Breast Abscess Healing with Homoeopathy: A Case Report.

Context: Breast abscess is the most common complication of acute bacterial mastitis usually referred to as pyogenic mastitis. It is usually encountered during lactation due to an infection with Staphylococcus aureus and streptococcal bacteria. These bacteria produce a severe inflammatory reaction leading to pus formation which is mainly treated by ultrasound-guided drainage or fine needle aspirations. We find that in this condition homoeopathic treatment can play an important role as it avoids such surgical procedures and helps in healing in a most gentle and rapid way. We report a successful single case study that opens up opportunities to take up more such cases to strengthen the results of this report. Case summary: A 23-year-old lactating mother came with complaints of pain and swelling with a collection of pus in the breast region and decreased breast milk secretion. Individualised homoeopathic medicine Silicea 200C was given to hasten suppuration and Belladonna 200C to treat inflammation.Thus, this case shows us how only few doses of medicine may be quickly helpful in managing a case of breast abscess without the need of any surgical procedures.

A Survey to Assess the Impact of COVID-19 Pandemic on Lifestyle in an Adult Age Group.

Context: A healthy lifestyle has been the need of the hour during the COVID 19 pandemic. Analyzing the current lifestyle patterns of many individuals can be the basis for finding solutions toward building a healthy future for India. Objectives: The study intended to evaluate the current lifestyles of adults in an urban setting in the midst of a pandemic and to examine the diseases that people could face with respect to their current lifestyles. Design: The research team performed a cross-sectional study. Setting: The survey was conducted in an urban setting in the Pimpri Chinchwad area of Pune, India. Participants: Participants were 500 men and women between the ages of 18 and 25. Outcome Measures: The research team created a survey with 13 multiple-choice questions. Results: The pandemic has taken a toll on people's mental and physical health. Social distancing and staying indoors for long periods are factors that have affected people's mental health. Conclusions: Efforts need to be made by individuals to focus not only on their physical health but also on their mental health.

Stem Cell Secretome Modulated by Arsenicum album 30C Ameliorates Lipopolysaccharide-induced Cytokine Storm in Blood Mononuclear Cells in vitro.

BACKGROUND: The therapeutic effectiveness of mesenchymal stem cells (MSCs) and their secretome can be enhanced by means of physical, chemical and biological preconditioning. Arsenicum album 30C (AA30) has been one of the leading homeopathic medicines used in prophylaxis against SARS-CoV-2 infection. AIMS: This study aimed to investigate whether AA30 preconditioning could influence the growth factors and cytokine profile of the human dental pulp-derived MSC (DPD-MSC) secretome. Also, to test the efficacy of the AA30-preconditioned DPD-MSC secretome in ameliorating the lipopolysaccharide (LPS)-induced cytokine storm in human peripheral blood mononuclear cells (PBMCs) as an in-vitro cellular model. METHODS: The cytotoxicity of AA30 was assessed in DPD-MSCs by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Growth factors and cytokine levels in the AA30-preconditioned DPD-MSC secretome were analysed by fluorescence-activated cell sorting (FACS) analysis. The angiogenic potential of the AA30-preconditioned DPD-MSC secretome was assessed by chick yolk-sac membrane (YSM) assay. Culture medium with 0.001% ethanol was used as vehicle control. The efficacy of the AA30-preconditioned DPD-MSC secretome in ameliorating the cytokine storm was assessed in LPS pre-treated PBMCs. The mRNA and protein expression of inflammatory markers such as IL-1ß, IL-6 and IL-10 were analysed by using RT-PCR and FACS analysis respectively. RESULTS: AA30 did not exhibit cytotoxicity in the concentration range of 1% to 50%. Furthermore, the AA30-preconditioned DPD-MSC secretome exhibited a significant increase in the levels of angiogenic factors, such as human angiopoietin-2, EPO and PDGF-AA, and decreased levels of cytokines, such as TNF-α, CXCL-8 and IL-6. The AA30-preconditioned DPD-MSC secretome showed augmented angiogenesis compared to vehicle controls. The DPD-MSC secretome ameliorated LPS-induced mRNA and protein expression of IL-1ß, IL-6 and IL-10 in PBMCs. CONCLUSION: The AA30-preconditioned DPD-MSC secretome augmented angiogenesis and ameliorated the LPS-induced cytokine storm in human PBMCs in vitro. Our data demonstrate that AA30 preconditioning enhances the therapeutic potency of MSCs and their secretome.

