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The mitochondrial anchor syntaphilin (SNPH) is a key mitochondrial protein normally expressed in axons to maintain neuronal health by positioning mitochondria along axons for metabolic needs. However, in 2019 we discovered a novel form of excitotoxicity that results when SNPH is misplaced into neuronal dendrites in disease models. A key unanswered question about this SNPH excitotoxicity is the pathologic molecules that trigger misplacement or intrusion of SNPH into dendrites. Here, we identified two different classes of pathologic molecules that interact to trigger dendritic SNPH intrusion. Using primary hippocampal neuronal cultures from mice of either sex, we demonstrated that the pro-inflammatory cytokine IL-1β interacts with NMDA to trigger SNPH intrusion into dendrites. First, IL-1β and NMDA each individually triggers dendritic SNPH intrusion. Second, IL-1β and NMDA do not act independently but interact. Thus, blocking NMDAR by the antagonist MK-801 blocks IL-1β from triggering dendritic SNPH intrusion. Further, decoupling the known interaction between IL-1β and NMDAR by tyrosine inhibitors prevents either IL-1β or NMDA from triggering dendritic SNPH intrusion. Third, neuronal toxicity caused by IL-1β or NMDA is strongly ameliorated in SNPH(−/−) neurons. Together, we hypothesize that the known bipartite IL-1β/NMDAR crosstalk converges to trigger misplacement of SNPH in dendrites as a final common pathway to cause neurodegeneration. Targeting dendritic SNPH in this novel tripartite IL-1β/NMDAR/SNPH interaction could be a strategic downstream locus for ameliorating neurotoxicity in inflammatory diseases. SIGNIFICANCE STATEMENT SNPH is a key mitochondrial protein normally expressed specifically in healthy axons to help position mitochondria along axons to match metabolic needs. In 2019 we discovered that misplacement of SNPH into neuronal dendrites causes a novel form of excitotoxicity in rodent models of multiple sclerosis. A key unanswered question about this new form of dendritic SNPH toxicity concerns pathologic molecules that trigger toxic misplacement of SNPH into dendrites. Here, we identified two major categories of pathologic molecules, the pro-inflammatory cytokines and NMDA, that interact and converge to trigger toxic misplacement of SNPH into dendrites. We propose that a dendritic mitochondrial anchor provides a novel, single common target for ameliorating diverse inflammatory and excitatory injuries in neurodegenerative diseases.

This is a controlled randomized trial which evaluated the clinical and molecular changes resulting from Integrated approach of yoga therapy (IAYT) as an adjunct regimen and compared it with usual care for the management of chronic low back pain patients.­­ We enrolled 29 adult patients with chronic low back pain (CLBP). Patients were randomly divided into two groups. Control group received the usual care of treatment as per institutional protocol. The yoga group received IAYT as an adjunct to usual care. Primary outcomes were pain Intensity assessed by verbal numerical rating scale (VNRS) and functional ability assessed by Modified Oswestry Disability Index (MODI). Secondary outcomes were pain catastrophizing, quality of life, fear of movement related to CLBP, type of pain, levels of ß-Endorphin and TNF α and Salivary CGRP. All parameters were measured at baseline, one month, and three months. Significant decrease in VNRS score at 1 and 3 months was observed in both the groups with yoga group showing a more significant reduction in pain over time than the control group (p=0.036). MODI improved significantly only in the yoga group at 1 and 3 months. Intergroup comparison revealed significantly better MODI over time in the yoga group (p< 0.001). DN4, PDQ, PCS, HADS (anxiety) and Euro QOL had a statistically significant improvement at 1 month and 3 months in the Yoga group compared to the Control group. The HADS (depression) had a statistically significant reduction scores in yoga group at 3 months compared to control group (p=0.012). There was a significant reduction in TNF- α values in the yoga group compared to baseline(p=0.004). IAYT therapy helped in addressing the psychological components of pain and improved quality of life patients with chronic low back pain compared to usual care.

