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As úlceras de pressão representam um problema de alta relevância na prática médica. Os pacientes acometidos apresentam pior evolução clínica, exigindo maior tempo de internamento e gerando maiores custos. Este artigo de revisão tem por objetivo apresentar e discutir, com base em evidências científicas, as medidas que visam à prevenção das úlceras de pressão. As recomendações incluídas neste artigo são baseadas em dados extraídos a partir de revisão bibliográfica de livros técnicos e artigos científicos obtidos nas seguintes bases de dados: 1. PubMed, 2. SciELO e 3. UpToDate Inc. Foram priorizados artigos publicados nos últimos cinco anos e eles foram avaliados criticamente, de modo a objetivar a certificação de que os métodos e os resultados apresentados eram válidos. Os pesquisadores incluíram, ainda, no estudo outros artigos consagrados pela literatura, com data de publicação superior a cinco anos, cujos dados foram analisados criticamente de modo a somente incluir informações atemporais.

INTRODUÇÃO: Indivíduos com síndrome coronariana aguda e menores taxas de filtração glomerular são associados a piores desfechos. Apesar de diversas fórmulas terem sido propostas para estimar a taxa de filtração glomerular, ainda não está definido qual delas teria o melhor poder de predição dos desfechos em pacientes idosos com síndrome coronariana aguda. OBJETIVO: Comparar três fórmulas para a taxa de filtração glomerular a fim de predizer a mortalidade intra-hospitalar e outros desfechos. MÉTODOS: Coorte retrospectiva intra-hospitalar com idosos acometidos com síndrome coronariana aguda, admitidos em Unidade de Terapia Intensiva Cardiológica, no período de 1 de janeiro a 31 de dezembro de 2013. Foram utilizadas as fórmulas Cockcroft-Gault, MDRD e CKD-EPI para o cálculo da taxa de filtração glomerular. RESULTADOS: Foram analisados 122 indivíduos, 51,6% do gênero masculino, com média de 73,5 anos. A mortalidade foi de 19,6%. As médias da taxa de filtração glomerular para Cockcroft-Gault, MDRD e CKD-EPI foram, respectivamente, de 70,24 mL/min. (± 33,35), 74,70 mL/min./1,73 m2 (± 30,91) e 69,79 mL/min./1,73 m2 (± 23,82). Verificou-se a relação de todas as fórmulas com óbito (p = 0,001 versus 0,028 versus 0,028), uso de antibióticos (p = 0,002 versus < 0,001 versus 0,001) e hemodiálise (p ≤ 0,001 versus 0,003 versus 0,003). A fórmula Cockcroft-Gault teve maior área sob a curva pelo método ROC (0,701 versus 0,634 versus 0,639) e foi a única com significância estatística (IC95% 0,579 - 0,822, p = 0,006) para mortalidade intra-hospitalar. CONCLUSÃO: A Cockcroft-Gault foi a fórmula com melhor acurácia para predizer mortalidade.

Objective The market for smartphone apps tracking menstrual cycles has expanded in recent years. These apps market themselves as empowering users to achieve their reproductive goals and maximize the chance of pregnancy. This paper presents the first open-access quantification of menstrual tracking app downloads globally, covering both the Global North and South. We also explore macro and micro-level reasons for app usage, testing national associations with downloads and analyzing user reviews. Methods We use data on app installations, reviews, and ratings from the Google Play Store and Apple App Store to estimate global app downloads using a Bayesian model. We perform regressions to test for national predictors of use, and multilingual topic models to analyze/cluster reviews left by users to understand individual reasons for use. Results We find that the majority of downloads are for three apps: Clue, Flo, and Period Tracker. Higher modern contraceptive prevalence and internet access are associated with more downloads, while low-income countries tend to have fewer. In low-income countries, a higher unmet need for family planning and total fertility rate are associated with more downloads. Individual reviews reveal the most common reasons for use are menstrual cycle tracking, achieving a pregnancy, community engagement, and avoiding pregnancy. Conclusion Existing research on menstrual tracking apps is largely confined to the Global North, but our study finds the use of these apps to be as prevalent throughout the Global South. Future research needs to urgently understand the implications these apps could have in a diversity of contexts.

