Clinico-radiological factors associated with aphasia outcome in post stroke patients: A prospective follow up study from eastern part of India.

BACKGROUND: Aphasia is a language disorder acquired secondary to brain damage. This study aims to evaluate clinical and radiological profile of patients with post stroke aphasia and factors affecting its recovery. METHODS: We conducted a prospective study of patients with first left Middle or Anterior Cerebral Artery infarct or Intracerebral Hemorrhage (ICH) with aphasia admitted within 14 days of stroke onset. Aphasia Quotient (AQ) was assessed at 2 weeks (AQ1) and 3 months (AQ2) using Western Aphasia Battery-Hindi version. Magnetic Resonance Imaging of brain with Diffusion Tensor Imaging (DTI) of bilateral Arcuate Fasciculus (AF) and Corticospinal Tract was done at admission, and stroke volume, Laterality Indices of Fractional Anisotropy (LI-FA), Mean Diffusivity (LI-MD), Radial Diffusivity (LI-RD), Axial Diffusivity (LI-AD) and Apparent Diffusion Coefficient (LI-ADC) were obtained. RESULTS: 36 patients [8 ICH and 28 Acute Ischemic Stroke (AIS)] were included. AQ1 and AQ2 were significantly higher in subcortical stroke than cortical. AQ2 and increase in AQ scores (including its subscores) were significantly higher in ICH than AIS. National Institutes of Health Stroke Scale score at admission and volume of stroke had significant negative correlation with AQ1 and AQ2. Laterality Index of Fractional Anisotropy of Arcuate Fasciculus [LI-FA (AF)] had significant positive correlation with AQ2 and naming score at 3 months. Laterality Index of Mean Diffusivity of Arcuate Fasciculus [LI-MD (AF)] had significant negative correlation with AQ1, AQ2 and all subcomponents of AQ2. Significant positive correlation was seen between improvements in Modified Rankin Scale score and AQ. CONCLUSION: The study shows that DTI can be used to predict severity of aphasia at follow up and recovery in language and motor functions occur in parallel.

Persistent facial pain in post-stroke patients, a hospital-based cohort study; experience from North India.

Background: Post-stroke pain is common after a stroke and might be underreported. We describe Persistent Facial Pain (PFP) developed in post-stroke patients. Method: ology: This was a prospective hospital-based cohort study of stroke patients, and patients were followed up. Out of 415 stroke patients, 26 developed PFP. Result: Out of all PFP patients, six patients had an ischemic stroke, and 20 had a hemorrhagic stroke. 57.7% of patients had hypertension, while 34.6 patients had diabetes. The stroke location was left-sided in 12 patients and right-sided in 14 patients. 46.15% of patients responded to venlafaxine, 30.77% responded to amitriptyline, and 23.08% responded to pregabalin. Conclusion: Persistent facial pain is a pain syndrome that might be missed in patients post-stroke. It might be more common in hemorrhagic stroke patients than in ischemic stroke patients. It responds adequately to antidepressants. A high index of suspicion is required to diagnose and appropriately manage these patients.

Stroke incidence, mortality, subtypes in rural and urban populations in five geographic areas of India (2018-2019): results from the National Stroke Registry Programme.

