Validation of a platinum bioelectrode model for preclinical electrical and biological performance evaluation.

High throughput testing of clinically representative Pt electrodes requires an inexpensive, efficient method of production. The aim of this study was to develop a facile platinum (Pt) model electrode (PME) and assess its production process, stability, and reproducibility. In this study a new model electrode was developed using representative substrates and dimensions as state-of-the-art electrode arrays used for neural stimulation. It was found that the PME is a highly reproducible robust system with similar electrochemical performance but with lower variability than other neural prosthetic arrays.Clinical Relevance- As an estimate these novel model electrodes cost 300 times less than a cochlear implant, can be manufactured in a tenth of the time and with a less than 10% failure rate. It is expected that model electrodes with low variability of electrical properties will significantly improve preclinical validation testing of electrochemical stimulation, surface modifications, and coatings.

Massive Subcutaneous Emphysema and Pneumothorax in a Case of Attacked by a Domesticated Bull - An Autopsy Based Diagnosis.

Subcutaneous emphysema is a condition when air or gas gets trapped within the subcutaneous layer. It is characterised by crackling feeling on palpation of the skin known as subcutaneous crepitation which is described as touching rice krispies. A 70 years male from hilly region of Nepal with agricultural background suffered multiple injuries sustained due to an attack by domesticated bull in his house. Upon the incident the injured male was taken to hospital, where he was declared "Brought Dead" by the Emergency Department of Dhulikhel Hospital, Kathmandu University Hospital. His body was brought for autopsy in Department of Forensic Medicine and Toxicology of Kathmandu University School of Medical Sciences. On complete autopsy, massive subcutaneous emphysema and pneumothorax was demonstrated. The details of finding are discussed in detail as follows.

Live-cell three-dimensional single-molecule tracking reveals modulation of enhancer dynamics by NuRD.

To understand how the nucleosome remodeling and deacetylase (NuRD) complex regulates enhancers and enhancer-promoter interactions, we have developed an approach to segment and extract key biophysical parameters from live-cell three-dimensional single-molecule trajectories. Unexpectedly, this has revealed that NuRD binds to chromatin for minutes, decompacts chromatin structure and increases enhancer dynamics. We also uncovered a rare fast-diffusing state of enhancers and found that NuRD restricts the time spent in this state. Hi-C and Cut&Run experiments revealed that NuRD modulates enhancer-promoter interactions in active chromatin, allowing them to contact each other over longer distances. Furthermore, NuRD leads to a marked redistribution of CTCF and, in particular, cohesin. We propose that NuRD promotes a decondensed chromatin environment, where enhancers and promoters can contact each other over longer distances, and where the resetting of enhancer-promoter interactions brought about by the fast decondensed chromatin motions is reduced, leading to more stable, long-lived enhancer-promoter relationships.

Hepatoprotective activity of Balsamodendron mukul extract against Paracetamol-induced liver toxicity in rats: In vivo pharmacological and toxicological evaluation.

Overuse of the antipyretic agent Paracetamol (PCM) is linked to hepatotoxicity, which limits its clinical use. The goal of this investigation was to find out how well Balsamodendron mukul (B. mukul) extract protects the liver from acute PCM poisoning. B. mukul extract was procured from a standard crude drug supplier in the local market. The PCM-induced hepatotoxicity was screened in experimental animals. Animals that were treated only with excessive PCM (2g/kg) had changes in their serum biomarkers (i.e., serum glutamate oxaloacetate transaminase, serum glutamate pyruvate transaminase, alkaline phosphatase, and serum total bilirubin), oxidative stress, Tumor Necrosis Factor-α (TNF-α), and Interleukin-1 proteins. B. mukul extracts of 245µg and 332µg revealed 50% of hydroxyl radical scavenging and lipid peroxidation inhibiting, respectively, which was found to be more significant when compared to ascorbic acid treatment. The outcomes confirmed that B. mukul extract has strong antioxidant activity, which leads to the inhibition of reactive oxygen species (ROS). Treatment with B. mukul extract at doses of 300 and 600mg/kg produced a dose-dependent reduction in the PCM-induced rise of the biochemical parameters. Silymarin at 100mg/kg body weight significantly prevented such rise in the study. Finally, the findings confirmed that the B. mukul extract has more potent than silymarin and revealed higher antioxidant and hepatoprotective activity, which could consider a novel approach for the reduction of PCM-induced liver toxicity.

