Cardiorespiratory fitness (CRF), a proxy for cardiovascular and respiratory function, has been linked to health outcomes, but its association with cognition and dementia risk remains unclear. We aimed to investigate the association of CRF with domain-specific cognitive function and dementia risk, taking genetic predisposition for dementia into account. Within the UK Biobank, 61,214 dementia-free participants aged 39-70 (mean age: 56.33 ± 8.15, 51.96% were female) were followed for up to 16 years to detect incident dementia. CRF score (measured in metabolic equivalent of task [MET] units) was estimated using a 6-min submaximal exercise test on a stationary bike and divided into tertiles (i.e., low, moderate, and high). Tests of global and domain-specific cognitive functions (including prospective memory, visual memory, verbal/numeric memory, and processing speed) were administered at baseline. Dementia was identified based on medical history and medical records. Genetic predisposition for dementia was estimated using the polygenic risk score for Alzheimer’s disease (PRS AD ), tertiled as low, moderate, or high level. Data were analyzed using linear regression, Poisson regression, and Laplace regression. The age- and sex-specific CRF ranged from -2.74 to 6.61 MET at baseline. In multi-adjusted linear regression, compared to low CRF, high CRF was related to better global cognitive function (β [95% confidence interval]: 0.05 [0.04, 0.06]), prospective memory (0.06 [0.04, 0.08]), verbal/numeric memory (0.11 [0.09, 0.13]), and processing speed (0.05 [0.03, 0.07]). Over the follow-up (median [interquartile range]: 11.52 [11.62–11.87] years), 553 individuals developed dementia. Compared to low CRF, the incidence rate ratio (IRR [95% CI]) of dementia was 0.61 (0.48–0.77) for high CRF, and the onset of dementia was delayed by 1.47 (95% CI: 0.64–2.30) years among people with high vs . low CRF. Among people with moderate/high genetic risk for dementia, high CRF can attenuate dementia risk by 35% (IRR = 0.65, 95% CI: 0.51–0.82). There was a trend of CRF to alleviate the genetic risk for dementia, but the additive interaction was not significant. High CRF is associated with better cognitive performance at baseline, and lower dementia risk over follow-up. High CRF could mitigate the impact of genetic predisposition on dementia risk by almost 40%.

Objective We aimed to investigate the association of cardiorespiratory fitness (CRF) with cognitive function and dementia risk, taking genetic predisposition for dementia into account.Methods Within the UK Biobank, 61 214 dementia-free participants aged 39-70 years were followed for up to 12 years. CRF score was estimated using a 6 min submaximal exercise test on a stationary bike and divided into tertiles (ie, low, moderate, and high; standardised by age and sex). Global cognitive function was evaluated at baseline. Dementia was identified based on medical history and medical records. Genetic predisposition for dementia was estimated using the polygenic risk score for Alzheimer's disease (PRSAD), tertiled as low, moderate, or high. Data were analysed using linear regression, Poisson regression, and Laplace regression.Results Compared with low CRF, high CRF was related to better global cognitive function (beta=0.05, 95% CI 0.04 to 0.07). Over the follow-up period, 553 individuals developed dementia. Compared with low CRF, the incidence rate ratio (IRR) of all dementia was 0.60 (95% CI 0.48 to 0.76) for high CRF, and the onset of all dementia was delayed by 1.48 (95% CI 0.58 to 2.39) years among people with high versus low CRF. Among people with a moderate/high polygenic risk score, high CRF attenuated all dementia risk by 35% (IRR 0.65, 95% CI 0.52 to 0.83).Conclusion High CRF is associated with better cognitive performance at baseline, and lower dementia risk long-term. High CRF could mitigate the impact of genetic predisposition on the development of dementia by 35%.

