Potential anxiolytic therapeutics from Hybanthus enneaspermus (L.) F. Muell. - mitigate anxiety by plausibly modulating the GABAA-Cl- channel.

Anxiety is a commonly prevailing psychological disorder that requires effective treatment, wherein phytopharmaceuticals and nutraceuticals could offer a desirable therapeutic profile. Hybanthus enneaspermus (L.) F. Muell. is a powerful medicinal herb, reportedly effective against several ailments, including psychological disorders. The current research envisaged evaluating the anxiolytic potential of the ethanolic extract of Hybanthus enneaspermus (EEHE) and its toluene insoluble biofraction (ITHE) employing experimental and computational approaches. Elevated Plus Maze, Light and Dark Transition, Mirror Chamber, Hole board and Open field tests were used as screening models to assess the antianxiety potential of 100, 200 and 400 mg/Kg body weight of EEHE and ITHE in rats subjected to social isolation, using Diazepam as standard. The brains of rats exhibiting significant anxiolytic activity were dissected for histopathological and biochemical studies. Antioxidant enzymes like catalase, superoxide dismutase, glutathione-S-transferase, glutathione peroxidase, glutathione reductase; and neurotransmitters viz. monoamines (serotonin, noradrenaline, dopamine), Gamma-aminobutyric acid (GABA), and glutamate were quantified in the different regions of rats' brain (cortex, hippocampus, pons, medulla oblongata, cerebellum). Chromatographic techniques were used to isolate phytoconstituents from the fraction exhibiting significant activity that were characterized by spectroscopic methods and subjected to in silico molecular docking. ITHE at 400 mg/Kg body weight significantly mitigated anxiety in all the screening models (p < 0.05), reduced the inflammatory vacuoles and necrosis (p < 0.05) and potentiated the antioxidant enzymes (p < 0.05). It enhanced the monoamines and GABA levels while attenuating glutamate levels (p < 0.01) in the brain. Three significant flavonoids viz. Quercitrin, Rutin and Hesperidin were isolated from ITHE. In silico docking studies of these flavonoids revealed that the compounds exhibited substantial binding to the GABAA receptor. ITHE displayed a promising pharmacological profile in combating anxiety and modulating oxidative stress, attributing its therapeutic virtues to the flavonoids present.

Exploring the neuropharmacological properties of scopoletin-rich Evolvulus alsinoides extract using in-silico and in-vitro methods.

OBJECTIVES: This study investigates the neuropharmacologic properties of Scopoletin, a bioactive compound in Evolvulus alsinoides (EA) extract, for managing cognitive impairment using in-vitro, in-silico, and zebrafish embryo toxicity assays. METHODS: The study estimates Scopoletin concentration in EA extract using HPTLC, assesses antioxidant properties using 2,2-Diphenyl-1-picrylhydrazyl (DPPH) and ferric reducing ability of plasma (FRAP) assays, and uses bioinformatic tools for scopoletin targets. Zebrafish embryo toxicity (ZET) is used to assess its toxicological profile. RESULTS: 0.0076% w/w Scopoletin in the samples was quantified using HPTLC, further studies on the DPPH (0.5 mM) and FRAP gave EC50 at 440.0 µg/ml and 84.29 µg/ml respectively. Twelve common targets associated with cognitive impairment (CI) were identified, along with possible pathways and molecular interactions. Our results indicate significant binding affinities of Scopoletin with ERAP1, SCN3A, and COMT. Molecular dynamics simulations further confirm the stability of these interactions. ZET assessment demonstrated mortality after 450 µg/ml concentration of EA extract. CONCLUSION: The study verifies the presence of Scopoletin in EA, along with their targets playing a crucial role in neurogenesis and neuroplasticity. The ZET demonstrated concentration-dependent effects, emphasizing the importance of dosage considerations in developing new formulations or therapeutics. This comprehensive study contributes valuable insight into the therapeutic potential of Scopoletin from EA for cognitive impairment, paving the way for further research.

Artificial neural network, machine learning modelling of compressive strength of recycled coarse aggregate based self-compacting concrete.