Background: Increasing stroke burden in India demands a long-term stroke surveillance framework. Earlier studies in India were urban-based, short term and provided limited data on stroke incidence and its outcomes. This gap is addressed by the establishment of five population-based stroke registries (PBSRs) of the National Stroke Registry Programme, India. This paper describes stroke incidence, mortality and age, sex, and subtypes distribution in the five PBSRs with urban and rural populations. Methods: First-ever incident stroke patients in age group ≥18 years, resident for at least one year in the defined geographic area, identified from health facilities were registered. Death records with stroke as the cause of death from the Civil Registration System (CRS) were included. Transient ischemic attack (TIA) was excluded. Three PBSRs (Cuttack, Tirunelveli, Cachar) included urban and rural populations. PBSRs in Kota and Varanasi were urban areas. The crude and age-standardized incidence rate (ASR) by age, sex, and residence (urban and rural), rate ratios of ASR, case fatality proportions and rates at day 28 after onset of stroke were calculated for years 2018-2019. Findings: A total of 13,820 registered first-ever stroke cases that included 985 death certificate-only cases (DCOs) were analysed. The pooled crude incidence rate was 138.1 per 100,000 population with an age-standardized incidence rate (ASR) of 103.4 (both sexes), 125.7 (males) and 80.8 (females). The risk of stroke among rural residents was one in seven (Cuttack), one in nine (Tirunelveli), and one in 15 (Cachar). Ischemic stroke was the most common type in all PBSRs. Age-standardized case fatality rates (ASCFR) per 100,000 population for pooled PBSRs was 30.0 (males) and 18.8 (females), and the rate ratio (M/F) ranged from 1.2 (Cuttack) to 2.0 (Cachar). Interpretation: Population-based registries have provided a comprehensive stroke surveillance platform to measure stroke burden and outcomes by age, sex, residence and subtype across India. The rural-urban pattern of stroke incidence and mortality shall guide health policy and programme planning to strengthen stroke prevention and treatment measures in India. Funding: The National Stroke Registry Programme is funded through the intramural funding of the Indian Council of Medical Research, Department of Health Research, Ministry of Health and Family Welfare, India.

NMR based Serum metabolomics revealed metabolic signatures associated with oxidative stress and mitochondrial damage in brain stroke.

Brain stroke (BS, also known as a cerebrovascular accident), represents a serious global health crisis. It has been a leading cause of permanent disability and unfortunately, frequent fatalities due to lack of timely medical intervention. While progress has been made in prevention and management, the complexities and consequences of stroke continue to pose significant challenges, especially, its impact on patient's quality of life and independence. During stroke, there is a substantial decrease in oxygen supply to the brain leading to alteration of cellular metabolic pathways, including those involved in mitochondrial-damage, leading to mitochondrial-dysfunction. The present proof-of-the-concept metabolomics study has been performed to gain insights into the metabolic pathways altered following a brain stroke and discover new potential targets for timely interventions to mitigate the effects of cellular and mitochondrial damage in BS. The serum metabolic profiles of 108 BS-patients were measured using 800 MHz NMR spectroscopy and compared with 60 age and sex matched normal control (NC) subjects. Compared to NC, the serum levels of glutamate, TCA-cycle intermediates (such as citrate, succinate, etc.), and membrane metabolites (betaine, choline, etc.) were found to be decreased BS patients, whereas those of methionine, mannose, mannitol, phenylalanine, urea, creatine and organic acids (such as 3-hydroxybutyrate and acetone) were found to be elevated in BS patients. These metabolic changes hinted towards hypoxia mediated mitochondrial dysfunction in BS-patients. Further, the area under receiver operating characteristic curve (ROC) values for five metabolic features (methionine, mannitol, phenylalanine, mannose and urea) found to be more than 0.9 suggesting their high sensitivity and specificity for differentiating BS from NC subjects.

Glutamate Receptor Dysregulation and Platelet Glutamate Dynamics in Alzheimer's and Parkinson's Diseases: Insights into Current Medications.

Two of the most prevalent neurodegenerative disorders (NDDs), Alzheimer's disease (AD) and Parkinson's disease (PD), present significant challenges to healthcare systems worldwide. While the etiologies of AD and PD differ, both diseases share commonalities in synaptic dysfunction, thereby focusing attention on the role of neurotransmitters. The possible functions that platelets may play in neurodegenerative illnesses including PD and AD are becoming more acknowledged. In AD, platelets have been investigated for their ability to generate amyloid-ß (Aß) peptides, contributing to the formation of neurotoxic plaques. Moreover, platelets are considered biomarkers for early AD diagnosis. In PD, platelets have been studied for their involvement in oxidative stress and mitochondrial dysfunction, which are key factors in the disease's pathogenesis. Emerging research shows that platelets, which release glutamate upon activation, also play a role in these disorders. Decreased glutamate uptake in platelets has been observed in Alzheimer's and Parkinson's patients, pointing to a systemic dysfunction in glutamate handling. This paper aims to elucidate the critical role that glutamate receptors play in the pathophysiology of both AD and PD. Utilizing data from clinical trials, animal models, and cellular studies, we reviewed how glutamate receptors dysfunction contributes to neurodegenerative (ND) processes such as excitotoxicity, synaptic loss, and cognitive impairment. The paper also reviews all current medications including glutamate receptor antagonists for AD and PD, highlighting their mode of action and limitations. A deeper understanding of glutamate receptor involvement including its systemic regulation by platelets could open new avenues for more effective treatments, potentially slowing disease progression and improving patient outcomes.

