Levels of Red Blood Cell Fatty Acids in Patients With Psychosis,Their Unaffected Siblings,and Healthy Controls

Background: Two recent meta-analyses showed decreased red blood cell (RBC) polyunsaturated fatty acids (FA) in schizophrenia and related disorders. However, both these meta-analyses report considerable heterogeneity, probably related to differences in patient samples between studies. Here, we investigated whether variations in RBC FA are associated with psychosis, and thus may be an intermediate phenotype of the disorder. Methods: For the present study, a total of 215 patients (87% outpatients), 187 siblings, and 98 controls were investigated for multiple FA analyses. Based on previous studies, we investigated docosahexaenoic acid (DHA), docosapentaenoic acid (DPA), arachidonic acid (AA), linoleic acid (LA), nervonic acid (NA), and eicasopentaenoic acid (EPA). On an exploratory basis, a large number of additional FA were investigated. Multilevel mixed models were used to compare the FA between the 3 groups. Results: Compared to controls, both patients and siblings showed significantly increased DHA, DPA, AA, and NA. LA was significantly higher in siblings compared to controls. EPA was not significantly different between the 3 groups. Also the exploratory FA were increased in patients and siblings. Conclusions: We found increased RBC FA DHA, DPA, AA, and NA in patients and siblings compared to controls. The direction of change is similar in both patients and siblings, which may suggest a shared environment and/or an intermediate phenotype. Differences between patient samples reflecting stage of disorder, dietary patterns, medication use, and drug abuse are possible modifiers of FA, contributing to the heterogeneity in findings concerning FA in schizophrenia patients.Key words: Schizophrenia, FA (fatty acid), AA (arachidonic acid), NA (nervonic acid), endophenotype, familial     

Mutation in human selenocysteine transfer RNA selectively disrupts selenoprotein synthesis

Selenium is a trace element that is essential for human health and is incorporated into more than 25 human selenocysteine-containing (Sec-containing) proteins via unique Sec-insertion machinery that includes a specific, nuclear genome–encoded, transfer RNA (tRNA^[Ser]Sec). Here, we have identified a human tRNA^[Ser]Sec mutation in a proband who presented with a variety of symptoms, including abdominal pain, fatigue, muscle weakness, and low plasma levels of selenium. This mutation resulted in a marked reduction in expression of stress-related, but not housekeeping, selenoproteins. Evaluation of primary cells from the homozygous proband and a heterozygous parent indicated that the observed deficit in stress-related selenoprotein production is likely mediated by reduced expression and diminished 2′-O-methylribosylation at uridine 34 in mutant tRNA^[Ser]Sec. Moreover, this methylribosylation defect was restored by cellular complementation with normal tRNA^[Ser]Sec. This study identifies a tRNA mutation that selectively impairs synthesis of stress-related selenoproteins and demonstrates the importance of tRNA modification for normal selenoprotein synthesis.     

Depressed expression of MuRF1 and MAFbx in areas remote of recent myocardial infarction: a mechanism contributing to myocardial remodeling?

Ventricular remodeling following myocardial infarction (MI) includes myocardial hypertrophy, a process requiring increased protein synthesis and sarcomere assembly. The anti-hypertrophic effect of MuRF1/MafBx, both muscle-specific E3-ubiquitin ligases, has been demonstrated in animal experiments and in cultured cardiomyocytes. We assessed MuRF1/MAFbx expression in myocardium remote of recently (<2 weeks) infarcted regions (MI), compared with patients undergoing coronary artery bypass surgery, with normal systolic function and without previous infarction (control or Con). Left ventricular myocardial biopsies were obtained from the contralateral normal zone in MI (n = 14) patients and from the Con (n = 12) group. MuRF-1/MAFbx expression was assessed using RT-PCR and Western blot (WB). In addition, the myocardial expression of TNF-α was measured (RT-PCR) and troponin I, β-myosin and phosphorylated Akt/Akt (pAkt/Akt) were quantified (WB). MuRF1 and MAFbx expression (mRNA and protein level) were significantly reduced in biopsies from MI patients. TNF-α was significantly higher in MI and exhibited a negative correlation with MuRF1 and MAFbx. The expression of troponin I and cardiomyocyte size were increased in MI in comparison to Con, whereas β-myosin expression was not altered. When compared with Con, pAkt/Akt was elevated. The results of the present study suggest that the atrogenes MuRF1/MAFbx are involved in regulating the hypertrophic response, characteristic of the early post-infarction remodeling phase. Reduced expression of MuRF1 and MAFbx in the myocardium might permit hypertrophy, which is supported by the elevation of troponin I. A regulatory role of TNF-α needs to be confirmed in further experiments.     

Ethnic differences in parathyroid hormone secretion and mineral metabolism in response to oral phosphate administration

Ethnic differences in bone metabolism have been reported and it has been suggested that these may be partly due to prolonged exposure to an elevated plasma parathyroid hormone (PTH) concentration or a decreased sensitivity to PTH. We explored ethnic differences in bone and mineral metabolism by 5 days of oral phosphate (P) loading to stimulate PTH secretion. Healthy older people from UK (B), The Gambia (G) and China (C), 15 individuals from each sex and ethnic group, were studied. Blood and urine samples were collected before and 2 h after P dose on days 1, 4 and 5 and on a control day. The induced changes (%) in PTH and markers of mineral and bone metabolism after 2 h and over 5 days were examined.At baseline, PTH, 1,25(OH)₂D and bone turnover markers were higher in Gambian subjects than in British and Chinese subjects (P ≤ 0.01).2 h after P loading, ionized calcium (iCa) decreased and PTH and plasma P (P) increased in all groups (P ≤ 0.01, n.s. between groups). Urinary P to creatinine ratio (uP/Cr) increased, the increase being greater in Chinese subjects than in British and Gambian subjects on days 4 and 5 (P ≤ 0.01). By day 5, fasting iCa was decreased and P increased in British and Gambian (P ≤ 0.01) but not in Chinese subjects. Fasting PTH and uP/Cr increased in all groups. There were ethnic differences in changes in bone markers, but the relationship with changes in PTH was comparable between groups.In conclusion, ethnic differences in mineral metabolism in response to 5-day P loading were found. Chinese subjects showed a more rapid renal clearance of P than British and Gambian counterparts and there were differences between the groups in the skeletal response to P loading, but no evidence was found for resistance to the resorbing effects of PTH.     

