Circadian Variation in Patient Characteristics and Outcomes in ST-Segment Elevation Myocardial Infarction

A morning peak in ST-segment elevation myocardial infarction (STEMI) has been described. The authors explored the relationship between variation of symptom onset, patient characteristics, and outcomes in two worldwide fibrinolytic trials. A total of 35 492 patients with STEMI were grouped into 8-h intervals by time of symptom onset: early (06:00 to 13:59?h), late-day (14:00 to 21:59?h), overnight (22:00 to 05:59?h). The authors correlated timing with patient characteristics and outcomes (adjusted for thrombolysis in myocardial infarction [TIMI] risk score) first in InTIME II-TIMI 17 trial (N?=?15 031), and confirmed in the ExTRACT-TIMI 25 trial (N?=?20 461). Timing was similar in the derivation (early 49%, late-day 30%, and overnight 21%; p?<?.001) and validation set (48%, 31%, and 21%, respectively; p?<?.001). Some patient characteristics consistently varied with time of symptom onset. Patients in the early cohort were older with poorer renal function. The late-day group had more smokers with higher initial heart rate and systolic blood pressure. Those with overnight symptom onset had higher rates of obesity, prior myocardial infarction, and treatment delays. Prior use of aspirin and beta-blockers was also highest in the overnight group. Relative to the early cohort, adjusted mortality was higher with late-day onset (derivation odds ratio [OR]: 1.19, p?=?.04; validation OR: 1.18, p?=?.01), but there was no excess in mortality overnight compared with early (derivation OR: .97, p?=?.72; validation OR: 1.01, p?=?.90). Composite endpoints followed similar patterns. This study indicates that circadian patterns in onset of STEMI continue to exist with patient characteristics differing by time of day. Despite a potential physiologic resistance to morning thrombolysis, outcomes were best in the early cohort, intermediate overnight, and worst with late-day symptom onset. Efforts to reduce smoking and improve control of blood pressure could reduce the number of patients with late-day onset of STEMI who experience the worst outcomes. (Author correspondence: owen@mogabgab.com)     

Eveningness associates with smoking and sleep problems among pregnant women

Sleep problems during pregnancy impair maternal health and increase the risk for adverse pregnancy outcome. The circadian preference toward eveningness has been associated with sleep problems in previous studies. Here, we studied whether evening-type women had more sleep problems during their pregnancy, as compared with other chronotypes, in a sample consisting of 1653 pregnant women from the Finnish CHILD-SLEEP Birth Cohort. Chronotype was assessed with a shortened version of the morningness–eveningness questionnaire. Pregnant evening-type women reported more sleep problems, including troubles of falling asleep (OR = 3.4, p < 0.0001), poor sleep quality (OR = 2.9, p < 0.01) and daily tiredness (OR = 3.2, p < 0.0001) than the morning-type women, even after controlling for sleep duration and sleep deprivation. They had higher scores on Epworth Sleepiness Scale (p < 0.05), Basic Nordic Sleep Questionnaire (p < 0.0001) and Global Seasonality Score (p < 0.01) and were also more often smokers, also during pregnancy (p < 0.001) and reported poorer general health (p < 0.001) than the morning-type women. They also reported having had more sleep problems during their childhood (OR = 1.5, p < 0.05) and adolescence (OR = 2.0, p < 0.001) than the morning-type women. Our results indicate that eveningness is associated with more sleep problems and unhealthy life habits during pregnancy.     

Thrombin activity throughout the acute phase of acute ST-elevation myocardial infarction and the relation to outcome

Background: Thrombin and plasmin play a central role in ongoing thrombosis and platelet activation in patients with acute ST-elevation myocardial infarction (STEMI). Data of thrombin and plasmin activity in the early course of STEMI and the relation to outcome are scarce.

Methods: We included 68 consecutive patients (53 male, 59?±?11.4 years) with STEMI who underwent acute catheter-based reperfusion therapy within the first 12?h after onset of symptoms. Blood samples were taken at admission and after 4, 8, 12 and 24?h. Thrombin activity and generation was measured by changes in the thrombin/antithrombin-III complex (TAT) and prothrombin fragment (F1.2); plasmin was measured by changes in the plasmin-α₂/antiplasmin complex (PAP). A follow-up with respect to the combined primary endpoint consisting of death, acute myocardial infarction or urgent need for revascularization up to 6 weeks post-discharge was carried out.

