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Since the earliest reports, advanced clipping systems have been developed, and it is possible to choose among many models with different structural and technical features. The main drawback of through-the-scope clips is their small size, which allows the compression of limited amounts of tissue needed for large-size vessel treatment. Therefore, the over-the-scope clip system was realized, allowing a larger and stronger mechanical compression of large tissue areas, with excellent results in achieving a definitive hemostasis in difficult cases. Many studies have analyzed the indications and efficacy of two-pronged endoclips and have shown good results for initial and permanent hemostasis. The aim of this review was to provide updated information on indications, positioning techniques, and results of clip application for endoscopic treatment of upper gastrointestinal non-variceal bleeding lesions.

Acute cholecystitis stands out as one of the most common surgical pathologies that should always be considered in a right-upper abdominal pain emergency. For this, the importance of a correct diagnosis is well described. However, it has been demonstrated that the simple combination of clinical (pain, Murphy’s sign) and laboratory (leukocytosis) parameters alone does not provide for ruling in or ruling out the diagnosis of this condition, unless accompanied by a radiological exam. For a long time, and still today, ultrasonography (US) is by far the first-to-proceed radiologic exam to perform, thanks to its rapidity and very high sensibility and specificity for the diagnosis of simple acute cholecystitis. However, acute cholecystitis can undergo some complications that US struggles to find. In addition to that, studies suggest that multidetector computed tomography (MDCT) is superior in showing complicated forms of cholecystitis in relation to sensibility and specificity and for its capability of reformatting multiplanar (MPR) reconstructions that give a more detailed view of complications. They have shown to be useful for a precise evaluation of vascular complications, the anatomy of the biliary tree, and the extension of inflammation to surrounding structures (i.e., colitis). Therefore, based also on our experience, in patients with atypical presentation, or in cases with high suspicion for a complicated form, a MDCT abdomen scan is performed. In this review, the principal findings are listed and described to create a CT classification of acute complications based on anatomical and topographic criteria.

The article discusses a case series evaluating the effectiveness of bimekizumab in treating genital psoriasis (GenPs) over 52 weeks. Twelve patients with moderate-to-severe GenPs were treated with bimekizumab, showing significant improvement in their condition. The study highlights bimekizumab's sustained positive trend in managing GenPs, with patients achieving clear/almost clear status and improved quality of life. While some patients experienced minor side effects, the overall response to treatment was consistent across different sexes and prior treatment experiences. [Extracted from the article]

Background: Chronic pain significantly impacts quality of life and poses substantial public health challenges. Buprenorphine, a synthetic analog of thebaine, is recognized for its potential in managing moderate to severe chronic pain with fewer side effects and a lower incidence of tolerance compared to traditional opioids. Objective: This retrospective study aimed to assess the long-term efficacy and safety of buprenorphine transdermal patches in patients with moderate and severe chronic pain, with a focus on pain relief sustainability and tolerance development. Methods: This retrospective observational study involved 246 patients prescribed buprenorphine transdermal patches. We evaluated changes in pain intensity using the Numeric Rating Scale (NRS), assessed opioid tolerance based on FDA guidelines for morphine-equivalent doses, and measured patientreported outcomes through the Patients' Global Impression of Change (PGIC). Any adverse events were also recorded. Results: Over the 36-month period, there was a significant reduction in NRS scores for both moderate and severe pain patients, demonstrating buprenorphine's sustained analgesic effect. Tolerance measurement indicated that no patients required increases in morphine-equivalent doses that would meet or exceed the FDA's threshold for opioid tolerance (60 mg/day of morphine or equivalent). Additionally, patient satisfaction was high, with the PGIC reflecting significant improvements in pain management and overall wellbeing. The side effects were minimal, with skin reactions and nausea being the most commonly reported but manageable adverse events. Conclusion: The study findings validate the long-term use of buprenorphine transdermal patches as an effective and safe option for chronic pain management, maintaining efficacy without significant tolerance development. These results support the continued and expanded use of buprenorphine in clinical settings, emphasizing its role in reducing the burdens of chronic pain and opioid-related side effects. Further research is encouraged to refine pain management protocols and explore buprenorphine's full potential in diverse patient populations. [ABSTRACT FROM AUTHOR]

