Irrational Beliefs,Dietary Habits and 10-Year Incidence of Type 2 Diabetes; the ATTICA Epidemiological Study (2002-2012)

OBJECTIVEThe aim of this study was to evaluate the dietary habits and irrational beliefs of apparently healthy individuals in relation to their 10-year diabetes incidence.METHODSThe ATTICA study (2002-2012) is a prospective population-based cohort study, in which 853 participants (453 men (aged 45 ± 13 years) and 400 women (aged 44 ± 18 years)) without a history of cardiovascular disease (CVD) underwent psychological evaluations. Among other things, participants completed the Irrational Beliefs Inventory (IBI, range 0-88), a brief, self-reported measure consistent with the Ellis model of psychological disturbance. Demographic characteristics, detailed medical history, and dietary and other lifestyle habits were evaluated as well. Diagnosis of diabetes at follow-up examination was based on the criteria of the American Diabetes Association.RESULTSMean IBI score was 53 ± 10 in men and 51 ± 11 in women (p = 0.68). IBI was positively associated with the 10-year type 2 diabetes incidence (hazard ratio: 1.14; 95% CI: 1.04-1.25) in both men and women, and even more distinctly associated with participants with the following characteristics: lower education status, married, overweight, smokers, anxiety and depressive symptomatology, and unhealthy dietary habits. Especially, participants with increased irrational beliefs and low adherence to the Mediterranean diet were 37% more likely to develop type 2 diabetes than those with the reverse status (hazard ratio: 3.70; 95% CI: 2.32-5.88).CONCLUSIONSThese data support the need for lifestyle changes towards healthier nutrition which can be achieved by educating people so that they are equipped to recognize false and unhelpful thoughts and thus to prevent negative psychological and clinical outcomes such as mental health disorders and type 2 diabetes.     

An endogenous glycosylphosphatidylinositol-specific phospholipase D releases basic fibroblast growth factor-heparan sulfate proteoglycan complexes from human bone marrow cultures

Basic fibroblast growth factor (bFGF) is a hematopoietic cytokine that stimulates stromal and stem cell growth. It binds to a glycosylphosphatidylinositol (GPI)-anchored heparan sulfate proteoglycan on human bone marrow (BM) stromal cells. The bFGF- proteoglycan complex is biologically active and is released by addition of exogenous phosphatidylinositol-specific phospholipase C. In this study, we show the presence of an endogenous GPI-specific phospholipase D (GPI-PLD) that releases the bFGF-binding heparan sulfate proteoglycan and the variant surface glycoprotein (a model GPI-anchored protein) from BM cultures. An involvement of proteases in this process is unlikely, because released proteoglycan contained the GPI anchor component, ethanol-amine, and protease inhibitors did not diminish the release. The mechanism of release is likely to involve a GPI-PLD and not a GPI-specific phospholipase C, because the release of variant surface glycoprotein did not reveal an epitope called the cross- reacting determinant that is exposed by phospholipase C-catalyzed GPI anchor cleavage. In addition, phosphatidic acid (which is specifically a product of GPI-PLD-catalyzed anchor cleavage) was generated during the spontaneous release of the GPI-anchored variant surface glycoprotein. We also detected GPI-PLD-specific enzyme activity and mRNA in BM cells. Therefore, we conclude that an endogenous GPI-PLD releases bFGF-heparan sulfate proteoglycan complexes from human BM cultures. This mechanism of GPI anchor cleavage could be relevant for mobilizing biologically active bFGF in BM. An endogenous GPI-PLD could also release other GPI-anchored proteins important for hematopoiesis and other physiologic processes.     

Secondary and tertiary structure modeling reveals effects of novel mutations in polycystic liver disease genes PRKCSH and SEC63

Waanders E, Venselaar H, te Morsche RHM, de Koning DB, Kamath PS, Torres VE, Somlo S, Drenth JPH. Secondary and tertiary structure modeling reveals effects of novel mutations in polycystic liver disease genes PRKCSH and SEC63. Polycystic liver disease (PCLD) is characterized by intralobular bile duct cysts in the liver. It is caused by mutations in PRKCSH, encoding hepatocystin, and SEC63, encoding Sec63p. The main goals of this study were to screen for novel mutations and to analyze mutations for effects on protein structure and function. We screened 464 subjects including 76 probands by direct sequencing or conformation‐sensitive capillary electrophoresis. We analyzed the effects of all known and novel mutations using a combination of splice site recognition, evolutionary conservation, secondary and tertiary structure predictions, Poly Phen , and p Mut and sift . We identified a total of 26 novel mutations in PRKCSH (n = 14) and SEC63 (n = 12), including four splice site mutations, eight insertions/ deletions, six non‐sense mutations, and eight missense mutations. Out of 48 PCLD mutations, 13 were predicted to affect splicing. Most mutations were located in highly conserved regions and homology modeling for two domains of Sec63p showed severe effects of the residue substitutions. In conclusion, we identified 26 novel mutations associated with PCLD and we provide in silico analysis in order to delineate the role of these mutations.     

Association between TNF-alpha -308G>A polymorphism and the development of acute coronary syndromes in Greek subjects: the CARDIO2000-GENE Study.