This research study aims to understand the application of Artificial Neural Networks (ANNs) to forecast the Self-Compacting Recycled Coarse Aggregate Concrete (SCRCAC) compressive strength. From different literature, 602 available data sets from SCRCAC mix designs are collected, and the data are rearranged, reconstructed, trained and tested for the ANN model development. The models were established using seven input variables: the mass of cementitious content, water, natural coarse aggregate content, natural fine aggregate content, recycled coarse aggregate content, chemical admixture and mineral admixture used in the SCRCAC mix designs. Two normalization techniques are used for data normalization to visualize the data distribution. For each normalization technique, three transfer functions are used for modelling. In total, six different types of models were run in MATLAB and used to estimate the 28th day SCRCAC compressive strength. Normalization technique 2 performs better than 1 and TANSING is the best transfer function. The best k-fold cross-validation fold is k = 7. The coefficient of determination for predicted and actual compressive strength is 0.78 for training and 0.86 for testing. The impact of the number of neurons and layers on the model was performed. Inputs from standards are used to forecast the 28th day compressive strength. Apart from ANN, Machine Learning (ML) techniques like random forest, extra trees, extreme boosting and light gradient boosting techniques are adopted to predict the 28th day compressive strength of SCRCAC. Compared to ML, ANN prediction shows better results in terms of sensitive analysis. The study also extended to determine 28th day compressive strength from experimental work and compared it with 28th day compressive strength from ANN best model. Standard and ANN mix designs have similar fresh and hardened properties. The average compressive strength from ANN model and experimental results are 39.067 and 38.36 MPa, respectively with correlation coefficient is 1. It appears that ANN can validly predict the compressive strength of concrete.

Acute toxicity appraisal of Saussurea heteromalla extract and development of its chemotherapeutic herbal dosage form.

Ethnopharmacological relevance of Saussurea species for anti-cancer compounds instigated us to develop chemotherapeutic herbal tablets. This study was an ongoing part of our previous research based on the scientific evaluation of Saussurea heteromalla (S. heteromalla) for anti-cancer lead compounds. In the current study, S. heteromalla herbal tablets (500 /800 mg) were designed and evaluated for anti-cancer activity. Arctigenin was found as a bioactive lead molecule with anti-cancer potential for cervical cancer. The in vitro results on the HeLa cell line supported the ethnopharmacological relevance and traditional utilization of S. heteromalla and provided the scientific basis for the management of cervical cancer as proclaimed by traditional practitioners in China. LD50 of the crude extract was established trough oral acute toxicity profiling in mice, wherein the minimum lethal dose was noticed as higher than 1000 mg/kg body weight orally. Chromatographic fingerprint analysis ensured the identity and consistency of S. heteromalla in herbal tablets in terms of standardization of the herbal drug. About 99.15% of the drug (S. heteromalla crude extract) was recovered in herbal tablets (RSD: 0.45%). In vitro drug release profile was found to be more than 87% within 1 h, which was also correlated with different mathematical kinetic models of drug release (r2 = 0.992), indicating that drug release from matrix tablets into the blood is constant throughout the delivery. The dosage form was found stable after an accelerated stability parameters study which may be used for anti-cervical cancer therapy in the future, if it qualifies successful preclinical investigation parameters.

Effect of metformin use on graft and patient survival in kidney transplant recipients with type 2 diabetes: a systematic review protocol.

