材料科学最新文献

Background and objective: Missing data and unmeasured confounding are key challenges for external comparator studies. This work evaluates bias and other performance characteristics depending on missingness and unmeasured confounding by means of two case studies and simulations.

Methods: Two case studies were constructed by taking the treatment arms from two randomised controlled trials and an external real-world data source that exhibited substantial missingness. The indications of the randomised controlled trials were multiple myeloma and metastatic hormone-sensitive prostate cancer. Overall survival was taken as the main endpoint. The effects of missing data and unmeasured confounding were assessed for the case studies by reporting estimated external comparator versus randomised controlled trial treatment effects. Based on the two case studies, simulations were performed broadening the settings by varying the underlying hazard ratio, the sample size, the sample size ratio between the experimental arm and the external comparator, the number of missing covariates and the percentage of missingness. Thereby, bias and other performance metrics could be quantified dependent on these factors.

Results: For the multiple myeloma external comparator study, results were in line with the randomised controlled trial, despite missingness and potential unmeasured confounding, while for the metastatic hormone-sensitive prostate cancer case study missing data led to a low sample size, leading overall to inconclusive results. Furthermore, for the metastatic hormone-sensitive prostate cancer study, missing data in important eligibility criteria led to further limitations. Simulations were successfully applied to gain a quantitative understanding of the effects of missing data and unmeasured confounding.

Conclusions: This exploratory study confirmed external comparator strengths and limitations by quantifying the impact of missing data and unmeasured confounding using case studies and simulations. In particular, missing data in key eligibility criteria were seen to limit the ability to derive the external comparator target analysis population accurately, while simulations demonstrated the magnitude of bias to expect for various settings.

Background: Contaminated environmental surfaces in the health care setting put patients at risk of acquiring health care-associated infections. Highlight (Kinnos) is a novel color-additive technology for disinfectant wipes that helps users visualize surfaces that have been cleaned by producing a transient color on wiped surfaces that fades off after effective cleaning.

Methods: To quantify the impact of real-time visual feedback on room cleanliness and efficiency, a pre-post quasi-experimental study was conducted by comparing Replicate Organism Detection and Counting (RODAC) plate counts and room turnaround times with and without the use of the color additive.

Results: Compared with the control group of disinfectant alone, disinfection with the color additive resulted in a 69.2% improvement in room cleanliness accompanied by a 5.9% faster room turnover time.

Discussion: As far as we know, this study is the first to publish on the impact of a novel color additive on the environment of care as measured by microbial culturing and room turnaround times, finding advantages in both metrics relative to the status quo.

Conclusions: The use of real-time visual feedback can improve the thoroughness of disinfection cleaning while maintaining operational efficiency.

(-)-Epicatechin (EPI) is beneficial for cardiovascular health. Trimethylamine N-oxide (TMAO), a gut microbe-derived food metabolite, is strongly associated with the risk of cardiovascular diseases. However, the effects and underlying mechanisms of EPI on TMAO-induced cardiac hypertrophy remain unclear. This study aimed to determine whether EPI inhibits TMAO-induced cardiac hypertrophy. Plasma levels of TMAO in control participants and patients with cardiac hypertrophy were measured and analyzed. Male C57BL/6 mice were randomly divided into control group, TMAO group, EPI group and TMAO + EPI group. According to the groups assignments, mice received intraperitoneal (i.p.) injection of normal saline or i.p. injection of TMAO (150 mg/kg/day) for 14 days. The EPI group was given intragastric (i.g.) administration of EPI alone (1 mg/kg/day) for 21 days, and TMAO + EPI group received i.g. administration of EPI for 7 days before starting i.p. injection of TMAO, continuing until the end of the TMAO treatment. Histological analyses of the mice's hearts was accessed by H&E and Masson staining. In vitro, H9c2 cells were induced to hypertrophy by TMAO (10 µM) for 24 h and were pre-treated with or without EPI (10 µM) for 1 h. Protein level of cardiac hypertrophy markers and Sp1/SIRT1/SUMO1 pathway were determined by western blot. The plasma level of TMAO was 2.66 ± 1.59 μmol/L in patients with cardiac hypertrophy and 0.62 ± 0.30 μmol/L in control participants. EPI attenuated TMAO-induced hypertrophy in H9c2 cells. In vivo, TMAO induced cardiac hypertrophy and impaired the cardiac function of mice. Pathological staining showed that TMAO induced cardiac hypertrophy and collagen deposition in mice. EPI treatment improved the cardiac function, inhibited the myocardial hypertrophy induced by TMAO. EPI significantly attenuated the TMAO-induced upregulation of ANP and BNP and the downregulation of SP1, SIRT1 and SUMO1 in vivo and in vitro. EPI may suppress TMAO-induced cardiac hypertrophy by activating the Sp1/SIRT1/SUMO1 signaling pathway.

