P2X7 receptor inhibition prevents atrial fibrillation in rodent models of depression.

AIMS: Depression, the most prevalent psychiatric disorder, is associated with the occurrence and development of atrial fibrillation (AF). P2X7 receptor (P2X7R) activation participates in the development of depression, but little attention has been given to its role in AF. This study was to investigate the effects of P2X7R on AF in depression models. METHODS AND RESULTS: Lipopolysaccharide (LPS) and chronic unpredictable stress (CUS) were carried out to induce depression in rodents. Behavioural assessments, atrial electrophysiological parameters, electrocardiogram (ECG) parameters, western blot, and histology were performed. Atrial fibrillation inducibility was increased in both LPS- and CUS-induced depression, along with the up-regulation of P2X7R in atria. CUS facilitated atrial fibrosis. CUS reduced heart rate variability (HRV) and increased the expression of TH and GAP43, representing autonomic dysfunction. Down-regulation of Nav1.5, Cav1.2, Kv1.5, Kv4.3, Cx40, and Cx43 in CUS indicated the abnormalities in ion channels. In addition, the expression levels of TLR4, P65, P-P65, NLRP3, ASC, caspase-1, and IL-1ß were elevated in depression models. Pharmacological inhibitor (Brilliant Blue G, BBG) or genetic deficiency of P2X7R significantly mitigated depressive-like behaviours; ameliorated electrophysiological deterioration and autonomic dysfunction; improved ion channel expression and atrial fibrosis; and prevented atrial NLRP3 inflammasome activation in the pathophysiological process of AF in depression models. CONCLUSION: LPS or CUS induces AF and promotes P2X7R-dependent activation of NLRP3 inflammasome, whereas pharmacological P2X7R inhibition or P2X7R genetic deficiency prevents atrial remodelling without interrupting normal atrial physiological functions. Our results point to P2X7R as an important factor in the pathology of AF in depression.

Association between loneliness and mild cognitive impairment in older adults: a meta-analysis of longitudinal studies.

OBJECTIVES: Prior studies reporting the effects of loneliness on mild impairment cognitive (MCI) have generated inconsistent results. This meta-analysis aimed to investigate the longitudinal association between loneliness and risk of MCI among community-dwelling middle-aged and older adults. METHOD: Five electronic databases were searched from inception to 9 May 2023. Eligible studies examined the longitudinal association between loneliness and cognitive outcomes, including incident MCI, cognitive impairment, and cognitive decline. Odds ratios (OR) and 95% confidence intervals (CIs) were calculated using random-effects or fixed-effects meta-analysis. Sensitivity analysis and subgroup analysis were conducted. Publication bias was examined using Egger's and Begg tests. RESULTS: Eight studies were included. Among the 45,032 participants, 10,570 were diagnosed with MCI/cognitive decline. Loneliness was positively associated with an increased risk of MCI (overall OR = 1.14; 95% CI = 1.05, 1.23), with moderate heterogeneity (I2 = 44.2%). Sensitivity analysis have minimal influence on the aforementioned pooled effect. Subgroup analyses indicated stronger associations in studies which employed incident MCI as cognitive outcome (OR = 2.55, 95%CI = 1.31, 1.83), were conducted in non-Asia countries (OR = 1.52, 95%CI = 0.95, 1.20), and reported no depression adjustment (OR = 1.51, 95%CI = 1.04, 1.25). The association between loneliness and MCI was stronger among males compare to females. The Egger test and Begg test showed no evidence of significant publication bias (p = .493; p = .474). CONCLUSION: The findings indicated that loneliness was associated with an increased risk of MCI. Future longitudinal studies should evaluate potential cases of MCI through comprehensive clinical assessments by practitioners to draw robust findings on the association of loneliness with MCI.

Loneliness was associated with an increased risk of MCI in older adults.The association between loneliness and MCI was stronger in the males compared to the females.Future studies are warranted to assess loneliness by validated scales and clinical assessments of MCI.

Trends in obesity and severe obesity prevalence in the United States from 1999 to 2018.

