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.     

An insight into the sialotranscriptome of Triatoma matogrossensis, a kissing bug associated with fogo selvagem in South America

Triatoma matogrossensis is a Hemiptera that belongs to the oliveirai complex, a vector of Chagas' disease that feeds on vertebrate blood in all life stages. Hematophagous insects' salivary glands (SGs) produce potent pharmacologic compounds that counteract host hemostasis, including anticlotting, antiplatelet, and vasodilatory molecules. Exposure to T. matogrossensis was also found to be a risk factor associated with the endemic form of the autoimmune skin disease pemphigus foliaceus, which is described in the same regions where Chagas' disease is observed in Brazil. To obtain a further insight into the salivary biochemical and pharmacologic diversity of this kissing bug and to identify possible allergens that might be associated with this autoimmune disease, a cDNA library from its SGs was randomly sequenced. We present the analysis of a set of 2,230 (SG) cDNA sequences, 1,182 of which coded for proteins of a putative secretory nature.     

Maternal antibodies from mothers of children with autism alter brain growth and social behavior development in the rhesus monkey

Antibodies directed against fetal brain proteins of 37 and 73 kDa molecular weight are found in approximately 12% of mothers who have children with autism spectrum disorder (ASD), but not in mothers of typically developing children. This finding has raised the possibility that these immunoglobulin G (IgG) class antibodies cross the placenta during pregnancy and impact brain development, leading to one form of ASD. We evaluated the pathogenic potential of these antibodies by using a nonhuman primate model. IgG was isolated from mothers of children with ASD (IgG-ASD) and of typically developing children (IgG-CON). The purified IgG was administered to two groups of female rhesus monkeys (IgG-ASD; n=8 and IgG-CON; n=8) during the first and second trimesters of pregnancy. Another control group of pregnant monkeys (n=8) was untreated. Brain and behavioral development of the offspring were assessed for 2 years. Behavioral differences were first detected when the macaque mothers responded to their IgG-ASD offspring with heightened protectiveness during early development. As they matured, IgG-ASD offspring consistently deviated from species-typical social norms by more frequently approaching familiar peers. The increased approach was not reciprocated and did not lead to sustained social interactions. Even more striking, IgG-ASD offspring displayed inappropriate approach behavior to unfamiliar peers, clearly deviating from normal macaque social behavior. Longitudinal magnetic resonance imaging analyses revealed that male IgG-ASD offspring had enlarged brain volume compared with controls. White matter volume increases appeared to be driving the brain differences in the IgG-ASD offspring and these differences were most pronounced in the frontal lobes.     

13th St. Gallen International Breast Cancer Conference 2013: Primary Therapy of Early Breast Cancer Evidence,Controversies, Consensus – Opinion of a German Team of Experts (Zurich 2013)

Zusammenfassung

Alle zwei Jahre findet in St. Gallen (Schweiz) die internationale Konsensuskonferenz zur Behandlung des primären Mammakarzinoms statt. Da sich das internationale Panel in St. Gallen aus Experten unterschiedlicher Länder zusammensetzt, spiegelt der Konsensus ein internationales Meinungsbild wider. Vor diesem Hintergrund erscheint es aus deutscher Sicht sinnvoll, die Abstimmungsergebnisse für den Therapiealltag in Deutschland zu konkretisieren. Eine deutsche Arbeitsgruppe mit acht Brustkrebsexperten, von denen zwei Mitglieder des internationalen St. Gallen-Panels sind, hat daher die Abstimmungsergebnisse der St. Gallen-Konsensuskonferenz (2013) für den Klinikalltag in Deutschland kommentiert. Inhaltliche Schwerpunkte der diesjährigen St. Gallen-Konferenz waren operative Fragestellungen der Brust und der Axilla, strahlentherapeutische und systemische Therapieoptionen sowie die klinische Relevanz der Tumorbiologie. Intensiv diskutiert wurde der klinische Einsatz von Multigen-Assays, inkl. ihrer Bedeutung für die individuelle Therapieentscheidung.     

Mental Health Literacy of University Students in Vietnam and Cambodia

Mental health literacy (MHL) refers to knowledge and attitudes that shape the recognition, management, and prevention of mental disorders. While the topic has been exhaustively researched in Western countries, research from Southeast Asia still is limited. Previous studies in this field showed a moderate recognition of mental disorders, a high prevalence of stigmatizing attitudes and a low willingness to seek professional help among Southeastern-Asian populations. This study explored the level of MHL among university students from different parts of Vietnam and Cambodia. Correlations with influencing factors (gender, age, study year, educational attainment of the parents, urban/rural origin, ethnicity, personal experiences with mental disorders) were also explored. An online survey, using a 30-item Vietnamese version of the Mental Health Literacy Scale (MHLS), was conducted at six university sites in Vietnam and Cambodia. Data of 1032 students from different study branches were included. The MHL of Vietnamese and Cambodian university students was lower, compared to samples from Australia or the UK. Females and students with a personal experience of mental disorders (self or family) showed a significantly higher MHL. No differences in MHL were found between students from different socioeconomic backgrounds (professional attainment of parents, urban/rural origin). Findings on the influence of ethnicity were inconclusive. MHL needs to be improved among the university students of Vietnam and Cambodia. Mental health promotion should specifically target male students, students from STEM branches, and international students.     

Dexmedetomidine and ketamine show distinct patterns of cell degeneration and apoptosis in the developing rat neonatal brain

Objective: Early exposure to common anesthetic and sedative agents causes widespread brain cell degeneration and apoptosis in the developing rat brain, associated with persistent learning deficits in rats. This study was designed to determine whether the α₂ adrenergic receptor agonist, dexmedetomidine, produces brain cell degeneration and apoptosis in postnatal day-7 rats in the same brain areas when compared to ketamine.

Methods: Systemic saline, ketamine 20?mg/kg, or dexmedetomidine at 30 or 45?μg/kg were given six times to postnatal day 7 rats (n = 6/group) every 90?min. Twenty-four hours after the initial injection, brain regions were processed and analyzed for cell degeneration using the silver stain and for apoptosis using activated caspase-3 immunohistochemistry.

Results: Exposure to ketamine resulted in significant cellular degeneration and apoptosis in limbic brain regions, but nonsignificant changes in primary sensory brain regions. In contrast, dexmedetomidine produced significant cellular degeneration and apoptosis in primary sensory brain regions, but nonsignificant changes in limbic regions.

Conclusions: These data show that ketamine and dexmedetomidine result in anatomically distinct patterns of cell degeneration and apoptosis in the brains of 7-day-old rat pups. The meaning and the clinical significance of these findings remain to be established.