Bile Acid-Induced Virulence Gene Expression of Vibrio parahaemolyticus Reveals a Novel Therapeutic Potential for Bile Acid Sequestrants

Vibrio parahaemolyticus, a bacterial pathogen, causes human gastroenteritis. A type III secretion system (T3SS2) encoded in pathogenicity island (Vp-PAI) is the main contributor to enterotoxicity and expression of Vp-PAI encoded genes is regulated by two transcriptional regulators, VtrA and VtrB. However, a host-derived inducer for the Vp-PAI genes has not been identified. Here, we demonstrate that bile induces production of T3SS2-related proteins under osmotic conditions equivalent to those in the intestinal lumen. We also show that bile induces vtrA-mediated vtrB transcription. Transcriptome analysis of bile-responsive genes revealed that bile strongly induces expression of Vp-PAI genes in a vtrA-dependent manner. The inducing activity of bile was diminished by treatment with bile acid sequestrant cholestyramine. Finally, we demonstrate an in vivo protective effect of cholestyramine on enterotoxicity and show that similar protection is observed in infection with a different type of V. parahaemolyticus or with non-O1/non-O139 V. cholerae strains of vibrios carrying the same kind of T3SS. In summary, these results provide an insight into how bacteria, through the ingenious action of Vp-PAI genes, can take advantage of an otherwise hostile host environment. The results also reveal a new therapeutic potential for widely used bile acid sequestrants in enteric bacterial infections

International Consensus Statement on Rhinology and Allergy: Rhinosinusitis

Background: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR‐RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR‐RS‐2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence‐based findings of the document. Methods: ICAR‐RS presents over 180 topics in the forms of evidence‐based reviews with recommendations (EBRRs), evidence‐based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary. Results: ICAR‐RS‐2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence‐based management algorithm is provided. Conclusion: This ICAR‐RS‐2021 executive summary provides a compilation of the evidence‐based recommendations for medical and surgical treatment of the most common forms of RS

Coagulation abnormalities in dengue hemorrhagic Fever: serial investigations in 167 Vietnamese children with Dengue shock syndrome.

The pathophysiological basis of hemorrhage in dengue infections remains poorly understood, despite the increasing global importance of these infections. A large prospective study of 167 Vietnamese children with dengue shock syndrome documented only minor prolongations of prothrombin and partial thromboplastin times but moderate to severe depression of plasma fibrinogen concentrations. A detailed study of 48 children revealed low plasma concentrations of the anticoagulant proteins C, S, and antithrombin III, which decreased with increasing severity of shock, probably because of capillary leakage. Concurrent increases in the levels of thrombomodulin, tissue factor, and plasminogen activator inhibitor type 1 (PAI-1) indicated increased production of these proteins. Thrombomodulin levels suggestive of endothelial activation correlated with increasing shock severity, whereas PAI-1 levels correlated with bleeding severity. Dengue virus can directly activate plasminogen in vitro. Rather than causing true disseminated intravascular coagulation, dengue infection may activate fibrinolysis primarily, degrading fibrinogen directly and prompting secondary activation of procoagulant homeostatic mechanisms

Histopathological characteristics of breast carcinomas at the Olabisi Onabanjo University Teaching Hospital, Sagamu Ogun State, Nigeria

This study examines the pathological grade as well as the estrogen progesterone receptor (ERPR) status in breast cancer materials from Olabisi Onabanjo University Teaching Hospital, Sagamu, Nigeria. All histopathologically diagnosed tissue samples from the department of Histopathology of the Olabisi Onabanjo University Teaching Hospital, Sagamu seen from January 2003 to December 2004 were examined and graded using the Elston and Ellis Modification of the Scarff-Bloom –Richardson grading system1 and stained for their estrogen/progesterone receptor status. Forty- seven cases of breast carcinoma were seen during the period under study. Of these, 44(93.7%) were invasive ductal carcinoma, with majority being poorly differentiated. Their ages ranged from 25-75 years with majority in the age group 40-59years. The mean age was 47.3 years. Of the 27 cases that had their ERPR status analyzed, 21 cases (77.8%) were ERPR negative, while only 3 (11.1%) were ERPR positive. This study shows that there is a predominance of high grade invasive ductal carcinomas that are likely to be ERPR negative. These features suggest a biologically aggressive form of breast cancer in Nigeria with the possibility of poor response to hormonal therapy. Nigerian Journal of Health and Biomedical Sciences Vol. 7 (1) 2008 pp. 23-2

Unmasking inequalities : sub-national maternal and child mortality data from two urban slums in Lagos, Nigeria tells the story

Nigeria has one of the highest maternal mortality ratios in the world as well as high perinatal mortality. Unfortunately, the country does not have the resources to assess this critical indicator with the conventional health information system and measuring its progress toward the goal of ending preventable maternal deaths is almost impossible. Médecins Sans Frontières (MSF) conducted a cross-sectional study to assess maternal and perinatal mortality in Makoko Riverine and Badia East, two of the most vulnerable slums of Lagos.; The study was a cross-sectional, community-based household survey. Nearly 4,000 households were surveyed. The sisterhood method was utilized to estimate maternal mortality and the preceding births technique was used to estimate newborn and child mortality. Questions regarding health seeking behavior were posed to female interviewees and self-reported data were collected.; Data was collected from 3963 respondents for a total of 7018 sisters ever married. The maternal mortality ratio was calculated at 1,050/100,000 live births (95% CI: 894-1215), and the lifetime risk of maternal death at 1:18. The neonatal mortality rate was extracted from 1967 pregnancies reported and was estimated at 28.4/1,000; infant mortality at 43.8/1,000 and under-five mortality at 103/1,000. Living in Badia, giving birth at home and belonging to the Egun ethnic group were associated with higher perinatal mortality. Half of the last pregnancies were reportedly delivered in private health facilities. Proximity to home was the main influencing factor (32.4%) associated with delivery at the health facility.; The maternal mortality ratio found in these urban slum populations within Lagos is extremely high, compared to the figure estimated for Lagos State of 545 per 100,000 live births. Urgent attention is required to address these neglected and vulnerable neighborhoods. Efforts should be invested in obtaining data from poor, marginalized, and hard-to-reach populations in order to identify pockets of marginalization needing additional resources and tailored approaches to guarantee equitable treatment and timely access to quality health services for vulnerable groups. This study demonstrates the importance of sub-regional, disaggregated data to identify and redress inequities that exist among poor, remote, vulnerable populations-as in the urban slums of Lagos