Device-measured sedentary behaviour and anxiety symptoms during adolescence: a 6-year prospective cohort study.

BACKGROUND: Sedentary behaviour is potentially a modifiable risk factor for anxiety disorders, a major source of global disability that typically starts during adolescence. This is the first prospective study of associations between repeated, device-based measures of sedentary behaviour and anxiety symptoms in adolescents. METHODS: A UK cohort with 4257 adolescents aged 12 at baseline (56% female). Main exposures were sedentary behaviour and physical activity measured using accelerometers for 7-days at ages 12, 14, and 16. Primary outcome was anxiety symptom scores at age 18 from a Clinical Interview Schedule-Revised. We used adjusted negative binomial regression and iso-temporal substitution methods to analyse the data. RESULTS: We found a positive association between sedentary behaviour at ages 12, 14, and 16, with anxiety symptoms at age 18, independent of total physical activity volume. Theoretically replacing an hour of daily sedentary behaviour for light activity at ages 12, 14, and 16, was associated with lower anxiety symptoms by age 18 by 15.9% (95% CI 8.7-22.4), 12.1% (95% CI 3.4-20.1), and 14.7% (95% CI 4-24.2), respectively. Whereas, theoretically replacing an hour of sedentary behaviour with moderate-to-vigorous physical activity was not associated with differences in anxiety symptoms. These results were robust to a series of sensitivity analyses. CONCLUSION: Sedentary behaviour is a possible risk factor for increasing anxiety symptoms during adolescence, independent of total physical activity volume. Instead of focusing on moderate-to-vigorous activity, replacing daily sedentary behaviour with light activity during adolescence could be a more suitable method of reducing future anxiety symptoms.

Impact of replacing sedentary behaviour with other movement behaviours on depression and anxiety symptoms: a prospective cohort study in the UK Biobank.

BACKGROUND: Sedentary behaviour is potentially a modifiable risk factor for depression and anxiety disorders, but findings have been inconsistent. To assess the associations of sedentary behaviour with depression and anxiety symptoms and estimate the impact of replacing daily time spent in sedentary behaviours with sleep, light, or moderate to vigorous physical activity, using compositional data analysis methods. METHODS: We conducted a prospective cohort study in 60,235 UK Biobank participants (mean age: 56; 56% female). Exposure was baseline daily movement behaviours (accelerometer-assessed sedentary behaviour and physical activity, and self-reported total sleep). Outcomes were depression and anxiety symptoms (Patient Health Questionnaire-9 and Generalised Anxiety Disorders-7) at follow-up. RESULTS: Replacing 60 min of sedentary behaviour with light activity, moderate-to-vigorous activity, and sleep was associated with lower depression symptom scores by 1.3% (95% CI, 0.4-2.1%), 12.5% (95% CI, 11.4-13.5%), and 7.6% (95% CI, 6.9-8.4%), and lower odds of possible depression by 0.95 (95% CI, 0.94-0.96), 0.75 (95% CI, 0.74-0.76), and 0.90 (95% CI, 0.90-0.91) at follow-up. Replacing 60 min of sedentary behaviour with moderate-to-vigorous activity and sleep was associated with lower anxiety symptom scores by 6.6% (95% CI, 5.5-7.6%) and 4.5% (95% CI, 3.7-5.2%), and lower odds of meeting the threshold for a possible anxiety disorder by 0.90 (95% CI, 0.89-0.90) and 0.97 (95%CI, 0.96-0.97) at follow-up. However, replacing 60 min of sedentary behaviour with light activity was associated with higher anxiety symptom scores by 4.5% (95% CI, 3.7-5.3%) and higher odds of a possible anxiety disorder by 1.07 (95% CI, 1.06-1.08). CONCLUSIONS: Sedentary behaviour is a risk factor for increased depression and anxiety symptoms in adults. Replacing sedentary behaviour with moderate-to-vigorous activity may reduce mental health risks, but more work is necessary to clarify the role of light activity.

The association between cardiorespiratory fitness and the incidence of common mental health disorders: A systematic review and meta-analysis.

