Cortical motor network modulation: Common mechanisms parallel efficient motor integration in implicit motor learning in healthy subjects and subthalamic neurostimulation in Parkinson’s disease

On the one hand, the neuronal circuitry and connectivity of the large-scale motor network play an important role in many human cognitive functions, i. e. in implicit motor learning. On the other hand, alterations in connectivity of the motor network are also a hallmark in the pathophysiology of a variety of psychological and neurological diseases, such as Parkinson’s disease. Here, we set out to study the motor network activity (more exactly the cortical and spinal aspects of it) under two different aspects: in healthy controls during implicit motor learning and in Parkinson’s disease patients in the conditions ‘stimulation off’ and ‘stimulation on’. To this end, 12 healthy controls and 20 Parkinson’s disease patients performed externally paced right finger movements with simultaneous recordings of a 64-channel EEG and EMG of the forearm muscles. The healthy controls performed the serial reaction time task. Parkinson’s disease patients conducted the baseline of this task with only random trials in the two conditions ‘stimulation off’ and ‘stimulation on ‘. Cortical and muscular activity was analyzed by time-frequency movement-related spectral perturbations and by power spectral density and corticospinal synchronization was assessed by time-frequency cross-spectra coherence. Clinically, Parkinson’s disease patients improved significantly with deep brain stimulation, assessed by the Unified Parkinson’s Disease Rating Scale III score, the reaction time and the error ratio. Deep brain stimulation lead to an increased cortical beta-band movement-related desynchronization, which was topographically spread over a wider cortical area. Besides, in ‘stimulation off’ after finger tap we found a premature beta-band rebound of the corticomuscular coherence to the extensor digitorum over the primary sensorimotor cortex, which was suppressed with stimulation on. The healthy controls presented with significantly reduced reaction times in the ‘sequence blocks’ compared to ‘random blocks’. In ‘sequence blocks’, power spectral density increased mainly over the right posterior parietal cortex but also over a larger left-hemispheric cortical area in alpha and low beta band. Alpha and beta band movement-related desynchronization presented most pronounced over the bilateral prefrontal, fronto-central and central channels. The movement-related desynchronization was significantly modulated over the course of implicit motor learning. The present findings reveal the impressive modulation of the motor network activity including cortical activations and corticospinal synchronizations introduced by deep brain stimulation therapy of the subthalamic nucleus in Parkinson’s disease

Reverse Shock Emission Revealed in Early Photometry in the Candidate Short GRB 180418A

We present observations of the possible short GRB 180418A in $\gamma$-rays, X-rays, and in the optical. Early optical photometry with the TAROT and RATIR instruments show a bright peak ($\approx$ 14.2 AB mag) between $T+28$ and $T+90$ seconds that we interpret as the signature of a reversal shock. Later observations can be modeled by a standard forward shock model and show no evidence of jet break, allowing us to constrain the jet collimation to $\theta_j> 7^\circ$. Using deep late-time optical observations we place an upper limit of $r>24$ AB mag on any underlying host galaxy. The detection of the afterglow in the \textit{Swift} UV filters constrains the GRB redshift to $z<1.3$ and places an upper bound on the $\gamma$-ray isotropic equivalent energy $E_{\rm{\gamma,iso}} < 3 \times 10^{51}$ erg. The properties of this GRB (e.g. duration, hardness ratio, energetic, and environment) lie at the intersection between short and long bursts, and we can not conclusively identify its type. We estimate that the probability that it is drawn from the population of short GRBs is 10\%-30\%.Comment: Accepted por publication in Ap

Lymphatic vessels help mend broken hearts

Experiments on zebrafish show that the regeneration of the heart after an injury is supported by lymphatic vessels

Intravenous versus epidural analgesia to reduce the incidence of gastrointestinal complications after elective pancreatoduodenectomy (the PAKMAN trial, DRKS 00007784): study protocol for a randomized controlled trial

