A prospective study of demographic profile, risk factors and pregnancy outcome in Hepatitis B and Hepatitis C virus positive pregnant women in a tertiary care centre

Background: Viral hepatitis is the most common liver disease in pregnancy and is also the most common cause of jaundice in pregnancy in tropical countries. Risk factors for transmission are intravenous drug abuse, surgical and dental procedures done without adequate sterilization of instruments, sexual route etc. Early diagnosis and management can prevent maternal and fetal complications. This study was done to evaluate the frequency, risk factors and pregnancy outcome in hepatitis B virus (HBV) and hepatitis C virus (HCV) positive antenatal women.Methods: This case control study was conducted in Teerthankar Mahaveer Medical College and Research Centre, Moradabad, Uttar Pradesh, India from January 2017 to June 2018 on total 2511 pregnant women. The serum samples were checked for presence of hepatitis B surface antigen (HBsAg) and presence of IgG antibodies to HCV. Analysis of sociodemographic profile, risk factors and pregnancy outcome were done in all HBV and HCV positive women.Results: Out of 2511 pregnant women, 292 were tested positive for hepatitis. Maximum number of women were in the age group of 21-30 years. Most of the seropositive women were multipara. Frequency of positivity was maximum for HCV (67.1%). The risk factors for transmission in study population were intravenous drug abuse, blood transfusion, history of surgery and tattooing.Conclusions: Hepatitis infection rate is increasing. Universal screening for HBV and HCV can be recommended in pregnant women in developing countries. Education and awareness of public and health care workers can reduce the risk of transmission.

Funding Opportunities of Extramural Grants for Oral Health Researchers in India - A Prospective Approach

Dental research funding is increasing all throughout the globe, yet India has a very small presence at this conference. These organizations fund studies and organize research programs to further dentistry and medical study in India. Writing a grant application for research in the field of oral health is a challenging task for modern dental health professionals. The administrative load at dentistry schools is only one example of the many obstacles to research in the Indian context. In the Indian context, the significance of oral health and associated research is low. Oral health research funding agency, and other related terms were used in a search of Google Scholar, Scopus, and PubMed Medline. This analysis aims to educate Indian oral health professionals about the availability of financial support from a variety of sources

Assessing The Knowledge and Awareness of Malaria Disease Among Healthcare Professionals and Community Workers of Meerut District: A Hospital Based Study

  Introduction: Malaria is a major public health problem in worldwide and causes high morbidity and mortality, despite global efforts to eradicate the disease. The purpose of the research is to analyse the perception and behavioural practices towards malaria detection among healthcare workers. Aim -To analyze the Knowledge & awareness among the healthcare professionals. Material & Method: The pilot cross-sectional survey was carried out for the period of two months. Study included health care professionals, doctors and community workers who were working in private hospitals. Convenience sampling was used and total 500 participants were included in the study. Results: The least knowledge and awareness were found in Category 3 workers. Conclusion The public health professionals must play a very important role by increasing awareness among population through appropriate education & counselling

Cell cycle-dependent regulation of the bi-directional overlapping promoter of human BRCA2/ZAR2 genes in breast cancer cells