Conventional Homeopathic Medicine and Its Relevance to Modern Medicine.

Context: Homeopathic medicine can be explained as a symptoms-based method of treatment, and it can act as an alternative treatment strategy against allopathy by focusing on the symptoms of illness, as opposed to causative agents as allopathic medicine does. Also, homeopathic medicines are extracted from nature rather than being chemically synthesized as western drugs are. Objective: The review intended to briefly describe the concept of homeopathic medicine, its emergence from a historical point of view, and its broader healing properties, providing examples of key homeopathic drugs and comparing them to modern medicines. Design: The research team performed a narrative review by searching databases like Pubmed, Google Scholar, and other national search engines. The search used the keywords homeopathic medicine, alternate medicine, materia medica, allium cepa, Zingiber officinale, penicillium, Agaricus muscaria, Botulinum toxin. Setting: Dr. D.Y. Patil Homoeopathic Medical College and Research Centre, Dr. D.Y. Patil Vidyapeeth (Deemed to be University), Pimpri, Pune. Results: This review highlights the rich sources homoeopathic drugs and their corelation with modern medicine. The current review focuses on the significance of the Homeopathic Materia Medica and on notable remedies in homeopathy that align with allopathy in addressing different pathological conditions, including treatments that the two types of medicine have in in common and that are effective in homeopathy. Conclusions: Many studies are being conducted to prove the mechanism of action of homoeopathic medicines. Droplet Evaporating Method (DEM), Raman, UltraViolet-Visible (UV-VIS) spectroscopy and Transmission Electron Microscopy (TEM) are commonly used methods to characterize homeopathic medicines at ultra-low concentration and many such studies will surely indicate how homoeopathic medicines act. Such research results may subsequently lead to the betterment of treatment procedures and the integration of homeopathic principles into mainstream medical practices.

Polycystic Ovarian Syndrome Treated with Individualized Homeopathy: A Case Report.

Introduction: Polycystic ovarian syndrome (PCOS) is a polygenic, multifactorial, syndromic disorder with reproductive, endocrine, and metabolic dysfunction seen in reproductive aged women (12-45 years). The exact cause is not known may involve increased luteinizing hormone, increased insulin levels, and a defect in androgen synthesis. The symptoms include anovulation, irregular menses, and hyperandrogenism. It is clinically manifested by hirsutism, acne, and androgenic alopecia. Health care practitioners continue to seek a cure for PCOS as it is increasing in frequency and is one of the major causes of anovulatory infertility. Methods: The case was recorded in the gynaecological department at the Homoeopathic Medical College and Research Centre. An 18- year-old female patient with PCOS was treated with individualised homeopathy (iHOM) medicine between 26th September 2019 and 26th November 2020. During the follow-up visits, treatment outcomes were assessed. To assess whether the changes were due to homoeopathic medicine, an assessment using the modified Naranjo criteria was performed. Results: Over an observational period of 1 year, beneficial result from iHOM medicine was seen. This treatment method can be used by the physicians in the treatment of PCOS as a complementary health practice. Conclusion: Considering the multi-factorial aetiology of PCOS, iHOM medicine with lifestyle modification is helpful in treating PCOS.

Indirect Estimation of Vertical Ground Reaction Force from a Body-Mounted INS/GPS Using Machine Learning.

Vertical ground reaction force (vGRF) can be measured by force plates or instrumented treadmills, but their application is limited to indoor environments. Insoles remove this restriction but suffer from low durability (several hundred hours). Therefore, interest in the indirect estimation of vGRF using inertial measurement units and machine learning techniques has increased. This paper presents a methodology for indirectly estimating vGRF and other features used in gait analysis from measurements of a wearable GPS-aided inertial navigation system (INS/GPS) device. A set of 27 features was extracted from the INS/GPS data. Feature analysis showed that six of these features suffice to provide precise estimates of 11 different gait parameters. Bagged ensembles of regression trees were then trained and used for predicting gait parameters for a dataset from the test subject from whom the training data were collected and for a dataset from a subject for whom no training data were available. The prediction accuracies for the latter were significantly worse than for the first subject but still sufficiently good. K-nearest neighbor (KNN) and long short-term memory (LSTM) neural networks were then used for predicting vGRF and ground contact times. The KNN yielded a lower normalized root mean square error than the neural network for vGRF predictions but cannot detect new patterns in force curves.