INTRODUCTION: Metformin is a first-line antihyperglycaemic agent for type 2 diabetes (T2DM). In addition to glycaemic control, it offers benefits related to cardiovascular health, weight neutrality and metabolic syndrome. However, its benefits in kidney transplant recipients remain unclear as metformin use is controversial in this population due to a lack of evidence and there are recommendations against its use in patients with poor kidney function. Hence, we seek to describe a protocol for a systematic review, which will assess the impact of metformin use on graft survival and mortality in kidney transplant recipients. METHODS: This protocol was guided by the standards of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Protocols 2015. We will search empirical databases such as MEDLINE, Embase, Cochrane Library, CINAHL and Web of Science Core Collection for relevant studies conducted in kidney transplant recipients using metformin, which report outcomes related to graft and patient survival. All studies meeting these criteria in adults and published in English from inception to 2023 will be included in our review. We will employ the Cochrane Risk of Bias Tool 2 for randomised controlled trials and the Risk of Bias in Non-randomised Studies of Intervention for non-randomised studies. We will present our data and study characteristics in a table format and determine if a meta-analysis can be performed by clinical and methodological heterogeneity, using the I2 statistics. If a meta-analysis cannot be performed, we will provide a narrative synthesis of included studies using the Synthesis Without Meta-Analysis Reporting Guideline. ETHICS AND DISSEMINATION: Ethical approval will not be required for this review as the data used will be extracted from already published studies with publicly accessible data. As this study will assess the impact of metformin use on graft and patient survival in kidney transplant recipients, evidence gathered through it will be disseminated using traditional approaches that include open-access peer-reviewed publication, scientific presentations and a report. We will also disseminate our findings to appropriate academic bodies in charge of publishing guidelines related to T2DM and transplantation, as well as patient and research centred groups. PROSPERO REGISTRATION NUMBER: CRD42023421799.

An assessment of treatment compliance using the Morisky scale-8 tool in adult hypertensive patients of Eastern India.

Background: Adequate management of hypertension is crucial for decreasing the likelihood of cardiovascular ailments and associated complications. Nonetheless, in the Indian context, maintaining compliance with prescribed hypertensive therapies presents a notable hurdle, impeding the attainment of favorable health outcomes. Thus, this study was conducted with the aim to evaluate the prevalence of treatment adherence and explore the diverse factors that impact adherence patterns among individuals diagnosed with hypertension. Material and Methods: A community-based cross-sectional questionnaire-based study was carried out among the diagnosed hypertensive patients from 12 purposefully selected villages of Khagaul block, Patna. A total of 262 participants were recruited in the study by using non-probability sampling. The 8-item Morisky Medication Adherence Scale (MMAS-8) was used for measuring adherence. The Statistical Package for the Social Sciences (SPSS) for Windows version 21.0 (SPSS Inc; Chicago, IL, USA) was used for statistical analysis of data. Result: As per MMAS scores, 10 (3.8%) had high, 133 (50.8%) moderate, and 119 (45.4%) poor adherence. However, good adherence was reported among geriatric patients [1.65 (1.01-2.7)], those with a history of absence of comorbidities [2.15 (1.21-3.85)], more than 5 years' duration of hypertension [3.2 (1.89-5.41)], once-a-day drug intake [2.8 (1.61-4.87)], and having controlled blood pressure [5.2 (3.08-8.96)]. Controlled blood pressure (AOR = 0.048, 0.023-0.098), perception of high benefit of treatment [0.497 (0.255-0.97)], and absence of comorbidity [0.016 (0.168-0.832)] were identified as predictors of good treatment adherence. Conclusion: Overall medication adherence in the current study was 54.6%. Achieving treatment adherence frequently demands proactive patient engagement, highlighting their active role in disease management. Also, involving the patient's caregivers can offer an additional tactic to tackle non-adherence stemming from forgetfulness of the patient.

Intense and problematic social media use and sleep difficulties of adolescents in 40 countries.

INTRODUCTION: Social media has become a ubiquitous part of everyday life; however, evidence suggests patterns of social media use can affect sleep health in children and adolescents. This study aimed to examine the associations of intense and problematic social media use (SMU) with sleep-onset difficulties in adolescence. METHODS: We analysed data from 212,613 adolescents aged 11-15 years (51.1% girls) from 40 European and North American countries that participated in the 2017/2018 Health Behaviour in School-aged Children survey. Intense SMU assessed how often respondents had online contact through social media, and problematic SMU was assessed by symptoms of addiction to social media. Sleep-onset difficulties were assessed using a self-reported item. Multilevel mixed-effects logistic regression was used to obtain the estimates. RESULTS: Sleep-onset difficulties were more common among girls than boys (27.1% vs 20.8%). Intense SMU was significantly associated with sleep-onset difficulties in boys in 17 countries and in girls in 25 countries, while problematic SMU was significantly associated in most of the participating countries. Overall, exposure to problematic SMU alone was highly associated with sleep-onset difficulties both in girls (OR 2.20, 2.04-2.38) and boys (OR 1.88, 1.73-2.04), while the association estimates for intense SMU were smaller and comparable across gender (Girls: OR 1.27, 1.23-1.31; Boys: OR 1.22, 1.18-1.27). Sensitivity analyses supported the above findings. CONCLUSIONS: Intense and/or problematic SMU were associated with sleep-onset difficulties across gender with associations being higher for problematic compared to intense SMU. Prospective research with objective measures is needed to understand the causal mechanisms underlying these relationships.

