Prognostic significance of CTNNB1 mutation in early stage endometrial carcinoma: a systematic review and meta-analysis

Background In the last years, mutations in the exon 3 of CTNNB1 have emerged as a possible prognostic factor for recurrence in early stage endometrioid endometrial carcinoma, especially in cases with no specific molecular profile (NSMP). Objective To define the prognostic value of CTNNB1 mutations in early stage endometrioid endometrial carcinoma, through a systematic review and meta-analysis. Methods Electronic databases were searched from their inception to November 2020 for all studies assessing the prognostic value of CTNNB1 mutation in early stage (FIGO I–II) endometrioid endometrial carcinoma. Odds ratio (OR) for tumor recurrence and hazard ratio (HR) for disease-free survival (DFS) were calculated with a significant p value < 0.05. Results Seven studies with 1031 patients were included. Four studies were suitable for meta-analysis of OR and showed significant association between CTNNB1 mutation and the absolute number of recurrence (OR = 3.000; p = 0.019); the association became stronger after excluding patients with known molecular status other than NSMP (HR = 5.953; p = 0.012). Three studies were suitable for meta-analysis of HR and showed no significant association between CTNNB1 mutation and decreased DFS (HR = 1.847; p = 0.303); the association became significant after excluding patients with known molecular status other than NSMP (HR = 2.831; p = 0.026). Conclusion CTNNB1 mutation is significantly associated with recurrence in early stage endometrioid endometrial carcinomas, especially in the NSMP, appearing potentially useful in directing adjuvant treatment.

Specificities and Commonalities of Carbapenemase-Producing Escherichia coli Isolated in France from 2012 to 2015

Carbapenemase-producing Escherichia coli (CP- Ec ) might be difficult to detect, as MICs can be very low. However, their absolute number and their proportion among carbapenem-resistant Enterobacterales have been increasing, as reported by WHO and national surveillance programs.

Healthcare financing in Egypt: a systematic literature review.

Background The Egyptian healthcare system has multiple stakeholders, including a wide range of public and private healthcare providers and several financing agents. This study sheds light on the healthcare system’s financing mechanisms and the flow of funds in Egypt. It also explores the expected challenges facing the system with the upcoming changes. Methods We conducted a systematic review of relevant papers through the PubMed and Scopus search engines, in addition to searching gray literature through the ISPOR presentations database and the Google search engine. Articles related to Egypt’s healthcare system financing from 2009 to 2019 were chosen for full-text review. Data were aggregated to estimate budgets and financing routes. Results We analyzed the data of 56 out of 454 identified records. Governmental health expenditure represented approximately one-third of the total health expenditure (THE). Total health expenditure as a percent of gross domestic product (GDP) was almost stagnant in the last 12 years, with a median of 5.5%. The primary healthcare financing source is out-of-pocket (OOP) expenditure, representing more than 60% of THE, followed by government spending through the Ministry of Finance, around 37% of THE. The pharmaceutical expenditure as a percent of THE ranged from 26.0 to 37.0%. Conclusions Although THE as an absolute number is increasing, total health expenditure as a percentage of GDP is declining. The Egyptian healthcare market is based mainly on OOP expenditures and the next period anticipates a shift toward more public spending after Universal Health Insurance gets implemented.

Infertility, Miscarriage, Stillbirth, and the Risk of Stroke Among Women: A Systematic Review and Meta-Analysis