<p>Abstract</p> <p>Background</p> <p>BRCA2 gene expression is tightly regulated during the cell cycle in human breast cells. The expression of BRCA2 gene is silenced at the G0/G1 phase of cell growth and is de-silenced at the S/G2 phase. While studying the activity of BRCA2 gene promoter in breast cancer cells, we discovered that this promoter has bi-directional activity and the product of the reverse activity (a ZAR1-like protein, we named ZAR2) silences the forward promoter at the G0/G1 phase of the cell. Standard techniques like cell synchronization by serum starvation, flow cytometry, N-terminal or C-terminal FLAG epitope-tagged protein expression, immunofluorescence confocal microscopy, dual luciferase assay for promoter evaluation, and chromatin immunoprecipitation assay were employed during this study.</p> <p>Results</p> <p>Human <it>BRCA2 </it>gene promoter is active in both the forward and the reverse orientations. This promoter is 8-20 fold more active in the reverse orientation than in the forward orientation when the cells are in the non-dividing stage (G0/G1). When the cells are in the dividing state (S/G₂), the forward activity of the promoter is 5-8 folds higher than the reverse activity. The reverse activity transcribes the ZAR2 mRNA with 966 nt coding sequence which codes for a 321 amino acid protein. ZAR2 has two C4 type zinc fingers at the carboxyl terminus. In the G0/G1 growth phase ZAR2 is predominantly located inside the nucleus of the breast cells, binds to the BRCA2 promoter and inhibits the expression of BRCA2. In the dividing cells, ZAR2 is trapped in the cytoplasm.</p> <p>Conclusions</p> <p><it>BRCA2 </it>gene promoter has bi-directional activity, expressing BRCA2 and a novel C4-type zinc finger containing transcription factor ZAR2. Subcellular location of ZAR2 and its expression from the reverse promoter of the BRCA2 gene are stringently regulated in a cell cycle dependent manner. ZAR2 binds to BRCA2/ZAR2 bi-directional promoter <it>in vivo </it>and is responsible, at least in part, for the silencing of BRCA2 gene expression in the G0/G1 phase in human breast cells.</p

Discussion of costs and financial burden in clinical practice: A survey of medical oncologists in Australia

Background A diagnosis of cancer is associated with significant physical, psychological and financial burden. Including costs of cancer is an important component of shared decision making. Doctors bear a responsibility towards educating patients about the financial aspects of care. Multiple organisations have advocated for price transparency and implementing Informed Financial Consent in the clinic. However, few studies have evaluated the perspectives of oncologists on the current state of this discussion. Aims The aim of this study is to determine the views and perspectives of medical oncologists regarding communication of costs and financial burden in patients with cancer. Methods We conducted a prospective cross-sectional online survey via REDCap. The survey was distributed to medical oncologists and advanced trainees currently registered with Medical Oncology Group of Australia (MOGA). Data was collected using the online survey comprising socio-demographic characteristics, discussion of costs and financial burden, and facilitators and barriers to these discussions. Results 547 members of MOGA were invited to participate in the study, and 106 of 547 MOGA members (19%) completed the survey. Most oncologists (66%) felt that it was their responsibility to discuss costs of care, however a majority of oncologists (59.3%) reported discussing costs with less than half of their patients. Only 25% of oncologists discussed financial concerns with more than half of their patients, and most oncologists were unfamiliar with cancer-related financial burden. Most Oncologists with greater clinical experience and those working in private practice were more likely to discuss costs with a majority of their patients. Conclusions Certain characteristics of medical oncologists and their practices were associated with reported prevalence of discussing costs of care and financial burden with their patients. In the context of rising costs of cancer care, interventions targeting modifiable factors such as raising oncologist awareness of costs of care and financial burden, screening for financial toxicity and availability of costs information in an easily accessible manner, may help increase the frequency of patient-doctor discussions about costs of care, contributing to informed decision-making and higher-quality cancer care

Differential regulation of microRNA-15a by radiation affects angiogenesis and tumor growth via modulation of acid sphingomyelinase

Producción CientíficaActivation of acid sphingomyelinase (SMPD1) and the generation of ceramide is a critical regulator of apoptosis in response to cellular stress including radiation. Endothelial SMPD1 has been shown to regulate tumor responses to radiation therapy. We show here that the SMPD1 gene is regulated by a microRNA (miR), miR-15a, in endothelial cells (ECs). Standard low dose radiation (2 Gy) upregulates miR-15a and decreases SMPD1 levels. In contrast, high dose radiation (10 Gy and above) decreases miR-15a and increases SMPD1. Ectopic expression of miR-15a decreases both mRNA and protein levels of SMPD1. Mimicking the effects of high dose radiation with a miR-15a inhibitor decreases cell proliferation and increases active Caspase-3 & 7. Mechanistically, inhibition of miR-15a increases inflammatory cytokines, activates caspase-1 inflammasome and increases Gasdermin D, an effector of pyroptosis. Importantly, both systemic and vascular-targeted delivery of miR-15a inhibitor decreases angiogenesis and tumor growth in a CT26 murine colorectal carcinoma model. Taken together, our findings highlight a novel role for miR mediated regulation of SMPD1 during radiation responses and establish proof-of-concept that this pathway can be targeted with a miR inhibitor.This work was supported by US NIH (grant R01HL137779 and R01HL143803) to S.AASTRO (Grant ID 534775

