Search

Abstract The genetic loci implicated in familial Parkinson’s disease (PD) have limited generalizability to the Indian PD population. We tested mutations and the frequency of known mutations in the SNCA gene in a PD cohort from India. We selected 298 PD cases and 301 age-matched controls for targeted resequencing (before QC), along with 363 PD genomes of Indian ancestry and 1029 publicly available whole genomes from India as healthy controls (IndiGenomes), to determine the frequency of monogenic SNCA mutations. The raw sequence reads were analyzed using an in-house analysis pipeline, allowing the detection of small variants and structural variants using Manta. The in-depth analysis of the SNCA locus did not identify missense or structural variants, including previously identified SNCA mutations, in the Indian population. The familial forms of SNCA gene variants do not play a major role in the Indian PD population and this warrants further research in the under-represented population.

This article takes a scholarship of teaching and learning approach to improve the authors teaching about Indige-nous content as non-Indigenous teacher educators. It explores how they attempted to incorporate Indigenous content and teaching practices into multicultural education classes and then reflect on how they could have improved their teaching practice. Both authors provide their unique positionality which provides context which is essential to consider when doing equity-based work such as teaching about/with Indigenous communities. The authors discuss their teaching experiences after they occurred with one another and then engage in an exploration via literature on teaching about Indigenous content. The outcomes of two years of co-reflection and analysis of the literature are shared in this article in hopes to help guide both the authors and other non-Indigenous instructors on how to improve their teaching and learning about Indigenous content in courses. The findings stress the importance of (1) acknowledging land as a conduit for domination, (2) recognizing all who teach us, and (3) Indigenous guest lecturers and intergenerational learning.

Abstract Significant attention has been given to low‐carbon smart manufacturing (SM) as a strategy for promoting sustainability and carbon‐free emissions in the manufacturing industry. The implementation of intelligent algorithms and procedures enables the attainment and enhancement of low‐carbon clever manufacturing processes. These algorithms facilitate real‐time monitoring and predictive maintenance, ensuring efficient and sustainable operations and data‐driven decision‐making, increasing resource utilisation, waste reduction, and energy efficiency. The research examines the utilisation of algorithms in the context of low‐carbon smart manufacturing, encompassing machine learning, optimisation algorithms, and predictive analytics. A comprehensive literature evaluation spanning from 2011 to 2023 is conducted to assess the significance of low‐carbon approaches in the context of smart manufacturing. An integrated approach is used using content analysis, network data analysis, bibliometric analysis, and cluster analysis. Based on the published literature the leading contributors to low‐carbon manufacturing research are India, China, United States, United Kingdom, Singapore, and Italy. The results have shown five main themes—Low‐carbon smart manufacturing and applications of Algorithms; Industry 4.0 technologies for low‐carbon manufacturing; low carbon and green manufacturing; Low‐carbon Manufacturing, and Product design and control; Lean Systems and Smart Manufacturing. The purpose of this study is to provide policymakers and researchers with a guide for the academic development of low‐carbon manufacturing by evaluating research efforts in light of identified research deficits.

Detecting z-drugs, a sedative-hypnotic medication, is also misused for criminal activities. Therefore, the analysis of urine samples is crucial for clinical and forensic purposes. We conducted a study where we developed, validated, and compared an analytical method for simultaneously detecting z-drugs in urine samples. Our approach uses the QuEChERS method for sample preparation, combined with liquid chromatography (LC) and gas chromatography (GC) coupled with tandem mass spectrometry (MS/MS). We optimized the QuEChERS method to effectively extract z-drugs from urine samples while minimizing matrix effects and achieving high recovery rates. After extraction, we split the samples into two parts for analysis using LC-MS/MS and GC–MS/MS. We validated our methods, and the results showed good linearity over a broad concentration range (1–200 ng/mL) for each z-drug. The limits of detection and quantification were within clinically relevant ranges, ensuring sensitivity for detecting z-drugs in urine samples. We compared the two chromatographic techniques by analyzing a set of urine samples spiked with known concentrations of z-drugs using both LC-MS/MS and GC–MS/MS methods and then applied to the real samples. The results were statistically analyzed to assess any significant differences in accuracy and precision above 95 %, and both methods offered reliable and consistent results with the samples as well. In conclusion, our analytical method coupled with both LC-MS/MS and GC–MS/MS using the QuEChERS approach provides a comprehensive and robust solution for the simultaneous detection of z-drugs in urine samples. The choice between the two chromatographic techniques can be based on the specific z-drugs of interest and the required analytical performance. This method holds promise for applications in clinical toxicology, forensic analysis, and monitoring z-drug usage.

Recent studies have shown that extracellular vesicles (EVs) secreted by various parasites are capable of modulating the host’s innate immune responses, such as by altering macrophage (Mϕ) phenotypes and functions. Studies have shown that Mϕ promote early host responses to amoebic infection by releasing proinflammatory cytokines that are crucial to combating amoebiasis. Here, we are reporting for the first time the effect of EVs released by Entamoeba histolytica (EhEVs) on human THP-1 differentiated Mϕ (THP-1 Mϕ). We show that the EhEVs are internalized by THP-1 Mϕ which leads to differential regulation of various cytokines associated with both M1 and M2 Mϕ. We also saw that EhEV treatment thwarted Type 2 immune-response-related transcriptome pSTAT6 in the THP-1 Mϕ. Furthermore, EhEVs stimulated Mϕ to reduce their energy demand by suppressing oxidative phosphorylation (OXPHOS) and adenosine triphosphate (ATP) production. Hence, the human parasite E. histolytica–derived EVs are capable of eliciting an immune response from Mϕ that may contribute to overall infection status.

Posterior cortical atrophy (PCA) is a rare neurodegenerative disorder characterized by predominant visual deficits due to its atrophy of the occipital lobes. Patients typically have preserved cognitive function during the early stages, making diagnosis more difficult when compared to other neurocognitive disorders. In this case, the patient presented predominantly with mood symptoms, delusions, and visual hallucinations. The disease course began 5 years ago with anxiety and insomnia. It developed into depressive symptoms including two suicide attempts (SAs), paranoia, and hallucinations. The diagnosis was eventually reached utilizing a thorough clinical exam, neuropsychological testing, MRI, positron emission tomography (PET), and dopamine transporter (DAT) scans. We conclude that mood or psychotic symptoms that emerge, escalate, or change dramatically at later ages merit further workup to evaluate for underlying neurodegenerative disorders.

