In a randomized trial involving patients at high bleeding risk who received 1 month of dual antiplatelet therapy after PCI, use of polymer-based zotarolimus-eluting stents was noninferior to use of ...polymer-free drug-coated stents with regard to safety and effectiveness composite outcomes.
Genome-wide association (GWA) studies have identified a large number of SNPs associated with disease phenotypes. As most GWA studies have been performed in populations of European descent, this ...Review examines the issues involved in extending the consideration of GWA studies to diverse worldwide populations. Although challenges exist with issues such as imputation, admixture and replication, investigation of a greater diversity of populations could make substantial contributions to the goal of mapping the genetic determinants of complex diseases for the human population as a whole.
Objectives This study sought to assess the extent and composition of atherosclerosis contributing to acute coronary syndrome events in women compared with men. Background Pathological studies suggest ...that plaque composition and burden may differ by sex. It is unclear whether sex impacts the extent, characteristics, and potential vulnerability of coronary plaques. Methods A total of 697 patients (24% women) with acute coronary syndromes were enrolled in the prospective, multicenter PROSPECT (Providing Regional Observations to Study Predictors of Events in the Coronary Tree) study. Three-vessel multimodality intracoronary imaging (quantitative coronary angiography, grayscale, and radiofrequency intravascular ultrasound IVUS) was performed after treatment of the culprit lesion(s). Events during a median 3.4-year follow-up were ascribed to recurrent culprit versus untreated nonculprit lesions. The authors performed a post hoc, sex-based subgroup analysis. Results Women were older and had more comorbid disease than men. By angiography, women had a similar number of angiographic culprit (p = 0.53) but fewer nonculprit (p = 0.05) lesions, and fewer vessels with nonculprit lesions (p = 0.048) compared with men even after multivariable adjustment (p = 0.002). By IVUS, women had fewer nonculprit lesions (p = 0.002), but similar plaque burden (PB) per lesion (55.6% vs. 55.3%; p = 0.35), and female sex was not predictive of severe (>70%) PB (p = 0.052). Plaque rupture was less common in women (6.6% vs. 16.3%; p = 0.002) even after adjusting for comorbidities (p = 0.004), as was the total necrotic core volume (p < 0.0001). The frequency of other plaque phenotypes was similar for men and women including pathological intimal thickening, thin-cap fibroatheromas (TCFA), and thick-cap fibroatheromas. Rates of major adverse cardiovascular events attributed to culprit and nonculprit lesions at 1-, 2-, and 3-year follow-up were not significantly different between men and women, although women were rehospitalized more frequently due to culprit lesion–related angina. For men, nonculprit lesion minimal lumen area ≤4.0 mm2 , PB ≥70%, and TCFA predicted nonculprit MACE at 3 years, whereas for women, only TCFA and PB were predictive. Conclusions The PROSPECT study validates that despite having more comorbid risk factors than men, women have less extensive coronary artery disease by both angiographic and IVUS measures, and that lesions in women compared with men have less plaque rupture, less necrotic core and calcium, similar plaque burden, and smaller lumens. TCFA may also be a stronger marker of plaque vulnerability in women than men.
Type-2 diabetes is associated with severe health outcomes, the effects of which are responsible for approximately 1/4
of the total healthcare spending in the United States (US). Current treatment ...guidelines endorse a massive number of potential anti-hyperglycemic treatment options in various combinations. Strategies for optimizing treatment selection are lacking. Real-world data from a nationwide population of over one million high-risk diabetic patients (HbA1c ≥ 9%) in the US is analyzed to evaluate the comparative effectiveness for HbA1c reduction in this population of more than 80 different treatment strategies ranging from monotherapy up to combinations of five concomitant classes of drugs across each of 10 clinical cohorts defined by age, insulin dependence, and a number of other chronic conditions. A causal deep learning approach developed on such data allows for more personalized evaluation of treatment selection. An average confounder-adjusted reduction in HbA1c of 0.69% -0.75, -0.65 is observed between patients receiving high vs low ranked treatments across cohorts for which the difference was significant. This method can be extended to explore treatment optimization for other chronic conditions.