BACKGROUND: The national obesity epidemic and trend of obesity prevalence have been characterized by a series of cross-sectional surveys in the United States, however, less is known about obesity prevalence trajectory by birth cohort. This study aimed to investigate whether trends in obesity and severe obesity prevalence varied by birth cohorts among 1940s-1990s in the United States. METHODS: Using data from the National Health and Nutrition Examination Survey 1999-2018. The trends of obesity and severe obesity prevalence were conducted with synthetic birth cohort. RESULTS: There were 60 981 participants (weighted mean age, 38.1 years; female, 50.1%) assigned in 6 birth cohorts (1990s, 1980s, 1970s, 1960s, 1950s, and 1940s) over 1999-2018. The prevalence of obesity and severe obesity increased significantly with age during all birth cohorts except for the 1940s (Ptrend <0.001). For obesity, a significant positive quadratic trend was observed among 1990s birth cohort (Pnon-linearity  = 0.037), while a significant positive linear trend (Plinearity <0.001) among 1980s, 1970s, 1960s, and 1950s birth cohorts. Corresponding to same weighted mean age, the prevalence of both obesity and severe obesity in younger birth cohorts were much higher than the older birth generations. CONCLUSIONS: The continued upward trend in obesity and severe obesity prevalence by birth cohort highlighted the need for continuing focus on surveillance of body mass index and identification, implementation, and evaluation of evidence-based interventions to address this major health problem in the United States.

Developmental trajectories of health-promoting behaviours among pregnant women: A longitudinal study.

AIMS AND OBJECTIVES: The aim of this study is to estimate differences in health-promoting behaviour levels throughout the pregnancy trimesters, to identify distinct patterns of health-promoting behaviour trajectories during pregnancy and to evaluate predictors of these trajectory group memberships. BACKGROUND: Promoting healthy lifestyle behaviours during pregnancy could decrease devastating outcomes for the mother and foetus. However, there is currently limited insight into the dynamics of health-promoting behaviours during pregnancy. DESIGN: An observational longitudinal study. METHODS: 158 pregnant women were recruited from June 2020 to June 2021 in Qingdao, China. The Health-Promoting Lifestyle Profile was used to assess health-promoting behaviours. Latent growth model was performed to compare health-promoting behaviours at different time points. Group-based trajectory model was applied to identify health-promoting behaviour trajectories. Multinomial logistic regression was adopted to determine the predictors of trajectory group memberships. We used the STROBE checklist to report this study. RESULTS: The entire sample of pregnant women experienced a significant increase in health-promoting behaviours during pregnancy. Three trajectories were identified including a 'low-increase behaviour trajectory (20.1% of sample)', a 'moderate-increase behaviour trajectory (58.0% of sample)' and a 'stable then increased behaviour trajectory (21.9% of sample)'. Low maternal sense of coherence, lack of pre-pregnancy exercise habit, artificial insemination and low monthly family income were significantly associated with the low-increase behaviour trajectory. High self-efficacy and pre-pregnancy exercise habit were significantly associated with the stable then increased behaviour trajectory. CONCLUSIONS: Pregnant women exhibit different health-promoting behaviours throughout the pregnancy trimesters. Meanwhile, three trajectories were identified among pregnant women. Thus, more attentions should be paid on early identification and targeted intervention in a future study. RELEVANCE OF CLINICAL PRACTICE: Healthcare providers should pay closer and earlier attention to identify women in the low-increase trajectory subgroup at the outset of pregnancy. Similarly, increased efforts should be made to improve maternal self-efficacy and develop good pre-pregnancy exercise habit in future study.

Effects of e-health interventions on health outcomes in patients with rheumatoid arthritis: a systematic review and meta-analysis.