PURPOSE: We investigated the association of a polymorphism within the promoter of TauNuF-alpha locus at the position -308 on the likelihood of having acute coronary syndromes (ACS) in Greek adults. METHODS: We studied demographic, lifestyle, and clinical information in 237 hospitalized patients (185 males) with a first event of an ACS and 237 matched by age and sex (controls) without any clinical evidence of coronary heart disease. Genotyping was performed by PCR-RFLP analysis. RESULTS: The genotype frequencies were in patients, 87% (n = 206), 12% (n = 29), and 1% (n = 2) for G/G, G/A, and A/A, and in controls, 96% (n = 227), 4% (n = 10), and 0% (n = 0) for G/G, G/A, and A/A, respectively (P = 0.04). After adjusting for age and sex, as well as various potential confounders, we observed that G/A or A/A genotypes were associated with 1.94-fold higher odds (95% CI 1.06 to 3.68) of ACS compared to G/G homozygotes. No gene to-gender or to-clinical syndrome interactions were observed. Further subgroup analysis showed that the distribution of TNF-alpha -308G>A polymorphism was associated with the presence of family history of CHD in patients, but not in controls. In particular, in G/A and A/A patients 17.2% reported family history of CHD, whereas in G/G patients, 34.5% reported family history (P = 0.036). CONCLUSIONS: Our findings may state a hypothesis of an association between the -308G>A TNF-alpha polymorphism the development of ACS and the presence of family history of CHD, in Greece.     

Human ES cell-derived neural rosettes reveal a functionally distinct early neural stem cell stage

Neural stem cells (NSCs) yield both neuronal and glial progeny, but their differentiation potential toward multiple region-specific neuron types remains remarkably poor. In contrast, embryonic stem cell (ESC) progeny readily yield region-specific neuronal fates in response to appropriate developmental signals. Here we demonstrate prospective and clonal isolation of neural rosette cells (termed R-NSCs), a novel NSC type with broad differentiation potential toward CNS and PNS fates and capable of in vivo engraftment. R-NSCs can be derived from human and mouse ESCs or from neural plate stage embryos. While R-NSCs express markers classically associated with NSC fate, we identified a set of genes that specifically mark the R-NSC state. Maintenance of R-NSCs is promoted by activation of SHH and Notch pathways. In the absence of these signals, R-NSCs rapidly lose rosette organization and progress to a more restricted NSC stage. We propose that R-NSCs represent the first characterized NSC stage capable of responding to patterning cues that direct differentiation toward region-specific neuronal fates. In addition, the R-NSC-specific genetic markers presented here offer new tools for harnessing the differentiation potential of human ESCs.     

Long-term adherence to the Mediterranean diet reduces the prevalence of hyperuricaemia in elderly individuals, without known cardiovascular disease: the Ikaria study

Background

The purpose of this study was to evaluate the impact of adherence to Mediterranean diet on serum uric acid (UA) levels in elderly individuals, without known cardiovascular disease.

Methods

During 2009, 281 females (75 ± 6 years old) and 257 males (75 ± 7 years old) permanent inhabitants of the island, were voluntarily enrolled. A diet score that assesses the inherent characteristics of the Mediterranean diet (MedDietScore, range 0-55) was applied. Serum levels of UA were determined using an enzymatic colorimetric test through the uricase-peroxidase method. Hyperuricaemia was defined as UA > 7 mg/dL in males and 6 mg/dL in females.

Results

Prevalence of hyperuricaemia was 34% in males and 25% in females (p = 0.02). Mean level of adherence to the Mediterranean diet was 35 ± 2. Linear regression analysis revealed that MedDietScore was inversely associated with UA levels (b ± SE: −1.48 ± 0.17, p < 0.001) in the overall sample, after controlling for hypertension, hypercholesterolemia, diabetes mellitus, creatinine clearance, physical activity, and coffee consumption. When the analysis was stratified by gender, MedDietScore was inversely associated with UA levels in males (b ± SE: −1.10 ± 0.42, p = 0.009), but not in females (b ± SE: 0.04 ± 0.41, p = 0.92).

Conclusion

Another cardioprotective effect of Mediterranean diet was revealed, through the modification of UA levels in elderly individuals. The potential different effect size as regards the relationship between diet and UA levels between genders, deserves further investigation.     

Germline mutation in BRAF codon 600 is compatible with human development: de novo p.V600G mutation identified in a patient with CFC syndrome

Champion KJ, Bunag C, Estep AL, Jones JR, Bolt CH, Rogers RC, Rauen KA, Everman DB. Germline mutation in BRAF codon 600 is compatible with human development: de novo p.V600G mutation identified in a patient with CFC syndrome. BRAF, the protein product of BRAF, is a serine/threonine protein kinase and one of the direct downstream effectors of Ras. Somatic mutations in BRAF occur in numerous human cancers, whereas germline BRAF mutations cause cardio‐facio‐cutaneous (CFC) syndrome. One recurrent somatic mutation, p.V600E, is frequently found in several tumor types, such as melanoma, papillary thyroid carcinoma, colon cancer, and ovarian cancer. However, a germline mutation affecting codon 600 has never been described. Here, we present a patient with CFC syndrome and a de novo germline mutation involving codon 600 of BRAF, thus providing the first evidence that a pathogenic germline mutation involving this critical codon is not only compatible with development but can also cause the CFC phenotype. In vitro functional analysis shows that this mutation, which replaces a valine with a glycine at codon 600 (p.V600G), leads to increased ERK and ELK phosphorylation compared to wild‐type BRAF but is less strongly activating than the cancer‐associated p.V600E mutation.