Arterial blood pressure lability, defined as rapid changes in arterial blood pressure, occurs commonly during anaesthesia. It is believed that hypertensive patients exhibit more lability during ...surgery and that lability is associated with poorer outcomes. Neither association has been rigorously tested. We hypothesized that hypertensive patients have more blood pressure lability and that increased lability is associated with increased 30 day mortality.
This was a retrospective single-centre study of surgical patients from July 2008 to December 2012. Intraoperative data were extracted from the electronic anaesthesia record. Lability was calculated as the modulus of the percentage change in mean arterial pressure between consecutive 5 min intervals. The number of episodes of lability >10% was tabulated. Multivariate logistic regression was performed to determine the association between lability and 30 day mortality using derivation and validation cohorts.
Inclusion criteria were met by 52 919 subjects. Of the derivation cohort, 53% of subjects were hypertensive and 42% used an antihypertensive medication. The median number of episodes of lability >10% was 9 (interquartile range 5–14) per patient. Hypertensive subjects demonstrated more lability than normotensive patients, 10 (5–15) compared with 8 (5–12), P<0.0001. In subjects taking no antihypertensive medication, lability >10% was associated with decreased 30 day mortality, odds ratio (OR) per episode 0.95 95% confidence interval (CI) 0.92–0.97, P<0.0001. This result was confirmed in the validation cohort, OR 0.96 (95% CI 0.93–0.99), P=0.01, and in hypertensive patients taking no antihypertensive medication, OR 0.96 (95% CI 0.93–0.99), P=0.002. Use of any antihypertensive medication class reduced this effect.
Intraoperative arterial blood pressure lability occurs more often in hypertensive patients. Contrary to common belief, increased lability was associated with decreased 30 day mortality.
Lipid nanoparticles (LNP) can provide a clinically effective method for delivering small interfering RNA (siRNA) to silence pathological genes in hepatocytes. The gene silencing potency of these ...LNP-siRNA systems has been shown to depend on a variety of factors including association with serum factors such as ApoE and the pKa of component ionizable lipids. Here we investigate the influence of LNP size, an important parameter affecting tissue penetration of LNP systems, on the pharmacokinetics, biodistribution, and hepatic gene silencing potency of LNP-siRNA systems following intravenous administration. For LNP systems stabilized by a polyethylene glycol (PEG)-lipid that can dissociate from the LNP following injection, it is shown that small (diameter≤30nm) systems are considerably less potent than their larger counterparts. This is attributed in part to the ability of other lipid components, particularly the ionizable amino-lipid, to dissociate from the LNP following dissociation of the PEG-lipid. Small LNP stabilized by PEG-lipids with slow dissociation rates exhibited much reduced amino-lipid dissociation rates, however such systems are relatively impotent due to the continued presence of the PEG coating. These results demonstrate the delicate balance between the in vivo potency of LNP-siRNA systems and the residence times of component lipids in the LNP particle itself and suggest new directions to optimize the in vivo gene silencing potency of small LNP-siRNA systems.
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A previous genetic study has suggested that schizophrenia, bipolar disorder, major depressive disorder, autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) share common ...disease-associated genes. However, whether individuals with first-degree relatives (FDRs) with schizophrenia have a higher risk of these major psychiatric disorders requires further investigation. This study used Taiwan's National Health Insurance Research Database and identified 151 650 patients with schizophrenia and 227 967 individuals with FDRs with schizophrenia. The relative risks (RRs) of schizophrenia and other major psychiatric disorders were assessed in individuals with FDRs with schizophrenia. The individuals with FDRs with schizophrenia exhibited higher RRs (95% confidence interval) of major psychiatric disorders, namely schizophrenia (4.76, 4.65-4.88), bipolar disorder (3.23, 3.12-3.35), major depressive disorder (2.05, 2.00-2.10), ASD (2.55, 2.35-2.77) and ADHD (1.31, 1.25-1.37) than were found in the total population. Several sensitivity analyses were conducted to confirm these results. A dose-dependent relationship was observed between the risks of major psychiatric disorders and the numbers of FDRs with schizophrenia. The increased risks of major psychiatric disorders were consistent in different family relationships, namely among parents, offspring, siblings and twins. Our study supports the familial dose-dependent co-aggregation of schizophrenia, bipolar disorder, major depressive disorder, ASD and ADHD, and our results may prompt governmental public health departments and psychiatrists to focus on the mental health of individuals with FDRs with schizophrenia.
University students are increasingly recognized as a vulnerable population, suffering from higher levels of anxiety, depression, substance abuse, and disordered eating compared to the general ...population. Therefore, when the nature of their educational experience radically changes-such as sheltering in place during the COVID-19 pandemic-the burden on the mental health of this vulnerable population is amplified. The objectives of this study are to 1) identify the array of psychological impacts COVID-19 has on students, 2) develop profiles to characterize students' anticipated levels of psychological impact during the pandemic, and 3) evaluate potential sociodemographic, lifestyle-related, and awareness of people infected with COVID-19 risk factors that could make students more likely to experience these impacts.
Cross-sectional data were collected through web-based questionnaires from seven U.S. universities. Representative and convenience sampling was used to invite students to complete the questionnaires in mid-March to early-May 2020, when most coronavirus-related sheltering in place orders were in effect. We received 2,534 completed responses, of which 61% were from women, 79% from non-Hispanic Whites, and 20% from graduate students.
