Health-related quality of life and depression in a sample of Latin American adults with rheumatoid arthritis.

OBJECTIVE: To compare the health related quality of life (HRQoL) and depression of individuals with rheumatoid arthritis (RA) to healthy controls in Colombia, as well as to examine the connections between these two variables in individuals with RA. METHOD: One hundred and three individuals with RA were recruited from ambulatory centers in Colombia. Seventy-three control participants were recruited from the local community. Both groups differed with respect to age, gender and marital status (P < 0.001), while education and socio-economic levels were similar. HRQoL was assessed using the Short Form-36 (SF-36) and depressive symptoms were assessed using the Patient Health Questionnaire-9 (PHQ-9). RESULTS: A multivariate analysis of covariance found that RA patients reported substantially higher depressive symptoms and lower HRQoL than healthy controls (P < 0.01 and P < 0.05, respectively). The effect sizes of the differences between patients and controls in HRQoL and depressive symptoms were all large. All SF-36 HRQoL variables were significantly correlated with depressive symptoms in patients and controls (P < 0.05). Social functioning and vitality were uniquely associated with depressive symptoms in the RA group (P < 0.01 and P < 0.05, respectively), whereas education and social functioning were uniquely associated with depressive symptoms in controls (P < 0.05 and P < 0.005, respectively). CONCLUSIONS: Research indicates that individuals with RA have deteriorated HRQoL, and this study extends these findings to a Colombian sample and highlights the importance of the independent relationship between depressive symptoms and vitality in this group of Colombians with RA.

Ancient transposable elements transformed the uterine regulatory landscape and transcriptome during the evolution of mammalian pregnancy.

A major challenge in biology is determining how evolutionarily novel characters originate; however, mechanistic explanations for the origin of new characters are almost completely unknown. The evolution of pregnancy is an excellent system in which to study the origin of novelties because mammals preserve stages in the transition from egg laying to live birth. To determine the molecular bases of this transition, we characterized the pregnant/gravid uterine transcriptome from tetrapods to trace the evolutionary history of uterine gene expression. We show that thousands of genes evolved endometrial expression during the origins of mammalian pregnancy, including genes that mediate maternal-fetal communication and immunotolerance. Furthermore, thousands of cis-regulatory elements that mediate decidualization and cell-type identity in decidualized stromal cells are derived from ancient mammalian transposable elements (TEs). Our results indicate that one of the defining mammalian novelties evolved from DNA sequences derived from ancient mammalian TEs co-opted into hormone-responsive regulatory elements distributed throughout the genome.

Psychological Functioning in Youth With Spina Bifida Living in Colombia, South America.

OBJECTIVE: No studies have examined psychological functioning among youth with spina bifida (SB) living in a developing country where access to mental health resources is often scarce. This study compared self-reported psychological functioning between youth with SB living in Colombia, South America, and a demographically matched comparison group of healthy Colombian children. METHODS: 22 children with SB and 22 comparison children completed assessments of depression and anxiety. Most (68.81%) participants were male, and the sample had a mean age of 13.25 years (SD = 2.65 years). RESULTS: Results revealed that children with SB reported greater total symptoms of depression (p < .05), but fewer worry-related symptoms of anxiety (p < .05). In addition, mean total scores for both depression and anxiety were in the nonclinical range for youth with SB. CONCLUSIONS: These findings highlight the need for targeted mental health (i.e., depression) services for poor children with SB living in Colombia.

The relationship between tumor MSLN methylation and serum mesothelin (SMRP) in mesothelioma.

Malignant pleural mesothelioma (MPM) remains a cancer of poor prognosis. It is hoped that implementation of effective screening biomarkers will lead to earlier diagnoses and improved outcomes. Serum-measured soluble mesothelin-related peptide (SMRP) has been demonstrated to have excellent specificity for MPM, but poor sensitivity precludes its use as a screening biomarker. Using a case series of MPM patients from the International Mesothelioma Program at the Brigham and Women's hospital, we sought to determine whether epigenetic change at the MSLN gene in patient tumors is responsible for the poor sensitivity of SMRP. We identified three potential target regions for CpG methylation silencing in the MSLN promoter, one of which was amenable to bisulfite pyrosequencing and located 214 bp upstream of the transcription start site. MSLN promoter methylation was significantly higher in normal pleura than tumor tissue (P < 6.0x10-9). Next, we compared cases according to serum SMRP status and observed that MSLN methylation was significantly higher among tumors from patients testing negative for SMRP (< 1.5nM) versus those that were SMRP positive (P < 0.03). These results demonstrate that MSLN is normally methylated in the pleura, and that methylation is lost in most tumors. However, in a subset of tumors methylation is retained, and this mechanism explains the poor sensitivity of the SMRP assay. These results may lead to additional biomarker targets that will resolve the poor sensitivity of the SMRP assay and allow implementation of screening among exposed populations.

A let-7 microRNA-binding site polymorphism in the KRAS 3' UTR is associated with reduced survival in oral cancers.

MicroRNA (miRNA)-binding site polymorphisms that could contribute to disease risk and prognosis are rapidly being identified and investigated as this genetic variation may have a potentially profound impact on human health. A recently described variant allele in the KRAS 3' untranslated region that arises in the let-7 miRNA complementary site (KRAS-LCS6) and leads to increased KRAS expression in lung cancer was examined for its association with the occurrence of head and neck squamous cell carcinoma (HNSCC). We examined the prevalence of the KRAS-LCS6 variant allele in a population-based case-control study of HNSCC to determine if this KRAS-LCS6 genotype was associated with disease occurrence and patient survival. Although the KRAS-LCS6 variant genotype was not associated with the overall risk of HNSCC, cases with the KRAS-LCS6 variant genotype had significantly reduced survival [hazard ratio (HR), 1.6; 95% confidence interval (CI), 1.0-2.5] in models controlled for confounders of survival. This risk was greatest in cases of oral cavity carcinoma (HR, 2.7; 95% CI, 1.4-5.3). These data demonstrate that cases with the KRAS-LCS6 variant have significantly reduced survival time and suggest that this variant may alter the phenotype or therapeutic response of this disease.