In recent years, there has been a surge in the popularity of fasting as a method to enhance one's health and overall well-being. Fasting is a customary practice characterized by voluntary refraining from consuming food and beverages for a specified duration, ranging from a few hours to several days. The potential advantages of fasting, including enhanced insulin sensitivity, decreased inflammation, and better cellular repair mechanisms, have been well documented. However, the effects of fasting on cancer therapy have been the focus of recent scholarly investigations. Doxorubicin (Dox) is one of the most widely used chemotherapy medications for cancer treatment. Unfortunately, cardiotoxicity, which may lead to heart failure and other cardiovascular issues, has been linked to Dox usage. This study aims to comprehensively examine the possible advantages and disadvantages of fasting concerning Dox-induced cardiotoxicity. Researchers have investigated the potential benefits of fasting in lowering the risk of Dox-induced cardiac damage to solve this problem. Nevertheless, new studies indicate that prolonged alternate-day fasting may adversely affect the heart's capacity to manage the cardiotoxic properties of Dox. Though fasting may benefit overall health, it is essential to proceed cautiously and consider the potential risks in certain circumstances.

The study aimed to investigate the impact of synaptotagmin 7 (SYT7) on the metastasis of epithelial ovarian cancer (EOC) and its potential mechanisms. This was achieved through the analysis of SYT7 expression levels and clinical relevance in EOC using bioinformatics analysis from TCGA. Additionally, the study examined the influence of SYT7 on the migration and invasion of EOC cells, as well as explored its molecular mechanisms using in vitro EOC cell lines and in vivo mouse xenograft models. Our research revealed that human EOC tissues exhibit significantly elevated levels of SYT7 compared to normal ovarian tissues, and that SYT7 expression is inversely correlated with overall survival. Suppression of SYT7 effectively impeded the migratory and invasive capabilities of CAOV3 cells, whereas overexpression of SYT7 notably accelerated tumor progression in A2780 cells. Mechanistic investigations demonstrated that SYT7 upregulates p-STAT3 and MMP2 in EOC cells. Importantly, treatment with the STAT3 inhibitor niclosamide effectively counteracted the oncogenic effects of SYT7 in EOC. The inhibition of SYT7 was found to significantly reduce in vivo tumor metastasis in a nude mouse xenograft model. Our findings suggest that the upregulation of SYT7 in EOC is associated with a negative prognosis, as it enhances tumor migration and invasion by activating the STAT3 signaling pathway. Thus, SYT7 might be utilized as a EOC prognostic marker and treatment target.

Rationale: Alcohol exposure during adolescence has been linked to long-lasting behavioral consequences, contributing to the development of alcohol use disorder. Negative affect and chronic pain during alcohol withdrawal are critical factors influencing problematic alcohol use and relapse. Our previous research demonstrated that adolescent intermittent ethanol (AIE) vapor exposure elicits sex-specific negative affect-like behavior in adult mice following stress exposure. Additionally, AIE induces persistent mechanical hypersensitivity, which is accompanied by increased activation of corticotropin-releasing factor receptor type 1 (CRFR1) neurons in the dorsolateral bed nucleus of the stria terminalis (dlBNST).

Objectives: This study extends previous work by investigating plasma corticosterone levels and CRFR1 protein expression in the dlBNST following restraint stress exposure in adult mice with an AIE history. We also aim to explore the role of dlBNST CRFR1 signaling in mediating negative affect-like behavior and mechanical hypersensitivity.

Results: Female mice exhibited elevated plasma corticosterone levels compared to males following restraint stress. Moreover, females with AIE history showed higher expression of CRFR1 protein in the dlBNST compared to air controls. Antagonism of CRFR1 in the dlBNST blocked AIE-induced mechanical hypersensitivity in adult females but did not affect stress-induced negative affect-like behavior. In alcohol-naïve females, intra-dlBNST administration of a CRFR1 agonist induced mechanical hypersensitivity.

Conclusions: These findings provide new insights into the neurobiological mechanisms underlying stress-induced negative affect and pain-related behavior, both influenced by a history of adolescent alcohol exposure. The results suggest that CRFR1 antagonists warrant further investigation for their potential in addressing alcohol-related chronic pain.

The Office of Disease Prevention and Health Promotion (ODPHP) at the US Department of Health and Human Services (HHS) oversees Healthy People 2030, the nation's decennial health promotion and disease prevention framework and plan, which sets national goals and identifies science-based measurable objectives with targets to evaluate efforts to improve health and well-being. With science recognizing the relationship between health and well-being, Healthy People 2030 is broadening its understanding of national-level well-being by gathering new data for and coordinating across the federal government on well-being. The addition of well-being in Healthy People 2030 elevates well-being as a national priority and creates opportunities for the well-being of the nation to be assessed, disparities to be identified, and collaborative efforts to be coordinated to support a society in which all people can achieve their full potential for health and well-being. This article discusses the inclusion of well-being to Healthy People 2030, details the approach and rationale for the selection of the national well-being metrics, and articulates opportunities for improving population-level well-being and federal collaboration.