Ethnicity in polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is the commonest gynecological endocrinopathy. Little is known about the exact etiopathogenesis and cardiometabolic mortality and morbidity in women with PCOS. PCOS is beyond the cosmetic concerns of an adolescent and fertility concerns of an adult and can cause serious unhealthy consequences in perimenopausal and postmenopausal age. This area needs to be assessed and addressed since the majority of these patients are lost to follow-up after completion of their families. Good evidence suggests that there are significant racial and ethnic differences in prevalence, insulin resistance, metabolic syndrome, hyperandrogenemia and the related cardiometabolic risk in women with PCOS.

Application of biomimetic surfaces and 3D culture technology to study the role of extracellular matrix interactions in neurite outgrowth and inhibition.

The microenvironment that cells experience during in vitro culture can often be far removed from the native environment they are exposed to in vivo. To recreate the physiological environment that developing neurites experience in vivo, we combine a well-established model of human neurite development with, functionalisation of both 2D and 3D growth substrates with specific extracellular matrix (ECM) derived motifs displayed on engineered scaffold proteins. Functionalisation of growth substrates provides biochemical signals more reminiscent of the in vivo environment and the combination of this technology with 3D cell culture techniques, further recapitulates the native cellular environment by providing a more physiologically relevant geometry for neurites to develop. This biomaterials approach was used to study interactions between the ECM and developing neurites, along with the identification of specific motifs able to enhance neuritogenesis within this model. Furthermore, this technology was employed to study the process of neurite inhibition that has a detrimental effect on neuronal connectivity following injury to the central nervous system (CNS). Growth substrates were functionalised with inhibitory peptides released from damaged myelin within the injured spinal cord (Nogo & OMgp). This model was then utilised to study the underlying molecular mechanisms that govern neurite inhibition in addition to potential mechanisms of recovery.

Case-control study of vitamin D status and adult multidrug-resistant pulmonary TB.

BACKGROUND: India has the highest prevalence of multidrug-resistant TB (MDR-TB) globally. Vitamin D deficiency is potentially an important risk factor for MDR-TB.METHODS: We conducted a case-control study of 90 newly diagnosed adult MDR-TB cases, 180 household controls and 82 non-household controls in Mumbai, India. Serum 25-hydroxyvitamin D (25(OH)D), anthropometry, clinical status and history, dietary data and sociodemographic data were collected from each participant. Interferon-gamma release assay (IGRA) was also performed in controls to assess latent TB. Multivariable regression was performed to estimate associations between 25(OH)D vs. case status and IGRA positivity.RESULTS: Mean participant age was 33.8 ± 12.0 years; 72.8% had 25(OH)D <20 ng/ml. Mean 25(OH)D was significantly (P < 0.05) lower in cases (12.5 ± 7.9) than both household (17.5 ± 11.2) and non-household controls (16.4 ± 9.1). In multivariable models, 25(OH)D concentration was inversely associated with MDR-TB case status among cases and household controls (OR 0.95 per 1 ng/ml, 95% CI 0.92-0.99; P = 0.015), and among cases and non-household controls (OR 0.94 per 1 ng/ml, 95% CI 0.89-1.00; P = 0.033); 53.6% of controls were IGRA-positive. 25(OH)D status was not associated with IGRA positivity.CONCLUSION: Vitamin D status was independently associated with MDR-TB case status. Research should evaluate the effectiveness of vitamin D supplementation in prevention and adjunctive treatment of MDR-TB.

Risk factors and outcome analysis of patients with intraoperative rupture (IOR) of ruptured cerebral aneurysm during microsurgical clipping.