Results: TAT values showed no significant change over time in patients with and without the primary endpoint but there was a borderline difference between these groups at 4?h after admission (event group 9.0 vs no event group 4.7?μg l^?1, p?=?0.057). F1.2 values were different between groups only after 24?h (event group 1.5 vs no event group 0.9?nmol l^?1, p?=?0.028) and did not differ in serial sampling of 24?h. PAP values were higher in patients with events after 4 and 8?h and declined over time in the group without events (p?<0.001). Odds ratios (OR) with respect to the primary endpoint were highest for TAT?>4.8?μg l^?1 at 0?h and TAT?>8.4?μg?l^?1 at 4?h (OR 7.1, 95% confidence interval (CI) 1.5–34, p?=?0.015 and OR 5.5, 95% CI 1.5–20.0, p?=?0.01, respectively). The predictive value of plasmin concentrations were equally high after 4?h (PAP?>962?μg l^?1; OR 6.8, 95% CI 1.8–26.2, p?=?0.005) and 8?h (PAP?>495?μg l^?1, OR 6.7, 95% CI 1.4–32.9, p?=?0.024). Values for F1.2 were only predictive after 24?h (F1.2?>0.85?nmol l^?1, OR 13, 95% CI 1.4–117.8, p?=?0.023).

Conclusions: Markers of thrombin and plasmin activity in acute STEMI are related to outcome. The marker for thrombin generation F1.2 becomes a significant predictor of outcome at 24?h after admission, reflecting the potentially adverse effects of ongoing thrombin generation. This underlines the potential for direct thrombin inhibition and individualization of treatment by thrombin markers in STEMI.     

The role of FOXP3 rs3761548 and rs2294021 polymorphisms in pediatrics acute lymphoblastic leukemia: association with risk and response to therapy

FOXP3 X-linked gene has crucial roles in the development and function of regulatory T cells. We investigated the association of FOXP3 rs3761548, rs3761549 and rs2294021 single nucleotide polymorphisms (SNPs) with acute lymphoblastic leukemia (ALL) susceptibility and response to therapy. Genotyping was performed in 247 patients and 210 healthy subjects. We observed a higher frequency of rs3761548 A carriers and rs2294021 C carriers (p?<?0.04) in male patients, and lower frequencies of rs3761548 AC genotype (p?=?0.04) and rs2294021 CT genotype (p?=?0.01) in female patients compared to controls. ACC (p?=?0.04) and ATC haplotypes (p?=?0.002) were associated with susceptibility to ALL. There was a significant correlation between the genotypes of rs3761548 and rs2294021 SNPs with event-free survival (EFS) and overall survival (OS). The rs3761548 A genotype in male patients was associated with increased risk of relapse (p?<?0.0001), shorter EFS, increased death rate (p?=?0.002) and shorter OS compared to C genotype (p?=?0.001). Similar significant results were observed for the relation of rs2294021 C genotype with response to therapy in male patients. In females, patients with rs3761548 AC genotype had longer EFS (p?=?0.02) and those with rs2294021 CT had longer EFS and OS (p?<?0.005). According to haplotype analysis, patients carrying ACC or ATC haplotypes had the highest number of WBCs and shorter EFS or OS, and patients with CCT haplotype had the lowest number of WBCs and longer EFS or OS. These results provided evidence for the impact of these polymorphisms on susceptibility and response to therapy in children with ALL.