Physician-patient communication of costs and financial burden of cancer and its treatment: a systematic review of clinical guidelines

Background Optimising the care of individuals with cancer without imposing significant financial burden related to their anticancer treatment is becoming increasingly difficult. The American Society of Clinical Oncology (ASCO) has recommended clinicians discuss costs of cancer care with patients to enhance shared decision-making. We sought information to guide oncologists’ discussions with patients about these costs. Methods We searched Medline, EMBASE and clinical practice guideline databases from January 2009 to 1 June 2019 for recommendations about discussing the costs of care and financial burden. Guideline quality was assessed with the AGREE-II instrument. Results Twenty-seven guidelines met our eligibility criteria, including 16 from ASCO (59%). 21 of 27 (78%) guidelines included recommendations about discussion or consideration of treatment costs when prescribing, with information about actual costs in four (15%). Recognition of the risk of financial burden or financial toxicity was described in 81% (22/27) of guidelines. However, only nine guidelines (33%) included information about managing the financial burden. Conclusions Current clinical practice guidelines have little information to guide physician-patient discussions about costs of anticancer treatment and management of financial burden. This limits patients’ ability to control costs of treatment, and for the healthcare team to reduce the incidence and severity of financial burden. Current guidelines recommend clinician awareness of price variability and high costs of treatment. Clinicians are recommended to explore cost concerns and address financial worries, especially in high risk groups. Future guidelines should include advice on facilitating cost transparency discussions, with provision of cost information and resources

BCL6-mediated repression of p53 is critical for leukemia stem cell survival in chronic myeloid leukemia

Chronic myeloid leukemia (CML) is induced by the oncogenic BCR-ABL1 tyrosine kinase and can be effectively treated for many years with tyrosine kinase inhibitors (TKIs). However, unless CML patients receive life-long TKI treatment, leukemia will eventually recur; this is attributed to the failure of TKI treatment to eradicate leukemia-initiating cells (LICs). Recent work demonstrated that FoxO factors are critical for maintenance of CML-initiating cells; however, the mechanism of FoxO-dependent leukemia initiation remained elusive. Here, we identified the BCL6 protooncogene as a critical effector downstream of FoxO in self-renewal signaling of CML-initiating cells. BCL6 represses Arf and p53 in CML cells and is required for colony formation and initiation of leukemia. Importantly, peptide inhibition of BCL6 in human CML cells compromises colony formation and leukemia initiation in transplant recipients and selectively eradicates CD34+ CD38− LICs in patient-derived CML samples. These findings suggest that pharmacological inhibition of BCL6 may represent a novel strategy to eradicate LICs in CML. Clinical validation of this concept could limit the duration of TKI treatment in CML patients, which is currently life-long, and substantially decrease the risk of blast crisis transformation

MARCKS is a Critical Downstream Mediator of IL-1-driven AML Progression

Acute myeloid leukemia (AML) is a cancer of the blood and bone marrow that is genetically heterogeneous, which has made finding lasting treatment options difficult. Of particular interest in the study of AML is the proinflammatory cytokine IL-1, which we have shown to promote the growth of AML cells while suppressing the growth of normal progenitors. An RNA-seq analysis of primary AML samples after IL-1 stimulation was performed and revealed that myristoylated alanine-rich C-kinase substrate (MARCKS) was a differentially expressed gene in AML compared to healthy controls. RNA-seq analysis of 451 primary patient samples also found MARCKS and IL1R1 expressions to be positively correlated. The results of qPCR and western blot experiments revealed that MARCKS mRNA expression, protein level, and activation are increased in primary AML cells compared to healthy controls after IL-1b treatment. To further elucidate the role of MARCKS in AML, genetic knockdown of MARCKS using doxycycline inducible shRNAs was performed in MOLM-14 and THP-1 cell lines. Results indicate that genetic knockdown of MARCKS reduces the viability, growth, and colony formation ability of AML cells in vitro. Understanding the role of MARCKS in IL-1-mediated AML is important for providing a potential avenue for targeted therapy