Observing Virtual Arms that You Imagine Are Yours Increases the Galvanic Skin Response to an Unexpected Threat

Multi-modal visuo-tactile stimulation of the type performed in the rubber hand illusion can induce the brain to temporarily incorporate external objects into the body image. In this study we show that audio-visual stimulation combined with mental imagery more rapidly elicits an elevated physiological response (skin conductance) after an unexpected threat to a virtual limb, compared to audio-visual stimulation alone. Two groups of subjects seated in front of a monitor watched a first-person perspective view of slow movements of two virtual arms intercepting virtual balls rolling towards the viewer. One group was instructed to simply observe the movements of the two virtual arms, while the other group was instructed to observe the virtual arms and imagine that the arms were their own. After 84 seconds the right virtual arm was unexpectedly “stabbed” by a knife and began “bleeding”. This aversive stimulus caused both groups to show a significant increase in skin conductance. In addition, the observation-with-imagery group showed a significantly higher skin conductance (p<0.05) than the observation-only group over a 2-second period shortly after the aversive stimulus onset. No corresponding change was found in subjects' heart rates. Our results suggest that simple visual input combined with mental imagery may induce the brain to measurably temporarily incorporate external objects into its body image

Targeting GD2-positive glioblastoma by chimeric antigen receptor empowered mesenchymal progenitors

Tumor targeting by genetically modified mesenchymal stromal/stem cells (MSCs) carrying anti-cancer molecules represents a promising cell-based strategy. We previously showed that the pro-apoptotic agent tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) can be successfully delivered by MSCs to cancer sites. While the interaction between TRAIL and its receptors is clear, more obscure is the way in which MSCs can selectively target tumors and their antigens. Several neuroectoderm-derived neoplasms, including glioblastoma (GBM), sarcomas, and neuroblastoma, express high levels of the tumor-associated antigen GD2. We have already challenged this cell surface disialoganglioside by a chimeric antigen receptor (CAR)-T cell approach against neuroblastoma. With the intent to maximize the therapeutic profile of MSCs delivering TRAIL, we here originally developed a bi-functional strategy where TRAIL is delivered by MSCs that are also gene modified with the truncated form of the anti-GD2 CAR (GD2 tCAR) to mediate an immunoselective recognition of GD2-positive tumors. These bi-functional MSCs expressed high levels of TRAIL and GD2 tCAR associated with a robust anti-tumor activity against GD2-positive GBM cells. Most importantly, the anti-cancer action was reinforced by the enhanced targeting potential of such bi-functional cells. Collectively, our results suggest that a truncated anti-GD2 CAR might be a powerful new tool to redirect MSCs carrying TRAIL against GD2-expressing tumors. This affinity-based dual targeting holds the promise to combine site-specific and prolonged retention of MSCs in GD2-expressing tumors, thereby providing a more effective delivery of TRAIL for still incurable cancers

The feasibility of measuring the activation of the trunk muscles in healthy older adults during trunk stability exercises

<p>Abstract</p> <p>Background</p> <p>As the older adult population increases, the potential functional and clinical burden of trunk muscle dysfunction may be significant. An evaluation of risk factors including the impact of the trunk muscles in terms of their temporal firing patterns, amplitudes of activation, and contribution to spinal stability is required. Therefore, the specific purpose of this study was to assess the feasibility of measuring the activation of trunk muscles in healthy older adults during specific leg exercises with trunk stabilization.</p> <p>Methods</p> <p>12 asymptomatic adults 65 to 75 years of age were included in the study. Participants performed a series of trunk stability exercises, while bilateral activation of abdominal and back extensor muscles was recorded by 24 pairs of Meditrace™ surface electrodes. Maximal voluntary isometric contractions (MVIC) were performed for electromyographic (EMG) normalization purposes. EMG waveforms were generated and amplitude measures as a percentage of MVIC were calculated along with ensemble average profiles. 3D kinematics data were also recorded, using an electromagnetic sensor placed at the left lateral iliac crest. Furthermore, a qualitative assessment was conducted to establish the participant's ability to complete all experimental tasks.</p> <p>Results</p> <p>Excellent quality abdominal muscle activation data were recorded during the tasks. Participants performed the trunk stability exercises with an unsteady, intermittent motion, but were able to keep pelvic motion to less than 10°. The EMG amplitudes showed that during these exercises, on average, the older adults recruited their abdominal muscles from 15–34% of MVIC and back extensors to less than 10% of MVIC. There were similarities among the abdominal muscle profiles. No participants reported pain during the testing session, although 3 (25%) of the participants reported delayed onset muscle soreness during follow up that was not functionally limiting.</p> <p>Conclusion</p> <p>Older adults were able to successfully complete the trunk stability protocol that was developed for younger adults with some minor modifications. The collected EMG amplitudes were higher than those reported in the literature for young healthy adults. The temporal waveforms for the abdominal muscles showed a degree of synchrony among muscles, except for the early activation from the internal oblique prior to lifting the leg off the table.</p

Measuring What Works: An Impact Evaluation of Women's Groups on Maternal Health Uptake in Rural Nepal.

