Is everybody always my friend? Perception of approachability in Williams syndrome

Individuals with Williams syndrome (WS) are well known for their friendly behaviour and tendency to approach strangers indiscriminately as if everybody were their friend. This tendency to approach strangers is mirrored in their ratings of unfamiliar face stimuli. Here we examined their perception of unfamiliar expressive faces and found that individuals with WS do not always see faces as being highly approachable. Happy faces were rated as more approachable by individuals with WS than by controls. In contrast, the other less approachable face stimuli were rated lower on approachability by individuals with WS than by controls. Thus, it appears that although individuals with WS will discriminate people in terms of approachability, they have difficulty inhibiting their strong compulsion towards social interaction. The form of this strong pro-social compulsion is discussed both in terms of friendliness and in terms of the heightened salience of social stimuli (social stimulus attraction).     

Pseudoaneurisma gigante da via de saída do ventrículo esquerdo: uma patologia rara

Pseudoaneurysm of the left ventricular outflow tract (LVOT) is a rare disease with high morbidity and mortality, resulting from left ventricular damage due to myocardial infarction, infective endocarditis or surgical trauma. A case of giant pseudoaneurysm of the LVOT, even more rarely reported in the literature, is described. The lesion was detected 12 years after aortic valve replacement for infective endocarditis in a young patient, a former intravenous drug user. As it is an uncommon disease, little is known about its clinical presentation and treatment.     

Sequential 18F-FDG PET/CT for early prediction of complete pathological response in breast and axilla during neoadjuvant chemotherapy

Purpose

To investigate the value of response monitoring in both the primary tumour and axillary nodes on sequential PET/CT scans during neoadjuvant chemotherapy (NAC) for predicting complete pathological response (pCR), taking the breast cancer subtype into account.

Methods

In 107 consecutive patients 290 PET/CT scans were performed at baseline (PET/CT1, 107 patients), after 2 – 3 weeks of chemotherapy (PET/CT2, 85 patients), and after 6 – 8 weeks (PET/CT3, 98 patients). The relative changes in SUVmax (from baseline) of the tumour and the lymph nodes and in both combined (after logistic regression), and the changes in the highest SUVmax between scans (either tumour or lymph node) were determined and their associations with pCR of the tumour and lymph nodes after completion of NAC were assessed using receiver operating characteristic (ROC) analysis.

Results

A pCR was seen in 17 HER2-positive tumours (65 %), 1 ER-positive/HER2-negative tumour (2 %), and 16 triple-negative tumours (52 %). The areas under the ROC curves (ROC-AUC) for the prediction of pCR in HER2-positive tumours after 3 weeks were 0.61 for the relative change in tumours, 0.67 for the combined change in tumour and nodes, and 0.72 for the changes in the highest SUVmax between scans. After 8 weeks equivalent values were 0.59, 0.42 and 0.64, respectively. In triple-negative tumours the ROC-AUCs were 0.76, 0.84 and 0.76 after 2 weeks, and 0.87, 0.93 and 0.88 after 6 weeks, respectively.

Conclusion

In triple-negative tumours a PET/CT scan after 6 weeks (three cycles) appears to be optimally predictive of pCR. In HER2-positive tumours neither a PET/CT scan after 3 weeks nor after 8 weeks seems to be useful. The changes in SUVmax of both the tumour and axillary nodes combined correlates best with pCR.     

The anti-apoptotic BAG3 protein is expressed in lung carcinomas and regulates small cell lung carcinoma (SCLC) tumor growth

BAG3, member the HSP70 co-chaperones family, has been shown to play a relevant role in the survival, growth and invasiveness of different tumor types. In this study, we investigate the expression of BAG3 in 66 specimens from different lung tumors and the role of this protein in small cell lung cancer (SCLC) tumor growth. Normal lung tissue did not express BAG3 while we detected the expression of BAG3 by immunohistochemistry in all the 13 squamous cell carcinomas, 13 adenocarcinomas and 4 large cell carcinomas. Furthermore, we detected BAG3 expression in 22 of the 36 SCLCs analyzed. The role on SCLC cell survival was determined by down-regulating BAG3 levels in two human SCLC cell lines, i.e. H69 and H446, in vitro and measuring cisplatin induced apoptosis. Indeed down-regulation of BAG3 determines increased cell death and sensitizes cells to cisplatin treatment. The effect of BAG3 down-regulation on tumor growth was also investigated in an in vivo xenograft model by treating mice with an adenovirus expressing a specific bag3 siRNA. Treatment with bag3 siRNA-Ad significantly reduced tumor growth and improved animal survival. In conclusion we show that a subset of SCLCs over express BAG3 that exerts an anti-apoptotic effect resulting in resistance to chemotherapy.     