Efficacy of perioperative systemic tranexamic acid along with topical hemocoagulase in decreasing axillary drain output in breast cancer patients undergoing axillary lymph node dissection: A randomized, double-blind, placebo-controlled, superiority trial.

BACKGROUND: Excess and prolonged axillary drainage is a frequent nuisance following axillary lymph node dissection (ALND) in breast cancer patients. No consensus exists about the best method to prevent this consistently and reliably. Tranexamic acid (TA) has been found to reduce the amount and duration of drainage, but the reduction is not optimal. We hypothesized that systemic administration of TA along with the topical application of hemocoagulase (H) to the axillary dissection bed may decrease the cumulative axillary drain output and shorten the requirement of drainage after ALND as compared to placebo. PATIENT AND METHODS: Seventy women undergoing ALND for breast carcinoma were randomized into two groups, the intervention (TA + H) group and the control (C) group. The cumulative drain output (primary objective), duration of drainage, incidence of seroma formation after drain removal, number of seroma aspirations required, volume of seroma aspirated, and incidence of surgical site infection (SSI) were compared. RESULTS: The mean cumulative output in the TA + H group was significantly lower than the C group (290 ± 200 mL vs. 552 ± 369 mL, p < 0.001). Axillary drains were removed significantly earlier in the TA + H group (6.6 ± 2.2 vs. 11.7 ± 6.0 days, p < 0.001), but the incidence of seroma formation (p = 0.34), number of aspirations required (p = 0.33), volume of seroma aspirated (p = 0.47), and the incidence of SSI (p = 0.07) were similar. CONCLUSIONS: Perioperative systemic administration of tranexamic acid along with topical application of H to the axillary dissection bed is effective in reducing cumulative axillary drain output after ALND. This strategy may also facilitate earlier removal of suction drains.

Comparative efficacy of family mediated intervention versus early intensive behavioural intervention on symptom domains in children with autism spectrum disorder: A randomized controlled trial.

BACKGROUND: Family Mediated Intervention (FMI) and Early Intensive Behavioural Intervention (EIBI) are found to be standard of care for children with Autism Spectrum Disorder (ASD). Comparison of their efficacy were assessed using ISAA as primary outcome measure. METHODS: This study was a parallel arm, open label, randomized active- controlled non-inferiority clinical trial. 50 Children diagnosed with ASD were randomized into FMI and EIBI groups. Clinical status was checked by using Indian scale for assessment of autism (ISAA), Oro- motor and sensory profile at baseline, after three and six months. RESULTS: Difference between change in mean ISAA score between FMI and EIBI group at the end of 6 months as per protocol (PP) analysis was -7.23 (CI=-18.41, 3.94), which was within pre-defined clinically relevant non-inferiority (NI) margin of - 24. FMI was found to be non-inferior to EIBI at the end of 6 months as the lower bound of 95% CI (-18.41) for ISAA score was higher than NI margin. ISAA scores were found to be statistically lower in both FMI and EIBI groups at the end point compared to baseline which indicated improvement in symptom severity. CONCLUSION: FMI was non-inferior to EIBI as therapy for children with ASD at the end of six months. Finding also indicated longer duration of treatment is required for FMI to be superior. FMI can be recommended for children with ASD in view of improved ISAA scores reported in our study. CLINICAL TRIAL REGISTRATION NUMBER: CTRI/2020/08/027099 (Registered with Clinical Trials Registry- India).