A Eu3+doped functional core-shell nanophosphor as fluorescent biosensor for highly selective and sensitive detection of dsDNA.

Lanthanide-doped core-shell nanomaterials have illustrated budding potential as luminescent materials, but their biological applications have still been very limited due to their aqueous solubility and biocompatibility. Here, we report a simple and cost-effective approach to construct a water-stable chitosan-functionalized lanthanoid-based core shell (Ca-Eu:Y2O3@SiO2) nanophosphor. The as-synthesized Ca-Eu:Y2O3@SiO2-chitosan (CEY@SiO2-CH) nanophosphor has been characterized for its structural, morphological, and optical properties, by employing different analytical tools. This sensing platform is suitable for dsDNA probing by tracing the "turn on" fluorescence signal generated by CEY@SiO2-CH nanophosphor with the addition of dsDNA. The ratio of fluorescence intensity enhancement is proportional to the concentration of dsDNA in the range 0.1-90 nM, with the limit of detection at ⁓16.1 pM under optimal experimental conditions. The enhancement in fluorescence response of functionalized core-shell phosphor with dsDNA is due to the antenna effect. Additionally, response of probe has been studied for the real samples displaying percent recovery in between 101 and 105, maximum RSD% upto 5.23 (n = 3). This outcome can be applied to the selective sensing of dsDNA through optical response. These findings establish the CEY@SiO2-CH a simple, portable, and potential candidate as a sensor for rapid and analytical detection of dsDNA.

Evaluating the Effect of Pregabalin in the Treatment of Carpal Tunnel Syndrome: A Prospective, Randomized, Triple-Blinded, Placebo-controlled Trial.

OBJECTIVE: This study aimed to determine the effectiveness of pregabalin for the control of symptoms in mild to moderate idiopathic Carpal tunnel syndrome (CTS). METHODS: In this randomized, placebo-controlled trial, 146 mild to moderate idiopathic CTS patients were randomized into pregabalin (n=74) and placebo groups (n=72). Per protocol, analysis was conducted with 131 patients; pregabalin (n=65) and placebo (n=66). The drug titration dose was 50 mg once daily for the first week, twice daily for the second week and thrice daily for the next 6 weeks. The primary outcome included a change in the Symptom Severity Scale and Functional Status Scale (FSS) of the Boston Carpal Tunnel Questionnaire after the eighth week. The secondary outcome was the change in clinical and electrophysiological grading after 8 weeks of therapy. RESULTS: There was a statistically significant improvement in the mean Symptom Severity Scale (14.92±3.72 vs. 16.55±4.45; P =0.025) and FSS (10.77±2.64 vs. 12.0±2.55; P =0.007) in the pregabalin group after 8 weeks. Mean clinical and electrophysiological grading changed significantly from 2.3±0.7 to 2.1±0.8 ( P =0.001) and 1.9±0.7 to 1.8±0.8 ( P =0.020), respectively in the pregabalin group but not in the placebo group. DISCUSSION: The results of this study demonstrates that pregabalin is effective in ameliorating symptoms and improving functional outcomes in mild to moderate idiopathic CTS.

Necroptosis executioner MLKL plays pivotal roles in agonist-induced platelet prothrombotic responses and lytic cell death in a temporal order.