Abstract The CMS detector, including its muon system, has been operating at the CERN LHC in increasingly challenging conditions for about 15 years. The muon detector was designed to provide excellent triggering and track reconstruction for muons produced in proton–proton collisons at an instantaneous luminosity ( $$\mathcal {L}$$ L ) of $$1 \times 10^{34}$$ 1 × 10 34 cm $$^{-2}$$ - 2 s $$^{-1}$$ - 1 . During the Run 2 data-taking period (2015–2018), the LHC achieved an instantaneous luminosity of twice its design value, resulting in larger background rates and making the efficient detection of muons more difficult. While some backgrounds result from natural radioactivity, cosmic rays, and interactions of the circulating protons with residual gas in the beam pipe, the dominant source of background hits in the muon system arises from proton–proton interactions themselves. Charged hadrons leaving the calorimeters produce energy deposits in the muon chambers. In addition, high-energy particles interacting in the hadron calorimeter and forward shielding elements generate thermal neutrons, which leak out of the calorimeter and shielding structures, filling the CMS cavern. We describe the method used to measure the background rates in the various muon subsystems. These rates, in conjunction with simulations, can be used to estimate the expected backgrounds in the High-Luminosity LHC. This machine will run for at least 10 years starting in 2029 reaching an instantaneous luminosity of $$\mathcal {L} = 5 \times \text {10}^\text {34}\,\text {cm}^\text {-2}\,\text {s}^\text {-1}$$ L = 5 × 10 34 cm -2 s -1 and increasing ultimately to $$\mathcal {L} = 7.5 \times \text {10}^\text {34}\,\text {cm}^\text {-2}\,\text {s}^\text {-1}$$ L = 7.5 × 10 34 cm -2 s -1 . These background estimates have been a key ingredient for the planning and design of the muon detector upgrade.

Arrhythmogenic cardiomyopathy is a severe genetic heart muscle disease characterized by fibro-fatty replacement of the myocardium. Pathogenic variants causal for this disease are mainly located in desmosomal genes, including desmoplakin (DSP). Renal epithelial cells were isolated from a patient carrying the heterozygous c.817C>T (p.Q273*, nonsense) pathogenic variant in DSP, and subsequently reprogrammed using the Cytotune®-iPS 2.0 Sendai Reprogramming Kit. An isogenic control line was generated using CRISPR/Cas9 genome editing. The resulting induced pluripotent stem cell lines were characterized and displayed the required traits for in vitro disease modeling.

Abstract The variability in response to conventional prostate cancer (PC) therapies, coupled with the emergent issue of drug resistance, underscores the critical need for innovative treatment strategies. Aerobic physical exercise reduced incidence of several cancers, but the mechanism underlying these effects associated the nanoemulsion not fully understood. The application of a lipid nanoemulsion (LDE) delivery system for docetaxel (DTX), showing marked enhancement in therapeutic efficacy when combined with aerobic physical exercise. This novel intervention potentiates the antitumor activity of LDE-delivered DTX by augmenting nanoparticle internalization and inducing cell cycle arrest. Our findings reveal that this synergistic treatment not only significantly reduces prostate weight and mitigates adenocarcinoma proliferation but also attenuates anti-apoptotic BCL-2 protein expression. Concurrently, it elevates pro-apoptotic proteins and diminishes inflammatory markers. Metabolic profiling of the combined therapy group disclosed additional benefits, such as reduced lipid and plasma glucose levels. Collectively, our data illuminate the profound impact of integrating LDE-mediated DTX delivery with structured physical exercise, which together spearhead a dual-front assault on PC. This multimodal approach heralds a new paradigm in PC management, accentuating the promise of combined pharmacological and non-pharmacological interventions to elevate tumor suppressor protein activity and refine patient outcomes.

