Unraveling Labrune Syndrome: A Case Report on the Neurological Phenotype in SNORD118-Negative Patients.

Labrune syndrome is a rare neurogenetic disorder with varied presentations. Here, we report the case of a 53-year-old male who presented with seizures, gait imbalance, and upper limb tremors for two years. Imaging studies revealed extensive leukodystrophy, multiple cerebral calcifications, and cystic lesions characteristic of Labrune syndrome. However, whole exome sequencing did not detect the SNORD118 mutation, typically associated with Labrune syndrome. Although the SNORD118 mutation is commonly found in Labrune syndrome, a few cases of the syndrome without this mutation have also been reported. This suggests the possibility that other yet undiscovered mutations may cause the same phenotype.

Rituximab Therapy for Immune-Mediated Neurological Diseases: Our Experience at a Tertiary Care Centre.

INTRODUCTION: Rituximab (RTX) is a monoclonal anti-CD20 chimeric antibody that inhibits B cell activity. However, it is an appealing substitute for traditional immunomodulatory drugs as a swiftly acting, targeted therapy with mounting evidence of efficacy and tolerance in numerous neuroinflammatory conditions. We discuss the scientific evidence for the use of RTX in neurological illnesses, as well as the dose, safety, and other practical elements of prescription. AIM: This study aims to assess and correlate the effects of RTX on immune-mediated neurological disorders. OBJECTIVES: The primary objective of this study is to determine the outcomes in patients treated with RTX for the following conditions: myasthenia gravis (MG), autoimmune encephalitis, multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), myelin oligodendrocyte glycoprotein antibody disease (MOGAD), immune-mediated peripheral neuropathy, and inflammatory muscle disease. The secondary objective is to assess adverse drug reactions in patients treated with RTX. METHODS: This is a prospective observational study conducted at a tertiary care centre. The data were analyzed for the period from May 2022 to May 2024. Approval was obtained from the institutional ethics committee before commencing the study, and written informed consent was obtained from all patients. RESULTS AND CONCLUSIONS: A total of 56 patients were included in the study. The distribution of patients according to diseases is as follows: MG (17), MS (11), NMOSD (10), MOGAD (7), immune-mediated peripheral neuropathy (6), autoimmune encephalitis (3), and inflammatory muscle disease (2). However, one patient was lost to follow-up in the autoimmune encephalitis group. All patients experienced improvements in symptoms, and no relapse episodes have been reported except for one patient who had a relapse in the inflammatory muscle disease group. During the infusion process, some adverse drug reactions, such as chills and rigors, were observed, and two patients experienced major side effects, such as Pott's disease and cryptogenic organizing pneumonia. Nevertheless, overall, rituximab shows promise as an off-label immunosuppressive treatment for the aforementioned neurological immune-mediated diseases.

An Unusual Case of Neurofascin 186 Neuropathy.

Among the diverse array of neuropathies, autoimmune neuropathy stands out as a distinctive subset, where the body's immune system mistakenly attacks its nerve tissues, triggering inflammation and nerve damage. NF 186, also known as neurofascin 186, is a cell adhesion molecule crucial for the integrity and functioning of the peripheral nervous system. This case report highlights the clinical presentation specific to NF 186-positive autoimmune neuropathy and also the treatment modalities.

Flavonoids as Potential Therapeutics Against Neurodegenerative Disorders: Unlocking the Prospects.

Neurodegeneration, the decline of nerve cells in the brain, is a common feature of neurodegenerative disorders (NDDs). Oxidative stress, a key factor in NDDs such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease can lead to neuronal cell death, mitochondria impairment, excitotoxicity, and Ca2+ stress. Environmental factors compromising stress response lead to cell damage, necessitating novel therapeutics for preventing or treating brain disorders in older individuals and an aging population. Synthetic medications offer symptomatic benefits but can have adverse effects. This research explores the potential of flavonoids derived from plants in treating NDDs. Flavonoids compounds, have been studied for their potential to enter the brain and treat NDDs. These compounds have diverse biological effects and are currently being explored for their potential in the treatment of central nervous system disorders. Flavonoids have various beneficial effects, including antiviral, anti-allergic, antiplatelet, anti-inflammatory, anti-tumor, anti-apoptotic, and antioxidant properties. Their potential to alleviate symptoms of NDDs is significant.

