Frailty and medication adherence among older adult patients with hypertension: a moderated mediation model.

Objective: Medication adherence has a critical impact on the well-being of older adult patients with hypertension. As such, the current study aimed to investigate the mediating role of health literacy between frailty and medication adherence and the moderating role of educational level. Methods: This cross-sectional study included patients admitted to the geriatric unit of a hospital. Participants were interviewed using the four-item Morisky Medication Adherence Scale, the Frailty Phenotype Scale, and the Health Literacy Management Scale. Spearman's correlation coefficients were used to assess the association between variables. Mediation and moderated mediation analyses were performed using Process version 4.1 via Model 4 and 14, respectively. Results: Data from 388 participants were analyzed. The median (IQR [P25-P75]) score for medication adherence was 4.00 (2.00-4.00). Results revealed that after controlling for age, sex, hypertension complication(s) and body mass index, frailty significantly contributed to medication adherence (ßtotal -0.236 [95% confidence interval (CI) -0.333 to -0.140]). Medication adherence was influenced by frailty (ßdirect -0.192 [95% CI -0.284 to -0.099]) both directly and indirectly through health literacy (ßindirect -0.044 [95% CI -0.077 to -0.014]). Educational level moderated the pathway mediated by health literacy; more specifically, the conditional indirect effect between frailty and medication adherence was significant among older adult hypertensive patients with low, intermediate, and high educational levels (effect -0.052 [95% CI -0.092 to -0.106]; effect -0.041 [95% CI -0.071 to -0.012]; effect -0.026 [95% CI -0.051 to -0.006]). The relationship between frailty and medication adherence in older adult patients with hypertension was found to have mediating and moderating effects. Conclusion: A moderated mediation model was proposed to investigate the effect of frailty on medication adherence. It was effective in strengthening medication adherence by improving health literacy and reducing frailty. More attention needs to be devoted to older adult patients with hypertension and low educational levels.

Next-generation sequencing facilitates genetic diagnosis and improves the management of patients with hearing loss in clinical practice.

BACKGROUND: Hearing loss (HL) is a prevalent sensorineural disorder, and is among the most etiologically heterogeneous disorders. With the advent of next-generation sequencing (NGS) technologies, hundreds of candidate genes can be analyzed simultaneously in a cost-effective manner. METHODS: Ninety-four patients from 87 families diagnosed with non-syndromic or syndromic HL were enrolled. A custom-designed HL panel and clinical exome sequencing (CES) were applied to explore molecular etiology in the cohort, and the efficacy of the two panels was examined. RESULTS: The etiologic diagnosis for HL has been identified for 36 out of 87 probands (41.4%), 28 with an autosomal recessive (AR) inheritance pattern and 8 with an autosomal dominant (AD) pattern. Candidate variants in 18 different genes were identified in the study cohort, 10 with AR inheritance pattern and 8 with AD pattern. Fourteen of the variants identified in the study were novel. CONCLUSIONS: The custom-designed HL panel covers almost all known HL-associated genes, and can be used as an effective clinical diagnostic platform; CES evaluates all exons related to clinical symptoms, and is also suitable for clinical diagnosis of HL. Next-generation sequencing facilitates genetic diagnosis and improves the management of patients with HL in the clinical practice.

Association of learning environment and self-directed learning ability among nursing undergraduates: a cross-sectional study using canonical correlation analysis.

OBJECTIVES: This study explores the relationship between the perception of the learning environment and self-directed learning (SDL) ability among nursing undergraduates. DESIGN, SETTING AND PARTICIPANTS: A cross-sectional study was conducted in December 2020 with 1096 junior and senior undergraduate nursing students (aged 16-22) from Wannan Medical College in Anhui Province, China. OUTCOME MEASURES: The Chinese version of the Dundee Ready Educational Environment Measure questionnaire and a validated Chinese version of college students' SDL ability scale were used to assess students' perceptions about their learning environment and their SDL ability. Canonical correlation analysis was performed to evaluate their correlation. RESULTS: The total score for the learning environment was 120.60 (scoring rate: 60.30%), and the score for SDL ability was 89.25 (scoring rate: 63.75%). Analysis indicated that the first canonical correlation coefficient was 0.701 and the contribution rate was 94.26%. The perception of the learning environment was mainly determined by students' perception of learning (SPL) and academic self-perceptions (SASP), with SDL ability mainly determined by self-management ability and cooperative learning ability. SPL and SASP were positively correlated with self-management ability and cooperative learning ability. Multiple linear regression analysis revealed that SPL, SASP, students' perceptions of atmosphere and students' social self-perceptions had a significant impact on SDL ability. CONCLUSIONS: The SDL ability of nursing undergraduates was not high. SPL and SASP were positively correlated with self-management ability and cooperative learning ability. Nursing educators can improve students' SDL ability by changing their learning environment, using, for example, new student-centred teaching methods.