The rapid growth of the global population, economy, and urbanization is significantly increasing energy consumption, necessitating the integration of renewable energy sources. This integration presents challenges that demand innovative solutions to maintain grid stability and efficiency. Smart grids offer enhanced reliability, efficiency, sustainability, and bi-directional communication. However, the reliance on advanced technologies in smart grids introduces vulnerabilities, particularly concerning adversarial attacks. This paper addresses two critical issues in smart grid fault prediction: the vulnerability of machine learning models to adversarial attacks and the operational challenges posed by false alarms. We propose a Bayesian Neural Network (BNN) framework for fault zone prediction that quantifies uncertainty in predictions, enhancing robustness and reducing false alarms. Our BNN model achieves up to 0.958 accuracy and 0.960 precision in fault zone prediction. To counter adversarial attacks, we developed an uncertainty-based detection scheme that leverages prediction uncertainty. This framework distinguishes between normal and adversarial data using predictive entropy and mutual information as metrics. It detects complex white-box adversarial attacks, which are challenging due to attackers’ detailed knowledge of the model, with a mean accuracy of 0.891 using predictive entropy and 0.981 using mutual information. The model’s performance, combined with minimal computational overhead, underscores its practicality and robustness for enhancing smart grid security.

Abstract Type T Large Granular Lymphocyte Leukemia (T-LGLL) is a chronic disorder characterized by the abnormal proliferation of clonal cytotoxic T cells. The intriguing association of T-LGLL with autoimmune and inflammatory diseases, the most prominent example being rheumatoid arthritis, raises questions about the underlying pathophysiologic relationships between these disorders which share several biological and clinical features, most notably neutropenia, which is considered as a clinical hallmark. Recent progress in molecular genetics has contributed to a better understanding of pathogenetic mechanisms, thus moving our knowledge in the field of LGL leukemias forward. Focusing on the constitutive activation of STAT3 pathway and the well-established role of STAT3 mutations in T-LGLL, we herein discuss whether the T cell clones occurring in comorbid conditions are the cause or the consequence of the immune-inflammatory associated events. Overall, this review sheds light on the intricate relationships between inflammation and cancer, emphasizing the importance of the STAT3 gene and its activation in the pathophysiology of these conditions. Gaining a deeper understanding of these underlying mechanisms seeks to pave the way for the development of novel targeted therapies for patients affected by inflammation-related cancers.

IntroductionGlioblastoma (grade IV) is the most aggressive primary brain tumor in adults, representing one of the biggest therapeutic challenges due to its highly aggressive nature. In this study, we investigated the impact of millimeter waves on tridimensional glioblastoma organoids derived directly from patient tumors. Our goal was to explore novel therapeutic possibilities in the fight against this challenging disease.MethodsThe exposure setup was meticulously developed in-house, and we employed a comprehensive dosimetry approach, combining numerical and experimental methods. Biological endpoints included a global transcriptional profiling analysis to highlight possible deregulated pathways, analysis of cell morphological changes, and cell phenotypic characterization which are all important players in the control of glioblastoma progression.Results and discussionOur results revealed a significant effect of continuous millimeter waves at 30.5 GHz on cell proliferation and apoptosis, although without affecting the differentiation status of glioblastoma cells composing the organoids. Excitingly, when applying a power level of 0.1 W (Root Mean Square), we discovered a remarkable (statistically significant) therapeutic effect when combined with the chemotherapeutic agent Temozolomide, leading to increased glioblastoma cell death. These findings present a promising interventional window for treating glioblastoma cells, harnessing the potential therapeutic benefits of 30.5 GHz CW exposure. Temperature increase during treatments was carefully monitored and simulated with a good agreement, demonstrating a negligible involvement of the temperature elevation for the observed effects. By exploring this innovative approach, we pave the way for improved future treatments of glioblastoma that has remained exceptionally challenging until now.