AIMS AND OBJECTIVES: To evaluate the effects of e-health interventions on disease activity, self-efficacy, pain and quality of life among patients with rheumatoid arthritis (RA). BACKGROUND: Prior systematic reviews have only reported the quality and features of e-health interventions in patients with RA. However, the effect of e-health interventions in patients with RA is unclear. DESIGN: Systematic review and meta-analysis. METHODS: This review was conducted following the PRISMA guideline. We searched 5 databases, including PubMed, EMBASE, CINAHL, Scopus and the Cochrane library. The risk of bias was assessed using the Cochrane risk of bias tool. The quality of the evidence was assessed via the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) criteria. Using a random-effects model adopted the standardised mean difference (SMD) with a 95% confidence interval (CI). A chi-squared test and an I2 test were used to assess heterogeneity. Subgroup analyses were conducted based on different controls. RESULTS: A total of 9 randomised control trials were included in this study. Compared with the control group, disease activity of the e-health group significantly decreased (SMD with 95% CI: -.17 [-.30, -.04], p = .01, I2  = 1%). Meanwhile, trials with usual care control had a larger effect on disease activity (SMD with 95% CI: -.21 [-.40, -.02], p = .03, I2  = 38%). The effect of e-health interventions on self-efficacy was controversial; pain and quality of life were negative in the currently included studies. The quality of evidence was rated as low for disease activity and very low for pain, self-efficacy and quality of life. CONCLUSIONS: The effect of e-health interventions on disease activity was statistically significant. More well-designed randomised controlled trials are still needed to verify the effects in the future. RELEVANCE TO CLINICAL PRACTICE: This study shows the potential value of e-health in improving health outcomes in patients with RA.

Reduced lung function predicts risk of incident type 2 diabetes: insights from a meta-analysis of prospective studies.

Epidemiological studies have repeatedly investigated the association between reduced pulmonary function and incident type 2 diabetes mellitus (T2DM). However, the results have been inconsistent. This meta-analysis aimed to clarify this association with prospective cohort studies. We searched PubMed, Web of Science (ISI), and Google Scholar for all studies (in English) reporting reduced lung function with a risk of T2DM. The measures of lung function included percentage of forced vital capacity for predicted values (FVC%pre), percentage of forced expiratory volume in the first second after expiration for predicted values (FEV1%pre) and FEV1-to-FVC ratio%. Summary risk ratios (RRs) and 95% confidence intervals (CIs) were calculated using fixed-effects or random-effects meta-analyses. A total of 5,480 incident T2DM patients among 88,799 individuals were identified from nine prospective cohort studies. Compared to the highest category of FVC%pre and FEV1%pre, the lowest category of FVC%pre and FEV1%pre were significantly associated with increased incident T2DM risk (FVC%pre: RR = 1.49, 95% CI: 1.39-1.59; FEV1%pre: RR = 1.52, 95% CI: 1.42-1.62). However, no significant relationship was found between the FEV1/FVC ratio and incident T2DM risk (RR = 1.01, 95% CI: 0.91-1.13). Current evidence suggests that restrictive rather than obstructive impairment of lung function is significantly associated with the incidence of T2DM. Further research is warranted to explore potential mediators of this relationship.

Association between pregnancy intention and smoking or alcohol consumption in the preconception and pregnancy periods: A systematic review and meta-analysis.

AIMS: To investigate the association between pregnancy intention and smoking or alcohol consumption in preconception and pregnancy periods. BACKGROUND: Suboptimal lifestyle such as smoking and alcohol consumption can lead to devastating outcomes on the maternal and foetus. Pregnancy intention exerts a significant effect on promoting healthy lifestyle behaviours. However, no reliable evidences confirmed pregnancy intention was associated with smoking and alcohol consumption before and during pregnancy. DESIGN: Systematic review and meta-analysis. METHODS: We performed a comprehensive search from databases including PubMed, Cochrane, Web of Science, IEEE Xplore, MEDLINE, ProQuest and Scopus from the inception of these databases up to November, 2020. All eligible studies exploring the association between pregnancy intention and smoking or alcohol consumption were included. The fixed- or random effect pooled measure was used to estimate the odds ratio (OR) or risk ratio (RR) and 95% CI. In addition, the PRISMA checklist was used in this meta-analysis. RESULTS: A total of 23 studies were included in this systematic review and meta-analysis. During pregnancy, the findings suggested that women with unplanned pregnancy were 68% more likely to consume cigarettes (OR = 1.68, 95% CI = 1.44-1.95) and 44% more likely to consume alcohol (OR = 1.44, 95% CI = 1.15-1.81) than those women with planned pregnancy. Meanwhile, during preconception, women with unplanned pregnancy were 30% more likely to consume cigarettes (OR = 1.30, 95% CI = 1.10-1.53) and 20% more likely to consume alcohol (OR = 1.20, 95% CI = 1.01-1.42) than those women with planned pregnancy. CONCLUSION: The findings suggested that women with unplanned pregnancy were more likely to follow unhealthy behaviours such as smoking and alcohol consumption before and during pregnancy. Health professionals should consider the women's desire for pregnancy to decrease preconception and pregnancy smoking or alcohol consumption in future studies. RELEVANCE OF CLINICAL PRACTICE: Pregnancy intention is the key determinant of smoking and alcohol consumption during preconception and pregnancy periods. Offering effective contraception in primary healthcare setting could prevent unplanned pregnancy. Meanwhile, popularising minimal alcohol consumption and comprehensive smoke-free legislation would be beneficial to improve reproductive outcomes.

