Adverse psychosocial working environments characterized by job strain (the combination of high demands and low control at work) are associated with an increased risk of depressive symptoms among ...employees, but evidence on clinically diagnosed depression is scarce. We examined job strain as a risk factor for clinical depression.
We identified published cohort studies from a systematic literature search in PubMed and PsycNET and obtained 14 cohort studies with unpublished individual-level data from the Individual-Participant-Data Meta-analysis in Working Populations (IPD-Work) Consortium. Summary estimates of the association were obtained using random-effects models. Individual-level data analyses were based on a pre-published study protocol.
We included six published studies with a total of 27 461 individuals and 914 incident cases of clinical depression. From unpublished datasets we included 120 221 individuals and 982 first episodes of hospital-treated clinical depression. Job strain was associated with an increased risk of clinical depression in both published relative risk (RR) = 1.77, 95% confidence interval (CI) 1.47-2.13 and unpublished datasets (RR = 1.27, 95% CI 1.04-1.55). Further individual participant analyses showed a similar association across sociodemographic subgroups and after excluding individuals with baseline somatic disease. The association was unchanged when excluding individuals with baseline depressive symptoms (RR = 1.25, 95% CI 0.94-1.65), but attenuated on adjustment for a continuous depressive symptoms score (RR = 1.03, 95% CI 0.81-1.32).
Job strain may precipitate clinical depression among employees. Future intervention studies should test whether job strain is a modifiable risk factor for depression.
To determine the natural history of portopulmonary hypertension (POPH), a retrospective screening‐right heart catheterization‐survival analysis of patients was performed. We categorized patients by ...three treatment subgroups: (1) no therapy for pulmonary hypertension (PH) or liver transplantation (LT), (2) therapy for PH alone and (3) therapy for PH followed by LT. Seventy‐four patients were identified between 1994 and 2007. Nineteen patients received no therapy for PH and no LT representing the natural history of POPH. Five‐year survival was 14%, and 54% had died within 1 year of diagnosis. Five‐year survival in 43 patients receiving therapy for PH but no LT was 45%, and 12% had died within 1 year of diagnosis. Twelve patients underwent LT and 5‐year survival for the nine receiving therapy for PH was 67% versus 25% in the three who were not pretreated with prostacyclin therapy. The survival of untreated patients with POPH was poor. Subgroups of patients selected to medical treatment with or without LT had better long‐term survival. Mortality did not correlate with baseline hemodynamic variables, type of liver disease or severity of hepatic dysfunction. Medical therapy for POPH should be considered in all patients with POPH, but the treatment effects and impact on those considered for LT still requires well‐designed, prospective study before practice guidelines can be suggested.
Given the dismal natural history of portopulmonary hypertension (1‐ and 5‐year survival 46 and 14%), medical therapy for portopulmonary hypertension should be considered.
Job strain, the most widely used indicator of work stress, is a risk factor for obesity-related disorders such as cardiovascular disease and type 2 diabetes. However, the extent to which job strain ...is related to the development of obesity itself has not been systematically evaluated. We carried out a systematic review (PubMed and Embase until May 2014) and meta-analysis of cohort studies to address this issue. Eight studies that fulfilled inclusion criteria showed no overall association between job strain and the risk of weight gain (pooled odds ratio for job strain compared with no job strain 1.04, 95% confidence interval (CI) 0.99-1.09, NTotal=18 240) or becoming obese (1.00, 95% CI 0.89-1.13, NTotal=42 222). In addition, a reduction in job strain over time was not associated with lower obesity risk (1.13, 95% CI 0.90-1.41, NTotal=6507). These longitudinal findings do not support the hypothesis that job strain is an important risk factor for obesity or a promising target for obesity prevention.