Necroptosis is a form of programmed cell death executed by receptor-interacting serine/threonine protein kinase 1 (RIPK1), RIPK3, and mixed lineage kinase domain-like (MLKL). Platelets are circulating cells that play central roles in haemostasis and pathological thrombosis. In this study we demonstrate seminal contribution of MLKL in transformation of agonist-stimulated platelets to active haemostatic units progressing eventually to necrotic death on a temporal scale, thus attributing a yet unrecognized fundamental role to MLKL in platelet biology. Physiological agonists like thrombin instigated phosphorylation and subsequent oligomerization of MLKL in platelets in a RIPK3-independent but phosphoinositide 3-kinase (PI3K)/AKT-dependent manner. Inhibition of MLKL significantly curbed agonist-induced haemostatic responses in platelets that included platelet aggregation, integrin activation, granule secretion, procoagulant surface generation, rise in intracellular calcium, shedding of extracellular vesicles, platelet-leukocyte interactions and thrombus formation under arterial shear. MLKL inhibition, too, prompted impairment in mitochondrial oxidative phosphorylation and aerobic glycolysis in stimulated platelets, accompanied with disruption in mitochondrial transmembrane potential, augmented proton leak and drop in both mitochondrial calcium as well as ROS. These findings underscore the key role of MLKL in sustaining OXPHOS and aerobic glycolysis that underlie energy-intensive platelet activation responses. Prolonged exposure to thrombin provoked oligomerization and translocation of MLKL to plasma membranes forming focal clusters that led to progressive membrane permeabilization and decline in platelet viability, which was prevented by inhibitors of PI3K/MLKL. In summary, MLKL plays vital role in transitioning of stimulated platelets from relatively quiescent cells to functionally/metabolically active prothrombotic units and their ensuing progression to necroptotic death.

Development and Evaluation of Some Molecular Hybrids of N-(1-Benzylpiperidin-4-yl)-2-((5-phenyl-1,3,4-oxadiazol-2-yl)thio) as Multifunctional Agents to Combat Alzheimer's Disease.

A series of some novel compounds (SD-1-17) were designed following a molecular hybridization approach, synthesized, and biologically tested for hAChE, hBChE, hBACE-1, and Aß aggregation inhibition potential to improve cognition and memory functions associated with Alzheimer's disease. Compounds SD-4 and SD-6 have shown multifunctional inhibitory profiles against hAChE, hBChE, and hBACE-1 enzymes in vitro. Compounds SD-4 and SD-6 have also shown anti-Aß aggregation potential in self- and acetylcholinesterase (AChE)-induced thioflavin T assay. Both compounds have shown a significant propidium iodide (PI) displacement from the cholinesterase-peripheral active site (ChE-PAS) region with excellent blood-brain barrier (BBB) permeability and devoid of neurotoxic liabilities. Compound SD-6 ameliorates cognition and memory functions in scopolamine- and Aß-induced behavioral rat models of Alzheimer's disease (AD). Ex vivo biochemical estimation revealed a significant decrease in malonaldehyde (MDA) and AChE levels, while a substantial increase of superoxide dismutase (SOD), catalase, glutathione (GSH), and ACh levels is seen in the hippocampal brain homogenates. The histopathological examination of brain slices also revealed no sign of neuronal or any tissue damage in the SD-6-treated experimental animals. The in silico molecular docking results of compounds SD-4 and SD-6 showed their binding with hChE-catalytic anionic site (CAS), PAS, and the catalytic dyad residues of the hBACE-1 enzymes. A 100 ns molecular dynamic simulation study of both compounds with ChE and hBACE-1 enzymes also confirmed the ligand-protein complex's stability, while quikprop analysis suggested drug-like properties of the compounds.

Vitamin D and inflammatory cytokines association in mild cognitive impaired subjects.

