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PurposeThe aim of this Intensive Care Medicine Rapid Practice Guideline (ICM‑RPG) was to formulate evidence‑based guidance for the use of dexmedetomidine for sedation in invasively mechanically ventilated adults in the intensive care unit (ICU).MethodsWe adhered to the methodology for trustworthy clinical practice guidelines, including use of the Grading of Recommendations Assessment, Development, and Evaluation approach to assess the certainty of evidence, and the Evidence-to-Decision framework to generate recommendations. The guideline panel comprised 28 international panelists, including content experts, ICU clinicians, methodologists, and patient representatives. Through teleconferences and web‑based discussions, the panel provided input on the balance and magnitude of the desirable and undesirable effects, the certainty of evidence, patients’ values and preferences, costs and resources, feasibility, acceptability, and research priorities.ResultsThe ICM‑RPG panel issued one weak recommendation (suggestion) based on overall moderate certainty of evidence: \"In invasively mechanically ventilated adult ICU patients, we suggest using dexmedetomidine over other sedative agents, if the desirable effects including a reduction in delirium are valued over the undesirable effects including an increase in hypotension and bradycardia\".ConclusionThis ICM-RPG provides updated evidence-based guidance on the use of dexmedetomidine for sedation in mechanically ventilated adults, and outlines uncertainties and research priorities.

In a growing economic and industrial development scenario, public policy can be used to encourage environment-friendly behaviour. In this context, it is a part of the Ecological ICMS, which is the VAT percentage of transfer raised by the States in favour of their municipalities, according to criteria established by law. In this paper, we seek to assess the contribution of the Ecological VAT in the State of Rio de Janeiro for the environmental development in this State. Therefore, of the 92 municipalities, data of budget expenses were collected for 87 of them (5 were excluded from analysis due to lack of information for some periods) in sanitation functions and environmental management from 2005 to 2012 and therefore the 4 years before and after the validity of the Ecological VAT (2009). From the collected data, the mean difference test was used (Wilcoxon). The hypothesis tested was that the institution of the Ecological VAT in the State of Rio de Janeiro generated an increase of municipal expenditures in sanitation functions and environmental management. The results indicated that the average spending on sanitation and environmental management of municipalities in the state of Rio de Janeiro before and after the ecological ICMS institution are, from a statistical point of view, different and that the this benefit has contributed to an increase of environmental investments there. Moreover, the average expense on environmental management showed the largest percentage increase in the periods before and after the start of the distribution of resources to the Ecological VAT, although spending on sanitation express a higher total sum. Num cenário de crescente desenvolvimento econômico-industrial, políticas públicas podem ser utilizadas para incentivar condutas ambientalmente corretas. Nesse contexto, insere-se o ICMS Ecológico, que corresponde ao repasse de percentual do ICMS arrecadado pelos estados em favor de seus municípios, conforme critérios estabelecidos em lei. Este trabalho busca avaliar a contribuição do ICMS Ecológico no âmbito do Rio de Janeiro para o desenvolvimento ambiental do estado. Para tanto, dos 92 municípios fluminenses, foram coletados dados das despesas orçamentárias de 87 (5 foram excluídos da análise em virtude da inexistência de informações em alguns períodos) nas funções saneamento e gestão ambiental do período de 2005 a 2012 e, portanto, dos 4 anos anteriores e posteriores à vigência do ICMS Ecológico (2009). A partir dos dados coletados, foi aplicado o teste de diferença de médias (Wilcoxon). A hipótese testada foi a de que a instituição do ICMS Ecológico no âmbito do estado do Rio de Janeiro gerou aumento das despesas municipais nas funções de saneamento e gestão ambiental. O resultado obtido indicou que as médias dos gastos com saneamento e gestão ambiental dos municípios antes e depois da instituição do ICMS Ecológico são, do ponto de vista estatístico, diferentes e que a instituição do benefício contribuiu para incremento de investimentos ambientais. Ademais, a média dos gastos com gestão ambiental foi a que apresentou maior aumento percentual nos períodos antes e despois do início da distribuição dos recursos do ICMS Ecológico, embora os gastos com saneamento expressem maior somatório total.  En un contexto de creciente desarrollo económico e industrial, las políticas públicas pueden ser utilizadas para incentivar conductas ambientalmente correctas. Este contexto, es parte del ICMS Ecológico, que corresponde con el porcentaje de pasar ICMS aplicado por los Estados en favor de sus municipios, de acuerdo con los criterios establecidos por la ley. En este trabajo, tratamos de evaluar la contribución del ICMS Ecológico bajo el Río de Janeiro para el desarrollo del medio ambiente en este estado. Por eso, los 92 municipios de Río de Janeiro, se recogen los datos de los gastos presupuestarios 87 (5 fueron excluidos del análisis debido a la falta de información en algunos períodos) en funciones de saneamiento y la gestión ambiental desde 2005 hasta 2012 y, por tanto, de 4 años antes y después de la validez del ICMS Ecológico (2009). A partir de los datos recogidos, se utilizó el test de diferencia de medias (Wilcoxon). La hipótesis probada fue que el establecimiento del ICMS Ecológico dentro de este estado genera un aumento de los gastos municipales en funciones de saneamiento y la gestión ambiental. El resultado obtenido indicó que las medidas de los gastos con saneamiento y la gestión ambiental de los municipios del estado de Río de Janeiro antes y después de la institución ICMS ecológico son desde un punto de vista estadístico, diferentes y que la institución de beneficio contribuyó al crecimiento de la inversión ambiental de esta entidad. Además, La medida con gestión ambiental fue que presento mayor incremento porcentual en los períodos antes y después de inicio de los recursos con el ICMS Ecológico, mismo que los gastos en saneamiento expresara suma total más alta.

