Germ-line GATA2 p.THR354MET mutation in familial myelodysplastic syndrome with acquired monosomy 7 and ASXL1 mutation demonstrating rapid onset and poor survival

While most myelodysplastic syndrome/acute myeloid leukemia cases are sporadic, rare familial cases occur and provide some insight into leukemogenesis. The most clearly defined familial cases result from inherited mutations in RUNX1 or CEBPA. Recently, novel germline mutations in GATA2 have been reported. We, therefore, investigated individuals from families with one or more first-degree relatives with myelodysplastic syndrome/acute myeloid leukemia with wild-type RUNX1 and CEBPA, for GATA2 mutations. Screening for other recurrent mutations was also performed. A GATA2 p.Thr354Met mutation was observed in a pedigree in which 2 first-degree cousins developed high-risk myelodys-plastic syndrome with monosomy 7. They were also observed to have acquired identical somatic ASXL1 mutations and both died despite stem cell transplantation. These findings confirm that germline GATA2 mutations predispose to familial myelodysplastic syndrome/acute myeloid leukemia, and that monosomy 7 and ASXL1 mutations may be recurrent secondary genetic abnormalities triggering overt malignancy in these families.     

Molecular analysis of oral bacteria in dental biofilm and atherosclerotic plaques of patients with vascular disease

Background

Oral bacteria have been detected in atherosclerotic plaques at a variable frequency; however, the connection between oral health and vascular and oral bacterial profiles of patients with vascular disease is not clearly established. The aim of this study was to evaluate the presence of oral bacterial DNA in the mouth and atherosclerotic plaques, in addition to assessing the patients’ caries and periodontal disease history.

Methods

Thirty samples of supragingival and subgingival plaque, saliva and atherosclerotic plaques of 13 patients with carotid stenosis or aortic aneurysm were evaluated, through real-time polymerase chain reaction, for the presence of Streptococcus mutans (SM), Prevotella intermedia (PI), Porphyromonas gingivalis (PG) and Treponema denticola (TD). All patients were submitted to oral examination using the DMFT (decayed, missing and filled teeth) and PSR (Periodontal Screening and Recording) indexes. Histopathological analysis of the atherosclerotic plaques was performed.

Results

Most of the patients were edentulous (76.9%). SM, PI, PG and TD were detected in 100.0%, 92.0%, 15.3% and 30.7% of the oral samples, respectively. SM was the most prevalent targeted bacteria in atherosclerotic plaques, detected in 100% of the samples, followed by PI (7.1%). The vascular samples were negative for PG and TD. There was a statistically significant difference (p < 0.05) between the presence of PG and TD in the oral cavity and vascular samples.

Conclusion

SM was found at a high frequency in oral and vascular samples, even in edentulous patients, and its presence in atherosclerotic plaques suggests the possible involvement of this bacterium in the disease progression.     

IL-27 regulates IL-4-induced chemokine production in human bronchial epithelial cells

IL-4 coordinates the Th2-type immune response in inflammatory diseases such as asthma. IL-27 can inhibit the development of both Th2 and Th1 cells. However, IL-27 can also drive naïve T cells to differentiate toward the Th1 phenotype. In this study, we investigated the effects of IL-27 on the activation of IL-4-induced human bronchial epithelial cells (BEAS-2B). Compared to controls, both IL-4 and IL-27 (25–100 ng/mL) increased the concentrations of CCL2 and IL-8 in a dose-dependent manner. However, compared to cells stimulated individually with IL-4 or IL-27, treatment with a combination of both cytokines reduced CCL2 and IL-8 concentrations in a dose- and time-dependent manner. IL-4 increased the activation of p38 MAPK, ERK1/2, STAT6 and NF-κB, while IL-27 increased the activation of p38 MAPK and ERK1/2 but not STAT6 and NF-κB. Compared to IL-4-stimulated cells, cells treated with both IL-27 and IL-4 displayed decreased activation of STAT6 and NF-κB but not ERK1/2 and p38 MAPK. Taken together, these results suggest that IL-27 plays a pro-inflammatory role when administered alone but downregulates bronchial epithelial cell activation when combined with IL-4. Therefore, IL-27 may be an interesting target for the treatment of Th2 inflammatory diseases.     

