Cancer as a defective network for NF-κB

In a recent review we addressed the role of the transcription factor NF-κB, in shaping the cancer microenvironment. NF-κB, which interacts with chromatin modulators by cell-specific dynamics, controls cell interactions during inflammation, and its abnormal feedback regulation is implicated in cancer. Inflammation normally reprograms cells through changes in key topological elements of chromosomal DNA. As a result, inflammation overrides cell phenotype: initially, reprogramming cell function halts processes that impede the response of a damaged tissue to the cause of the harm, and eventually, late reprogramming of cells will replenish tissue structure and restore function. Each cell type provides a distinct resource for restoration of tissue integrity, tissue function, and for replenishment of the responsiveness of the immune system. Modulators of NF-κB transcriptional activity alter key aspects of gene expression and tissue integrity. NF-κB network alterations confer transcriptional plasticity to cancer

Impact of a stress management program on weight loss, mental health and lifestyle in adults with obesity: a randomized controlled trial

Aim: To evaluate the impact of a stress management program on weight loss, depression, anxiety and stress as well as on the adoption of healthy lifestyle in adults with obesity. Methods: Adults with obesity who sought help for weight loss at a medical obesity clinic were consecutively enrolled in the study and were randomly assigned to the intervention or control group. All participants received standard instructions for a healthy lifestyle. The intervention group attended an 8-week stress management program that comprised diaphragmatic breathing, progressive muscle relaxation, guided visualization and instructions about healthy nutrition/dietary habits. Anthropometric parameters were assessed and several questionnaires were completed by all participants, at the beginning and at the end of the study. Results: A total of 45 adults (mean age±SD 45.7±10.55 years) with obesity were enrolled in the study; 22 in the intervention group and 23 in the control group. Participants in the two groups were matched for age and BMI. Participants in the intervention group achieved a significantly larger reduction in BMI compared to the control group (ΔBMI -3.1 vs. -1.74 kg/m2 respectively, P<0.001). In addition, they displayed ameliorated depression and anxiety scores and a reduction in the health locus of control based on chance

Greek Validation of Emotional Eating Scale for Children and Adolescents

Aim: In this study, we focused on the Greek validation of the Emotional Eating Scale for Children and Adolescents (EES-C). Methods: Our sample consisted of 150 students in primary and secondary school settings from two different areas of Greece. Child Depression Inventory (CDI) and State and Trait Anxiety in Children (STAIC) were also used for validation purposes. Results: The principal component factor analysis for construct validity generated three subscales: eating in response to anger/anxiety, feeling unsettled and depression. The EES-C tool was found with high internal reliability (Cronbach's Alpha 0.917). Conclusions: EES-C is a valid and reliable instrument to detect the emotional eating in children and adolescents in Greece

Stress Management in Women with Hashimoto’s thyroiditis: A Randomized Controlled Trial

Aim: Stress has been implicated in the pathogenesis of Hashimoto's thyroiditis (HT), nevertheless evidence is scarce regarding the effect of stress management on individuals suffering from HT. The purpose of this study was to evaluate the impact of an 8-week stress management intervention on the anti-thyroid peroxidase (anti-TPO) and anti-thyroglobulin (anti-TG) antibodies as well as thyroid-stimulating hormone (TSH) levels of women with HT. Secondary endpoints included the effect on the patients’ lifestyle, body mass index (BMI), depression, anxiety and stress. Methods: This was a two-arm parallel group (stress management intervention vs. standard care groups) randomized controlled study. Adult women with Hashimoto's thyroiditis, completed questionnaires on stress, anxiety, depression and lifestyle, at the beginning of the programme and 8 weeks later. Laboratory thyroid function tests (anti-TPO, anti-TG antibodies and TSH) were also measured at baseline and at the end of the study. Results: A total of 60 women with HT, aged 25-76 years, participated in the study (30 patients in each group). After eight weeks, patients in the intervention group demonstrated statistically significant beneficial decrements in the rate change of anti-TG titers and the levels of stress, depression and anxiety as well as better lifestyle scores, compared to the control group.   

Dynamic aberrant NF-κB spurs tumorigenesis: A new model encompassing the microenvironment

Recently it was discovered that a transient activation of transcription factor NF-κB can give cells properties essential for invasiveness and cancer initiating potential. In contrast, most oncogenes to date were characterized on the basis of mutations or by their constitutive overexpression. Study of NF-κB actually leads to a far more dynamic perspective on cancer: tumors caused by diverse oncogenes apparently evolve into cancer after loss of feedback regulation for NF-κB. This event alters the cellular phenotype and the expression of hormonal mediators, modifying signals between diverse cell types in a tissue. The result is a disruption of stem cell hierarchy in the tissue, and pervasive changes in the microenvironment and immune response to the malignant cells

Polycystic Ovary Syndrome and Insulin Physiology: An Observational Quantitative Serum Proteomics Study in adolescent, Normal-Weight Females