Background: Dengue virus (DENV) causes an important disease and directly affects public health, being the arbovirus that presents the highest number of infections and deaths in the Western Brazilian Amazon. This virus is divided into 4 serotypes that have already circulated in the region. Methodology: Molecular characterization of a cohort containing 841 samples collected from febrile patients between 2021 and 2023 was analyzed using a commercial kit to detect the main arboviruses circulating in Brazil: Zika, DENV-1, DENV-2, DENV-3, DENV-4 and, Chikungunya. Subsequently, Sanger sequencing was performed for positive samples. Results: The cohort detected 162 positive samples, 12 for DENV-1 and 150 identified as DENV-2, indicating co-circulation of serotypes. The samples were subjected to sequencing and the analysis of the sequences that obtained good quality revealed that 5 samples belonged to the V genotype of DENV-1 and 46 were characterized as DENV-2 Cosmopolitan genotype—lineage 5. Conclusion: The results allowed us to identify for the first time the Cosmopolitan genotype in Rondônia, Brazilian Western Amazon, and its fast spread dispersion.

The design of micro-finned tube heat exchangers is a complex task due to intricate geometry, heat transfer goals, material selection, and manufacturing challenges. Nowadays, mathematical models provide valuable insights, aid in optimization, and allow us to explore various design parameters efficiently. However, existing empirical models often fall short in facilitating an optimal design because of their limited accuracy, sensitivity to assumption, and context dependency. In this scenario, the use of Machine and Deep Learning (ML and DL) methods can enhance accuracy, manage nonlinearity, adjust to varying conditions, decrease dependence on assumptions, automatically extract pertinent features, and provide scalability. Indeed, ML and DL techniques can derive valuable insights from datasets, contributing to a comprehensive understanding. By means of multiple ML and DL methods, this paper addresses the challenge of estimating key parameters in micro-finned tube heat exchangers such as the heat transfer coefficient (HTC) and frictional pressure drop (FPD). The methods have been trained and tested using an experimental dataset consisting of over a thousand data points associated with flow condensation, involving various tube geometries. In this context, the Artificial Neural Network (ANN) demonstrates superior performance in accurately estimating parameters with MAEs in the range below 4.5% for both HTC and FPD. Finally, recognizing the importance of comprehending the internal mechanisms of the black-box ANN model, the paper explores its interpretability aspects.

Abstract Chemotherapy resistance is considered one of the main causes of tumor relapse, still challenging researchers for the identification of the molecular mechanisms sustaining its emergence. Here, we setup and characterized chemotherapy-resistant models of Medulloblastoma (MB), one of the most lethal pediatric brain tumors, to uncover targetable vulnerabilities associated to their resistant phenotype. Integration of proteomic, transcriptomic and kinomic data revealed a significant deregulation of several pathways in resistant MB cells, converging to cell metabolism, RNA/protein homeostasis, and immune response, eventually impacting on patient outcome. Moreover, resistant MB cell response to a large library of compounds through a high-throughput screening (HTS), highlighted nucleoside metabolism as a relevant vulnerability of chemotolerant cells, with peculiar antimetabolites demonstrating increased efficacy against them and even synergism with conventional chemotherapeutics. Our results suggest that drug-resistant cells significantly rewire multiple cellular processes, allowing their adaptation to a chemotoxic environment, nevertheless exposing alternative actionable susceptibilities for their specific targeting.

Increasing plastic contamination poses a serious threat to marine organisms. Microplastics (MPs) ingestion can represent a risk for the organism itself and for the ultimate consumer. Through the analysis of the gastrointestinal tract, coupled with stable isotope analysis on the muscle tissue, this study provides insights into the relationship between MPs pollution and ecology in two commercial marine species caught in the Central Tyrrhenian Sea: Aristaeomorpha foliacea and Parapenaeus longirostris. Stable isotope analysis was conducted to determine the trophic position and the trophic niche width. The gastrointestinal tracts were processed, and the resultant MPs were analysed under FT-IR spectroscopy to estimate the occurrence, abundance, and typology of the ingested MPs. The trophic level of the species was similar (P. longirostris TP = 3 ± 0.10 and A. foliacea TP = 3.1 ± 0.08), with an important trophic niche overlap, where 38% and 52% of P. longirostris and A. foliacea has ingested MPs, respectively. Though species-level differences may not be evident regarding MP’s abundance per individual, a high degree of dissimilarity was noted in the typologies of ingested particles. This research provides valuable insights into how MPs enter marine trophic webs, stressing that isotopic niche analysis should be combined with other methods to explain in detail the differences in MPs ingestion.

