Chronotype,bed timing and total sleep time in seniors

Many older adults (seniors) experience problems with getting enough sleep. Because of the link between sleep and circadian rhythms, changes in bedtime lead to changes in the amount of sleep obtained. Although primarily determined genetically, chronotype changes with advancing age towards a more morning-type (M-type) orientation. In a 2006 study, we have found a linear relationship, by which the earlier a senior’s bedtime, the more sleep she/he will obtain. The aim of this study was to see whether this relationship differs for M-type seniors, as compared to seniors outside the M-type category. Retired seniors (n?=?954, 535?M, 410F, 65?years+, mean age 74.4?years) taking part in a telephone interview were divided into M-types and Other types (O-types) using the Composite Scale of Morningness (CSM). The relationship between bedtime and Total Sleep Time (TST), and between rise-time and TST, was tested using linear regression separately for M-types and O-types. For each participant, habitual bedtime, rise-time and total Sleep Time (TST) [after removing time spent in unwanted wakefulness] were obtained using a telephone version of the Sleep Timing Questionnaire (STQ). Both chronotype groups showed a significant linear relationship between bedtime and TST (p?<?0.001); with earlier bedtimes leading to more TST (M-type 5.6?min; O-type 4.4?min per 10?min change [slope difference p?=?0.05]); and an opposite relationship between rise-time and TST with earlier rise-times leading to less TST (M-type 6.7?min; O-type 4.2?min per 10?min change [slope difference p?=?0.001]). M-types retired to bed 56?min earlier (p?<?0.001), awoke 93?min earlier (p?<?0.001) and obtained 23?min less TST (p?<?0.001) than O-types. In conclusion, both chronotypes showed TST to be related in a linear way to bedtime and rise-time; the overall shorter TST in M-types was due to them rising 93?min earlier, but only retiring to bed 56?min earlier than O-types; as well as having a steeper rise-time versus TST relationship.     

Irregular 24-hour activity rhythms and the metabolic syndrome in older adults

Circadian rhythms – near 24?h intrinsic biological rhythms – modulate many aspects of human physiology and hence disruption of circadian rhythms may have an important impact on human health. Experimental work supports a potential link between irregular circadian rhythms and several key risk factors for cardiovascular disease including hypertension, obesity, diabetes and dyslipidemia, collectively termed the metabolic syndrome. While several epidemiological studies have demonstrated an association between shift-work and the components of the metabolic syndrome in working-age adults, there is a relative paucity of data concerning the impact of non-occupational circadian irregularity in older women and men. To address this question, we studied 7 days of actigraphic data from 1137 older woman and men participating in the Rush Memory and Aging Project, a community-based cohort study of the chronic conditions of aging. The regularity of activity rhythms was quantified using the nonparametric interdaily stability metric, and was related to the metabolic syndrome and its components obesity, hypertension, diabetes and dyslipidemia. More regular activity rhythms were associated with a lower odds of having the metabolic syndrome (OR?=?0.69, 95% CI?=?0.60–0.80, p?=?5.8?×?10^?7), being obese (OR?=?0.73, 95% CI?=?0.63–0.85, p?=?2.5?×?10^?5), diabetic (OR?=?0.76, 95% CI?=?0.65–0.90, p?=?9.3?×?10^?4), hypertensive (OR?=?0.78, 95% CI?=?0.66–0.91, p?=?2.0?×?10^?3) or dyslipidemic (OR?=?0.82, 95% CI?=?0.72–0.92, p?=?1.2?×?10^?3). These associations were independent of differences in objectively measured total daily physical activity or rest, and were not accounted for by prevalent coronary artery disease, stroke or peripheral artery disease. Moreover, more regular activity rhythms were associated with lower odds of having cardiovascular disease (OR?=?0.83; 95% CI?=?0.73–0.95, p?=?5.7?×?10^?3), an effect that was statistically mediated by the metabolic syndrome. We conclude that irregular activity rhythms are associated with several key components of the metabolic syndrome in older community-dwelling adults, and that the metabolic syndrome statistically partially mediates the association between activity rhythms and prevalent cardiovascular disease. Although additional longitudinal and experimental studies are needed to conclusively delineate the causal relationships underlying these associations, these findings are consistent with preclinical data, and add further support for investigations of the irregularity of activity rhythms as a potential therapeutic target to decrease the burden of cardiovascular disease in older adults.     