Rifampicin in the Treatment of Refractory Diabetic Foot Ulcer and Diabetic Foot Osteomyelitis-an Observational Study.

INTRODUCTION: Refractory diabetic foot ulcer (rDFU) and osteomyelitis (diabetic foot osteomyelitis [DFO]) are a major problem in people with diabetes. Often resulting from multidrug-resistant polymicrobial infection, these may result in amputation or nonhealing ulcers. In this nonrandomized open-label study, we looked at the outcome of treatment with rifampicin in patients with nonhealing diabetic foot ulcers. MATERIAL AND METHODS: Patients with DFUs (n = 67, n = 55 with DFO) unresponsive to conventional antimicrobial therapy for >3 months (rDFU) were taken as the study group. All patients received rifampicin for a minimum of 3 months (maximum 6 months if DUFs did not heal after 3 months) in addition to standard antibiotics and compared with similar kind of DFUs (n = 68, n = 55 DFO) who formed the control group, treated with conventional antimicrobial therapy. Patients were followed up for 12 months. Healing of DFU at 6 months and amputation were primary endpoints of the study. RESULTS: In total, 43 patients (64.2%) in the rifampicin group healed at 3 months and another 4 patients healed when rifampicin was continued for 6 months (n = 47, 70.1%). In the control group, 11 patients healed at 3 months (16.2%) and 25 patients healed at 6 months (36.8%). In total, 14 patients (20.9%) in the study group and 29 patients (42.6%) in the control group had to undergo minor amputation. Comparison between the rate of healing at 3 and 6 months and minor amputation between the study group and control group showed statistically significant results (P ≤ .00001, <.00001, and .008, respectively). In total, 6 and 8 patients despite healing of the primary ulcer had a subsequent recurrence of ulcer in the rifampicin and control group, respectively. CONCLUSION: Rifampicin used in conjunction with other standard poly-microbial therapy in refractory complex diabetic foot ulcer unresponsive to standard antimicrobial therapy, can significantly improve wound healing as well as decrease the need for amputation in addition to standard of care.

Case Report: Chorea as a Rare Manifestation of Secondary Adrenal Insufficiency.

The word "chorea" comes from the Latin word "choreus," which means dancing movement. Chorea is defined as a hyperkinetic movement disorder characterized by uncontrolled, unintended, jerky, brief, irregular, random movements involving the limbs or facial muscles. Here, we discuss the case of a 48-year-old male with hypothyroidism for two years, which is well-controlled with medication. He presented with behavioral disturbances for the past seven months and choreiform movements affecting all four limbs, his tongue, and his face for the past six months. Investigations revealed hyponatremia and low serum osmolality. An MRI of the brain showed the empty sella sign. Further investigations revealed low levels of adrenocorticotropic hormone (ACTH), prolactin, and testosterone. Considering the diagnosis of chorea with euvolemic hyponatremia due to secondary adrenal insufficiency, the patient was started on tetrabenazine, trihexyphenidyl, oral hydrocortisone, and gradual correction of sodium level. The patient's condition improved during the hospital stay, and he continues to do well in routine follow-ups.

Effect of COVID-19 on Stress and Biomarkers: An Exploratory Cross-Sectional Study.

