under neutral to alkaline pH conditions, offering a comprehensive framework for environmental remediation.

Utility of Itraconazole in Combination with Liposomal Amphotericin B in Rhizopus oryzae Associated Mucormycosis-An Exploratory Study.

BACKGROUND: During the COVID-19 pandemic-associated mucor epidemic, acute antifungal drug shortage necessitated the exploration of other antifungals based on culture sensitivity. Itraconazole is a cheap, safe, and effective antifungal in sensitive cases. METHODOLOGY: We enrolled itraconazole-sensitive COVID-19-associated mucormycosis during the mucormycosis pandemic. After the intensive phase course of liposomal amphotericin B, Itraconazole was offered in susceptible cases during the maintenance phase along with standard of care. These patients were clinically and radiologically followed for 6 months. RESULTS: We enrolled 14 patients (Male: Female-11:3) of Rhino-orbito-cerebral mucormycosis (ROCM) which included 12 diabetics. All patients had facial swelling, orbital swelling, visual impairment, and headache. MRI showed involvement of bilateral sinus (10/14), orbital extension (13/14), cavernous sinus (5/14), cerebral part of the internal carotid artery (3/14), and brain infarcts (4/14). All 14 patients showed sensitivity to Itraconazole with 12 having minimum inhibitory concentration (MIC) ≤ 1 µg/ml and 2 having MIC ≤ 2 µg/ml. Follow-up at 6 months showed clinical improvement in the majority (11/14) and radiological improvement in six out of seven scanned patients. CONCLUSION: Our study shows the potential therapeutic role of oral Itraconazole in ROCM.

Exploring the Therapeutic Potential of Petiveria alliacea L. Phytochemicals: A Computational Study on Inhibiting SARS-CoV-2's Main Protease (Mpro).

The outbreak of SARS-CoV-2, also known as the COVID-19 pandemic, is still a critical risk factor for both human life and the global economy. Although, several promising therapies have been introduced in the literature to inhibit SARS-CoV-2, most of them are synthetic drugs that may have some adverse effects on the human body. Therefore, the main objective of this study was to carry out an in-silico investigation into the medicinal properties of Petiveria alliacea L. (P. alliacea L.)-mediated phytocompounds for the treatment of SARS-CoV-2 infections since phytochemicals have fewer adverse effects compared to synthetic drugs. To explore potential phytocompounds from P. alliacea L. as candidate drug molecules, we selected the infection-causing main protease (Mpro) of SARS-CoV-2 as the receptor protein. The molecular docking analysis of these receptor proteins with the different phytocompounds of P. alliacea L. was performed using AutoDock Vina. Then, we selected the three top-ranked phytocompounds (myricitrin, engeletin, and astilbin) as the candidate drug molecules based on their highest binding affinity scores of -8.9, -8.7 and -8.3 (Kcal/mol), respectively. Then, a 100 ns molecular dynamics (MD) simulation study was performed for their complexes with Mpro using YASARA software, computed RMSD, RMSF, PCA, DCCM, MM/PBSA, and free energy landscape (FEL), and found their almost stable binding performance. In addition, biological activity, ADME/T, DFT, and drug-likeness analyses exhibited the suitable pharmacokinetics properties of the selected phytocompounds. Therefore, the results of this study might be a useful resource for formulating a safe treatment plan for SARS-CoV-2 infections after experimental validation in wet-lab and clinical trials.

Comparative Evaluation of Multiplex PCR, RLEP PCR and LAMP PCR in Urine, Stool and Blood Samples for the Diagnosis of Pediatric Leprosy - A Cross-Sectional Study.

OBJECTIVE: To compare the diagnostic efficacy of multiplex polymerase chain reaction (PCR), Mycobacterium leprae-specific repetitive element (RLEP) PCR and loop-mediated isothermal amplification (LAMP) PCR in the diagnosis of pediatric leprosy as an alternative to slit-skin smear (SSS) examination. METHODS: A cross-sectional study was performed on 26 children aged 0-18 years with characteristic skin lesions of leprosy. SSS examination for acid fast bacilli (AFB) was performed for all children. Additionally, urine, stool and blood samples were tested by three PCR techniques - multiplex, RLEP and LAMP. The results of these tests were compared with each other and with results of SSS examination for acid fast bacilli (AFB) using appropriate statistical tests. RESULTS: Out of 26 patients studied, SSS examination was positive for AFB in 7 cases (26.9%). In blood samples, the positivity of multiplex PCR, RLEP PCR and LAMP PCR was 84.6%, 80.8%, and 80.8%, respectively. Multiplex PCR in blood samples was positive in 100% (n = 7) of SSS positive cases and 84.2% (16 out of 19) of the SSS negative cases (P < 0.001). The positivity of all PCR methods in urine and stool samples was significantly lesser than in blood. CONCLUSION: Multiplex PCR in blood sample is a superior diagnostic tool for pediatric leprosy compared to RLEP PCR and LAMP PCR as well as SSS examination.

