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Abstract Local skin flaps are frequently employed for wound closure to address surgical, traumatic, congenital, or oncologic defects. (1) Despite their clinical utility, skin flaps may fail due to inadequate perfusion, ischemia/reperfusion injury (IRI), excessive cell death, and associated inflammatory response. (2) All of these factors contribute to skin flap necrosis in 10–15% of cases and represent a significant surgical challenge. (3, 4) Once flap necrosis occurs, it may require additional surgeries to remove the entire flap or repair the damage and secondary treatments for infection and disfiguration, which can be costly and painful. (5) In addition to employing appropriate surgical techniques and identifying healthy, well-vascularized tissue to mitigate the occurrence of these complications, there is growing interest in exploring cell-based and pharmacologic augmentation options. (6) These agents typically focus on preventing thrombosis and increasing vasodilation and angiogenesis while reducing inflammation and oxidative stress. Agents that modulate cell death pathways such as apoptosis and autophagy have also been investigated. (7) Implementation of drugs and cell lines with potentially beneficial properties have been proposed through various delivery techniques including systemic treatment, direct wound bed or flap injection, and topical application. This review summarizes pharmacologic- and cell-based interventions to augment skin flap viability in animal models, and discusses both translatability challenges facing these therapies and future directions in the field of skin flap augmentation.

The RNA exosome is an evolutionarily-conserved ribonuclease complex critically important for precise processing and/or complete degradation of a variety of cellular RNAs. The recent discovery that mutations in genes encoding structural RNA exosome subunits cause tissue-specific diseases makes defining the role of this complex within specific tissues critically important. Mutations in the RNA exosome component 3 (EXOSC3) gene cause Pontocerebellar Hypoplasia Type 1b (PCH1b), an autosomal recessive neurologic disorder. The majority of disease-linked mutations are missense mutations that alter evolutionarily-conserved regions of EXOSC3. The tissue-specific defects caused by these amino acid changes in EXOSC3 are challenging to understand based on current models of RNA exosome function with only limited analysis of the complex in any multicellular model in vivo. The goal of this study is to provide insight into how mutations in EXOSC3 impact the function of the RNA exosome. To assess the tissue-specific roles and requirements for the Drosophila ortholog of EXOSC3 termed Rrp40, we utilized tissue-specific RNAi drivers. Depletion of Rrp40 in different tissues reveals a general requirement for Rrp40 in the development of many tissues including the brain, but also highlight an age-dependent requirement for Rrp40 in neurons. To assess the functional consequences of the specific amino acid substitutions in EXOSC3 that cause PCH1b, we used CRISPR/Cas9 gene editing technology to generate flies that model this RNA exosome-linked disease. These flies show reduced viability; however, the surviving animals exhibit a spectrum of behavioral and morphological phenotypes. RNA-seq analysis of these Drosophila Rrp40 mutants reveals increases in the steady-state levels of specific mRNAs and ncRNAs, some of which are central to neuronal function. In particular, Arc1 mRNA, which encodes a key regulator of synaptic plasticity, is increased in the Drosophila Rrp40 mutants. Taken together, this study defines a requirement for the RNA exosome in specific tissues/cell types and provides insight into how defects in RNA exosome function caused by specific amino acid substitutions that occur in PCH1b can contribute to neuronal dysfunction.

Introdução/Objetivos: As infecções do trato urinário (ITU) são em sua maioria causadas por bactérias da ordem Enterobacterales, principalmente por Escherichia coli uropatogênica (UPEC). Esta linhagem apresenta fatores de virulência que a torna capaz de colonizar e infectar o trato urinário. Apesar da maioria dos quadros de ITU ser solucionado com terapia antimicrobiana, linhagens de UPEC resistentes aos antimicrobianos representam uma séria ameaça a saúde pública. Este trabalho teve por objetivo avaliar a prevalência de Escherichia coli em uroculturas, bem como seu perfil de suscetibilidade aos antimicrobianos e os fenótipos de resistência. Métodos: Trata-se de um estudo descritivo, retrospectivo que analisou uroculturas de paciente ambulatoriais e hospitalares, no período de janeiro de 2020 a dezembro de 2021. Este estudo foi aprovado pelo Comitê de Ética em Pesquisa com Seres Humanos. Resultados: Das uroculturas analisadas, 858 foram positivas para bactérias, sendo a Escherichia coli a espécie predominante com 27,2% (n = 233) dos isolados. Das 858 uroculturas, 608 foram provenientes de pacientes hospitalizados, sendo 124 (20,4%) isolados de UPEC neste grupo e 250 foram de pacientes ambulatoriais, com 109 (43,6%) isolados de UPEC. Observou-se o seguinte perfil de resistência aos antimicrobianos das linhagens isoladas nas amostras hospitalares e ambulatoriais, respectivamente: 65% e 32% para Ampicilina, 56% e 26% para Amoxicilina + Ácido clavulânico, 50% e 26 % para Ciprofloxacino, 42% e 33% para Sulfazotrim, 38% e 20% para Cefepime, 17% e 8% para Gentamicina e 2,5% e 0,4% para ertapenem, Meropenem e Imipenem. Das linhagens de Escherichia coli resistentes aos beta-lactâmicos, 43 (18%) apresentaram fenótipos de resistência do tipo beta lactamase de espectro ampliado (ESBL) e 7 (3%) foram produtoras de carbapenemases. Conclusão: Escherichia coli é a espécie mais isolada de uroculturas. UPEC apresentou taxas de resistência a todos os antimicrobianos testados, produzindo fenótipos do tipo ESBL e carbapenemase, principalmente em ambiente hospitalar.

