Serologic status at 10 months of infants born to hepatitis B positive mothers given prophylaxis - A prospective cohort study

Rationale: Perinatal exposure is the most common mode of transmission of hepatitis B (HB) infection in neonates. Prevention of perinatal transmission of HB is important to decrease overall carrier state. Objectives: To estimate the rate of HB carrier status among children born to HB surface antigen (HBsAg) positive mothers at 10 months of age measured by HBsAg status and to assess the efficacy of prophylaxis (HB vaccine [HBV] and HB immunoglobulin [HBIG] administration) as measured by the anti-HBs titer at 10th month of age. Methodology: This was a hospital based prospective cohort study of infants born to HBsAg positive motherbetween April 2008 and October 2008 with a follow-up at 6 weeks, 14 weeks, and 10 months of age. After informed consent from the parents, 0.5 ml of recombinant vaccine was given to all. HBIG was given to only those who could afford to buy it. At 6 and 14 weeks of age, 0.5 ml of recombinant vaccine was given according to the IAP immunization schedule along with other UIP vaccines to all neonates. At 10 months of age (plus 1 week), 69 infants completed 3 doses of HBV. Anti-HBs titer and HBsAg status were measured. Anti-HBs titer >100 IU/L was taken as a good responder. Results: Total 125 infants were initially recruited. Allwere vaccinated with HBV within 12 h of birth. HBIG was given to 96 infants (76.8%) and only 69 (55.2%) completed 3rd visit. Carrier state in infants born to HBsAg positive mothers at 10 months of age was 1/69 (1.44%). 43/69 (62.35%) had good antibody response out of which, 41 were given both HBV and HBIG. In those given only vaccine, 2/7 (28.55%) had good antibody response (p=0.02). Conclusion: Combined HB vaccine and immunoglobulin had a better antibody response in the study as reported earlier. The carrier state was 1.44%

A CASE REPORT ON CHARMADAL THROUGH PANCHAKARMA W.S.R. TO ECZEMA

Charmadal is a type of Kshudrakushta characterized with symptoms such as redness, itching, pustules, pain and cracks in the skin and tenderness. Most of the symptoms of Eczema can be correlated with Charmadal as mentioned in Ayurvedic classics. A diagnosed case of Eczema came with chief complaints of red patches on skin associated with severe itching, burning and dryness over different body parts (on face, neck, upper arm) since 4 years with complaint of oozing of blood from the patches after itching. No satisfactory treatment is present except topical steroids, but in Ayurveda text line of treatment for Charmadal is present i.e., Virechana Karma”. Before giving Virechana treatment SCORAD (Scoring atopic dermatitis) was 26.55% and after follow up SCORAD 86.05%. Before Virechana treatment DLQI was 25% (extremely large effect on patient’s life) and after follow up DLQI was 4% (small effect on patient life). The results of the study showed that when Virechana Karma was performed, it increased the efficacy of oral Ayurveda medicines in the patient of Charmadal. Virechana improved the condition of patient to very much extent

MANAGEMENT OF IRRITABLE BOWEL SYNDROME THROUGH AYURVEDA: A CASE STUDY

Irritable bowel syndrome (IBS) is a gastrointestinal disorder characterized by altered bowel habits and abdominal pain in the absence of detectable structural abnormalities. The pathogenesis of IBS is poorly understood, although roles for abnormal gut motor and sensory activity, central neural dysfunction, psychological disturbances, stress, and luminal factors have been proposed. About 10-15% of the population is affected at some time but only 10% of these consult their doctor because of symptoms. In Ayurveda, IBS can be correlated to Grahani Roga due to similarity in their clinical presentation. In this case an effort was made to treat a 32 years old male patient having symptoms of Muhurbaddha Muhurshithil (episode of constipated and loose stools), Apakwa Malapravritti (Stool with mucus), Udarshool (abdominal pain). Patient treated with various Panchakarma (five Bio-cleaning Ayurvedic therapies) procedures like Basti (herbal medicated enema), Takra Dhara (pouring Herbal medicated butter milk on head) and oral medications. At the end of 60 days of treatment patient got significant improvement in episode of constipated and loose stools (75%), distension of abdomen (75%), anorexia (100%) and stool with mucus (100%)

A Systematic review on the Ayurveda concept of Immunity w.s.r. to Covid-19 and other viral infection

System protect us from infections through various lines of defence is called immune system. If immune system is not functioning as it should, it can result in disease. This system is divided into two types: innate and adaptive immunity. First line of defence consists of physical, chemical and cellular defense against pathogen is innate immunity. Adaptive or acquired immunity is second line immunity against non-self-pathogen. In this article focus to give a way to understand the concept of immunology in Ayurveda and its role to prevent disease along with its type as Vyadhiutpada Pratishedhakatva (like as innate immunity) and Vyadhivala Virodhitva (like as acquired immunity), factors responsible for immunity and way to strengthen it naturally. Comparing the concept of Ayurveda with viral infections found now a days and how it interpreted for managing by using Ayurveda principle

Breast cancer stem-like cells are inhibited by diosgenin, a steroidal saponin, by the attenuation of the Wnt ß-catenin signaling via the Wnt antagonist secreted frizzled related protein-4