To determine the obstetrical outcomes of women delivered for the diagnosis of intrahepatic cholestasis of pregnancy (ICP).Retrospective study of singleton pregnancies diagnosed with ICP between 1 May 2014 and 31 December 2017. Population was analyzed based on bile acids: normal (10 µmol/L), mild (10 to 40 µmol/L), moderate-severe (40 µmol/L), and not obtained. Receiver operating characteristic curves established critical values for aspartate aminotransferase (AST) and alanine aminotransferase (ALT) to predict elevated bile acids. Statistical analyses included χBile acids were normal in 39 (45.9%) women, 30 (35.3%) had mild cholestasis, 10 (11.8%) had moderate-severe cholestasis and not obtained for six (7%) women. Gestational diabetes was more common in mild cholestasis (ICP should not be presumed in patients with pruritus. This practice may lead to early term delivery and associated complications.

Multiple sclerosis (MS) is a complex disease of the central nervous system (CNS) that involves an intricate and aberrant interaction of immune cells leading to inflammation, demyelination, and neurodegeneration. Due to the heterogeneity of clinical subtypes, their diagnosis becomes challenging and the best treatment cannot be easily provided to patients. Biomarkers have been used to simplify the diagnosis and prognosis of MS, as well as to evaluate the results of clinical treatments. In recent years, research on biomarkers has advanced rapidly due to their ability to be easily and promptly measured, their specificity, and their reproducibility. Biomarkers are classified into several categories depending on whether they address personal or predictive susceptibility, diagnosis, prognosis, disease activity, or response to treatment in different clinical courses of MS. The identified members indicate a variety of pathological processes of MS, such as neuroaxonal damage, gliosis, demyelination, progression of disability, and remyelination, among others. The present review analyzes biomarkers in cerebrospinal fluid (CSF) and blood serum, the most promising imaging biomarkers used in clinical practice. Furthermore, it aims to shed light on the criteria and challenges that a biomarker must face to be considered as a standard in daily clinical practice.

Background Yoga is an ancient system of wellness with Asana and Pranayama as its most popular and propagated modules for management of lifestyle disorders. Objectives The aim of the study was to characterise the liver abnormalities, biochemical changes, and stress levels after Yoga intervention in prediabetic females. Materials and methods 37 females were randomly divided into Yoga practising and non-practising control groups. The Yoga practising group performed Diabetic Yoga Protocol (DYP) for 3 months. Parameters including size of liver, fatty infiltration, and grade of severity were measured using ultrasonography along with biochemical parameters and stress levels at baseline and after Yoga practice. Results The glycosylated hemoglobin (HbA1c) and glucose levels were found significantly reduced in prediabetic (p = 0.015) women after practising DYP, although cholesterol levels increased in menopausal women. No escalation of fatty liver was noted among women practising DYP. Conclusion DYP reduced the HbA1c and stress levels and therefore, could be a cost-effective tool for preventing prediabetes to diabetes progression.

A data recording sheet (DRS) is a specialized document with a predefined format used to enter data related to and/or obtained from an experiment or to follow a protocol for assessing product quality. This is also a tool that can help an experimenter/researcher/study director in data verification, validation, and including the integrity of the project. The DRS should be coded and indexed, which can help finding its location in the laboratory or institution. This data can be collected on the DRS both manually as well as electronically. The present chapter describes the significance of DRS in academic research laboratories and summarizes the method of creating and using a DRS in different quality management systems.

Background: Patients suffering from diabetes mellitus are two to three times more vulnerable to develop depressive symptomatology. Purpose: To report the association between depression and high-risk diabetes in India. Methods: A total of 1,606 adults were recruited for the study. A patient health questionnaire was used to determine the depression on the basis of score. A statistical analysis was done using analysis of covariance (ANCOVA) and binary logistic regression to determine the association between diabetes categories and four degrees of depression. Results: Out of 1,606 participants, 52.6% were males and 47.4% were females, 56.4% belonged to the urban area and 43.6% to the rural area. However, 19.5% (314) had diabetes; 29.1% of diabetes individuals had minimal depression, 38.7% had mild, 17.2% moderate, 12.0% moderately severe, and 3.1% had severe depression. In the self-reported diabetic participant group ( N = 142), there was a significantly higher degree of severe depression (3.3%) in the uncontrolled group (HbA1c >7%) as compared to the well-controlled diabetes group (HbA1c Conclusion: This study found that there is a positive association between depression and uncontrolled diabetes in male gender.

