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BACKGROUND/OBJECTIVE Gait speed is an important indicator for assessing overall health status. Previous studies have reported the important role of sensory function in gait speed; however, the underlying mechanism is still unclear. This study aimed to examine whether cognition mediates the association of sensory function with gait speed among English older adults. METHODS Gait speed was assessed by "timed walking test". Hearing was measured by using a hearing screening device. Vision was self-reported. Cognition was assessed by questionnaire. Baron and Kenny's causal steps method and Sobel test were used to examine the mediating effect. RESULTS Among 4,197 participants aged 60 years and older, 13.5% had poor hearing and 12.6% had poor vision, 2.6% had both poor hearing and poor vision. Multiple linear regression models suggested that poor hearing (β= - 1.905, p

Objective To explore the effect of sleep duration at baseline on the incident IADL disability among middle-aged and older Chinese, and test whether cognition mediates this causality. Methods Data were collected from wave 1 (2011-2012) to wave 3 (2015-2016) of the China Health and Retirement Longitudinal Study (CHARLS). Sleep duration was self-reported at baseline. Cognitive function, including episodic memory and mental intactness were measured via a questionnaire. IADL was assessed at baseline and follow-up. Baron and Kenny's causal steps and Karlson/Holm/Breen (KHB) method were conducted to examine the mediating effect. Results A total of 10,328 participants free of IADL disability at baseline were included in this study. Over 4 years of follow-up, 17.1% of participants developed IADL disability. Compared to 7-8 h sleep duration, both short sleep (OR=1.460; 95% CI: 1.261-1.690 for sleeping ≤5 h; OR= 1.189; 95% CI: 1.011-1.400 for sleeping 5-7 h) and long sleep (OR=1.703; 95% CI: 1.269-2.286 for sleeping >9 h) were linked with incident IADL disability. KHB method identified significant mediating effect of cognition on the relationship between extreme sleep durations (≤5 h or >9 h) and IADL disability and the proportional mediation through cognition was 21.32% and 21.06% for sleeping ≤5 h and >9 h, respectively. Conclusion Both short (sleeping ≤5 h) and long sleep duration (sleeping >9 h) predicted incident IADL disability. Cognition partially mediated the effect of extreme sleep durations on IADL disability.

To explore the optimal way to manage patients with high-grade squamous intraepithelial lesion (HSIL) and positive margin by identifying the risk factors for its recurrence and residue. A retrospective study was conducted on 267 cases of a pathologically confirmed HSIL with positive margin following conization by loop electrosurgical excisional procedure (LEEP) between January 2010 and December 2015. One hundred two cases were selected for regular follow-up every 6 months, and 165 cases were selected for a second surgery (repeat cervical conization or hysterectomy) within 3 months of initial LEEP. We analyzed the association between recurrent or residual diseases and these factors: age, menopausal status, ThinPrep cytologic test (TCT) results, high-risk human papillomavirus (HR-HPV) infection, pathological grades of the margin, number of involved margins, and glandular involvement. The recurrence rate among 102 cases who underwent follow-up was 17.6% (18/102). The factors: atypical squamous cells of undetermined significance cannot exclude HSIL (ASC-H) or higher lesions in the pre-LEEP TCT (P = .038), persistent HR-HPV infection at the 6th month post-LEEP (P = .03), HSIL-positive margin (P = .003), and multifocal-involved margin (P = .002) were significantly associated with recurrent disease, while age, menopause, and pre-LEEP HR-HPV infection were not associated with recurrent disease (P > .05). The residual rate among 165 patients who underwent a second surgery was 45.5% (75/165), of which 15 cases were residual cervical cancer. The factors: menopause (P = .02), ≥ASC-H in pre-LEEP TCT (P = .04), pre-LEEP HR-HPV infection (P = .04), ≥HSIL-positive margin (P .05). For patients with a positive margin after LEEP, regular follow-up or second surgery should be selected according to fertility requirement and pathological characteristics of the positive margin, as well as TCT and HR-HPV infection condition.