A systematic review and meta-analysis of higher expression of folate receptor alpha (FOLR1) predicts poor cancer prognosis

Abstract

Folate receptor alpha (FOLR1), a glycosylphosphatidylinositol-linked protein, is a well characterized folate transporter. However, the prognostic power of FOLR1 in cancer remains controversial. We conducted a meta-analysis to assess the prognostic roles of FOLR1 on different cancers. Twelve studies involving 4471 patients were included in this meta-analysis. The pooled analysis indicated that high FOLR1 significantly predicted poor overall survival (OS) (pooled hazard ratio (HR)?=?0.78, 95% confidence interval (CI)?=?0.64–0.94, p?=?0.009) and the disease-free survival (DFS) (HR?=?1.25, 95% CI?=?1.07–1.47, p?=?0.005). Subgroup analyses based on tumour type found that high FOLR1 level was associated with poor OS in breast cancer (HR?=?2.66, 95% CI?=?1.54–4.59, p?=?0.0005) and endometrial carcinoma (HR?=?1.30, 95% CI?=?1.05–1.61, p?=?0.02). However, FOLR1 has relatively weakly correlation with gender, tumour size and chemotherapy. Additionally, overexpression of FOLR1 was correlated with grade, FIGO stage, vital status and nodule status. The present meta-analysis indicated that the high expression of FOLR1 is associated with the poor survival of cancer patients, which is helpful for the clinical decision-making process.     

Evidence for a relationship between chronotype and reproductive function in women

There is evidence for the reciprocal interaction between circadian oscillation and reproduction, and disruption of circadian rhythms has been associated with impaired menstrual functions and reduced fertility in women. However, only little information is available on the relationship between reproduction and chronotype. The aim of the present study is to better assess this relationship. The participants (aged 25 to 74?yrs) were selected randomly from the Finnish Population Information System. The data from 2672 female participants of the National FINRISK Survey 2007 were analyzed to test the associations between chronotype (morning, intermediate, or evening) and reproductive features. Of the participants, 139 (5.6%) were evening, 1217 (48.7%) intermediate, and 1145 (45.8%) morning chronotypes. Among the participants aged 25 to 54?yrs, the duration of menstrual cycle was longer among evening chronotypes (28.8?±?4.4?d) than among morning (27.7?±?2.6?d; p?<?0.01) and intermediate (27.8?±?3.3?d; p?=?0.05) chronotypes. Significant correlations were found between the higher morningness-eveningness scores (the more of morning chronotype) and the shorter durations of menstrual bleeding, both in the whole sample (p?<?0.001) and after limiting the analyses to women younger than 55?yrs (p?<?0.05). In multivariable analyses on the whole sample, as compared with morning chronotypes, intermediate chronotypes had a significantly longer duration of menstrual bleeding (B?=?0.160, 95% confidence interval [CI]?=?0.044 to 0.276; p?<?0.01) as well as a higher odds for difficulties in getting pregnant (odds ratio [OR]?=?1.464, 95% CI?=?1.118 to 1.917; p?<?0.01). Our findings suggest that chronotype is related to the reproductive function in women.     

Association between circadian genes,bipolar disorders and chronotypes

Abnormalities in circadian rhythms play an important role in the pathogenesis of bipolar disorders (BD). Previous genetic studies have reported discrepant results regarding associations between circadian genes and susceptibility to BD. Furthermore, plausible behavioral consequences of at-risk variants remain unclear since there is a paucity of correlates with phenotypic biomarkers such as chronotypes. Here, we combined association studies with a genotype/phenotype correlation in order to determine which circadian genes variants may be associated with the circadian phenotypes observed in patients with BD. First, we compared the allele frequencies of 353 single nucleotide polymorphisms spanning 21 circadian genes in two independent samples of patients with BD and controls. The meta-analysis combining both samples showed a significant association between rs774045 in TIMELESS (OR?=?1.49 95%CI[1.18–1.88]; p?=?0.0008) and rs782931 in RORA (OR?=?1.31 95%CI[1.12–1.54]; p?=?0.0006) and BD. Then we used a “reverse phenotyping approach” to look for association between these two polymorphisms and circadian phenotypes in a subsample of patients and controls. We found that rs774045 was associated with eveningness (p?=?0.04) and languid circadian type (p?=?0.01), whereas rs782931 was associated with rigid circadian type (p?=?0.01). Altogether, these findings suggest that these variants in the TIMELESS and RORA genes may confer susceptibility to BD and impact on circadian phenotypes in carriers who thus had lower ability to properly adapt to external cues.     