PURPOSE: To analyse baseline characteristics of patients with intraoperative rupture (IOR) or non-IOR who underwent microsurgical clipping for ruptured intracranial aneurysms. Additionally, to asses functional outcome in terms of Glasgow Outcome Scale (GOS) at 6 and 12 months. METHODS: A retrospective analysis of 471 patients who underwent microsurgical clipping for ruptured intracranial aneurysms from 2007 to 2018 in Nepal Mediciti Hospital, Nepal. Patients who underwent surgery for unruptured aneurysm were excluded from the study. The association of the base line characteristic in IOR and non-IOR were analysed. Variables analysed were the Hunt and Hess Scale (HHS) dichotomized as (1-3) and (4-5), Modified Fisher Scale dichotomized as (0-2) and (3-4), type of rupture, use of brain retractor, timing of IOR during surgery, aneurysmal factors (size of the neck, location, lobulation) and time of surgery. Outcome, GOS dichotomized into favourable (4-5) and unfavourable (1-3), assessed at 6 months and 12 months. RESULTS: Out of 471 patients treated for ruptured intracranial aneurysm, IOR occurred in 57 (12.10%) with mean age 49.47 (SD ±12.9), occurred more in smoker than non-smoker (45.6% vs. 18.6%; p=.000) and regular alcohol consumers (36.8% vs. 17.9%; p=.004). Favourable outcome with GOS (4-5) at 6 months was observed among patients with lower HHS (1-3), p=.025 and lower MFS (0-2), p=.04. However, outcome at 12 months was better associated with MFS (p=.013) and aneurysm size (p=.038), with more favourable outcome associated with aneurysm less than 10 mm. CONCLUSIONS: Alcohol consumption and smoking are associated risk factors that may contribute to IOR. HHS and MFS are strong predictors of outcome for IOR patients at 6 months. However, at 12 months, MFS is more predictive of outcome. Aneurysms greater than 10 mm had a strong association with outcome at 12 months than 6 months.

TB case fatality and recurrence in a private sector cohort in Mumbai, India.

BACKGROUND: Half of India´s three million TB patients are treated in the largely unregulated private sector, where quality of care is often poor. Private provider interface agencies (PPIAs) seek to improve private sector quality of care, which can be measured in terms of case fatality and recurrence rates.METHODS: We conducted a retrospective cohort survey of 4,000 private sector patients managed by the PATH PPIA between 2014 and 2017. We estimated treatment and post-treatment case-fatality ratios (CFRs) and recurrence rates. We used Cox proportional hazards models to identify predictors of fatality and recurrence. Patient loss to follow-up was adjusted for using selection weighting.RESULTS: The treatment CFR was 7.1% (95% CI 6.0-8.2). At 24 months post-treatment, the CFR was 2.4% (95% CI 1.7-3.0) and the recurrence rate was 1.9% (95% CI 1.3-2.5). Treatment fatality was associated with age (HR 1.02, 95% CI 1.02-1.03), clinical diagnosis (HR 0.61, 95% CI 0.45-0.84), treatment duration (HR 0.09, 95% CI 0.06-0.10) and adherence. Post-treatment fatality was associated with treatment duration (HR 0.87, 95% CI 0.79-0.91) and adherence.CONCLUSIONS: We found a moderate treatment phase CFR among PPIA-managed private sector patient with low rates of post-treatment fatality and recurrence. Routine monitoring of patient outcomes after treatment would strengthen PPIAs and inform future post TB interventions.

Development, validation, and application of an RP-HPLC method for concurrent quantification of Minoxidil and Finasteride in a topical solution for hair regrowth.