Electronic waste generation is increasing dramatically throughout the world. Consequently, this increase in E-waste harms the environment, health, and other aspects of human life. Moreover, hazardous substances and the informal disposal of E-waste severely threaten human health and the environment. Saudi Arabia is the largest Arab country in terms of electronic waste generation and is the Arab country that generates the most E-waste. Over the past few decades, several initiatives and policy implementations have been undertaken in the country. However, the management of E-waste is still a source of distress and an unresolved issue. Sustainable development requires much more effort, primarily efficient E-waste management, which can only be achieved by establishing a formal collection system, early forecasting, and accurate estimations. The purpose of this study is to provide an overview of the fundamental and emerging trends in E-waste production worldwide and in Saudi Arabia. This paper aims to summarize the hazardous elements present in E-waste, their dangerous effects, and the economic potential for recycling E-waste as a means of developing sustainable communities. This study explores the practices regarding efficient E-waste management and E-waste estimation and prediction globally, specifically in Saudi Arabia and other Arab countries. This study suggests that more than the use of a single management probe will be needed to achieve significant results. Instead, a complementary approach can be used to achieve the most effective results. Additionally, people should be aware of the importance of handling and recycling E-waste. This study emphasizes the importance of formal collection and documentation to ensure effective monitoring and sustainable development in any developed country.

Purpose – This study proposes a digital humanitarianism dynamic capability (DHDC) paradigm that explores the direct effects of DHDC on disaster risk reduction (DRR) and the mediating effects of process-oriented dynamic capabilities (PODC) on the relationship between DHDC and DRR. Design/methodology/approach – To validate the proposed model, the authors used an offline survey to gather data from 260 district magistrates in India managing the COVID-19 pandemic. Findings – The results affirm the importance of the DHDC system for DRR. The findings depict that the impact of PODC on DRR in the DHDC system is negligible. This study can help policymakers in planning during emergencies. Research limitations/implications – Technological innovation has reshaped the way humanitarian organizations (HOs) respond to humanitarian crises. These organizations are able to provide immediate aid to affected communities through digital humanitarianism (DH), which involves significant innovations to match the specific needs of people in real-time through online platforms. Despite the growing need for DH, there is still limited know-how regarding how to leverage such technological concepts into disaster management. Moreover, the impact of DH on DRR is rarely examined. Originality/value – The present study examines the impact of the dynamic capabilities of HOs on DRR by applying the resource-based view (RBV) and dynamic capability theory (DCT).

This review aims to evaluate the existing literature on Vaccine Supply Chain Management (VSCM). All relevant articles between 2002 and 2022 were systematically collected. The retrieved articles were further analyzed using bibliometric data analysis techniques. The unit of analysis is research papers published from 2002 to 2022. Vaccine Supply Chain Management (VSCM) literature has gained prominence since early 2000 and has now become voluminous. A review is the first endeavor to provide a unified body of literature. This study contributes to the existing research through insights from the bibliometric analysis and critical measurement of the literature. The results show 4288 papers on VSCM in the last 20 years. The top five countries contributing to VSCM literature are the USA, France, China, the United Kingdom, and Switzerland. Supply chain, vaccine, immunization, and Vaccine Supply Chain Management are the high-frequency keywords in the area of VSCM. The research hotspots mainly focus on healthcare, drugs, and manufacturers. In light of the COVID-19 era, this review paper indicates the area of VSCM is diversified. This study is useful for policymakers and other stakeholders to understand the existing issues in VSCM. The research trends and patterns from the literature review of VSCM will help in designing AAA (agile, adaptive, and aligned) VSCM in the future from the viewpoint of public health. This study attempts to analyze existing works, trends, developments, and potential research directions.

Release of α-synuclein aggregates by neurons instigates spread of pathology in synucleinopathies, but the mechanism remains unclear. Here the authors show that neuronally generated α-synuclein aggregates accumulate within neuronal lysosomes and are released via SNARE-dependent lysosomal exocytosis.

Psychological and mental well-being has become a topic of concern worldwide after the hit of the COVID-19 pandemic. It has triggered enormous global health care vulnerabilities and resulted in full and partial lockdowns to prevent the new case. This research study provides a comprehensive overview of the published international scientific studies on the effect of COVID-19 on the psychological well-being of young adults. This study aims to review the top-cited authors, documents, journals, productive countries, the most used keywords, and trending themes in this area. Articles related to psychological well-being during the COVID-19 pandemic from January 2020 to December 2022 were extracted from the Scopus database with specified keywords. In total, 482 documents were retrieved as original articles and bibliometric analysis, thematic analysis and content analysis are performed and analyzed. The results show that the United States has contributed the largest publications followed by the United Kingdom and Italy. Through the cluster analysis, it is found that many articles have been published and considered the psychological and mental impact of COVID-19. Young adults from both developed and developing countries are majorly affected by the COVID-19 pandemic. The pandemic prioritizes the importance of global psychological well-being and health care. This study focused on different aspects, such as stress, resilience, and the mental health of young adults. The research findings of this study put forth the urgent need to provide preventive policies and intervention procedures to address the psychological health of young adults and proposed a conceptual framework.