Association of COVID-19 vs Influenza With Risk of Arterial and Venous Thrombotic Events Among Hospitalized Patients.

Importance: The incidence of arterial thromboembolism and venous thromboembolism in persons with COVID-19 remains unclear. Objective: To measure the 90-day risk of arterial thromboembolism and venous thromboembolism in patients hospitalized with COVID-19 before or during COVID-19 vaccine availability vs patients hospitalized with influenza. Design, Setting, and Participants: Retrospective cohort study of 41 443 patients hospitalized with COVID-19 before vaccine availability (April-November 2020), 44 194 patients hospitalized with COVID-19 during vaccine availability (December 2020-May 2021), and 8269 patients hospitalized with influenza (October 2018-April 2019) in the US Food and Drug Administration Sentinel System (data from 2 national health insurers and 4 regional integrated health systems). Exposures: COVID-19 or influenza (identified by hospital diagnosis or nucleic acid test). Main Outcomes and Measures: Hospital diagnosis of arterial thromboembolism (acute myocardial infarction or ischemic stroke) and venous thromboembolism (deep vein thrombosis or pulmonary embolism) within 90 days. Outcomes were ascertained through July 2019 for patients with influenza and through August 2021 for patients with COVID-19. Propensity scores with fine stratification were developed to account for differences between the influenza and COVID-19 cohorts. Weighted Cox regression was used to estimate the adjusted hazard ratios (HRs) for outcomes during each COVID-19 vaccine availability period vs the influenza period. Results: A total of 85 637 patients with COVID-19 (mean age, 72 [SD, 13.0] years; 50.5% were male) and 8269 with influenza (mean age, 72 [SD, 13.3] years; 45.0% were male) were included. The 90-day absolute risk of arterial thromboembolism was 14.4% (95% CI, 13.6%-15.2%) in patients with influenza vs 15.8% (95% CI, 15.5%-16.2%) in patients with COVID-19 before vaccine availability (risk difference, 1.4% [95% CI, 1.0%-2.3%]) and 16.3% (95% CI, 16.0%-16.6%) in patients with COVID-19 during vaccine availability (risk difference, 1.9% [95% CI, 1.1%-2.7%]). Compared with patients with influenza, the risk of arterial thromboembolism was not significantly higher among patients with COVID-19 before vaccine availability (adjusted HR, 1.04 [95% CI, 0.97-1.11]) or during vaccine availability (adjusted HR, 1.07 [95% CI, 1.00-1.14]). The 90-day absolute risk of venous thromboembolism was 5.3% (95% CI, 4.9%-5.8%) in patients with influenza vs 9.5% (95% CI, 9.2%-9.7%) in patients with COVID-19 before vaccine availability (risk difference, 4.1% [95% CI, 3.6%-4.7%]) and 10.9% (95% CI, 10.6%-11.1%) in patients with COVID-19 during vaccine availability (risk difference, 5.5% [95% CI, 5.0%-6.1%]). Compared with patients with influenza, the risk of venous thromboembolism was significantly higher among patients with COVID-19 before vaccine availability (adjusted HR, 1.60 [95% CI, 1.43-1.79]) and during vaccine availability (adjusted HR, 1.89 [95% CI, 1.68-2.12]). Conclusions and Relevance: Based on data from a US public health surveillance system, hospitalization with COVID-19 before and during vaccine availability, vs hospitalization with influenza in 2018-2019, was significantly associated with a higher risk of venous thromboembolism within 90 days, but there was no significant difference in the risk of arterial thromboembolism within 90 days.

Weight gain from early to middle adulthood increases the risk of incident asthma later in life in the United States: a retrospective cohort study.