A topical solution comprising of Minoxidil (MXL) and Finasteride (FNS) for alopecia is formulated in the present work, which essentially contains a lipid-Lauroglycol FCC as a penetration enhancer. The objective of the proposed work was to develop a rapid, simple, and robust reverse phase high performance liquid chromatographic (RP-HPLC) method to determine MXL and FNS in the said formulation. Herein, the chromatographic conditions were optimized based on the theoretical principles of separation and physicochemical properties such as pKa and log P of both the Active Pharmaceutical Ingredients (APIs). The separation was accomplished on an Inertsil® ODS-3 C18 column (150mm×4.6mm; 5µm of particle size) at 25°C by using a mobile phase composed of 70:30 v/v ratio of Methanol and Milli-Q water along with 0.5% Triethylamine at pH 6.4 adjusted with Ortho Phosphoric Acid. Drug peaks showed a good resolution at 210nm. The retention times for MXL and FNS were found to be 2.40min and 6.39min, respectively. The developed method was found to be linear (R2≥0.998) in a concentration range of 5-100µg/mL for both the drugs. The method was validated according to the ICH guidelines Q2 (R1). The ability of the method to differentiate between the types formulations was demonstrated by the in vitro diffusion data performed using a highly sophisticated Strat-M® membrane. The cumulative amount of drug released (MXL and FNS) at the end of 24hours was maximum for the topical formulation containing lipids prepared using isopropyl alcohol and propylene glycol as the base.

Age-related changes in amplitude, latency and specialization of ERP responses to faces and watches.

Healthy aging is associated with impairments in face recognition. While earlier research suggests that these impairments arise during memory retrieval, more recent findings suggest that earlier mechanisms, at the perceptual stage, may also be at play. However, results are often inconsistent and very few studies have included a non-face control stimulus to facilitate interpretation of results with respect to the implication of specialized face mechanisms vs. general cognitive factors. To address these issues, P100, N170 and P200 event-related potentials (ERPs) were measured during processing of faces and watches. For faces, age-related differences were found for P100, N170 and P200 ERPs. For watches, age-related differences were found for N170 and P200 ERPs. Older adults showed less selective and less lateralized N170 responses to faces, suggesting that ERPs can detect age-related de-differentiation of specialized face networks. We conclude that age-related impairments in face recognition arise in part from difficulties in the earliest perceptual stages of visual information processing. A working model is presented based on coarse-to-fine analysis of visually similar exemplars.

COVID-19 pandemic and its positive impacts on environment: an updated review.

In December, 2019 in Wuhan city of China, a novel coronavirus (SARS-CoV-2) has garnered global attention due to its rapid transmission. World Health Organization (WHO) termed the infection as Coronavirus Disease 2019 (COVID-19) after phylogenic studies with SARS-CoV. The virus causes severe respiratory infections with dry cough, high fever, body ache and fatigue. The virus is primarily transmitted among people through respiratory droplets from COVID-19 infected person. WHO declared this COVID-19 outbreak a pandemic and since February, 2020 affected countries have locked down their cities, industries and restricted the movement of their citizens to minimize the spread of the virus. In spite of the negative aspects of coronavirus on the globe, the coronavirus crises brought a positive impact on the natural environment. Countries where the movement of citizens was seized to stop the spread of coronavirus infection have experienced a noticeable decline in pollution and greenhouse gases emission. Recent research also indicated that this COVID-19-induced lockdown has reduced the environmental pollution drastically worldwide. In this review, we have discussed some important positive impacts of coronavirus on environmental quality by compiling the recently published data from research articles, NASA (National Aeronautics and Space Administration) and ESA (European Space Agency).

Changes in cellular structure of heat-treated Salmonella in low-moisture environments.