Abstract Hepatitis Delta is a disease caused by exposure to hepatitis B (HBV) and hepatitis D (HDV) viruses, usually with a more severe clinical outcome when compared to an HBV monoinfection. To date, the real prevalence of HDV infection is underestimated and detection methods are poorly available, especially in more endemic regions. Therefore, a one-step RT-qPCR method for quantification of HDV-RNA was developed. Biological samples were selected between 2017 and 2023 from patients at the Ambulatório Especializado em Hepatites Virais of the Centro de Pesquisa em Medicina Tropical de Rondônia and Serviço de Assistência Especializada and underwent the test developed by this study and a second quantitative RT-qPCR assay. The slope of the initial quantitative assay was − 3.321 with an efficiency of 100.04% and amplification factor equal to 2. Analysis of the repeatability data revealed a Limit of Quantification of 5 copies/reaction and Limit of Detection (95%) of 2.83 copies per reaction. In the diagnostic sensitivity tests, there was an accuracy of 97.37% when compared to the reference test. This assay proved to be highly efficient and reproducible, making it a valuable tool to monitor hepatitis Delta patients and assess the risk of disease progression, as well as the effectiveness of treatment.

Glyphosate and glufosinate are among the most widely used pesticides in agriculture worldwide. Their extensive use leads to the presence of their residues on crops and in the surrounding environment. Beehives, bees, and apiculture products can represent potential sources for the accumulation of these substances and their metabolites, and the consequences for bee health, as well as the level of risk to human health from consuming contaminated food, are still unclear. Furthermore, information on the contamination levels of honey and other beehive products by these compounds remains poorly documented. This study is part of a broader research effort aimed at developing specific analytical methods for monitoring the level of these contaminants in bee products. The methodology employed enabled the acquisition of preliminary information concerning the levels of glyphosate and glufosinate contamination in honey samples obtained from various retailers in Italy to assess compliance with the limits established by Regulation 293/2013. The liquid chromatography tandem mass spectrometry analysis of the 30 honey samples revealed quantifiable levels of glyphosate in eight samples, with contamination ranging from 5.4 to 138.5 ng/g. Notably, one sample of the wildflower type showed residue levels nearly three times the maximum residue limit. Additionally, trace levels of glyphosate contamination were detected in another ten samples. It is noteworthy that glufosinate and its metabolites were not detected in any of the analyzed samples within the established method’s detection ranges.

No contexto de preocupações sobre a densidade da produção de conhecimentos, o presente ensaio teve como objetivo sistematizar uma reflexão sobre abordagens teórico-conceituais para investigar dimensões institucionais colocadas em ação em análises de continuidades/mudanças das Políticas Públicas de Esporte e Lazer (PPELs). Sem a pretensão de realizar um estudo de revisão, mas inspirados em movimentos analítico-reflexivos do novo institucionalismo, selecionamos, estudamos e produzimos sistematizações baseadas em 29 pesquisas desenvolvidas no Brasil. Com base nisso apontamos e delimitamos 4 abordagens teórico-metodológicas emergentes, entendidas como movimentos de adensamento do campo e possibilidades investigativas das dimensões institucionais. Apontamos essas abordagens como caminhos de aprofundamento investigativos que fazem sentido no campo das PPELs no Brasil.