The precise characterization of the lobular architecture of the liver has been subject of investigation since the earliest historical publications, but an accurate model to describe the hepatic ...lobular microanatomy is yet to be proposed. Our aim was to evaluate whether Voronoi diagrams can be used to describe the classic liver lobular architecture. We examined the histology of normal porcine and human livers and analyzed the geometric relationships of various microanatomic structures utilizing digital tools. The Voronoi diagram model described the organization of the hepatic classic lobules with overall accuracy nearly 90% based on known histologic landmarks. We have also designed a Voronoi-based algorithm of hepatic zonation, which also showed an overall zonal accuracy of nearly 90%. Therefore, we have presented evidence that Voronoi diagrams represent the basis of the two-dimensional organization of the normal liver and that this concept may have wide applicability in liver pathology and research.
Context.
It is thought that solar energetic ions associated with coronal and interplanetary shock waves are accelerated to high energies by the diffusive shock acceleration mechanism. For this ...mechanism to be efficient, intense magnetic turbulence is needed in the vicinity of the shock. The enhanced turbulence upstream of the shock can be produced self-consistently by the accelerated particles themselves via streaming instability. Comparisons of quasi-linear-theory-based particle acceleration models that include this process with observations have not been fully successful so far, which has motivated the development of acceleration models of a different nature.
Aims.
Our aim is to test how well our self-consistent quasi-linear SOLar Particle Acceleration in Coronal Shocks (SOLPACS) simulation code, developed earlier to simulate proton acceleration in coronal shocks, models the particle foreshock region.
Methods.
We applied SOLPACS to model the energetic storm particle (ESP) event observed by the STEREO A spacecraft on November 10, 2012.
Results.
All but one main input parameter of SOLPACS are fixed by the in situ plasma measurements from the spacecraft. By comparing a simulated proton energy spectrum at the shock with the observed one, we were able to fix the last simulation input parameter related to the efficiency of particle injection to the acceleration process. A subsequent comparison of simulated proton time-intensity profiles in a number of energy channels with the observed ones shows a very good correspondence throughout the upstream region.
Conclusions.
Our results strongly support the quasi-linear description of the foreshock region.
The vascular strain is very high during heavy handgrip exercise, but the intensity and kinetics to reach peak blood flow, and peak oxygen uptake, are uncertain. We included 9 young (25 ± 2 yr) ...healthy males to evaluate blood flow and oxygen uptake responses during continuous dynamic handgrip exercise with increasing intensity. Blood flow was measured using Doppler-ultrasound, and venous blood was drawn from a deep forearm vein to determine arteriovenous oxygen difference (a-vO
) during 6-min bouts of 60, 80, and 100% of maximal work rate (WR
), respectively. Blood flow and oxygen uptake increased (
< 0.05) from 60%WR
557 ± 177(SD) ml/min; 56.0 ± 21.6 ml/min to 80%WR
(679 ± 190 ml/min; 70.6 ± 24.8 ml/min), but no change was seen from 80%WR
to 100%WR
Blood velocity (49.5 ± 11.5 to 58.1 ± 11.6 cm/s) and brachial diameter (0.49 ± 0.05 to 0.50 ± 0.06 cm) showed concomitant increases (
< 0.05) with blood flow from 60% to 80%WR
whereas no differences were observed in a-vO
Shear rate also increased (
< 0.05) from 60% (822 ± 196 s
) to 80% (951 ± 234 s
) of WR
The mean response time (MRT) was slower (
< 0.05) for blood flow (60%WR
50 ± 22 s; 80%WR
51 ± 20 s; 100%WR
51 ± 23 s) than a-vO
(60%WR
29 ± 9 s; 80%WR
29 ± 5 s; 100%WR
20 ± 5 s), but not different from oxygen uptake (60%WR
44 ± 25 s; 80%WR
43 ± 14 s; 100%WR
41 ± 32 s). No differences were observed in MRT for blood flow or oxygen uptake with increased exercise intensity. In conclusion, when approaching maximal intensity, oxygen uptake appeared to reach a critical level at ~80% of WR
and be regulated by blood flow. This implies that high, but not maximal, exercise intensity may be an optimal stimulus for shear stress-induced small muscle mass training adaptations.
