Correction: Dhaliwal et al. Developments and Prospects in Imperative Underexploited Vegetable Legumes Breeding: A Review. Int. J. Mol. Sci. 2020, 21, 9615.

In the publication [...].

Tricompartmental Microcarriers with Controlled Release for Efficient Management of Parkinson's Disease.

Parkinson's is a progressive neurodegenerative disease of the nervous system. It has no cure, but its symptoms can be managed by supplying dopamine artificially to the brain.This work aims to engineer tricompartmental polymeric microcarriers by electrohydrodynamic cojetting technique to encapsulate three PD (Parkinson's disease) drugs incorporated with high encapsulation efficiency (∼100%) in a single carrier at a fixed drug ratio of 4:1:8 (Levodopa (LD): Carbidopa(CD): Entacapone (ENT)). Upon oral administration, the drug ratio needs to be maintained during subsequent release from microparticles to enhance the bioavailability of primary drug LD. This presents a notable challenge, as the three drugs vary in their aqueous solubility (LD > CD > ENT). The equilibrium of therapeutic release was achieved using a combination of FDA-approved polymers (PLA, PLGA, PCL, and PEG) and the disc shape of particles. In vitro studies demonstrated the simultaneous release of all the three therapeutics in a sustained and controlled manner. Additionally, pharmacodynamics and pharmacokinetics studies in Parkinson's disease rats induced by rotenone showed a remarkable improvement in PD conditions for the microparticles-fed rats, thereby showing a great promise toward efficient management of PD.

Prediction of Long-Term Poor Clinical Outcomes in Cerebral Venous Thrombosis Using Neural Networks Model: The BEAST Study.

Introduction: Risk prediction models are commonly performed with logistic regression analysis but are limited by skewed datasets. We utilised neural networks (NNs) model to identify independent predictors of poor outcomes in cerebral venous thrombosis (CVT) due to the limitations of logistic regression (LR) analysis with complex datasets. Methods: We evaluated 1309 adult CVT patients from the prospective BEAST (Biorepository to Establish the Aetiology of Sinovenous Thrombosis) study. The area under the receiver operating characteristic (AUROC) curve confirmed the goodness-of-fit of prediction models. The normalised importance (NI) of the NNs determines the significance of independent predictors. Results: The stepwise logistic regression model found thrombolysis (OR 32.1; 95% CI 3.6-287.0; P=0.002), craniotomy (OR 6.9; 95% CI 1.3-36.8; P=0.02), and cerebral haemorrhage (OR 4.5; 95% CI 1.3-15.4; P=0.01) as predictors of poor clinical outcome with the AUROC of 0.71. Conversely, the NNs model identified major independent predictors of long-term poor clinical outcomes as cerebral haemorrhage (NI 100%) and thrombolysis (NI 98%), as well as trivial predictors of age (NI 2.8%) and altered mental status (NI 3.5%). The accuracy of the NNs model was 95.1% and 94.1% for self-learned randomly selected training and testing samples with an AUROC of 0.82. Positive and negative predictive values for poor outcomes were 13.2% and 97.1% for the LR model, compared with the NNs model of 18.8% and 98.7%, respectively. Conclusion: Cerebral haemorrhage and thrombolysis was a strong independent predictor, whereas age merely impacts the long-term poor clinical outcome in adult CVT. Integrating unorthodox neural networks risk prediction model can improve decision-making as it outperforms conventional logistic regression with complex datasets.

Rapid NETosis Is an Effector Mechanism to Combat Ocular Herpes Infection.