Mitochondria are the respiratory organelles of eukaryotes and their evolutionary history is deeply intertwined with that of eukaryotes. The compartmentalization of respiration in mitochondria occurs within cristae, whose evolutionary origin has remained unclear. Recent discoveries, however, have revived the old notion that mitochondrial cristae could have had a pre-endosymbiotic origin. Mitochondrial cristae are likely homologous to the intracytoplasmic membranes (ICMs) used by diverse alphaproteobacteria for harnessing energy. Because the Mitochondrial Contact site and Cristae Organizing System (MICOS) that controls the development of cristae evolved from a simplified version that is phylogenetically restricted to Alphaproteobacteria (alphaMICOS), ICMs most probably transformed into cristae during the endosymbiotic origin of mitochondria. This inference is supported by the sequence and structural similarities between MICOS and alphaMICOS, and the expression pattern and cellular localization of alphaMICOS. Given that cristae and ICMs develop similarly, alphaMICOS likely functions analogously to mitochondrial MICOS by culminating ICM development with the creation of tubular connections and membrane contact sites at the alphaproteobacterial envelope. Mitochondria thus inherited a pre-existing ultrastructure adapted to efficient energy transduction from their alphaproteobacterial ancestors. The widespread nature of purple bacteria among alphaproteobacteria raises the possibility that cristae evolved from photosynthetic ICMs.

Brain-computer interface (BCI) can be used as a real-time bidirectional information gateway between the brain and machines. In particular, rapid progress in invasive BCI, propelled by recent developments in electrode materials, miniature and power-efficient electronics, and neural signal decoding technologies has attracted wide attention. In this review, we first introduce the concepts of neuronal signal decoding and encoding that are fundamental for information exchanges in BCI. Then, we review the history and recent advances in invasive BCI, particularly through studies using neural signals for controlling external devices on one hand, and modulating brain activity on the other hand. Specifically, regarding modulating brain activity, we focus on two types of techniques, applying electrical stimulation to cortical and deep brain tissues, respectively. Finally, we discuss the related ethical issues concerning the clinical application of this emerging technology.

The zona pellucida plays a crucial role in the process of fertilization to early embryonic development, including cellular arrangement and communication between blastomeres. However, little is known regarding the role of the zona pellucida in pre- and post-implantation embryonic development associated with gene expression. We investigated the effect of zona pellucida removal on pre- and post-implantation development of mouse embryos. After zona pellucida removal of two-cell stage embryos was performed by acid Tyrode's solution, which is commonly used for zona pellucida treatment, compaction occurred earlier in zona pellucida-free than zona pellucida-intact embryos. In addition, the expression of differentiation-related genes in the inner cell mass and trophectoderm was significantly altered in zona pellucida-free blastocyst compared with zona pellucida-intact embryos. After embryo transfer, the rate of implantation and live fetuses was lower in zona pellucida-free embryos than in control embryos, whereas the fetal weight at E17.5 was not different. However, placental weight significantly increased in zona pellucida-free embryos. RNA-sequencing analysis of the placenta showed that a total of 473 differentially expressed genes significantly influenced the biological process. The present study suggests that zona pellucida removal by acid Tyrode's solution at the two-cell stage not only disturbs the expression pattern of inner cell mass-/trophectoderm-related genes but affects the post-implantation development of mouse embryos. Overall, this study provides deeper insight into the role of the zona pellucida during early embryonic development and the viability of post-implantation development. Summary Sentence Zona pellucida removal by acid Tyrode's solution affects the inner cell mass/trophectoderm differentiation; a lower fetal rate, higher placental weight, and a total of 473 differentially expressed genes during post-implantation development in mice. Graphical Abstract

Este trabalho analisa se houve mudança na participação de diferentes setores dos territórios de planejamento de Sergipe por meio da arrecadação do ICMS no período 2016-2020. Para tanto, foi utilizado o método diferencial-estrutural com a mudança proposta por Esteban-Marquillas (1972). Os principais resultados indicam que, apesar de a região da Grande Aracaju ainda ser o principal motor produtivo do estado, houve expressiva interiorização de alguns setores, como agricultura e comércio, que se tornaram especializados e competitivos em diversos territórios do planejamento do estado. A indústria e os serviços, por sua vez, apesar de ainda apresentarem vantagem competitiva na maioria dos territórios, vêm perdendo seu grau de especialização ao longo do período.