This study evaluated blood flow regulation and oxygen uptake during small muscle mass forearm exercise with high to maximal intensity. Despite utilizing only a fraction of cardiac output, blood flow reached a plateau at 80% of maximal work rate and regulated peak oxygen uptake. Furthermore, the results revealed that muscle contractions dictated bulk oxygen delivery and yielded three times higher peak blood flow in the relaxation phase compared with mean values.
Certain women experience negative mood symptoms during the menstrual cycle and progesterone addition in estrogen treatments. In women with PMDD increased negative mood symptoms related to ...allopregnanolone increase during the luteal phase of ovulatory menstrual cycles. In anovulatory cycles no symptom or sex steroid increase occurs. This is unexpected as positive modulators of the GABA-A receptor are generally increasing mood. This paradoxical effect has brought forward a hypothesis that the symptoms are provoked by allopregnanolone the GABA-A receptor system. GABA-A is the major inhibitory system in the brain. Positive modulators of the GABA-A receptor include the progesterone metabolites allopregnanolone and pregnanolone, benzodiazepines, barbiturates, and alcohol. GABA-A receptor modulators are known, in low concentrations to induce adverse, anxiogenic effects whereas in higher concentrations show beneficial, calming properties. Positive GABA-A receptor modulators induce strong paradoxical effects e.g. negative mood in 3-8% of those exposed, while up to 25% have moderate symptoms thus similar as the prevalence of PMDD, 3-8% among women in fertile ages, and up to 25% have moderate symptoms of premenstrual syndrome (PMS). The mechanism behind paradoxical reaction might be similar among them who react on positive GABA-A receptor modulators and in women with PMDD. In women the severity of these mood symptoms are related to the allopregnanolone serum concentrations in an inverted U-shaped curve. Negative mood symptoms occur when the serum concentration of allopregnanolone is similar to endogenous luteal phase levels, while low and high concentrations have less effect on mood. Low to moderate progesterone/allopregnanolone concentrations in women increases the activity in the amygdala (measured with fMRI) similar to the changes seen during anxiety reactions. Higher concentrations give decreased amygdala activity similar as seen during benzodiazepine treatment with calming anxiolytic effects. Patients with PMDD show decreased sensitivity in GABA-A receptor sensitivity to diazepam and pregnanolone while increased sensitivity to allopregnanolone. This agrees with findings in animals showing a relation between changes in alpha4 and delta subunits of the GABA-A receptor and anxiogenic effects of allopregnanolone.
These findings suggest that negative mood symptoms in women with PMDD are caused by the paradoxical effect of allopregnanolone mediated via the GABA-A receptor.
Abstract Some women have negative mood symptoms, caused by progestagens in hormonal contraceptives or sequential hormone therapy or by progesterone in the luteal phase of the menstrual cycle, which ...may be attributed to metabolites acting on the GABA-A receptor. The GABA system is the major inhibitory system in the adult CNS and most positive modulators of the GABA-A receptor (benzodiazepines, barbiturates, alcohol, GABA steroids), induce inhibitory (e.g. anesthetic, sedative, anticonvulsant, anxiolytic) effects. However, some individuals have adverse effects (seizures, increased pain, anxiety, irritability, aggression) upon exposure. Positive GABA-A receptor modulators induce strong paradoxical effects including negative mood in 3%–8% of those exposed, while up to 25% have moderate symptoms. The effect is biphasic: low concentrations induce an adverse anxiogenic effect while higher concentrations decrease this effect and show inhibitory, calming properties. The prevalence of premenstrual dysphoric disorder (PMDD) is also 3%–8% among women in fertile ages, and up to 25% have more moderate symptoms of premenstrual syndrome (PMS). Patients with PMDD have severe luteal phase-related symptoms and show changes in GABA-A receptor sensitivity and GABA concentrations. Findings suggest that negative mood symptoms in women with PMDD are caused by the paradoxical effect of allopregnanolone mediated via the GABA-A receptor, which may be explained by one or more of three hypotheses regarding the paradoxical effect of GABA steroids on behavior: (1) under certain conditions, such as puberty, the relative fraction of certain GABA-A receptor subtypes may be altered, and at those subtypes the GABA steroids may act as negative modulators in contrast to their usual role as positive modulators; (2) in certain brain areas of vulnerable women the transmembrane Cl− gradient may be altered by factors such as estrogens that favor excitability; (3) inhibition of inhibitory neurons may promote disinhibition, and hence excitability. This article is part of a Special Issue entitled: Neuroactive Steroids: Focus on Human Brain.