BACKGROUND: Physical activity is associated with a lower incidence of common mental health disorder, but less is known about the impact of cardiorespiratory fitness (CRF). METHODS: In this review, we systematically evaluated the relationship between CRF and the incidence of common mental health disorders in prospective cohort studies. We systematically searched six major electronic databases from inception to 23rd of May 2019. We assessed study quality using the Newcastle-Ottawa scale. RESULTS: We were able to pool the hazard ratios (HRs) and 95% confidence intervals (CIs) of four studies including at least 27,733,154 person-years of data. We found that low CRF (HR = 1.47, [95% CI 1.23 - 1.76] p < 0.001 I2 = 85.1) and medium CRF (HR = 1.23, [95% CI 1.09 - 1.38] p < 0.001 I2 = 87.20) CRF are associated with a 47% and 23% greater risk of a common mental health disorders respectively, compared with high CRF. We found evidence to suggest a dose-response relationship between CRF and the risk of common mental health disorders. LIMITATIONS: We were only able to identify a small number of eligible studies from our search and heterogeneity was substantial in the subsequent meta-analysis. CONCLUSIONS: Our findings indicate that there is a longitudinal association between CRF levels and the risk of a common mental health disorder. CRF levels could be useful for identifying and preventing common mental health disorders at a population-level.

A systematic review and meta-analysis of clinical predictors of lithium response in bipolar disorder.

OBJECTIVE: To determine clinical predictors of lithium response in bipolar disorder. METHODS: Systematic review of studies examining clinical predictors of lithium response was conducted. Meta-analyses were performed when ≥2 studies examined the same potential predictor. RESULTS: A total of 71 studies, including over 12 000 patients, identified six predictors of good response: mania-depression-interval sequence [odds ratio (OR): 4.27; 95% CI: 2.61, 6.97; P < 0.001], absence of rapid cycling (OR for rapid cycling: 0.30; 95% CI: 0.17, 0.53; P < 0.001), absence of psychotic symptoms (OR for psychotic symptoms: 0.52; 95% CI: 0.34, 0.79; P = 0.002), family history of bipolar disorder (OR: 1.61; 95% CI: 1.03, 2.52; P = 0.036), shorter prelithium illness duration [standardised mean difference (SMD): -0.26; 95% CI: -0.41, -0.12; P < 0.001] and later age of onset (SMD: 0.17; 95% CI: 0.02, 0.36; P = 0.029). Additionally, higher body mass index was associated with poor response in two studies (SMD: -0.61; 95% CI: -0.90, -0.32; P < 0.001). There was weak evidence for number of episodes prior to lithium treatment (SMD: -0.42; 95% CI: -0.84, -0.01; P = 0.046), number of hospitalisations before lithium (SMD: -0.40; 95% CI: -0.81, 0.01; P = 0.055) and family history of lithium response (OR: 10.28; 95% CI: 0.66, 161.26; P = 0.097). CONCLUSIONS: The relative importance of these clinical characteristics should be interpreted with caution because of potential biases and confounding.

Home and neighbourhood built environment features in family-based treatment for childhood obesity.

BACKGROUND: Family-based behavioural weight loss treatment (FBT) for childhood obesity helps families develop strategies to facilitate healthy choices in their home and other environments (e.g. home neighbourhood). The current study examines how the home food environment, both pre-FBT and post-FBT, and the neighbourhoods in which families live are associated with child weight and weight-related outcomes in FBT. METHODS: Parent-child dyads (n = 181) completed a 16-session FBT programme and completed home environment, anthropometric and child dietary/activity assessments at pre-FBT and post-FBT. Parents reported on availability of food, electronics and physical activity equipment in the home. The neighbourhood food and recreation environments around each dyad's residence was characterized using existing data within a geographic information system. RESULTS: Families successfully made healthy home environment modifications during FBT. Regression models showed reducing RED (e.g. high-energy-dense and low-nutrient-dense) foods and electronics in the home during FBT had positive effects on child weight and weight-related outcomes. No neighbourhood food or recreation environment variables were significantly related to outcomes, although having a larger density of public recreation spaces was associated with increases in physical activity at the trend-level. CONCLUSIONS: Modifying the home environment, specifically reducing RED foods and electronics, may be particularly important for FBT success.

Curiosity killed the cat: no evidence of an association between cat ownership and psychotic symptoms at ages 13 and 18 years in a UK general population cohort.

