High serum folate is associated with brain atrophy in older diabetic people with vitamin B12 deficiency

Previous studies have reported the adverse cognitive effects of high folate status in older individuals with vitamin B12 (VB12) deficiency. Thus, the aim of this study was to investigate how high serum folate and VB12 deficiency could collaboratively aggravate neuronal degeneration. In total, 146 older non-demented diabetic individuals with an average age of 75 ± 3.9 were recruited. VB12 deficiency and high folate status were based on high serum methylmalonic acid (MMA) concentrations (> 0.3 μmol/L) and the serum folate concentration being in the top tertile (> 31.4 nmol/L) respectively. Among these subjects, there were 20 with elevated MMA and high folate. The structural magnetic resonance imaging data of these subjects were analyzed by performing flexible factorial analysis with the “folate level” and “MMA level” added as main effects, and the interaction effect of folate and VB12 on brain volume was evaluated. The results showed significant gray matter atrophy of the right middle occipital gyrus and the opercular part of the inferior frontal gyrus in subjects with a simultaneous high folate status and VB12 deficiency. Together with previous observational studies on cognitive function, this study lends support to the notion that high serum folate concentrations in older people with VB12 deficiency may be associated with increased neurodegeneration..     

Glycosylated hemoglobin-defined prediabetes and cardiovascular risk markers in rural India: the Nallampatti noncommunicable disease study

The aim of this study is to assess the associations between glycosylated hemoglobin in the prediabetes range and cardiovascular risk markers in a rural South Indian population. Local Ethics Committee approval and informed consent was obtained from all participants. Inclusion criteria were participants, aged ≥20 and ≤85 years, from Nallampatti, a classical farming village from Tamil Nadu State, India. Those with known history of diabetes were excluded from this analysis. All participants were administered a detailed questionnaire, had anthropometric measurements including height, weight, and waist circumference. Bloods were drawn for random blood glucose, glycosylated hemoglobin, nonfasting lipid profile, cystatin C, uric acid, and hemoglobin. All participants had carotid intima thickness done by high-resolution B-mode carotid ultrasound. Progressive hyperglycemia across the glucose tolerance continuum based on glycosylated hemoglobin levels in a rural South Indian population seems to be associated with worsening cardiovascular risk markers. A cut-off value of ≥6% (42 mmol/mol) seems to herald a much more significant increase in such markers. Long-term follow-up of this cohort for incident cardiovascular disease will help to substantiate the associations between glycosylated hemoglobin levels within the prediabetes range and cardiovascular disease in an Indian population. Evidence-based race-specific criteria for diagnosis of prediabetes and diabetes are the need of the hour for risk stratification and appropriate management.     

Skleromyxödem

Scleromyxedema is a rare disorder that frequently affects multiple extracutaneous organ systems and is usually associated with monoclonal gammopathy. The pathogenesis of scleromyxedema is unknown. The clinical course is chronic and progressive and can lead to marked morbidity or death. The skin findings consist of multiple waxy papules and indurated plaques. Progressive skin involvement can lead to decreased mobility of the mouth and joints. Extracutaneous manifestations occur in the musculoskeletal or cardiovascular system, in the gastrointestinal or respiratory tract, or in the kidneys. There are no approved or evidence-based treatment options available for scleromyxedema. High-dose immunoglobulins are considered the treatment of choice, followed by lenalidomide (or thalidomide) and systemic glucocorticosteroids, or in severe cases even autologous hematopoetic stem cell transplantation. Long-term maintenance treatment is usually required and close clinical follow-up is necessary as recurrence of scleromyxedema is common after withdrawal of an effective therapy.     

Do Meaning in life,Ideological Commitment,and Level of Religiosity,Related Adolescent Substance Abuse and Attitude?

The present study focuses on expanding and broadening the connection between meaning in life and psychoactive substance abuse. Since professional literature presents an individual’s meaning in life as an immunizing factor against substance abuse, the present study sought to examine the impact of level of religiosity and level of ideological-political commitment, through the prism of meaning in life, on the attitudes adopted by adolescents towards such abuse, and their actual use of the various substances. The findings of the study, in which 1032 Israeli adolescents aged 14 to 18 took part, supported the hypothesis whereby a high level of religiosity “immunizes” against psychoactive substance abuse. However, they also indicate that despite the negative approach to it among individuals with high levels of ideological commitment, no significant correlation can be found between ideological commitment and actual psychoactive substance abuse. The study findings underscore the importance of both religion and ideological commitment in the formation of meaning in life by youth, as well as the impact of social supervision and perceived norms in their environment, with regard to their willingness to attempt using psychoactive substances, and their actual use thereof. The study findings contribute both to research and practical application when constructing programs for the prevention of normative adolescent substance abuse.     

Autism Spectrum Disorder and School Bullying: Who is the Victim? Who is the Perpetrator?

While a growing number of studies indicate associations between experiences of bullying and autism spectrum disorder (ASD), it is not clear what roles comorbid behavioral problems may play. We investigated the experiences of children with ASD as victims and/or perpetrators of bullying. Children with ASD epidemiologically ascertained participated in a cross-sectional study. Although children with ASD showed significantly increased risk for bullying involvement compared to community children, after controlling for comorbid psychopathology and other demographic factors, increased risks for being perpetrators or victim-perpetrators disappeared while risk for being bullied/teased continued to be significantly elevated. This finding will help guide medical, educational and community personnel to effectively identify children with ASD at risk for school bullying and develop interventions.     

Tumor-associated Endo180 requires stromal-derived LOX to promote metastatic prostate cancer cell migration on human ECM surfaces

The diverse composition and structure of extracellular matrix (ECM) interfaces encountered by tumor cells at secondary tissue sites can influence metastatic progression. Extensive in vitro and in vivo data has confirmed that metastasizing tumor cells can adopt different migratory modes in response to their microenvironment. Here we present a model that uses human stromal cell-derived matrices to demonstrate that plasticity in tumor cell movement is controlled by the tumor-associated collagen receptor Endo180 (CD280, CLEC13E, KIAA0709, MRC2, TEM9, uPARAP) and the crosslinking of collagen fibers by stromal-derived lysyl oxidase (LOX). Human osteoblast-derived and fibroblast-derived ECM supported a rounded ‘amoeboid-like’ mode of cell migration and enhanced Endo180 expression in three prostate cancer cell lines (PC3, VCaP, DU145). Genetic silencing of Endo180 reverted PC3 cells from their rounded mode of migration towards a bipolar ‘mesenchymal-like’ mode of migration and blocked their translocation on human fibroblast-derived and osteoblast-derived matrices. The concomitant decrease in PC3 cell migration and increase in Endo180 expression induced by stromal LOX inhibition indicates that the Endo180-dependent rounded mode of prostate cancer cell migration requires ECM crosslinking. In conclusion, this study introduces a realistic in vitro model for the study of metastatic prostate cancer cell plasticity and pinpoints the cooperation between tumor-associated Endo180 and the stiff microenvironment imposed by stromal-derived LOX as a potential target for limiting metastatic progression in prostate cancer.