Light exposure at night is associated with subclinical carotid atherosclerosis in the general elderly population: The HEIJO-KYO cohort

Epidemiological and cellular biological studies indicate the influence of impaired circadian biological rhythmicity on atherosclerosis. Increased exposure to light at night (LAN) is common in modern life, and LAN exposure is the most important environmental cue for circadian misalignment. However, the association between LAN exposure and atherosclerosis has never been explored in humans. In this cross-sectional study, we measured nighttime light intensity in the bedroom along with the intima-media thickness (IMT) of the common carotid artery using ultrasonography in 700 elderly individuals (mean age 71.6 years). Averages of mean and maximal carotid IMT were 0.88?±?0.15?mm and 1.09?±?0.32?mm, respectively. Median intensity of LAN exposure was 0.74?lux (interquartile range, 0.08–3.34). Both mean and maximal carotid IMT significantly increased across quartiles of increasing LAN intensity (p for trend?=?0.002 and <0.001, respectively). After adjustment for confounding factors, including age, gender, body mass index, current smoking status, hypertension, diabetes, dyslipidemia, sleep medication, estimated glomerular filtration rate, nocturia, bedtime, duration in bed (scotoperiod), day length (photoperiod), urinary 6-sulfatoxymelatonin excretion and daytime and nighttime physical activity, multivariate linear regression models revealed significant associations of LAN exposure with carotid IMT measurements [mean: β, 0.032 (fourth versus first quartiles); 95% confidence intervals (CI), 0.002–0.061; p?=?0.037; maximal: β, 0.100 (fourth versus first quartiles); 95% CI, 0.034–0.165; p?=?0.003]. In conclusion, these results suggested that LAN exposure in home settings is significantly associated with subclinical carotid atherosclerosis in the general elderly population.     

Chronotype and Breast Cancer Risk in a Cohort of US Nurses

The aim of this study was to examine the relation between chronotype and breast cancer risk. We analyzed the association between chronotype (definite morning type, probable morning type, probable evening type, definite evening type, or neither morning nor evening type) and breast cancer risk among 72 517 women in the Nurses’ Health Study II (NHS II). Chronotype was self-reported in 2009, and 1834 breast cancer cases were confirmed among participants between 1989 and 2007; a 2-yr lag period was imposed to account for possible circadian disruptions related to breast cancer diagnosis. Age- and multivariable-adjusted logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Participants who self-reported as neither morning nor evening type had a 27% increased risk of breast cancer (multivariable-adjusted OR?=?1.27, 95% CI?=?1.04–1.56), compared with definite morning types. None of the other chronotypes were significantly associated with breast cancer risk (multivariable-adjusted OR?=?0.99, 95% CI?=?0.87–1.12 for probable morning versus definite morning types; OR?=?0.96, 95% CI?=?0.84–1.09 for probable evening versus definite morning types; and OR?=?1.15, 95% CI?=?0.98–1.34 for definite evening versus definite morning types). Overall, chronotype was not associated with breast cancer risk in our study. A modestly increased risk among neither morning nor evening types may indicate circadian disruption as a potentially underlying mechanism; however, more studies are needed to confirm our results.     

A systematic review and meta-analysis of the association of transforming growth factor β receptor I 6A/9A gene polymorphism with ovarian cancer risk

Abstract

Ovarian cancer is the leading cause of cancer-related death in women. This meta-analysis was conducted to evaluate the association of transforming growth factor β receptor I (TβR-I) 6A/9A gene polymorphism with ovarian cancer risk. The association literatures were identified from PubMed and Cochrane Library on 1 October 2013, and eligible reports were recruited and synthesized. Four reports were recruited into this meta-analysis for the association of TβR-I 6A/9A gene polymorphism with ovarian cancer risk. 6A allele and 6A/6A genotype of TβR-I were associated with the ovarian cancer risk (6A: OR?=?1.24, 95% CI: 1.02–1.51, p?=?0.03; 6A/6A: OR?=?2.30, 95% CI: 1.01–5.22, p?=?0.05). However, TβR-I 9A/9A genotype was not associated with the risk of ovarian cancer (OR?=?0.82, 95% CI: 0.66–1.02, p?=?0.08). In conclusion, TβR-I 6A allele and 6A/6A genotype are associated with the ovarian cancer risk. However, more studies should be performed to confirm this relationship in the future.     