ABSTRACT tRNA-derived fragments have been reported in many different organisms and have diverse cellular roles, such as regulating gene expression, inhibiting protein translation, silencing transposable elements, and modulating cell proliferation. In particular, tRNA halves, a class of tRNA fragments produced by the cleavage of tRNAs in the anti-codon loop, have been widely reported to accumulate under stress and regulate translation in cells. Here, we report the presence of tRNA-derived fragments in Entamoeba, with tRNA halves being the most abundant. We further established that tRNA halves accumulate in the parasites upon different stress stimuli such as oxidative stress, heat shock, and serum starvation. We also observed differential expression of tRNA halves during developmental changes of trophozoite-to-cyst conversion, with various tRNA halves accumulating during early encystation. In contrast to other systems, the stress response does not appear to be mediated by a few specific tRNA halves, as multiple tRNAs appear to be processed during the various stresses. Furthermore, we identified some tRNA-derived fragments associated with Entamoeba Argonaute proteins, EhAgo2-2 and EhAgo2-3, which have a preference for different tRNA-derived fragment species. Finally, we show that tRNA halves are packaged inside extracellular vesicles secreted by amoebas. The ubiquitous presence of tRNA-derived fragments, their association with the Argonaute proteins, and the accumulation of tRNA halves during multiple different stresses, including encystation, suggest a nuanced level of gene expression regulation mediated by different tRNA-derived fragments in Entamoeba. IMPORTANCE In the present study, we report for the first time the presence of tRNA-derived fragments in Entamoeba. tRNA-derived fragments were identified by bioinformatics analyses of small-RNA sequencing data sets from the parasites and also confirmed experimentally. We found that tRNA halves accumulated in parasites exposed to environmental stress or during the developmental process of encystation. We also found that shorter tRNA-derived fragments are bound to Entamoeba Argonaute proteins, indicating that they may have a potential role in the Argonaute-mediated RNA-interference pathway, which mediates robust gene silencing in Entamoeba. We noticed that in response to heat shock, the protein translation levels were elevated in the parasites. This effect was reversed in the presence of an analog of leucine, which also reduced the levels of the tRNA halves in the stressed cells. Our results suggest that tRNA-derived fragments in Entamoeba have a possible role in regulating gene expression during environmental stress.

Extracellular vesicles (EVs) are lipid-membrane-bound structures produced naturally by all cells and have a variety of functions. EVs act as vehicles for transporting important molecular signals from one cell to another. Several parasites have been shown to secrete EVs, and their biological functions have been extensively studied. EVs have been shown to facilitate communication with the host cells (such as modulation of the host’s immune system or promoting attachment and invasion into the host cells) or for communication between parasitic cells (e.g., transferring drug-resistance genes or factors modulating stage conversion). It is clear that EVs play an important role in host–parasite interactions. In this review, we summarized the latest research on the EVs secreted by protozoan parasites and their role in host–parasite and parasite–parasite communications.

Abstract We fine mapped the leukocyte antigen (HLA) region in 13,770 Parkinson’s disease (PD) patients, 20,214 proxy-cases, and 490,861 controls of European origin. Four HLA types were associated with PD after correction for multiple comparisons, HLA-DQA1*03:01, HLA-DQB1*03:02, HLA-DRB1*04:01, and HLA-DRB1*04:04. Haplotype analyses followed by amino acid analysis and conditional analyses suggested that the association is protective and primarily driven by three specific amino acid polymorphisms present in most HLA-DRB1*04 subtypes—11V, 13H, and 33H (OR = 0.87, 95% CI: 0.83–0.90, p

Supply Chain processes are continuously marred by myriad factors including varying demands, changing routes, major disruptions, and compliance issues. Therefore, supply chains require monitoring and ongoing optimization. Data science uses real-time data to provide analytical insights, leading to automation and improved decision making. RFID is an ideal technology to source big data, particularly in supply chains, because RFID tags are consumed across supply chain process, which includes scanning raw materials, completing products, transporting goods, and storing products, with accuracy and speed. This study carries out a systematic literature review of research articles published during the timeline (2000-2021) that discuss the role of RFID technology in developing decision support systems that optimize supply chains in light of Industry 4.0. Furthermore, the study offers recommendations on operational efficiency of supply chains while reducing the costs of implementing the RFID technology. The core contribution of this paper is its analysis and evaluation of various RFID implementation methods in supply chains with the aim of saving time effectively and achieving cost efficiencies.

Tramadol (TD) has been prescribed frequently in many countries for more than 40 years, but there is a risk of its misuse and trafficking. As a result, drug analysis has numerous legal and socially relevant implications, making it an essential part of modern analytical chemistry. Thus, the method for the detection of TD and its phase I and phase II metabolites in human urine has been developed and validated using a rapid and efficient approach combining liquid chromatography-tandem mass spectrometry (LC-MS/MS) with electrospray ionization. The sample preparation was best performed using dispersive liquid–liquid microextraction. Analysis was performed using an HyPRITY Cl8 column, and isocratic elution with methanol: water (35:65) with 0.2% formic acid was used. TD and its metabolites were detected at 264.2 (TD/M0) with a base peak at 58.2, 250.3758 (M1), 250.3124 (M2), 236.3976 (M3), 222.5361 (M4), and 236.4475 (M5) m/z peaks. TD showed linearity between 0.1 and 160 ng/mL (R2 = 0.9981). The accuracy ranged from 95.56 to 100.21% for the three concentration levels, while the between- and within-day RSD ranged from 1.58 to 3.92%. The absolute TD recovery was 96.29, 96.91, and 94.31% for the concentrations of 5, 50, and 150 ng/mL, respectively. TD’s phase I metabolites, M1–5 along with nine phase II metabolites, such as sulfo- and glucurono-conjugated metabolites, oxidative TD derivatives, and sulfo-conjugated metabolites were also identified in the urine samples. The pharmacokinetics and metabolism data given provide information for the design of possible future research disorders, evaluating drug mechanism and neurotoxicity and for the effective application screening of TD.

The current study aims to improve clarithromycin bioavailability and effectiveness in complicated intra-abdominal infection management. Therefore, clarithromycin-loaded submicron dual lipid carriers (CLA-DLCs) were developed via hot high shear homogenization technique and evaluated for colloidal parameters, release behavior, stability study, and in-vitro antibiofilm activity. Bioavailability and therapeutic efficacy of optimized formulation on hampering cytokines storm induction was determined in E. coli-induced peritonitis. The developed CLA-DLCs (particle size 326.19 ± 24.14 nm, zeta potential −31.34 ± 2.81 mV, and entrapment efficiency 85.78 ± 4.01%) exhibited smooth spherical shapes and sustained in vitro release profiles. Long-term stability study of optimized CLA-DLCs ensured maintenance of colloidal parameters for 1 year at room temperature. In vitro antimicrobial studies revealed 3.43-fold higher anti-biofilm activity of CLA-DLCs compared with clarithromycin. In addition, the relative bioavailability of CLA-DLCs was enhanced 5.89-fold compared to pure drug in rats. The remarkable decrease in microbial burden in blood as well as tissues, along with oxidative stress markers (lipid peroxidation, myeloperoxidase activity, and carbonylated protein level) and immunological markers (total leukocyte count, neutrophil migration, NO, TNF-, and IL-6) on treatment with CLA-DLCs enhanced the survival in a rat model of peritonitis compared with the pure drug and untreated groups. In conclusion, CLA-DLCs hold promising potential in management of intra-abdominal infections and prevention of associated complications.

