Periodontitis and Systemic Diseases: A Review

Periodontitis is one of the inflammatory-infectious diseases of the oral cavity, which results in an alteration in the production of host inflammatory mediators. Oral cavity has plentiful diverse bacteria that can spread different sites of the body particularly in immune compromised individuals and results in various systemic diseases. As the oral cavity is the mirror image of our systemic health, hence maintenance of oral health is equally important. This paper reviews the etiology of periodontitis and systemic relation

Reducing maternal infection after assisted vaginal birth in a diverse and deprived population

Postpartum maternal sepsis is a leading cause of maternal mortality and morbidity. A single dose of prophylactic antibiotics following assisted vaginal births has been shown to significantly reduce postpartum maternal infection in a landmark multicentre randomised controlled trial, which led to its national recommendation. This project aimed to improve the local implementation of prophylactic antibiotics following assisted vaginal births to reduce postnatal maternal infections. Using a prospectively collated birth register, data were collected retrospectively on prophylactic antibiotics administration and postnatal maternal infection rates after assisted vaginal births at the Sandwell and West Birmingham Hospitals National Health Service Trust in North-West Birmingham of the UK. The data were collected from routinely used electronic health records over three audit cycles (n=287) between 2020 and 2023. A mixed-method approach was used to improve the use of prophylactic antibiotics: (1) evidence-based journal clubs targeting doctors in training, (2) presentations of results after all three audit cycles at our and (3) expedited a formal change of local guidelines to support prophylactic antibiotics use. Prophylactic antibiotic administration increased from 13.2% (December 2021) to 90.7% (July 2023), associated with a reduction in maternal infection rates (18.2% when prophylaxis was given vs 22.2% when no prophylaxis was given). However, we observed a gradual increase in the overall postnatal maternal infection rates during the project period. Our repeat audit identified prophylactic antibiotics were regularly omitted after deliveries in labour ward rooms (59.3%), compared with 100% of those achieved in theatre. After further interventions, prophylactic antibiotics administration rates were comparable between these clinical areas (>90%) in 2023. Together, we have demonstrated a simple set of interventions that induced sustainable changes in practice. Further evaluation of other modifiable risk factors and infection rates following all deliveries is warranted in view of the gradual increase in the overall postnatal maternal infection rates

Towards messages that matter: Understanding and addressing HIV and SRH risks among married young people in India

Although there is increasing interest in young people\u27s sexual and reproductive health (SRH) situations and needs in India, married young people have received little attention as a vulnerable group with distinct needs because marriage is assumed to be safe and because married youth are assumed to face none of the stigma that their unmarried counterparts experience in accessing SRH services. However, emerging evidence shows that within this subpopulation, married young women and men constitute groups with distinct risks of HIV and other poor SRH outcomes. There remains a need to better understand their unique vulnerabilities and to design programs that take into account their special circumstances. The Population Council and the Family Planning Association of India undertook a research project intended to better understand the situation and vulnerabilities faced by married young women and men, and to develop communication materials for married young women and men and training materials for providers to address HIV and other SRH risks experienced by these subpopulations. The study was conducted in rural settings in Guntur district of Andhra Pradesh, and in Dhar and Guna districts of Madhya Pradesh

The Orphan Nuclear Receptor LRH-1 and ERα Activate GREB1 Expression to Induce Breast Cancer Cell Proliferation

BACKGROUND: Liver Receptor Homolog 1 (LRH-1, NR5A2) is an orphan nuclear receptor that is over-expressed in cancers in tissues such as the breast, colon and pancreas. LRH-1 plays important roles in embryonic development, steroidogenesis and cholesterol homeostasis. In tumor cells, LRH-1 induces proliferation and cell cycle progression. High LRH-1 expression is demonstrated in breast cancers, positively correlating with ERα status and aromatase activity. LRH-1 dependent cellular mechanisms in breast cancer epithelial cells are poorly defined. Hence in the present study we investigated the actions of LRH-1 in estrogen receptor α (ERα) positive breast cancer cells. RESULTS: The study aimed to investigate LRH-1 dependent mechanisms that promote breast cancer proliferation. We identified that LRH-1 regulated the expression of Growth Regulation by Estrogen in Breast Cancer 1 (GREB1) in MCF-7 and MDA-MB-231 cells. Over-expression of LRH-1 increased GREB1 mRNA levels while knockdown of LRH-1 reduced its expression. GREB1 is a well characterised ERα target gene, with three estrogen response elements (ERE) located on its promoter. Chromatin immunoprecipitation studies provided evidence of the co-localisation of LRH-1 and ERα at all three EREs. With electrophoretic mobility shift assays, we demonstrated direct binding of LRH-1 to EREs located on GREB1 and Trefoil Factor 1 (TFF1, pS2) promoters. LRH-1 and ERα co-operatively activated transcription of ERE luciferase reporter constructs suggesting an overlap in regulation of target genes in breast cancer cells. Over-expression of LRH-1 resulted in an increase in cell proliferation. This effect was more pronounced with estradiol treatment. In the presence of ICI 182,780, an ERα antagonist, LRH-1 still induced proliferation. CONCLUSIONS: We conclude that in ER-positive breast cancer cells, LRH-1 promotes cell proliferation by enhancing ERα mediated transcription of target genes such as GREB-1. Collectively these findings indicate the importance of LRH-1 in the progression of hormone-dependent breast cancer and implicate LRH-1 as a potential avenue for drug development

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Global, regional, and national age-sex-specific mortality for 282 causes of death in 195 countries and territories, 1980-2017: a systematic analysis for the Global Burden of Disease Study 2017.