Association between chemokine receptor 5 delta32 polymorphism and susceptibility to cancer: a meta-analysis

Abstract

Objective: To explore whether the functional chemokine receptor 5 delta32 (CCR5-Δ32) polymorphism is associated with susceptibility to cancer. Methods: A meta-analysis was conducted on the association between the CCR5-Δ32 polymorphism and cancer using (i) allele contrast and (ii) the dominant model. Results: Thirteen articles, including 16 comparative studies on a total of 3087 patients and 3735 controls, were included in the meta-analysis. These studies encompassed breast cancer (n?=?3), bladder cancer (n?=?3), cervical cancer (n?=?2), pancreatic cancer (n?=?2), prostate cancer (n?=?2), head and neck cancer (n?=?2), lymphoma (n?=?1), gallbladder cancer (n?=?1), skin cancer (n?=?1) and mixed cancer (n?=?1). The meta-analysis revealed an association between cancer and the CCR5-Δ32 allele (OR?=?1.368, 95% CI?=?1.064–1.758, p?=?0.014), and stratification by ethnicity showed an association between the CCR5-Δ32 allele and cancer in Indians (OR?=?2.480, 95% CI?=?1.247–4.932, p?=?0.010). The meta-analysis also revealed an association between breast cancer and the CCR5-Δ32 allele (OR?=?1.689, 95% CI?=?1.012–2.821, p?=?0.045). However, allele contrast and the dominant model failed to reveal an association between the CCR5-Δ32 polymorphism and bladder cancer, cervical cancer, pancreatic cancer, prostate cancer, and head and neck cancer. Conclusions: This meta-analysis demonstrates that the CCR5-Δ32 polymorphism is associated with susceptibility to cancer in Indians and is associated with breast cancer.     

Chronotype and postmenopausal breast cancer risk among women in the California Teachers Study

ABSTRACT

Chronotype is the behavioral manifestation of an individual’s underlying circadian rhythm, generally characterized by one’s propensity to sleep at a particular time during the 24 hour cycle. Evening chronotypes (“night owls”) generally suffer from worse physical and mental health compared to morning chronotypes (“morning larks”) – for reasons that have yet to be explained. One hypothesis is that evening chronotypes may be more susceptible to circadian disruption, a condition where the coordinated timing of biologic processes breaks down. The role of chronotype as an independent or modifying risk factor for cancer has not been widely explored. The objective of the current study was to evaluate the risk of breast cancer associated with chronotype in a case-control study nested within the California Teachers Study (CTS) cohort. The study population consisted of 39686 post-menopausal CTS participants who provided information on chronotype by completing a questionnaire in 2012–2013. 2719 cases of primary invasive breast cancer diagnosed from 1995/1996 through completion of the chronotype questionnaire were identified by linkage of the CTS to the California Cancer Registry. 36967 CTS participants who had remained cancer-free during this same time period served as controls. Chronotype was ascertained by responses to an abbreviated version of the Horne-Ostberg Morningness-Eveningness Questionnaire (MEQ) and was characterized into five categories: definite morning, more morning than evening, neither morning or evening, more evening than morning, definite evening. Multivariable unconditional logistic regression analyses were performed to estimate the odds ratios (ORs) and 95% confidence intervals (95% CIs) for each of the chronotypes, adjusted for established breast cancer risk factors. Compared to definite morning types, definite evening types had an increased risk of breast cancer with elevated ORs that were statistically significant in both the crude (OR = 1.24, 95% CI: 1.10–1.40) and fully-adjusted models (OR = 1.20, 95% CI: 1.06–1.35). The risk estimates in the fully-adjusted model for all other chronotypes did not significantly differ from one. These results suggest that evening chronotype may be an independent risk factor for breast cancer among a population of women who are not known to have engaged in any substantial night shift work. Further research in other populations of non-shift workers is warranted.     

Associations of chronotype with social jetlag and behavioral problems in preschool children