BACKGROUND: Data describing the effects of weight change across adulthood on asthma are important for the prevention of asthma. This study aimed to investigate the association between weight change from early to middle adulthood and risk of incident asthma. METHODS: Using data from the National Health and Nutrition Examination Survey (NHANES), we performed a nationally retrospective cohort study of the U.S. general population. A total of 20,771 people aged 40-74 years with recalled weight at young and middle adulthood were included in the cohort. Four weight change groups were categorized: stable non-obesity, non-obesity to obesity, obesity to non-obesity, and stable obesity. Hazard ratios (HRs) and 95% confidence intervals (CIs) relating weight change to incident asthma over 10 years of follow-up were calculated using Cox models adjusting for covariates. RESULTS: Compared with the stable non-obesity group, the HRs of incident asthma were 1.63 (95% CI = 1.29 to 2.07, P < 0.001) for the non-obesity to obesity group, 1.41 (95% CI = 0.97 to 2.05, P = 0.075) for stable obesity group, and 1.21 (95% CI = 0.41 to 3.62, P = 0.730) for the obesity to non-obesity group. In addition, participants who gained more than 20 kg from young to middle adulthood had a HR of 1.53 (95% CI = 1.15 to 2.03, P = 0.004), compared with those whose weight remained stable (weight change within 2.5 kg). CONCLUSIONS: Weight gain from early to middle adulthood was associated with higher risk of incident asthma as compared to those who maintained normal weight. Thus, maintaining normal weight throughout adulthood might be important for the primary prevention of adult-onset asthma.

Validity of ICD-10-CM diagnoses to identify hospitalizations for serious infections among patients treated with biologic therapies.

PURPOSE: Identifying hospitalizations for serious infections among patients dispensed biologic therapies within healthcare databases is important for post-marketing surveillance of these drugs. We determined the positive predictive value (PPV) of an ICD-10-CM-based diagnostic coding algorithm to identify hospitalization for serious infection among patients dispensed biologic therapy within the FDA's Sentinel Distributed Database. METHODS: We identified health plan members who met the following algorithm criteria: (1) hospital ICD-10-CM discharge diagnosis of serious infection between July 1, 2016 and August 31, 2018; (2) either outpatient/emergency department infection diagnosis or outpatient antimicrobial treatment within 7 days prior to hospitalization; (3) inflammatory bowel disease, psoriasis, or rheumatological diagnosis within 1 year prior to hospitalization, and (4) were dispensed outpatient biologic therapy within 90 days prior to admission. Medical records were reviewed by infectious disease clinicians to adjudicate hospitalizations for serious infection. The PPV (95% confidence interval [CI]) for confirmed events was determined after further weighting by the prevalence of the type of serious infection in the database. RESULTS: Among 223 selected health plan members who met the algorithm, 209 (93.7% [95% CI, 90.1%-96.9%]) were confirmed to have a hospitalization for serious infection. After weighting by the prevalence of the type of serious infection, the PPV of the ICD-10-CM algorithm identifying a hospitalization for serious infection was 80.2% (95% CI, 75.3%-84.7%). CONCLUSIONS: The ICD-10-CM-based algorithm for hospitalization for serious infection among patients dispensed biologic therapies within the Sentinel Distributed Database had 80% PPV for confirmed events and could be considered for use within pharmacoepidemiologic studies.

MiR-485-3p promotes proliferation of osteoarthritis chondrocytes and inhibits apoptosis via Notch2 and the NF-κB pathway.