     

Age- and sex-related changes in vibrotactile sensitivity of hand and face in neurotypical adults

Abstract

Sensory perception decreases with age, and is altered as a function of sex. Very little is known about the age- and sex-related changes in vibrotactile detection thresholds (VDTs) of the face relative to the glabrous hand. This study utilized a single-interval up/down (SIUD) adaptive procedure to estimate the VDT for mechanical stimuli presented at 5, 10, 50, 150, 250, and 300?Hz at two sites on the face, including the right non-glabrous surface of the oral angle and the right lower lip vermilion; and on the hand on the glabrous surface of the distal phalanx of the right dominant index finger. Eighteen right-handed healthy younger adults and 18 right-handed healthy older adults participated in this study. VDTs were significantly different between the three stimulus sites (p?<?0.0001), and dependent on stimulus frequency (p?<?0.0001) and the sex of the participants (p?<?0.005). VDTs were significantly higher for older adults when compared to younger adults for the finger stimulation condition (p?<?0.05). There were significant differences (p?<?0.05) in cheek and lower lip VDTs between male and female subjects. Difference in the VDTs between the three stimulation sites is presumed to reflect the unique typing and distribution of mechanoreceptors in the face and hand. Age-related differences in finger skin sensitivity are likely due to changes in the physical structure of skin, changes in the number and morphology of the mechanoreceptors, differences in the functional use of the hand, and its central representation. Sex-related differences in the VDTs may be due to the differences in tissue conformation and thickness, mechanoreceptor densities, skin hydration, or temperature characteristics.     

Major Increase in Prevalence of Overweight and Obesity between 1987 and 2001 among Danish Adults

Objective: The aim of the study was to examine the secular trends in the prevalence of obesity (BMI ≥ 30.0 kg/m²) and overweight (25.0 ≤ BMI < 30.0 kg/m²) in Danish adults between 1987 and 2001. Research Methods and Procedures: The study included self‐reported weight and height of 10, 094 men and 9897 women 16 to 98 years old, collected in a series of seven independent cross‐sectional surveys. Prevalence and changes in prevalence of obesity and overweight stratified by sex and age groups were determined Results: The prevalence of obesity more than doubled between 1987 and 2001, in men from 5.6% to 11.8% [odds ratio (OR) = 2.3, 95% confidence interval (CI) = 1.9 to 2.8, p < 0.0001] and in women from 5.4% to 12.5% (OR = 2.6, 95% CI = 2.1 to 3.2, p < 0.0001), with the largest increase among the 16‐ to 29‐year‐old subjects (men, from 0.8% to 7.5%, OR = 10.2, 95% CI = 4.1 to 25.3, p < 0.0001; women, from 1.4% to 9.0% OR = 7.0, 95% CI = 3.5 to 14.1, p < 0.0001). Between 1987 and 2001, the prevalence of overweight increased from 34% to 40% in men and from 17% to 27% in women. Discussion: The prevalence of overweight and obesity in Denmark has increased substantially between 1987 and 2001, particularly among young adults, a development that resembles that of other countries. There is clearly a need for early preventive efforts in childhood to limit the number of obesity‐related complications in young adults.     

Lead Accumulation as Possible Risk Factor for Primary Open-Angle Glaucoma

The objective of this study was to investigate the relationship between preeclampsia and iodine levels and magnesium concentration in the blood of subjects in the northeast Anatolia region where iodine deficiency is common. Blood specimens were obtained from 24 preeclamptic and 16 healthy pregnant women. Iodine levels in blood were determined by the Foss method based on the Sandell–Kolthoff reaction. Serum protein-bound iodine (PBI) levels and magnesium concentration in maternal blood were lower in patients with severe preeclampsia compared to normal pregnant women (8.46?±?1.22 vs. 11.46?±?1.71 μg/dL, p?<?0.001, 1.63?±?0.05 vs. 1.86?±?0.05 mg/dL, p?<?0.001, respectively). Serum PBI levels and magnesium concentration in umbilical cord blood were higher in patients with severe preeclampsia than in normal pregnant women (8.84?±?1.9 vs. 7.33?±?1.07 μg/dL, p?<?0.05, 2.48?±?0.03 vs. 2.02?±?0.01 mg/dL, p?<?0.001, respectively). There was a positive correlation between the serum PBI levels in maternal blood and magnesium concentration in maternal blood in patients with severe preeclampsia (r?=?0.41, p?<?0.05). Thus, iodine may be one factor contributing to the pathophysiology of preeclampsia. Iodine supplementation may be effective therapy in preeclamptic in pregnant women.     