The timing, duration, and intensity of sleep are determined by the interaction between a sleep-wake-dependent homeostatic process and a sleep-wake-independent, intrinsic, clock-like circadian process. Chronotype represents individual differences in diurnal preferences, which are not only genetically determined but also influenced by social and environmental factors. Thus, the discrepancy between biological and social clocks, so-called “social jetlag”, occurs. Chronotype, social jetlag, and the links between chronotype and behavioral problems are well documented in adults and adolescents. However, such studies on young children are limited. We conducted a survey of sleep and health for preschool children attending kindergarten or childcare centers in Wako, Okayama and Kurashiki cities, Japan, between May and July 2012. A total of 654 children aged 4–6 years (342 boys and 312 girls, with an average age of 4.7 years) were assessed using the Children’s ChronoType Questionnaire and the Strength and Difficulties Questionnaire. Morning (M)-type, neither (N)-type and evening (E)-type accounted for 36.2%, 54.0% and 9.8% of the participants, respectively. The weekday-to-weekend differences in midsleep time – originally proposed as the concept of social jetlag – were 11, 25 and 35?min for M-, N- and E-types, respectively. There was a negative correlation between chronotype and sleep period during weekdays (p?<?0.001) and a positive correlation on weekends (p?<?0.001). The weekday-to-weekend difference in sleep period was 0.5?h for E-types, whereas there was no difference for M-types. Binomial logistic regression analyses were used to examine the links between chronotype and behavioral problems, adjusted for participants’ sex, age, childcare programs and locations. Chronotype was significantly associated with hyperactivity/inattention: N-type (adjusted OR?=?1.74, 95% CI?=?1.03–2.95, p?<?0.05) and E-type (adjusted OR?=?2.47, 95% CI?=?1.18–5.20, p?<?0.05). E-type was significantly associated with conduct problems (adjusted OR?=?2.11, 95% CI?=?1.03–4.31, p?<?0.05) and peer problems (adjusted OR?=?2.75, 95% CI?=?1.18–6.44, p?<?0.05). The results suggest that E-type children are vulnerable to higher social jetlag and more behavioral problems. The immature adjustment function of their endogenous circadian pacemakers may not be able to correct a small but significant social jetlag to synchronize with their social clocks. Furthermore, guidance based on chronobiological evidence is required for parents, teachers and health professionals to help children achieve optimal sleep and reduce behavioral problems.     

Associations between chronotype,morbidity and mortality in the UK Biobank cohort

Later chronotype (i.e. evening preference) and later timing of sleep have been associated with greater morbidity, including higher rates of metabolic dysfunction and cardiovascular disease (CVD). However, no one has examined whether chronotype is associated with mortality risk to date. Our objective was to test the hypothesis that being an evening type is associated with increased mortality in a large cohort study, the UK Biobank. Our analysis included 433 268 adults aged 38–73 at the time of enrolment and an average 6.5-year follow-up. The primary exposure was chronotype, as assessed through a single self-reported question-defining participants as definite morning types, moderate morning types, moderate evening types or definite evening types. The primary outcomes were all-cause mortality and mortality due to CVD. Prevalent disease was also compared among the chronotype groups. Analyses were adjusted for age, sex, ethnicity, smoking, body mass index, sleep duration, socioeconomic status and comorbidities. Greater eveningness, particularly being a definite evening type, was significantly associated with a higher prevalence of all comorbidities. Comparing definite evening type to definite morning type, the associations were strongest for psychological disorders (OR 1.94, 95% CI 1.86–2.02, p = < 0.001), followed by diabetes (OR 1.30, 95% CI 1.24–1.36, p = < 0.001), neurological disorders (OR 1.25, 95% CI 1.20–1.30, p = < 0.001), gastrointestinal/abdominal disorders (OR 1.23, 95% CI 1.19–1.27, p = < 0.001) and respiratory disorders (OR 1.22, 95% CI 1.18–1.26, p = < 0.001). The total number of deaths was 10 534, out of which 2127 were due to CVD. Greater eveningness, based on chronotype as an ordinal variable, was associated with a small increased risk of all-cause mortality (HR 1.02, 95% CI 1.004–1.05, p = 0.017) and CVD mortality (HR 1.04, 95% CI 1.00–1.09, p = 0.06). Compared to definite morning types, definite evening types had significantly increased risk of all-cause mortality (HR 1.10, 95% CI 1.02–1.18, p = 0.012). This first report of increased mortality in evening types is consistent with previous reports of increased levels of cardiometabolic risk factors in this group. Mortality risk in evening types may be due to behavioural, psychological and physiological risk factors, many of which may be attributable to chronic misalignment between internal physiological timing and externally imposed timing of work and social activities. These findings suggest the need for researching possible interventions aimed at either modifying circadian rhythms in individuals or at allowing evening types greater working hour flexibility.     

Social jetlag negatively correlates with academic performance in undergraduates

Discrepancies between sleep timing on workdays and weekends, also known as social jetlag (SJL), affect the majority of the population and have been found to be associated with increased health risk and health-impairing behaviors. In this study, we explored the relationship between SJL and academic performance in a sample of undergraduates of the Semmelweis University. We assessed SJL and other sleep-related parameters with the Munich ChronoType Questionnaire (MCTQ) (n?=?753). Academic performance was measured by the average grade based on weekly test results as well as scores acquired on the final test (n?=?247). The average mid-sleep point on free days in the Hungarian sample fits well the regression line plotted for longitudes within the Central European Time Zone and chronotypes, confirming that sunlight has a major impact on chronotype. Multivariate analysis showed negative effect of SJL on the weekly average grade (p?=?0.028, n?=?247) during the lecture term with its highly regular teaching schedules, while this association disappeared in the exam period (p?=?0.871, n?=?247) when students had no scheduled obligations (lower SJL). We also analyzed the relationship between the time of the weekly tests and academic performance and found that students with later sleep times on free days achieved worse in the morning (p?=?0.017, n?=?129), while the inverse tendency was observed for the afternoon test-takers (p?=?0.10, n?=?118). We did not find significant association between academic performance and sleep duration or sleep debt on work days. Our data suggest that circadian misalignment can have a significant negative effect on academic performance. One possible reason for this misalignment is socially enforced sleep times.     