The value of whole tumor apparent diffusion coefficient histogram parameters in predicting meningiomas progesterone receptor expression.

This letter provides a critical assessment of a previous study on the utility of whole tumor apparent diffusion coefficient (ADC) histogram characteristics in predicting meningioma progesterone receptor expression. While acknowledging the benefits of employing classical diffusion-weighted imaging (DWI) for non-invasive tumor evaluation, it also emphasizes significant drawbacks. Advanced imaging techniques such as diffusion tensor imaging (DTI) and diffusion kurtosis imaging (DKI) were not used in the study, which could have provided a more comprehensive understanding of tumor microstructure and heterogeneity. Furthermore, the inclusion of necrotic and cystic areas in ADC analysis may distort results due to their different diffusion properties. While focusing on first-order ADC histogram characteristics is useful, it ignores the potential insights gained from higher-order features and texture analysis. These limitations indicate that future research should combine improved imaging modalities with thorough analytical methodologies to increase the predictive value of imaging biomarkers for meningioma features and progesterone receptor expression.

Role of ulinastatin in steroid-induced pancreatitis.

Steroid-induced acute pancreatitis is a rare form of pancreatitis that requires intensive care and has a high morbidity and mortality rate as there is no specific treatment. Management of steroid-induced pancreatitis is generally non-specific and supportive. Here, we are presenting a man in his 40s presented with epigastric pain, fever and vomiting. The patient was diagnosed case of rheumatoid arthritis, for which he was receiving regular 5 mg oral prednisolone therapy. Based on history, and clinical, biochemical and radiological imaging a diagnosis of steroid-induced pancreatitis was made, which was successfully managed with the help of ulinastatin and other supportive treatments. A serine protease inhibitor like ulinastatin may be used early in the clinical management of steroid-induced pancreatitis.

Comprehensive benchmarking of CNN-based tumor segmentation methods using multimodal MRI data.

Magnetic resonance imaging (MRI) has become an essential and a frontline technique in the detection of brain tumor. However, segmenting tumors manually from scans is laborious and time-consuming. This has led to an increasing trend towards fully automated methods for precise tumor segmentation in MRI scans. Accurate tumor segmentation is crucial for improved diagnosis, treatment, and prognosis. This study benchmarks and evaluates four widely used CNN-based methods for brain tumor segmentation CaPTk, 2DVNet, EnsembleUNets, and ResNet50. Using 1251 multimodal MRI scans from the BraTS2021 dataset, we compared the performance of these methods against a reference dataset of segmented images assisted by radiologists. This comparison was conducted using segmented images directly and further by radiomic features extracted from the segmented images using pyRadiomics. Performance was assessed using the Dice Similarity Coefficient (DSC) and Hausdorff Distance (HD). EnsembleUNets excelled, achieving a DSC of 0.93 and an HD of 18, outperforming the other methods. Further comparative analysis of radiomic features confirmed EnsembleUNets as the most precise segmentation method, surpassing other methods. EnsembleUNets recorded a Concordance Correlation Coefficient (CCC) of 0.79, a Total Deviation Index (TDI) of 1.14, and a Root Mean Square Error (RMSE) of 0.53, underscoring its superior performance. We also performed validation on an independent dataset of 611 samples (UPENN-GBM), which further supported the accuracy of EnsembleUNets, with a DSC of 0.85 and an HD of 17.5. These findings provide valuable insight into the efficacy of EnsembleUNets, supporting informed decisions for accurate brain tumor segmentation.

Exploring the genetic variability in yield, nutritional and digestibility traits in oat grains through ruminant nutrition.