Abstract Background Cardiometabolic diseases (CMDs) including heart disease, stroke, and type 2 diabetes have been individually linked to depression. However, their combined impact on depression risk is unclear. We aimed to examine the association between cardiometabolic multimorbidity and depression and explore the role of genetic background in this association. Methods Within the Swedish Twin Registry, 40,080 depression-free individuals (mean age 60 years) were followed for 18 years. Cardiometabolic multimorbidity was defined as having ≥2 CMDs. CMDs and depression were ascertained based on the National Patient Register. Cox regression was used to estimate the CMD-depression association in a classical cohort study design and a matched co-twin design involving 176 twin pairs. By comparing the associations between monozygotic and dizygotic co-twins, the contribution of genetic background was estimated. Results At baseline, 4809 (12.0%) participants had one CMD and 969 (2.4%) had ≥2 CMDs. Over the follow-up period, 1361 participants developed depression. In the classical cohort design, the multi-adjusted hazard ratios (95% confidence interval [CIs]) of depression were 1.52 (1.31–1.76) for those with one CMD and 1.83 (1.29–2.58) for those with ≥2 CMDs. CMDs had a greater risk effect on depression if they developed in mid-life (<60 years) as opposed to late life (≥60 years). In matched co-twin analysis, the CMD-depression association was significant among dizygotic twins (HR = 1.63, 95% CI, 1.02–2.59) but not monozygotic twins (HR = 0.90, 95% CI, 0.32–2.51). Conclusions Cardiometabolic multimorbidity is associated with an elevated risk of depression. Genetic factors may contribute to the association between CMDs and depression.

Background: The association between kidney function and dementia risk and the mechanisms underlying this relationship remain unclear. Methods: Within the UK Biobank, 191 970 dementia-free participants aged >= 60 (mean age: 64.1 +/- 2.9 years) were followed for 16 years to detect incident dementia. Serum creatinine and Cystatin C were measured at baseline to calculate estimated glomerular filtration rate (eGFR, mL/min/1.73 m(2)). Kidney function was categorized as normal (eGFR >= 90), mildly impaired (60 <= eGFR < 90), or moderately to severely impaired (eGFR < 60). Dementia was assessed based on self-reported medical history and medical records. During the follow-up, a subsample of 12 637 participants underwent brain MRI scans. Volumes of total brain, gray matter, white matter, hippocampus, and white matter hyperintensities were assessed. Results: Over the follow-up, 5 327 (2.8%) participants developed dementia. Compared to normal kidney function, there was an increased risk of dementia with moderate to severely impaired kidney function (hazard ratio = 1.53, 95% confidence interval [CI]: 1.32-1.76) but not mildly impaired kidney function. In Laplace regression, dementia onset among people with moderate to severely impaired kidney function occurred 1.53 (95% CI: 0.98-2.08) years earlier than those with normal kidney function. Moderate to severely impaired kidney function was related to significantly lower gray matter volume (beta = -0.11, 95% CI: -0.19 to -0.03), but not to other brain magnetic resonance imaging measures. Conclusions: Impaired kidney function is associated with about 50% increased risk of dementia and anticipates dementia onset by more than 1.5 years. Brain neurodegeneration may underlie the kidney function-dementia association.

Adenosine, which may be formed by all cells during relative energy or oxygen deficit, may act as an autocoid by modifying the function of other cells in the local environment. In asthmatic, but not normal, subjects, inhalation of adenosine causes a marked bronchoconstriction which may be reduced by the purinoceptor antagonist theophylline, sodium cromoglycate, nedocromil sodium, histamine, H1-antagonists and cyclo-oxygenase inhibitors. Repeated exposure to adenosine induces a state of tachyphylaxis and cross-tachyphylaxis with exercise-induced bronchoconstriction but not with that provoked by allergen. Although the mechanisms by which adenosine induces changes in airways function are not clear, it is suggested that it has an indirect effect, possibly by up-regulating bronchoconstrictor factors already present in asthma such as mast cell mediator release or neuronal reflexes.