An Automatic Aggregator of Power Flexibility in Smart Buildings Using Software Based Orchestration.

This paper presents a software-based modular and hierarchical building energy management system (BEMS) to control the power consumption in sensor-equipped buildings. In addition, the need of this type of solution is also highlighted by presenting the worldwide trends of thermal energy end use in buildings and peak power problems. Buildings are critical component of smart grid environments and bottom-up BEMS solutions are need of the hour to optimize the consumption and to provide consumption side flexibility. This system is able to aggregate the controls of the all-controllable resources in building to realize its flexible power capacity. This system provides a solution for consumer to aggregate the controls of 'behind-the-meter' small loads in short response and provide 'deep' demand-side flexibility. This system is capable of discovery, status check, control and management of networked loads. The main novelty of this solution is that it can handle the heterogeneity of the installed hardware system along with time bound changes in the load device network and its scalability; resulting in low maintenance requirements after deployment. The control execution latency (including data logging) of this BEMS system for an external control signal is less than one second per connected load. In addition, the system is capable of overriding the external control signal in order to maintain consumer coziness within the comfort temperature thresholds. This system provides a way forward in future for the estimation of the energy stored in the buildings in the form of heat/temperature and use buildings as temporary batteries when electricity supply is constrained or abundant.

The Bdnf and Npas4 genes are targets of HDAC3-mediated transcriptional repression.

BACKGROUND: Histone deacetylase-3 (HDAC3) promotes neurodegeneration in various cell culture and in vivo models of neurodegeneration but the mechanism by which HDAC3 exerts neurotoxicity is not known. HDAC3 is known to be a transcriptional co-repressor. The goal of this study was to identify transcriptional targets of HDAC3 in an attempt to understand how it promotes neurodegeneration. RESULTS: We used chromatin immunoprecipitation analysis coupled with deep sequencing (ChIP-Seq) to identify potential targets of HDAC3 in cerebellar granule neurons. One of the genes identified was the activity-dependent and neuroprotective transcription factor, Neuronal PAS Domain Protein 4 (Npas4). We confirmed using ChIP that in healthy neurons HDAC3 associates weakly with the Npas4 promoter, however, this association is robustly increased in neurons primed to die. We find that HDAC3 also associates differentially with the brain-derived neurotrophic factor (Bdnf) gene promoter, with higher association in dying neurons. In contrast, association of HDAC3 with the promoters of other neuroprotective genes, including those encoding c-Fos, FoxP1 and Stat3, was barely detectable in both healthy and dying neurons. Overexpression of HDAC3 leads to a suppression of Npas4 and Bdnf expression in cortical neurons and treatment with RGFP966, a chemical inhibitor of HDAC3, resulted in upregulation of their expression. Expression of HDAC3 also repressed Npas4 and Bdnf promoter activity. CONCLUSION: Our results suggest that Bdnf and Npas4 are transcriptional targets of Hdac3-mediated repression. HDAC3 inhibitors have been shown to protect against behavioral deficits and neuronal loss in mouse models of neurodegeneration and it is possible that these inhibitors work by upregulating neuroprotective genes like Bdnf and Npas4.

Continuous Analysis of Running Mechanics by Means of an Integrated INS/GPS Device.

This paper describes a single body-mounted sensor that integrates accelerometers, gyroscopes, compasses, barometers, a GPS receiver, and a methodology to process the data for biomechanical studies. The sensor and its data processing system can accurately compute the speed, acceleration, angular velocity, and angular orientation at an output rate of 400 Hz and has the ability to collect large volumes of ecologically-valid data. The system also segments steps and computes metrics for each step. We analyzed the sensitivity of these metrics to changing the start time of the gait cycle. Along with traditional metrics, such as cadence, speed, step length, and vertical oscillation, this system estimates ground contact time and ground reaction forces using machine learning techniques. This equipment is less expensive and cumbersome than the currently used alternatives: Optical tracking systems, in-shoe pressure measurement systems, and force plates. Another advantage, compared to existing methods, is that natural movement is not impeded at the expense of measurement accuracy. The proposed technology could be applied to different sports and activities, including walking, running, motion disorder diagnosis, and geriatric studies. In this paper, we present the results of tests in which the system performed real-time estimation of some parameters of walking and running which are relevant to biomechanical research. Contact time and ground reaction forces computed by the neural network were found to be as accurate as those obtained by an in-shoe pressure measurement system.