Background: Despite substantial improvements in surgical and anesthesiological practices leading to decreased mortality of less than 5 % at high-volume centers, pancreatic surgery is still associated with high morbidity rates of up to 50 %. Attention is increasingly directed toward the optimization of perioperative management to reduce complications and enhance postoperative recovery. Currently, two different strategies for postoperative pain management after pancreatoduodenectomy are being routinely used: patient-controlled intravenous analgesia and thoracic epidural analgesia. Evidence is lacking to assess which strategy entails fewer postoperative complications. Methods/design: The PAKMAN trial is designed as an adaptive, pragmatic, randomized, controlled, multicenter, open-label, superiority trial with two parallel study groups. A total of 370 patients scheduled for elective pancreatoduodenectomy will be randomized after giving written informed consent, and 278 patients are needed for analysis. Patients with chronic pancreatitis, severe chronic obstructive pulmonary disease (COPD), American Society of Anesthesiologists (ASA) physical status classification ≥ IV, or chronic pain syndrome will be excluded. The group A intervention includes intraoperative general anesthesia and postoperative patient-controlled intravenous analgesia; the group B intervention comprises combined intraoperative general anesthesia and epidural analgesia with postoperative epidural analgesia. The primary endpoint of this trial is a composite of the gastrointestinal complications (delayed gastric emptying, pancreatic fistula, biliary leak, gastrointestinal bleeding, and postoperative ileus) up to postoperative day 30. The aim is to investigate whether the frequency of gastrointestinal complications following pancreatoduodenectomy can be reduced by 15 % using postoperative, patient-controlled intravenous analgesia compared with epidural analgesia. Discussion: Several previous studies investigating the two different strategies for postoperative pain management have mainly focused on their effectiveness in pain control. However, the PAKMAN trial is the first to compare them with regard to their impact on the surgical endpoint “postoperative gastrointestinal complications” after pancreatoduodenectomy. Trial registration: German Clinical Trials Register, DRKS0000778

Fragilidades no apoio social à pessoa idosa: uma Revisão de Escopo

OBJETIVO: Identificar elementos caracterizadores da Síndrome da Insuficiência Familiar (SIF) na pessoa idosa que vive na comunidade. MÉTODO: Scoping Review, desenvolvida segundo Prisma-ScR Checklist, com busca de documentos em português, inglês e espanhol nas bases PUBMED, SCOPUS, APA-PSYCNET, CINAHL, LILACS e EMBASE, sem limite temporal. Critérios de elegibilidade/exclusão foram construídos a partir da estratégia PCC: a) População - pessoas acima de 60 anos e redes de apoio; b) Conceito - literatura sobre apoio social e suas fragilidades; e c) Contexto - estudos transversais e longitudinais, revisões, artigos teóricos, capítulos de livro, teses e dissertações, focados na população de idosos comunitários. 467 estudos tiveram títulos e resumos lidos por 2 pesquisadores independentes, selecionando-se 180 estudos para leitura integral. Um terceiro pesquisador independente atuou como juiz. 79 estudos compuseram o corpus da Revisão. RESULTADOS: a SIF surge da interação de fatores contextuais, relacionais e individuais da pessoa idosa e de quem a apoia ou deveria apoiá-la. Caracteriza-se pela discrepância entre demandas da pessoa idosa e a oferta de apoio social adequado, que pode (ou não) existir. Redes de apoio menos responsivas às demandas pessoa idosa não se ativam quando necessário ou se ativam, mas sem prover o apoio na qualidade e dimensões ideais, podendo comprometer o exercício da autonomia e independência. CONCLUSÃO: mudanças nos padrões populacionais de macronível têm contribuído para fragilização do suporte social às pessoas idosas. A identificação dos elementos que influenciam e caracterizam SIF possibilitará a avaliação e o desenvolvimento de políticas públicas e intervenções voltadas ao seu manejo. Palavras-chave: Pessoa idosa; Apoio social; Relações Familiares; Violência contra a Pessoa Idos

Is neoadjuvant chemotherapy followed by surgery the appropriate treatment for esophagogastric signet ring cell carcinomas? A systematic review and meta-analysis