CONTEXT: Osteoarthritis (OA) is one of the leading causes of disability worldwide. microRNAs (miRs) has been shown to be involved in multiple pathological processes during OA. But the possible mechanism of miR-485-3p in OA remains unclear. OBJECTIVE: This study was designed to identify the effect of miR-485-3p on OA. METHODS: miR-485-3p expression in the cartilage of OA patients and healthy controls was detected. OA cell model was established by lipopolysaccharide (LPS). miR-485-3p expression in SW1353 and CHON-001 chondrocytes treated with LPS was detected. After overexpressing miR-485-3p in chondrocytes, cell proliferation, and apoptosis were detected. Apoptosis-, extracellular matrix (ECM)-, inflammatory-, and oxidative stress-related factors were detected. The target gene of miR-485-3p was predicted by online software and verified by dual luciferase reporter gene assay. Notch2 was intervened in CHON-001 chondrocytes to detect proliferation and apoptosis. Finally, the phosphorylation of NF-κB pathway-related proteins was detected. RESULTS: miR-485-3p expression was low in OA patients and LPS-treated chondrocytes. After LPS treatment, the proliferation of SW1353 and CHON-001 chondrocytes was decreased, and apoptosis was increased. The above outcomes were reversed after overexpressing miR-485-3p. Overexpressing miR-485-3p also reduced ECM degradation, inflammation and oxidative stress in chondrocytes. miR-485-3p could target Notch2. After LPS treatment, the NF-κB pathway was activated, but miR-485-3p overexpression inhibited the pathway. Notch2 inhibition promoted proliferation and inhibited apoptosis of LPS-treated CHON-001 chondrocytes, and inhibited the NF-κB pathway. CONCLUSION: Overexpression of miR-485-3p inhibited Notch2 and the NF-κB pathway, and promoted proliferation of OA chondrocytes and inhibited apoptosis.

Prevalence of overweight and obesity in Chinese children and adolescents from 2015.

BACKGROUND: To update the prevalence of overweight and obesity in children and adolescents from 2015. METHODS: Data for this study were obtained from children and adolescents aged 7-17 years with measured weight and height from the National Surveys on Chinese Students' Constitution and Health in 2015. RESULTS: Measurements from 29 418 children and adolescents (14 480 boys and 14 938 girls) were analysed. Among children and adolescents aged 7-17 years, the prevalence of obesity was 13.2% (95% CI = 12.8-13.7%) in 2015. Moreover, the prevalence of obesity for children aged 7-12 years (20.3% (95% CI = 19.5-21.1%)) was significantly higher than in adolescents aged 13-17 years (9.6% (95% CI = 9.2-10.0%)) (p < 0.001). COMMENT: Obesity was much worse in children than adolescents in China; future studies are warranted to understand why these differences may be occurring.

SAR exploration at the C-3 position of tetrahydro-ß-carboline sstr3 antagonists.

MK-4256, a tetrahydro-ß-carboline sstr3 antagonist, was discontinued due to a cardiovascular (CV) adverse effect observed in dogs. Additional investigations revealed that the CV liability (QTc prolongation) was caused by the hERG off-target activity of MK-4256 and was not due to sstr3 antagonism. In this Letter, we describe our extensive SAR effort at the C3 position of the tetrahydro-ß-carboline structure. This effort resulted in identification of 5-fluoro-pyridin-2-yl as the optimal substituent on the imidazole ring to balance sstr3 activity and the hERG off-target liability.

Prevalence of hemorrhagic fever with renal syndrome in Yiyuan County, China, 2005-2014.

BACKGROUND: Hemorrhagic fever with renal syndrome (HFRS) is highly endemic in mainland China, where human cases account for 90 % of the total global cases. Yiyuan County is one of the most serious affected areas in China. Therefore, there is an urgent need for monitoring and predicting HFRS incidence in Yiyuan to make the control of HFRS more effective. METHODS: The study was based on the reported cases of HFRS from the National Notifiable Disease Surveillance System. The demographic and spatial distributions of HFRS in Yiyuan were established. Then we fit autoregressive integrated moving average (ARIMA) models and predict the HFRS epidemic trend. RESULTS: There were 362 cases reported in Yiyuan during the 10-year study period. The human infections in the fall and winter reflected a seasonal characteristic pattern of Hantaan virus (HTNV) transmission. The best model was ARIMA (2, 1, 1) × (0, 1, 1)12 (AIC value 516.86) with a high validity. CONCLUSION: The ARIMA model fits the fluctuations in HFRS frequency and it can be used for future forecasting when applied to HFRS prevention and control.

Linoleic acid and breast cancer risk: a meta-analysis.