Glycyrrhiza glabra L. (belonging to the family Leguminosae), commonly known as Licorice, is a popular medicinal plant that has been used in traditional medicine worldwide for its ethnopharmacological efficacy in treating several ailments. Natural herbal substances with strong biological activity have recently received much attention. The main metabolite of glycyrrhizic acid is 18β-glycyrrhetinic acid (18βGA), a pentacyclic triterpene. A major active plant component derived from licorice root, 18βGA has sparked a lot of attention due to its pharmacological properties. The current review thoroughly examines the literature on 18βGA, a major active plant component obtained from Glycyrrhiza glabra L. The current work provides insight into the pharmacological activities of 18βGA and the potential mechanisms of action involved. The plant contains a variety of phytoconstituents such as 18βGA, which has a variety of biological effects including antiasthmatic, hepatoprotective, anticancer, nephroprotective, antidiabetic, antileishmanial, antiviral, antibacterial, antipsoriasis, antiosteoporosis, antiepileptic, antiarrhythmic, and anti-inflammatory, and is also useful in the management of pulmonary arterial hypertension, antipsychotic-induced hyperprolactinemia, and cerebral ischemia. This review examines research on the pharmacological characteristics of 18βGA throughout recent decades to demonstrate its therapeutic potential and any gaps that may exist, presenting possibilities for future drug research and development.

In this study, a two-stage mathematical model has been developed that facilitates tactical planning of supply of apples from the various location of farmers to the marketplaces and then to the cold storage facilities. The model enables efficient network planning by finding the most suitable and cost-effective dispatching method operating in multiple stages using a mixed fleet of jeeps and trucks. The model aims to optimize the cost and demand. The paper used a multi-stage model to examine the most effective and efficient route for the supply. Kullu, Himachal Pradesh has been taken as the case location, which is famous as key apple production location in India. The lack of infrastructure in the area poses challenges for the farmers to select a mix of both trucks and jeeps to make their goods available in the market. The present paper attempts to address these issues, facilitating an effective transportation planning of apple produce.

Aims: To determine the applicability of Moyer's probability tables in North Indian population of 16–18 year olds and to formulate a new regression equation for the same group of population. Setting and Design: Evaluative Study. Methods and Material: 1000 children aged 16–18 years were selected as sample for the measurement of mesiodistal widths of permanent mandibular incisors, maxillary and mandibular canines and premolars using study models. The recorded values were then subjected to statistical analysis. Statistical Analysis Used: Software Package for Social Sciences (SPSS) software version 22.0. Results: The actual widths of the canine and premolars showed highly significant differences in maxilla and in mandible (P < 0.001), compared to widths predicted by Moyer's probability table at 75th percentile. Conclusion: Moyer's mixed dentition analysis was not an accurate method for prediction in North Indian population as it showed overestimation of tooth sizes. Hence, new regression equation has been formulated for the same.

Abstract Heterozygous de novo mutations in the neuronal protein Munc18‐1 cause syndromic neurological symptoms, including severe epilepsy, intellectual disability, developmental delay, ataxia, and tremor. No disease‐modifying therapy exists to treat these disorders, and while chemical chaperones have been shown to alleviate neuronal dysfunction caused by missense mutations in Munc18‐1, their required high concentrations and potential toxicity necessitate a Munc18‐1‐targeted therapy. Munc18‐1 is essential for neurotransmitter release, and mutations in Munc18‐1 have been shown to cause neuronal dysfunction via aggregation and co‐aggregation of the wild‐type protein, reducing functional Munc18‐1 levels well below hemizygous levels. Here, we identify two pharmacological chaperones via structure‐based drug design, that bind to wild‐type and mutant Munc18‐1, and revert Munc18‐1 aggregation and neuronal dysfunction in vitro and in vivo, providing the first targeted treatment strategy for these severe pediatric encephalopathies.

The purpose of this research is to identify the key Circular Economy dimensions (CE-D) in Agri-tourism industry and to determine the performance of these dimensions using AHP-TOPSIS method. The research is carried out in two stages, firstly 11 CE-D were identified using systematic literature review. In stage two, industrial experts validate and finalize 9 CE-D which can decide the overall performance of Agri-Tourism Networks. The AHP analysis shows that Destination Attractiveness is valued highest for making CE decisions, whereas, community contributions and sustainable livelihoods valued second and third as important dimensions. Moreover, TOPSIS shows that Pithoragarh is emerged as the best cluster among all Agri-tourism clusters selected for the study, whereas, Almora stood in second position. The Agri-food clusters are becoming more complex and flexible and started putting pressure on existing supply chains to re-design the existing value chain and incorporate more sustainable practices and performances. The identification of Circular Economy Dimensions (CE-D) to evaluate the performance of clusters can serve as guiding tool for the Agri-tourism Practioners and policy makers. Besides, the study examines relevant issues related to CE in Agri-tourism clusters, major advantages and challenges of building CE driven Agri-tourism clusters. The limitation of the study is the geographical coverage and limited demography of the respondents. The research study is among very few works on evaluating Agri-tourism supply chain practices in India, with the case reference of Uttarakhand.

Our aim was to determine whether the genetic liability to sleep and pain-related traits have a causal effect on risk of neurodegeneration in individuals of predominantly European ancestry. We selected five neurodegenerative disorders, namely, age-related macular degeneration (AMD), Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), and Parkinson's disease (PD). Sleep duration (SD), short sleep (SS), long sleep (LS), chronotype (CHR), morning person (MP), insomnia (INS), and multisite chronic pain (MCP) were considered as exposures. We conducted Mendelian randomization (MR) using an inverse-variance weighted (IVW) method to compute causal effect estimates using latest available GWAS data sets. The MP phenotype was observed as the strongest risk factor for genetic liability to AMD (ORIVW = 1.192; 95% CI 1.078, 1.318, P = 0.0007). We observed suggestive evidence of risky effects of CHR on AMD (P = 0.0034), SS on AD (P = 0.0044), and INS on ALS (P = 0.0123). However, we failed to observe any role of pain. The results were robust on sensitivity analyses. Our study highlighted the role of MP as a risk factor for AMD.