Histone deacetylase 3 is necessary for proper brain development.

The functional role of histone deacetylase 3 (HDAC3) in the developing brain has yet to be elucidated. We show that mice lacking HDAC3 in neurons and glia of the central nervous system, Nes-Cre/HDAC3 conditional KO mice, show major abnormalities in the cytoarchitecture of the neocortex and cerebellum and die within 24 h of birth. Later-born neurons do not localize properly in the cortex. A similar mislocalization is observed with cerebellar Purkinje neurons. Although the proportion of astrocytes is higher than normal, the numbers of oligodendrocytes are reduced. In contrast, conditional knockout of HDAC3 in neurons of the forebrain and certain other brain regions, using Thy1-Cre and calcium/calmodulin dependent protein kinase II α-Cre for ablation, produces no overt abnormalities in the organization of cells within the cortex or of cerebellar Purkinje neurons at birth. However, both lines of conditional knockout mice suffer from progressive hind limb paralysis and ataxia and die around 6 weeks after birth. The mice display an increase in overall numbers of cells, higher numbers of astrocytes, and Purkinje neuron degeneration. Taken together, our results demonstrate that HDAC3 plays an essential role in regulating brain development, with effects on both neurons and glia in different brain regions.

Incidence of and risk factors for small vulnerable newborns in north India: a secondary analysis of a prospective pregnancy cohort.

BACKGROUND: Globally, recent estimates have shown there have been 3·6 million stillbirths and neonatal deaths in 2022, with nearly 60% occurring in low-income and middle-income countries. The Small Vulnerable Newborn Consortium has proposed a framework combining preterm birth (<37 weeks of gestation), small for gestational age (SGA) by INTERGROWTH-21st standard, and low birthweight (<2500 g) under the category small vulnerable newborns (SVN). Reliable data on SVN from sub-Saharan Africa, central Asia, and south Asia are sparse. We aimed to estimate the incidence of SVN and its types, and quantify risk factors, both overall and trimester-specific, from a pregnancy cohort in north India. METHODS: In the GARBH-Ini (Interdisciplinary Group for Advanced Research on Birth Outcomes-DBT India Initiative) pregnancy cohort, 8000 participants were enrolled with less than 20 weeks' gestation between May 11, 2015, and Aug 8, 2020, at a secondary-care hospital in north India. The cohort was followed up across the antenatal period for a detailed study on preterm birth. We conducted a secondary analysis of cohort data for the outcome of SVN, classified into its types: preterm-SGA, preterm-nonSGA, and term-SGA. We estimated the relative risk and population attributable fraction of candidate risk factors for SVN (modified Poisson regression) and its types (multinomial regression). FINDINGS: 7183 (89·9%) of 7990 participants completed the study. Among 6206 newborns included for analysis, the incidence of SVN was 48·4% (35·1% term-SGA newborns [n=2179], 9·7% preterm-nonSGA newborns [n=605], and 3·6% preterm-SGA newborns [n=222]). Compared with term-nonSGA newborns, proportions of stillbirths and neonatal deaths within 72 h of birth among SVN were three times and 2·5 times higher, respectively. Preterm-SGA newborns had the highest incidence of stillbirth (15 [6·8%] of 222) and neonatal deaths (six [4·2%] of 142). Low body-mass index (BMI <18·5 kg/m2) of participants at the start of pregnancy was associated with higher risk for preterm-SGA (adjusted relative risk [RR] 1·61 [95% CI 1·17-2·22]), preterm-nonSGA (1·35 [1·09-1·68]), and term-SGA (1·44 [1·27- 1·64]), with population attributable fraction ranging from 8·7% to 13·8%. Pre-eclampsia (adjusted RR 1·48 [95% CI 1·30-1·71]), short cervical length (1·15 [1·04-1·26]), and bacterial vaginosis (1·13 [0·88-1·45]) were other important antenatal risk factors. INTERPRETATION: In a comprehensive analysis of SVN and its types from north India, we identified risk factors to guide prioritisation of interventions. Complemented with risk-stratification tools, this focused approach will enhance antenatal care, and accelerate achievement of Sustainable Development Goals-namely, to end preventable deaths of newborns and children younger than 5 years by 2030 (target 3·2). FUNDING: Department of Biotechnology, Government of India and Grand Challenges India-Biotechnology Industry Research Assistance Council, Government of India. TRANSLATION: For the Hindi translation of the abstract see Supplementary Materials section.