BACKGROUND: Global development goals increasingly rely on country-specific estimates for benchmarking a nation's progress. To meet this need, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2016 estimated global, regional, national, and, for selected locations, subnational cause-specific mortality beginning in the year 1980. Here we report an update to that study, making use of newly available data and improved methods. GBD 2017 provides a comprehensive assessment of cause-specific mortality for 282 causes in 195 countries and territories from 1980 to 2017. METHODS: The causes of death database is composed of vital registration (VR), verbal autopsy (VA), registry, survey, police, and surveillance data. GBD 2017 added ten VA studies, 127 country-years of VR data, 502 cancer-registry country-years, and an additional surveillance country-year. Expansions of the GBD cause of death hierarchy resulted in 18 additional causes estimated for GBD 2017. Newly available data led to subnational estimates for five additional countries-Ethiopia, Iran, New Zealand, Norway, and Russia. Deaths assigned International Classification of Diseases (ICD) codes for non-specific, implausible, or intermediate causes of death were reassigned to underlying causes by redistribution algorithms that were incorporated into uncertainty estimation. We used statistical modelling tools developed for GBD, including the Cause of Death Ensemble model (CODEm), to generate cause fractions and cause-specific death rates for each location, year, age, and sex. Instead of using UN estimates as in previous versions, GBD 2017 independently estimated population size and fertility rate for all locations. Years of life lost (YLLs) were then calculated as the sum of each death multiplied by the standard life expectancy at each age. All rates reported here are age-standardised

Knowledge and attitude toward informed consent in medical and dental practitioners, of Bhopal City, India

Background: Consent is a lawful right of a patient that makes a decision their involvement in clinical procedures. The meaning of consent is that patient not to be touched or in nevertheless treated without their permission, it deems like an endorsed inquiry for their protection. Concept of consent is an endeavor by which the patient can take part in clinical judgment concerning their treatment and protect each and every patient against any litigation. Thus, knowledge and approach of consent are foremost important due to encroachment in clinical procedures in dental and medical field as well as it is also important for general population. Aim and Objectives: The aim of the study was to appraise the knowledge and attitude toward informed consent in medical and dental practitioners of Bhopal city, India. Materials and Methods: A cross-sectional assessment was carried out among 200 medical and dental practitioners of Bhopal city. A self-administered, close-ended planned questionnaire was used to evaluate their knowledge and attitude regarding informed consent. This questionnaire consists of 10 and 5 questions of knowledge and attitude, respectively. The response format was obtained by a 3-point Likert scale. Statistical analysis was done using SPSS version 20; Chi-square test was used for data analysis. Result: Knowledge and attitude regarding informed consent were uneven amid medical and dental professionals. Although it was slight higher in medical professionals. Conclusion: An unbalanced knowledge of informed consent in medical and dental professionals recommended; a need to conduct assort of awareness programs and workshops regarding informed consent. Thus, this gap of knowledge can fill and an affirmative attitude can develop

Microbial Flora on Aprons of Dental Healthcare Professionals

Objective : To determine the microbial flora present on aprons of dental healthcare professionals in a dental college & hospital. Materials and methods: Total 100 aprons of dental healthcare professionals were included in the study. An informed consent and questionnaire was taken. A cross sectional survey was designed with bacterial contamination of aprons in three predetermined areas (chest, pocket, sleeves). Result: It was observed that 66% of dental healthcare professionals used to wash their aprons once in a week with self grading by the participants, 92% of aprons were moderately clean. 71% of dental health care professionals used to wear their aprons while eating and at nonclinical areas. 88% of chest,84% of pocket and 71% of sleeves of aprons showed growth of microorganisms. Staphylococcus aureus was the most predominant isolate followed by Bacillus species and other all isolates were either environmental microorganisms or skin commensals. Methicillin Resistant Staphylococcus aureus (MRSA) was also found, which was a matter of concern. Conclusions: Aprons are a potential source of cross infection even in dental settings. It is recommended that guidelines should be there for handling and washing procedures of aprons

MiR-155 Negatively Regulates Anti-Viral Innate Responses among HIV-Infected Progressors

HIV infection impairs host immunity, leading to progressive disease. An anti-retroviral treatment efficiently controls viremia but cannot completely restore the immune dysfunction in HIV-infected individuals. Both host and viral factors determine the rate of disease progression. Among the host factors, innate immunity plays a critical role; however, the mechanism(s) associated with dysfunctional innate responses are poorly understood among HIV disease progressors, which was investigated here. The gene expression profiles of TLRs and innate cytokines in HIV-infected (LTNPs and progressors) and HIV-uninfected individuals were examined. Since the progressors showed a dysregulated TLR-mediated innate response, we investigated the role of TLR agonists in restoring the innate functions of the progressors. The stimulation of PBMCs with TLR3 agonist-poly:(I:C), TLR7 agonist-GS-9620 and TLR9 agonist-ODN 2216 resulted in an increased expression of IFN-α, IFN-β and IL-6. Interestingly, the expression of IFITM3, BST-2, IFITM-3, IFI-16 was also increased upon stimulation with TLR3 and TLR7 agonists, respectively. To further understand the molecular mechanism involved, the role of miR-155 was explored. Increased miR-155 expression was noted among the progressors. MiR-155 inhibition upregulated the expression of TLR3, NF-κB, IRF-3, TNF-α and the APOBEC-3G, IFITM-3, IFI-16 and BST-2 genes in the PBMCs of the progressors. To conclude, miR-155 negatively regulates TLR-mediated cytokines as wel l as the expression of host restriction factors, which play an important role in mounting anti-HIV responses; hence, targeting miR-155 might be helpful in devising strategic approaches towards alleviating HIV disease progression