Background Anxiety and stress in COVID-19 lead to continual pro-inflammatory cytokine activity resulting in excessive inflammation. Levels of different bio indices of COVID-19 may predict clinical outcomes and the severity of COVID-19 disease and may correlate with anxiety and stress levels. Objectives To measure the level of anxiety in COVID-19 patients using the coronavirus anxiety scale (CAS) as an assessment of psychological stress. To measure the levels of blood biomarkers and biochemical and hematological markers of inflammation in COVID-19. To record and measure the indices of short-term HRV in COVID-19 patients to assess their physiological and psychological stress levels. To determine the relationship between anxiety scores, levels of laboratory indices (blood biomarkers), and HRV parameters across mild, moderate and severe cases of COVID-19. Material and method A total of 300 COVID-19 patients aged between 18 and 55 years were included. A questionnaire-based CAS was used to assess anxiety levels. Short-term HRV was recorded to measure stress. Blood biomarkers: Biochemical and hemato-cytological markers of inflammation were measured. Statistical analyses were performed using the SPSS software version 20.0. Results Anxiety and stress increased with the severity of COVID-19. A positive correlation was detected between anxiety and serum ferritin, IL-6, MCV, and MCH levels, and a negative correlation between the corona anxiety score and RBC count. The increase in the severity of COVID-19 showed elevated levels of WBC count, neutrophil%, platelet count, neutrophil/lymphocyte ratio, serum ferritin, D-dimer, C-reactive protein, procalcitonin, interleukin-6, and lactate dehydrogenase, and decreased lymphocyte and monocyte percentages. The increase in the severity of COVID-19 decreased lymphocyte, monocyte, and eosinophil counts. Conclusion The Corona Anxiety Scale and heart rate variability can be used as complementary tools to index COVID-19-related anxiety and stress. An association exists between immune dysregulation and heart rate variability, which can be used to predict the inflammatory response and prognosis of COVID-19.

Semen Quality in Males Suffering From COVID-19: A Pilot Study.

Background It is well known that some viral infections may affect male fertility. Coronavirus disease (COVID-19) can lead to multiorgan damage through the angiotensin-converting enzyme-2 receptor, abundant in testicular tissue. However, little information is available regarding the shedding of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in semen and its impact on spermatogenesis and fertility potential. We planned to investigate the presence of SARS-CoV-2 in the semen of COVID-19 males and to study the effect of COVID-19 on semen quality and sperm DNA fragmentation index. Material and method Thirty COVID-19 male patients aged 19-45 registered to AIIMS Patna hospital participated in the survey between October 2020 and April 2021. We conducted a real-time reverse transcriptase test on all the semen samples. Detailed semen analysis, including the sperm DNA Fragmentation Index, was done at first sampling that is during COVID-19. After 74 days of the first sampling, we obtained the second sampling and repeated all the above tests. Results All semen samples collected in the first and second sampling tested with real-time reverse transcription-polymerase chain reaction (RT-PCR) were negative for SARS-CoV-2. In the first sampling, semen volume, vitality, total motility, sperm concentration, total sperm count, % normal morphology, % cytoplasmic droplet, and fructose were significantly lower. In contrast, semen agglutination, % head defect, DNA Fragmentation Index, liquefaction time, semen viscosity, and leukocytes were increased. These findings were reversed at the second sampling but not to the optimum level. All these findings were statistically significant (p < 0.05 for all). Thus, COVID-19 negatively affects semen parameters, including sperm DNA fragmentation index. Conclusion Although we could not find SARS-CoV-2 in the semen, the semen quality remained poor until the second sampling. Assisted reproductive technology (ART) clinics and sperm banking facilities should consider assessing the semen of COVID-19 males and exclude men with a positive history of SARS-CoV-2 until their semen quality returns to normal.

Comparative evaluation of chelating efficacy of nano-chitosan, pomegranate extract, and ethylenediaminetetraacetic acid on primary radicular dentin: An in vitro study.