Introduction Heart failure is a major contributor to morbidity and mortality in the geriatric population, with no promising therapy currently available with considerable benefit. Testosterone therapy is an emerging viable treatment option given its beneficial effects, including improving cardiac functional capacity, alleviating symptoms and low cost, among others.Methods We have planned an open-label, parallel design, 1:1 randomised controlled trial, which aims to recruit 986 adult males above the age of 60 diagnosed with chronic stable heart failure fulfilling the eligibility criteria. The participants will be randomised into 2 groups of 493 each. Both groups will receive standard recommended treatment regimen of chronic stable heart failure and intervention arm participants will receive additional testosterone gel. All participants will be assessed at baseline, 4 weeks, 6 weeks and 12 weeks. The primary endpoints will assess the differences in functional capacity, frailty and quality of life at 3 months compared with baseline. The secondary endpoints will include the mean change from baseline at 3 months in cardiac remodelling using echocardiography, serum brain natriuretic peptide levels, the incidence of adverse drug reaction.Statistical analysis The data will be analysed with the help of SPSS 23 software. Primary objectives of change in 6-minute walk test, frailty index and quality of life will be analysed using the student’s t-test. The statistical significance will be defined as p value

Background: The relationship between the level of motivation and personality disorder (PD) in patients with opioid dependence syndrome is understudied. Method: A cross-sectional study was conducted on consecutively selected 100 adult inpatients with opioid dependence syndrome. All participants were assessed on ICD-10-AM Symptom Checklist for Mental Disorders, University of Rhode Island Change Assessment (URICA), Stage of Change Readiness and Treatment Eagerness Scale (SOCRATES 8D), International Personality Disorder Examination (IPDE), and Severity of Opioid Dependence Questionnaire (SODQ). Results: Most patients expressed the level of motivation at contemplation level, medium level of recognition for the need for change, and high levels of ambivalence and taking steps for change. PD was diagnosed in 40% of the patients. The most common PD identified was dissocial, followed by an emotionally unstable personality disorder-impulsive type. There was no statistically significant difference in URICA, SOCRATES 8D, or SODQ scores in opioid-dependent patients with and without PDs. Patients with severe opioid dependence reported higher readiness to change. Conclusion: Most of the patients with opioid dependence syndrome presenting for treatment are at the contemplation level of motivation. More than one-third of patients with opioid dependence syndrome have PD. A diagnosis of comorbid PD is unrelated to the level of motivation in patients with opioid dependence syndrome. Further multicentric research on personality and PD in a diverse sociocultural population with opioid use disorders is needed.

Asthma is a polygenic chronic inflammatory respiratory disease devastating the quality of life and state economies. Therefore, utilization of natural products as a therapeutic approach has attained wider consideration for development of novel drugs for asthma management. Bromelain, a mixture of natural bioactive cysteine proteases abundantly found in pineapple stem, has allured attention for its pharmacological activities. However, poor stability in gastric milieu, high dose and immunogenicity associated with prolonged use hinders its oral use. Therefore, need exists to explore alternative route of bromelain administration to achieve its plausible benefits. The present study investigated the preclinical prospects of nasal administration of bromelain on systemic bioavailability, tissue distribution and it's in vivo anti-histaminic, bronchodilator and anti-asthmatic activity in animal models. Pharmacokinetic studies revealed 1.43-fold higher relative bioavailability with faster absorption of bromelain on nasal administration at one-fourth oral dose. The enhanced cellular uptake and localization of bromelain in tissues of lung was observed significantly. Furthermore, faster onset and enhanced antihistaminic, bronchodilator and anti-asthmatic activity on bromelain's nasal administration signified faster absorption and higher in vivo stability of bromelain. Nasal administration significantly achieved decrease in level of oxidative and immunological markers along with restoration of antioxidant enzymes at considerably one-fourth dose administered orally. These findings distinctly manifested that nasal administration could be a substantial and effective route for bromelain delivery with enduring competency in asthma management.

This study was focussed on development of curcumin loaded solid binary lipid nanoparticles (C-SBLNs) to ameliorate stability, uptake and therapeutic potential of curcumin during inflammatory bowel disease (IBD). C-SBLNs with nano-size range (210.56 ± 41.22 nm) and high entrapment efficiency (83.12 ± 6.57%) were prepared by solvent emulsification evaporation method using binary lipids i.e. stearic acid and tristearin after optimizing various formulation and process variables. Physicochemical characterization of C-SBLNs by ATR-FTIR confirmed drug entrapment whereas thermal and pXRD study corroborated loss of crystallinity of drug into C-SBLNs. Lyophilized C-SBLNs were found to be spherical shaped with good gastrointestinal stability and prolonged drug release up to 24 h. Optimized C-SBLNs formulation displayed significantly enhanced cellular uptake and localization in inflamed tissues during IBD. Oral administration of C-SBLNs in DSS induced colitis model revealed significant reduction in leucocyte infiltration, oxidative stress, pro-inflammatory cytokine (TNF-α) secretion and maintenance of colonic structure similar to healthy animal group compared to curcumin. Thus, in vitro and preclinical findings of study clearly confirmed that C-SBLNs could be a stable and efficacious alternative platform for curcumin delivery with strong competence in IBD chemotherapy.

The 4-allyl guaiacol is a natural phenolic molecule that has been widely studied for its antioxidant capacity against reactive-oxygen-species-mediated cellular damage. Therefore, we hypothesized that concomitant use of an antioxidant and NSAID may decrease the risk of gastrointestinal toxicity and make the therapy safer. To address the gastrointestinal toxicity of conventional NSAIDs, a new S-naproxen-4-allyl guaiacol chimera (MAS-1696) was computationally developed, chemically synthesized, and tested for anti-inflammatory effectiveness and gastrointestinal safety. The inhibitory potency of MAS-1696 tested against cyclooxygenase-2 (COX2), 15-lipoxygenase-2 (15-LOX2), and lipoxygenase-5 (5-LOX) in vitro revealed a stronger inhibition of COX2. Furthermore, the MAS-1696 chimera increased the COX selectivity index by 23% as compared to the parent compound naproxen, implying higher efficacy and gastric safety. In vivo data showed that MAS-1696 was less likely to cause gastrointestinal harm than naproxen while also exerting anti-inflammatory and analgesic effects equivalent to or superior to naproxen. In conclusion, MAS-1696 is orally active, bio-labile, and crystalline, making it a medication that may be administered orally.