Multiple Sclerosis (MS) is a complex disease of the central nervous system (CNS) that involves the intricate interplay of different immune cells going awry leading to inflammation, demyelination, and neurodegeneration. Its diagnosis is quite arduous because of the baffling number of symptoms it elicits and the varied clinical manifestation it presents. The simplified criteria (in form of Macdonald’s Criteria) which have got modified several times is now the single most important criteria accepted by neurology bodies for diagnosing MS. Biomarkers from time to time have been explored to simplify the diagnosis and prognosticate MS along with anecessity to monitor treatment outcome. In recent years, research on biomarkers has advanced rapidly due to their ability to be easily and rapidly measured, their specificity, safety, and their ability to yield precise results. Biomarkers are classified into various categories including predictive, diagnostic, prognostic, related to disease activity, and monitoring treatment outcome. Each representative of the disease activity category reflects a variety of pathological processes of MS such as neuroaxonal loss, gliosis, demyelination, disability progression, remyelination, etc. This review discusses several promising serum and cerebrospinal fluid biomarkers and imaging biomarkers used in clinical practice. Myelin oligodendrocyte glycoprotein antibody disease which is recently recognized as a definite disease will also be discussed. Furthermore, it sheds light on the criteria and the challenges a biomarker faces to be considered as a standard one.

Background: The deprivation of oxygen reaching the tissues (also termed as hypoxia) affects the normal functioning of the body. This results in development of many diseases like ischemia, glaucoma, MCI (Mild Cognitive Impairment), pulmonary and cerebral edema, stress and depression. There are no effective drugs that can treat such diseases. Despite such failure, alternative interventions such as mind-body techniques (MBTs) have not been adequately investigated. Methods: The first part of this review has been focused on philosophical aspects of various MBTs besides evolving an ayurgenomic perspective. The potential of MBTs as a preventive non-pharmacological intervention in the treatment of various general and hypoxic pathologies has been further described in this section. In the second part, molecular, physiological, and neuroprotective roles of MBTs in normal and hypoxic/ischemic conditions has been discussed. Results: In this respect, the importance of and in vivo studies has also been discussed. Conclusions: Although several studies have investigated the role of protective strategies in coping with the hypoxic environment, the efficacy of MBTs at the molecular level has been ignored.

Objectives: The objective of this research work is to find the effect of providing hotbox at skirt to shell junction of a pressure vessel on the stresses induced at this junction. Methods/Statistical Analysis: In present work, since the vessel is to be supported at some elevation from ground, a conical skirt support is used. Two models of skirt to shell junction are made, in Unigraphics 10, one without hotbox while other with hotbox. A thermo-structural analysis of models is performed using ANSYS Workbench15. Stress linearization is done and stresses are limited to code allowable to ensure protection against plastic collapse and local failure. Findings: The result of finite element analysis for the case of model without hotbox shows that thermal stresses as high as 329 MPa are induced at the y-ring, which is much higher than the allowable stress at that temperature. When a hotbox is provided at this region, the stress is found to be reduced to 35.082 MPa, which is less than the allowable stress. So, the vessel will work safely if a hotbox of minimum 480 mm length is provided at the critical junction of skirt and shell. Stress is linearized at five stress classification lines. The linearized stresses and their combinations for four load cases are compared with the code allowable limit, and are found to be less than allowable stress. This ensures the protection of vessel against plastic collapse and local failure. Application/Improvements: Such analysis is needed to be performed for long vessels supported on skirt type of support, as the total vessel loads will be transferred to skirt from this junction only.

Background and Purpose: A plethora of studies have been conducted in the past, which have proven the salutary effects of yoga practice. Yoga and other mind body techniques are deemed as stress relievers and have shown therapeutic effectiveness in preventing the development and progression of several lifestyle diseases including Diabetes. Yoga practice may help in managing Diabetes by regulating the glucose levels in blood. In this study we have evaluated the efficacy of three months of AYUSH-approved Diabetic Yoga Protocol (DYP) on high-risk individuals.