Predictors of poor medication adherence of older people with hypertension.

AIMS: To explore the risk factors for poor medication adherence in older people with hypertension. DESIGN: A cross-sectional study. METHODS: Participants were administered with a self-report questionnaire about their demographic characteristics; additionally, their four-item Morisky Medication Adherence Scale scores were calculated. The STROBE checklist was applied as the reporting guideline for this study (File S1). RESULTS: Univariate analysis indicated that the following five factors were statistically significantly associated with medication adherence: education level (χ2  = 8.073, p = .045), co-living (χ2  = 11.364, p = .010), hypertension complications (χ2  = 10.968, p = .001), admission blood pressure (χ2  = 8.876, p = .003), and falls (χ2  = 6.703, p = .010). Multivariable binary logistic regression analysis showed that there were four statistically significant predictors, such as people who lived with spouses and offspring (OR = 3.004, p = .017), and those who had high admission blood pressure (OR = 1.910, p = .003) had a greater risk of poor medication adherence, whereas those without hypertension complications (OR = 0.591, p = .026) and those without falls (OR = 0.530, p = .046) had a lower risk. RELEVANCE TO CLINICAL PRACTICE: We believe that these findings contribute to the identification of high-risk people with poor adherence, allowing nurses to identify people with poor adherence in a timely manner, and pay attention to the people's medication.

Pregnancy Outcomes After Human Papillomavirus Vaccination in Periconceptional Period or During Pregnancy: A Systematic Review and Meta-analysis.

Background: National immunization schedules in many countries recommend HPV vaccination for females until the age of 26 years, and thus substantial numbers with reproductive age may be exposed to HPV vaccines. Objective: To assess whether inadvertent HPV vaccine exposures in the periconceptional period or during pregnancy were associated with increased risks for adverse pregnancy outcomes. Search strategy: A search of PubMed, Cochrane Library, China National Knowledge Infrastructure (CNKI), and WanFang databases (until March 31, 2019) was performed. Selection criteria: Studies that assess the risk of adverse pregnancy outcomes in HPV vaccine exposed/unexposed pregnancies were included. The adverse pregnancy outcomes included spontaneous abortion, stillbirth, small for sestational age, preterm birth, and birth defects. Data collection and analysis: The pooled relative risk (RR) was applied for the effect measure of the study. RRs and 95% confidence interval (CI) were measured when the paper did not report the effect. Heterogeneity between studies was assessed using the Cochrane's Q and I2 statistics. Main results: Of 374 identified citations, 8 met inclusion criteria. Compared with the unexposed pregnancies, HPV vaccine exposed pregnancies were associated with no higher risk for spontaneous abortion (RR, 0.99 [95% CI, 0.90 to 1.08]); stillbirth (RR, 1.16 [95% CI, 0.71 to 1.90]); small for gestational age (RR, 0.96 [95% CI, 0.86 to 1.07]); preterm birth (RR, 1.04 [95% CI, 0.91 to 1.18]); or birth defects (RR, 1.18 [95% CI, 0.97 to 1.43]). Conclusions: Inadvertent bivalent/quadrivalent HPV vaccination during pregnancy was not associated with significantly greater risks of adverse pregnancy outcomes.

Development of a community-based hearing loss prevention and control service model in Guangdong, China.

BACKGROUND: Hearing loss is a prevalent sensorineural disorder and a major public health issue in China. It is suggested that half of all cases of hearing loss can be prevented through public health measures. However, national strategies for hearing healthcare are not implemented well in Guangdong and some other regions in China. METHODS: To develop a community-based service model for the prevention and control of hearing loss in Guangdong, we integrated the model with multiple maternal and child healthcare models, and set up a series of clinical programs along with an optimum timeline for the preventive measures and intervention treatments to take place. A total of 36,090 families were enrolled in the study, including 358 high-risk families and 35,732 general-risk families. RESULTS: The study lasted for 6.5 years, and 30,769 children were born during that period. A total of 42 children were born with congenital deafness; 17 of them were born into families with advanced genetic risks for hearing loss, 9 were born with specific medical conditions, and 16 were born into general-risk families. About one third of them were diagnosed prenatally, others were diagnosed within 3 months of age, and 72% of them received interventions initiated before 6 months of age. 13 children presented with delayed hearing loss; 9 of them were diagnosed with delayed hereditary sensorineural deafness in neonatal period, and 4 were diagnosed within 3 months after onset. Timely interventions were provided to them, with appropriate referrals and follow-ups. Beside these, 80 families were identified with genetic susceptibility to aminoglycoside ototoxicity. Detailed medication guides were provided to prevent aminoglycoside-induced hearing loss. Moreover, through health education and risk reduction strategies, the prevalence of TORCH syndrome decreased from 10.7 to 5.2 per 10,000. Additionaly, the awareness rates of health knowledge about hearing healthcare significantly increased in the cohort. CONCLUSIONS: Adapting national strategies for local or district projects could be an important step in implementing hearing loss prevention measures, and developing community-based service models could be of importance in carrying them out.