Purpose: To assess knowledge, awareness and attitude of high school children involved in various sports activities regarding avulsion, reimplantation and mouthguard use. Materials and Methods: An interview-based study was conducted among high school children in the age group of 8–16 years (n = 1105). A questionnaire was given to children and parents which included questions based on knowledge of children regarding avulsion, reimplantation, consequences of losing teeth, mouthgards and their usage and preferred media for tooth transportation. The research proposal was submitted to the ethics committee and the study design was approved. Data analysis included descriptive statistics and Statistical Package for the Social Sciences (SPSS) software. Results: Only 37.6% of the children knew that their teeth can be completely knocked out with injury and 20.1% knew that a knocked-out tooth can be replanted. The preferred media for tooth transportation were gauze/cotton (27.2%), handkerchief (17.5%), paper (14%), water (13.8%) and cellophane (1.3%), i.e. 81.3% of the children preferred dry transport media. Among the children playing contact sport, 53.8% did not know about mouthguards and the rest 46.2% knew about it, but most of them never used it. Conclusion: Considering the lack of awareness among children, as well as the people around them, there appears to be a crucial need for education of public and to determine dental manpower and dentists to increase awareness.

Background: Nomophobia is a portmanteau for “no mobile phone” and phobia or mobile phone addiction. Nomophobia refers to discomfort, anxiety, nervousness, or anguish caused by being out of contact with a mobile phone. There is a paucity of literature from India on this emerging mental health condition. Objectives: The objectives of this study were to assess the prevalence of nomophobia and its relationship with depression, anxiety, and quality of life among adolescent students. Materials and Methods: A cross-sectional study was carried out in 1386 high school students aged between 14 and 17 years. The Nomophobia Questionnaire (NMP-Q) was used to assess nomophobia. Beck's Depression Inventory (BDI), Beck's Anxiety Inventory (BAI), and Short Form-36 (SF-36) were used to measure depression, anxiety, and quality of life, respectively. Results: Out of 1386 adolescents, 569 (41.05%), 303 (21.86%), and 82 (5.1%) have mild, moderate, and severe nomophobia, respectively. There were significantly more males with nomophobia. There was a statistically significant relationship between NMP-Q score and BDI, BAI, and SF-36 scores. A significant positive correlation was observed between NMP-Q score and scores on BDI and BAI and a significant negative correlation between SF-36 score. Conclusion: The results of the study indicate that nomophobia is an emerging mental health condition, especially in male adolescents. Nomophobia is significantly associated with depression, anxiety, and poor quality of life. Multicentric studies are needed to better understand this disorder.

Background: To better understand the psychiatric disorders and cognition in Parkinson's disease (PD) and its impact on quality of life (QoL), patients need to be studied soon after diagnosis, before initiation of dopamine replacement therapy. Aim: This study aims to compare the nature and frequency of psychiatric morbidity, cognitive dysfunction, and quality of life in drug-naive patients with PD and healthy controls. Materials and Methods: The cross-sectional, comparative study was conducted in tertiary care center. Fifty drug-naive PD patients and fifty healthy controls were included and assessed on Modified Hoehn and Yahr scale, PD Questionnaire 8, Kolkata cognitive screening battery, General Health Questionnaire-12, and Hamilton Anxiety and Depression Rating Scale (HAM-A and HAM-D). Results: The mean scores of HAM-A and HAM-D of patients with PD were significantly higher than that of the comparison group. The patients with PD had statistically significant impairment in verbal fluency, Mini-Mental State Examination, calculation, memory immediate recall, visuoconstructional ability, and memory (delayed recall and recognition) in comparison to patients without PD. No statistically significant difference was observed with respect to object naming between the two groups. Conclusion: QoL of a PD patient is adversely affected by both the motor and nonmotor symptoms of the disease such as depression, anxiety, apathy, sleep disturbances, and cognitive impairment. The link between nonmotor symptoms and reduced QoL has important implications for the management of PD because the nonmotor symptoms often appear before patients are given anti-parkinsonian therapy. Screening of nonmotor symptoms in early stage of disease will decrease the morbidity and mortality and improve the QoL.

Over the past two decades, our understanding of Parkinson's disease (PD) has been gleaned from the discoveries made in familial and/or sporadic forms of PD in the Caucasian population. The transferability and the clinical utility of genetic discoveries to other ethnically diverse populations are unknown. The Indian population has been under-represented in PD research. The Genetic Architecture of PD in India (GAP-India) project aims to develop one of the largest clinical/genomic bio-bank for PD in India. Specifically, GAP-India project aims to: (1) develop a pan-Indian deeply phenotyped clinical repository of Indian PD patients; (2) perform whole-genome sequencing in 500 PD samples to catalog Indian genetic variability and to develop an Indian PD map for the scientific community; (3) perform a genome-wide association study to identify novel loci for PD and (4) develop a user-friendly web-portal to disseminate results for the scientific community. Our “hub-spoke” model follows an integrative approach to develop a pan-Indian outreach to develop a comprehensive cohort for PD research in India. The alignment of standard operating procedures for recruiting patients and collecting biospecimens with international standards ensures harmonization of data/bio-specimen collection at the beginning and also ensures stringent quality control parameters for sample processing. Data sharing and protection policies follow the guidelines established by local and national authorities.We are currently in the recruitment phase targeting recruitment of 10,200 PD patients and 10,200 healthy volunteers by the end of 2020. GAP-India project after its completion will fill a critical gap that exists in PD research and will contribute a comprehensive genetic catalog of the Indian PD population to identify novel targets for PD.