Severity and mortality associated with COVID-19 among children hospitalised in tertiary care centres in India: a cohort study.

Background: It is critical to identify high-risk groups among children with COVID-19 from low-income and middle-income countries (LMICs) to facilitate the optimum use of health system resources. The study aims to describe the severity and mortality of different clinical phenotypes of COVID-19 in a large cohort of children admitted to tertiary care hospitals in India. Methods: Children aged 0-19 years with evidence of SARS-CoV-2 infection (real time polymerase chain reaction or rapid antigen test positive) or exposure (anti-SARS-CoV-2 antibody, or history of contact with SARS-CoV-2) were enrolled in the study, between January 2021 and March 2022 across five tertiary hospitals in India. All study participants enrolled prospectively and retrospectively were followed up for three months after discharge. COVID-19 was classified into severe (Multisystem Inflammatory Syndrome in Children (MIS-C), severe acute COVID-19, 'unclassified') or non-severe disease. The mortality rates were estimated in different phenotypes. Findings: Among 2468 eligible children enrolled, 2148 were hospitalised. Signs of illness were present in 1688 (79%) children with 1090 (65%) having severe disease. High mortality was reported in MIS-C (18.6%), severe acute COVID-19 (13.3%) and the unclassified severe COVID-19 disease (12.3%). Mortality remained high (17.5%) when modified MIS-C criteria was used. Non-severe COVID-19 disease had 14.1% mortality when associated with comorbidity. Interpretation: Our findings have important public health implications for low resource settings. The high mortality underscores the need for better preparedness for timely diagnosis and management of COVID-19. Children with associated comorbidity or coinfections are a vulnerable group and need special attention. MIS-C requires context specific diagnostic criteria for low resource settings. It is important to evaluate the clinical, epidemiological and health system-related risk factors associated with severe COVID-19 and mortality in children from LMICs. Funding: Department of Biotechnology, Govt of India and Department of Maternal, Child and Adolescent Health and Aging, WHO, Geneva, Switzerland.

Testosterone modulates pituitary vasotocin receptor expression and adrenal activity in osmotically stressed chicken.

Regulation of arginine vasotocin (AVT), avian neurohypophyseal hormone, is an important component of the hypothalamo-pituitary-adrenal axis. Changes in plasma osmolality levels and sex steroids are known to affect AVT gene expression. The present study reports the effect of water deprivation and testosterone treatment independently, as well as simultaneously, on the pituitary vasotocin receptor VT2R expression and adrenal steroidogenic activity in sexually immature male chicken (Gallus gallus). Birds were divided into four groups- control, water deprived (WD), testosterone injected (TE) and TE treated water deprived (TE+WD). WD decreased and TE treatment alone or in combination with WD (TE+WD) increased VT2R expression compared to the control. Expression of pro-opiomelanocortin (POMC) was also studied since this gene is a polypeptide precursor of ACTH and is under the negative feedback of adrenal corticoids. TE treatment as well as WD separately or when coupled together decreased the POMC mRNA expression in the pituitary but stimulated adrenal steroidogenic activity. Further, VT2R expression decreased in TE+WD compared to TE group, but it was not different from the vehicle treated control group suggesting that the suppressive effect of WD on VT2R expression was inhibited by the stimulatory effect of testosterone. Similarly, although both TE and WD decreased POMC expression and increased steroidogenic activity, no further decrease or increase in these parameters was observed when these two (WD and TE) treatments were combined together. Although, the exact mechanism is not clear, data indicate a stimulatory action of testosterone on VT2R expression and adrenal function despite a decreased expression of POMC mRNA. Results also suggest that testosterone treatment to sexually immature birds, in addition to its effect on hypothalamic AVT neurons (earlier study) and pituitary VT2R expression (present study), masks or inhibits osmotic stress-induced alterations in pituitary-adrenal activity.

COVID-19 vaccination hesitancy in India: State of the nation and priorities for research.