An Electroanalytical Enzymeless α-Fe2O3-ZnO Hybrid Nanostructure-Based Sensor for Sensitive Quantification of Nitrite Ions.

Nitrite monitoring serves as a fundamental practice for protecting public health, preserving environmental quality, ensuring food safety, maintaining industrial safety standards, and optimizing agricultural practices. Although many nitrite sensing methods have been recently developed, the quantification of nitrite remains challenging due to sensitivity and selectivity limitations. In this context, we present the fabrication of enzymeless iron oxide nanoparticle-modified zinc oxide nanorod (α-Fe2O3-ZnO NR) hybrid nanostructure-based nitrite sensor fabrication. The α-Fe2O3-ZnO NR hybrid nanostructure was synthesized using a two-step hydrothermal method and characterized in detail utilizing x-ray diffraction (XRD), field emission scanning electron microscopy (FESEM), transmission electron microscopy (TEM), and X-ray photoelectron spectroscopy (XPS). These analyses confirm the successful synthesis of an α-Fe2O3-ZnO NR hybrid nanostructure, highlighting its morphology, purity, crystallinity, and elemental constituents. The α-Fe2O3-ZnO NR hybrid nanostructure was used to modify the SPCE (screen-printed carbon electrode) for enzymeless nitrite sensor fabrication. The voltammetric methods (i.e., cyclic voltammetry (CV) and differential pulse voltammetry (DPV)) were employed to explore the electrochemical characteristics of α-Fe2O3-ZnO NR/SPCE sensors for nitrite. Upon examination of the sensor's electrochemical behavior across a range of nitrite concentrations (0 to 500 µM), it is evident that the α-Fe2O3-ZnO NR hybrid nanostructure shows an increased response with increasing nitrite concentration. The sensor demonstrates a linear response to nitrite concentrations up to 400 µM, a remarkable sensitivity of 18.10 µA µM-1 cm-2, and a notably low detection threshold of 0.16 µM. Furthermore, its exceptional selectivity, stability, and reproducibility make it an ideal tool for accurately measuring nitrite levels in serum, yielding reliable outcomes. This advancement heralds a significant step forward in the field of environmental monitoring, offering a potent solution for the precise assessment of nitrite pollution.

Identification of biochemical indices for brown spot (Bipolaris oryzae) disease resistance in rice mutants and hybrids.

Brown spot caused by Bipolaris oryzae is a major damaging fungal disease of rice which can decrease the yield and value of produce due to grain discoloration. The objectives of the current study were to investigate and understand the biochemical indices of brown spot disease resistance in rice. A total of 108 genotypes (mutant and hybrid) along with Super Basmati and parent RICF-160 were evaluated against brown spot disease. The genotypes exhibiting resistant and susceptible responses to brown spot disease according to the IRRI standard disease rating scale were screened and selected. To study the biochemical response mechanism, forty five selected genotypes along with Super Basmati and RICF-160 were analyzed using the biochemical markers. The physiological and biochemical analysis provided valuable insights and confirmed the resistance of rice hybrids and mutants against brown spot disease. Positive correlations were observed among stress bio-markers and disease response. Rice genotypes i.e. Mu-AS-8, Mu-AS-19, Mu-AS-20 and Mu-AS-35 exhibited moderate resistant response while Hy-AS-92, Hy-AS-98, Hy-AS-99, Hy-AS-101, Hy-AS-102 and Hy-AS-107 showed resistant response to brown spot disease. Brown spot resistant rice genotypes had lesser values of malondialdehyde and total oxidant status and higher antioxidant activities i.e. superoxide dismutase, peroxidase, total phenolic content and lycopene. The selected resistant rice genotypes had resistance capacity against Bipolaris oryzae stress. In conclusion, identified resistant mutants i.e. Mu-AS-8, Mu-AS-19, Mu-AS-20 and Mu-AS-35 and hybrids i.e. Hy-AS-92, Hy-AS-98, Hy-AS-99, Hy-AS-101, Hy-AS-102 and Hy-AS-107 could be used in rice breeding program to achieve sustainable rice production by coping the emerging challenge of brown spot disease under variable climate conditions.