Validity of the Japanese version of the Munich ChronoType Questionnaire

To assess circadian preference with a score, the Morningness-Eveningness Questionnaire (MEQ) has been used for more than 3 decades now. More recently, the Munich ChronoType Questionnaire (MCTQ) was developed: it asks for sleep-wake behavior on work and free days and uses the midpoint of sleep on free days (MSF), corrected for sleep debt accumulated during the work week as an indicator of chronotype (MSF_sc). In this study, we developed a Japanese version of the MCTQ by using a translation/back-translation approach including an examination of its semantic validity. In a subsequent questionnaire survey, 450 adult men and women completed the Japanese versions of the MCTQ and MEQ. Results showed that MEQ scores were significantly negatively correlated with mid-sleep parameters assessed by the MCTQ, on both, work and free days, as well as with the chronotype measure MSF_sc (r?=??0.580 to ?0.652, all p?<?0.001). As in the original German version, the strongest correlation was observed between MEQ score and MSF. A physiological validation study using dim light melatonin onset as a circadian phase marker (N?=?37) showed a high correlation between chronotype as assessed with the MSF_sc (r?=?0.542, p?<?0.001), and less so for MEQ score (r?=??0.402, p?=?0.055). These results demonstrate the validity of the Japanese MCTQ and provide further support of the adequacy of the MCTQ as a chronotype measure.     

Meta-analysis of transforming growth factor β receptor I 6A/9A gene polymorphism and breast cancer risk: the picture remains murky

Abstract

Breast cancer is currently the second most common cancer worldwide and the most frequent malignant tumor among women. However, the exact contribution of various allelic alterations remains unclear. This meta-analysis was conducted to evaluate the association of the transforming growth factor β receptor I 6A/9A (TβR-I 6A/9A) gene polymorphism with breast cancer risk. Relevant studies were identified from PubMed and Cochrane Library on 1 October 2013, and eligible reports were recruited and synthesized. Eleven reports that included a total of 12 studies were recruited into this meta-analysis for the association of the TβR-I 6A/9A gene polymorphism and breast cancer risk. The results indicated that overall the TβR-I 6A allele was associated with breast cancer risk (OR?=?1.33, 95% CI: 1.02–1.73, p?=?0.04). However, the TβR-I 6A/6A and 9A/9A genotypes were not associated with an increased risk of developing breast cancer (6A/6A: OR?=?1.71, 95% CI: 0.95–3.08, p?=?0.07; 9A/9A: OR?=?0.82, 95% CI: 0.66–1.02, p?=?0.08). In the Caucasian population, no such association could be established. In conclusion, the TβR-I 6A allele might represent a risk factor for breast cancer risk, but significantly larger data sets from a larger number of studies, including studies that allow ethnicity, subgroup analysis and environmental impact evaluation, are required to maximize statistical significance and meta-analysis robustness.     

Ex vivo and in vivo T cell-depleted allogeneic stem cell transplantation in patients with acute myeloid leukemia in first complete remission resulted in similar overall survival: on behalf of the ALWP of the EBMT and the MSKCC

Background

Graft-versus-host disease (GVHD) is one of the leading causes of non-relapse mortality and morbidity after allogeneic hematopoietic stem cell transplantation (allo-HCT).

Methods

We evaluated the outcomes of two well-established strategies used for GVHD prevention: in vivo T cell depletion using antithymocyte globulin (ATG) and ex vivo T cell depletion using a CD34-selected (CD34+) graft. A total of 525 adult patients (363 ATG, 162 CD34+) with intermediate or high-risk cytogenetics acute myeloid leukemia (AML) in first complete remission (CR1) were included. Patients underwent myeloablative allo-HCT using matched related or unrelated donors.