Human leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1), an immunoinhibitory receptor, is expressed on most types of hematopoietic cells and some tumor cells. LAIR-1 plays an inhibitory role in immune cell maturation, differentiation, and activation. LAIR-1 is also involved in some autoimmune diseases and tumors. However, the mechanism controlling the regulation of the LAIR-1 gene is still unknown. In order to elucidate the molecular mechanisms involved in LAIR-1 regulation, in the present study, we cloned and characterized the promoter region of LAIR-1 gene using a series of truncated promoter plasmids in luciferase reporter assays. Our results show that the basic core promoter of LAIR-1 is located within the region -256/-8 relative to the translational start site. Our further studies indicate that five ETS transcription factors: ELF-1, ETV-4, ETV-3L, ETS-1 and ETS-2, can up-regulate the LAIR-1 basic promoter activity. Of these, ETS-2 is the most effective transcription factor. Moreover, ETS-2 was confirmed to interact directly with the basic promoter of LAIR-1. This study presents the first description of regions/factors capable of up-regulation the promoter activity of LAIR-1. This new knowledge contributes to understanding of the molecular mechanisms involved in LAIR-1 associated immune regulation and diseases.

Objectives To evaluate the dose-response relationships between alcohol consumption and functional limitations in older European men, and explore the role of muscle strength as a mediator of these relationships. Design Cross-sectional study of older men participating in the Survey of Health, Aging and Retirement in Europe (SHARE). Setting Urban and rural households in 17 European countries and Israel. Participants A total of 17 870 men aged 65 years and older from the SHARE (Wave 6, 2015) were included in this study. Measurements Outcome variables were functional limitations: mobility limitation, arm function limitation, and fine motor limitation. Main exposure variable was alcohol consumption. Mediating factor was grip strength. Basic demographics, life habits, and health status were considered as potential confounders. Dose-response analyses with restricted cubic splines and the Karlson/Holm/Breen method were conducted. Results A total of 17 870 participants were included in this study. Dose-response analyses revealed that moderate alcohol consumption was related to the lower odds of reporting mobility limitation (≤35 units/wk) and arm function limitation (≤41 units/wk), with a minimum odds ratio (OR) occurring at 10 units/week drinks for mobility limitation (OR = .71; 95% confidence interval [CI] = .62-.81) and arm function limitation (OR = .66; 95% CI = .59-.75). The odds of reporting the fine motor limitation monotonically increased with alcohol consumption when alcohol consumption was beyond 15 units/week. No significant mediating effect of grip strength on the relationships between alcohol consumption and mobility limitation and arm function limitation was found. Conclusion Moderate alcohol consumption has a protective role in mobility and arm function limitation in older European men. Grip strength is not the main mediator of these associations, suggesting that the protective effect is independent of muscle strength. Alcohol consumption is associated with higher odds of reporting fine motor limitation in older European men. J Am Geriatr Soc 67:2331-2337, 2019.

Ethnopharmacological relevance Traditional Chinese medicine Astragalus membranaceus (Fisch.) Bunge (AM) has been utilized for the treatment of diabetes mellitus and its complications for centuries. Astragalus polysaccharides (APS), the main bioactive ingredient extracted from the root of AM, is prescribed widely in China and has definite cardioprotective effect during diabetic cardiomyopathy (DCM). Endoplasmic reticulum (ER) stress-induced apoptosis played a crucial role in the progression of DCM. However, the regulatory mechanisms of APS on ER stress pathway haven't been comprehensively studied so far. Aim of the study: The aim of this study was to identify the effect of APS on cardiomyocyte apoptosis and to investigate the mechanisms for the anti-apoptotic effect of APS during DCM. Materials and methods DCM rat model was induced by intraperitoneal streptozotocin (STZ) injection and treated with APS for 16 weeks. Cardiac function, pathological changes and apoptotic cells were assessed by echocardiography, hematoxylin-eosin (HE) staining and TUNEL assay, respectively. Expressions of key molecules in ER stress pathway were detected by Western blot analysis. Cardiomyocytes were exposed to high glucose (HG) and treated with APS for 24 h. Cell viability, apoptosis and protein expressions were assessed by MTT, flow cytometer and Western blot analysis, respectively. Moreover, lentivirus over-expressing (OE) C/EBP homologous protein (CHOP) was employed to further investigate the causative role of ER stress pathway in APS-mediated effect on cardiomyocyte apoptosis. Results In vivo, the results demonstrated that APS could improve heart function and attenuate myocardial apoptosis in DCM rat model. Further study demonstrated that APS could down-regulate the protein expressions of activating transcription factor 6 (ATF6) and protein kinase RNA-like ER kinase (PERK) related factors of ER stress pathway. In vitro, APS significantly inhibit HG stimulated H9C2 cell apoptosis and the expressions of ATF6 and PERK related proteins of ER stress pathway. However, after CHOP-OE lentivirus transfection, the protective effects of APS were diminished as increased apoptotic rate and higher expression of CHOP. Conclusions APS could attenuate cardiomyocyte apoptosis via down-regulating the expression of ATF6 and PERK related factors of ER stress pathway in DCM rats and HG-stimulated H9C2 cells.