Cystatin C,NT-proBNP,and inflammatory markers in acute heart failure: insights into the cardiorenal syndrome

Background: Inflammation is thought to be a mediator in the pathophysiology of the cardiorenal syndrome. We evaluated the interactions between kidney function, cardiac stress, and various inflammatory cytokines in patients with acute heart failure (AHF). The effect on 1-year mortality was also assessed.

Methods and results: Plasma levels of cystatin C, NT-proBNP, and inflammatory cytokines (interleukin [IL]-6, tumor necrosis factor-α [TNF-α], IL-10) were measured in consecutive patients (n?=?465) hospitalized for AHF. After adjustment for demographic characteristics and comorbidities, TNF-α had the strongest relation with renal function (β?=?0.39, P?<?0.0001). Elevated TNF-α levels were seen in patients with high cystatin C, irrespective of NT-proBNP. Levels of IL-6 (β?=?0.26, P?<?0.0001) and IL-10 (β?=?0.15, P?<?0.01), but not TNF-α, were associated with NT-proBNP. Moreover, the most elevated levels of IL-6 were seen in patients with combined high NT-proBNP and high cystatin C. Cox regression analysis found IL-6 above median to be independently predictive of mortality (hazard ratio 1.9; 95% CI 1.2–2.9, P?=?0.003). TNF-α was not significantly associated with prognosis in the overall population after adjustment for multiple covariates, but improved risk stratification in the subgroup with low cystatin C and NT-proBNP.

Conclusion: Levels of TNF-α in AHF are related to kidney function, but not to NT-proBNP. IL-6 seems to be more associated with cardiac stress. Patients with severe dual organ dysfunction have the highest levels of IL-6 and TNF-α. Different relations of inflammatory cytokines to renal function and cardiac stress need to be considered when evaluating heart–kidney interactions.     

HLA-C locus alleles may modulate the clinical expression of psoriatic arthritis

The aim of the present study was to evaluate the relative contribution of human leukocyte antigen (HLA)-C locus alleles in determining the risk and the clinical expression of psoriatic arthritis (PsA). One hundred PsA patients were randomly selected and grouped into three disease subsets: oligoarthritis (n = 40), polyarthritis (n = 25) and spondylitis (n = 35). The HLA-C locus profile of this cohort was studied by methods based on molecular biology and was compared with that of 45 patients with psoriasis vulgaris and 177 healthy blood donors from the same ethnic origin. HLA-Cw*0602 was found associated with both psoriasis (odds ratio (OR) 6.2; 95% confidence interval (CI) 3.1 to 12.5; p < 0.0001) and PsA (OR 6.2; 95% CI 3.6 to 10.8; p < 0.0001); however, this allele was equally found among the PsA subsets. HLA-Cw6-positive patients showed a longer psoriasis-arthritis latency period (p = 0.012). HLA-Cw*0701 was found under-represented in PsA in comparison with controls (OR 0.5; 95% CI 0.3 to 0.9; p = 0.04), as was HLA-Cw*0802 (OR 0.3; 95% CI 0.08 to 1; p = 0.05). A positive association was found between psoriatic spondylitis and HLA-Cw*0702 (OR 5.0; 95% CI 1.4 to 25; p = 0.01). HLA-Cw*0602 seems to confer a general risk for psoriasis, but the presence of other HLA-C locus alleles may explain an additional arthritogenic risk. HLA-C alleles may modulate some aspects of the clinical expression of PsA, but these findings need confirmation.     

Correlation of GSTP1 gene variants of male Iraqi waterpipe (Hookah) tobacco smokers and the risk of lung cancer

