Novel therapies against aggressive differentiated thyroid carcinomas

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Using local texture maps of brain MR images to detect Mild Cognitive Impairment

Early detection of Alzheimer's disease is expected to aid in the development and monitoring of more effective treatments. Classification methods have been proposed to distinguish Alzheimer's patients from normal controls using Magnetic Resonance Images. However, their performance drops when classifying patients at a prodromal stage, such as in Mild Cognitive Impairment. Most often, the features used in these classification tasks are related to structural measures such as volume, shape and tissue density. However, microstructural changes have been shown to arise even earlier than these larger-scale alterations. Taking this into account, we propose the use of local statistical texture maps that make no assumptions regarding the location of the affected brain regions. Each voxel contains texture information from its local neighborhood and is used as a feature in the classification of normal controls and Mild Cognitive Impairment patients. The proposed approach obtained an accuracy of 87% (sensitivity 85%, specificity 95%) with Support Vector Machines, outperforming the 63% achieved by the local gray matter density feature

Suicidal intoxication by copper sulphate

Poster apresentado no 60th Annual Meeting of the American Academy of Forensic Sciences, 18-23 Fevereiro, 2008, Washington, DC, EUAPortugal is traditionally an agricultural country, consequently intoxications by pesticides are very common. An 81 year old male, diabetic, with chronic renal failure, was admitted at the hospital with a suspicion of voluntary ingestion of copper sulfate. Four days later he died. At the autopsy it was possible to see a green colouration of the nails, (...)N/

Hypoxia inhibits colonic uptake of the microbiota-generated forms of vitamin B1 via HIF-1α-mediated transcriptional regulation of their transporters

Hypoxia exerts profound effects on cell physiology, but its effect on colonic uptake of the microbiota-generated forms of vitamin B1 (i.e., thiamin pyrophosphate [TPP] and free thiamine) has not been described. Here, we used human colonic epithelial NCM460 cells and human differentiated colonoid monolayers as in vitro and ex vivo models, respectively, and were subjected to either chamber (1%

Enterotoxigenic Escherichia coli heat-labile toxin drives enteropathic changes in small intestinal epithelia

Enterotoxigenic E. coli (ETEC) produce heat-labile (LT) and/or heat-stable (ST) enterotoxins, and commonly cause diarrhea in resource-poor regions. ETEC have been linked repeatedly to sequelae in children including enteropathy, malnutrition, and growth impairment. Although cellular actions of ETEC enterotoxins leading to diarrhea are well-established, their contributions to sequelae remain unclear. LT increases cellular cAMP to activate protein kinase A (PKA) that phosphorylates ion channels driving intestinal export of salt and water resulting in diarrhea. As PKA also modulates transcription of many genes, we interrogated transcriptional profiles of LT-treated intestinal epithelia. Here we show that LT significantly alters intestinal epithelial gene expression directing biogenesis of the brush border, the major site for nutrient absorption, suppresses transcription factors HNF4 and SMAD4 critical to enterocyte differentiation, and profoundly disrupts microvillus architecture and essential nutrient transport. In addition, ETEC-challenged neonatal mice exhibit substantial brush border derangement that is prevented by maternal vaccination with LT. Finally, mice repeatedly challenged with toxigenic ETEC exhibit impaired growth recapitulating the multiplicative impact of recurring ETEC infections in children. These findings highlight impacts of ETEC enterotoxins beyond acute diarrheal illness and may inform approaches to prevent major sequelae of these common infections including malnutrition that impact millions of children

α-actinin accounts for the bioactivity of actin preparations in inducing STAT target genes in

Damage-associated molecular patterns (DAMPs) are molecules exposed or released by dead cells that trigger or modulate immunity and tissue repair. In vertebrates, the cytoskeletal component F-actin is a DAMP specifically recognised by DNGR-1, an innate immune receptor. Previously we suggested that actin is also a DAMP in Drosophila melanogaster by inducing STATdependent genes (Srinivasan et al., 2016). Here, we revise that conclusion and report that aactinin is far more potent than actin at inducing the same STAT response and can be found in trace amounts in actin preparations. Recombinant expression of actin or a-actinin in bacteria demonstrated that only a-actinin could drive the expression of STAT target genes in Drosophila. The response to injected a-actinin required the same signalling cascade that we had identified in our previous work using actin preparations. Taken together, these data indicate that a-actinin rather than actin drives STAT activation when injected into Drosophila

Elective surgery cancellations due to the COVID-19 pandemic: global predictive modelling to inform surgical recovery plans.

BACKGROUND: The COVID-19 pandemic has disrupted routine hospital services globally. This study estimated the total number of adult elective operations that would be cancelled worldwide during the 12 weeks of peak disruption due to COVID-19. METHODS: A global expert response study was conducted to elicit projections for the proportion of elective surgery that would be cancelled or postponed during the 12 weeks of peak disruption. A Bayesian β-regression model was used to estimate 12-week cancellation rates for 190 countries. Elective surgical case-mix data, stratified by specialty and indication (surgery for cancer versus benign disease), were determined. This case mix was applied to country-level surgical volumes. The 12-week cancellation rates were then applied to these figures to calculate the total number of cancelled operations. RESULTS: The best estimate was that 28 404 603 operations would be cancelled or postponed during the peak 12 weeks of disruption due to COVID-19 (2 367 050 operations per week). Most would be operations for benign disease (90·2 per cent, 25 638 922 of 28 404 603). The overall 12-week cancellation rate would be 72·3 per cent. Globally, 81·7 per cent of operations for benign conditions (25 638 922 of 31 378 062), 37·7 per cent of cancer operations (2 324 070 of 6 162 311) and 25·4 per cent of elective caesarean sections (441 611 of 1 735 483) would be cancelled or postponed. If countries increased their normal surgical volume by 20 per cent after the pandemic, it would take a median of 45 weeks to clear the backlog of operations resulting from COVID-19 disruption. CONCLUSION: A very large number of operations will be cancelled or postponed owing to disruption caused by COVID-19. Governments should mitigate against this major burden on patients by developing recovery plans and implementing strategies to restore surgical activity safely

Diversity and ethics in trauma and acute care surgery teams: results from an international survey

Background Investigating the context of trauma and acute care surgery, the article aims at understanding the factors that can enhance some ethical aspects, namely the importance of patient consent, the perceptiveness of the ethical role of the trauma leader, and the perceived importance of ethics as an educational subject. Methods The article employs an international questionnaire promoted by the World Society of Emergency Surgery. Results Through the analysis of 402 fully filled questionnaires by surgeons from 72 different countries, the three main ethical topics are investigated through the lens of gender, membership of an academic or non-academic institution, an official trauma team, and a diverse group. In general terms, results highlight greater attention paid by surgeons belonging to academic institutions, official trauma teams, and diverse groups. Conclusions Our results underline that some organizational factors (e.g., the fact that the team belongs to a university context or is more diverse) might lead to the development of a higher sensibility on ethical matters. Embracing cultural diversity forces trauma teams to deal with different mindsets. Organizations should, therefore, consider those elements in defining their organizational procedures. Level of evidence Trauma and acute care teams work under tremendous pressure and complex circumstances, with their members needing to make ethical decisions quickly. The international survey allowed to shed light on how team assembly decisions might represent an opportunity to coordinate team member actions and increase performance