Epidemiology of symptoms of common mental disorders among elite Gaelic athletes: a prospective cohort study

Objective: Scientific knowledge about symptoms of common mental disorders among elite Gaelic athletes is lacking. Consequently, this study aimed to (i) determine the prevalence, comorbidity and 6-month incidence of symptoms of common mental disorders (distress, anxiety/depression, sleep disturbance, adverse alcohol use) among elite Gaelic athletes and (ii) evaluate their association with potential stressors (severe musculoskeletal injuries, surgeries, recent life events, career dissatisfaction).

Methods: An observational prospective cohort study by means of questionnaires was conducted over six months among elite Gaelic athletes (N=204). Using validated questionnaires to assess symptoms of common mental disorders as well as several stressors, an electronic questionnaire was set up and distributed by the Gaelic Players’ Association.

Results: Prevalence ranged from 23% for adverse alcohol use to 48% for anxiety/depression. Around 24% of the participants reported at baseline two symptoms. Six-month incidence ranged from 11% for sleep disturbance to 21% for anxiety/depression. Severe musculoskeletal injury, surgery, recent life events and career dissatisfaction led to an increased risk for common mental disorders.

Conclusion: Our findings indicate that raising the self-awareness of all stakeholders in Gaelic sports about common mental disorders should be prioritized, as well as the evidence-based development and application of adequate preventive and supportive measures.     

Plasma phospholipid transfer protein activity is lowered by 24-h insulin and acipimox administration: blunted response to insulin in type 2 diabetic patients.

Cholesteryl ester transfer protein (CETP) transfers cholesteryl esters from HDL to VLDL and LDL. Phospholipid transfer protein (PLTP) transfers phospholipids between lipoproteins, converts HDL3 into larger and smaller particles, and is involved in pre-beta-HDL generation. We examined the effects of 24-h hyperinsulinemia (30 mU x kg(-1) x h(-1)) and 24-h Acipimox (250 mg/4 h) on plasma lipids as well as CETP and PLTP activities (measured with exogenous substrate assays) in eight healthy and eight type 2 diabetic subjects. After 24 h of insulin, plasma free fatty acids (FFAs), HDL cholesterol, and plasma apolipoprotein AI decreased in healthy subjects and type 2 diabetic patients (P < 0.05). Plasma triglycerides did not significantly change in either group. After 24 h of Acipimox, all parameters, including plasma triglycerides, decreased in both groups (P < 0.05). Insulin decreased plasma PLTP activity by 17.6% after 24 h in healthy subjects (P < 0.05) and 10.2% in diabetic patients (P < 0.05 vs. baseline; P < 0.05 vs. healthy subjects). Acipimox lowered PLTP activity by 10.3% in healthy subjects (P < 0.05) and 11.3% in diabetic patients (P < 0.05). When insulin was infused for 3 h after Acipimox, a further decrease was found only in healthy subjects. Plasma CETP activity decreased by 9.5% after 24 h of insulin in healthy subjects (P < 0.05), but not in diabetic patients. Acipimox did not decrease plasma CETP activity in either group. In healthy subjects, the PLTP responses with insulin and Acipimox were larger than the changes in CETP activity (P < 0.05). These findings suggest that there is a metabolic link between the regulation of plasma FFA and PLTP, but not CETP. The PLTP response to insulin is blunted in type 2 diabetes.     

Insulin decreases plasma cholesteryl ester transfer but not cholesterol esterification in healthy subjects as well as in normotriglyceridaemic patients with type 2 diabetes

BACKGROUND: Plasma cholesterol esterification (EST) and subsequent cholesteryl ester transfer (CET) from high-density lipoproteins (HDLs) towards apolipoprotein (apo) B-containing lipoproteins are key steps in HDL metabolism. MATERIALS AND METHODS: The effects of exogenous hyperinsulinaemia on plasma CET and EST, measured with isotope methods, were evaluated in 10 male normotriglyceridaemic (plasma triglycerides <2.0 mmol L-1) patients with type 2 diabetes and 10 individually matched healthy subjects during a two-step hyperinsulinaemic euglycaemic clamp over 6-7 h. RESULTS: No between-group differences in baseline plasma lipid parameters were observed, but the HDL cholesteryl ester content was lower (P < 0.02) and the HDL triglyceride content was higher (P < 0.05) in diabetic patients. Baseline CET and EST were similar in the groups. In both groups, hyperinsulinaemia decreased plasma triglycerides (P < 0.01) and the HDL triglyceride content (P < 0.01) compared with saline infusion in healthy subjects, whereas the HDL cholesteryl ester content increased (P < 0.05 vs. saline infusion) in diabetic patients. CET was similarly decreased by hyperinsulinaemia in both groups (P < 0.01 vs. saline infusion). In contrast, the change in EST in either group was not different from that during saline administration. In the combined group, baseline CET was positively correlated with plasma triglycerides (Rs = 0.68, P < 0.01). The HDL cholesteryl ester content was negatively (Rs = -0.48, P < 0.05) and the HDL triglyceride content was positively (Rs = 0.64, P < 0.01) correlated with CET. CONCLUSION: Insulin infusion decreases plasma CET in conjunction with a fall in triglycerides but does not decrease cholesterol esterification in healthy and type 2 diabetic subjects, indicating that acute hyperinsulinaemia has a different effect on these processes involved in HDL metabolism. Despite unaltered fasting plasma CET, HDL core lipid composition was abnormal in diabetic patients, suggesting that additional mechanisms may contribute to changes in HDL metabolism in diabetes mellitus.     