It is well established that selected lifestyle factors are individually associated with lower risk of chronic diseases, but how combinations of these factors are associated with disease-free ...life-years is unknown.
To estimate the association between healthy lifestyle and the number of disease-free life-years.
A prospective multicohort study, including 12 European studies as part of the Individual-Participant-Data Meta-analysis in Working Populations Consortium, was performed. Participants included 116 043 people free of major noncommunicable disease at baseline from August 7, 1991, to May 31, 2006. Data analysis was conducted from May 22, 2018, to January 21, 2020.
Four baseline lifestyle factors (smoking, body mass index, physical activity, and alcohol consumption) were each allocated a score based on risk status: optimal (2 points), intermediate (1 point), or poor (0 points) resulting in an aggregated lifestyle score ranging from 0 (worst) to 8 (best). Sixteen lifestyle profiles were constructed from combinations of these risk factors.
The number of years between ages 40 and 75 years without chronic disease, including type 2 diabetes, coronary heart disease, stroke, cancer, asthma, and chronic obstructive pulmonary disease.
Of the 116 043 people included in the analysis, the mean (SD) age was 43.7 (10.1) years and 70 911 were women (61.1%). During 1.45 million person-years at risk (mean follow-up, 12.5 years; range, 4.9-18.6 years), 17 383 participants developed at least 1 chronic disease. There was a linear association between overall healthy lifestyle score and the number of disease-free years, such that a 1-point improvement in the score was associated with an increase of 0.96 (95% CI, 0.83-1.08) disease-free years in men and 0.89 (95% CI, 0.75-1.02) years in women. Comparing the best lifestyle score with the worst lifestyle score was associated with 9.9 (95% CI 6.7-13.1) additional years without chronic diseases in men and 9.4 (95% CI 5.4-13.3) additional years in women (P < .001 for dose-response). All of the 4 lifestyle profiles that were associated with the highest number of disease-free years included a body-mass index less than 25 (calculated as weight in kilograms divided by height in meters squared) and at least 2 of the following factors: never smoking, physical activity, and moderate alcohol consumption. Participants with 1 of these lifestyle profiles reached age 70.3 (95% CI, 69.9-70.8) to 71.4 (95% CI, 70.9-72.0) years disease free depending on the profile and sex.
In this multicohort analysis, various healthy lifestyle profiles appeared to be associated with gains in life-years without major chronic diseases.
It has been a long-lasting debate whether the heart's stroke volume (SV) increases at high aerobic intensities or plateau. Further, sex and level of aerobic power are shown to influence the response. ...The purpose of this study was to investigate the SV at increasing intensities in elite female athletes and moderately trained females. 13 elite athletes and 11 moderately trained controls with maximal oxygen consumption (VO(2max)) of 67.1 ± 6.1 and 49.5 ± 2.3 mL ∙ min (- 1) ∙ kg (- 1), respectively, were recruited. SV was measured at rest, and running on a treadmill at 40%, 60%, 80% and 100% of VO(2max) using the single breath acetylene uptake (SB) technique. Both groups showed a significant (p<0.05) increase in SV from 40% of VO2max to VO(2max), with increases from 105.3 ± 19.0 to 129.1 ± 16.3 mL∙ beat(-1) for the elite females and from 68.7 ± 21.7 to 82.7 ± 14.0 mL ∙ beat (- 1) for the moderately trained. No differences were observed between groups in these increases, but the elite athletes displayed a larger (p<0.05) SV at all intensities. It is concluded that the SV increases at high aerobic intensities both in elite athlete females and moderately trained females.
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