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.

TRAUMATIC BRAIN INJURY AND ITS IMPLICATIONS FOR BEHAVIORAL HEALTH FACTORS.

The constant increase in the level of traumatic brain injuries in recent years, the frequent cases of disability and mortality associated with them require in-depth comprehensive research to study the problem on the ground, its medical, social, and economic aspects, which is very important for improving organizational measures to reduce traumatization among all age groups of the population. Objectives - to determine the presence and nature of structural damage associated with traumatic brain injury. The presence and nature of structural damage associated with traumatic brain injury. The studies included data on the treatment of victims with traumatic brain injuries from 2016 to 2020 on the basis of the Surgical Clinic of the Azerbaijan Medical University. Among the victims, men accounted for 77.9% and women 22.1%. In a prospective comparative study, after signing informed consent, 299 people of different sexes were included, of which 90 were victims with isolated TBI. The inclusion criteria for the study were as follows: victims with a verified diagnosis of TBI; age over 18; patients without concomitant somatic pathology. In a gender-comparative analysis of the revealed data, an injury combined with fractures of the bones of the extremities was recorded in 77 (81.1%) males and 18 of their female opponents, who also received TBI and accounted for 18.9%. Also high, especially in the male half of the examined injured persons, was the frequency of occurrence of TBI combinations with rib fractures and injuries of the chest organs, such injuries were registered in 41 victims, which accounted for 77.4% of all the above combined TBI. Somewhat less in both sex groups was TBI in combination with traumatic injuries of organs and tissues of the abdominal region, as well as with mixed injuries (χ2 criterion is 2.066; Df=4; p=0.724). The lowest level of TBI was observed in people under the age of 20 and older than 70 years, in other groups this figure increased sharply, reaching a maximum at the age of 20-29 and 40-49 years, and stabilized in the age groups over 49 years. The maximum number of cases associated with partial or complete loss of consciousness was recorded in persons aggravated by simultaneous traumatization of the upper or lower extremities and chest, as well as in isolated TBI.

Cultural factors and family influences on adolescent oral health: qualitative research in a socially disadvantaged population.

AIM: This qualitative study sought to assess the influence of cultural factors and family on oral health behaviour of 12- to 15-year-old adolescents from the socially disadvantaged population. DESIGN: A qualitative design was developed with focus group discussions (FGDs) among 12- to 15-year-old adolescents. Four focus groups (n = 32 participants) were created from a selected sample to capture oral health beliefs and practices, oral health-seeking behaviour along with other relevant information. Focus group discussions were audio-recorded, transcribed verbatim and translated. Data were analysed thematically and structural coding was applied. RESULTS: Three key themes that emerged from FGDs were importance of oral health; role of family in oral health behaviour; and beliefs influencing access, prevention and treatment of oral diseases. Cultural background, family values and beliefs were imperative in moulding the behaviour of adolescents towards oral health. The use of traditional oral hygiene aides was a norm in this population. CONCLUSIONS: Findings of the study provide greater insights into the authoritative role of family and cultural barriers in the uptake of dental services. The study also highlights the potential value of qualitative research and emphasizes the need to integrate oral health-associated cultural beliefs and attitudes of the adolescents towards a wider evidence base.

Predictors of hospital length of stay and long-term care facility placement in aneurysmal subarachnoid hemorrhage.