BACKGROUND: Mild cognitive impairment (MCI) is a prodromal stage of Alzheimer's disease (AD). The association of low Vitamin D and chronic inflammation in the onset of cognitive decline in the elderly population has been established but the variable population-based study is still lacking. METHODOLOGY: The present study aims to investigate the level of plasma Vitamin D, pro-inflammatory cytokines IL-1ß, IL-6, TNF-α, cognitive performance, and white matter changes in the elderly population in the North-Eastern part of Uttar Pradesh, India. RESULTS: 70 participants with (Mean age- 75.14 ± 1.24, Male/Female- 50/20) with an Mini Mental State Examination (MMSE) score of (24.82 ± 1.82) and Montreal Cognitive Assessment Test (MOCA) score (21.83 ± 1.75), were cognitive decline, against the 70 healthy controls (Mean Age-73.18 ± 1.43; Male/Female- 50/20) with MMSE score (28.1 ± 1.5) and MOCA (28.5 ± 1.65), White matter variable Fractional Anisotropy (FA) and Apparent Diffusion Coefficient (ADC) values in MCI subject was found significantly altered in Right temporal lobe, Corpus Callosum (Right) and Hippocampus body (Right), Hippocampus body (left), Hippocampus head (Right) and Hippocampus head (Left)as compared with healthy controls. The level of cytokines IL-1ß, IL-6, TNF-α, was significantly high in MCI subjects as compared with controls. Further lower Vitamin D level in plasma was detected in MCI as compared with healthy controls. CONCLUSION: The result from the present study depicts that chronic inflammation and lower Vitamin D level influences neurodegeneration and decline in cognitive performance in the elderly population. These variables can be used as biomarkers for early identification of AD and interventional strategies can be designed for prevention at the prodromal stage of AD.

Spectrum of neurological diseases across gangetic belt: a hospital based prospective observational study.

OBJECTIVE: Neurological disorders are the most common cause of morbidity and mortality in riverside cities. Earlier studies reported the presence of heavy metals in the riverside of Gangetic belt. Our study objective was to determine the prevalence of neurological diseases in Ganga riverside and further divided into sections as just across riverside within 25 kms and non-riverside as 25 kms away from the Ganga river. METHODS: This was a prospective observational study conducted in a tertiary care hospital of selected Gangetic belt. RESULTS: A total of 2016 patients were recorded in this period. Mean age of the participants was 47.89 years, majority were males 59.2%. Most of the patients n = 1154 were from within 25 kms of Ganga riverside and n = 862 patients were from non-riverside (25 kms away from Ganga river). Common neurological diseases were ischemic stroke 22.7%, haemorrhagic stroke 20.7%, seizures 13.7%, septic encephalopathy 9.4%, neuropathy 8.9%, Parkinson's disease 4.3%, myopathy 4.1%, myelitis 2.8%, headache 2.4%, amyotrophic lateral sclerosis 1.9% and functional disorder 1.9%. CONCLUSION: Present study showed that neurological diseases were more common in Ganga riverside and stroke including ischemic and hemorrhagic are most common neurological diseases noted in our study.

Efficacy of Duloxetine in Patients with Central Post-stroke Pain: A Randomized Double Blind Placebo Controlled Trial.

OBJECTIVE: Central post-stroke pain (CPSP) refers to neuropathic pain in areas of the body corresponding to stroke lesions. Duloxetine, a serotonin-norepinephrine reuptake inhibitor, is safe and effective against neuropathic pain. In this randomized double-blind placebo-controlled study, we studied the effect of duloxetine in CPSP patients. METHODS: Consecutive patients satisfying the inclusion criteria were enrolled in the study and were randomized in a simple 1:1 randomization to duloxetine and placebo groups. Baseline demographic, clinical and imaging data were obtained. Prespecified primary outcome was comparison of change in pain intensity from baseline to 4 weeks, as assessed on Numeric Rating Scale (NRS) in both groups. Prespecified secondary outcomes were comparison of change in average pain severity from baseline to 4 weeks as measured on Short-form McGill Pain Questionnaire-2 (SFMPQ-2) score and Pain Disability Index (PDI) score and comparison of Patient Global Impression of Change (PGIC) score at the end of 4 weeks of treatment in both groups. Duloxetine at doses of 30 mg and similarly appearing placebo tablets were given and the dose was doubled if there was no response at the end of 2 weeks. Response to treatment was defined as ≥2 points reduction of NRS pain score. RESULTS: In total, 82 patients were enrolled in the study, 41 in each group. There was a significant difference in reduction in NRS score between duloxetine and placebo group from baseline (6.51 ± 1.03 vs 6.37 ± 1.41) to 4 weeks (3.02 ± 1.70 vs 4.40 ± 1.77, P = .02 for difference in reduction between groups). SFMPQ-2 score (P = .032) and Pain Disability Index score (P = .005) also differ significantly from baseline to 4 weeks between the two groups. PGIC score at the end of 4 weeks was significantly different between the two groups (5.15 ± 1.54 vs 3.89 ± 1.51; P < .001). Responder rate (defined as % of patients with ≥ 2 points reduction on NRS pain score from baseline to end of 4 weeks), on post hoc analysis was found to be significantly higher in duloxetine group (80.5%) than placebo group (43.9%) (P = .042). CONCLUSIONS: Duloxetine can be an effective treatment option for patients with moderate to severe central post-stroke pain.