Ionizing radiation (IR) from terrestrial sources is continually an unprotected peril to human beings. However, the medical radiation and global radiation background are main contributors to human exposure and causes of radiation sickness. At high-dose exposures acute radiation sickness occurs, whereas chronic effects may persist for a number of years. Radiation can increase many circulatory, age related and neurodegenerative diseases. Neurodegenerative diseases occur a long time after exposure to radiation, as demonstrated in atomic bomb survivors, and are still controversial. This review discuss the role of IR in neurodegenerative diseases and proposes an association between neurodegenerative diseases and exposure to IR.

Axonal damage is widely accepted as a major cause of permanent functional disability in Multiple Sclerosis (MS). In relapsing-remitting MS, there is a possibility of remyelination by myelin producing cells and restoration of neurological function. The purpose of this study was to delineate the pathophysiological mechanisms underpinning axonal injury through hitherto unknown factors present in cerebrospinal fluid (CSF) that may regulate axonal damage, remyelinate the axon and make functional recovery possible. We employed primary cultures of rat unmyelinated cerebellar granule neurons and treated them with CSF obtained from MS and Neuromyelitis optica (NMO) patients. We performed microarray gene expression profiling to study changes in gene expression in treated neurons as compared to controls. Additionally, we determined the influence of gene-gene interaction upon the whole metabolic network in our experimental conditions using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) program. Our findings revealed the downregulated expression of genes involved in glucose metabolism in MS-derived CSF-treated neurons and upregulated expression of genes in NMO-derived CSF-treated neurons. We conclude that factors in the CSF of these patients caused a perturbation in metabolic gene(s) expression and suggest that MS appears to be linked with metabolic deformity.

Hope from the regeneration promoting effects of stem cells have provided new insights for understanding diseases that were previously thought to have a limited prognostic improvement upon medical intervention. This is especially indicated in neurodegenerative diseases, which until the discovery and research in stem cells were thought to have minimal regenerative capabilities. This review covers various treatment modalities involving different types of stem cells, such as human embryonic stem cells, induced pluripotent stem cells, mesenchymal stem cells and neural stem cells, which have been tested for various neurodegenerative disorders such as Multiple Sclerosis, Alzheimer’s disease, Parkinson’s disease and Age Related Macular Degeneration.

This paper captures the experiences of the faculty members of a relatively new graduate social work program situated in the largely rural state of Haryana India in reframing the foundation year practicum through community-based and engaged action learning in small villages. Located within Bhagat Phool Singh Vishwavidyalaya (BPSMV), north India's first all women public university, the mission of which is to enhance women's engagement in the greater society through post-secondary, professional and character education, the department is educating social workers for community engagement in social development and in the development of women as an empowered group in society, particularly at the village level. Over a three-year period, the faculty has successfully launched and sustained action learning as an alternative to the traditional practicum in social work education, enhanced civic engagement among students and faculty in three rural villages, and further developed community social work as a principal foc...

The convolution associated with memory is being resolved with advancement in neuroscience. According to the concurrent assumptions, synaptic plasticity forms one of the basis of memory formation, stabilization and strengthening. In Alzheimer's disease (AD), which is generally characterized by memory dysfunction, connections amongst the cells in the brain are attenuated or lost leading to degeneration of neural networks. Numerous attempts have been made to find new therapies for memory dysfunction with increasing attention and investments being laid on herbal drugs. Many herbal plants and extracts have already documented beneficial results when tested for antiamnesic effects. Brahmi (Bacopa monniera) is one such common herbal drug, which is employed for a long time in the Indian and Chinese medical system in order to treat several disorders. Previous research has shown that Brahmi exerts many pharmacological effects including memory boosting capacity in the treatment of Alzheimer's disease and Schizophrenia, exhibiting antiparkinsonian, antistroke, and anticonvulsant potentials. The present review discusses the chemical constituents of Brahmi along with in vitro and in vivo studies based on the pharmacological effects exerted by it. The efficacy of Brahmi in treating various disorders has evoked sufficient research in recent years and now it is a time to launch multiple clinical trials.