Ethnic disparities in problem behaviour in adolescence contribute to ethnic disparities in social class in adulthood

BACKGROUND: It is important for prevention of social class disparities to know how ethnic disparities in social class arise among migrant children. We contribute to this understanding by examining the role of problem behaviour in adolescence. METHODS: Prospective observational study with 753 Dutch native and 217 Turkish migrant adolescents (11-18 year) followed for 10 years. Internalising and externalising problems were assessed in adolescence and employment status and occupational level were assessed in adulthood. The difference in odds ratios (OR) before and after adjustment for internalising and externalising problems was an indication of the predictive value of disparities in internalising and externalising problems for the development of social class disparities. RESULTS: A total of 135 (62%) of the Turkish and 602 (80%) of the Dutch adults were employed. Internalising and externalising problems were not associated with employment status. Of the employed, 65 (48%) Turkish and 179 (30%) Dutch adults worked in low-level occupations (p < 0.0001). Internalising and externalising problems were associated with both ethnicity and occupation. The OR for low-level occupation for Turkish adults was 1.78 (1.19-2.65), indicating ethnic disparities. Adjustment for internalising problems lowered the OR with 36% to 1.50 (0.97-2.31), and adjustment for externalising problems lowered it with 8% to 1.72 (1.15-2.57). Findings were similar for men and women and did not vary by age. CONCLUSIONS: Ethnic disparities in occupational level in adulthood could partly be attributed to disparities in mental health between Turkish migrants and Dutch natives in adolescence. Prevention of ethnic disparities in mental health at young age may therefore also contribute to the prevention of occupational differences in adulthood.     

Symptoms of preclinical dementia in general practice up to five years before dementia diagnosis

OBJECTIVES:To investigate which symptoms are indicative of preclinical dementia in general practice and whether subjects with preclinical dementia have an increased contact frequency with their general practitioner (GP). METHODS: Individuals with preclinical dementia (n = 75) and non-demented controls (n = 125) were selected from the Dutch GP registration network (RNH). Number of visits and odds ratio for the risk of subsequent dementia of various symptoms were analysed. Analyses were done separately for each 12-month period, in the 5 years prior to the diagnosis of dementia. RESULTS: In the 5 years prior to diagnosis, subjects with preclinical dementia visited their GP more often than controls. Gait disturbances were the earliest predictor. Cognitive complaints were predictive for dementia in the 3 years before diagnosis. All other symptoms, except vascular symptoms, were predictive in the year prior to diagnosis. Sensitivity was highest for cognitive symptoms (0.58) and gait disturbances (0.47) in the year before diagnosis. CONCLUSION:Preclinical dementia is associated with an increased contact frequency between patient and GP at least 5 years prior to the diagnosis of dementia. Gait disturbances and cognitive complaints are the earliest symptoms of preclinical dementia.     

Partial matrix excision or orthonyxia for ingrowing toenails

BACKGROUND: We wanted to evaluate whether partial matrix excision and orthonyxia are equally effective in the treatment of ingrown toenails of the hallux. STUDY DESIGN: We conducted a prospective randomized clinical trial with 12-month observer-blinded followup, in the surgical outpatient department of a teaching hospital. We randomized 105 consecutive patients with a total of 109 ingrown toenails to either partial matrix excision (n=58) or an orthonyxia procedure (n=51). The main outcomes measurements were rate of recurrence after 12 months, postoperative morbidity, and time to complete recovery. RESULTS: The 12-month followup was completed in 55 of 58 patients undergoing partial matrix excision and 47 of 51 patients having orthonyxia. There were four ingrown toenails, four recurrences in the partial matrix excision group, and eight in the orthonyxia group (NS, p=0.14). Postoperative morbidity parameters (redness, pus, postoperative bleeding); time to complete recovery, wearing shoes (p < 0.01), and performing activities of daily living and hobbies; postoperative symptoms; and patient satisfaction all favored orthonyxia. CONCLUSIONS: Partial matrix excision and orthonyxia are equally effective treatments for ingrown toenails. But the orthonyxia procedure showed better results, with less postoperative morbidity, shorter time to complete recovery, fewer postoperative symptoms, and greater patient satisfaction.     

Recruitment in an indicated prevention program for externalizing behavior - parental participation decisions

Background  

Parents are the ones who decide whether or not to participate in parent focused prevention trials. Their decisions may be affected by internal factors (e.g., personality, attitudes, sociodemographic characteristics) or external barriers. Some of these barriers are study-related and others are intervention-related. Internal as well as external barriers are especially important at the screening stage, which aims to identify children and families at risk and for whom the indicated prevention programs are designed. Few studies have reported their screening procedure in detail or analyzed differences between participants and dropouts or predictors of dropout. Rates of participation in prevention programs are also of interest and are an important contributor to the efficacy of a prevention procedure.