AIMS: Salmonella cells desiccated in an environment with low-water activity (aw ) show longer survival times and enhanced resistance to heat. However, little is known about the cellular ultrastructure of Salmonella in low-aw environment in relation to the survival and persistence during desiccation. MATERIALS AND RESULTS: In this study, Salmonella Enteritidis strain PT30 was dehydrated by exposure to air or by mixing with wheat flour (aw 0·30 at room temperature) for 7 days followed by heat treatment at 80°C for 10, 20, 60 min respectively. Transmission electron microscopy (TEM) was employed to examine and compare the ultrastructure of heat-treated S. Enteritidis cells after desiccation with the cells suspended in trypticase soy broth (TSB). Cells suspended in TSB broth showed disrupted ribosomes, congregated proteins and denatured DNA. However, no significant alterations were observed in the ultrastructure of the desiccated cells after heat treatment. The number of desiccated S. Enteritidis cells decreased by <1·5 log CFU per gram after 80°C treatment for 60 min, however, cells suspended in TSB declined more than 5 log10 CFU per mL at 80°C within 5 min. CONCLUSIONS: A drastic difference in the number of survivors and cellular ultrastructure was observed between vegetative and air or food-dried S. Enteritidis cells after subjecting to heat treatment at 80°C. No significant ultrastructure changes were observed in desiccated cells after heat treatment except for roughening and corrugating surfaces. SIGNIFICANCE AND IMPACT OF THE STUDY: This study provides a direct comparison to illustrate how desiccation influences the cell ultrastructure before/after heat treatment, which will aid in better understanding of the fundamental mechanism underlying the increased thermal resistance of Salmonella cells in low-aw environment.

Sexual Dimorphism of Greater Sciatic Notch among Nepalese Population by Three Dimensional CT Images of Pelvis.

Background Sex identification from the skeletal remains, is the first and the foremost step encountered by forensic experts. Hip bone being comparatively robust is resistant to damage and scores even in improperly preserved skeletons. It is also widely agreed that the greater sciatic notch (GSN) holds the greatest degree of sexual dimorphism. Objective To study the role of greater Sciatic Notch parameters in sex determination among Nepalese population by means of reconstructed Multi Slice Three-Dimensional Computed Tomography (MDCT) images. Method The CT images of individuals who underwent pelvic CT in the Department of Radiology, Dhulikhel Hospital were included in the study. Measurements of width, depth, angles and indices of greater sciatic notch were measured and calculated. Data were entered and analyzed using SPSS (Statistical Package for Social Sciences) version 25.0. Result There was a significant difference between means of all greater sciatic notch parameters (p > 0.001) between sex showing sexual dimorphism except depth (p=0.65). By using limiting point, 78.18% male and 83.64% female were correctly classified by using total width. Total angle, Posterior segment and Total width had sensitivity and specificity exceeding 80% and overall accuracy of 87% to 92% in all parameters except depth by receiver-operator characteristic curve analysis. Conclusion Application of 3D-CT virtual images in the present study helped us to easily quantify greater sciatic notch parameters. The important greater sciatic notch predictors for sex determination in Nepalese population were determined which would help forensic experts in ascertaining the sex of an unknown individual.

Should vitamin D be routinely checked for all chronic obstructive pulmonary disease patients?

AIMS AND OBJECTIVES: This study aimed to compare the vitamin D levels between chronic obstructive pulmonary disease (COPD) patients and healthy controls and to describe the correlation between vitamin D levels and lung functions. METHODS: Fifty COPD patients (cases) and 30 healthy volunteers (controls) were recruited and their serum vitamin D level was measured together with lung function (forced vital capacity and forced expiratory volume in 1 s [FEV1]) by spirometry. vitamin D was categorized as ≤20 nmol/l: deficient, 21-50 nmol/l: inadequate, and ≥51 nmol/l as sufficient. RESULTS: In this case-control cross-sectional study, lower vitamin D levels were associated with lower lung function in both cases as well as controls, the effect being more pronounced in cases. Mean FEV1 at vitamin D ≤20 nmol/l (0.98 ± 0.40 vs. controls 1.93 ± 0.24 with P = 0.006), mean FEV1 at vitamin D 21-50 nmol/l (1.55 ± 0.54 vs. 2.20 ± 0.31 with P = 0.000), and mean FEV1 at vitamin D ≥51 nmol/l (2.06 ± 0.54 vs. 2.20 ± 0.31 with P = 0.002). Moreover, the severity of predicted postbronchodilator FEV1% was also much lower among COPD cohort versus healthy volunteers (mean FEV1%: cases 47.88 ± 14.22 vs. controls 58.76 ± 15.05 with P = 0.002). CONCLUSIONS: Importantly, lung function in both the groups was affected by decreased vitamin D level; decrease in FEV1 was more pronounced among COPD patients compared to controls showing more expiratory airflow limitation. Vitamin D levels are associated with changes in lung function in cases of COPD as well as healthy controls. Larger studies to confirm the association in Indian context are required and routine assessment of vitamin D may be undertaken to obviate the effects of low vitmain D level on lung function.