Background: Identification of breast cancer stem cells as the chemo-resistant and tumor-initiating population represents an important milestone in approaching anticancer therapies. Targeting this minor subpopulation of chemo- and radio-resistant stem-like cells, termed as the cancer stem cells (CSCs) and their eradication could significantly enhance clinical outcomes. Most of the presently administered chemotherapeutics target the tumor bulk but are ineffective against the CSCs. We report here that diosgenin (DG), a naturally occurring steroidal saponin, could effectively inhibit CSCs from three breast cancer cell lines, MCF7, T47D and MDA-MB-231, by inducing apoptosis and inhibiting the CSC associated phenotypes. Methods: CSCs were enriched in these cells lines, characterized for CSC traits by immunocytochemistry and flow cytometry. Proliferation and apoptosis assays were performed in these breast CSCs in the presence of DG to obtain the inhibitory concentration. Apoptosis was confirmed with gene expression analysis, Western blotting and propidium iodide staining. TCF-LEF reporter assay, sFRP overexpression and RNAi silencing studies were performed to study regulation of the Wnt pathway. Statistical significance was evaluated by a two-sided Student's t-test. Results: Using the TCF-LEF reporter system, we show the effect of DG on CSCs is predominantly through the network regulating CSC self renewal, the Wnt ß-catenin pathway. Specifically, the Wnt antagonist, the secreted frizzled related protein 4, (sFRP4), had a defining role in the action of DG. Gain-of-function of sFRP4 in CSCs could improve the response to DG wherein CSC mediators were inhibited, ß-catenin was down regulated and the effectors of epithelial to mesenchymal transition and pro-invasive markers were repressed. Conversely, the loss-of-function of sFRP4 had a reverse effect on the CSC population which therein became enriched, their response to DG treatment was modest, ß-catenin levels increased, GSK3ß expression decreased and the expression of epithelial markers of CSC was completely abrogated. Conclusion: These findings demonstrate the effect of DG on inhibiting the resilient breast CSCs which could provide a benchmark for the development of DG-based therapies in breast cancer treatment. © 2017 Bhuvanalakshmi, Basappa, Rangappa, Dharmarajan, Sethi, Kumar and Warrier

Stemness, Pluripotentiality, and Wnt Antagonism: sFRP4, a Wnt antagonist Mediates Pluripotency and Stemness in Glioblastoma

Background: Chemotherapeutic resistance of glioblastoma has been attributed to a self-renewing subpopulation, the glioma stem cells (GSCs), which is known to be maintained by the Wnt β−catenin pathway. Our previous findings demonstrated that exogeneous addition of the Wnt antagonist, secreted fizzled-related protein 4 (sFRP4) hampered stem cell properties in GSCs. Methods: To understand the molecular mechanism of sFRP4, we overexpressed sFRP4 (sFRP4 OE) in three human glioblastoma cell lines U87MG, U138MG, and U373MG. We also performed chromatin immunoprecipitation (ChIP) sequencing of sFRP4 OE and RNA sequencing of sFRP4 OE and sFRP4 knocked down U87 cells. Results: We observed nuclear localization of sFRP4, suggesting an unknown nuclear role. ChIP-sequencing of sFRP4 pulldown DNA revealed a homeobox Cphx1, related to the senescence regulator ETS proto-oncogene 2 (ETS2). Furthermore, miRNA885, a p53-mediated apoptosis inducer, was upregulated in sFRP4 OE cells. RNA sequencing analysis suggested that sFRP4-mediated apoptosis is via the Fas-p53 pathway by activating the Wnt calcium and reactive oxygen species pathways. Interestingly, sFRP4 OE cells had decreased stemness, but when knocked down in multipotent mesenchymal stem cells, pluripotentiality was induced and the Wnt β-catenin pathway was upregulated. Conclusions: This study unveils a novel nuclear role for sFRP4 to promote apoptosis by a possible activation of DNA damage machinery in glioblastoma

Protocol for the China PEACE (Patient-centered Evaluative Assessment of Cardiac Events) retrospective study of coronary catheterisation and percutaneous coronary intervention

Introduction: During the past decade, the volume of percutaneous coronary intervention (PCI) in China has risen by more than 20-fold. Yet little is known about patterns of care and outcomes across hospitals, regions and time during this period of rising cardiovascular disease and dynamic change in the Chinese healthcare system. Methods and analysis Using the China PEACE (Patient-centered Evaluative Assessment of Cardiac Events) research network, the Retrospective Study of Coronary Catheterisation and Percutaneous Coronary Intervention (China PEACE-Retrospective CathPCI Study) will examine a nationally representative sample of 11 900 patients who underwent coronary catheterisation or PCI at 55 Chinese hospitals during 2001, 2006 and 2011. We selected patients and study sites using a two-stage cluster sampling design with simple random sampling stratified within economical-geographical strata. A central coordinating centre will monitor data quality at the stages of case ascertainment, medical record abstraction and data management. We will examine patient characteristics, diagnostic testing patterns, procedural treatments and in-hospital outcomes, including death, complications of treatment and costs of hospitalisation. We will additionally characterise variation in treatments and outcomes by patient characteristics, hospital, region and study year. Ethics and dissemination The China PEACE collaboration is designed to translate research into improved care for patients. The study protocol was approved by the central ethics committee at the China National Center for Cardiovascular Diseases (NCCD) and collaborating hospitals. Findings will be shared with participating hospitals, policymakers and the academic community to promote quality monitoring, quality improvement and the efficient allocation and use of coronary catheterisation and PCI in China. Registration details http://www.clinicaltrials.gov (NCT01624896)