BACKGROUND: Few COVID-19 vaccines were anticipated in India in early 2021. However, little was known about COVID-19 vaccination acceptance among the public. We conducted a nationwide study to understand the public's perception about COVID-19 vaccines in December 2020. METHOD: An online survey was deployed using a multi-item validated questionnaire via social media websites and networking platforms for adults in India. We asked participants about vaccination willingness, concerns about vaccination, and their sociodemographic characteristics. RESULTS: Nationwide, 1638 participants from 27 states/union territories took the survey where the majority of the participant were males (55%), 18-30 years old (52%), urban dwellers (69%), college-educated (81%), without a history of COVID-19 infection (92%). More than a fifth were either unaware of the vaccines (20.63%) or were not sure if they will get the vaccine (27%), and 10% refused to obtain the vaccine. Almost 70% of the population had concerns regarding the vaccines. Statistically significant differences (p<0.01) in awareness about vaccine and acceptability were observed based on age, educational qualifications, and employment status. CONCLUSION: While the majority of Indians would accept the vaccine, given the large population of India, even a small proportion of hesitant individuals would translate to millions of unvaccinated individuals. Strategic measures and policy decisions to enhance the rate of COVID-19 vaccination should be continuously planned and implemented in India.

Longitudinal Serology of SARS-CoV-2-Infected Individuals in India: A Prospective Cohort Study.

Clinical and epidemiological characteristics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are now widely available, but there are few data regarding longitudinal serology in large cohorts, particularly those from low-income and middle-income countries. We established an ongoing prospective cohort of 3,840 SARS-CoV-2-positive individuals according to RT-PCR in the Delhi-National Capital Region of India to document clinical and immunological characteristics during illness and convalescence. The immunoglobulin G (IgG) responses to the receptor binding domain (RBD) and nucleocapsid were assessed at 0 to 7 days, 10 to 28 days, and 6 to 10 weeks after infection. The clinical predictors of seroconversion were identified by multivariable regression analysis. The seroconversion rates during the postinfection windows of 0 to 7 days, 10 to 28 days, and 6 to 10 weeks were 46%, 84.7%, and 85.3%, respectively (N = 743). The proportion with a serological response increased with the severity of coronavirus disease 2019 (COVID-19). All participants with severe disease, 89.6% with mild to moderate infection, and 77.3% of asymptomatic participants had IgG antibodies to the RBD antigen. The threshold values for the nasopharyngeal viral RNA RT-PCR of a subset of asymptomatic and symptomatic seroconverters were comparable (P = 0.48) to those of nonseroconverters (P = 0.16) (N = 169). This is the first report of longitudinal humoral immune responses to SARS-CoV-2 over a period of 10 weeks in South Asia. The low seropositivity of asymptomatic participants and differences between assays highlight the importance of contextualizing the understanding of population serosurveys.

Osmotic stress induced alteration in the expression of arginine vasotocin receptor VT2 in the pituitary gland and adrenal function of domestic fowl.

The role of arginine vasotocin in the regulation of the pituitary-adrenal axis of domestic fowl was analyzed by studying the expression of its recently cloned pituitary receptor VT2 and adrenal activity following osmotic stress. Four days of water deprivation induced an increase in plasma osmolality-a known stimulator of AVT synthesis and release from hypothalamic magnocellular neurons. Water deprivation also decreased pituitary mRNA levels for both the VT2 receptor and for pro-opiomelanocortin (POMC). Despite a decrease in the expression of VT2 mRNA, immunoreactive-VT2 receptor levels in the pituitary increased, suggesting a possible role for post-transcriptional mechanisms in the regulation of this receptor. Further, adrenal activity (as judged by adrenal weight, cholesterol content, 3beta hydroxysteroid dehydrogenase, cortical cord width and cortico-medullary ratio) showed stimulation in water-deprived chicken as compared to control. On the basis of present findings, it is concluded that water deprivation down regulates the mRNA expression of AVT receptor VT2 as well as POMC but stimulates adrenal function. It is also suggested that in addition to the release of magnocellular AVT into the neurohypophysis to act as antidiuretic hormone following water deprivation, AVT may also modulate HPA axis to cope with the osmotic stress.

Corticosterone- or metapyrone-induced alterations in adrenal function and expression of the arginine vasotocin receptor VT2 in the pituitary gland of domestic fowl, Gallus gallus.