BACKGROUND: Congenital or early life infection with Toxoplasma gondii has been implicated in schizophrenia aetiology. Childhood cat ownership has been hypothesized as an intermediary marker of T. gondii infection and, by proxy, as a risk factor for later psychosis. Evidence supporting this hypothesis is, however, limited. METHOD: We used birth cohort data from the Avon Longitudinal Study of Parents and Children (ALSPAC) to investigate whether cat ownership in pregnancy and childhood (ages 4 and 10 years) was associated with psychotic experiences (PEs) in early (age 13, N = 6705) and late (age 18, N = 4676) adolescence, rated from semi-structured interviews. We used logistic regression to examine associations between cat ownership and PEs, adjusting for several sociodemographic and socioeconomic factors, household characteristics and dog ownership. Missing data were handled via multiple imputation. RESULTS: Cat ownership during pregnancy was not associated with PEs at age 13 years [adjusted odds ratio (OR) 1.15, 95% confidence interval (CI) 0.97-1.35] or 18 years (OR 1.08, 95% CI 0.86-1.35). Initial univariable evidence that cat ownership at ages 4 and 10 years was associated with PEs at age 13 years did not persist after multivariable adjustment (4 years: OR 1.18, 95% CI 0.94-1.48; 10 years: OR 1.12, 95% CI 0.92-1.36). There was no evidence that childhood cat ownership was associated with PEs at age 18 years. CONCLUSIONS: While pregnant women should continue to avoid handling soiled cat litter, given possible T. gondii exposure, our study strongly indicates that cat ownership in pregnancy or early childhood does not confer an increased risk of later adolescent PEs.

Childhood interleukin-6, C-reactive protein and atopic disorders as risk factors for hypomanic symptoms in young adulthood: a longitudinal birth cohort study.

BACKGROUND: There are no existing longitudinal studies of inflammatory markers and atopic disorders in childhood and risk of hypomanic symptoms in adulthood. This study examined if childhood: (1) serum interleukin-6 (IL-6) and C-reactive protein (CRP); and (2) asthma and/or eczema are associated with features of hypomania in young adulthood. METHOD: Participants in the Avon Longitudinal Study of Parents and Children, a prospective general population UK birth cohort, had non-fasting blood samples for IL-6 and CRP measurement at the age of 9 years (n = 4645), and parents answered a question about doctor-diagnosed atopic illness before the age of 10 years (n = 7809). These participants completed the Hypomania Checklist at age 22 years (n = 3361). RESULTS: After adjusting for age, sex, ethnicity, socio-economic status, past psychological and behavioural problems, body mass index and maternal postnatal depression, participants in the top third of IL-6 values at 9 years, compared with the bottom third, had an increased risk of hypomanic symptoms by age 22 years [adjusted odds ratio 1.77, 95% confidence interval (CI) 1.10-2.85, p < 0.001]. Higher IL-6 levels in childhood were associated with adult hypomania features in a dose-response fashion. After further adjustment for depression at the age of 18 years this association remained (adjusted odds ratio 1.70, 95% CI 1.03-2.81, p = 0.038). There was no evidence of an association of hypomanic symptoms with CRP levels, asthma or eczema in childhood. CONCLUSIONS: Higher levels of systemic inflammatory marker IL-6 in childhood were associated with hypomanic symptoms in young adulthood, suggesting that inflammation may play a role in the pathophysiology of mania. Inflammatory pathways may be suitable targets for the prevention and intervention for bipolar disorder.

The effect of sibutramine prescribing in routine clinical practice on cardiovascular outcomes: a cohort study in the United Kingdom.