Antifungal substances are essential for managing fungal infections in humans, animals, and plants, and their usage has significantly increased due to the global rise in fungal infections. However, the extensive application of antifungal agents in pharmaceuticals, personal care products, and agriculture has led to their widespread environmental dissemination through various pathways, such as excretion, improper disposal, and agricultural runoff. Despite advances in wastewater treatment, many antifungal compounds persist in the environment, affecting non-target organisms and contributing to resistance development. This study investigates the environmental impact of two novel antifungal agents, VT-1161 and T-2307, recently introduced as alternatives for treating resistant Candida spp. We assessed their ecotoxicity and mutagenicity using multiple bioassays: immobilization of Daphnia magna, growth inhibition of Raphidocelis subcapitata, luminescence inhibition of Aliivibrio fischeri, and mutagenicity on Salmonella typhimurium strain TA100. Results indicate that both VT-1161 and T-2307 exhibit lower toxicity compared to existing antifungal compounds, with effective concentrations (EC50) causing 50% response ranging from 14.34 to 27.92 mg L−1. Furthermore, both agents were classified as less hazardous based on the Globally Harmonized System of Classification and Labeling of Chemicals. Despite these favorable results, further research is needed to understand their environmental behavior, interactions, and potential resistance development among non-target species. Our findings highlight the importance of comprehensive environmental risk assessments to ensure the sustainable use of new antifungal agents. [ABSTRACT FROM AUTHOR]

Chronic neuropathic pain (NP) is an increasingly prevalent disease and leading cause of disability which is challenging to treat. Several distinct classes of drugs are currently used for the treatment of chronic NP, but each drug targets only narrow components of the underlying pathophysiological mechanisms, bears limited efficacy, and comes with dose-limiting side effects. Multimodal therapies have been increasingly proposed as potential therapeutic approaches to target the multiple mechanisms underlying nociceptive transmission and modulation. However, while preclinical studies with combination therapies showed promise to improve efficacy over monotherapy, clinical trial data on their efficacy in specific populations are lacking and increased risk for adverse effects should be carefully considered. Drug-drug co-crystallization has emerged as an innovative pharmacological approach which can combine two or more different active pharmaceutical ingredients in a single crystal, optimizing pharmacokinetic and physicochemical characteristics of the native molecules, thus potentially capitalizing on the synergistic efficacy between classes of drugs while simplifying adherence and minimizing the risk of side effects by reducing the doses. In this work, we review the current pharmacological options for the treatment of chronic NP, focusing on combination therapies and their ongoing developing programs and highlighting the potential of co-crystals as novel approaches to chronic NP management.

To address and mitigate the environmental impacts of synthetic greenhouse gases it’s crucial to quantify their emissions to the atmosphere on different spatial scales. Atmospheric Inverse modelling is becoming a widely used method to provide observation-based estimates of greenhouse gas emissions with the potential to provide an independent verification tool for national emission inventories. A sensitivity study of the FLEXINVERT+ model for the optimisation of the spatial and temporal emissions of long-lived greenhouse gases at the regional-to-country scale is presented. A test compound HFC-134a, the most widely used refrigerant in mobile air conditioning systems, has been used to evaluate its European emissions in 2011 to be compared with a previous study. Sensitivity tests on driving factors like—observation selection criteria, prior data, background mixing ratios, and station selection—assessed the model’s performance in replicating measurements, reducing uncertainties, and estimating country-specific emissions. Across all experiments, good prior (0.5–0.8) and improved posterior (0.6–0.9) correlations were achieved, emphasizing the reduced sensitivity of the inversion setup to different a priori information and the determining role of observations in constraining the emissions.The posterior results were found to be very sensitive to background mixing ratios, with even slight increases in the baseline leading to significant decrease of emissions.

Health is a key aspect of our modern society that requires a multidisciplinary approach and that needs to bring together professionals, academics and decision makers in order to bridge the gap between current scientific knowledge and policies. The International One Health Conference: A systemic approach to manage urban and natural resources (One-Health 22) was held on 27–28 September 2022 in Catania (Italy) and aimed to share and discuss systemic approaches to One Health to efficiently manage urban and natural resources. The One health conceptual framework and its applications in the urban resilience domain and health care sector have been at the core of the congress’ dialogues. The Conference activated synergic dialogues among disciplinary research fields and action domains among researchers, experts and students.