BackgroundThe impact of neoadjuvant chemotherapy (nCTX) on survival and tumor response in patients with esophagogastric signet ring cell carcinoma (SRCC) is still controversial.MethodsTwo independent reviewers performed a systematic literature search in Medline, CENTRAL, and Web of Science including prospective and retrospective two-arm non-randomized and randomized controlled studies (RCTs). Data was extracted on overall survival (OS) and tumor regression in resected esophagogastric SRCC patients with or without nCTX. Survival data was analyzed using published hazard ratios (HR) if available or determined it from other survival data or survival curves. OS and histopathological response rates by type of tumor (SRCC vs. non-SRCC) were also investigated.ResultsOut of 559 studies, ten (1 RCT, 9 non-RCTs) were included in this meta-analysis (PROSPERO CRD42022298743) investigating 3,653 patients in total. The four studies investigating survival in SRCC patients treated with nCTX + surgery vs. surgery alone showed no survival benefit for neither intervention, but heterogeneity was considerable (HR, 1.01; 95% CI, 0.61–1.67; p = 0.98; I2 = 89%). In patients treated by nCTX + surgery SRCC patients showed worse survival (HR, 1.45; 95% CI, 1.21–1.74; p &lt; 0.01) and lower rate of major histopathological response than non-SRCC patients (OR, 2.47; 95% CI, 1.78–3.44; p &lt; 0.01).ConclusionThe current meta-analysis could not demonstrate beneficial effects of nCTX for SRCC patients. Histopathological response to and survival benefits of non-taxane-based nCTX seem to be lower in comparison to non-SRC esophagogastric cancer. However, certainty of evidence is low due to the scarcity of high-quality trials. Further research is necessary to determine optimal treatment for SRCC patients.Systematic Review Registrationhttps://www.crd.york.ac.uk/, PROSPERO (CRD42022298743)

Implementation and testing of the first prompt search for gravitational wave transients with electromagnetic counterparts

Aims. A transient astrophysical event observed in both gravitational wave (GW) and electromagnetic (EM) channels would yield rich scientific rewards. A first program initiating EM follow-ups to possible transient GW events has been developed and exercised by the LIGO and Virgo community in association with several partners. In this paper, we describe and evaluate the methods used to promptly identify and localize GW event candidates and to request images of targeted sky locations. Methods. During two observing periods (Dec 17 2009 to Jan 8 2010 and Sep 2 to Oct 20 2010), a low-latency analysis pipeline was used to identify GW event candidates and to reconstruct maps of possible sky locations. A catalog of nearby galaxies and Milky Way globular clusters was used to select the most promising sky positions to be imaged, and this directional information was delivered to EM observatories with time lags of about thirty minutes. A Monte Carlo simulation has been used to evaluate the low-latency GW pipeline's ability to reconstruct source positions correctly. Results. For signals near the detection threshold, our low-latency algorithms often localized simulated GW burst signals to tens of square degrees, while neutron star/neutron star inspirals and neutron star/black hole inspirals were localized to a few hundred square degrees. Localization precision improves for moderately stronger signals. The correct sky location of signals well above threshold and originating from nearby galaxies may be observed with ~50% or better probability with a few pointings of wide-field telescopes.Comment: 17 pages. This version (v2) includes two tables and 1 section not included in v1. Accepted for publication in Astronomy & Astrophysic

A multi-targeted approach to suppress tumor-promoting inflammation

Cancers harbor significant genetic heterogeneity and patterns of relapse following many therapies are due to evolved resistance to treatment. While efforts have been made to combine targeted therapies, significant levels of toxicity have stymied efforts to effectively treat cancer with multi-drug combinations using currently approved therapeutics. We discuss the relationship between tumor-promoting inflammation and cancer as part of a larger effort to develop a broad-spectrum therapeutic approach aimed at a wide range of targets to address this heterogeneity. Specifically, macrophage migration inhibitory factor, cyclooxygenase-2, transcription factor nuclear factor-κB, tumor necrosis factor alpha, inducible nitric oxide synthase, protein kinase B, and CXC chemokines are reviewed as important antiinflammatory targets while curcumin, resveratrol, epigallocatechin gallate, genistein, lycopene, and anthocyanins are reviewed as low-cost, low toxicity means by which these targets might all be reached simultaneously. Future translational work will need to assess the resulting synergies of rationally designed antiinflammatory mixtures (employing low-toxicity constituents), and then combine this with similar approaches targeting the most important pathways across the range of cancer hallmark phenotypes