INTRODUCTION: The advent of squamous cell carcinomas (SCC) from chronic dermatoses is known but little explored. Although rare, tumors originating there have a worse prognosis, in part due to late diagnosis. OBJECTIVES: This study aims to survey cases of squamous cell carcinoma developed on previous dermatoses diagnosed between 2000 and 2020 in a tertiary health service. METHODS: This is a quantitative and retrospective study through biopsy reports survey and medical records review. RESULTS: From an initial list of 11,249 histological reports compatible with squamous cell carcinoma, we obtained a final list of 10 patients. The study findings corroborate the literature regarding some known risk factors: abundant and chronic sun exposure, older than 50 years, lower skin phototypes, and immunosuppression. We also found a high frequency of smoking and lichenoid dermatoses (5/10 patients) in the studied population, including chronic cutaneous lupus erythematosus and hypertrophic lichen planus. CONCLUSIONS: It is not possible to predict the primary risk factors for the development of squamous cell carcinomas regarding previous dermatoses, although there is a tendency for their appearance in lichenoid dermatoses and those with longer evolution.

Abstract The ICARUS collaboration employed the 760-ton T600 detector in a successful 3-year physics run at the underground LNGS laboratory, performing a sensitive search for LSND-like anomalous $$\nu _e$$ ν e appearance in the CERN Neutrino to Gran Sasso beam, which contributed to the constraints on the allowed neutrino oscillation parameters to a narrow region around 1 eV $$^2$$ 2 . After a significant overhaul at CERN, the T600 detector has been installed at Fermilab. In 2020 the cryogenic commissioning began with detector cool down, liquid argon filling and recirculation. ICARUS then started its operations collecting the first neutrino events from the booster neutrino beam (BNB) and the Neutrinos at the Main Injector (NuMI) beam off-axis, which were used to test the ICARUS event selection, reconstruction and analysis algorithms. ICARUS successfully completed its commissioning phase in June 2022. The first goal of the ICARUS data taking will be a study to either confirm or refute the claim by Neutrino-4 short-baseline reactor experiment. ICARUS will also perform measurement of neutrino cross sections with the NuMI beam and several Beyond Standard Model searches. After the first year of operations, ICARUS will search for evidence of sterile neutrinos jointly with the Short-Baseline Near Detector, within the Short-Baseline Neutrino program. In this paper, the main activities carried out during the overhauling and installation phases are highlighted. Preliminary technical results from the ICARUS commissioning data with the BNB and NuMI beams are presented both in terms of performance of all ICARUS subsystems and of capability to select and reconstruct neutrino events.

Trachoma is the world-leading infectious cause of preventable blindness and is caused by the bacteria Chlamydia trachomatis. In developing countries, diagnosis is usually based on clinical evaluation. Serological-based tests are cheaper than molecular-based ones, but the latter are more sensitive and specific. The present study developed a new duplex qPCR which concomitantly detects the C. trachomatis cryptic plasmid and the human 18S rRNA gene, with an LOD95% for C. trachomatis DNA of 13.04 genome equivalents per reaction. The new qPCR was tested using 50 samples from an endemic area and 12 from a non-endemic area that were previously characterized using direct immunofluorescence assay (DFA) and clinical evaluation. Among the 50 endemic samples, 3 were found to be positive by clinical evaluation (6%), 18 were found to be positive by DFA (36%), and 48 were found to be positive by qPCR (96%). Next, the new duplex qPCR was validated using 50 samples previously characterized by qPCR. Validation was carried out on a benchtop instrument (ABI7500) or on a portable point-of-care instrument (Q3-Plus), showing 95% specificity and 100% sensitivity. The ubiquitous presence of C. trachomatis DNA in samples from the endemic region confirms that constant monitoring is of paramount importance for the effective measurement of the elimination of trachoma. The newly developed duplex qPCR presented in this study, along with its validation in a portable qPCR system, constitutes important tools toward achieving this goal.

Introduction Leptomeningeal carcinomatosis results from metastatic neoplastic cells that reach the leptomeninges through the cerebrospinal fluid. The presentation of the disease is variable, making prognosis challenging. However, the presence of intracranial hypertension is common, which has prompted new treatments to mitigate this effect.

