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Nowadays, chronic alcoholism and its health implications represent a global concern. Over three million deaths are linked to chronic alcohol intake every year. This article aims to spread awareness about the negative impact ethanol can have on almost every organ in the body, especially the liver. Understanding ethanol metabolism and the cellular pathways through which alcohol increases liver oxidative stress may prevent a broad spectrum of hepatic lesions such as steatosis, steatohepatitis, and, ultimately, cirrhosis. After a short review of ethanol metabolism and liver oxidative stress, each hepatic lesion will be individually discussed regarding the mechanism of apparition, treatment, and future targeted therapies.

This 10-year retrospective cohort study at a single-center clinic in Germany aimed to analyze the outcomes of endometrial cancer patients and explore the impact of lymphovascular invasion (LV) on patient outcomes and disease-free survival (DFS). Identifying correlations among demographic data, tumor characteristics, treatment modalities, and survival outcomes could enhance patient management and improve survival rates. The study encompassed patients diagnosed and treated for endometrial cancer from January 2010 to December 2020. Clinical and pathological data were extracted from medical records for 311 patients, focusing on variables such as age, histological type, tumor grade, type of surgical treatment, and adjuvant therapies. Survival analysis was conducted using the Kaplan–Meier method and multivariate Cox proportional hazard models to identify factors independently associated with survival. The study demonstrated that lymphovascular invasion significantly impacted survival outcomes on Kaplan–Meier analysis (log-rank p-value = 0.0058). Patients with LV showed a marked decrease in DFS compared to those without LV invasion, with a median DFS of 3.2 years and a hazard ratio of 2.18 (95% CI: 1.56–3.04, p < 0.001). Furthermore, high-grade tumors and p53 positivity were strongly associated with reduced DFS, with hazard ratios of 1.93 (p = 0.001) and 2.11 (p < 0.001), respectively. Patients with distant metastasis exhibited the most significant decline in survival, with a hazard ratio of 5.56 (95% CI: 2.45–10.18, p < 0.001). Despite comprehensive surgical and adjuvant therapies, these high-risk factors dictated poorer outcomes. The presence of lymphovascular invasion, high-grade tumors, and genetic markers like MSI and p53 are pivotal in predicting the course of endometrial cancer. This study underscores the necessity for aggressive management strategies in patients exhibiting these high-risk features to potentially improve prognosis and survival outcomes. The findings advocate for enhanced therapeutic strategies tailored to the biological behavior of the tumor, thereby aiming to elevate the overall survival rates for women diagnosed with endometrial cancer.

This paper estimates family spillovers in high school major choice in Sweden, where admission to oversubscribed majors is determined based on GPA. Using a regression discontinuity design, we find large sibling and intergenerational spillovers that depend on the sex mix of a dyad. Same-sex siblings copy one another, while younger brothers recoil from an older sister’s choices. Fathers and mothers influence sons but not their daughters, except when a mother majors in the male-dominated program of engineering. Back-of-the-envelope calculations reveal that these within-family spillovers have sizable implications for the sex composition of majors. (JEL I21, J12, J13, J16)

AbstractDespite cold-water coral (CWC) reefs being considered biodiversity hotspots, very little is known about the main processes driving their morphological development. Indeed, there is a considerable knowledge gap in quantitative experimental studies that help understand the interaction between reef morphology, near-bed hydrodynamics, coral growth, and (food) particle transport processes. In the present study, we performed a 2-month long flume experiment in which living coral nubbins were placed on a reef patch to determine the effect of a unidirectional flow on the growth and physiological condition of Lophelia pertusa. Measurements revealed how the presence of coral framework increased current speed and turbulence above the frontal part of the reef patch, while conditions immediately behind it were characterised by an almost stagnant flow and reduced turbulence. Owing to the higher current speeds that likely promoted a higher food encounter rate and intake of ions involved in the calcification process, the coral nubbins located on the upstream part of the reef presented a significantly enhanced average growth and a lower expression of stress-related enzymes than the downstream ones. Yet, further experiments would be needed to fully quantify how the variations in water hydrodynamics modify particle encounter and ion intake rates by coral nubbins located in different parts of a reef, and how such discrepancies may ultimately affect coral growth. Nonetheless, the results acquired here denote that a reef influenced by a unidirectional water flow would grow into the current: a pattern of reef development that coincides with that of actual coral reefs located in similar water flow settings. Ultimately, the results of this study suggest that at the local scale coral reef morphology has a direct effect on coral growth thus, indicating that the spatial patterns of living CWC colonies in reef patches are the result of spatial self-organisation.