Clinical, humanistic, and economic burden of osteoarthritis among noninstitutionalized adults in the United States.

OBJECTIVE: To estimate the burden of osteoarthritis (OA) among noninstitutionalized adults (≥18 years of age) in the US. DESIGN: Weighted nationally representative data from the 2015 Medical Expenditure Panel Survey were used to estimate OA prevalence in noninstitutionalized adults and compare adults with OA to those without OA for clinical (pain interference with activities [PIA], functional limitations), humanistic (health-related quality-of-life [HRQoL]) and economic outcomes (healthcare costs, wage loss). Productivity/wage loss was estimated among employed working-age adults (18-64 years). Multivariable regression analyses examined the associations between OA and outcomes. RESULTS: In 2015, 10.5% (25.6 million) of noninstitutionalized US adults reported having any OA. Regression analyses indicated that adults with OA were significantly more likely than those without OA to report moderate (adjusted odds ratios [AOR] 1.99; 95% confidence interval [CI] 1.65-2.40] or severe PIA (AOR 2.59; 95% CI 2.21-3.04), any functional limitation (AOR 2.51; 95% CI 2.21-2.85), and poorer HRQoL on the SF-12 version 2 Physical Component Summary score (adjusted beta [standard error] -3.88 [0.357]; P < 0.001). Adjusted incremental annual total healthcare costs and lost wages among adults with OA relative to those without OA were $1778 and $189 per person, respectively, resulting in estimated national excess costs of $45 billion and $1.7 billion, respectively. CONCLUSIONS: OA affects approximately 10% of noninstitutionalized adults in the US, resulting in substantial clinical, humanistic, and economic burdens.

Human articular cartilage mechanosensitivity is related to histological degeneration - a functional MRI study.

OBJECTIVE: To investigate changes in response to sequential pressure-controlled loading and unloading in human articular cartilage of variable histological degeneration using serial T1ρ mapping. METHOD: We obtained 42 cartilage samples of variable degeneration from the medial femoral condyles of 42 patients undergoing total knee replacement. Samples were placed in a standardized artificial knee joint within an MRI-compatible whole knee-joint compressive loading device and imaged before (δ0), during (δld1, δld2, δld3, δld4, δld5) and after (δrl1, δrl2, δrl3, δrl4, δrl5) pressure-controlled loading to 0.663 ± 0.021 kN (94% body weight) using serial T1ρ mapping (spin-lock multigradient echo sequence; 3.0T MRI system [Achieva, Philips]). Reference assessment included histology (Mankin scoring) and conventional biomechanics (Tangent stiffness). We dichotomized sample into intact (n = 21) and degenerative (n = 21) based on histology and analyzed data using Mann Whitney, Kruskal Wallis, one-way ANOVA tests and Spearman's correlation, respectively. RESULTS: At δ0, we found no significant differences between intact and degenerative samples, while the response-to-loading patterns were distinctly different. In intact samples, T1ρ increases were consistent and non-significant, while in degenerative samples, T1ρ increases were significantly higher (P = 0.004, δ0 vs δld1, δ0 vs δld3), yet undulating and variable. With unloading, T1ρ increases subsided, yet were persistently elevated beyond δ0. CONCLUSION: Cartilage mechanosensitivity is related to histological degeneration and assessable by serial T1ρ mapping. Unloaded, T1ρ characteristics are not significantly different in intact vs degenerative cartilage, while load bearing is organized in intact cartilage and disorganized in degenerative cartilage.