Analysis of serum metabolic profiles in women with endometrial cancer and controls in a population-based case-control study

Context: Endometrial cancer is associated with metabolic disturbances related to its underlying risk factors, including obesity and diabetes. Identifying metabolite biomarkers associated with endometrial cancer may have value for early detection, risk assessment, and understanding etiology. Objective: The objective of the study was to evaluate the reliable measurement of metabolites in epidemiological studies with nonstandardized blood collection; confirm previously reported correlations of metabolites with body size; and assess differences in metabolite levels between cases and controls. Design: This was the Polish Endometrial Cancer Study (2001-2003). Setting: This study was a population-based case-control study. Patients: Patients included 250 cases and 250 controls. Intervention: The intervention included the measurement of serum metabolite levels of 15 amino acids, 45 acylcarnitines, and nine fatty acids. Main Outcome Measure: The main outcome measure was endometrial cancer. Results: Body mass index was correlated with levels of valine (r = 0.26, P = 3.4 × 10(-5)), octenoylcarnitine (r = 0.24, P = 1.5 × 10(-4)), palmitic acid (r = 0.26, P = 4.4 × 10(-5)), oleic acid (r = 0.28, P = 9.9 × 10(-6)), and stearic acid (r = 0.26, P = 2.9 × 10(-5)) among controls. Only stearic acid was inversely associated with endometrial cancer case status (quartile 4 vs. quartile 1: odds ratio 0.37, 95% confidence interval 0.20-0.69, P for trend = 1.2 × 10(-4)). Levels of the C5-acylcarnitines, octenoylcarnitine, decatrienoylcarnitine, and linoleic acid were significantly lower in cases than controls (odds ratios ranged from 0.21 to 0.38). Conclusions: These data demonstrate that previously reported variations in metabolomic profiles with body mass index can be replicated in population-based studies with nonfasting blood collection protocols. We also provide preliminary evidence that large differences in metabolite levels exist between cases and controls, independent of body habitus. Our findings warrant assessment of metabolic profiles, including the candidate markers identified herein, in prospectively collected blood samples to define biomarkers and etiological factors related to endometrial cancer.     

A novel variant in plakophilin-2 gene detected in a family with arrhythmogenic right ventricular cardiomyopathy

Aims  

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is characterized by fibrofatty replacement of muscular fibers predominantly in the right ventricle and with ventricular arrhythmias as the main clinical manifestation. Mutations in several components of the desmosome genes have been identified and mutations of the plakophilin-2 (PKP-2) gene are a common cause of ARVC. The aim of this study is to investigate the correlation between genotype and phenotype in a family with a novel PKP-2 variant.     

Inhibition of Intra-Abdominal Adhesions: A Comparison of Hemaseel APR and Cryoprecipitate Fibrin Glue

Our previous studies demonstrated fibrin glue (FG) prepared from cryoprecipitate (cryo) inhibits intra-abdominal adhesions in rats. A new FG, Hemaseel APR, is Food and Drug Administration (FDA) approved for hemostasis during cardiac surgery and splenic trauma. This study was undertaken to determine if Hemaseel FG prevents intra-abdominal adhesions, and to compare it to cryo FG. Forty-five rats underwent laparotomy. Bilateral peritoneal-muscular defects were created. Polypropylene mesh was sewn into each defect with a running silk suture. The bowel was abraded with gauze. The rats were then randomized to mesh covered with Hemaseel FG, cryo FG, or control. On postoperative day 7, the severity of adhesions were graded by percentage of mesh covered by adhesion (0-100%) and degree of adhesion (0-3). The mean percentage of mesh covered by adhesion was 9% for Hemaseel FG, 43% for cryo FG (p = .005), and 65% for the controls (p < .0001). The mean density adhesion score was 0.5 for Hemaseel FG, 1.2 for cryo FG (p = .04), and 2.1 for the controls (p < .0001). In the Hemaseel FG group, 77% of patches had no adhesions, compared with 37% in the cryo FG group (p = .004) and 13% in the controls (p < .0001). Thus, Hemaseel FG significantly decreases intra-abdominal adhesions, and is more effective than cryo FG.     

Validation of an Arabic multi-informant psychiatric diagnostic interview for children and adolescents: Development and Well Being Assessment-Arabic (DAWBA-Arabic)

Background

Countries in the Arab region lack a valid Arabic psychiatric diagnostic interview for children and adolescents. We set out to establish the diagnostic validity of the Arabic version of the Development and Well Being Assessment (DAWBA-Arabic), a multi-informant structured interview for predicting DSM-IV-TR diagnoses.

Methods

The DAWBA was translated, updated, and administered to 45 participants (child and adolescent psychiatric outpatients and their parents) as part of a clinic registry. Two clinicians, blinded to their respective diagnoses, formulated the DAWBA diagnoses. Participants also underwent a clinical evaluation by a child and adolescent psychiatrist who generated clinical diagnoses according to the DSM-IV-TR.