Background: Irrigation is a crucial aspect of root canal treatment, and it is imperative to employ chelating agents to eliminate the smear layer during biomechanical preparation. They in turn react with mineral content of dentin, leading to decreased strength and increased susceptibility to fracture. Aims: This study aimed to assess and compare mineral loss and microhardness from primary root canal dentin following the usage of different irrigating solutions and determine the least detrimental irrigant among the tested solutions. Materials and Methods: Sixty-six primary anterior teeth were divided into three groups with 22 in each- Group I: 17% ethylenediaminetetraacetic acid (EDTA) Group II: 0.2% Nano chitosan Group III: Pomegranate extract. The decoronated teeth were split longitudinally. Half of it was directly subjected to Vickers test, and the other half was immersed in a magnetic stirrer bath containing test solution to record the mineral loss from solution. Postmicrohardness values were recorded on the specimen and compared with initial values. Statistical Analysis Used: Statistical analysis was done using SPSS software (Version 20, SPSS, IBM, Armonk, NY, U. S. A). Results: Descriptive statistics were calculated, and the groups were compared using analysis of variance test and post hoc Tukey test. Pomegranate extract showed least effect on mineral content and microhardness compared to 17% EDTA and 0.2% nano chitosan. P ≤ 0.05 was considered statistically significant. Conclusion: Pomegranate aril extract showed better results with selected parameters.

Evaluation of Spirometric Measures and Quality of Sleep in Tuberculosis Patients and Their Non-Tuberculosis Family Caregivers.

Background and Aim Tuberculosis (TB) patients may present with depression and poor sleep as co-morbidities. This presents great challenges including the stigma of increased risk of developing TB while taking care of such patients. This study aims to determine the lung functions, quality of sleep in tuberculosis patients in comparison with non-tuberculosis (non-TB) family caregivers. Methods TB patients and their family caregivers (60 each) visiting the Directly Observed Therapy Short-course (DOTS) clinic at a tertiary care hospital were assessed for spirometric parameters and quality of sleep. Spirometry measurements were performed using a portable, computerized, pre-calibrated, electronic, dry type of machine. Pulmonary function impairment pattern and severity were assessed from spirometry results using a percentage of the predicted values of Forced Vital Capacity (FVC) and Forced Expiratory Volume in one second (FEV1). Descriptive statistics and t-tests were applied using SPSS version 19.0. p≤0.05 was considered significant. Results TB patients had a significantly more (p=0.000) sleep disturbance, daytime dysfunction, and higher mean global Pittsburgh Sleep Quality Index (PSQI) score (9.56±3.97) compared to their non-TB family caregivers (4.36±2.07). The spirometric measures were reduced in TB patients and showed significant differences in actual measures of all parameters except FVC (actual). The % predicted measures of FEV1, FEF 25%-75%, PEFR, and MVV showed significant differences in comparison to their non-TB family caregivers. Conclusions The present study shows that TB patients have a poor quality of sleep and pulmonary functions compared to their non-TB family caregivers. Health care workers need to develop systematic strategies to screen the symptoms of mental disorders in tuberculosis patients and their family caregivers to enable better management of this population.

A review of π-conjugated polymer-based nanocomposites for metal-ion batteries and supercapacitors.

Owing to their extraordinary properties of π-conjugated polymers (π-CPs), such as light weight, structural versatility, ease of synthesis and environmentally friendly nature, they have attracted considerable attention as electrode material for metal-ion batteries (MIBs) and supercapacitors (SCPs). Recently, researchers have focused on developing nanostructured π-CPs and their composites with metal oxides and carbon-based materials to enhance the energy density and capacitive performance of MIBs and SCPs. Also, the researchers recently demonstrated various novel strategies to combine high electrical conductivity and high redox activity of different π-CPs. To reflect this fact, the present review investigates the current advancements in the synthesis of nanostructured π-CPs and their composites. Further, this review explores the recent development in different methods for the fabrication and design of π-CPs electrodes for MIBs and SCPs. In review, finally, the future prospects and challenges of π-CPs as an electrode materials for strategies for MIBs and SCPs are also presented.

Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immune checkpoint inhibitor-related adverse events.

Immune checkpoint inhibitors (ICIs) are the standard of care for the treatment of several cancers. While these immunotherapies have improved patient outcomes in many clinical settings, they bring accompanying risks of toxicity, specifically immune-related adverse events (irAEs). There is a need for clear, effective guidelines for the management of irAEs during ICI treatment, motivating the Society for Immunotherapy of Cancer (SITC) to convene an expert panel to develop a clinical practice guideline. The panel discussed the recognition and management of single and combination ICI irAEs and ultimately developed evidence- and consensus-based recommendations to assist medical professionals in clinical decision-making and to improve outcomes for patients.