Ozgul Muneyyirci-Delale1,2, Jenny Anopa1, Cassandra Charles1, Deepali Mathur1, Rudolph Parris1, Jed B Cutler2, Ghadir Salame1,2, Ovadia Abulafia1,21Department of Obstetrics and Gynecology, SUNY Downstate Medical Center, New York, NY, USA; 2Department of Obstetrics and Gynecology, Kings County Hospital Center, New York, NY, USAPurpose: Evaluate the efficacy of norethindrone acetate in the resolution of symptoms and regression of recurrent endometrioma.Patients and methods: Retrospective chart review at SUNY Downstate Medical Center of patients with a history of surgical excision of endometrioma (with histological confirmation) and recurrent endometrioma (demonstrated by strict sonographic criterion of endometrioma) who were willing to undergo follow-up. Patients were prescribed norethindrone acetate to be taken daily with follow-up sonograms until cysts regressed. Statistical analysis included Student's t-test and a simple linear regression model to assess cyst regression over time during treatment.Results: Degree of pain was significantly lower on treatment when compared to baseline (P < 0.00001). Cyst size was significantly smaller in as little as 3 months (P < 0.0001). Average rate of regression with continuous treatment was 0.025 ± 0.015 cm/day. Total mean ± standard deviation regression time is 10.28 ± 8.25 months.Conclusion: Norethindrone acetate was effective in eradicating symptoms and producing complete regression of recurrent endometriomas. It should be considered for patients who are likely to adhere to a prolonged treatment regimen and comply with recommendations for surveillance with serial sonograms.Keywords: endometriosis, regression, dysmenorrhea, medical therapy

Objective: Uterine leiomyoma is associated with increased BMD in Caucasian women and is largely attributed to the state of hyperestrogenemia associated with disease. This relationship, however, has not been previously described in African–American women. We aim to assess BMD in African–American women with symptomatic uterine leiomyoma. Design: Case–control study. Materials & methods: 29 African–American women with uterine leiomyoma signed an Institutional Review Board (IRB) approved consent form at a reproductive clinic of an inner city hospital in Brooklyn, NY, USA. BMD and T-score of lumbar spine was compared with a controlled group matched for age, race and BMI. BMD of lumbar spine was measured using Hologic QDR 4200 in both groups. Data are presented as mean ± SEM. Results: For the entire study population the mean age (years) was 42.07 ± 1.15, and the BMI (kg/m2) was 29.37 ± 0.93 in patients with uterine leiomyoma and 30.07 ± 1.06 for the control group (p = 0.07). There was a significant difference in the mean BMD (cm2) between the uterine leiomyoma group (1.17 ± 0.03) compared with control (1.05 ± 0.02 p < 0.01). The T-score for the uterine leiomyoma group was significantly higher compared with the control group (0.31 ± 0.25 and −0.74 ± 0.21 with p < 0.01). The prevalence of osteopenia (T-score

The present paper is a study on State initiated women's empowerment scheme named Sakshar Mahila Samooh (SMS). It is a group of rural literate women in each village as resource pool for the development of village community. One SMS was selected using purposive sampling to understand the scheme and to study the process of empowerment through qualitative approach. In-depth interviews of 25 members of SMS were taken and analysed manually to draw the factors responsible in the process of empowerment. The study found that the approach of SMS is more integrated since it has psychosocial empowerment as the base and economic empowerment as the outcome. Increased participation is leading to social action in the form of demonstrations and formation of sustained economic self help groups. The study shows that critical consciousness through support groups and psychosocial, health and legal awareness may ignite the realisation of oppression and develop alternative action.