ABSTRACT Ocular Surface Squamous Neoplasia (OSSN) is a neoplasm of ocular surface present in the interpalpebral area having feeder vessel. It is more common in middle age group and present as a mass lesion or chronic ocular irritation. Treatment is chemo reduction, surgical excision, cryotherapy and excision with adjuvant chemotherapy. There is high rate of recurrence in OSSN. Here, a case of 79-year-old female patient with painless mass over conjunctiva and cornea was presented. The mass was whitish, shiny and placoid extending from 9 o’clock to 5 o’clock position covering half of the corneal surface with feeder vessel. Gelatinous or leucoplakic OSSN was managed with chemoreduction and monotherapy with mitomycin C. No recurrence was reported during more than 2 years follow-up at the peripheral health institution.

Chronic neuropathic pain (NP) is a growing clinical problem for which effective treatments, aside from non-steroidal anti-inflammatory drugs and opioids, are lacking. Cannabinoids are emerging as potentially promising agents to manage neuroimmune effects associated with nociception. In particular, Δ9-tetrahydrocannabinol (THC), cannabidiol (CBD), and their combination are being considered as therapeutic alternatives for treatment of NP. This study aimed to examine whether sex affects long-term outcomes on persistent mechanical hypersensitivity 7 weeks after ceasing cannabinoid administration. Clinically relevant low doses of THC, CBD, and a 1:1 combination of THC:CBD extracts, in medium chain triglyceride (MCT) oil, were orally gavaged for 14 consecutive days to age-matched groups of male and female sexually mature Sprague Dawley rats. Treatments commenced one day after surgically inducing a pro-nociceptive state using a peripheral sciatic nerve cuff. The analgesic efficacy of each phytocannabinoid was assessed relative to MCT oil using hind paw mechanical behavioural testing once a week for 9 weeks. In vivo intracellular electrophysiology was recorded at endpoint to characterize soma threshold changes in primary afferent sensory neurons within dorsal root ganglia (DRG) innervated by the affected sciatic nerve. The thymus, spleen, and DRG were collected post-sacrifice and analyzed for long-term effects on markers associated with T lymphocytes at the RNA level using qPCR. Administration of cannabinoids, particularly the 1:1 combination of THC, elicited a sustained mechanical anti-hypersensitive effect in males with persistent peripheral NP, which corresponded to beneficial changes in myelinated Aβ mechanoreceptive fibers. Specific immune cell markers associated with T cell differentiation and pro-inflammatory cytokines, previously implicated in repair processes, were differentially up-regulated by cannabinoids in males treated with cannabinoids, but not in females, warranting further investigation into sexual dimorphisms that may underlie treatment outcomes.

Introduction: Psoriasis and vitiligo are among the most common chronic skin diseases, which have a negative impact on the psychosocial well-being. Patients may experience social rejection and stigmatization. So, the aim of this present study is to assess and compare the self-esteem and quality of life (QoL) in patients with vitiligo, psoriasis and healthy controls and its relationship with age and gender. Materials and Methods: A cross-sectional and comparative study was conducted at a tertiary care hospital, Udaipur, Rajasthan, with a sample of total 150 cases, 50 each of psoriasis, vitiligo and healthy controls, aged between 18-64years. The assessment of all subjects was done for quality of life and self-esteem by using scales Short Form-36 (SF-36) and Rosenberg Self-Esteem Scale (RSES) respectively. Results: The results of our study showed that the self-esteem& quality of life was low in psoriatic patients when compared to vitiligo patients (p-0.000) and healthy controls (p-0.009). No relationship was found in patients of psoriasis and vitiligo between age and gender with regards to self-esteem and quality of life except poor social function domain of QoL, which was observed in middle age group (40-64years) patients of psoriasis. Conclusion: While evaluating and arranging treatment of psoriasis and vitiligo patients, these results in poor psychosocial functioning should be considered and along with dermatologic interventions, psychiatric approaches should also be included for a better outcome.

Background and Aims: Emergency front of neck access (FONA) is the final step in a Can't Intubate–Can't Oxygenate (CICO) scenario. In view of maintaining simplicity and promoting standardized training, the 2015 Difficult Airway Society guidelines recommend surgical cricothyroidotomy using scalpel, bougie, and tube (SBT) as the preferred technique. Material and Methods: We undertook a survey over a 2-week period to evaluate the knowledge and training, preferred rescue technique, and confidence in performing the SBT technique. Data were collected from both anesthetists and surgeons. Results: One hundred and eighty-nine responses were collected across four hospitals in the United Kingdom. The majority of participants were anesthetists (55%). One hundred and eleven (59%) respondents were aware of the national guidelines (96.2% among anesthetists and 12.9% among surgeons). Only 71 (37.6%) respondents indicated that they had formal FONA training within the last one year. Seventy-five anesthetists (72.8%) knew that SBT equipment was readily available in their department, while most surgeons (81.2%) did not know what equipment available. One hundred and five (55.5%) respondents were confident in performing surgical cricothyroidotomy in a situation where the membrane was palpable and only in 33 (17.5%) where the cricothyroid membrane was not palpable. Conclusion: This survey has demonstrated that despite evidence of good training for anesthetists in FONA, there are still shortfalls in the training and knowledge of our surgical colleagues. In an emergency, surgeons may be required to assist or secure an airway in a CICO situation. Regular multidisciplinary training of all clinicians working with anesthetized patients should be encouraged and supported.

Long-distance intracellular transport of organelles, mRNA, and proteins (“cargo”) occurs along the microtubule cytoskeleton by the action of kinesin and dynein motor proteins, but the vast network of factors involved in regulating intracellular cargo transport are still unknown. We capitalize on the Drosophila melanogaster S2 model cell system to monitor lysosome transport along microtubule bundles, which require enzymatically active kinesin-1 motor protein for their formation. We use an automated tracking program and a naive Bayesian classifier for the multivariate motility data to analyze 15,683 gene phenotypes and find 98 proteins involved in regulating lysosome motility along microtubules and 48 involved in the formation of microtubule filled processes in S2 cells. We identify innate immunity genes, ion channels, and signaling proteins having a role in lysosome motility regulation and find an unexpected relationship between the dynein motor, Rab7a, and lysosome motility regulation.