Background and Purpose: Stroke is one of the leading causes of mortality, and women are impacted more from stroke than men in terms of their absolute number and in having worse outcomes. A growing number of studies have explored the association between pregnancy complications, pregnancy outcomes, and stroke. Limited studies, however, have investigated links involving infertility, miscarriage, and stillbirth, which could plausibly be associated via a background of endocrine conditions, endothelial dysfunction, and chronic systematic inflammation. This review aims to summarize current evidence and provide up-to-date information on the associations of infertility, miscarriage, and stillbirth, with stroke incidence. Methods: A comprehensive literature search was conducted for cohort and case-control studies on associations between infertility, miscarriage, stillbirth, and stroke up to September 26, 2020. Seven databases were searched: PubMed, Embase, Cochrane, CINIHL, PsyclNFO, Wanfang, and CNKI. Random-effects models were used to estimate the pooled hazard ratios (HRs) and 95% CIs. Results: Sixteen cohort studies and 2 case-control studies enrolling 7 808 521 women were included in this meta-analysis. Women who had experienced miscarriage or stillbirth were at higher risk of stroke (miscarriage: HR, 1.07 [95% CI, 1.00–1.14]; stillbirth: HR, 1.38 [95% CI, 1.11–1.71]) than other women. The HRs of stroke for each additional miscarriage and stillbirth were 1.13 (95% CI, 0.96–1.33) and 1.25 (95% CI, 1.06–1.49), respectively. In subgroup analysis, increased risk of stroke was associated with repeated miscarriages and stillbirths (miscarriage ≥3: HR, 1.42 [95% CI, 1.05–1.90]; stillbirth ≥2: HR, 1.14 [95% CI, 1.04–1.26]). Associations between infertility and stroke were inconsistent and inconclusive (HR, 1.07 [95% CI, 0.87–1.32]). Conclusions: Miscarriage and stillbirth are associated with increased risk of stroke among women, which could be used as a contributing risk factor to help identify women at higher risk of stroke.

Immunization Trials with Recombinant Major Sperm Protein of the Bovine Lungworm Dictyocaulus viviparus

The lungworm Dictyocaulus viviparus is one of the most economically important bovine parasites in temperate climate regions. Following infection, D. viviparus induces a temporary protective immunity, and a vaccine based on attenuated, infective larvae is commercially available. However, due to several disadvantages of the live vaccine, the development of a recombinant subunit vaccine is highly desirable. Therefore, the major sperm protein (MSP), which is essential for the parasite’s reproduction, was tested as a recombinantly Escherichia coli-expressed glutathione-S-transferase (GST)-fused vaccine antigen in immunization trials with two different adjuvants, Quil A and Al(OH)3. Calves (N = 4 per group) were immunized on study day (SD) 0, 21 and 42 and given a challenge infection on SD 63–65. The two control groups received only the respective adjuvant. Based on geometric means (GM), a 53.64% reduction in larvae per female worm was observed in the rMSP Quil A group vs. its control group (arithmetic means (AM): 54.43%), but this difference was not statistically significant. In the rMSP Al(OH)3 group, the mean number of larvae per female worm was even higher than in the respective control group (GM: 9.24%, AM: 14.14%). Furthermore, male and female worm burdens and the absolute number of larvae did not differ significantly, while the Al(OH)3 control group harbored significantly longer worms than the vaccinated group. Vaccinated animals showed a rise in rMSP-specific antibodies, particularly IgG and its subclass IgG1, and the native protein was detected by immunoblots. Although rMSP alone did not lead to significantly reduced worm fecundity, it might still prove useful as part of a multi-component vaccine.

Counting fluorescently labeled proteins in tissues in the spinning disk microscope using single-molecule calibrations

Quantification of molecular numbers and concentrations in living cells is critical for testing models of complex biological phenomena. Counting molecules in cells requires estimation of the fluorescence intensity of single molecules, which is generally limited to imaging near cell surfaces, in isolated cells, or where motions are diffusive. To circumvent this difficulty, we have devised a calibration technique for spinning-disk confocal (SDC) microscopy, commonly used for imaging in tissues, that uses single-step bleaching kinetics to estimate the single-fluorophore intensity. To cross-check our calibrations, we compared the brightness of fluorophores in the SDC microscope to those in the total-internal-reflection (TIRF) and epifluorescence microscopes. We applied this calibration method to quantify the number of EB1-eGFP proteins in the comets of growing microtubule ends and to measure the cytoplasmic concentration of EB1-eGFP in sensory neurons in fly larvae. These measurements allowed us to estimate the dissociation constant of EB1-eGFP from the microtubules as wells as the GTP-tubulin cap size. Our results show the unexplored potential of single-molecule imaging using spinning disk confocal microscopy and provide a straight-forward method to count the absolute number of fluorophores in tissues which can be applied to a wide range of biological systems and imaging techniques.