Effect of BMI on the Thermogenic Response to Cold Exposure and Associated Changes in Metabolism and Browning Markers in Adult Humans

IntroductionBrown adipose tissue (BAT) serves to produce heat by nonshivering thermogenesis. Activation of BAT increases energy expenditure and is seen as a putative strategy to treat obesity. There are conflicting data on the capacity for cold-induced thermogenesis in individuals with higher BMI.MethodsTo investigate the effect of BMI on cold-induced stimulation of energy expenditure, changes in the metabolic profile, and the expression of browning markers in subcutaneous white adipose tissue (scWAT), healthy adults (N = 173, 50.9% females) with a median age of 26.0 (interquartile range [IQR]: 23.0; 28.0) years and a median body mass index (BMI) of 23.6 [IQR: 21.9; 26.6] kg/m² were exposed to short-term mild cold exposure (CE). Resting energy expenditure (REE) was measured by indirect calorimetry and blood sampling was conducted at baseline and after CE. In a subgroup of participants with obesity, subcutaneous abdominal fat biopsies were taken before and after CE.ResultsThe cold-induced median increase in REE was 74 (IQR: −28; 241) kcal/day (p < 0.001). This increase negatively correlated with BMI (p < 0.001). Participants with BMI 18.5–24.9 kg/m² displayed a significant median increase of 103 kcal/day (p < 0.001), participants with overweight or obesity were not able to increase REE (23, p = 0.468 or −30 kcal/day, p = 0.917, respectively). In participants with obesity, expression of cell death activator in scWAT after CE was upregulated in females (p = 0.034).ConclusionsPersons with overweight and obesity do not increase REE in response to CE, presumably reflecting lower BAT activity. Likewise, the metabolic response to cold is diminished in participants with elevated BMI.     

An ultrastructural study of cell death in the CA1 pyramidal field of the hippocapmus in rats submitted to transient global ischemia followed by reperfusion

In the course of ischemia and reperfusion a disruption of release and uptake of excitatory neurotransmitters occurs. This excitotoxicity triggers delayed cell death, a process closely related to mitochondrial physiology and one that shows both apoptotic and necrotic features. The aim of the present study was to use electron microscopy to characterize the cell death of pyramidal cells from the CA1 field of the hippocampus after 10 min of transient global ischemia followed by short reperfusion periods. For this study 25 adult male Wistar rats were used, divided into six groups: 10 min of ischemia, 3, 6, 12 and 24 h of reperfusion and an untouched group. Transient forebrain ischemia was produced using the 4-vessel occlusion method. The pyramidal cells of the CA1 field from rat hippocampus submitted to ischemia exhibited intracellular alterations consistent with a process of degeneration, with varied intensities according to the reperfusion period and bearing both apoptotic and necrotic features. Gradual neuronal and glial modifications allowed for the classification of the degenerative process into three stages: initial, intermediate and final were found. With 3 and 6 h of reperfusion, slight and moderate morphological alterations were seen, such as organelle and cytoplasm edema. Within 12 h of reperfusion, there was an apparent recovery and more 'intact' cells could be identified, while 24 h after the event neuronal damage was more severe and cells with disrupted membranes and cell debris were identified. Necrotic-like neurons were found together with some apoptotic bodies with 24 h of reperfusion. Present results support the view that cell death in the CA1 field of rat hippocampus submitted to 10 min of global transient ischemia and early reperfusion times includes both apoptotic and necrotic features, a process referred to as parapoptosis.     

The New European Society for Clinical Nutrition and Metabolism Definition of Malnutrition: Application for Nutrition Assessment and Prediction of Morbimortality in an Emergency Service

Background : Recently, the European Society for Clinical Nutrition and Metabolism (ESPEN) provided novel consensus criteria for malnutrition diagnosis. This study aimed to evaluate the applicability of this instrument in combination with different nutrition screening tools (1) to identify malnutrition and (2) to predict morbidity and mortality in hospitalized patients. Materials and Methods : Observational prospective study in 750 adults admitted to the emergency service of a tertiary public hospital. Subjective Global Assessment (SGA—reference method) and the new ESPEN criteria were used to assess nutrition status of patients, who were initially screened for nutrition risk using 4 different tools. Outcome measures included length of hospital stay, occurrence of infection, and incidence of death during hospitalization, analyzed by logistic regression. Results : There was a lack of agreement between the SGA and ESPEN definition of malnutrition, regardless of the nutrition screening tool applied previously (κ = ?0.050 to 0.09). However, when Malnutrition Screening Tool and Nutritional Risk Screening–2002 (NRS‐2002) were used as the screening tool, malnourished patients according to ESPEN criteria showed higher probability of infection (relative risk [RR], 1.54; 95% confidence interval [CI], 1.02–2.31 and RR, 2.06; 95% CI, 1.37–3.10, respectively), and when the NRS‐2002 was used, the risk for death was 2.7 times higher (hazard ratio, 2.69; 95% CI, 1.07–6.81) in malnourished patients than in well‐nourished patients. Conclusion : Although the new ESPEN criteria had a poor diagnostic value, it seems to be a prognostic tool among hospitalized patients, especially when used in combination with the NRS‐2002.     