Depletion of M. tuberculosis GlmU from infected murine lungs effects the clearance of the pathogen

M. tuberculosis N-acetyl-glucosamine-1-phosphate uridyltransferase (GlmUMtb) is a bi-functional enzyme engaged in the synthesis of two metabolic intermediates N-acetylglucosamine-1-phosphate (GlcNAc-1-P) and UDP-GlcNAc, catalyzed by the C- and N-terminal domains respectively. UDP-GlcNAc is a key metabolite essential for the synthesis of peptidoglycan, disaccharide linker, arabinogalactan and mycothiols. While GlmUMtb was predicted to be an essential gene, till date the role of GlmUMtb in modulating the in vitro growth of Mtb or its role in survival of pathogen ex vivo / in vivo have not been deciphered. Here we present the results of a comprehensive study dissecting the role of GlmUMtb in arbitrating the survival of the pathogen both in vitro and in vivo. We find that absence of GlmUMtb leads to extensive perturbation of bacterial morphology and substantial reduction in cell wall thickness under normoxic as well as hypoxic conditions. Complementation studies show that the acetyl- and uridyl- transferase activities of GlmUMtb are independently essential for bacterial survival in vitro and GlmUMtb is also found to be essential for mycobacterial survival in THP-1 cells as well as in guinea pigs. Depletion of GlmUMtb from infected murine lungs, four weeks post infection, led to significant reduction in the bacillary load. The administration of Oxa33, a novel oxazolidine derivative that specifically inhibits GlmUMtb, to infected mice resulted in significant decrease in the bacillary load. Thus our study establishes GlmUMtb as a strong candidate for intervention measures against established tuberculosis infections

Targeting the PI3K/Akt signaling pathway in gastric carcinoma: A reality for personalized medicine?

Frequent activation of phosphatidylinositol-3 kinases (PI3K)/Akt/mTOR signaling pathway in gastric cancer (GC) is gaining immense popularity with identification of mutations and/or amplifications of PIK3CA gene or loss of function of PTEN, a tumor suppressor protein, to name a few; both playing a crucial role in regulating this pathway. These aberrations result in dysregulation of this pathway eventually leading to gastric oncogenesis, hence, there is a need for targeted therapy for more effective anticancer treatment. Several inhibitors are currently in either preclinical or clinical stages for treatment of solid tumors like GC. With so many inhibitors under development, further studies on predictive biomarkers are needed to measure the specificity of any therapeutic intervention. Herein, we review the common dysregulation of PI3K/Akt/mTOR pathway in GC and the various types of single or dual pathway inhibitors under development that might have a superior role in GC treatment. We also summarize the recent developments in identification of predictive biomarkers and propose use of predictive biomarkers to facilitate more personalized cancer therapy with effective PI3K/Akt/mTOR pathway inhibition

The medically managed patient with severe symptomatic aortic stenosis in the TAVR era: Patient characteristics, reasons for medical management, and quality of shared decision making at heart valve treatment centers

Background Little is known about patients with severe symptomatic aortic stenosis (AS) who receive medical management despite evaluation at a heart valve treatment center. Objective We identified patient characteristics associated with medical management, physician-reported reasons for selecting medical management, and patients’ perceptions of their involvement and satisfaction with treatment selection. Methods and results Of 454 patients evaluated for AS at 9 established heart valve treatment centers from December 12, 2013 to August 19, 2014, we included 407 with severe symptomatic AS. Information was collected using medical record review and survey of patients and treating physicians. Of 407 patients, 212 received transcatheter aortic valve replacement (TAVR), 124 received surgical aortic valve replacement (SAVR), and 71 received medical management (no SAVR/TAVR). Thirty-day predicted mortality was higher in patients receiving TAVR (8.7%) or medical management (9.8%) compared with SAVR (3.4%) (P<0.001). Physician-reported reasons for medical management included patient preference (31.0%), medical futility (19.7%), inoperability/anatomic infeasibility (11.3%), and inadequate vascular access (8.5%). Compared with patients receiving AVR, medically managed patients were less likely to report that they received enough information about the pros and cons of treatment options (P = 0.03), that their physicians involved them in treatment decisions (P<0.001), and that final decisions were the right ones (P<0.001). Conclusions Patient preference was the most common physician-reported reason for selecting non-invasive AS management, yet patients not undergoing AVR after valve center evaluation reported being less likely to receive sufficient education about treatment options and more likely to feel uncertain about final treatment decisions. Greater attention to shared decision making may improve the experience of care for this vulnerable group of patients