Purpose: Neutrophils are known mediators of innate immunity, yet their effector function in herpesvirus infections remains poorly understood. Here, we elucidate the mechanistic action and pivotal role of neutrophil extracellular traps (NETs) during herpes simplex virus type 1 (HSV-1) ocular infection. Methods: Neutrophils were collected from mice for HSV-1 infection, fluorescence imaging, and immunoblotting assay. Tear samples from healthy subjects and patients with HSV-1 and mice were collected at L. V. Prasad Eye Institute, India, and at the University of Illinois, USA, respectively. For the in vivo study, C57BL/6 mice as well as diversity outbred mice were infected with HSV-1 (McKrae strain) followed by tear fluid collection at various time points (0-10 days). Samples were used for Flow cytometry, ELISA, and immunofluorescence assay. Human transcriptomic profile of keratitis dataset was used evaluate NETosis signaling pathways. We also performed neutrophil depletion studies. Results: Our data revealed a discernible temporal NET formation (NETosis) predominantly in the infected eye, across normal and diversity outbred murine models and human cases of HSV-1 infection. HSV-1 instigates swift NETosis governed by caspase-1 activation and myeloperoxidase secretion. Distinct accumulations of neutrophils, remaining unengaged in NET release in the contralateral eye post-infection, hinting at a proactive defensive posture in the uninfected eye. Moreover, neutrophil depletion accentuated ocular pathology, augmented viral load, and escalated disease scores, substantiating the protective effects of NETs in curtailing viral replication. Conclusions: Our report uncovers a previously unexplored mechanism of NETosis through pro-inflammatory cell death in response to ocular HSV-1 infection, and HPSE up-regulation, identifying new avenues for future studies.

Comparative bioactivity assessment of bixin pigment and associated phytochemicals extracted from annatto seeds using conventional and green solvents.

Nutraceuticals, that include food ingredients and bioactives from natural products, confer physiological health benefits and protection against chronic diseases. Annatto is a tropical shrub grown in Central and South America and parts of India. Its seeds are rich in the edible carotenoid-derived apocarotenoid pigment, bixin, which is used as a natural colorant in food, textiles, and cosmetics, and is now gaining attention for its potential health-promoting attributes. Here, we compared a green solvent (ethyl lactate) based extraction of bixin and associated metabolites in annatto seeds (crushed and seed coat) with two other conventional solvents (acetone and acid-base). Bixin was characterized in the extracts using UV-visible- and FTIR-spectroscopy and thin-layer chromatography. The bixin-containing solvent extracts were then profiled for other co-existing metabolites using GC-MS analysis, which were found to be sesquiterpenes, terpenes, terpenoids, phytosterols, and tocotrienols. Their bioactivity was evaluated based on antioxidant and wound-healing efficacies and compared with pure bixin, using NIH-3T3 fibroblast cells in-vitro. Pure bixin, as well as the annatto solvent extracts, showed strong antioxidant and wound healing properties, wherein pure bixin and green solvent extract (ethyl lactate coat) exhibited higher levels of antioxidant activity, achieving 46.00% and 44.60% reduction in MDA levels, respectively, as well as enhanced wound-healing activity, with 54.09% and 53.60% wound closure within 24 h. The green solvent extracts of annatto seeds revealed: (a) differential bioactive profiles in annatto seeds (crushed and seed coat) in comparison with other solvents, and (b) strong antioxidant and wound healing properties. Thus, ethyl lactate extraction shows strong potential for sustainable environmental friendly production of functional foods/nutraceuticals from annatto seeds.

Gene-Gene Interaction Between Factor-XI and ABO Genes in Cerebral Venous Thrombosis: The BEAST Study.

BACKGROUND AND OBJECTIVES: Gene-gene interactions likely contribute to the etiology of multifactorial diseases such as cerebral venous thrombosis (CVT) and could be one of the main sources of known missing heritability. We explored Factor XI (F11) and ABO gene interactions among patients with CVT. METHODS: Patients with CVT of European ancestry from the large Bio-Repository to Establish the Aetiology of Sinovenous Thrombosis (BEAST) international collaboration were recruited. Codominant modelling was used to determine interactions between genome-wide identified F11 and ABO genes with CVT status. RESULTS: We studied 882 patients with CVT and 1,205 ethnically matched control participants (age: 42 ± 15 vs 43 ± 12 years, p = 0.08: sex: 71% male vs 68% female, p = 0.09, respectively). Individuals heterozygous (AT) for the risk allele (T) at both loci (rs56810541/F11 and rs8176645/ABO) had a 3.9 (95% CI 2.74-5.71, p = 2.75e-13) increase in risk of CVT. Individuals homozygous (TT) for the risk allele at both loci had a 13.9 (95% CI 7.64-26.17, p = 2.0e-15) increase in risk of CVT. The presence of a non-O blood group (A, B, AB) combined with TT/rs56810541/F11 increased CVT risk by OR = 6.8 (95% CI 4.54-10.33, p = 2.00e15), compared with blood group-O combined with AA. DISCUSSION: Interactions between factor XI and ABO genes increase risk of CVT by 4- to 14-fold.