BACKGROUND: There is a need for studies evaluating maternal health interventions in low-income countries. This paper evaluates one such intervention designed to promote maternal health among rural women in Nepal. METHODS AND RESULTS: This was a five-year controlled, non-randomised, repeated cross-sectional study (2007, 2010, 2012) of a participatory community-based maternal health promotion intervention focusing on women's groups to improve maternal health services uptake. In total 1,236 women of childbearing age, who had their last child ≤ two years ago, were interviewed. Difference-in-Difference estimation assessed the effects of the intervention on selected outcome variables while controlling for a constructed wealth index and women's characteristics. In the first three years (from 2007 to the 2010), the intervention increased women's likelihood of attending for antenatal care at least once during pregnancy by seven times [OR = 7.0, 95%CI (2.3; 21.4)], of taking iron and folic acid by three times [OR = 3.0, 95%CI (1.2; 7.8)], and of seeking four or more antenatal care visits of two times, although not significantly [OR = 2.2, 95%CI (1.0; 4.7)]. Over five years, women were more likely to seek antenatal care at least once [OR = 3.0, 95%CI (1.5; 5.2)], to take iron/folic acid [OR = 1.9, [95% CI (1.1; 3.2)], and to attend postnatal care [OR = 1.5, [95% CI (1.1; 2.2)]. No improvement was found on attending antenatal care in the first trimester, birthing at an institution or with a skilled birth attendant. CONCLUSION: Community-based health promotion has a much stronger effect on the uptake of antenatal care and less on delivery care. Other factors not easily resolved through health promotion interventions may influence these outcomes, such as costs or geographical constraints. The evaluation has implications for policy and practice in public health, especially maternal health promotion

Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.

Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability

Local ATP generation by brain-type creatine kinase (CK-B) facilitates cell motility

Contains fulltext : 76049.pdf (publisher's version ) (Open Access)BACKGROUND: Creatine Kinases (CK) catalyze the reversible transfer of high-energy phosphate groups between ATP and phosphocreatine, thereby playing a storage and distribution role in cellular energetics. Brain-type CK (CK-B) deficiency is coupled to loss of function in neural cell circuits, altered bone-remodeling by osteoclasts and complement-mediated phagocytotic activity of macrophages, processes sharing dependency on actomyosin dynamics. METHODOLOGY/PRINCIPAL FINDINGS: Here, we provide evidence for direct coupling between CK-B and actomyosin activities in cortical microdomains of astrocytes and fibroblasts during spreading and migration. CK-B transiently accumulates in membrane ruffles and ablation of CK-B activity affects spreading and migration performance. Complementation experiments in CK-B-deficient fibroblasts, using new strategies to force protein relocalization from cytosol to cortical sites at membranes, confirmed the contribution of compartmentalized CK-B to cell morphogenetic dynamics. CONCLUSION/SIGNIFICANCE: Our results provide evidence that local cytoskeletal dynamics during cell motility is coupled to on-site availability of ATP generated by CK-B

Cavernoma gigante: relato de dois casos Giant cavernous angioma: report of two cases

Angiomas cavernosos ou hemangiomas ou ainda cavernomas são malformações do sistema nervoso central, classificadas como lesões cerebrais vasculares ocultas, frequentemente assintomáticas, sendo relativamente raras. Definidas histologicamente como massas compactas cavernosas ou canais sinusoidais de vários tamanhos, com paredes finas no interior do parênquima cerebral e sem intervenção do tecido glial. Podem ocorrer em qualquer faixa etária inclusive em neonatos. Na maioria das vezes são lesões de tamanho reduzido, localizadas no interior do parênquima encefálico. Angiograficamente não mostram alterações com circulação patológica, podendo mesmo não ser diagnosticados pela tomografia, sendo o exame ideal para o seu diagnóstico a ressonância magnética de crânio. Os cavernomas são lesões histologicamente benignas mas, dependendo de sua localização, podem trazer grandes transtornos neurológicos e ser irressecáveis. A exérese cirúrgica da lesão é o tratamento de escolha se a lesão for única e em localização favorável e estiver desencadeando sintomatologia neurológica prejudicial ao paciente. Apresentamos dois casos de cavernomas gigantes que apresentaram boa evolução após ressecção cirúrgica completa. Descritos como gigantes, foram encontrados apenas três casos individuais na literatura .<br>Cavernous angiomas or haemangiomas or yet cavernomas are malformations of the central nervous system classified as occult vascular brain lesions. These rare lesions are clinically silent. They are defined by the presence of abnormally large vascular cavities or sinusoids channels of variable size, with sharp walls, located inside but not invading the brain parenchyma. They can occur at any age, including the neonatal period. Most of the small lesions are located inside the brain parenchyma. No abnormal circulation can be demonstrated in angiography and CT scan can be helpful for diagnosis only in rare occasions. Magnetic resonance is the best exam to demonstrate the lesion. Despite the benign character some lesions may cause neurologic dysfunction when their removal may be difficult. Complete extirpation is the best treatment if the lesion is favorable located and is causing neurological dysfunction. Two cases of giant cavernomas with good outcome after total removal are present. Only three cases of giant cavernomas were reported in the literature

Simulation Validation from a Bayesian Perspective

Bayesian epistemology offers a powerful framework for characterizing scientific inference. Its basic idea is that rational belief comes in degrees that can be measured in terms of probabilities. The axioms of the probability calculus and a rule for updating (e.g., Bayesian conditionalization) emerge as constraints on the formation of rational belief. Bayesian epistemology has led to useful explications of notions such as confirmation. It thus is natural to ask whether Bayesian epistemology offers a useful framework for thinking about the inferences implicit in the validation of computer simulations. The aim of this chapter is to answer this question. Bayesian epistemology is briefly summarized and then applied to validation. Updating is shown to form a viable method for data-driven validation. Bayesians can also express how a simulation obtains prior credibility because the underlying conceptual model is credible. But the impact of this prior credibility is indirect since simulations at best provide partial and approximate solutions to the conceptual model. Fortunately, this gap between the simulations and the conceptual model can be addressed using what we call Bayesian verification. The final part of the chapter systematically evaluates the use of Bayesian epistemology in validation, e.g., by comparing it to a falsificationist approach. It is argued that Bayesian epistemology goes beyond mere calibration and that it can provide the foundations for a sound evaluation of computer simulations