Steroid hormones, including progestagens, estrogens, androgens, corticosteroids, and their precursor cholesterol, perform essential functions in the successful establishment and maintenance of pregnancy and normal fetal development. As the core endocrine organ at the prenatal stage, the human placenta is involved in the biosynthesis, metabolism, and delivery of steroid hormones. Steroidogenic pathways are tightly regulated by placenta-intrinsic cytochrome P450 and hydroxysteroid dehydrogenase. However, the relationship between placental steroidogenic enzyme expression and adverse pregnancy outcomes is controversial. In this review, we summarize the possible upstream regulatory mechanisms of placental steroidogenic enzymes in physiologic and pathophysiologic states. We also describe the human placental barrier model and examine the potential of single-cell sequencing for evaluating the primary functions and cellular origin of steroidogenic enzymes. Finally, we examine the existing evidence for the association between placental steroidogenic enzyme dysregulation and adverse pregnancy outcomes.

Objective We aimed to identify which amino acids are associated with CVDs in adults with type 2 diabetes and compare the results in two different populations. Method This study consisted of two study populations, 718 participants with type 2 diabetes aged 18 to 89 were from Dalian metabolomics research (DMR), and 11,002 participants with type 2 diabetes aged 40 to 70 years were from the UK biobank (UKB). Type 2 diabetes and CVDs were defined using self-reported medical history and medical records. Plasma amino-acid metabolites including alanine (Ala), glutamine (Gln), glycine (Gly), histidine (His), leucine (Leu), phenylalanine (Phe), tyrosine (Tyr), and valine (Val) were assessed through liquid chromatography-mass spectrometry or high-throughput nucleic magnetic resonance spectroscopy metabolomic analysis. Stepwise logistic regression was used in data analysis. Results Among DMR participants, 74 (10.31%) had CVDs, and 1607 (14.61%) in UKB. In multi-adjusted logistic regression, Ala was positively associated with CVDs both in DMR (β = 0.048, 95% CI: 0.022– 0.074) and UKB (β = 0.009, 95% CI: 0.000– 0.018) participants. Lower Tyr was associated with CVDs in DMR (β=-0.035, 95% CI: -0.061– -0.008), while lower Gly (β=-0.017, 95% CI: -0.026– -0.007) and Val (β= -0.031 95% CI: -0.026– -0.007), and higher Gln (β = 0.010, 95% CI: 0.002– 0.018) and Leu (β = 0.024, 95% CI: 0.007– 0.041) were associated with CVDs in UKB. Conclusions High Ala may be an indicator for CVDs in DMR and UKB participants with type 2 diabetes. Tyr, Gly, Val, or Leu is associated with CVDs in type 2 diabetes among DMR/UKB participants.

To examine the association between reproductive duration and postmenopausal depression (taking the use of hormone replacement therapy [HRT] into account).

BACKGROUND:Although age at menopause has been linked to mortality, the association between the entire reproductive lifespan and mortality remains unclear. OBJECTIVE:This study aimed to examine to what extent life-course reproductive duration is associated with all-cause mortality and explore the role of a healthy lifestyle and familial background in such an association. STUDY DESIGN:A total of 11,669 women (mean age, 63.54 years) from the Swedish Twin Registry were followed for up to 19 years. Information on reproductive duration (the interval between ages at menarche and menopause) and lifestyle factors (including smoking, alcohol consumption, and physical activity; divided into unfavorable/intermediate/favorable) was collected on the basis of a structured questionnaire. Survival status was obtained from the Sweden Cause of Death Register. The data were analyzed using generalized estimating equation models, Laplace regression, and conditional logistic regression. RESULTS:In the generalized estimating equation model, compared with those with ≤34 reproductive years, the odds ratio (95% confidence interval) of all-cause mortality was 0.79 (0.68-0.90) for those with ≥40 reproductive years, which prolonged survival time by 0.84 (0.24-1.43) years. Women with ≥40 reproductive years plus a favorable lifestyle (odds ratio, 0.28; 95% confidence interval, 0.23-0.35) were at a lower risk of all-cause mortality than those with <40 reproductive years plus an unfavorable lifestyle. An additive interaction between ≥40 reproductive years and a favorable lifestyle on all-cause mortality was observed (attributable proportion, 0.584; 95% confidence interval, 0.016-1.151). The odds ratios in conditional logistic regression and generalized estimating equation models did not differ significantly (P=.67). CONCLUSION:A longer reproductive lifespan is associated with reduced all-cause mortality and prolongs survival by 0.84 years. A favorable lifestyle may amplify the beneficial effect of longer reproductive lifespan on mortality. Familial background does not account for the observed association.