Oat is a dual-purpose crop used for both food and feed for animals. The objective of this work is to characterize oat varieties for their genetic diversity in yield, physical traits, and nutritional composition, aiming to identify potential parent varieties for breeding programs to develop new oat varieties for improved livestock feed and diverse industrial applications. To conduct, chemical analysis for protein and carbohydare fractions, energy and digestible nutrient estimated, stastical analyses performed to assess genetic variations for traits among vaieties. Significant genetic variation (p < 0.05) for grain yield, grain density, sieving percentage, crude protein, ether extract, neutral and acid detergent fiber, cellulose, lignin, neutral and acid detergent insoluble nitrogen were observed in grains of eight oat varieties. All protein fractions exhibited significant differences (p < 0.05). Total carbohydrate content ranged significantly (p < 0.05) from 73 % to 79 %. The grains contained higher levels of intermediately degradable starch and pectin (54.12-60.16 %) compared to the slowly degradable cell wall (26-33 %), lignin bounded cell wall (6-10 %), and rapidly degradable sugars (2-8%). Significant variation (p < 0.05) was observed in terms of gross energy, digestible energy, metabolizable energy, net energy for maintenance and lactation about (2 Mcal/kg dry matter), gain (1.6-1.8 Mcal/kg dry matter), total digestible nutrients, digestible dry matter, rumen degradable protein, and total digestible nutrients related to crude protein, fatty acid, neutral detergent fiber, and non-fiber carbohydrate. Organic matter and ether extract were positively associated (p < 0.01) with total digestible nutrients, digestible and metabolizable energy, dry matter digestible and truly digestible non fibrous cabohydrates, while neutral and acid detergent fiber and cellulose showed negative correlation. The research shows that oat varieties vary widely in their yield, physical features, and nutritional content, offering potential for breeding better varieties for both animal feed and industrial uses.

Hyperkinetic and Hypokinetic Movement Disorders in SSPE: A Systematic Review of Case Reports and Case Series.

Background: Subacute Sclerosing Panencephalitis (SSPE) typically presents with periodic myoclonus; however, a spectrum of movement disorders including dystonia, chorea, tremor, and parkinsonism have also been described. This review aims to evaluate the array of movement disorders in SSPE, correlating them with neuroimaging findings, disease stages, and patient outcomes. Methods: A comprehensive review of published case reports and case series was conducted on patients with SSPE exhibiting movement disorders other than periodic myoclonus. PRISMA guidelines were followed, and the protocol was registered with PROSPERO (2023 CRD42023434650). A comprehensive search of multiple databases yielded 37 reports detailing 39 patients. Dyken's criteria were used for SSPE diagnosis, and the International Movement Disorders Society definitions were applied to categorize movement disorders. Results: The majority of patients were male, with an average age of 13.8 years. Approximately, 80% lacked a reliable vaccination history, and 39% had prior measles infections. Dystonia was the most common movement disorder (49%), followed by parkinsonism and choreoathetosis. Rapid disease progression was noted in 64% of cases, with a disease duration of ≤6 months in 72%. Neuroimaging showed T2/FLAIR MR hyperintensities, primarily periventricular, with 26% affecting the basal ganglia/thalamus. Brain biopsies revealed inflammatory and neurodegenerative changes. Over half of the patients (56%) reached an akinetic mute state or died. Conclusion: SSPE is associated with diverse movement disorders, predominantly hyperkinetic. The prevalence of dystonia suggests basal ganglia dysfunction.

Insight on Pediatric Burn Morbidity and Mortality at a Tertiary Indian Burn Care Center: A Case For Burn Prevention.

Pediatric burns pose a significant health burden in LMICs. Despite efforts to address burn prevention and management, morbidity and mortality rates remain high, particularly among children. Understanding pediatric burn epidemiology and predictors of clinical outcomes is crucial for developing effective prevention strategies and improving patient-care. This retrospective cohort study analyzed pediatric burn patients admitted to a tertiary burn-center in India, between March-2022 and December-2023. Demographic date, burn characteristics, treatments, complications and outcomes were collected. Statistical analysis, including logistic and linear regression, was conducted to identify predictors of mortality, sepsis, and hospital stay length. Among 332 pediatric burn patients, median age was 3 years, with a male predominance. Scald burns were the most common, followed by electrical and flame burns. Median total body surface area burned was 20%, with upper and lower extremities most affected. The incidence of electrical burns increased with age and was associated with a longer length of stay. Mortality rate was 14.2%, with age >10 years, male gender, and TBSA >30% predicting mortality. Complications like sepsis significantly increased mortality risk, while deep burns were associated with longer hospital stays. This study underscores importance of targeted prevention efforts and specialized care. Scald burns among young children highlight the need for safer cooking practices, while the high incidence of electrical burns in older children suggests age-specific education interventions are necessary. Predictors of mortality identified can guide risk assessment and resource allocation, emphasizing the importance of infection control and wound management strategies in improving outcomes.