Pancreatic Parenchymal Atrophy and Pancreatic Fat Accumulation Measured by Multidetector Computed Tomography as a Stable Marker of Chronic Progressive Type 2 Diabetes Mellitus-A Cross Sectional Observational Study.

Background The most crucial step in the management of type 2 diabetes is identifying its pathogenesis and progression. Fat accumulation in the pancreas and decreased parenchymal volume can influence pancreatic function due to insulin resistance or ß-cell dysfunction. This study aims to find out the difference in pancreatic volume and fat content by using contrast-enhanced computed tomography (CECT) between normal subjects and patients with different durations of type 2 diabetes mellitus (T2DM). Methods This was a cross-sectional study. Patients who underwent CECT abdomen for the evaluation of conditions other than pancreatic origin were included. The study group was divided into three subgroups according to the duration of diabetes as <5 years, 5 to 10 years, and >10 years. In total, 40 nondiabetic controls were included. Pancreatic fat volume and parenchymal volume were measured in cm 3 using CECT. Correlation between pancreatic parenchymal and fat volume with the duration of T2DM as well as with levels of hemoglobin A1c, random blood sugar, serum triglyceride, low-density lipoproteins, and high-density lipoproteins was done. Results T2DM patients had significantly ( p < 0.001) lower pancreatic parenchymal volume (mean value of 57.08 ± 8.26 cm 3 in diabetics and 72.23 ± 3.41 cm 3 in controls) and higher pancreatic fat volume (mean value of 3.08 ± 1.90 cm 3 in diabetics and 0.67 ± 0.27cm 3 in controls) as compared to nondiabetic controls. In patients with T2DM, as the duration of T2DM increased, pancreatic parenchymal volume decreased and pancreatic fat volume increased. Conclusion Reduction in pancreatic volume and fat deposition may have a role in the onset and progression of diabetes. Determining the pancreatic volume and fat content would be useful for identifying high-risk patients and determining the pathogenesis of the development of diabetes.

MCN portfolio: An efficient portfolio prediction and selection model using multiserial cascaded network with hybrid meta-heuristic optimization algorithm.

Generally, financial investments are necessary for portfolio management. However, the prediction of a portfolio becomes complicated in several processing techniques which may cause certain issues while predicting the portfolio. Moreover, the error analysis needs to be validated with efficient performance measures. To solve the problems of portfolio optimization, a new portfolio prediction framework is developed. Initially, a dataset is collected from the standard database which is accumulated with various companies' portfolios. For forecasting the benefits of companies, a Multi-serial Cascaded Network (MCNet) is employed which constitutes of Autoencoder, 1D Convolutional Neural Network (1DCNN), and Recurrent Neural Network (RNN) is utilized. The prediction output for the different companies is stored using the developed MCNet model for further use. After predicting the benefits, the best company with the highest profit is selected by Integration of Artificial Rabbit and Hummingbird Algorithm (IARHA). The major contribution of our work is to increase the accuracy of prediction and to choose the optimal portfolio. The implementation is conducted in Python platform. The result analysis shows that the developed model achieves 0.89% and 0.56% regarding RMSE and MAE measures. Throughout the analysis, the experimentation of the developed model shows enriched performance.

Functional and Radiological Outcomes of Miniature Plate Osteosynthesis in Metacarpal and Phalangeal Fractures of Hand: A Prospective Study.

INTRODUCTION:  There are several operative modes to address hand fractures to gain better anatomical and functional results including external fixator, percutaneous K-wire fixation, lag screw fixation, tension band wiring, intra-medullary nails or wires, and plate-screw fixation. We evaluated the results of plate osteosynthesis in fractures of metacarpals and phalanges in a prospective manner. MATERIAL AND METHODS:  A total 50 adults (19-60 years) of either sex having 58 fractures managed by miniature plate osteosynthesis and followed for a minimum six months (6-19), including metacarpal and phalangeal fractures (unstable or serial fractures), intra-articular fractures, fracture-dislocation of proximal interphalangeal and distal interphalangeal joints with joint incongruity or subluxation were enrolled while contaminated compound fractures, pathological fractures and cases of reimplantation were excluded from study. Clinical assessment was done using the American Society for Surgery of the Hand (ASSH), total active flexion (TAF), total active range of motion (TAM) score, and the Disabilities of the Arm, Shoulder, and Hand (quick DASH) score while sequential radiographs were done at each follow-up. RESULT: All the fractures had perfect union clinically as well as radiologically with a mean duration of six weeks while functional outcomes in reference to clinical scores were observed excellent and fair in all cases. None of the cases had any loss of reduction, loosening of the implant, or other major complications. CONCLUSIONS: Miniature plate fixation provides enough stability in metacarpal and phalanges fractures, thereby allowing immediate active movements, which leads to excellent functional outcomes and early return to normal activities.