Glutathione-S-transferases (GSTs) play a role in the detoxification of environmental chemicals and mutagens, such as those inhaled during tobacco smoking. There have been conflicting reports concerning GST polymorphisms as risk factors in the development of lung cancer. No studies focused on Arab populations exposed to Waterpipe (WP) tobacco smoke have been undertaken. Here Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) and gene sequencing were applied to analyze allelic variations in GSTP1-rs1695 and -rs1138272 amongst 123 lung cancer patients and 129 controls. The data suggest that WP smoking raised the risk of lung cancer more than three-fold (OR?3.6; 95% CI 2.1–6.0; p?<?0.0001). However, there was no significant association between individual GSTP1 polymorphisms and the risk of lung cancer. In contrast, analysis of the rs1695 and rs1138272 combination suggested that the risk of lung cancer was raised more than two-fold for carriers of the GSTP1-rs1695 (G) allele (OR?2.5; 95% CI 1.0–6.4; p?<?0.05), however, the presence of the GSTP1-rs1138272 (T) allele, in addition to GSTP1-rs1695, did not significantly change the risk ratio (OR?2.8; 95% CI 1.4–5.7; p?<?0.004). WP tobacco smokers who carried the GSTP1-rs1695, but not GSTP1-rs1138272, allele were similarly susceptible to lung cancer (OR 2.4; 95% CI 1.1–5.3; p?<?0.03). Hence, the results suggest that smoking WP tobacco and carrying GSTP1-rs1695 polymorphisms are risk factors for lung cancer in Arab Iraqi males.

     

The GALA study: relationship between galectin-3 serum levels and short- and long-term outcomes of patients with acute heart failure

Objective: We tested the hypothesis that early measurement of galectin-3 at the emergency department (ED) during an episode of acute heart failure (AHF) allows predicting short- and long-term outcomes.

Methods: We performed an exploratory study including 115 patients consecutively diagnosed with AHF in a single ED. Clinical and analytical variables were recorded. The primary endpoint was 30-day all-cause mortality, and secondary endpoints were 30-day composite outcome (death, rehospitalization or ED reconsultation, whichever first) and 1-year mortality.

Results: Seven patients (6.1%) died within 30?days and 43 (37.4%) within 1?year. The 30-day composite endpoint was observed in 21.1% of patients. Galectin-3 was correlated with NT-proBNP and the glomerular filtration rate but not with age and s-cTnI. Measured at time of ED arrival, galectin-3 showed good discriminatory capacity for 30-day mortality (AUC ROC: 0.732; 95% CI 0.512–0.953; p?=?0.041) but not for 1-year mortality (0.521; 0.408–0.633; p?=?0.722). Patients with galectin-3 concentrations?>42?μg/L had an OR?=?7.67(95%CI?=?1.57-37.53; p?=?0.012) for 30-day mortality. Conversely, NT-proBNP only showed predictive capacity for 1-year mortality (0.642; 0.537–0.748; p?=?0.014). Patients with NT-proBNP concentrations?>5400?ng/L had an OR?=?4.34 (95%CI?=?1.93-9.77; p?<?0.001) for 1-year mortality. These increased short- (galectin-3) and long-term (NT-proBNP) risks remained significant after adjustment for age or renal function. s-cTnI failed in both short- and long term death prediction. No biomarker predicted the short-term composite endpoint.

Conclusion: These results suggest that galectin-3 could help to monitor the risk of short-term mortality in unselected patients with AHF attended in the ED.     

Evaluation of mediators of oxidative stress and inflammation in patients with acute appendicitis

Context: This study aims to explore the potential of new inflammatory markers for improving the challenging diagnosis of acute appendicitis (AA).

Methods: Levels of IL-1, IL-6, IL-8, IL-10, CRP, INF-γ, and TNF-α in serum were measured in 73 patients with AA. Oxidative stress and antioxidant enzymes were analyzed.

Results: Serum levels of interleukins, TNF-α, and INF-γ were significantly elevated in patients with appendicitis (p?<?0.0001), except for IL-10, which presented decreased levels. There were no significant differences in SOD (p?=?0.29), CAT (p?=?0.19), or TBARS levels (p?=?0.18), whereas protein carbonyls presented significant increase (p?<?0.0001).

Conclusion: Evaluating these biomarkers could aid in diagnosing AA.     