Assessment of Non-Motor Symptoms of Parkinson's Disease and Their Impact on the Quality of Life: An Observatiobnal Study.

Background: During the past decade the view of Parkinson's disease (PD) as a motor disorder has changed significantly and currently it is recognized as a multisystem disorder with diverse non-motor symptoms (NMS). Aims: The present study aimed to evaluate and characterize the NMS and study their impact on quality of life (QoL) in a PD patient cohort. Material and Methods: This was a cross-sectional study where 92 PD patients fulfilling the UK Parkinson's disease society brain bank criteria were enrolled from a movement disorder clinic. All patients were evaluated using unified Parkinson's disease rating scale, non-motor symptoms scale (NMSS) for the non-motor symptoms, and Parkinson's disease questionnaire-39 (PDQ-39) for the QoL. The impact of NMS on QoL was assessed statistically. Results: A total of 92 patients were enrolled with a mean age of 55.40 ± 7.37 years, mean age of onset of disease 51.62 ± 6.38 years, and mean disease duration of 3.78 ± 1.54 years. Type of disease was akinetic rigid variant in 29.3% (n = 27), tremor predominant type in 36.9%(n = 34), and mixed type in 33.6% (n = 31). Mean Hoehn and Yahr stage was 2.12 ± 0.54. In the NMSS, most common symptom was sleep and fatigue (83%), followed by urinary tract symptoms (63%), mood and cognition (51%), cardiovascular symptoms and falls (43%), gastrointestinal tract symptoms (38%), and sexual function (33%). Univariate analyses showed that all NMS domains had a significant correlation with PDQ-39 with P < 001. Conclusion: Our study shows that NMS in PDare fairly common and significantly impact the QoL.

Epley Maneuver Versus Gans Repositioning Maneuver in Treating Posterior Canal BPPV and Familial Incidence of BPPV: Protocol for A Randomized Controlled Trial.

Benign paroxysmal positional vertigo (BPPV) is a widely recognized vestibular disorder which occurs with short periods of paroxysmal vertigo produced in specific positions. This investigation targets contrasting the adequacy of two unique moves utilized in the management of posterior canal BPPV (PC-BPPV). One is traditional procedure, Epley repositioning maneuver (ERM) and another is Gans Repositioning maneuver (GRM). To compare the efficacy of maneuvers on vertigo and dizziness for people with posterior canal BPPV using Dix hallpike test, Vertigo Analogue Scale (VAS) and Dizziness Handicap Inventory (DHI), 100 people will be recruited confirming to eligibility criteria for this two group (ERM group and GRM group) participant and assessor blinded randomized control study. After Participants will be randomly assigned to either group, the respective maneuver will be performed one or two times until the symptoms resolve. Post maneuver instructions will be demonstrated to each subject nicely. Then, family history will be taken using a questionnaire. Outcomes will be taken once after giving maneuver and then, once after 1 month of treatment. Main outcome variables include VAS, DHI, and Dix hallpike test negativity. If the results indicate that Gans Manoeuvre is equivalent to Epley manoeuvre, then in older and postural compromised BPPV patients who has cervical related neck stiffness and pain or any other disorder, where Epley manoeuvre can not be given as it involves neck extension and rotation, Gans manoeuvre can be given. Trial registration: Clinical Trials Registry (CTRI/2019/10/021681). October 16, 2019. Supplementary Information: The online version contains supplementary material available at 10.1007/s12070-021-02762-y.