A green and economic approach to synthesize magnetic Lagenaria siceraria biochar (γ-Fe2O3-LSB) for methylene blue removal from aqueous solution.

In the printing and textile industries, methylene blue (a cationic azo dye) is commonly used. MB is a well-known carcinogen, and another major issue is its high content in industrial discharge. There are numerous removal methodologies that have been employed to remove it from industrial discharge; however, these current modalities have one or more limitations. In this research, a novel magnetized biochar (γ-Fe2O3-LSB) was synthesized using Lagenaria siceraria peels which were further magnetized via the co-precipitation method. The synthesized γ-Fe2O3-LSB was characterized using FTIR, X-ray diffraction, Raman, SEM-EDX, BET, and vibrating sample magnetometry (VSM) for the analysis of magnetic properties. γ-Fe2O3-LSB showed a reversible type IV isotherm, which is a primary characteristic of mesoporous materials. γ-Fe2O3-LSB had a specific surface area (SBET = 135.30 m2/g) which is greater than that of LSB (SBET = 11.54 m2/g). γ-Fe2O3-LSB exhibits a saturation magnetization value (Ms) of 3.72 emu/g which shows its superparamagnetic nature. The batch adsorption process was performed to analyze the adsorptive removal of MB dye using γ-Fe2O3-LSB. The adsorption efficiency of γ-Fe2O3-LSB for MB was analyzed by varying parameters like the initial concentration of adsorbate (MB), γ-Fe2O3-LSB dose, pH effect, contact time, and temperature. Adsorption isotherm, kinetic, and thermodynamics were also studied after optimizing the protocol. The non-linear Langmuir model fitted the best to explain the adsorption isotherm mechanism and resulting adsorption capacity ( q e =54.55 mg/g). The thermodynamics study showed the spontaneous and endothermic nature, and pseudo-second-order rate kinetics was followed during the adsorption process. Regeneration study showed that γ-Fe2O3-LSB can be used up to four cycles. In laboratory setup, the cost of γ-Fe2O3-LSB synthesis comes out to be 162.75 INR/kg which is low as compared to commercially available adsorbents. The results obtained suggest that magnetic Lagenaria siceraria biochar, which is economical and efficient, can be used as a potential biochar material for industrial applications in the treatment of wastewater.

Coma in adult cerebral venous thrombosis: The BEAST study.

BACKGROUND AND PURPOSE: Coma is an independent predictor of poor clinical outcomes in cerebral venous thrombosis (CVT). We aimed to describe the association of age, sex, and radiological characteristics of adult coma patients with CVT. METHODS: We used data from the international, multicentre prospective observational BEAST (Biorepository to Establish the Aetiology of Sinovenous Thrombosis) study. Only positively associated variables with coma with <10% missing data in univariate analysis were considered for the multivariate logistic regression model. RESULTS: Of the 596 adult patients with CVT (75.7% women), 53 (8.9%) patients suffered coma. Despite being a female-predominant disease, the prevalence of coma was higher among men than women (13.1% vs. 7.5%, p = 0.04). Transverse sinus thrombosis was least likely to be associated with coma (23.9% vs. 73.3%, p < 0.001). The prevalence of superior sagittal sinus thrombosis was higher among men than women in the coma sample (73.6% vs. 37.5%, p = 0.01). Men were significantly older than women, with a median (interquartile range) age of 51 (38.5-60) versus 40 (33-47) years in the coma (p = 0.04) and 44.5 (34-58) versus 37 (29-48) years in the non-coma sample (p < 0.001), respectively. Furthermore, an age- and superior sagittal sinus-adjusted multivariate logistic regression model found male sex (odds ratio = 1.8, 95% confidence interval [CI] = 1.0-3.4, p = 0.04) to be an independent predictor of coma in CVT, with an area under the receiver operating characteristic curve of 0.61 (95% CI = 0.52-0.68, p = 0.01). CONCLUSIONS: Although CVT is a female-predominant disease, men were older and nearly twice as likely to suffer from coma than women.