OBJECTIVE: Prior studies on linoleic acid, the predominant n-6 fatty acid, and breast cancer risk have generated inconsistent results. We performed a meta-analysis to summarize the evidence regarding the relationship of dietary and serum linoleic acid with breast cancer risk. DESIGN: Pertinent studies were identified by a search of PubMed and EMBASE. The fixed- or random-effect pooled measure was selected based on between-study heterogeneity. RESULTS: Eight prospective cohort studies and four prospective nested case-control studies, involving 10 410 breast cancer events from 358 955 adult females across different countries, were included in present study. Compared with the lowest level of linoleic acid, the pooled relative risk (RR; 95 % CI) of breast cancer was 0·98 (0·93, 1·04) for the highest level of linoleic acid. The pooled RR (95 % CI) for dietary and serum linoleic acid were 0·99 (0·92, 1·06) and 0·98 (0·88, 1·08), respectively. The RR (95 % CI) of breast cancer was 0·97 (0·91, 1·04), 0·95 (0·85, 1·07), 0·96 (0·86, 1·07), 0·98 (0·87, 1·10) and 0·99 (0·85, 1·14) for linoleic acid intake of 5, 10, 15, 20 and 25 g/d, respectively. The risk of breast cancer decreased by 1 % (RR=0·99; 95 % CI 0·93, 1·05) for every 10 g/d increment in linoleic acid intake. CONCLUSIONS: This meta-analysis indicated that both dietary linoleic acid intake and serum linoleic acid level were associated with decreased risk of breast cancer, although none of the associations were statistically significant. Further investigations are warranted.

Discovery of substituted (4-phenyl-1H-imidazol-2-yl)methanamine as potent somatostatin receptor 3 agonists.

We report SAR studies on a novel non-peptidic somatostatin receptor 3 (SSTR3) agonist lead series derived from (4-phenyl-1H-imidazol-2-yl)methanamine. This effort led to the discovery of a highly potent low molecular weight SSTR3 agonist 5c (EC50=5.2 nM, MW=359). The results from molecular overlays of 5c onto the L-129 structure indicate good alignment, and two main differences of the proposed overlays of the antagonist MK-4256 onto the conformation of 5c lead to inversion of antagonism to agonism.

Mediation of smoking abstinence self-efficacy on the association of nicotine dependence with smoking cessation.

BACKGROUND: The nicotine dependence (ND) has negative and smoking abstinence self-efficacy (SASE) has positive effects on successful smoking cessation, but scant data is now available for what is the mediating role of SASE on the relationship between ND and successful smoking cessation. The aim of this study was to assess the abovementioned mediation. METHODS: A case-control study was conducted with 642 successful spontaneous quitters as the cases, and 700 failed spontaneous quitters as the controls. ND and SASE were evaluated by Fagerström Test for Nicotine Dependence (FTND) scale and SASE scale, respectively. Propensity score as covariate in the regression model was used to adjust for potential confounders of age, age of smoking initiation, occupation, educational level and marital status. Total effect was decomposed into direct and indirect (mediating) effect using logistic regression based on the KHB method proposed by Holm et al. RESULTS: After adjusting for the aforementioned potential confounders, the mediating effects among the total effect of ND on successful spontaneous smoking cessation were 32.90%, 12.14%, 35.64% and 83.03% for the total score of SASE and its three context-specific situation scores, i.e. positive/social situation, negative/affective situation and habit/addictive situation, respectively. CONCLUSIONS: This study indicates that SASE has a partial mediating effect on the association of ND with successful spontaneous smoking cessation. To boost the smokers' SASE could increase the probability of successful smoking cessation.

Integrative analysis of a cross-loci regulation network identifies App as a gene regulating insulin secretion from pancreatic islets.

Complex diseases result from molecular changes induced by multiple genetic factors and the environment. To derive a systems view of how genetic loci interact in the context of tissue-specific molecular networks, we constructed an F2 intercross comprised of >500 mice from diabetes-resistant (B6) and diabetes-susceptible (BTBR) mouse strains made genetically obese by the Leptin(ob/ob) mutation (Lep(ob)). High-density genotypes, diabetes-related clinical traits, and whole-transcriptome expression profiling in five tissues (white adipose, liver, pancreatic islets, hypothalamus, and gastrocnemius muscle) were determined for all mice. We performed an integrative analysis to investigate the inter-relationship among genetic factors, expression traits, and plasma insulin, a hallmark diabetes trait. Among five tissues under study, there are extensive protein-protein interactions between genes responding to different loci in adipose and pancreatic islets that potentially jointly participated in the regulation of plasma insulin. We developed a novel ranking scheme based on cross-loci protein-protein network topology and gene expression to assess each gene's potential to regulate plasma insulin. Unique candidate genes were identified in adipose tissue and islets. In islets, the Alzheimer's gene App was identified as a top candidate regulator. Islets from 17-week-old, but not 10-week-old, App knockout mice showed increased insulin secretion in response to glucose or a membrane-permeant cAMP analog, in agreement with the predictions of the network model. Our result provides a novel hypothesis on the mechanism for the connection between two aging-related diseases: Alzheimer's disease and type 2 diabetes.