Retrospective analysis of adverse effects associated with pyrethrins-containing products

The Pyrethrins Stewardship Program (PSP) was established to better understand adverse effects following exposure to pyrethrins-containing insecticide products. Running from April 2010 through December 2016, symptomatic dermal and inhalation exposures were entered into Phase I of the PSP and analyzed for exposure details and nature of the effects reported. Phase II consisted of an in-depth telephone interview using an enhanced questionnaire to investigate additional exposure details. Phase III scored the association between exposure and reported effects. Based on the data collected and analyzed, we conclude that: (1) Both in absolute number and relative to the wide distribution and use by consumers, adverse respiratory or dermal events after product exposure were rare; (2) Most outcomes for the reported events involving either dermal or respiratory effects were of minor severity and self-limiting; (3) None of the data collected and analyzed indicate that pyrethrins-containing products, including those formulated with synthetic pyrethroids and/or synergists, pose a significant risk of serious dermal or respiratory reactions even in cases where the exposed individual reported having allergies or asthma; (4) No additional label warnings or other mitigation techniques are warranted with pyrethrins-containing products formulated with or without synthetic pyrethroids and/or synergists.

World Stroke Organization (WSO): Global Stroke Fact Sheet 2022

Stroke remains the second-leading cause of death and the third-leading cause of death and disability combined (as expressed by disability-adjusted life-years lost – DALYs) in the world. The estimated global cost of stroke is over US$721 billion (0.66% of the global GDP). From 1990 to 2019, the burden (in terms of the absolute number of cases) increased substantially (70.0% increase in incident strokes, 43.0% deaths from stroke, 102.0% prevalent strokes, and 143.0% DALYs), with the bulk of the global stroke burden (86.0% of deaths and 89.0% of DALYs) residing in lower-income and lower-middle-income countries (LMIC). This World Stroke Organisation (WSO) Global Stroke Fact Sheet 2022 provides the most updated information that can be used to inform communication with all internal and external stakeholders; all statistics have been reviewed and approved for use by the WSO Executive Committee as well as leaders from the Global Burden of Disease research group.

Analysis of Factors Associated with the Risk of Suicide in a Brazilian Capital: Cross-Sectional Study

Suicide and suicide attempts are considered global health problems. With regard to the main causes of unnatural deaths, Brazil ranks as the eighth country with the highest absolute number of suicides. The aim of this study was to analyze the factors associated with the risk of suicide in a metropolitan city in Brazil. This was a cross-sectional study carried out in Recife, in the northeast region of Brazil. Epidemiological surveillance was conducted on the information systems regarding attempted suicide, suicide, and undetermined deaths in the period from 2007 to 2017. A record linkage between the information systems was performed. Descriptive statistics, bivariate analysis, and logistic regression were performed with an adopted a significance level of 5%. In the city of Recife, there were 4495 suicide attempts in the period, and the most frequent suicide attempts were by single females, aged between 20 and 39 years old, and who used either medication or poison to die by suicide. A total of 141 individuals died by suicide, and exogenous intoxication was the most common method. Knowing the common characteristics and associated factors of those who attempt and die by suicide is key for the development of prevention policies and intervention strategies for suicide.

Shifts in preference for Natural American Spirit and associated belief that one’s own cigarette brand might be less harmful than other brands: results from Waves 1–4 of the Population Assessment of Tobacco and Health (PATH) Study (2013–2018)

IntroductionPeople believe that cigarettes using ‘organic,’ ‘additive-free’ or similar descriptors are less harmful than other cigarettes. Natural American Spirit (NAS) is the most popular US cigarette brand using these descriptors. This cohort study describes changes in US smokers’ odds of preferring NAS and changes in NAS smokers’ odds of believing their brand might be less harmful than other brands.MethodsData come from four waves (2013–2018) of the Population Assessment of Tobacco and Health (PATH) Study. Generalised estimating equations produced population-averaged estimates of relationships between (1) NAS brand preference and wave and (2) belief that one’s own brand might be less harmful than other brands, wave and NAS brand preference. Models tested interactions by age group and sexual minority status.ResultsThe odds that smokers preferred NAS increased by 60% in W4 relative to W1. Disproportionate preference by younger adult and sexual minority smokers was observed. The odds that NAS smokers believed their own brand might be less harmful decreased by 50% between W1 and W4, but this perception was still 16 times higher for NAS compared with non-NAS smokers. Given the increasing preference for NAS, there was no significant change in the absolute number of NAS smokers who believed their own brand might be less harmful (W1: 562 122 (95% CI 435 190 to 689 055) vs W4: 580 378 (95% CI 441 069 to 719 689)).ConclusionsBoth brand popularity and concentration of brand-related harm perceptions are important for understanding population impact of changes in cigarette marketing.