Emerging drugs for the treatment of herpetic keratitis.

INTRODUCTION: Herpes simplex keratitis stands as a prominent factor contributing to infectious blindness among developed nations. On a global scale, over 60% of the population tests positive for herpes simplex virus type-1 (HSV-1). Despite these statistics, there is currently no vaccine available for the virus. Moreover, the conventional nucleoside drugs prescribed to patients are proving ineffective in addressing issues related to drug resistance, recurrence, latency, and the escalating risk of vision loss. Hence, it is imperative to continually explore all potential avenues to restrict the virus. This review article centers on the present treatment methods for HSV-1 keratitis (HSK), highlighting the ongoing clinical trials. It delves into the emerging drugs, their mode-of-action and future therapeutics. AREAS COVERED: The review focuses on the significance of a variety of small molecules targeting HSV-1 lifecycle at multiple steps. Peer-reviewed articles and abstracts were searched in MEDLINE, PubMed, Embase, and clinical trial websites. EXPERT OPINION: The exploration of small molecules that target specific pathways within the herpes lifecycle holds the potential for substantial impact on the antiviral pharmaceutical market. Simultaneously, the pursuit of disease-specific biomarkers has the capacity to usher in a transformative era in diagnostics within the field.

Design, optimization, and evaluation of topical gel of Cardiospermum halicacabum and Ricinus communis L. leaves extract for the treatment of rheumatoid arthritis.

This research aims to develop and assess the anti-arthritic properties of a topically herbal gel including leaf extracts from Cardiospermum halicacabum and Ricinus communis L. in rats. Utilizing gelling agents carbopol 940 (2.5, 5, 7.5 g), nine herbal gel compositions were created. Prepared formulations were then assessed for physical appearance, spreadability, viscosity, net content, pH, extrudability, in vitro diffusion profile, and main skin irritant tests. According to the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) recommendations, the stability research for the topical herbal gel composition was completed, and Freund's Complete Adjuvant (FCA) induced arthritis technique was used to assess the anti-arthritic efficacy. Additional procedures included measuring the body weight, paw volume, biochemical and hematological variables, histological analysis, and in vitro serum biomarker detection. The prepared gels followed the instructions and were uniform and stable. F5 performed better than the other compositions in terms of release kinetics (97.20%). The gel proved safe and non-toxic since no erythema or edema was seen during the skin irritation test. Comparing the herbal gel F5 comprising carbopol 940 to rats with arthritis, the topical treatment showed considerable (p < .001) anti-arthritic effect. The anti-arthritic action of the gel formulations was confirmed by decreased paw volume, absence of agglutination in reacting protein and rheumatic factor, a decline in TNFα level, restoration to baseline biochemical and hematological characteristics, decrease in thymus and spleen weight, and histopathological study.

CryoEM structures reveal how the bacterial flagellum rotates and switches direction.

Bacterial chemotaxis requires bidirectional flagellar rotation at different rates. Rotation is driven by a flagellar motor, which is a supercomplex containing multiple rings. Architectural uncertainty regarding the cytoplasmic C-ring, or 'switch', limits our understanding of how the motor transmits torque and direction to the flagellar rod. Here we report cryogenic electron microscopy structures for Salmonella enterica serovar typhimurium inner membrane MS-ring and C-ring in a counterclockwise pose (4.0 Å) and isolated C-ring in a clockwise pose alone (4.6 Å) and bound to a regulator (5.9 Å). Conformational differences between rotational poses include a 180° shift in FliF/FliG domains that rotates the outward-facing MotA/B binding site to inward facing. The regulator has specificity for the clockwise pose by bridging elements unique to this conformation. We used these structures to propose how the switch reverses rotation and transmits torque to the flagellum, which advances the understanding of bacterial chemotaxis and bidirectional motor rotation.

Thoracolumbar fracture-dislocation in a two-year-old female child following child abuse: A case report and literature review.

Child abuse is a matter of serious concern that can often result in devastating injuries. Incidence of spinal injuries from child abuse has been reported in <1-3 % of spinal injury cases. In the present study, a case of thoracolumbar translational injury (AO type C) is presented following an incidence of child abuse in a 2-year-old female. After successful management with operative fixation, the child showed a remarkable recovery in her neurological function with ambulatory power.