[Association of cytochrome P450 2A6 gene polymorphisms with smoking behaviors:a Meta-analysis].

OBJECTIVE: A Meta-analysis was performed to assess the association of defective hepatic cytochrome P450 2A6 (CYP2A6) gene with smoking behaviors. METHODS: All eligible studies published up to 2014 were searched out from PubMed, China National Knowledge Internet (CNKI), ISI Web of knowledge (ISI), vip citation databases (VIP), Chinese BioMedical Literature (CBM) and Elsevier Science Direct, searching words were "smok*","nicotine dependence","CYP2A6","cytochrome P450 2A6","polymorphism","mut*"and"varia*", while 436 articles were concluded. Meta-analysis was performed using Statal 3.1. RESULTS: A total of ten studies were finally included. We didn't find a significant effect of defective CYP2A6 gene on smoking initiation (fixed effect model (FEM): OR = 0.90, 95%CI: 0.78-1.03, I(2) = 25.8%), smoking persistence (random effect model (REM): OR = 0.85, 95%CI: 0.59-1.23, I(2) = 66.3%) and smoking cessation (REM: OR = 0.89, 95%CI: 0.57-1.40, I(2) = 67.1%). But it showed a significant protective effect of CYP2A6*4 on smoking initiation (FEM: OR = 0.78, 95%CI: 0.61-0.99, I(2) = 28.2%), smoking persistence (FEM: OR = 0.53, 95%CI: 0.36-0.77, I(2) = 41.0%) and smoking cessation (REM: OR = 0.49, 95%CI: 0.31-0.80, I(2) = 0.0%). CONCLUSIONS: This Meta-analysis suggested that there was not a protective effect of defective CYP2A6 gene against smoking behaviors. But smokers with whole CYP2A6 gene deletion would be less likely to start smoking, less smoking persistence and more likely to quit smoking successful than smokers with wild CYP2A6 gene.

Efficacy of cognitive behavioral therapy for insomnia in the perinatal period: a meta-analysis of randomized controlled trials.

The meta-analysis aims to explore the effect of cognitive behavioral therapy for insomnia (CBT-I) in the perinatal period. Randomized controlled trials (RCTs) assessed the effects of CBT-I in perinatal women with insomnia, published in English, were eligible. Electronic searches were performed using PubMed, Embase (Elsevier), PsycINFO (Ebsco), and Web of Science (Clarivate Analytics). Insomnia Severity Index (ISI) as the primary outcome was used to estimate the pooled effects and durable efficacy of CBT-I. The secondary outcome measures were Edinburgh Postnatal Depression Scale (EPDS) and Pittsburgh Sleep Quality Index (PSQI). Of 46 studies reviewed, seven studies met the inclusion criteria. The meta-analysis indicated significant improvement in insomnia as measured with the ISI (standardized mean difference (SMD) = - 0.62, 95% confidence intervals (CI) - 0.77, - 0.47, I2 = 28%). At the follow-up time point, the meta-analysis indicated the durable efficacy of CBT-I (SMD = - 0.47, 95% CI - 0.90, - 0.03, I2 = 73%). Definite improvement of CBT-I on EPDS (SMD = -0.31, 95% CI - 0.55, - 0.06, I2 = 33%) and PSQI (SMD = - 0.82, 95% CI - 1.27, - 0.38, I2 = 68%) score change post-intervention were found. In sub-analyses, CBT-I had similar effect sizes, independent of possible modifiers (study population, comparison group, delivery format, etc.). This meta-analysis demonstrates that CBT-I is effective in alleviating insomnia, depression, and sleep quality among perinatal women. It is equally important to find that CBT-I has a durable efficacy on insomnia in the perinatal period. However, it is necessary to include larger samples and conduct rigorous RCTs to further explore this issue. Supplementary Information: The online version contains supplementary material available at 10.1007/s41105-023-00502-z.