Background: Aneurysmal subarachnoid hemorrhage (aSAH) is frequently associated with complications, extended hospital length of stay (LOS) and high health care related costs. We sought to determine predictors for hospital LOS and discharge disposition to a long-term care facility (LTCF) in aSAH patients. Methods: We performed a retrospective study of a prospectively collected cohort of consecutive patients with aSAH admitted to an academic referral center from 2016 to 2021. Multiple linear regression was performed to identify predictors for hospital LOS. We then created a 10-point scoring system to predict discharge disposition to a LTCF. Results: In a cohort of 318 patients with confirmed aSAH, mean age was 57 years (SD 13.7), 61% were female and 70% were white. Hospital LOS was longer for survivors (median 19 days, IQR 14-25) than for non-survivors (median 5 days, IQR 2-8; p < 0.001). Main predictors for longer LOS for this cohort were ventriculoperitoneal shunt (VPS) requirement (p < 0.001), delayed cerebral ischemia (p = 0.026), and pneumonia (p = 0.014). The strongest predictor for LTCF disposition was age older than 60 years (OR 1.14, 95% CI 1.07-1.21; p < 0.001). LTCF score had high accuracy in predicting discharge disposition to a LTCF (area under the curve [AUC] 0.83; 95% CI 0.75-0.91). Forty-one percent of patients who were discharged to a LTCF had significant functional recovery at 3 months post-discharge. Conclusions: VPS requirement and aSAH related complications were associated with longer hospital LOS compared to other factors. LTCF score has high accuracy in predicting discharge disposition to a LTCF.

Superior haplotypes towards the development of blast and bacterial blight-resistant rice.

Rice blast and bacterial leaf blight, are major disease, significantly threatens rice yield in all rice growing regions under favorable conditions and identification of resistance genes and their superior haplotypes is a potential strategy for effectively managing and controlling this devastating disease. In this study, we conducted a genome-wide association study (GWAS) using a diverse set of 147 rice accessions for blast and bacterial blight diseases in replications. Results revealed 23 (9 for blast and 14 for BLB) significant marker-trait associations (MTAs) that corresponded to 107 and 210 candidate genes for blast and BLB, respectively. The haplo-pheno analysis of the candidate genes led to the identification of eight superior haplotypes for blast, with an average SES score ranging from 0.00 to 1.33, and five superior haplotypes for BLB, with scores ranging from 1.52cm to 4.86cm superior haplotypes. Among these, superior haplotypes LOC_OS12G39700-H4 and LOC_Os06g30440-H33 were identified with the lowest average blast scores of 0.00-0.67, and superior haplotype LOC_Os02g12660-H39 exhibited the lowest average lesion length (1.88 - 2.06cm) for BLB. A total of ten accessions for blast and eight accessions for BLB were identified carrying superior haplotypes were identified. These haplotypes belong to aus and indx subpopulations of five countries (Bangladesh, Brazil, India, Myanmar, and Pakistan). For BLB resistance, eight accessions from six countries (Bangladesh, China, India, Myanmar, Pakistan, and Sri Lanka) and four subpopulations (aus, ind1A, ind2, and ind3) were identified carrying superior haplotypes. Interestingly, four candidate genes, LOC_Os06g21040, LOC_Os04g23960, LOC_Os12g39700, and LOC_Os01g24640 encoding transposon and retrotransposon proteins were among those with superior haplotypes known to play a crucial role in plant defense responses. These identified superior haplotypes have the potential to be combined into a single genetic background through haplotype-based breeding for a broader resistance spectrum against blast and bacterial blight diseases.

Comparison of the Effects of Blood Pressure Parameters on Rebleeding and Outcomes in Unsecured Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Elevated systolic blood pressure (SBP) has been linked to preprocedural rebleeding risk and poor outcome in patients with aneurysmal subarachnoid hemorrhage (aSAH). This study seeks to compare the effects of SBP and mean arterial pressure (MAP) on rebleeding and functional outcomes in aSAH patients. METHODS: We performed a retrospective study of a prospectively collected cohort of consecutive patients with aSAH admitted to an academic center in 2016-2023. Binary regression analysis was used to determine the association between BP parameters and outcomes including rebleeding and poor outcome defined as modified Rankin Scale 4-6 at 3 months postdischarge. RESULTS: The cohort included 324 patients (mean age 57 years [standard deviation 13.4], 61% female). Symptomatic rebleeding occurred in 34 patients (11%). Higher BP measurements were recorded in patients with rebleeding and poor outcome, however, only MAP met statistical significance for rebleeding (odds ratio {OR} 1.02 for 1 mmHg increase in MAP, 95% confidence interval {CI}: 1.001-1.03, P = 0.043; OR 1 per 1 mmHg increase in SBP, 95% CI 0.99-1.01; P = 0.06)) and for poor outcome (OR 1.01 for 1 mmHg increase in MAP, 95% CI: 1.002-1.025, P = 0.025; OR 1 for 1 mmHg increase in SBP, 95% CI: 0.99-1.02, P = 0.23) independent of other predictors. CONCLUSIONS: MAP may appear to be slightly better correlated with rebleeding and poor outcomes in unsecured aSAH compared to SBP. Larger prospective studies are needed to identify and mitigate risk factors for rebleeding and poor outcome in aSAH patients.