Genetic testing for Prader-Willi syndrome and Angelman syndrome in the clinical practice of Guangdong Province, China.

BACKGROUND: Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are clinically distinct neurodevelopmental disorders caused by absence of paternally or maternally expressed imprinted genes on chromosome 15q11.2-q13.3 region. METHODS: 3331 individuals was recruited from June 2013 to December 2016 under an institutional review board-approved protocol of informed consent. The methylation-specific PCR was employed as a first-tier screening test. The multiplex-fluorescent-labeled STR linkage analysis was carried out to define the underlying genetic mechanisms. The chromosomal microarray analysis was employed to identify chromosomal breakpoints in confirmed cases, and to detect other chromosomal abnormalities in undiagnosed cases. Genetic counseling and recurrence risk assessment were provided to families with affected individuals. RESULTS: The methylation-specific PCR identified 36 PWS suspected patients and 13 AS suspected patients. UBE3A sequence analysis identified another 1 patient with AS. The STR linkage analysis define the underlying genetic mechanisms. Thirty PWS patients were with paternal deletions on chromosome region 15q11-q13, 5 with isodisomic uniparental disomy and 1 with mixed segmental isodisomic/ heterodisomic uniparental disomy of maternal chromosome 15. Twelve AS patients were with maternal deletions, 1 with isodisomic uniparental disomy and 1 with UBE3A gene mutation. The chromosomal microarray analysis identified chromosomal breakpoints in confirmed cases, and detected chromosomal abnormalities in another 4 patients with clinically overlapped features but tested negative for PWS/AS. Genetic counseling was offered to all families with affected individuals. CONCLUSIONS: Identifying the disorders at early age, establishing the molecular mechanisms, carrying out treatment intervention and close monitoring can significantly improve the prognosis of PWS/AS patients.

Sulforaphane and myricetin act synergistically to induce apoptosis in 3T3­L1 adipocytes.

The aim of the present study was to investigate whether sulforaphane (SFN) and myricetin (Myr) synergistically induce apoptosis in adipocytes. The viability of mature 3T3­L1 adipocytes treated with 40 µM SFN and/or 100 µM Myr was assessed using an MTT assay. Apoptosis was assessed by Hoechst 33258 nuclear staining, and by detection of single­stranded DNA using an enzyme­linked immunosorbent assay. Compared with the effects of each compound alone, the combination of SFN and Myr synergistically reduced cell viability, induced apoptosis, increased pro­apoptotic Bcl­2 associated X protein expression, decreased anti­apoptotic B­cell lymphoma­2 expression, enhanced Bcl­2­associated death promoter (Bad) translocation from the cytoplasm to the mitochondria, and reduced Bad phosphorylation at Ser112. These effects were accompanied by increased cleavage of caspase 3 and poly­ADP­ribose­polymerase. In addition, combined SFN and Myr treatment significantly decreased the protein expression levels of phosphorylated AKT serine/threonine kinase 1 (Akt) at Ser473, as well as the phosphorylation of the downstream protein ribosomal protein, S6 kinase ß­1. Therefore, SFN plus Myr was a more potent inducer of apoptosis in 3T3­L1 adipocytes than either compound alone. The results of the present study suggest that the mechanism of SNF/Myr­induced apoptosis involved activation of the Akt­mediated mitochondrial apoptotic pathway. This may aid treatment of animal models of obesity and preclinical testing.

Sulforaphane protects MLE-12 lung epithelial cells against oxidative damage caused by ambient air particulate matter.

