Diabetes mellitus type 2 as an underlying,comorbid or consequent state of mental disorders

Somatic disturbances that occur in parallel with psychiatric diseases are a major challenge in clinical practice. Various factors contribute to the development of mental and somatic disorders. Type 2 diabetes mellitus (T2DM) is a significant health burden worldwide, and the prevalence of diabetes in adults is increasing. The comorbidity of diabetes and mental disorders is very common. By sharing a bidirectional link, both T2DM and mental disorders influence each other in various manners, but the exact mechanisms underlying this link are not yet elucidated. The potential mechanisms of both mental disorders and T2DM are related to immune and inflammatory system dysfunction, oxidative stress, endothelial dysfunction, and metabolic disturbances. Moreover, diabetes is also a risk factor for cognitive dysfunction that can range from subtle diabetes-associated cognitive decline to pre-dementia and dementia. A complex re-lationship between the gut and the brain also represents a new therapeutic approach since gut-brain signalling pathways regulate food intake and hepatic glucose production. The aim of this minireview is to summarize and present the latest data on mutual pathogenic pathways in these disorders, emphasizing their complexity and interweaving. We also focused on the cognitive performances and changes in neurodegenerative disorders. The importance of implementing integrated approaches in treating both of these states is highlighted, along with the need for individual therapeutic strategies.     

Molecular mechanisms of synaptic specificity

Synapses are specialized junctions that mediate information flow between neurons and their targets. A striking feature of the nervous system is the specificity of its synaptic connections: an individual neuron will form synapses only with a small subset of available presynaptic and postsynaptic partners. Synaptic specificity has been classically thought to arise from homophilic or heterophilic interactions between adhesive molecules acting across the synaptic cleft. Over the past decade, many new mechanisms giving rise to synaptic specificity have been identified. Synapses can be specified by secreted molecules that promote or inhibit synaptogenesis, and their source can be a neighboring guidepost cell, not just presynaptic and postsynaptic neurons. Furthermore, lineage, fate, and timing of development can also play critical roles in shaping neural circuits. Future work utilizing large-scale screens will aim to elucidate the full scope of cellular mechanisms and molecular players that can give rise to synaptic specificity.     

Fourier components of inhomogeneously broadened water resonances in breast: a new source of MRI contrast.

High spectral and spatial resolution (HiSS) MR data were acquired at 1.5 T using echo-planar spectroscopic imaging from patients with suspicious breast lesions. The water resonances in small voxels are inhomogenously broadened and often have distinct components. Images were calculated with intensity proportional to the Fourier components of the water resonance in each voxel at different offsets from the peak frequency. The results demonstrate that in breast the off-peak Fourier component images of water are qualitatively different from those derived from the peak height of the water resonance. These differences most likely reflect underlying anatomy or physiology. In conventional images, the superposition of the various Fourier components of the water signal may cause loss of detail. The synthesis of water Fourier component images from high spectral and spatial resolution data may provide a new form of contrast, and increase sensitivity to subvoxel physiology and anatomy.     

Prooxidant–antioxidant balance,hsTnI and hsCRP: mortality prediction in haemodialysis patients,two-year follow-up

Oxidative stress and inflammation are highly intertwined pathophysiological processes. We analyzed the markers of these processes and high-sensitive troponin I (hsTnI) for mortality prediction in patients on haemodialysis. This study enrolled a total of 62 patients on regular haemodialysis. The patients were monitored for two years, and the observed outcomes were all-cause and cardiovascular mortality. Blood samples were taken before one dialysis session for analysis of the baseline concentrations of prooxidant–antioxidant balance (PAB), total antioxidant status (TAS), total oxidative status (TOS), hsTnI, hsCRP and resistin. The overall all-cause mortality was 37.1% and CVD mortality 16.1%. By univariate and multivariate logistic regression, our findings suggest that good predictors of all-cause mortality include hsCRP and PAB (p?p?p?p?p?=?.001). Our data suggest that hsCRP and PAB are very good predictors of all-cause mortality. For CVD complications and mortality prediction in HD patients, the most sensitive parameters appear to be hsTnI and hsCRP.     

Acetaminophen intake and risk of asthma, hay fever and eczema in early adolescence

A positive association between acetaminophen intake and allergic diseases has recently been reported in developed countries with impaired oxidant/antioxidant balance and promotion of atopy as proposed underlying mechanisms. The aim of the study was to explore the relationship between acetaminophen intake and asthma, hay fever, and eczema in The Republic of Macedonia as a country with acetaminophen intake not physician-controlled, high passive smoke exposure and dietary antioxidant intake, and moderately low prevalence of allergic diseases. Self-reported data obtained through the standardized International Study of Asthma and Allergies in Childhood Phase Three written questionnaires of 3026 adolescents aged 13/14 years from randomly selected schools in Skopje, the capital of Macedonia, were used. The frequency of current acetaminophen intake--both unadjusted and adjusted for confounding factors--was correlated to current and ever-diagnosed asthma, hay fever and eczema by odds ratios (OR, 95% CI) in binary logistic regression. Use of acetaminophen at least once monthly increased the risk of current wheeze (adjusted OR 2.04, 1.31-3.20 p = 0.002), asthma 'ever' (adjusted OR 2.77, 1.06-7.26 p=0.039), current allergic rhinoconjunctivitis (adjusted OR 2.95, 1.79-4.88 p=0.000) and hay fever 'ever' (adjusted OR 2.25, 1.36-3.70 p=0.002). A significant association between frequent acetaminophen intake and atopic eczema and also between infrequent acetaminophen intake and investigated allergic diseases was not established. The findings suggest an increased risk of asthma and hay fever, but not atopic eczema associated with frequent acetaminophen use in a developing country.     

Age-associated changes in CD90 expression on thymocytes and in TCR-dependent stages of thymocyte maturation in male rats

To elucidate the effects of ageing on T-cell-maturation, in 3- and 18-month-old rats, we analysed the expression of: (i) CD4/CD8/TCRalphabeta and (ii) Thy-1, which is supposed to be a regulator of TCRalphabeta signalling, and thereby the thymocyte selection thresholds. Since an essential role for TCRalphabeta signalling in the development of CD4+25+T(reg)-cells was suggested, the frequency of these cells was also quantified. We demonstrated that, as for mice, early thymocyte differentiational steps within the CD4-8- double negative (DN) developmental stage are age-sensitive. Furthermore, we revealed that TCRalphabeta-dependent stages of T-cell development are affected by ageing, most likely due to an impaired expression of Thy-1 on TCRalphabeta(low) thymocytes entering selection processes. The diminished frequency of the post-selection CD4+8+ double positive (DP) cells in aged rats, together with an overrepresentation of mature single positive (SP) cells, most probably suggests more efficient differentiational transition from the DP TCRalphabeta(high) to the SP TCRalphabeta(high) developmental stage, which is followed by an increase in pre-migration proliferation of the mature SP cells. Moreover, the study indicated impaired intrathymic generation of CD4+25+T(reg)-cells in aged rats, thus providing a possible explanation for the increased frequency of autoimmune diseases in ageing.