Exploratory factor analysis on close-ended responses resulted in two latent constructs, which we used to identify profiles of students with latent profile analysis, including high (45% of sample), moderate (40%), and low (14%) levels of psychological impact. Bivariate associations showed students who were women, were non-Hispanic Asian, in fair/poor health, of below-average relative family income, or who knew someone infected with COVID-19 experienced higher levels of psychological impact. Students who were non-Hispanic White, above-average social class, spent at least two hours outside, or less than eight hours on electronic screens were likely to experience lower levels of psychological impact. Multivariate modeling (mixed-effects logistic regression) showed that being a woman, having fair/poor general health status, being 18 to 24 years old, spending 8 or more hours on screens daily, and knowing someone infected predicted higher levels of psychological impact when risk factors were considered simultaneously.
Inadequate efforts to recognize and address college students' mental health challenges, especially during a pandemic, could have long-term consequences on their health and education.
Twin and family studies have shown that same-sex sexual behavior is partly genetically influenced, but previous searches for specific genes involved have been underpowered. We performed a genome-wide ...association study (GWAS) on 477,522 individuals, revealing five loci significantly associated with same-sex sexual behavior. In aggregate, all tested genetic variants accounted for 8 to 25% of variation in same-sex sexual behavior, only partially overlapped between males and females, and do not allow meaningful prediction of an individual's sexual behavior. Comparing these GWAS results with those for the proportion of same-sex to total number of sexual partners among nonheterosexuals suggests that there is no single continuum from opposite-sex to same-sex sexual behavior. Overall, our findings provide insights into the genetics underlying same-sex sexual behavior and underscore the complexity of sexuality.
Hypothyroidism has been associated with significantly elevated risk for hepatocellular carcinoma (HCC), although the precise underlying mechanisms remain unknown at present. Thyroid hormone (T3) and ...its receptor (TR) are involved in metabolism and growth. Endoglin is a T3/TR candidate target gene identified from our previous studies. Here, we demonstrated that T3 positively regulates endoglin mRNA and protein levels, both in vitro and in vivo. The thyroid hormone response elements of endoglin were identified at positions -2114/-2004 and -2032/-1973 of the promoter region using the electrophoretic mobility shift assay and chromatin immunoprecipitation assay. Endoglin was downregulated in the subgroups of HCC patients and significantly associated with histology grade (negative association, P=0.001), and this expression level was significantly associated with TRα1 in these HCC patients. Our results clearly indicate that p21 is involved in T3-mediated suppression of cell proliferation. Knock down of endoglin expression in HCC cells facilitated p21 polyubiquitination and promoted cell proliferation in the presence of T3. The data collectively suggest that T3/TR signaling suppresses cell proliferation by upregulating endoglin, in turn, affecting p21 stability. The results indicate that endoglin has a suppressor role to inhibit cell proliferation in HCC cell lines.
Major depression is a debilitating psychiatric illness that is typically associated with low mood and anhedonia. Depression has a heritable component that has remained difficult to elucidate with ...current sample sizes due to the polygenic nature of the disorder. To maximize sample size, we meta-analyzed data on 807,553 individuals (246,363 cases and 561,190 controls) from the three largest genome-wide association studies of depression. We identified 102 independent variants, 269 genes, and 15 genesets associated with depression, including both genes and gene pathways associated with synaptic structure and neurotransmission. An enrichment analysis provided further evidence of the importance of prefrontal brain regions. In an independent replication sample of 1,306,354 individuals (414,055 cases and 892,299 controls), 87 of the 102 associated variants were significant after multiple testing correction. These findings advance our understanding of the complex genetic architecture of depression and provide several future avenues for understanding etiology and developing new treatment approaches.
Objectives
To discern the diagnostic accuracy between the updated diagnostic consensus of the Asian Working Group for Sarcopenia (AWGS) in 2019 (AWGS 2019) and the previous AWGS 2014 guidelines.
...Design
A prospective population-based cohort study.
Setting and Participants
The study included 731 older community-dwelling adults aged ≥ 65 years who participated in face-to-face interviews and were followed up for 11-year mortality until 31 Mar 2022.
Measurements
We utilized a handgrip strength dynamometer to measure participants’ muscle strength, while their walking speed was determined by a timed 6-meter walk test at their usual pace. Additionally, muscle mass was measured using dual-energy X-ray absorptiometry scanning. Sarcopenia was defined as the presence of low muscle mass in combination with weakness and/or slowness both by AWGS 2014 and 2019 criteria.
Results
The present study followed 731 participants (mean age 73.4 ± 5.4 years, men predominant 52.8%) over a period of 11 years, yielding 5927 person-years and 159 deaths. Prevalence of sarcopenia defined by AWGS 2019 and 2014 criteria were 8.5% and 6.8%, respectively. Sarcopenia defined by AWGS 2019 (HR 1.62, 95% CI 1.04–2.54, p=0.034) but not AWGS 2014 was significantly associated with mortality in community-living older adults after adjusting for potential confounders such as age, sex, education, drinking, disease burden and serum level of testosterone. The study also found that the AWGS 2019 criteria had a better model fitness than AWGS 2014 criteria in predicting mortality.
Conclusion
AWGS 2019 criteria outperformed AWGS 2014 in identifying sarcopenia risk and predicting mortality. Screening for sarcopenia in older adults may improve health outcomes by identifying those at increased mortality risk.
We report a giant, ∼22%, electroresistance modulation for a metallic alloy above room temperature. It is achieved by a small electric field of 2 kV/cm via piezoelectric strain-mediated ...magnetoelectric coupling and the resulting magnetic phase transition in epitaxial FeRh/BaTiO_{3} heterostructures. This work presents detailed experimental evidence for an isothermal magnetic phase transition driven by tetragonality modulation in FeRh thin films, which is in contrast to the large volume expansion in the conventional temperature-driven magnetic phase transition in FeRh. Moreover, all the experimental results in this work illustrate FeRh as a mixed-phase model system well similar to phase-separated colossal magnetoresistance systems with phase instability therein.
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