Urinary Exosomes Identify Inflammatory Pathways in Vancomycin Associated Acute Kidney Injury.

BACKGROUND: Vancomycin is commonly used as a first line therapy for gram positive organisms such as methicillin resistant Staphylococcusaureus. Vancomycin-induced acute kidney injury (V-AKI) has been reported in up to 43% of patients, especially in those with higher targeted trough concentrations. The precise mechanism of injury in humans remains elusive, with recent evidence directed towards proximal tubule cell apoptosis. In this study, we investigated the protein contents of urinary exosomes in patients with V-AKI to further elucidate biomarkers of mechanisms of injury and potential responses. METHODS: Urine samples from patients with V-AKI who were enrolled in the DIRECT study and matched healthy controls from the UAB-UCSD O'Brien Center Biorepository were included in the analysis. Exosomes were extracted using solvent exclusion principle and polyethylene glycol induced precipitation. Protein identity and quantification was determined by label-free liquid chromatography mass spectrometry (LC/MS). The mean peak serum creatinine was 3.7 ± 1.4 mg/dL and time to kidney injury was 4.0 ± 3.0 days. At discharge, 90% of patients demonstrated partial recovery; 33% experienced full recovery by day 28. Proteomic analyses on five V-AKI and 7 control samples revealed 2009 proteins in all samples and 251 proteins significantly associated with V-AKI (Pi-score > 1). The top discriminatory proteins were complement C3, complement C4, galectin-3-binding protein, fibrinogen, alpha-2 macroglobulin, immunoglobulin heavy constant mu and serotransferrin. CONCLUSION: Urinary exosomes reveal up-regulation of inflammatory proteins after nephrotoxic injury in V-AKI. Further studies are necessary in a large patient sample to confirm these findings for elucidation of pathophysiologic mechanisms and validation of potential injury biomarkers.

Clinical Features and Outcome of Stroke with COVID-19. COVID-19 Stroke Study Group (CSSG), India.

BACKGROUND AND PURPOSE: Occurrence of stroke has been reported among patients with COVID-19. The present study compares clinical features and outcomes of stroke patients with and without COVID-19. METHODS: The COVID-19 Stroke Study Group (CSSG) is a multicentric study in 18 sites across India to observe and compare the clinical characteristics of patients with stroke admitted during the current pandemic period and a similar epoch in 2019. The present study reports patients of stroke with and without COVID-19 (CoVS and non-CoVS, respectively) seen between February 2020 and July 2020. Demographic, clinical, treatment, and outcome details of patients were collected. RESULTS: The mean age and gender were comparable between the two groups. CoVS patients had higher stroke severity and extent of cerebral involvement on imaging. In-hospital complications and death were higher among CoVS patients (53.06% vs. 17.51%; P < 0.001) and (42.31% vs. 7.6%; P < 0.001), respectively. At 3 months, higher mortality was observed among CoVS patients (67.65% vs. 13.43%; P < 0.001) and good outcome (modified Rankin score [mRS]: 0-2) was seen more often in non-CoVS patients (68.86% vs. 33.33%; P < 0.001). The presence of COVID-19 and baseline stroke severity were independent predictors of mortality. CONCLUSIONS: CoVS is associated with higher severity, poor outcome, and increased mortality. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and baseline stroke severity are independent predictors of mortality.

Payment incentives and the use of higher-cost drugs: a retrospective cohort analysis of intravenous iron in the Medicare population.