Maternal Nutrition Status Associated with Pregnancy-Related Adverse Outcomes

Although maternal nutrition has an impact on fetal development and gestational outcome, tracking maternal nutrition in outpatient practice is still complex and involves proper technical capacitation in this area. Nevertheless, the association between nutritional variables may broaden the ability to predict the occurrence of gestational disorders and prevention management. We aimed to identify factors that could indicate the probability of adverse outcomes in mid-pregnancy. From a cohort of 1165 nulliparous pregnant women without any previous disease, the nutritional status was assessed by body mass index (BMI) and mid-upper arm circumference (MUAC), associated with dietary patterns and sociodemographic characteristics. Two predictive models with nutritional status for screening the occurrence of adverse outcomes of preterm birth, gestational diabetes mellitus, small-for-gestational-age newborns and preeclampsia were developed. The odds of adverse outcomes were higher in non-white (p < 0.05) obese women and with high protein consumption. There was no significant difference between the models, with an overall accuracy of 63% for both models and a probability of success in predicting adverse outcomes (BMI = 61%, MUAC = 52%). This study of Brazilian pregnant nulliparous women offers two possible options for early tracking of adverse gestational outcomes that should be further externally validated.     

Risk factors and impact of major bleeding in critically ill patients receiving heparin thromboprophylaxis

Purpose

Bleeding frequently complicates critical illness and may have serious consequences. Our objectives are to describe the predictors of major bleeding and the association between bleeding and mortality in medical–surgical critically ill patients receiving heparin thromboprophylaxis.

Methods

We prospectively studied patients from 67 intensive care units and six countries enrolled in a thromboprophylaxis trial (NCT00182143) comparing dalteparin with unfractionated heparin. Patients with trauma, orthopedic surgery or neurosurgery were excluded. Trained research coordinators used a validated tool to document bleeding, which underwent duplicate independent blinded adjudication. Major bleeding was defined as hypovolemic shock, bleeding into critical sites, requiring an invasive intervention or transfusion of at least two units of red blood cells, or associated with hypotension or tachycardia in the absence of other causes. Adjusted Cox proportional hazard regression analysis was used to identify major bleeding predictors and the association between bleeding and mortality.

Results

Among 3,746 patients, bleeding occurred in 208 [5.6 %, 95 % confidence interval (CI) 4.9–6.3 %]. Time-dependent predictors were prolonged activated partial thromboplastin time [hazard ratio (HR) 1.10, 1.05–1.14 per 10 s increase], lower platelet count (HR 1.16, 1.09–1.24 per 50 × 10⁹/L decrease), therapeutic heparin (HR 3.26, 1.72–6.17), antiplatelet agents (HR 1.38, 1.02–1.88), renal replacement therapy (HR 1.75, 1.20–2.56), and recent surgery (HR 1.64, 1.01–2.65). Type of pharmacologic thromboprophylaxis was not associated with bleeding. Patients with bleeding had a higher risk of in-hospital death (HR 2.09, 1.69–2.57).

Conclusions

As major bleeding has modifiable risk factors and is associated with in-hospital mortality, strategies to mitigate these factors should be evaluated in critically ill patients.     

Myelin basic protein-specific T lymphocytes proliferation and programmed cell death in demyelinating diseases

A dynamic equilibrium between proliferation and programmed cell death (PCD) of auto-reactive T lymphocytes plays a pivotal role in the prevention of autoimmune diseases. We analyzed T lymphocytes myelin basic protein (MBP)-specific PCD and proliferation in demyelinating diseases. Results showed that MBP-specific PCD was significantly decreased in CD4+ and CD8+ T lymphocytes of progressive multifocal leukoencephalopathy (PML), not determined leukoencephalopathy (NDLE), and acute MS (AMS) patients compared to patients with stable MS (SMS) and healthy controls. MBP-specific proliferation/PCD rates were high in CD4+ T lymphocytes of PML, NDLE, and AMS patients, and in CD8+ T cells of PML and AMS individuals alone. Alterations of the balance between MBP-specific proliferation and PCD are present in demyelinating diseases and could play a major role in the pathogenesis of these diseases.