Use of Ceftriaxone as a Predictor of Good Outcome in Stroke Patients: A Retrospective Chart Review.

Background: Whether ceftriaxone (CEFT) has any added advantage other than its antibiotics effect in stroke as a neuroprotective agent is not known, and this forms the base of this study. Purpose: We tried to assess the predictive role of the use of CEFT with respect to outcome in stroke patients. Methods: A retrospective chart review was conducted from a stroke registry over consecutive stroke patients admitted at a tertiary teaching institute from January 2017 to December 2018. Patients were categorized into three groups on the basis of antibiotics they received; patients without antibiotic treatment (NAB), piperacillin plus tazobactam treatment, and the CEFT treatment group. The outcome was assessed by the modified Rankin Scale at three months in good (0-3) and poor outcomes (4-6). Results: A total of 390 stroke patients were analyzed with ages ranging between 20 and 95 years and 151 of them were females. It was found that the severity at three months was significantly lower in those patients who were given CEFT antibiotic (P = 0.04; OR = 0.626; 95% CI [0.396, 0.990]). Conclusion: Stroke patients in CEFT-treated group have a better outcome compared to piperacillin-tazobactam therapy or without antibiotics use at three months. This study indicates the possibility of an additional neuroprotective effect of CEFT apart from its antibacterial property.

Raised Blood Urea Nitrogen-Creatinine Ratio as a Predictor of Mortality at 30 Days in Spontaneous Intracerebral Hemorrhage: An Experience from a Tertiary Care Center.

Background: Spontaneous intracerebral hemorrhage (SICH) accounts for 7.5%-30% of all strokes and carries higher morbidity and mortality. Raised blood urea nitrogen and creatinine ratio (BUNR) is a marker of dehydration and related to poor outcome in stroke patients. However, the ratio varies between 15 and 80 in different studies. The aim of the present study was to assess BUNR as an independent predictor of mortality and its sensitivity and specificity in predicting outcome in the SICH population. Materials and Methods: Patients above the age of 18 years with SICH who were admitted in the Department of Neurology at Sir Sunderlal Hospital, Banaras Hindu University between January 2018 and July 2020 were enrolled in the study and prospectively followed up. Demographic, clinical, radiological, and outcome parameters were recorded. Results: A total of 217 patients were included. Of these, 137 (63%) were males. Seventy-one patients died during the initial 30 days. Number of patients with intraventricular hemorrhage (IVH; P = 0.003), higher mean intracerebral hemorrhage (ICH) volume (P < 0.001) and midline shift (P = 0.021), and poor Glasgow Coma Scale (GCS) score (<9) (P = 0.040) was more in the group which did not survive. Mean level of urea was significantly lower among survivors than in those who died (P = 0.001). BUNR was also significantly higher in those who died than in those who survived (P = 0.001). BUNR with a cutoff value of 39.17 was significantly associated with mortality at 30 days with a sensitivity and specificity of 61.97% and 62.33%, respectively. On performing two different multivariable logistic studies, it was found that model B with BUNR ratio as a predictor of mortality out performed model A (without BUNR). Conclusions: The study showed that SICH was associated with significant mortality. Independent predictors of death at 30 days were lower GCS on admission, larger hematoma volume, and BUNR of more than 39.17.