Background: Polycystic ovary syndrome (PCOS) is a common endocrine disorder associated with insulin resistance, even in the absence of overweight/obesity. The aim of the present study is to examine the global serum proteomic profile of adolescent, normal‐weight females with PCOS in order to gain novel insight in the association of this endocrine disorder with insulin physiology and to identify novel circulating markers that can guide intervention protocols. Methods: Non‐depleted serum from normal‐weight (BMI: 18–23 kg m^(−2)), adolescent females (13–21 years old) with PCOS (n = 20) is compared to BMI‐ and age‐matched healthy controls (n = 20) using our 3D quantitative proteomics methodology. Serum samples from study participants are randomly pooled to form four biological replicates of females with PCOS and four of healthy controls (n = 5 per sample pool). Results: One‐hundred and twenty‐six proteins are differentially expressed in females with PCOS compared to controls. Gene ontology analysis shows significant enrichment for terms related to inflammatory immune response, metabolism and insulin‐like growth factor receptor signaling pathway. Circulating levels of IGF‐1 and ‐2 and IGFBP‐2, ‐3, and ‐4 are found to be lower in females with PCOS compared to healthy controls. Conclusions: The present serum proteomics study provides insight into the pro‐inflammatory status and insulin dysregulation in young females with PCOS and identifies potential serological markers that can guide early intervention protocols

Polycystic Ovary Syndrome and Insulin Physiology: An Observational Quantitative Serum Proteomics Study in adolescent, Normal-Weight Females

Background: Polycystic ovary syndrome (PCOS) is a common endocrine disorder associated with insulin resistance, even in the absence of overweight/obesity. The aim of the present study is to examine the global serum proteomic profile of adolescent, normal‐weight females with PCOS in order to gain novel insight in the association of this endocrine disorder with insulin physiology and to identify novel circulating markers that can guide intervention protocols. Methods: Non‐depleted serum from normal‐weight (BMI: 18–23 kg m^(−2)), adolescent females (13–21 years old) with PCOS (n = 20) is compared to BMI‐ and age‐matched healthy controls (n = 20) using our 3D quantitative proteomics methodology. Serum samples from study participants are randomly pooled to form four biological replicates of females with PCOS and four of healthy controls (n = 5 per sample pool). Results: One‐hundred and twenty‐six proteins are differentially expressed in females with PCOS compared to controls. Gene ontology analysis shows significant enrichment for terms related to inflammatory immune response, metabolism and insulin‐like growth factor receptor signaling pathway. Circulating levels of IGF‐1 and ‐2 and IGFBP‐2, ‐3, and ‐4 are found to be lower in females with PCOS compared to healthy controls. Conclusions: The present serum proteomics study provides insight into the pro‐inflammatory status and insulin dysregulation in young females with PCOS and identifies potential serological markers that can guide early intervention protocols

Rare Variant Enrichment Analysis Supports GREB1L as a Contributory Driver Gene in the Etiology of Mayer-Rokitansky-Küster-Hauser Syndrome

Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is characterized by aplasia of the female reproductive tract; the syndrome can include renal anomalies, absence or dysgenesis, and skeletal anomalies. While functional models have elucidated several candidate genes, only WNT4 (MIM: 603490) variants have been definitively associated with a subtype of MRKH with hyperandrogenism (MIM: 158330). DNA from 148 clinically diagnosed MRKH probands across 144 unrelated families and available family members from North America, Europe, and South America were exome sequenced (ES) and by family-based genomics analyzed for rare likely deleterious variants. A replication cohort consisting of 442 Han Chinese individuals with MRKH was used to further reproduce GREB1L findings in diverse genetic backgrounds. Proband and OMIM phenotypes annotated using the Human Phenotype Ontology were analyzed to quantitatively delineate the phenotypic spectrum associated with GREB1L variant alleles found in our MRKH cohort and those previously published. This study reports 18 novel GREB1L variant alleles, 16 within a multiethnic MRKH cohort and two within a congenital scoliosis cohort. Cohort-wide analyses for a burden of rare variants within a single gene identified likely damaging variants in GREB1L (MIM: 617782), a known disease gene for renal hypoplasia and uterine abnormalities (MIM: 617805), in 16 of 590 MRKH probands. GREB1L variant alleles, including a CNV null allele, were found in 8 MRKH type 1 probands and 8 MRKH type II probands. This study used quantitative phenotypic analyses in a worldwide multiethnic cohort to identify and strengthen the association of GREB1L to isolated uterine agenesis (MRKH type I) and syndromic MRKH type II

Rare Variant Enrichment analysis Supports

Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is characterized by aplasia of the female reproductive tract; the syndrome can include renal anomalies, absence or dysgenesis, and skeletal anomalies. While functional models have elucidated several candidate genes, onl

Global variation in diabetes diagnosis and prevalence based on fasting glucose and hemoglobin A1c

Fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c) are both used to diagnose diabetes, but these measurements can identify different people as having diabetes. We used data from 117 population-based studies and quantified, in different world regions, the prevalence of diagnosed diabetes, and whether those who were previously undiagnosed and detected as having diabetes in survey screening, had elevated FPG, HbA1c or both. We developed prediction equations for estimating the probability that a person without previously diagnosed diabetes, and at a specific level of FPG, had elevated HbA1c, and vice versa. The age-standardized proportion of diabetes that was previously undiagnosed and detected in survey screening ranged from 30% in the high-income western region to 66% in south Asia. Among those with screen-detected diabetes with either test, the age-standardized proportion who had elevated levels of both FPG and HbA1c was 29-39% across regions; the remainder had discordant elevation of FPG or HbA1c. In most low- and middle-income regions, isolated elevated HbA1c was more common than isolated elevated FPG. In these regions, the use of FPG alone may delay diabetes diagnosis and underestimate diabetes prevalence. Our prediction equations help allocate finite resources for measuring HbA1c to reduce the global shortfall in diabetes diagnosis and surveillance