We aimed to identify the role of vascular endothelial growth factor (VEGF) and monocyte chemoattractant protein (MCP-1) as a serum biomarker of symptomatic carotid atherosclerotic plaque in North Indian population. Individuals with symptomatic carotid atherosclerotic plaque have high risk of ischemic stroke. Previous studies from western countries have shown an association between VEGF and MCP-1 levels and the incidence of ischemic stroke. In this study, venous blood from 110 human subjects was collected, 57 blood samples of which were obtained from patients with carotid plaques, 38 neurological controls without carotid plaques, and another 15 healthy controls who had no history of serious illness. Serum VEGF and MCP-1 levels were measured using commercially available enzyme-linked immunosorbent assay. We also correlated the data clinically and carried out risk factor analysis based on the detailed questionnaire obtained from each patient. For risk factor analysis, a total of 70 symptomatic carotid plaque cases and equal number of age and sex matched healthy controls were analyzed. We found that serum VEGF levels in carotid plaque patients did not show any significant change when compared to either of the controls. Similarly, there was no significant upregulation of MCP-1 in the serum of these patients. The risk factor analysis revealed that hypertension, diabetes, and physical inactivity were the main correlates of carotid atherosclerosis (p 0.05). We conclude that the pathogenesis of carotid plaques may progress independent of these inflammatory molecules. In parallel, risk factor analysis indicates hypertension, diabetes, and sedentary lifestyle as the most significant risk factors of ischemic stroke identified in North India. This could be helpful in early identification of subjects at risk for stroke and devising health care strategies.

Avascular tissues such as a cartilage contains a unique type of cell called as the chondrocyte. We, however, have not understood the origin of the chondrocyte population and how this population is maintained in the normal tissue. In spite of being considered to be a simple tissue, scientist had always faced difficulties to engineer this tissue. This is because different structural regions of the articular cartilage were never understood. In addition to this, the limited self-repair potential of cartilage tissue and lack of effective therapeutic options for the treatment of damaged cartilage has remained an unsolved problem. Mesenchymal stem cell based therapy may provide a solution for cartilage regeneration. This is due to their ability to differentiate into chondrogenic lineage when appropriate conditions are provided. An ideal cell source, a three-dimensional cell culture, a suitable scaffold material that accomplishes all the necessary properties and bioactive factors in specific amounts are required to induce chondrocyte differentiation and proliferation. Cartilage tissue engineering is a promising and rapidly expanding area of research that assures cartilage regeneration. However, many unsolved questions concerning the mechanism of engraftment of chondrocytes following transplantation in vivo, biological safety after transplantation and the retention of these cells for lifetime remain to be addressed that is possible only through years of extensive research. Further studies are therefore required to estimate the long-term sustainability of these cells in the native tissue, to identify well suited delivery materials and to have a thorough understanding of the mechanism of interaction between the chondrocytes and extracellular matrix and time is not far when this cell based therapy will provide a comprehensive cure to cartilage disease.

Uterine leiomyoma is associated with increased BMD in Caucasian women and is largely attributed to the state of hyperestrogenemia associated with disease. This relationship, however, has not been previously described in African-American women. We aim to assess BMD in African-American women with symptomatic uterine leiomyoma.Case-control study.29 African-American women with uterine leiomyoma signed an Institutional Review Board (IRB) approved consent form at a reproductive clinic of an inner city hospital in Brooklyn, NY, USA. BMD and T-score of lumbar spine was compared with a controlled group matched for age, race and BMI. BMD of lumbar spine was measured using Hologic QDR 4200 in both groups. Data are presented as mean ± SEM.For the entire study population the mean age (years) was 42.07 ± 1.15, and the BMI (kg/m²) was 29.37 ± 0.93 in patients with uterine leiomyoma and 30.07 ± 1.06 for the control group (p = 0.07). There was a significant difference in the mean BMD (cm²) between the uterine leiomyoma group (1.17 ± 0.03) compared with control (1.05 ± 0.02 p0.01). The T-score for the uterine leiomyoma group was significantly higher compared with the control group (0.31 ± 0.25 and -0.74 ± 0.21 with p0.01). The prevalence of osteopenia (T-score-1) was lower for the leiomyoma group when compared with controls, (p0.02).Consistent with data from the white population with uterine leiomyoma, our data showed a significantly higher BMD in African-American women with uterine leiomyoma, compared with an age- and race-matched cohort. The implications of these findings remain to be investigated and further confirmed in future longitudinal studies.