BACKGROUND/OBJECTIVES: The marketing authorization for the weight loss drug sibutramine was suspended in 2010 following a major trial that showed increased rates of non-fatal myocardial infarction and cerebrovascular events in patients with pre-existing cardiovascular disease. In routine clinical practice, sibutramine was already contraindicated in patients with cardiovascular disease and so the relevance of these influential clinical trial findings to the 'real World' population of patients receiving or eligible for the drug is questionable. We assessed rates of myocardial infarction and cerebrovascular events in a cohort of patients prescribed sibutramine or orlistat in the United Kingdom. SUBJECTS/METHODS: A cohort of patients prescribed weight loss medication was identified within the Clinical Practice Research Datalink. Rates of myocardial infarction or cerebrovascular event, and all-cause mortality were compared between patients prescribed sibutramine and similar patients prescribed orlistat, using both a multivariable Cox proportional hazard model, and propensity score-adjusted model. Possible effect modification by pre-existing cardiovascular disease and cardiovascular risk factors was assessed. RESULTS: Patients prescribed sibutramine (N=23,927) appeared to have an elevated rate of myocardial infarction or cerebrovascular events compared with those taking orlistat (N=77,047; hazard ratio 1.69, 95% confidence interval 1.12-2.56). However, subgroup analysis showed the elevated rate was larger in those with pre-existing cardiovascular disease (hazard ratio 4.37, 95% confidence interval 2.21-8.64), compared with those with no cardiovascular disease (hazard ratio 1.52, 95% confidence interval 0.92-2.48, P-interaction=0.0076). All-cause mortality was not increased in those prescribed sibutramine (hazard ratio 0.67, 95% confidence interval 0.34-1.32). CONCLUSIONS: Sibutramine was associated with increased rates of acute cardiovascular events in people with pre-existing cardiovascular disease, but there was a low absolute risk in those without. Sibutramine's marketing authorization may have, therefore, been inappropriately withdrawn for people without cardiovascular disease.

A systematic review and meta-analysis of premature mortality in bipolar affective disorder.

OBJECTIVE: To review and complete meta-analysis of studies estimating standardised mortality ratios (SMRs) in bipolar affective disorder (BPAD) for all-cause and cause-specific mortalities. METHOD: Cause-specific mortality was grouped into natural and unnatural causes. These subgroups were further divided into circulatory, respiratory, neoplastic and infectious causes, and suicide and other violent deaths. Summary SMRs were calculated using random-effects meta-analysis. Heterogeneity was examined via subgroup analysis and meta-regression. RESULTS: Systematic searching found 31 studies meeting inclusion criteria. Summary SMR for all-cause mortality = 2.05 (95% CI 1.89-2.23), but heterogeneity was high (I(2) = 96.2%). This heterogeneity could not be accounted for by date of publication, cohort size, mid-decade of data collection, population type or geographical region. Unnatural death summary SMR = 7.42 (95% CI 6.43-8.55) and natural death = 1.64 (95% CI 1.47-1.83). Specifically, suicide SMR = 14.44 (95% CI 12.43-16.78), other violent death SMR = 3.68 (95% CI 2.77-4.90), deaths from circulatory disease = 1.73 (95% CI 1.54-1.94), respiratory disease = 2.92 (95% CI 2.00-4.23), infection = 2.25 (95% CI 1.70-3.00) and neoplasm = 1.14 (95% CI 1.10-1.21). CONCLUSION: Despite considerable heterogeneity, all summary SMR estimates and a large majority of individual studies showed elevated mortality in BPAD compared to the general population. This was true for all causes of mortality studied.

Short communication: Genetic parameters of individual fatty acids in milk of Canadian Holsteins.

The objective of the present study was to estimate heritabilities of milk fatty acids (FA) and genetic and phenotypic correlations among milk FA and milk production traits in Canadian Holsteins. One morning milk sample was collected from each of 3,185 dairy cows between February and June 2010 from 52 commercial herds enrolled in Valacta (Ste-Anne-de-Bellevue, Quebec, Canada). Individual FA percentages (g/100 g of total FA) were determined for each sample by gas chromatography. After editing the data, 2,573 cows from 46 herds remained. Genetic parameters were estimated using multitrait animal models fitted under REML. The model included fixed effects of age at calving and stage of lactation each nested within parity and random effects of herd-year-season of calving, animal, and residual. The pedigree of animals with data was traced back 5 generations on both the male and female sides to account for relationships among animals. The estimates of heritability for individual FA ranged from 0.01 to 0.39, with standard errors ranging from 0.01 to 0.06. Generally, monounsaturated FA (MUFA) and saturated FA (SFA) showed higher heritability estimates than polyunsaturated FA (PUFA). Overall, SFA were negatively genetically correlated with MUFA and PUFA, whereas genetic correlations between MUFA and PUFA were positive. The SFA showed positive associations with fat yield and fat percentage, whereas unsaturated FA were negatively associated with fat yield and fat percentage. Bovine milk FA composition could be improved through genetic selection, and selection for MUFA or against SFA could alter the bovine milk fat profile in a desirable direction.