Treatment of Failed Proximal Femoral Nail Anti-rotation Asia (PFNA2) in a Severely Osteoporotic Patient With a Revision Stem.

An intertrochanteric fracture is a prevalent and perilous kind of fracture that often affects older persons. A customized implant, proximal femoral nail anti-rotation Asia (PFNA2) is being used expressly in unstable intertrochanteric fractures in people with osteoporosis. In this case report, we examined a female osteoporosis patient, age 74, who underwent a failed PFNA2 procedure. Subsequently, the patient had bipolar hemiarthroplasty as a treatment. To prevent mechanical failure, it is crucial to strive for a high level of reduction quality and precise alignment of the central blade throughout hip X-ray procedures. Improved surgical proficiency and skill are crucial for managing patients with severe osteoporosis and prolonged weight-bearing requirements, hence reducing the occurrence of postoperative problems. Depending on the cause of the failure and the individual circumstances of the patient when internal fixation fails, it is recommended to either replace the joint with a prosthetic or reapply fixation. These interventions may facilitate the production of beneficial healing outcomes.

Robotic Neck Dissection in Head and Neck Cancer via Modified BABA Technique.

INTRODUCTION: Neck dissection forms an important component in the surgical management of head and neck cancers. By using the conventional techniques of neck dissection, a conspicuous scar is inevitable for the patients. The development of robotic assisted neck dissection provides for a scar-free neck along with good oncological and functional outcomes. METHODS: A prospective observational study was conducted in our institute from 2020 March to 2022 March, where robotic-assisted neck dissections performed via the modified bilateral axillo-breast insufflation technique. RESULTS: Eighty-two patients underwent robotic neck dissections in our institute. Notably, 79 patients were treatment-naïve. The average docking time was 12 min and console time was 160 ± 15 min. The mean lymph node yield was 28.2. The average post-operative stay was 5.6 days. The average follow-up was noted to be 6.4 months. The mean cosmetic satisfaction score in our patients was 4.45. Only one patient presented with nodal recurrence, who was identified as a defaulter for adjuvant treatment. Robotic neck dissection gives similar functional and oncological outcomes as compared with conventional neck dissection. Patients had excellent cosmetic satisfaction following the procedure. The limitations of these techniques include high cost of procedure and longer operating time. This is a level IV evidence study. CONCLUSION: Although good oncological, functional, and cosmetic outcomes have been attained in robotic assisted neck dissection, further randomized controlled studies need to be conducted to justify the added costs, cosmetic advantage, and the time taken. LEVEL OF EVIDENCE: Level IV Laryngoscope, 2024.

Impact of healthcare-associated infections within 7-days of acute stroke on health outcomes and risk of care-dependency: a multi-centre registry-based cohort study.

Healthcare-associated infections (HCAIs) in patients admitted with acute conditions remain a major challenge to healthcare services. Here, we assessed the impact of HCAIs acquired within 7-days of acute stroke on indicators of care-quality outcomes and dependency. Data were prospectively collected (2014-2016) from the Sentinel Stroke National Audit Programme for 3309 patients (mean age = 76.2 yr, SD = 13.5) admitted to four UK hyperacute stroke units (HASU). Associations between variables were assessed by multivariable logistic regression (odds ratios, 95% confidence intervals), adjusted for age, sex, co-morbidities, pre-stroke disability, swallow screening, stroke type and severity. Within 7-days of admission, urinary tract infection (UTI) and pneumonia occurred in 7.6% and 11.3% of patients. Female (UTI only), older age, underlying hypertension, atrial fibrillation, previous stroke, pre-stroke disability, intracranial haemorrhage, severe stroke, and delay in swallow screening (pneumonia only) were independent risk factors of UTI and pneumonia. Compared to patients without UTI or pneumonia, those with either or both of these HCAIs were more likely to have prolonged stay (> 14-days) on HASU: 5.1 (3.8-6.8); high risk of malnutrition: 3.6 (2.9-4.5); palliative care: 4.5 (3.4-6.1); in-hospital mortality: 4.8 (3.8-6.2); disability at discharge: 7.5 (5.9-9.7); activity of daily living support: 1.6 (1.2-2.2); and discharge to care-home: 2.3 (1.6-3.3). In conclusion, HCAIs acquired within 7-days of an acute stroke led to prolonged hospitalisation, adverse health consequences and risk of care-dependency. These findings provide valuable information for timely intervention to reduce HCAIs, and minimising subsequent adverse outcomes.