US Generic Antiseizure Medication Supply Chain: Observations from Analysis of US Government Databases.

BACKGROUND: Generic drug manufacturing has shifted away from the U.S. in the last few decades. The medication supply chain, from manufacturers to resellers, has become increasingly globalized and complex. This has led to bottlenecks in their manufacture resulting in medication shortages. Review of this process as it pertains to antiseizure medications (ASM) shows gaps in our comprehension of its complexities. Understanding these processes will be essential for preventing medication shortages. OBJECTIVES: The aim of this research is to examine the generic ASM supply with an emphasis on production, labeling, and repackaging. METHODS: Data from the United States Food and Drug Administration (FDA) and the National Library of Medicine (NLM) website DailyMed was used to evaluate supply chain details to gather information on antiseizure medication formulations, manufacturing locations, and labeling. RESULTS: Out of 3142 ASM-related active National Drug Code (NDC-9) codes, 2663 NDC-9 codes with Abbreviated New Drug Application (ANDA) status were included in the analysis. Most (94.8 %) were enteral, with only 5.2 % being parenteral (intravenous and intramuscular route). We identified the manufacturing country for 82 % of these codes, corresponding to 306 unique ANDA numbers. 119 manufacturing sites in 12 countries produce generic ASM Finished Dosage Forms (FDF): 103 for enteral and 21 for parenteral. India is the main producer of enteral ASM FDFs with 49 sites, followed by the US with 36. Regarding parenteral formulation, five countries had 21 unique manufacturing locations. 42 % of the 103 enteral ASM FDFs manufacturing sites produced multiple ASM FDFs, with one facility making eight distinct ASMs. 34.4 % of facilities were associated with over 3 ANDAs, and 15.1 % with more than 5. 22.7 % of ANDAs lacked a manufacturing facility identifier. Repackaged ASM FDFs constituted 48 % of NDC-9 s. Gabapentin and pregabalin were the most common oral ASMs. CONCLUSIONS: India is the major source for generic ASM FDFs manufacturing, leading to concerns about overall supply dependency on that country. There is a paucity of facilities for the global supply of parenteral ASM FDFs. There is missing data for many NDC-9 codes emphasizing urgency for transparency in the supply chain.

Revealing the associated microflora hosted by the globally significant parasite Trichostrongylus colubriformis.

Trichostrongylus colubriformis is a parasitic helminth that primarily infects small ruminants, causing substantial economic losses in the livestock industry. Exploring the microbiome of this helminth might provide insights into the potential influence of its microbial community on the parasite's survival. We characterised the intestinal microbiome of T. colubriformis that had been collected from the duodenum of sheep, and compared the helminth microbiome with the duodenal microbiome of its host, aiming to identify contributions from the helminth's environment. At the same time, we explored the isolation of fastidious organisms from the harvested helminth. Primary alpha and beta diversity analyses of bacterial species revealed statistically significant differences between the parasite and the host, in terms of species richness and ecological composition. 16S rRNA differential abundance analysis showed that Mycoplasmoides and Stenotrophomonas were significantly present in T. colubriformis but not in the duodenal microbiome of the sheep. Furthermore, two bacteria, Aeromonas caviae and Aeromonas hydrophila, were isolated from T. colubriformis. Examinations of the genome highlight differences in genome size and profiles of antimicrobial resistance genes. Our results suggest that T. colubriformis carries a specific bacterial community that could be supporting the helminth's long-term survival in the host's digestive system.