Short communication: Estimates of heritabilities and genetic correlations among milk fatty acid unsaturation indices in Canadian Holsteins.

The objectives of the present study were to estimate genetic parameters of milk fatty acid unsaturation indices in Canadian Holsteins. Data were available on milk fatty acid composition of 2,573 Canadian Holstein cows from 46 commercial herds enrolled in the Québec Dairy Production Centre of Expertise, Valacta (Sainte-Anne-de-Bellevue, Quebec, Canada). Individual fatty acid percentages (g/100 g of total fatty acids) were determined for each milk sample by gas chromatography. The unsaturation indices were calculated as the ratio of an unsaturated fatty acid to the sum of that unsaturated fatty acid and its corresponding substrate fatty acid, multiplied by 100. A mixed linear model was fitted under REML for the statistical analysis of milk fatty acid unsaturation indices. The statistical model included the fixed effects of parity, age at calving, and stage of lactation, each nested within parity, and the random effects of herd-year-season of calving, animal, and residual. Estimates of heritabilities for the C14, C16, C18, conjugated linoleic acid, and total unsaturation indices were 0.48, 0.25, 0.29, 0.14, and 0.19, respectively. Phenotypic and genetic correlation estimates among unsaturation indices were all positive and ranged from 0.20 to 0.65 and 0.23 to 0.81, respectively. The estimates of heritabilities and genetic correlations for milk fatty acid unsaturation indices suggest that genetic variation exists among cows in milk fatty acid unsaturation, and the proportions of desirable unsaturated fatty acids from a human health point of view may be increased in bovine milk through genetic selection.

Stearoyl-CoA desaturase 1 3'UTR SNPs and their influence on milk fatty acid composition of Canadian Holstein cows.

Stearoyl-CoA desaturase 1 (SCD1) catalyses the synthesis of conjugated linoleic acid (CLA) and mono-unsaturated fatty acids (MUFA) in the mammary gland of ruminant animals. Considerable variations in CLA and MUFA have been reported among animals of the same contemporary group. We hypothesized that single nucleotide polymorphisms (SNPs) in the 5' and 3' untranslated regions (UTRs) of the SCD1 gene would influence the production of SCD1 enzyme and consequently its activity in the mammary gland, which may account for some of the observed within breed variations in CLA and MUFA. The 5' and 3'UTRs of the SCD1 gene of 46 Holsteins and 35 Jerseys were analysed for SNPs by sequencing. No SNPs were identified in the 5'UTR, while 14 SNPs were identified in the 3'UTR region. Further analysis revealed three haplotype structures or regulatory variants in Holsteins: named H1, H2 and H3 and only H1 and H3 in Jerseys. An IRES motif was found in the H1 variant. A subsequent association study involving the milk fatty acid profiles of 862 Holstein cows found the H1 regulatory variant to be associated with higher C10 and C12 desaturase indices and consequently with higher contents of C10:1 and C12:1 relative to the H3 variant. The effects of the H2 variant were intermediate to those of H1 and H3. SNPs in the 3'UTR of the SCD1 gene could therefore explain some of the within-breed variations in MUFA content of milk fat.

Aziridinyl anions from a chiral, nonracemic 2-isopropylidineaziridine: surprisingly diastereoselective alkylation reactions.

Lithiation and alkylation of a 2-isopropylidineaziridine bearing an (S)-alpha-methylbenzyl group on nitrogen proceeds with high levels of diastereocontrol (80-90% de).

Asymmetric synthesis of 2-substituted piperidines using a multi-component coupling reaction: rapid assembly of (S)-coniine from (S)-1-(1-phenylethyl)-2-methyleneaziridine.

(S)-Coniine is made using a reaction which assembles the piperidine ring by the sequential formation of four new chemical bonds and installs the C-2 stereogenic centre with high levels of diastereocontrol (90% de).

Reproductive responses of Holstein-Friesian cattle to the climatic conditions of central Sudan.