OBJECTIVES: Medicare Part B payment methods incentivize the use of more expensive injectable and infused drugs. We examined prescribing patterns in the context of intravenous (IV) iron, for which multiple similarly safe and efficacious formulations exist, with wide variations in price. STUDY DESIGN: We conducted a retrospective cohort analysis of IV iron utilization and payment in the Medicare population between 2015 and 2017. METHODS: This analysis used a national, random 20% sample of Medicare fee-for-service beneficiaries with Part B claims for IV iron between January 2015 and December 2017-a period before, during, and after a national shortage of iron dextran. This sample included 66,710 Medicare fee-for-service beneficiaries with at least 1 Part B claim for IV iron. RESULTS: The greatest increase in utilization occurred in the most expensive iron formulation, ferric carboxymaltose; its market share rose from 27.4% of use in 2015 to 47.7% in 2017. The use of a less expensive formulation, iron dextran, decreased from 26.7% to 18.7% over the same period. An alternative payment model in Maryland hospitals was associated with markedly less utilization of ferric carboxymaltose, accounting for 4.7% of IV iron utilization in Maryland hospitals. CONCLUSIONS: There was an increase in the dispensing of a higher-priced IV iron formulation associated with a shortage of a less expensive drug that persisted once the shortage ended. These findings in IV iron have broader implications for Part B drug payment policy because the price of the drug determines the physician and health system payment.

Palladium-Catalyzed Insertion of Ethylene and 1,1-Disubstituted Difunctional Olefins: An Experimental and Computational Study.

Insertion or coordination copolymerization of ethylene with di-substituted olefins is challenging and the choice of di-substituted mono-functional olefin versus di-substituted di-functional olefin (DDO) appears to be decisive. Here we show that DDO-inserted species are amenable to ethylene insertion and polymerization. DDOs such as 2-acetamidoacrylic acid (AAA), methyl 2-acetamidoacrylate (MAAA), and ethyl 2-cyanoacrylate (ECA) were treated with palladium complex [{P∧O}PdMe(L)] (P∧O=κ2 -P,O-Ar2 PC6 H4 SO2 O with Ar=2-MeOC6 H4 ; L=C2 H6 OS) and the existence of respective insertion intermediates in moderate yield (up to 37 %) was established. These intermediates were exposed to ethylene and corresponding ethylene-inserted products were isolated and characterized. A careful comparison with three model compounds confirmed ethylene insertion and polymerization. Thus, the combined experimental and computational investigations show that DDO-inserted species can undergo ethylene insertion and polymerization.

Base mediated spirocyclization of quinazoline: one-step synthesis of spiro-isoindolinone dihydroquinazolinones.

A novel approach for the spiro-isoindolinone dihydroquinazolinones has been demonstrated from 2-aminobenzamide and 2-cyanomethyl benzoate in the presence of KHMDS as a base to get moderate yields. The reaction has been screened in various bases followed by solvents and a gram scale reaction has also been executed under the given conditions. Based on the controlled experiments a plausible reaction mechanism has been proposed. Further the substrate scope of this reaction has also been studied.

Pd-Iminocarboxylate Complexes and Their Behavior in Ethylene Polymerization.

Designing co-catalyst-free late transition metal complexes for ethylene polymerization is a challenging task at the interface of organometallic and polymer chemistry. Herein, a set of new, co-catalyst-free, single-component catalytic systems for ethylene polymerization have been unraveled. Treatment of anthranilic acid with various aldehydes produced four iminocarboxylate ligands (L1-L4) in very good to excellent yield (75-92 %). The existence of 2-((2-methoxybenzylidene)amino) benzoic acid (L1) has been unambiguously demonstrated using NMR spectroscopy, MS and single-crystal X-ray diffraction. A neutral Pd-iminocarboxylate complex [{N O}PdMe(L1)] (N O=κ2 -N,O-ArCHNC6 H4 CO2 with Ar=2-MeOC6 H4 ) C1 was prepared by treating stoichiometric amount of L1.Na with palladium precursor. The identity of C1 was confirmed by 1-2D NMR spectroscopy and single-crystal X-ray diffraction studies. Along the same lines, palladium complexes C2-C4 were prepared from ligands L2-L4 respectively. In-situ high-pressure NMR investigations revealed that these Pd complexes are amenable to ethylene insertion and undergo facile ß-H elimination to produce propylene. These palladium complexes were then evaluated in ethylene polymerization reaction and various reaction parameters were screened. When C1-C4 were exposed to ethylene pressures of 10-50 bar, formation of low-molecular-weight polyethylene was observed.