LINE1 methylation levels associated with increased bladder cancer risk in pre-diagnostic blood DNA among US (PLCO) and European (ATBC) cohort study participants

Global methylation in blood DNA has been associated with bladder cancer risk in case-control studies, but has not been examined prospectively. We examined the association between LINE1 total percent 5-methylcytosine and bladder cancer risk using pre-diagnostic blood DNA from the United States-based, Prostate, Lung, Colorectal, Ovarian Cancer Screening Trial (PLCO) (299 cases/676 controls), and the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) cohort of Finnish male smokers (391 cases/778 controls). Logistic regression adjusted for age at blood draw, study center, pack-years of smoking, and sex was used to estimate odd ratios (ORs) and 95% confidence intervals (CIs) using study- and sex-specific methylation quartiles. In PLCO, higher, although non-significant, bladder cancer risks were observed for participants in the highest three quartiles (Q2–Q4) compared with the lowest quartile (Q1) (OR = 1.36, 95% CI: 0.96 -1.92). The association was stronger in males (Q2–Q4 vs. Q1 OR = 1.48, 95% CI: 1.00–2.20) and statistically significant among male smokers (Q2–Q4 vs. Q1 OR = 1.83, 95% CI: 1.14–2.95). No association was found among females or female smokers. Findings for male smokers were validated in ATBC (Q2–Q4 vs. Q1: OR = 2.31, 95% CI: 1.62–3.30) and a highly significant trend was observed (P = 8.7 × 10^?7). After determining that study data could be combined, pooled analysis of PLCO and ATBC male smokers (580 cases/1119 controls), ORs were significantly higher in Q2-Q4 compared with Q1 (OR = 2.03, 95% CI: 1.52–2.72), and a trend across quartiles was observed (P = 0.0001). These findings suggest that higher global methylation levels prior to diagnosis may increase bladder cancer risk, particularly among male smokers.     

Stent Thrombosis is the Primary Cause of ST-Segment Elevation Myocardial Infarction following Coronary Stent Implantation: A Five Year Follow-Up of the SORT OUT II Study

Background

The widespread use of coronary stents has exposed a growing population to the risk of stent thrombosis, but the importance in terms of risk of ST-segment elevation myocardial infarctions (STEMIs) remains unclear.

Methods

We studied five years follow-up data for 2,098 all-comer patients treated with coronary stents in the randomized SORT OUT II trial (mean age 63.6 yrs. 74.8% men). Patients who following stent implantation were readmitted with STEMI were included and each patient was categorized ranging from definite- to ruled-out stent thrombosis according to the Academic Research Consortium definitions. Multivariate logistic regression was performed on selected covariates to assess odds ratios (ORs) for definite stent thrombosis.

Results

85 patients (4.1%), mean age 62.7 years, 77.1% men, were admitted with a total of 96 STEMIs, of whom 60 (62.5%) had definite stent thrombosis. Notably, definite stent thrombosis was more frequent in female than male STEMI patients (81.8% vs. 56.8%, p = 0.09), and in very late STEMIs (p = 0.06). Female sex (OR 3.53 [1.01–12.59]) and clopidogrel (OR 4.43 [1.03–19.01]) was associated with increased for definite stent thrombosis, whereas age, time since stent implantation, use of statins, initial PCI urgency (STEMI [primary PCI], NSTEMI/unstable angina [subacute PCI] or stable angina [elective PCI]), and glucose-lowering agents did not seem to influence risk of stent thrombosis.

Conclusion

In a contemporary cohort of coronary stented patients, stent thrombosis was evident in more than 60% of subsequent STEMIs.     

Sex-Differences in the Metabolic Health of Offspring of Parents with Diabetes: A Record-Linkage Study