Ambient air particulate matter with aerodynamic diameters ≤2.5 µm (PM2.5) can cause pulmonary injury. Oxidative stress is thought to be an important mechanism of PM2.5-mediated toxicity. Sulforaphane (SFN), a compound derived from cruciferous vegetables, is a well-known potent antioxidant; however, its protective effect on lung epithelial cells exposed to PM2.5 is unclear. The results showed that SFN pre-treatment markedly inhibited PM2.5-induced apoptosis of the type II alveolar epithelial cell line MLE-12 by elevating glutathione S-transferase levels and decreasing reactive oxygen species. SFN pre-treatment down-regulated the expression of the pro-apoptotic proteins Bax and Bad, and reduced the activity of caspase-3, while it up-regulated the expression of the anti-apoptotic protein Bcl-2. Moreover, SFN induced the activation of the Akt and ERK pathways, and up-regulated the expression of Nrf2 and its downstream antioxidant genes NQO-1 and HO-1. This is the first study to demonstrate that SFN could protect MLE-12 cells against PM2.5-induced oxidative damage via activation of the Nrf2 pathway and inhibition of the mitochondrial apoptotic pathway; therefore, SFN may be a promising compound for preventing PM2.5-triggered pulmonary cell damage.

Plasma trans-fatty acids levels and mortality: a cohort study based on 1999-2000 National Health and Nutrition Examination Survey (NHANES).

BACKGROUND: Trans-fatty acids (TFAs) occur in small amounts in nature but became widely produced by the food industry. The hazardous effects of different TFA subtypes to human health are controversial. We aimed to evaluate the association of plasma TFAs levels (elaidic acid, vaccenic acid, palmitelaidic acid, and linoelaidic acid) with mortality. METHODS: Utilizing 1999-2000 Nutrition Examination Survey (NHANES) and linked mortality data, we performed a cohort study with 1456 participants and used Cox proportional hazards models and penalized smoothing spline plots to elucidate the relationships between TFAs and all-cause, cardiovascular diseases (CVD) and cancer mortality. RESULTS: During 16,034 person-years of follow-up, a total of 221 deaths occurred. In the multivariate model, including mutual adjustment for the 4 TFA subtypes, elaidic acid associated with higher all-cause mortality (hazard ratio (HR) = 2.00, 95% confidence interval (CI) = 1.18 to 3.40, fourth quartiles versus second quartiles) and CVD mortality (HR = 1.64, 95% CI = 1.07 to 2.50, per 10 units increase). Higher palmitelaidic acid levels were associated with increased cancer mortality (HR = 2.91, 95% CI = 1.09 to 7.81, fourth quartiles versus second quartiles). A J-shaped pattern was observed in the regression curve of elaidic acid and all-cause mortality, as well palmitelaidic acid and cancer mortality. CONCLUSIONS: Plasma elaidic acid levels are associated with higher risk of all-cause and CVD mortality, and palmitelaidic acid levels are associated with higher cancer mortality in later life. Further studies are needed to investigate current inconsistent results in this field and the possible underlying mechanisms.

Sulforaphane induces apoptosis in adipocytes via Akt/p70s6k1/Bad inhibition and ERK activation.

Sulforaphane (SFN), an isothiocyanate isolated from cruciferous vegetables, possesses anti-oxidant and anti-cancer bioactivities. Moreover, SFN exerts its pro-apoptotic effects in some cancer lines. However, the effects and mechanisms of SFN on the regulation of apoptosis of adipocytes are still unknown. In this study, we found that SFN induced significant apoptosis in 3T3-L1 adipocytes and markedly decreased the cellular lipid content. Western blot demonstrated that SFN-induced apoptosis was mediated via the mitochondrial apoptosis pathway based on increased cleavage of poly-ADP-ribose-polymerase (PARP), release of cytochrome c into the cytoplasm, and activation of caspase-3, as well as decreased Bcl-2/Bax ratio. In addition, SFN markedly decreased phosphorylation of Akt and downstream proteins, p70s6k1 and Bad, and increased phosphorylation of ERK. Therefore, our findings clarified that SFN could induce 3T3-L1 adipocyte apoptosis via down-regulation of the Akt/p70s6k1/Bad pathway and up-regulation of the ERK pathway, suggesting SFN may be a promising agent for the treatment or prevention of obesity.

Molecular pathways regulating the formation of brown-like adipocytes in white adipose tissue.

Adipose tissue is functionally composed of brown adipose tissue and white adipose tissue. The unique thermogenic capacity of brown adipose tissue results from expression of uncoupling protein 1 in the mitochondrial inner membrane. On the basis of recent findings that adult humans have functionally active brown adipose tissue, it is now recognized as playing a much more important role in human metabolism than was previously thought. More importantly, brown-like adipocytes can be recruited in white adipose tissue upon environmental stimulation and pharmacologic treatment, and this change is associated with increased energy expenditure, contributing to a lean and healthy phenotype. Thus, the promotion of brown-like adipocyte development in white adipose tissue offers novel possibilities for the development of therapeutic strategies to combat obesity and related metabolic diseases. In this review, we summarize recent advances in understanding the molecular mechanisms involved in the recruitment of brown-like adipocyte in white adipose tissue.