Results

Two-year overall survival estimate was 69.9% (95% CI, 58.5–69.4) in the ATG group and 67.6% (95% CI, 60.3–74.9) in the CD34+ group (p?=?0.31). The cumulative incidence of grade II–IV acute GVHD and chronic GVHD was higher in the ATG cohort [HR 2.0 (95% CI 1.1–3.7), p?=?0.02; HR 15.1 (95% CI 5.3–42.2), p?<?0.0001]. Parameters associated with a lower GVHD-free relapse-free survival (GRFS) were ATG [HR 1.6 (95% CI 1.1–2.2), p?=?0.006], adverse cytogenetic [HR 1.7 (95% CI 1.3–2.2), p?=?0.0004], and the use of an unrelated donor [HR 1.4 (95% CI 1.0–1.9), p?=?0.02]. There were no statistical differences between ATG and CD34+ in terms of relapse [HR 1.52 (95% CI 0.96–2.42), p?=?0.07], non-relapse mortality [HR 0.96 (95% CI 0.54–1.74), p?=?0.90], overall survival [HR 1.43 (95% CI 0.97–2.11), p?=?0.07], and leukemia-free survival [HR 1.25 (95% CI 0.88–1.78), p?=?0.21]. Significantly, more deaths related to infection occurred in the CD34+ group (16/52 vs. 19/112, p?=?0.04).

Conclusions

These data suggest that both ex vivo CD34-selected and in vivo ATG T cell depletion are associated with a rather high OS and should be compared in a prospective randomized trial.

     

Differences in circadian patterns between rural and urban populations: An epidemiological study in countryside

The physiological pattern of the sleep–wake cycle is influenced by external synchronizing agents such as light and social patterns, creating variations in each individual’s preferred active and sleep periods. Because of the demands of a 24-h working society, it may be imperative for many people to adapt their sleep patterns (physiologically) to their daily activities. Therefore, we analyzed the difference in sleep patterns and chronobiological parameters between an essentially rural farming and urban small-town populations. We studied 5942 subjects (women, 67.1%, N?=?3985; mean age, 44.3?±?13.1 years), from which the chronotype, circadian sleep pattern, and period of light exposure were collected using the Munich Chronotype Questionnaire (MCTQ). A structured questionnaire was also made for collection of social and demographic information. Compared with the urban population (N?=?3427, 57.7%), the rural population (N?=?2515, 42.3%) presented a more predominantly early sleep pattern, as determined by the mid-sleep phase (rural: 2.26?±?1.16; urban: 3.15?±?1.55; t-test, p?<?0.001). We also found less social jetlag (rural: 0.32; urban: 0.55; Mann–Whitney U test, p?<?0.001) and higher light-exposure (rural: 9.55?±?2.31; urban: 8.46?±?2.85; t test, p?<?0.001) in the rural population. Additionally, the rural population presented a higher prevalence of psychiatric disorders (rural: 156, 6.20%; urban: 165, 4.80%; Chi-square, p?<?0.05), and a lower prevalence of metabolic diseases (rural: 143, 5.70%; urban: 225, 6.60%; Chi-square, p?<?0.05). The significant difference in sleep parameters, chronotype, and light exposure between groups remained after multivariate regression analysis (r^2?=?0.41, F?=?297.19, p?<?0.001, β?=?1.208). In this study, there was a significant difference between the rural and urban populations in natural light exposure and sleeping patterns. Because of agricultural work schedules, rural populations spend considerable time outside that is an obligation related to work schedules. Our results emphasize the idea that latitude may not be the main factor influencing individual circadian habits. Rather, circadian physiology adapts to differences in exposure to light (natural and artificial) as well as social and work schedules.     

Time preference of headache attack and chronotype in migraine and tension-type headache