Results

Inter-rater reliabilities were .93, .82, and .72 for disruptive disorders, mood disorders and anxiety disorders respectively. Agreement between DAWBA and clinical diagnoses was substantial for disruptive disorders (κ = .0.82) and mood disorders (κ = 0.74), and moderate for anxiety disorders (κ = 0.46).

Conclusion

The DAWBA-Arabic could serve as a valid and reliable clinical tool for assessing psychiatric disorders among children and adolescents in the Arab region.     

Reliability and validity of the Arabic Screen for Child Anxiety Related Emotional Disorders (SCARED) in a clinical sample

This study aimed at investigating the reliability and validity of the Arabic Screen for Child Anxiety Related Emotional Disorders (SCARED) as a first child and adolescent anxiety screening tool in the Arab World. The English parent (SCARED-P) and child (SCARED-C) versions were translated into Arabic and administered along with the Arabic Strengths and Difficulties Questionnaire (SDQ) to 77 parents and 67 children attending a Psychiatry clinic. DSM-IV-TR diagnoses were made by a psychiatrist without knowledge of the scale scores. Internal consistency was confirmed by Cronbach's α=0.92 for SCARED-P and 0.91 for SCARED-C. Their subscales had internal consistencies between 0.65 and 0.89. Parent–child agreement was r=0.67, p<0.001. SCARED-P demonstrated good discriminant validity between participants with anxiety disorders and those with other psychiatric disorders (t(72)=3.13, p=0.003). For SCARED-C, this difference was significant when participants with depressive disorders were excluded (t(43)=2.58, p=0.01). Convergent validity was evident through a significant correlation between SCARED-P and the parent SDQ emotional subscale (r=0.70, p<0.001), and SCARED-C and the child SDQ emotional subscale (r=0.70, p<0.001). Divergent validity with the SDQ hyperactivity subscale was observed as no significant correlation was found. Overall, the Arabic SCARED demonstrated satisfactory psychometric properties in a clinical sample in Lebanon.     

Adolescent depression and adult labor market marginalization: a longitudinal cohort study

European Child & Adolescent Psychiatry - Adolescent depression is linked to adult ill-health and functional impairment, but recent research suggests that individual/contextual factors might...     

Can South Asian Countries Cope with the Mental Health Crisis Associated with COVID-19?

International Journal of Mental Health and Addiction -     

Pannexin‐1 and P2X7‐Receptor Are Required for Apoptotic Osteocytes in Fatigued Bone to Trigger RANKL Production in Neighboring Bystander Osteocytes

Osteocyte apoptosis is required to induce intracortical bone remodeling after microdamage in animal models, but how apoptotic osteocytes signal neighboring “bystander” cells to initiate the remodeling process is unknown. Apoptosis has been shown to open pannexin‐1 (Panx1) channels to release adenosine diphosphate (ATP) as a “find‐me” signal for phagocytic cells. To address whether apoptotic osteocytes use this signaling mechanism, we adapted the rat ulnar fatigue‐loading model to reproducibly introduce microdamage into mouse cortical bone and measured subsequent changes in osteocyte apoptosis, receptor activator of NF‐κB ligand (RANKL) expression and osteoclastic bone resorption in wild‐type (WT; C57Bl/6) mice and in mice genetically deficient in Panx1 (Panx1KO). Mouse ulnar loading produced linear microcracks comparable in number and location to the rat model. WT mice showed increased osteocyte apoptosis and RANKL expression at microdamage sites at 3 days after loading and increased intracortical remodeling and endocortical tunneling at day 14. With fatigue, Panx1KO mice exhibited levels of microdamage and osteocyte apoptosis identical to WT mice. However, they did not upregulate RANKL in bystander osteocytes or initiate resorption. Panx1 interacts with P2X₇R in ATP release; thus, we examined P2X₇R‐deficient mice and WT mice treated with P2X₇R antagonist Brilliant Blue G (BBG) to test the possible role of ATP as a find‐me signal. P2X₇RKO mice failed to upregulate RANKL in osteocytes or induce resorption despite normally elevated osteocyte apoptosis after fatigue loading. Similarly, treatment of fatigued C57Bl/6 mice with BBG mimicked behavior of both Panx1KO and P2X₇RKO mice; BBG had no effect on osteocyte apoptosis in fatigued bone but completely prevented increases in bystander osteocyte RANKL expression and attenuated activation of resorption by more than 50%. These results indicate that activation of Panx1 and P2X₇R are required for apoptotic osteocytes in fatigued bone to trigger RANKL production in neighboring bystander osteocytes and implicate ATP as an essential signal mediating this process. © 2016 American Society for Bone and Mineral Research.     

Prestroke Mobility and Dementia as Predictors of Stroke Outcomes in Patients Over 65 Years of Age: A Cohort Study From The Swedish Dementia and Stroke Registries

Objectives

To explore the association between prestroke mobility dependency and dementia on functioning and mortality outcomes after stroke in patients>65 years of age.