Maternal diabetes in pregnancy affects offspring health. The impact of parental diabetes on offspring health is unclear. We investigated the impact of parental diabetes on the metabolic-health of adult-offspring who did not themselves have diabetes. Data from the Generation Scotland: Scottish Family Health Study, a population-based family cohort, were record-linked to subjects’ own diabetes medical records. From F₀-parents, we identified F₁-offspring of: mothers with diabetes (OMD, n = 409), fathers with diabetes (OFD, n = 468), no parent with diabetes (ONoPD, n = 2489). Metabolic syndrome, body, biochemical measurements and blood-pressures were compared between F₁-offspring groups by sex. A higher proportion of female OMD had metabolic syndrome than female OFD or ONoPD (P<0.0001). In female offspring, predictors of metabolic syndrome were: having a mother with diabetes (OR = 1.78, CI 1.03–3.07, [reference ONoPD]), body mass index (BMI, OR = 1.21, CI 1.13–1.30) and age (OR = 1.03, CI 1.01–1.06). In male offspring, predictors of metabolic syndrome were: BMI (OR = 1.18, CI 1.09–1.29) and percent body-fat (OR = 1.12, CI 1.05–1.19). In both sexes, OMD had higher blood-pressures than OFD (P<0.0001). In females, OMD had higher glucose (P<0.0001) and percent body-fat (P<0.0001) compared with OFD or ONoPD. OMD and OFD both had increased waist-measurements (P<0.0001), BMI (P<0.0001) and percent body-fat (P<0.0001) compared with ONoPD. Female OMD and OFD had lower HDL-cholesterol levels (P<0.0001) than female ONoPD. Parental diabetes is associated with higher offspring-BMI and body-fat. In female offspring, maternal diabetes increased the odds of metabolic syndrome, even after adjusting for BMI. Further investigations are required to determine the mechanisms involved.     

Expression of Clock Genes in Human Subcutaneous and Visceral Adipose Tissues

Disrupted circadian rhythms are associated with obesity and metabolic alterations, but little is known about the participation of peripheral circadian clock machinery in these processes. The aim of the present study was to analyze RNA expression of clock genes in subcutaneous (SAT) and visceral (VAT) adipose tissues of male and female subjects in AM (morning) and PM (afternoon) periods, and its interactions with body mass index (BMI). Ninety-one subjects (41?±?11 yrs of age) presenting a wide range of BMI (21.4 to 48.6?kg/m²) were included. SAT and VAT biopsies were obtained from patients undergoing abdominal surgeries. Clock genes expressions were evaluated by qRT-PCR. The only clock gene that showed higher expression (p?<?.0001) in SAT in comparison to VAT was PER1 of female (372%) and male (326%) subjects. Different patterns of expression between the AM and PM periods were observed, in particular REV-ERBα, which was reduced (p?<?.05) at the PM period in SAT and VAT of both women and men (women: ～53% lower; men: ～78% lower), whereas CLOCK expression was not altered. Relationships between clock genes were different in SAT vs. VAT. BMI was negatively correlated with SATPER1 (r?=??.549; p?=?.001) and SATPER2 (r?=??.613; p?=?.0001) and positively with VATCLOCK (r?=?.541; p?=?.001) and VATBMAL1 (r?=?.468; p?=?.007) only in women. These data suggest that the circadian clock machinery of adipose tissue depots differs between female and male subjects, with a sex-specific effect observed for some genes. BMI correlated with clock genes, but at this moment it is not possible to establish the cause-effect relationship. (Author correspondence: mzanquetta@gmail.com)     

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.     

CRP velocity and short-term mortality in ST segment elevation myocardial infarction

Context: There is a known association between C-reactive protein (CRP) levels and adverse outcomes in patients presenting with ST-elevation myocardial infarction (STEMI). The optimal time frame to measure CRP for risk stratification is not known.

Objective: The aim of the current study was to evaluate the relation between the change in CRP velocity (CRPv) and 30-d mortality among STEMI patients.

Material and methods: We included consecutive patients with a diagnosis of STEMI who presented to Tel-Aviv Medical Center between 2008 and 2014 and had their CRP measured with a wide range assay (wr-CRP) at least twice during the 24?h after admission. CRPv was defined as the change in wr-CRP concentration (mg/l) divided by the change in time (in hours) between the two measurements.

Results: The study population comprised of 492 patients, mean age was 62?±?14, 80% were male. CRPv was significantly higher among patients who died within 30 d of admission (1.42?mg/l versus 0.18?mg/l, p?<?0.001). In a multivariate regression model adjusted to multiple confounders, CRPv was independently associated with 30-d mortality (OR 1.39, 95% CI: 1.20–1.62, p?<?0.001).

Conclusion: CRPv might be an independent and rapidly measurable biomarker for short-term mortality in patients presenting with STEMI.