Although children start to adopt gender stereotypes by the age of three, there is less evidence about how early they start to sanction other children’s counter-stereotypical behaviors. The present ...study explored the two processes in a single design, comparing younger/older preschool boys and girls and using a two-task procedure involving (a) categorization of pictures of masculine/feminine colors, toys, and objects as more suited for boys/girls or both and (b) descriptions and evaluations of boys/girls playing with gender counter-stereotypic toys. One hundred Serbian children aged 3–4 or 6–7 years-old, balanced by gender, were individually interviewed. Although all three sets of stimuli were stereotyped, toys were stereotyped more often than colors and objects. Overall stereotyping, as well as stereotyping of colors and toys, was more frequent in the older group. Gender differences were more complex, showing some gender x age interactions wherein boys stereotyped masculine stimuli more often than girls did; the older boys, but not the other groups, sanctioned counter stereotypical behavior more often than accepted it; and boys’ behaviors were sanctioned more often than girls’. Finally, stereotyping and sanctioning were strongly positively related. Our study shows that, at early preschool ages, children are not only aware of gender norms, but also ready to sanction peers violating them. Boys seem to be more likely to stereotype, particularly the masculine stimuli, and be sanctioned for not conforming to stereotypes. The findings can help educators and media identify groups that need to be empowered to explore behaviors beyond gender-prescribed roles.
Disturbance of the tight junction (TJ) complexes between brain endothelial cells leads to increased paracellular permeability, allowing leukocyte entry into inflamed brain tissue and also ...contributing to edema formation. The current study dissects the mechanisms by which a chemokine, CCL2, induces TJ disassembly. It investigates the potential role of selective internalization of TJ transmembrane proteins (occludin and claudin-5) in increased permeability of the brain endothelial barrier in vitro. To map the internalization and intracellular fate of occludin and claudin-5, green fluorescent protein fusion proteins of these TJ proteins were generated and imaged by fluorescent microscopy with simultaneous measurement of transendothelial electrical resistance. During CCL2-induced reductions in transendothelial electrical resistance, claudin-5 and occludin became internalized via caveolae and further processed to early (EEA1+) and recycling (Rab4+) endosomes but not to late endosomes. Western blot analysis of fractions collected from a sucrose gradient showed the presence of claudin-5 and occludin in the same fractions that contained caveolin-1. For the first time, these results suggest an underlying molecular mechanism by which the pro-inflammatory chemokine CCL2 mediates brain endothelial barrier disruption during CNS inflammation.
A probiotic-related benefit for the host is inherently linked to metabolic activity and integration in the gut ecosystem. To facilitate these, probiotics are often combined with specific prebiotics ...in a synbiotic formulation. Here, we propose an approach for improving probiotic metabolic activity and engraftment. By cultivating the probiotic strain in the presence of a specific prebiotic (preconditioning), the bacterial enzymatic machinery is geared towards prebiotic consumption. Today, it is not known if preconditioning constitutes an advantage for the synbiotic concept. Therefore, we assessed the effects galacto-oligosaccharide (GOS) addition and preconditioning on GOS of Limosilactobacillus reuteri DSM 17938 on ex vivo colonic metabolic profiles, microbial community dynamics, and osteoblastogenesis. We show that adding GOS and preconditioning L. reuteri DSM 17938 act on different scales, yet both increase ex vivo short-chain fatty acid (SCFA) production and engraftment within the microbial community. Furthermore, preconditioned supernatants or SCFA cocktails mirroring these profiles decrease the migration speed of MC3T3-E1 osteoblasts, increase several osteogenic differentiation markers, and stimulate bone mineralization. Thus, our results demonstrate that preconditioning of L. reuteri with GOS may represent an incremental advantage for synbiotics by optimizing metabolite production, microbial engraftment, microbiome profile, and increased osteoblastogenesis.