A Behavioral Intervention to Reduce Excessive Gestational Weight Gain

Objectives Excessive gestational weight gain (GWG) is a key modifiable risk factor for negative maternal and child health. We examined the efficacy of a behavioral intervention in preventing excessive GWG. Methods 230 pregnant women (87.4 % Caucasian, mean age = 29.2 years; second parity) participated in the longitudinal Glowing study (clinicaltrial.gov #NCT01131117), which included six intervention sessions focused on GWG. To determine the efficacy of the intervention in comparison to usual care, participants were compared to a matched contemporary cohort group from the Arkansas Pregnancy Risk Assessment Monitoring Survey (PRAMS). Results Participants attended 98 % of intervention sessions. Mean GWG for the Glowing participants was 12.7 ± 2.7 kg for normal weight women, 12.4 ± 4.9 kg for overweight women, and 9.0 ± 4.2 kg for class 1 obese women. Mean GWG was significantly lower for normal weight and class 1 obese Glowing participants compared to the PRAMS respondents. Similarly, among those who gained excessively, normal weight and class 1 obese Glowing participants had a significantly smaller mean weight gain above the guidelines in comparison to PRAMS participants. There was no significant difference in the overall proportion of the Glowing participants and the proportion of matched PRAMS respondents who gained in excess of the Institute of Medicine GWG guidelines. Conclusions for Practice This behavioral intervention was well-accepted and attenuated GWG among normal weight and class 1 obese women, compared to matched participants. Nevertheless, a more intensive intervention may be necessary to help women achieve GWG within the Institute of Medicine’s guidelines.     

Epidemiologic confirmation that fruit consumption influences mercury exposure in riparian communities in the Brazilian Amazon

Since deforestation has recently been associated with increased mercury load in the Amazon, the problem of mercury exposure is now much more widespread than initially thought. A previous exploratory study suggested that fruit consumption may reduce mercury exposure. The objectives of the study were to determine the effects of fruit consumption on the relation between fish consumption and bioindicators of mercury (Hg) exposure in Amazonian fish-eating communities. A cross-sectional dietary survey based on a 7-day recall of fish and fruit consumption frequency was conducted within 13 riparian communities from the Tapajós River, Brazilian Amazon. Hair samples were collected from 449 persons, and blood samples were collected from a subset of 225, for total and inorganic mercury determination by atomic absorption spectrometry. On average, participants consumed 6.6 fish meals/week and ate 11 fruits/week. The average blood Hg (BHg) was 57.1 +/- 36.3 microg/L (median: 55.1 microg/L), and the average hair-Hg (HHg) was 16.8 +/- 10.3 microg/g (median: 15.7 microg/g). There was a positive relation between fish consumption and BHg (r = 0.48; P<0.0001), as well as HHg (r =0.34; P<0.0001). Both fish and fruit consumption entered significantly in multivariate models explaining BHg (fish: beta = 5.6, P<0.0001; fruit: beta = -0.5, P = 0.0011; adjusted model R2 = 36.0%) and HHg levels (fish: beta = 1.2, P<0.0001; fruit: beta = -0.2, P = 0.0002; adjusted model R2 = 21.0%). ANCOVA models showed that for the same number of fish meals, persons consuming fruits more frequently had significantly lower blood and HHg concentrations. For low fruit consumers, each fish meal contributed 9.8 microg/L Hg increase in blood compared to only 3.3 microg/L Hg increase for the high fruit consumers. In conclusion, fruit consumption may provide a protective effect for Hg exposure in Amazonian riparians. Prevention strategies that seek to maintain fish consumption while reducing Hg exposure in fish-eating communities should be pursued.     

The death toll of French former prisoners

Several studies have documented that ex-prisoners are at higher risk of death than the general population but only one study, concerning one single prison, has examined the French case. This study relies on a nationally representative sample of all inmates released from French prisons between June and December 2002. A linkage between two administrative databases makes it possible to study mortality within 5 years after release. The magnitude of ex-prisoners’ excess mortality is similar to that observed in other studies. The standardized mortality ratio is 3.6 (95% CI 3.1–4.1). Excess mortality after release is especially high between the ages of 30 and 50. Inmates incarcerated for at least 5 years have lower risks of dying (OR 0.4, 95% CI 0.2–0.9). We also find that adjusted sentences are protective (OR 0.6, 95% CI 0.3–0.9).