Several human diseases are caused by enteroviruses and are currently clinically untreatable, pushing the research to identify new antivirals. A notable number of benzo[d][1,2,3]triazol-1(2)-yl derivatives were designed, synthesized, and in vitro evaluated for cytotoxicity and antiviral activity against a wide spectrum of RNA positive- and negative-sense viruses. Five of them (11b, 18e, 41a, 43a, 99b) emerged for their selective antiviral activity against Coxsackievirus B5, a human enteroviruses member among the Picornaviridae family. The EC50 values ranged between 6 and 18.5 μM. Among all derivatives, compounds 18e and 43a were interestingly active against CVB5 and were selected to better define the safety profile on cell monolayers by transepithelial resistance test (TEER). Results indicated compound 18e as the hit compound to investigate the potential mechanism of action by apoptosis assay, virucidal activity test, and the time of addition assay. CVB5 is known to be cytotoxic by inducing apoptosis in infected cells; in this study, compound 18e was proved to protect cells from viral infection. Notably, cells were mostly protected when pre-treated with derivative 18e, which had, however, no virucidal activity. From the performed biological assays, compound 18e turned out to be non-cytotoxic as well as cell protective against CVB5 infection, with a mechanism of action ascribable to an interaction on the early phase of infection, by hijacking the viral attachment process.

Additional file 3: Tables S2. Working status (full-time compared with ‘other’) by demographic variables in a random sample of community-dwelling, working-aged people (n = 6064) in South Australia (unweighted data). Table S3. Odds ratios of complete model of associations of breathlessness with working status stratified by age in a random sample of community-dwelling, working-aged people (n = 6064) in South Australia (weighted data). Table S4. Odds ratios of complete model of associations of breathlessness with working status stratified by sex in a random sample of community-dwelling, working-aged people (n = 6064) in South Australia (weighted data).

BackgroundCirculating microRNAs (miRNAs) have been found to have different expressions in different phases of acute myocardial infarction. The profiles of plasma exosome miRNAs in patients with ST-segment elevation myocardial infarction (STEMI) at 3–6 months postinfarction are unknown.ObjectiveThe aim of this study was to assess the profiles of plasma exosome miRNAs in patients with STEMI in comparison with healthy volunteers and to select specific exosome miRNAs related to pathophysiological changes post-STEMI.MethodsPlasma and echocardiography parameters were collected from 30 patients 3–6 months after STEMI and 30 healthy volunteers. Plasma exosome miRNAs were assessed by using high-throughput sequence (Illumina HiSeq 2500) and profile of the plasma exosome miRNAs was established in 10 patients and 6 healthy volunteers. The specific exosome miRNAs related to heart diseases were selected according to the TargetScan database. The specificity of the selected exosome miRNAs was evaluated in additional 20 post-STEMI patients and 24 healthy volunteers by using quantitative PCR (qPCR). Left ventricular remodeling (LVR) was defined using the European Association of Cardiovascular Imaging criteria according to echocardiography examination. Correlations between expression of the specific miRNAs and echocardiography parameters of LVR were assessed using the Spearman correlation analysis.ResultsTwenty eight upregulated miRNAs and 49 downregulated miRNAs were found in patients 3–6 months after STEMI (p &lt; 0.01) in comparison with the healthy volunteers. The two least expressed and heart-related exosome miRNAs were hsa-miR-181a-3p (0.64-fold, p &lt; 0.01) and hsa-miR-874-3p (0.50-fold, p &lt; 0.01), which were further confirmed by using qPCR and demonstrated significant specificity in another 20 patients with post-STEMI comparing to 24 healthy volunteers [area under the curve (AUC) = 0.68, p &lt; 0.05; AUC = 0.74, p &lt; 0.05]. The expression of hsa-miR-181a-3p was downregulated in patients with LV adverse remodeling in comparison with patients without LV adverse remodeling and healthy volunteers.ConclusionCirculating exosome miR-874-3p and miR-181a-3p were downregulated in patients with STEMI postinfarction. Exosome hsa-miR-181a-3p might play a potential role in the development of LVR in patients with post-STEMI.