Gastronomy, as one of the most important segments in tourism, allows tourists to discover the cultural roots of the destination, so it is motives for planning a tourist visit. This paper is a pilot ...study for Belgrade, and therefore can be used for other destinations in the country and the world. The aim of this paper is to examine the attitudes of employees about the impression of guest tourists on the gastronomic offer of Belgrade. The methodology used in this paper is based on a questionnaire (n = 303), the survey was conducted among employees in the hospitality sector.Based on the obtained results it is proven that the guests are satisfied with the offer of food and drinks, and that traditional cousine and beverage are motives for visiting the restaurant. It can be concluded that when visiting a restaurant, the gastronomic offer is an important segment in the overall experience.
: To evaluate the clinical outcomes and complication rate of laparoscopic appendectomy in children operated on during the daytime versus nighttime.
: A total of 303 children who underwent ...laparoscopic appendectomy for acute appendicitis between 1 January 2020 and 31 December 2022 were enrolled in this retrospective study. The patients were divided into two study groups. The first group consisted of the patients who underwent laparoscopic appendectomy during the day shift from 07:00-21:00 (
= 171), while the patients in the second group underwent laparoscopic appendectomy during the night shift from 21:00-07:00 (
= 132). The groups were compared for baseline clinical and laboratory data, treatment outcomes, and complications. The Mann-Whitney U test was used to compare continuous variables, while the Chi-square test was used to compare categorical variables. A two-sided Fisher's exact test was used when the frequency of events in a certain cell was low. All
values less than 0.05 were considered significant.
: The proportion of complicated appendicitis was almost the same in both patient groups (
= 63, 36.8% vs.
= 49, 37.1%,
= 0.960). Out of the total number of patients presenting during the daytime and nighttime, 11 (6.4%) and 10 (7.6%) developed a postoperative complication, respectively (
= 0.697). Additionally, rates of readmission (
= 5 (2.9%) vs.
= 2 (1.5%);
= 0.703), redo-surgery (
= 3 (1.7%) vs.
= 0;
= 0.260), conversion to open surgery (
= 0 vs.
= 1 (0.8%);
= 0.435) and length of hospital stay (
= 3 (IQR 1, 5) vs.
= 3 (IQR 2, 5);
= 0.368) did not differ significantly between daytime and nighttime appendectomies. The duration of the surgery was significantly shorter in patients presenting during the day than in those presenting at night (26 min (IQR 22, 40) vs. 37 min (31, 46);
< 0.001).
: Different shift times did not affect the treatment outcomes or complication rates for children receiving laparoscopic appendectomy.
In March 2022, an outbreak of Q fever (Coxiella burnetii) with non‐occupational exposure was confirmed in a semi‐urban area in Čavle, Croatia. Veterinary and human epidemiological investigations were ...conducted to identify the source of the outbreak and to implement appropriate control measures. Three farms were settled next to each other near the homes of the first human cases at the end of the street. The closest farm was less than 500 meters away. These farms contained 161 adult sheep and goats. Among the animal samples analysed, all 16 goats (100%) and 24/50 sheep (48%) tested positive for C. burnetii IgM/IgG antibodies, phase I and II. One out of five sheeps' vaginal swabs were C. burnetti DNA positive. Human testing revealed 20 confirmed and three probable cases (9/23 pneumonia, 2/23 hepatitis, 21/23 fever), with three hospitalizations, and one death. Twenty‐seven cases were discarded following negative laboratory results. The epidemiological investigation revealed airborne transmission as the most likely route of transmission. Multiple logistic regression analyses were used to evaluate risk factors for Q fever infection. Persons who were near the farms (≤750 m) (OR 4.5; 95% CI = 1.1–18.3) and lived in the nearest street to the farms had the highest risk of contracting Q fever (OR 3.7; 95% CI = 1.1–13.6). Decreased rainfall compared to monthly averages was recorded in the months prior to the outbreak with several days of strong wind in January preceding the outbreak. This was the largest Q fever outbreak in the county in the last 16 years, which was unexpected due to its location and non‐occupational exposure. To stop the outbreak, numerous intensive biosecurity measures were implemented. The outbreak highlights the importance of urban development strategies to limit the number of animal housing near residential areas while providing regular biosecurity measures to prevent infections in livestock.
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