Computational exploration of the dual role of the phytochemical fortunellin: Antiviral activities against SARS-CoV-2 and immunomodulatory abilities against the host.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infections generate approximately one million virions per day, and the majority of available antivirals are ineffective against it due to the virus's inherent genetic mutability. This necessitates the investigation of concurrent inhibition of multiple SARS-CoV-2 targets. We show that fortunellin (acacetin 7-O-neohesperidoside), a phytochemical, is a promising candidate for preventing and treating coronavirus disease (COVID-19) by targeting multiple key viral target proteins. Fortunellin supports protective immunity while inhibiting pro-inflammatory cytokines and apoptosis pathways and protecting against tissue damage. Fortunellin is a phytochemical found in Gojihwadi kwath, an Indian traditional Ayurvedic formulation with an antiviral activity that is effective in COVID-19 patients. The mechanistic action of its antiviral activity, however, is unknown. The current study comprehensively evaluates the potential therapeutic mechanisms of fortunellin in preventing and treating COVID-19. We have used molecular docking, molecular dynamics simulations, free-energy calculations, host target mining of fortunellin, gene ontology enrichment, pathway analyses, and protein-protein interaction analysis. We discovered that fortunellin reliably binds to key targets that are necessary for viral replication, growth, invasion, and infectivity including Nucleocapsid (N-CTD) (-54.62 kcal/mol), Replicase-monomer at NSP-8 binding site (-34.48 kcal/mol), Replicase-dimer interface (-31.29 kcal/mol), Helicase (-30.02 kcal/mol), Papain-like-protease (-28.12 kcal/mol), 2'-O-methyltransferase (-23.17 kcal/mol), Main-protease (-21.63 kcal/mol), Replicase-monomer at dimer interface (-22.04 kcal/mol), RNA-dependent-RNA-polymerase (-19.98 kcal/mol), Nucleocapsid-NTD (-16.92 kcal/mol), and Endoribonuclease (-16.81 kcal/mol). Furthermore, we identify and evaluate the potential human targets of fortunellin and its effect on the SARS-CoV-2 infected tissues, including normal-human-bronchial-epithelium (NHBE) and lung cells and organoids such as pancreatic, colon, liver, and cornea using a network pharmacology approach. Thus, our findings indicate that fortunellin has a dual role; multi-target antiviral activities against SARS-CoV-2 and immunomodulatory capabilities against the host.

Effect of Emotional Valence on Working Memory of Psychogenic Non-Epileptic Seizures (PNES) Patients.

Background The present study investigated how emotional valence influenced the working memory of patients with psychogenic non-epileptic seizures (PNES) as compared to healthy individuals. Methods Emotional-N-Back task (E-N-back task) was administered to 15 PNES patients and equal number of healthy individuals. A 2 × 3 one-way analysis of variance (ANOVA) was used. Correct detection (accuracy) and reaction (RT) time were recorded as behavioral performance measures. Results The ANOVA result of correct detection (accuracy) measure revealed significant difference in the performance of patients with PNES as compared with healthy individual, F (2, 48) = 17.08, p = 0.001. However, on the measure of reaction time (RT), both groups performed equally and there was no significant difference, F (2, 48) = 1.13, p = 0.33. Also the results of present study showed that patients with PNES are quicker in identifying unpleasant picture stimuli, which is evident from their mean comparison: unpleasant ( M = 65.55, SD = 15.66), pleasant ( M = 58.22, SD = 20.03), and neutral ( M = 45.11, SD = 23.13). Conclusion Conclusively, the finding of the present study shows a significant effect of emotional valence on working memory of patients with PNES on the measure of correct detection (accuracy), but not for second measure, i.e., reaction time this clearly reveals that patients with PNES are poor at emotional-cognitive integration, specifically at working memory level.

"Oxygen Pheriwala:" An innovative model for SARS-CoV-2 screening in resource-limited settings.

The second wave of SARS-CoV-2 infection came as a hypoxic emergency and situation became worse in rural India, where undiagnosed COVID-19 patients died without any diagnosis or intervention. The primary aim of this innovative model was the early diagnosis of suspected SARS-CoV-2 cases, providing empirical treatment and timely referral to appropriate COVID care facilities. Fever was measured with infrared thermometer and oxygen saturation level with pulse oximeter. A total of 8203 people were screened, of which 274 persons were febrile and 69 (25%) were hypoxic too. Sixty-four out of 69 (93%) patients turned COVID-19 positive on reverse transcription-polymerase chain reaction. At the end of 3 weeks, 48/64 (75%) patients were successfully discharged. This model can be easily implemented in resource-limited regions to identify and prioritize the patients not only in this pandemic but also in outbreak of other communicable diseases.