Background Apoptosis plays a critical role in the progression of diabetic cardiomyopathy (DC). Astragalus polysaccharides (APS), an extract of astragalus membranaceus (AM), is an effective cardioprotectant. Currently, little is known about the detailed mechanisms underlying cardioprotective effects of APS. The aims of this study were to investigate the potential effects and mechanisms of APS on apoptosis employing a model of high glucose induction of apoptosis in H9C2 cells. Methods A model of high glucose induction of H9C2 cell apoptosis was adopted in this research. The cell viabilities were analyzed by MTT assay, and the apoptotic response was quantified by flow cytometry. The expression levels of the apoptosis related proteins were determined by Real-time PCR and western blotting. Results Incubation of H9C2 cells with various concentrations of glucose (i.e., 5.5, 12.5, 25, 33 and 44 mmol/L) for 24 h revealed that cell viability was reduced by high glucose dose-dependently. Pretreatment of cells with APS could inhibit high glucose-induced H9C2 cell apoptosis by decreasing the expressions of caspases and the release of cytochrome C from mitochondria to cytoplasm. Further experiments also showed that APS could modulate the ratio of Bcl-2 to Bax in mitochondria. Conclusions APS decreases high glucose-induced H9C2 cell apoptosis by inhibiting the expression of pro-apoptotic proteins of both the extrinsic and intrinsic pathways and modulating the ratio of Bcl-2 to Bax in mitochondria.

To estimate whether the associations of obesity, physical activity, vision and grip strength with functional mobility were modified by age.Data from The Irish Longitudinal Study on Ageing (2009-2012) were analyzed and 5001 individuals were included in this study. Mobility was assessed by the timed up and go test (TUG-test). Main exposure variables were obesity, physical activity, visual acuity and grip strength at baseline. Multiple linear regression models were fitted to assess the associations of baseline main exposure variables with 2-year follow-up functional mobility and potential confounders were adjusted. Stratified analyses by age were used to assess the interaction between main exposures and age on functional mobility.Multiple linear regression models identified significant interactions of obesity (P 0.001), vigorous physical activity (P = 0.001), vision (P 0.001) and grip strength (P 0.001) with age on functional mobility. Stratified analyses suggested that the risk effect of obesity on functional mobility was greater in middle-aged group (β = 0.025, P 0.001) than in older group (β = 0.016, P = 0.017). The protective effects of high level of physical activity and grip strength on functional mobility were stronger in older group (β = -0.023, P = 0.004 for physical activity; β = -0.002, P 0.001 for grip strength) than in middle-aged group (β = -0.012, P = 0.008 for physical activity; β = -0.0015, P 0.001 for grip strength). The benefit of better vision on functional mobility was observed in middle-aged group only (β = -0.032, P = 0.002).Non-obesity, higher level of physical activity, vision and grip strength at baseline were associated with better mobility performance among middle-aged and older Irish. And these associations were modified by age.

Background Observational studies and meta-analyses suggested that increased total fruits and vegetables consumption have a protective role in incidence of type 2 diabetes mellitus (T2DM). However, we still don't know whether the subtypes, such as citrus fruits and cruciferous vegetables (CV), have a preventive role. Methods We systematically searched the MEDLINE and EMBASE databases up to December 31, 2014. Summary relative risks (SRRs) and 95% confidence intervals (CIs) were calculated using random-effects models. Results Seven distinct prospective cohort studies (five articles) were identified for this study. A total of 16,544 incident cases of type 2 diabetes were ascertained among 306,723 participants with follow-up periods ranging from 4.6 to 24 years. Based on four prospective cohort studies, we found that overall, consumption of CV had a protective role in the T2DM incidence (highest vs. lowest analysis: SRR=0.84, 95% CI: 0.73 to 0.96), with evidence of significant heterogeneity ( P =0.09, I 2 =54.4%). This association was independent of the main risk factors for cardiovascular disease: smoking, alcohol use, BMI, and physical activity etc. Consumption of citrus fruits did not have a protective role in the T2DM development (highest vs. lowest analysis: SRR=1.02, 95% CI: 0.96 to 1.08), with no evidence of significant heterogeneity ( P =0.49, I 2 =0). Conclusions Higher consumption of CV, but not citrus fruits, is associated with a significantly decreased risk of type 2 diabetes. Further large prospective studies are needed to elucidate both relationships.