The environmental transition, and more specifically the energy transition, represents today a new challenge for territories and our Planet Earth, to the understanding of which geographers contribute with their analytical tools, and by participating in interdisciplinary research institutions, such as the Institute of Environmental Transition at the Sorbonne University (SU-ITE). After recalling the multiple definitions of transition, and the approaches that can be associated with it, the objectives of SU-ITE are presented. An example of the contribution of geographers to this institute is presented, the analysis and mapping of the discourses of the nations having concluded the Paris agreement on climate change. These methods prove to be relevant for understanding the new world divisions and for anticipating the limits of the application of this agreement, 5 years after COP 21.

Este estudo tem como objetivo analisar como a ideia de meritocracia na educação acaba reforçando a desigualdade na medida em que opta por critérios de avaliação limitados. Trata-se de uma pesquisa exploratória de caráter hermenêutico e teórico-bibliográfico ancorado nos escritos de Nussbaum (2012; 2014; 2015), Bachelard (1996), Dubet (2004), entre outros autores. Busca responder à seguinte questão: por que processos avaliativos educacionais baseados em medições e meritocracia acabam justificando a desigualdade e promovendo a injustiça social? Os resultados expõem que as avaliações baseadas em critérios meritocráticos não são capazes de medir todas as esferas da vida, tornando-se limitados ao propor o que as pessoas são capazes de ser e fazer. Tendo em vista a necessidade de se criar uma escola democrática e justa, conclui-se que a teoria das capacidades são um meio de buscar a individualidade e habilidades dos sujeitos, agregando na apreensão de conhecimento e na auto reflexão.

Introduction: at present, smoking appears as one of the main health problems worldwide. Objective: to characterize the people who smoke psycho-socially in La Palma municipality during 2017. Method: an observational, descriptive and cross-sectional study was carried out in the health area belonging to Pedro Borras Astorga University Polyclinic; the target group consisted of 6625 patients dispensed as smokers, the sample was chosen by simple random sampling consisting of 863 smokers who met the inclusion criteria. Theoretical, empirical and descriptive statistics which included absolute and relative frequency were applied. Results: 59,7 % of smokers were male, 71,3 % belonged to the age group of 25 to 59 years old, 57,3% only completed elementary school, the marital status of divorced-separated prevailed with 40,0 %; there was a 53,8 % average dependence on nicotine addiction, 91,0 % was motivated to smoke to reduce stress and 75,7 % of smokers presented the risk factors of living into dysfunctional families. Conclusions: smoking is a health problem, it influences on the morbidity and mortality rates of the population of La Palma municipality, consequently prevention and control actions should be taken to diminish the risk factors, to achieve quality of life in the population exposed to this risky addiction.

Background: Radiation-induced fibrosis (RIF) is a debilitating sequelae of radiation therapy that has been shown to improve with topical treatment with the iron chelator deferoxamine (DFO). We investigated whether DFO exerts this effect through attenuation of ferroptosis, a recently described iron-dependent pathway of cell death., Methods: Adult C57BL/6J mice were treated with topical DFO or ferrostastin-1 (Fer-1) and irradiated with 30 Grays of ionizing radiation to the dorsal skin to promote development of chronic RIF. Immunofluorescent staining with 4-hydroxynonenal (4-HNE) antibody was carried out directly following irradiation to assess ferroptosis activity. Perfusion testing with laser Doppler was performed throughout the healing interval. Eight weeks following radiation, dorsal skin was harvested and analyzed histologically and biomechanically., Results: Immunohistochemical staining demonstrated lower presence of 4-HNE in non-irradiated skin, DFO-treated skin, and Fer-1-treated skin compared to irradiated, untreated skin. DFO resulted in histological measurements (dermal thickness and collagen content) that resembled normal skin, while Fer-1 treatment yielded less significant improvements. These results were mirrored by analysis of extracellular matrix ultrastructure and biomechanical testing, which recapitulated the ability of topical DFO treatment to alleviate RIF across these parameters while Fer-1 resulted in less notable improvement. Finally, perfusion levels in DFO treated irradiated skin were similar to measurements in normal skin, while Fer-1 treatment did not impact this feature., Conclusions: Ferroptosis contributes to the development of RIF and attenuation of this process leads to reduced skin injury. DFO further improves RIF through additional enhancement of perfusion not seen with Fer-1., Competing Interests: Competing interests Dr. Michael Longaker holds equity in TauTona Group, the DFO cream supplier. Dr. Derrick Wan and Dr. Michael Longaker hold a patent for DFO conditioning in irradiated tissue. Additional Declarations: Competing interest reported. Dr. Michael Longaker holds equity in TauTona Group, the DFO cream supplier. Dr. Derrick Wan and Dr. Michael Longaker hold a patent for DFO conditioning in irradiated tissue.