The avian neurohypophyseal hormone arginine vasotocin (AVT) is known to be involved in the regulation of adrenocorticotropin (ACTH) release by interacting with the VT2 receptor (VT2R), which is homologous to the mammalian vasopressin V1b receptor (V1bR). To study the role of glucocorticoid in the expression and regulation of the VT2R, corticosterone (1 or 5mg/bird/day) or metapyrone (10 or 50mg/kg body weight/day) were administered daily for 8 days to white leghorn chickens. While low doses were ineffective, a high dose of corticosterone upregulated, while metapyrone downregulated, pituitary VT2R mRNA expression and ir-VT2 in the cephalic lobe of the anterior pituitary. Further, although no change was observed in the expression of POMC mRNA, adrenal activity (as judged by the changes in total cholesterol, 3beta HSD, cortical cord width and cortico-medullary ratio) exhibited suppression or stimulation following treatment with corticosterone or metapyrone, respectively. In view of the classical negative feedback effect of glucocorticoids at the level of hypothalamic CRH neurons and pituitary corticotrophs, high corticosterone level-induced suppression of the CRH-ACTH axis may have been masked by VT2R-mediated stimulation of corticotrophs, and hence the POMC mRNA level did not change. The same argument could be used for metapyrone. It is concluded that expression of the VT2 receptor is regulated by glucocorticoids in chicken. These findings confirm a role for AVT, mediated by the VT2 receptor, in regulating ACTH secretion during stress and suggest that corticotroph VT2 receptor levels may be dynamically regulated depending on the HPA axis activity.

Pre-existing H4K16ac levels in euchromatin drive DNA repair by homologous recombination in S-phase.

The homologous recombination (HR) repair pathway maintains genetic integrity after DNA double-strand break (DSB) damage and is particularly crucial for maintaining fidelity of expressed genes. Histone H4 acetylation on lysine 16 (H4K16ac) is associated with transcription, but how pre-existing H4K16ac directly affects DSB repair is not known. To answer this question, we used CRISPR/Cas9 technology to introduce I-SceI sites, or repair pathway reporter cassettes, at defined locations within gene-rich (high H4K16ac/euchromatin) and gene-poor (low H4K16ac/heterochromatin) regions. The frequency of DSB repair by HR is higher in gene-rich regions. Interestingly, artificially targeting H4K16ac at specific locations using gRNA/dCas9-MOF increases HR frequency in euchromatin. Finally, inhibition/depletion of RNA polymerase II or Cockayne syndrome B protein leads to decreased recruitment of HR factors at DSBs. These results indicate that the pre-existing H4K16ac status at specific locations directly influences the repair of local DNA breaks, favoring HR in part through the transcription machinery.

Estradiol (E2)- and tamoxifen (Tmx)-bound ER-alpha (ERα) interact differentially with histone deacetylases 1 and 3 (HDACs 1 and 3).

Although ERα activation properties have been intensively studied, this is not the case for their repressive properties. In this report, the ERα ligand binding domain (LBD) is shown to interact both with a deacetylase function and with HDAC1 and HDAC3. Ligands do not affect binding to the deacetylase activity or to HDAC1. In distinction, E2 reduced LBD binding to HDAC3, whereas Tmx had no effect. Knock-down of either HDAC1 or 3 led to increased transcriptional activity by both HDACs, presumably by decreased repression. In distinction, only HDAC3 knock-down led to increased activity in the presence of Tmx. In summary, ERα differentially interacts with HDACs 1 and 3 to regulate transcriptional activity.

Advance Teaching of Fundamentals of Homoeopathy (ATFH): redefining competency based approach

The curriculumin academic medicine is defined by writing effective Learning objectives (LO). LO iselaborated based on perceptions of unbiased written aspects,of course, the rationale in statements is explained and tested through the completion of educational activity. These are the foundations for defining the outcomes in building up strong educational policieswhich are instructionalaligned through predefined effective curriculum courseswith added mapped outcomes. This letter provides the ongoing aspect of the development of Homoeopathic education in India regulated by the National Commission for Homoeopathy for the subject course of Advance Teaching of Fundamentals of Homoeopathy (ATFH). The essential components for the ATFHsubject course with LO and outcome assessment is been discussed and would provide a new arena of academic research in building up rationale in the programed [Doctor of Homoeopathy(MD,(Hom).