Optogenetic Inhibition of the Orbitofrontal Cortex Disrupts Inhibitory Control during Stop-Change Performance in Male Rats.

Historically, the orbitofrontal cortex (OFC) has been implicated in a variety of behaviors ranging from reversal learning and inhibitory control to more complex representations of reward value and task space. While modern interpretations of the OFC's function have focused on a role in outcome evaluation, these cognitive processes often require an organism to inhibit a maladaptive response or strategy. Single-unit recordings from the OFC in rats performing a stop-change task show that the OFC responds strongly to STOP trials. To investigate the role that the OFC plays in stop-change performance, we expressed halorhodopsin (eNpHR3.0) in excitatory neurons in the OFC and tested rats on the stop-change task. Previous work suggests that the OFC differentiates between STOP trials based on trial sequence (i.e., gS trials: STOP trials preceded by a GO vs sS trials: STOP trials preceded by a STOP). We found that yellow light activation of the eNpHR3.0-expressing neurons significantly decreased accuracy only on STOP trials that followed GO trials (gS trials). Further, optogenetic inhibition of the OFC speeded reaction times on error trials. This suggests that the OFC plays a role in inhibitory control processes and that this role needs to be accounted for in modern interpretations of OFC function.

Bilateral Renal Cell Carcinoma in the Horseshoe Kidney With Metastasis in Gallbladder, Pancreas and Duodenum: A Report of a Rare Case and Literature Review.

Horseshoe kidney is the most common renal fusion anomaly and is associated with various complications, ranging from infections to neoplasms. While renal cell carcinoma (RCC) is the most frequent renal neoplasm in adults, its occurrence in a horseshoe kidney is rare, and bilateral involvement is rarer. Furthermore, RCC metastasizing to organs is known and rare sites of metastasis are also documented. The report presents a unique case of bilateral RCC in a horseshoe kidney with synchronous metastasis to the gallbladder, pancreas, and duodenum. This presentation, involving metastasis to these specific organs, is exceedingly uncommon, making it a rarest of rare possibilities. The current case report underscores the importance of vigilant monitoring and comprehensive evaluation in patients with horseshoe kidneys, as they may be predisposed to unusual complications like RCC and rare site metastasis.

Opioid-free anesthesia using a combination of ketamine and dexmedetomidine in patients undergoing laparoscopic cholecystectomy: a randomized controlled trial.

BACKGROUND: Opioids administered as bolus doses or continuous infusions are widely used for major and daycare surgeries. Opioid-free anesthesia is multimodal anesthesia and analgesia that does not use opioids, benefiting patients from opioid-related adverse effects. We compared the postoperative analgesic requirements of patients scheduled for elective laparoscopic cholecystectomy under opioid-free and opioid-based anesthesia. METHODS: Study included 88 patients aged 18-60 years with American Society of Anesthesiologists physical status 1 and 2 who underwent elective laparoscopic cholecystectomy. Participants were randomly divided into two groups with 44 in each. The opioid-free group was administered an intravenous bolus of ketamine and dexmedetomidine, whereas fentanyl was used in opioid group. Primary outcome was to compare the total amount of fentanyl consumed by both groups during 6 h postoperative period. Episodes of postoperative nausea and vomiting (PONV) and vital signs were noted throughout the postoperative period to analyze the secondary outcomes. RESULTS: Both groups had similar demographic characteristics. The opioid-free group required lesser analgesia within the first 2 h (61.4 ± 17.4 vs. 79.0 ± 19.4 of fentanyl, P < 0.001), which was statistically significant. However, fentanyl consumption was comparable between the groups at 6 h (152 ± 28.2 vs. 164 ± 33.4, P = 0.061). Compared with 4.5% of the participants in the opioid-free group, 34% of those in the opioid-based group developed moderate PONV. CONCLUSIONS: Opioid-free anesthesia in patients undergoing laparoscopic cholecystectomy reduced the requirement of analgesia in first two-hour postoperative period and was associated with decreased PONV.

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.

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.