ABSTRACT

Migraine attacks have a time preference of headache attack (TPHA). Chronotype is the propensity for an individual to sleep at a particular time during a 24-h period. However, limited evidence exists regarding the association between TPHA and chronotype in individuals with migraine or tension-type headache (TTH). The aim of the present study is to investigate TPHA and chronotype in individuals with migraine and TTH, which are two of the most common primary headaches. One hundred sixty-nine first-visit migraine and TTH participants were consecutively enrolled. Information on sleep onset time and wake up time on workdays and free days, and TPHA were investigated with a face-to-face interview using a questionnaire booklet. Chronotype was assessed, using the midpoint of sleep on free days, corrected for sleep extension on free days (MSFsc), by subtracting one-half of the average weekly sleep duration. Headache frequency per month, headache intensity, impact of headache, sleep quality, daytime sleepiness, insomnia severity, and mood status were also assessed. Time preference of headache attack was reported for 45.5% and 44.8% of participants with migraine and TTH, respectively. Migraineurs with TPHA had an earlier MSFsc than did migraineurs without TPHA (1:18 a.m. ± 282 min vs. 4:18 a.m. ± 186 min; p = .022). Among migraineurs with TPHA, a later MSFsc was associated with a later preferential time of attack (β = 1.3, 95% confidence interval [CI] = 0.6–2.1, p = .004). A later MSFsc was significantly correlated with a higher headache frequency per month among migraineurs with TPHA (β = 1.9, 95% CI = 0.3–3.4, p = .023), but was not significantly correlated among migraineurs without TPHA (β = 1.4, 95% CI ?1.7–4.4, p = .332). Among TTH participants with TPHA, MSFsc was not significantly associated with a preferential time of attack (β = ?0.2, 95% CI = ?1.0 to 0.6, p = .611). Headache frequency was not associated with MSFsc among TTH participants with TPHA (β = 0.2, 95% CI = ?1.2 to 1.6, p = .792) or among TTH participants without TPHA (β = 0.4, 95% CI = ?0.5 to 1.3, p = .354). In conclusion, approximately one-half of participants with migraine and TTH reported having TPHA. Migraineurs with TPHA had an earlier chronotype than did migraineurs without TPHA. A later chronotype was associated with increased headache frequency and a later time of attack among migraineurs with TPHA. Among participants with TTH, TPHA and headache frequency were not significantly associated with chronotype.     

The association between chronotype and perceived academic stress to depression in medical students

Depression is a multifactorial illness that is highly prevalent among medical students (MS). Chronotypes, which reflect circadian preference in humans, as well as academic stress have been associated with depression in different populations. However, it is not known how chronotype and stress might alone or in combination, associate with depression in MS. Thus, we aimed to evaluate the association between stress, chronotype and depression in MS. In a cross-sectional study, we evaluated a total of 1068 medical students from a public Medical School in Mexico City. The Patient Health Questionnaire-9 (PHQ-9) was used to evaluate depressive symptom severity and the presence of a current depressive episode with a cutoff score of 10 or higher. The Morning-Evening Questionnaire (MEQ) was used to establish chronotype and the Academic Stress Inventory was used to measure perceived academic stress (PAS). We observed that depressive symptom severity was higher in non-morning chronotypes and moderate/severe PAS groups. A factorial ANOVA showed an association between PAS groups and depressive symptom severity. Linear regression showed an association between depressive symptom severity and variables such as PAS scores (p = 0.001), family history of depression (p = 0.001), gender (p = 0.001) and academic year (p = 0.029). Logistic regression analysis showed that evening chronotype (OR: 2.3, 95% CI: 1.2–4.3, p = 0.01) and severe PAS (OR: 4.4, 95% CI: 2.8–7.0, p = 0.0001) were associated with depression. Further, MS with the combination of severe PAS and morning (OR: 5.9, 95% CI: 1.6–22.2, p = 0.01), intermediate (OR: 7.5, 95% CI: 2.3–24.4, p = 0.001) or evening (OR: 10.6, 95% CI: 2.8–40.0, p = 0.001) chronotypes showed a greater association with depression than any PAS or chronotype group alone. Being female, perceiving restricted or limited economic resources, having severe scores of academic stress, and evening chronotype were associated with an increased probability to suffer a current depressive episode. Collectively, these results show that chronotype and PAS are factors associated with depression in MS, and when combined promote this association. Our results might aid in early identification of MS susceptible to depression. Future research could focus on the implementation of simple, low cost preventive strategies, such as chronotype-oriented academic schedules.     

Tumour necrosis factor-α gene polymorphisms in asbestos-induced diseases

Background: Tumour necrosis factor (TNF)-α influences the pathogenesis of lung fibrosis and carcinogenesis in normal cells. Polymorphisms of this gene have been suggested to be associated with susceptibility to lung diseases.

Methods: Association studies were performed in German subjects, using control subjects (n?=?177), pulmonary fibrosis patients (n?=?612) and bronchial carcinoma patients (n?=?374).

Results: Compared with a healthy (control) group, a significant result could be obtained for the asbestosis (patient) group (crude odds ratio (OR_crude)?=?1.57; 95% confidence interval (CI) 1.05–2.36; p?=?0.03), especially with severe lung asbestosis (OR_crude?=?4.15; 95% CI 1.06–16.16; p?=?0.04). A significant association was revealed when comparing asbestosis patients (OR_crude?=?4.08; 95% CI 1.53–10.54; p?=?0.004 and OR_adjusted?=?3.89; 95% CI 1.49–10.17; p?=?0.006) with asbestos-induced lung cancer patients.

Conclusion: The results confirm the hypothesis that TNF-α polymorphisms are associated with asbestos-induced fibrotic or malignant lung diseases in Germans.