Summary: Mutations in MPV17 are a major contributor to mitochondrial DNA (mtDNA) depletion syndromes, a group of inherited genetic conditions due to mtDNA instability. To investigate the role of MPV17 in mtDNA maintenance, we generated and characterized a Drosophila melanogaster Mpv17 (dMpv17) KO model showing that the absence of dMpv17 caused profound mtDNA depletion in the fat body but not in other tissues, increased glycolytic flux and reduced lifespan in starvation. Accordingly, the expression of key genes of glycogenolysis and glycolysis was upregulated in dMpv17 KO flies. In addition, we demonstrated that dMpv17 formed a channel in planar lipid bilayers at physiological ionic conditions, and its electrophysiological hallmarks were affected by pathological mutations. Importantly, the reconstituted channel translocated uridine but not orotate across the membrane. Our results indicate that dMpv17 forms a channel involved in translocation of key metabolites and highlight the importance of dMpv17 in energy homeostasis and mitochondrial function.

This article explores Swedish Police Authority strategies on creating a sense of safety through social media. Previous research has generally focused on proximity policing, practices of informing citizens, proactive police work, crime reduction, surveillance, and preservation of trust and less on the digital creation of a sense of safety. The study consists of semistructured interviews with 20 police officers, media strategists, and communicators from the Swedish Police Authority in a region associated with high crime rates. The results of this national case study indicate that a social media–driven creation of a sense of safety depends on how the intertwined strategies of transmediality, presence, and transparency are communicatively handled. This article adds to the literature by demonstrating how the Swedish Police in Police Region South (PRS) use and understand social media to create a sense of safety.

Abstract Cardiovascular diseases are the leading cause of death in the world and arterial hypertension (AH) accounts for 13.8% of deaths caused by cardiovascular diseases. Strength training interventions could be an important alternative tool for blood pressure control, however, consistent evidence and the most effective training protocol for this purpose are yet to be established. The current study used the Cochrane methodology to systematically review randomized controlled trials (RCTs) that investigated the effect of strength training on blood pressure in hypertensive patients. A systematic search was conducted in the PubMed, EMBASE, Scopus, Cochrane Library, and World Health Organization databases. This review included controlled trials that evaluated the effect of strength training for 8 weeks or more in adults with arterial hypertension, published up to December 2020. Data are described and reported as the weighted mean difference of systolic and diastolic pressure and a 95% confidence interval. Protocol registration: PROSPERO registration number CRD42020151269. A total of 14 studies were identified, including a combined total of 253 participants with hypertension. The meta-analysis showed that mean values of systolic blood pressure (SBP) and diastolic blood pressure (DBP) decreased significantly after strength training interventions. The strongest effect of strength training on decreasing blood pressure was observed in protocols with a moderate to vigorous load intensity (> 60% of one-repetition maximum-1RM), a frequency of at least 2 times per week, and a minimum duration of 8 weeks. We concluded that strength training interventions can be used as a non-drug treatment for arterial hypertension, as they promote significant decreases in blood pressure.

Abstract Colon cancer is one of the leading causes of death worldwide. In recent years, cannabinoids have been extensively studied for their potential anticancer effects and symptom management. Several in vitro studies reported anandamide’s (AEA) ability to block cancer cell proliferation and migration, but evidence from in vivo studies is still lacking. Thus, in this study, the effects of AEA exposure in zebrafish embryos transplanted with HCT116 cells were evaluated. Totally, 48 hpf xenografts were exposed to 10 nM AEA, 10 nM AM251, one of the cannabinoid 1 receptor (CB1) antagonist/inverse agonists, and to AEA + AM251, to verify the specific effect of AEA treatment. AEA efficacy was evaluated by confocal microscopy, which demonstrated that these xenografts presented a smaller tumor size, reduced tumor angiogenesis, and lacked micrometastasis formation. To gain deeper evidence into AEA action, microscopic observations were completed by molecular analyses. RNA seq performed on zebrafish transcriptome reported the downregulation of genes involved in cell proliferation, angiogenesis, and the immune system. Conversely, HCT116 cell transcripts resulted not affected by AEA treatment. In vitro HCT116 culture, in fact, confirmed that AEA exposure did not affect cell proliferation and viability, thus suggesting that the reduced tumor size mainly depends on direct effects on the fish rather than on the transplanted cancer cells. AEA reduced cell proliferation and tumor angiogenesis, as suggested by socs3 and pcnp mRNAs and Vegfc protein levels, and exerted anti-inflammatory activity, as indicated by the reduction of il-11a, mhc1uba, and csf3b mRNA. Of note, are the results obtained in groups exposed to AM251, which presence nullifies AEA’s beneficial effects. In conclusion, this study promotes the efficacy of AEA in personalized cancer therapy, as suggested by its ability to drive tumor growth and metastasis, and strongly supports the use of zebrafish xenograft as an emerging model platform for cancer studies.