Dietary corn oil versus olive oil enhances HDL protein turnover and lowers HDL cholesterol levels in hamsters.

We studied the effect of dietary olive and corn oil on high-density lipoprotein (HDL) metabolism in golden Syrian hamsters. The animals were fed a semipurified diet containing 0.1% cholesterol and 40 energy % in the form of either olive or corn oil for a period of nine weeks. Hamsters fed corn oil had significantly lower very-low density and low-density lipoprotein (VLDL+LDL) cholesterol concentrations than those fed olive oil (0.98+/-0.24 vs. 1.40+/-0.34 mmol/l, means+/-S.D., n = 12), as well as significantly lower HDL cholesterol concentrations (3.31+/-0.50 vs. 3.91+/-0.12 mmol/l). The binding capacity of 125I-labelled HDL to liver membranes was 33% higher in the hamsters fed corn oil instead of olive oil (571+/-29 vs. 429+/-24 ng HDL protein/mg membrane protein, P<0.05, n = 4). HDL protein kinetics were studied with 125I-HDL using a constant infusion technique. Both HDL fractional catabolic rate (0.255+/-0. 058 vs. 0.121+/-0.023 /h, P<0.01, n = 5) and transport rate (2.386+/-0. 753 vs. 1.218+/-0.101 mg/h, P<0.01, n = 5) were about 2-fold higher in the hamsters fed corn oil. The rate of plasma cholesterol esterification by lecithin: cholesterol acyltransferase (LCAT) was essentially the same for the two diets. It is concluded that the low HDL level in the hamsters fed corn oil diets is linked with increased HDL binding and degradation in the liver and possibly other tissues. Due to increased HDL protein turnover, the capacity for reverse cholesterol transport is increased in hamsters fed corn oil despite the relative low HDL concentrations     

KRAS mutation analysis: a comparison between primary tumours and matched liver metastases in 305 colorectal cancer patients

Background:

KRAS mutation is a negative predictive factor for treatment with anti-epidermal growth factor receptor antibody in metastatic colorectal cancer (CRC). KRAS mutation analysis is usually performed on primary tumour tissue because metastatic tissue is often not available. However, controversial data are available on the concordance of test results between primary tumours and corresponding metastases. We assessed the concordance of KRAS mutation status in a study of 305 primary colorectal tumours and their corresponding liver metastases.

Methods:

Patients with histologically confirmed CRC who underwent surgical resection of the primary tumour and biopsy or surgical resection of the corresponding liver metastasis were included. KRAS mutation analysis was performed for codons 12 and 13.

Results:

KRAS mutation was detected in 108 out of 305 primary tumours (35.4%). In 11 cases (3.6%), we found a discordance between primary tumour and metastasis: 5 primary tumours had a KRAS mutation with a wild-type metastasis, 1 primary tumour was wild type with a KRAS mutation in the metastasis, and in 5 cases the primary tumour and the metastasis had a different KRAS mutation.

Conclusion:

We observed a high concordance of KRAS mutation status of 96.4% (95% CI 93.6–98.2%) between primary colorectal tumours and their corresponding liver metastases. In only six patients (2.0% 95% CI 0.7–4.2%), the discordance was clinically relevant. In this largest and most homogenous study to date, we conclude that both primary tumours and liver metastases can be used for KRAS mutation analysis.     

Development of a multi-layered psychosocial care system for children in areas of political violence

Few psychosocial and mental health care systems have been reported for children affected by political violence in low- and middle income settings and there is a paucity of research-supported recommendations. This paper describes a field tested multi-layered psychosocial care system for children (focus age between 8-14 years), aiming to translate common principles and guidelines into a comprehensive support package. This community-based approach includes different overlapping levels of interventions to address varying needs for support. These levels provide assessment and management of problems that range from the social-pedagogic domain to the psychosocial, the psychological and the psychiatric domains. Specific intervention methodologies and their rationale are described within the context of a four-country program (Burundi, Sri Lanka, Indonesia and Sudan). The paper aims to contribute to bridge the divide in the literature between guidelines, consensus & research and clinical practice in the field of psychosocial and mental health care in low- and middle-income countries.     

4-1BB-mediated expansion affords superior detection of in vivo primed effector memory CD8 T cells from melanoma sentinel lymph nodes

We have been studying the re-activation of tumor-associated antigen (TAA)-specific CD8⁺ T cells in sentinel lymph nodes (SLN) of melanoma patients upon intradermal administration of the CpG-B oligodeoxynucleotide PF-3512676. To facilitate functional testing of T cells from small SLN samples, high-efficiency polyclonal T cell expansion is required. In this study, SLN cells were expanded via classic methodologies with plate- or bead-bound anti-CD3/CD28 antibodies and with the K562/CD32/4-1BBL artificial APC system (K32/4-1BBL aAPC) and analyzed for responsiveness to common recall or TAA-derived peptides. K32/4-1BBL-expanded T cell populations contained significantly more effector/memory CD8⁺ T cells. Moreover, recall and melanoma antigen-specific CD8⁺ T cells were more frequently detected in K32/4-1BBL-expanded samples as compared with anti-CD3/CD28-expanded samples. We conclude that K32/4-1BBL aAPC are superior to anti-CD3/CD28 antibodies for the expansion of in vivo-primed specific CD8⁺ T cells and that their use facilitates the sensitive monitoring of functional anti-tumor T cell immunity in SLN.