The aim of this qualitative case study is to examine the phenomenon of female students' disproportionate representation in senior level Physical Health Education (PHE) classes. The subject for this teacher's Masters level project arose from the first author's personal observations while teaching across several schools in British Columbia, Canada. Through semi-structured interviews with self-identified female participants, we explore female subject choice and if, along with possible reasons why, females may avoid participation in senior level (grade 11-12) mixed gender PHE activity courses. This discussion asserts that females mostly make conscious choices to avoid mixed gender courses at the senior level for several key reasons; females feel silenced by their male peers, PHE is not an inclusive environment, and females perceive their male counterparts assert dominance over them in PHE class. This paper continues with a discussion regarding reinforced gendered norms and their effect on perceived barriers to female participation in schools, and concludes with suggestions for how schools and educators might support female students' participation.

Introduction/Aim: Alterations in extracellular glutamate levels have been previously found to contribute to cancer-induced bone pain (CIBP). Increased activity of system xc-, a cystine-glutamate membrane antiporter, has been previously implicated in our lab in these nociceptive behaviours. System xc- subunit xCT, is further positively regulated by signal transducer and activator of transcription 3 (STAT3). In the current investigation, we hypothesized that DR-1–55-mediated inhibition of pSTAT3 will lead to decreased nociceptive behaviours in a validated xCT overexpression model of CIBP. Methods: Using a murine xenograft CIBP model, a high glutamate-releasing xCT/pSTAT3 overexpressing human breast cancer cell line (T47D clone) was injected into the distal epiphysis of the femur of female nude mice. Nociceptive behaviours were monitored through automated von Frey, dynamic weight bearing, and open field testing for the study duration. Three weeks after cell inoculation, a 14-day schedule of intraperitoneal injections of DR-1–55 or vehicle were administered. Results: In vitro, there were elevated levels of glutamate, IL-6, and IL- 1β exhibited in the T47D clone. These cells also showed significant nociceptive behaviours earlier than the T47D wild type (WT). Treatment with DR-1–55 significantly delayed the onset and severity of spontaneous and induced nociceptive behaviours, as seen with behavioural testing. Discussion/Conclusions: This study shows that targeting pSTAT3 may be a viable treatment when managing CIBP, and can be a molecule of interest in future studies.

Huntington′s Disease (HD) is an autosomal dominant progressive degenerative disorder of the basal ganglia characterized by motor, cognitive, and psychiatric manifestations, with an estimated prevalence of 1.75 per 100,000. It can present any time between infancy and senescence. Mood disorders, obsessive compulsive symptoms, psychosis, delirium, sexual disorders, and ′frontal′ syndromes, have been reported in patients with HD. Delusions are seen in only about 5-12%. Indian data on HD has been largely through case reports. Given this background, we present an uncommon case with clinical features suggestive of HD and organic delusional disorder. This case report presents the psychiatric and neurological features of a 39-year-old male, who presented with abnormal choreiform movements since eight years, followed by a delusion of infidelity, and a family history suggestive of HD. Differential diagnosis and laboratory results, including neuroimaging and treatment, are presented. Delusions are the common manifestation of psychosis in patients with brain disorders, occurring more often than a formal thought disorder. Lesions of the temporal lobes or caudate nuclei and bilateral brain involvement are common in disorders manifesting psychosis. However, reasons for the infrequent occurrence of delusions in HD, in comparison to other neurodegenerative disorders, are unknown.

In this paper, fuzzy logic is meshed with sliding mode control, in order to control vibrations of a cantilevered plate. Test plate is instrumented with a piezoelectric sensor patch and a piezoelectric actuator patch. Finite element method is used to obtain mathematical model of the test plate. A design approach of a sliding mode controller for linear systems with mismatched time-varying uncertainties is used in this paper. It is found that chattering around the sliding surface in the sliding mode control can be checked by the proposed fuzzy sliding mode control approach. With presented fuzzy sliding mode approach the actuator voltage time response has a smooth decay. This is important because an abrupt decay can excite higher modes in the structure. Fuzzy rule base consisting of nine rules, is generated from the sliding mode inequality. Experimental implementation of the control approach verify the theoretical findings. For experimental implementation, size of the problem is reduced using modal truncation technique. Modal displacements as well as velocities of first two modes are observed using real-time kalman observer. Real time implementation of fuzzy logic based control has always been a challenge because a given set of rules has to be executed in every sampling interval. Results in this paper establish feasibility of experimental implementation of presented fuzzy logic based controller for active vibration control.

What is social justice-informed co-teaching? Why is it important? How can it enrich social justice pedagogy? While the answers to these questions may vary depending on context and perspective, they are nevertheless useful to address. Each of these questions will be discussed in this research paper. This auto-ethnographic narrative inquiry adds to the literature on social justice-informed co-teaching in an innovative way. It critically examines the purposeful endeavor of two professors who used social justice thinking to guide their co-teaching practice, and simultaneously used co-teaching to enrich their social justice pedagogy. At once, this paper is a lived experience, a story, and a research study. In deconstructing two narratives, the authors articulate specific ways in which co-teaching, as a practice, presents unique opportunities for social justice learning. Implications for research and practice in teacher education programs, teaching practices and field- experiences, and co-teachers themselves are shared in the closing segment of the paper.

An article by Sasidharan et al. recently published in the journal Molecules [1] claimed to show the hepatoprotective effects of lantadene A against acetaminophen-induced liver damage in mice. While reading this paper, I came across certain points that need to be clarified and taken up in the interest of science and other scientists working in this area.

Pleomorphic adenoma originally called the mixed tumour is a neoplasm commonly involving major salivary glands. The spectrum of malignancy in pleomorphic adenoma comprises three distinct entities – Carcinoma ex-pleomorphic adenoma, carcinosarcoma and benign metastasising pleomorphic adenoma. Carcinoma ex-pleomorphic adenoma consists of pleomorphic adenoma with a malignant epithelial component. Occasionally, carcinomas ex-pleomorphic adenoma develops metastasis. Here we are reporting a case of benign pleomorphic adenoma arising in parotid gland which turned into malignancy after four years. The patient developed facial nerve paralysis suggesting malignant transformation. Along the course of the disease, the patient developed regional metastasis to lymph nodes and neck and distant metastasis to liver. This case report emphasises the role of advanced imaging modalities in the early diagnosis of the condition and evaluation of metastasis. The patients with this condition should be treated early for favorable outcome and investigated for distant metastasis.