Data were evaluated from a purebred Holstein herd (n = 1274) kept near Khartoum, a hot and dry area, from 1990 to 1996. The mixed model procedure in SAS was used to analyse the reproductive traits. The mean gestation length, days dry, number of services per conception, days from calving to first oestrus, days from calving to conception, calving interval and breeding efficiency were 279 days, 104 days, 4.2, 85.8 days, 208.9 days, 486.2 days and 74.9%, respectively. Factors that had significant effects (p < 0.01) on all the reproductive measures under study were the year and month of calving, and parity. The heritability estimates for all traits under investigation were zero. The repeatability estimates for the numbers of services per conception, days from calving to conception, days from calving to first oestrus and calving interval were 0.21 +/- 0.021, 0.12 +/- 0.024, 0.03 +/- 0.018 and 0.00, respectively. The phenotypic correlation for calving interval with numbers of service per conception was 0.05, that with days from calving to first oestrus was 0.06 and that with days from calving to conception was 0.07. Other correlations ranged from 0.00 to 0.28. The simple correlation coefficients between production and reproductive measures ranged from -0.06 to 0.45.

Genetic and environmental effects on the productivity of Holstein-Friesian cattle under the climatic conditions of central Sudan.

A herd of 370 Holstein-Friesian cows were maintained in Central Sudan, Khartoum for intensive dairy production during the period 1990-1996. The area is characterized by high temperatures during the day and cools down at night, with an average thermal-humidity index (THI) of 74.8. The average adjusted lactation milk yield, milk yield per day, milk yield per day of calving interval and lactation length of the animals in the herd were 5117 +/- 123 (SE) kg, 14.7 +/- 0.25 kg, 11.3 +/- 0.36 kg and 350 +/- 8.0 days, respectively. Heifers calved at 25.2 +/- 2.3 (SD) months of age. The variation was large, which suggested large environmental fluctuations. Sire variance contributed 1.35% and 19.6% to the total variance in cows and heifers, respectively, while cow within sire contributed 19%. The heritabilities of total lactation yield, 305-day yield, milk per day of lactation, milk per day of calving interval, and lactation length in heifers were 0.78 +/- 0.24, 0.36 +/- 0.34, 0.39 +/- 0.24, 0.23 +/- 0.23, and 0.23 +/- 0.22, respectively. In cows, the heritability estimates were 0.05 +/- 0.24, 0.06 +/- 0.24, 0.08 +/- 0.24, 0.00 and 0.00 for the same traits, respectively. The repeatabilities of total lactation yield, 305-day yield, milk per day, milk per day of calving interval and lactation length were 0.02 +/- 0.03, 0.22 +/- 0.03, 0.17 +/- 0.02, 0.05 +/- 0.02 and 0.00, respectively. Regression analysis showed that, for each unit increase in THI, milk yield decreased by 0.29 +/- 0.04 kg. The stress usually caused by the combined effects of temperature and humidity was not severe in this area.

Markers within the regulatory region of the growth hormone receptor gene and their association with milk-related traits in Holsteins.

We studied sequence variations in the regulatory region of the bovine growth hormone receptor gene. A polymerase chain reaction (PCR)-based method for detecting AluI, AccI, and StuI restriction fragment length polymorphisms (RFLPs) in the 5' flanking region of the bovine growth hormone receptor gene was developed and tested for association with milk-related traits in Holstein bulls. Allele frequencies of the polymorphisms in two groups of Holstein progeny-tested bulls born from 1950 to 1970 and in the 1980s, respectively, were estimated. The allele frequency of the AluI(-) allele was 0.63 and 0.42 in the bulls from 1950 to 1970 and in the 1980s, respectively. The frequency of the StuI(-) allele was 0.14 and 0.07 in the two respective bull groups. Allele frequency for AccI(-) allele was about 0.22 in both bull groups. The differences in allele frequencies for the AluI polymorphism in the two bull groups were significantly different (P < or = .005). The AluI(+/+) bulls had a higher estimated breeding value (EBV) for fat (P < or = .016) than AluI(-/-) bulls. The average effect of allele substitution for the AluI polymorphism was +/- 8 for fat EBV. The AluI polymorphism could be further evaluated for use in marker-assisted selection in dairy cattle.