Background. Type 2 diabetes has been associated with increased risk of gynecologic cancers, yet the effect of gestational diabetes mellitus (GDM) on gynecologic cancers is unclear. Objectives. To examine associations between GDM history and subsequent gynecologic cancers in parous women, and to explore whether gestational hypertension (GH) plays a role in the associations. Study design. The population-based cohort study included 15,941 individuals from the Swedish Twin Registry. The history of GDM and GH was ascertained based on self-reports. Incident cases of gynecologic cancers (including cancers of the cervix, uterus, ovaries and other female genitalia) were obtained from the National Patients Registry and the Swedish Cancer Registry. Generalized estimating equation models were applied to analyze associations between GDM and gynecologic cancers. Stratified analysis was used to explore whether associations between GDM and gynecologic cancers differed by GH. Additive and multiplicative interactions were calculated between GDM and GH. Results. Of all participants, 350 (2.2%) had GDM, and 1762 (11.1%) had incident gynecologic cancers. No statistically significant associations were found between GDM and risks of any gynecologic cancers. However, GDM was associated with an increased risk of ovarian cancer (OR = 5.29, 95% CI: 1.63-17.19) in women with GH. Interactions between GDM and GH were observed on the additive scale (Attributable proportion due to interaction: 0.86, 95% CI 0.42-1.30, P < 0.001). Conclusions. The associations between GDM and risks of gynecologic cancers were not evident, but the effect of GDM on the risk of ovarian cancer was modified by GH. Further validation in larger cohorts is warranted. (c) 2021 Published by Elsevier Inc.

目的 了解医学生对人乳头瘤状病毒(HPV)和 HPV疫苗的知晓率、认知度和接种意愿,分析影响接种意愿的因素和原因.方法 于2018年10月采用分层随机抽样的方法,随机选取天津市某高校不同专业共1 106名医学生进行问卷调查.应用多变量改良版的Poisson回归模型分析影响疫苗接种意愿的相关因素.结果 共发放问卷1 106份,有效问卷1 098份(99.28%) .医学生对HPV 及其疫苗的知晓率为 63 .48%,总认知合格率为 58 .93%.医学生中 HPV 疫苗接种意愿率为82. 88%,HPV疫苗接种率仅为2 .46%.单因素分析结果显示,女性的疫苗接种意愿率高于男性(χ2 ＝159 .88) ,预防和其他专业的接种意愿率高于临床专业(χ2 ＝6 .62) ,少数民族高于汉族(χ2 ＝5 .15) ,无性行为者高于有性行为者(χ2 ＝6 .49) ,对 HPV及其疫苗知晓者高于不知晓者(χ2 ＝28 .96) ,对HPV认知合格者高于不合格者(χ2 ＝17 .62) ,以上差异均具有统计学意义(均 P＜0 .05) ;多因素分析结果显示,女性(RR＝7 .74 ,95% CI :5 .23～11 .47) 、知晓HPV及其疫苗者(RR＝1 .85 ,95% CI :1 .27～2 .69) 、对 HPV认知合格者(RR＝1 .47 ,95% CI :1 .02～2 .11)更愿意接种疫苗.结论 医学生对 HPV及其疫苗的知晓率和认知度较高,但对HPV传播途径和HPV疫苗相关知识等认识不足.接受调查者中HPV疫苗接种率低,但接种意愿积极.卫生部门及高校应加强对大学生HPV相关知识的宣传教育,同时需制定适合中国国情的疫苗接种政策,并加强对疫苗质量的监管,有助于 HPV疫苗在大学生中的推广和普及.