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RESUMO: O objetivo deste artigo é caracterizar as posições filosóficas antagônicas à visão realista de lógica e matemática subscrita por Gottlob Frege, que são três: psicologismo idealista, psicologismo empirista e formalismo puro. A primeira é a concepção segundo a qual os conceitos matemáticos seriam obtidos por abstração empírica a partir de agregados. A segunda subscreve a tese de que a objetividade da matemática se assenta em categorias cognitivas humanas. A terceira, o formalismo puro, não constitui uma proposta de fundamentação da matemática, mas sim uma proposta que dispensa uma fundamentação filosófica para esta disciplina. PALAVRAS-CHAVE: Frege, matemática, idealismo, empirismo, formalismo.

Abstract In this Forum, six scholars reflect on Rahul Rao’s recent book Out of Time: The Queer Politics of Postcoloniality from other geographies, themes and radical possibilities. Part I offers dialogues with Out of Time from Trump’s USA and Brazil’s ‘hetero-military’ dictatorship and Portuguese colonial roots. Emerson Maione and Renan Quinalha explore how Rao’s elaborations of homonationalism, homocapitalism, homoromanticism and ‘pink-washing’ more generally travel in new contexts and how the ‘fetishization of law’ can mislead investigations of queer-, homo- and transphobias.

Introduction: Long-COVID-19 impacts health-related quality of life (HR-QoL) but data is scarce. The aim of this study was to describe and prospectively assess the prevalence and risk factors for long-COVID-19 after hospital discharge, and to evaluate its impact on patient HR-QoL. Methods: Single-centre longitudinal study including all COVID-19 patients discharged between December 2020 and February 2021. Patients were contacted remotely at three, six and nine months. Data were collected as follows: 1) Long-COVID-19 symptoms were self-reported; 2) HRQoL were assessed using the 3-level EuroQoL-5D (EQ-5D-3L) questionnaire. Pregnant women, demented, bedridden, and non-Portuguese-speaking patients were excluded. Results: The three-, six- and nine-month assessments were completed by 152, 117 and 110 patients (median age: 61 years; male sex: 56.6%). Long-COVID-19 (≥ 1 symptom) was reported by 66.5%, 62.4% and 53.6% of patients and HR-QoL assessment showed impairment of at least some domain in 65.8%, 69.2% and 55.4% of patients at three, six and nine months, respectively. Fatigue was the most common long-COVID-19 symptom. Anxiety/depression domain was the most frequently affected in all three time-points, peaking at six months (39%), followed by pain/discomfort and mobility domains. Long-COVID-19 was associated with the impairment of all EQ-5D-3L domains except for self-care domain at each time-point. Neither intensive care unit admission nor disease severity were associated with long-COVID-19 nor with impairment of any EQ-5D-3L domain. After adjusting for sex, age, frailty status, and comorbid conditions, long-COVID-19 remained significantly associated with HR-QoL impairment at three (OR 4.27, 95% CI 1.92 – 9.52, p < 0.001), six (OR 3.46, 95% CI 1.40 – 8.57, p = 0.007) and nine months (OR 4.13, 95% CI 1.62 – 10.55, p = 0.003) after hospital discharge. In a longitudinal analysis, patients reporting long-COVID-19 at three months had an EQ-5D-3L index value decreased by 0.14 per visit (p < 0.001) compared to those without long-COVID-19 and both groups had a non-significant change in mean EQ-5D-3L index over the nine-month period (time-point assessment, Z = 0.91, p = 0.364). Conclusion: Clinical sequelae associated with long-COVID-19 can persist for at least nine months after hospital discharge in most patients and can impair long-term HR-QoL in more than half of patients regardless of disease severity, and clinicodemographic characteristics.

Human cytomegaloviruses (HCMVs) employ many different mechanisms to escape and subvert the host immune system, including expression of the viral IgG Fcγ receptors (vFcγRs) RL11 (gp34), RL12 (gp95), RL13 (gpRL13), and UL119 (gp68) gene products. The role of vFcγRs in HCMV pathogenesis has been reported to operate in infected cells by interfering with IgG-mediated effector functions. We found that gp34 and gp68 are envelope proteins that bind and internalize human IgGs on the surface of infected cells. Internalized IgGs are then transported on the envelope of viral particles in a vFcR-dependent mechanism. This mechanism is also responsible for the incorporation on the virions of the anti-gH neutralizing antibody MSL-109. Intriguingly, we show that gp68 is responsible for MSL-109 incorporation, but it is dispensable for other anti-HCMV antibodies that do not need this function to be transported on mature virions. HCMV-infected cells grown in presence of anti-HCMV monoclonal antibodies generate a viral progeny still infective and possible to be neutralized. This is the first example of a virus carrying neutralizing IgGs on its surface and their possible role is discussed.