Objective: There are lingering concerns in the United States about home birth. We used 2 large (n = 50,043; n = 62,984), national community birth registries to compare maternal and neonatal outcomes for planned home versus planned birth center births.

Methods: To compare outcomes by intended birth site, we used logistic regressions, controlling for demographic and pregnancy risk variables. Maternal outcomes included intrapartum or postpartum transfer to hospital, hospitalization, cesarean, and hemorrhage; neonatal outcomes included neonatal transfer, hospitalization, neonatal intensive care unit admission, and intrapartum or neonatal death. Analyses were conducted twice, once in each dataset.

Results: Individuals who planned home births had a lower incidence of all types of transfers, compared with those who planned birth center births, but in one dataset only, experienced more cesareans [adjusted odds ratio (95% CI): 1.32 (1.02-1.70); 0.95 (0.88-1.03)]. Planned home birth was associated with lower adjusted odds of maternal hospitalization in one dataset but not the other [0.97 (0.54-1.74); 0.85 (0.76-0.95)], and was not associated with hemorrhage. Neonatal outcomes likewise were either not associated with a planned birthplace or suggested home birth was safer: hospitalization [0.77 (0.53-1.11), 0.90 (0.82-0.98)], neonatal intensive care unit admission [0.54 (0.28-1.00), 0.97 (0.86-1.10)]. There was no observable association with intrapartum or neonatal death: 1.07 (0.68-1.67; only calculated once because of small numbers of events).

Conclusions: Planned home births are as safe as planned birth center births for low-risk pregnancies. Current guidelines advising against planned home births are not supported by these data.

Bacteriotherapy represents an attractive approach for both prophylaxis and treatment of human diseases. However, combining probiotic bacteria in "cocktails" is underexplored, despite its potential as an alternative multi-target therapy. Herein, three-strain probiotic mixtures containing different combinations of Bacillus (Bc.) coagulans [ATB-BCS-042], Levilactobacillus (Lv.) brevis [THT 0303101], Lacticaseibacillus (Lc.) paracasei [THT 031901], Bacillus subtilis subsp. natto [ATB-BSN-049], Enterococcus faecium [ATB-EFM-030], and Bifidobacterium (Bf.) animalis subsp. lactis [THT 010802] were prepared. Four cocktails (PA: Bc. coagulans + Lv. brevis + Lc. paracasei, PB: Bc. subtilis subsp. natto + Lv. brevis + Lc. paracasei, PC: E. faecium + Lv. brevis + Lc. paracasei, PD: Bc. coagulans + Lv. brevis + Bf. animalis subsp. lactis) were tested using a short-term (72 h) simulation of the human colonic microbiota in a final dose of 6 × 10⁹ CFU. All these probiotic mixtures significantly increased butyrate production compared to the parallel control experiment. PA and PB promoted a bifidogenic effect and facilitated lactobacilli colonization. Furthermore, reporter gene assays using the AhR_HT29-Lucia cell line revealed that fermentation supernatants from PA and PB notably induced AhR transactivity. Subsequent examination of the metabolic outputs of PA and PB in intestinal epithelial models using cell culture inserts suggested no significant impact on the transepithelial electrical resistance (TEER). Assessment of the expression of proinflammatory and anti-inflammatory cytokines, as well as AhR-related target genes in the Caco-2 cell monolayers indicated that PB's metabolic output upregulated most of the measured endpoints. This in vitro investigation evaluated the potential impact of four multispecies probiotic mixtures in the human colonic microbiota and identified a promising formulation comprising a combination of Bc. subtilis subsp. natto, Lv. brevis, and Lc. paracasei as a promising formulation for further study.

Certain nutritional practices may reduce menstrual-related symptoms, but there is no current consensus on what foods/supplements are sufficiently evidenced to warrant promotion to reduce menstrual symptoms of naturally menstruating individuals. This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Two online databases were searched for published experimental studies that investigated the effects of foods/supplements on menstrual-related symptoms in eumenorrhoeic women. Extracted data and study characteristics were tabulated and grouped on the basis of food/supplement intervention and dosage compared with UK dietary reference values (DRV) and safe upper limits. In total, twenty-eight studies and twenty-one different foods/supplement interventions were included in the review. None of the studies reported a negative effect on symptoms, twenty-three reported a positive effect and five had no effect. Eighteen different ways of measuring menstrual-related symptoms were described across the studies. The results indicate a lack of consistency in studies to confidently provide information to eumenorrheic, naturally menstruating women regarding the use of foods/supplements to reduce menstrual symptoms. Determination of menstrual-related symptoms varied along with dose and duration of food or supplements provided. These data provide some evidence for the use of vitamin D, calcium, zinc and curcumin to reduce menstrual-related symptoms of non-hormonal contraceptive users, on an individual basis; however, further investigation is required prior to implementation with a focus on robust protocols to determine and measure changes in menstrual symptoms, with interventions adhering to DRV and safe upper limits.