The aim of these guidelines is to provide evidence‑based guidance for temperature control in adults who are comatose after resuscitation from either in-hospital or out-of-hospital cardiac arrest, regardless of the underlying cardiac rhythm. These guidelines replace the recommendations on temperature management after cardiac arrest included in the 2021 post-resuscitation care guidelines co-issued by the European Resuscitation Council (ERC) and the European Society of Intensive Care Medicine (ESICM). The guideline panel included thirteen international clinical experts who authored the 2021 ERC-ESICM guidelines and two methodologists who participated in the evidence review completed on behalf of the International Liaison Committee on Resuscitation (ILCOR) of whom ERC is a member society. We followed the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach to assess the certainty of evidence and grade recommendations. The panel provided suggestions on guideline implementation and identified priorities for future research. The certainty of evidence ranged from moderate to low. In patients who remain comatose after cardiac arrest, we recommend continuous monitoring of core temperature and actively preventing fever (defined as a temperature > 37.7 °C) for at least 72 h. There was insufficient evidence to recommend for or against temperature control at 32–36 °C or early cooling after cardiac arrest. We recommend not actively rewarming comatose patients with mild hypothermia after return of spontaneous circulation (ROSC) to achieve normothermia. We recommend not using prehospital cooling with rapid infusion of large volumes of cold intravenous fluids immediately after ROSC.

Based on the continuous change of the market and the transformation of consumer demand, traditional embroidery technology is urgently in need of reform and innovation. This paper applies the topological structure to the computerized embroidery machine, which enables the mechanization and digitization of traditional embroidery. This paper employs the ICM method to concentrate on the topological level of the structure, utilizing the strategies of “material optimization,” “cross-section optimization,” and “shape optimization” to identify its continuity and microprocessibility and to incorporate the topological variables into the overall structure. We separate the low-level design variables from the topological variables, thereby creating more independent design variables. The structure of the presser foot and needle bar mechanism of the embroidery machine is optimized based on ICM topology. Researchers conduct simulation experiments on the optimized virtual prototype of the embroidery machine. A multidimensional analysis of embroidery products produced by the embroidery machine optimized based on ICM topology was conducted through a questionnaire survey. Consumers purchased 68.43% of the products in the category of “daily necessities,” 66.23% evaluated the practicality of the products, and 71.24% purchased the products because they “favor the traditional embroidery craftsmanship.” The above data shows that products made according to the method described in this paper are practical. The data mentioned above indicates that embroidery products created using the method outlined in this paper are useful in everyday life and do not damage traditional embroidery stitches.

Background An analysis of colorectal cancer epithelial cells showed two intrinsic subtypes called iCMS2 and iCMS3, in addition to the bulk consensus subtypes (CMS1-4). The intrinsic subtypes can be prognostically important and may prove predictive of response to treatment. We present a method for calculating the iCMS subtypes that is robust to technical variation, is designed for single-sample applications and is highly prognostic in unseen data. Results A single-sample classifier (SSC) was developed based on non-parametric correlation similarity with gene expression centroids, synthetically created by resampling samples with known iCMS classes from public datasets that have been used in the derivation of the iCMS classification. We selected the subset of iCMS genes (N = 201) with the strongest epithelial expression in colorectal cancer, aiming to reduce unrelated, non-epithelial variation. The SSC calculates the most likely iCMS class based on the distribution of the classes of the nearest centroids with either an absolute cutoff or K-nearest-neighbors voting. In the unseen GTR cohort, SSC nearest-class accuracy was 88% vs the previously published NTP predictor, which reached 75.4% without correction. Similarly, nearest-class accuracy was 90% in the public E-MTAB-12862. In extended tests simulating various perturbations, calls remained stable with extensive noise, partial gene loss, low purity, and synthetic iCMS2/3 admixtures. In addition, the SSC was applied to data from the VELOUR trial, for which reference iCMS calls were also available. The SSC iCMS was prognostic for OS in iCMS2 vs iCMS3 (p < 0.00001) and performed at least as well as the reference iCMS, which was also prognostic (p = 0.0001). In the E-MTAB-12862 data, the SSC was prognostic in metastatic patients (N = 114), and in a multivariable model including stage, grade, age at diagnosis (all of which were prognostic) and CMS across the full cohort (N = 1062). The previously published NTP was not prognostic in this cohort. Conclusions The iCMS-SSC enables robust, single-sample iCMS calling without batch correction, improves resilience to technical/biological perturbations, and retains prognostic signal in clinical-trial data. Its epithelial gene focus and multi-centroid, rank-based design support deployment for screening, stratification, and retrospective biomarker analyses. Computation is significantly faster than NTP and parallel-ready. An open-source R implementation is provided. ( https://github.com/CRCrepository/iCMS.SSC ).