Exploring Heparanase Levels in Tears: Insights From Herpes Simplex Virus-1 Keratitis Patients and Animal Studies.

Purpose: Heparanase (HPSE) cleaves heparan sulfate proteoglycans during herpes simplex virus-1 (HSV-1) infection, aiding in viral egress and disease progression. Its action has been well established in in vitro and in vivo models, but its relevance in human patients remains unclear. This study aimed to specifically evaluate tear HPSE levels of patients with herpes simplex keratitis (HSK) and to correlate these findings with a commonly used murine model. Methods: Tear samples from patient and mice samples were collected at LV Prasad Eye Institute, Hyderabad, India, and at the University of Illinois, Chicago, IL, respectively. Tears were collected from HSV-1 patients, bacterial/fungal keratitis cases, and healthy individuals. For in vivo study, C57BL/6 mice were infected with HSV-1 (McKrae strain) followed by tear fluid collection at various time points (0-10 days). Results: The HSV-1, bacterial keratitis, fungal keratitis, and healthy control groups each had 30 patients. There was a significant difference in HPSE expression in the HSV-1 infected eyes (1.55 ± 0.19 units/mL) compared to HSV-1 contralateral eyes (1.23 ± 0.13 units/mL; P = 0.82), bacterial keratitis eyes (0.87 ± 0.15 units/mL; P = 0.0078), fungal keratitis eyes (0.64 ± 0.09 units/mL; P < 0.00001), and normal controls (0.53 ± 0.06 units/mL; P < 0.00001). C57BL/6 mice tear HPSE expression in infected eyes was 0.66 to 5.57 ng heparan sulfate (HS) removed per minute when compared to non-infected eye (range, 0.70-3.67 ng HS removed per minute). Conclusions: To the best of our knowledge, this study is the first to report elevated HPSE levels in the tears of patients with different forms of HSV-1 keratitis, and it confirms similar findings in a murine model, providing a valuable basis for future in vivo and clinical research on HSV-1 ocular infection.

Integrated analysis of transcriptome and genome variations in pediatric T cell acute lymphoblastic leukemia: data from north Indian tertiary care center.

INTRODUCTION: T-cell acute lymphoblastic leukemia (T-ALL) is a genetically heterogeneous disease with poor prognosis and inferior outcome. Although multiple studies have been perform on genomics of T-ALL, data from Indian sub-continent is scarce. METHODS: In the current study we aimed to identify the genetic variability of T-ALL in an Indian cohort of pediatric (age ≤ 12 years) T-ALL patients (n = 25) by whole transcriptome sequencing along with whole exome sequencing and correlated the findings with clinical characteristics and disease outcome. RESULTS: The median age was 7 years (range 3 -12 years). RNA sequencing revealed a definitive fusion event in 14 cases (56%) (including a novel fusions) with STIL::TAL1 in 4 (16%), followed by NUP21::ABL1, TCF7::SPI1, ETV6::HDAC8, LMO1::RIC3, DIAPH1::JAK2, SETD2::CCDC12 and RCBTB2::LPAR6 in 1 (4%) case each. Significant aberrant expression was noted in RAG1 (64%), RAG2 (80%), MYCN (52%), NKX3-1 (52%), NKX3-2 (32%), TLX3 (28%), LMO1 (20%) and MYB (16%) genes. WES data showed frequent mutations in NOTCH1 (35%) followed by WT1 (23%), FBXW7 (12%), KRAS (12%), PHF6 (12%) and JAK3 (12%). Nearly 88.2% of cases showed a deletion of CDKN2A/CDKN2B/MTAP genes. Clinically significant association of a better EFS and OS (p=0.01) was noted with RAG2 over-expression at a median follow up of 22 months, while a poor EFS (p=0.041) and high relapse rate (p=0.045) was observed with MYB over-expression. CONCLUSION: Overall, the present study demonstrates the frequencies of transcriptomic and genetic alterations from Indian cohort of pediatric T-ALL and is a salient addition to current genomics data sets available in T-ALL.