T-cell large granular lymphocyte leukemia (T-LGLL) is a chronic lymphoproliferative disorder characterized by the clonal expansion of T-cell large granular lymphocytes (T-LGL). Immunophenotypic and genotypic features contribute to discriminate symptomatic (CD8+ STAT3-mutated T-LGLL) from clinically indolent patients, this latter group including CD8+ wildtype (wt), CD4+ STAT5B-mutated and wt cases. T-LGL lymphoproliferation is sustained both by somatic gain-offunction mutations (i.e., STAT3 and STAT5B) and by pro-inflammatory cytokines, but little information is available on the activity of T-LGLL non-leukemic cells. In this study, we characterized pro-inflammatory cells in the peripheral blood of T-LGLL patients and analyzed their role in supporting the leukemic growth. In symptomatic patients we found that cell populations not belonging to the leukemic component showed a discrete pro-inflammatory pattern. In particular, CD8+ STAT3-mutated cases showed a skewed Th17/Treg ratio and an abnormal distribution of monocyte populations characterized by increased intermediate and non-classical monocytes. We also demonstrated that monocytes released high levels of interleukin-6 after CCL5 stimulation, a chemokine specifically expressed only by leukemic LGL. Conversely, in asymptomatic cases an altered distribution of monocyte populations was not detected. Moreover, T-LGLL patients’ monocytes showed abnormal activation of signaling pathways, further supporting the different pathogenic role of monocytes in patients in discrete clinical settings. Altogether, our data contribute to deepening the knowledge on the different cell subtypes in T-LGLL, focusing particularly on non-leukemic cell populations and thus offering the rationale for new therapeutic strategies.

The increased transmissibility of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has generated variants of concern (VOCs) throughout the pandemic, responsible for waves of cases worldwide. To monitor mutations in the S gene of SARS-CoV-2 in different variants, we evaluated 1497 individuals with COVID-19 in western Amazonia in the period April 2021 to July 2022. The epidemiological and clinical data of the individuals were collected; subsequently, the samples were extracted using a commercial kit, the viral load was assessed, and viral genomes were sequenced. We analyzed the quality and mutations of the genomes and maximum likelihood phylogenetic inference. However, 3 main clusters were observed, referring to Gamma (52.91%), Delta (24.38%), and Omicron (20.38%) VOCs with wide distribution in all health regions of the Rondônia state. Regarding the vaccination profile, there was a higher percentage of unvaccinated and partially vaccinated individuals, with more representatives by the Gamma variant. A total of 1412 sequences were suitable for mutation analysis in the S gene region. The Omicron VOC showed 38 mutations, with the Delta and Gamma variants with 16 and 17, respectively. The VOC Omicron and Gamma shared 4 mutations E484K, H655Y, N501Y, and N679K with high frequency, and Delta and Omicron 2 mutations (T478K and T95I). Regarding the comparison between the frequency of mutations for each variant concerning the vaccination groups, there were no changes in mutations for each group. In conclusion, the study showed a temporal increase in mutations and subvariants for characterized strains. Furthermore, the vaccination profile did not impact significant changes in the mutational profile yet remains a determining factor for severe disease.