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Este artigo tem como objetivo refletir sobre a atenção básica à saúde do idoso no Brasil, na perspectiva de construção coletiva de novo olhar e trilhar novos caminhos na superação do modelo tradicional de cuidado ao idoso, com seus desafios, preconceitos, adversidades e sua complexidade social, cultural, psicológica e física. Geriatria & Gerontologia. 2008;3(2):122-125.

Abstract Background Violence against health professionals is a growing problem that affects the quality of care provided and the well-being of workers. In the Alentejo region (Southern Portugal), the Regional Health Administration has been developing strategies to prevent and combat this phenomenon, namely, through the implementation of the Action Plan for the Prevention of Violence in the Health Sector. Violence in the health sector includes all situations in which a worker in the Ministry of Health's health institutions is exposed to any type of violence related to their work, putting their safety, well-being or health at risk, or that of others. The aim of this study was to analyze the perceptions and practices of local focal points (e.g.,departments, services, offices or functional units) on violence against health professionals in the Alentejo region. Methods Semi-structured interviews were carried out local focal points in the Alentejo region. The sampling was selected for convenience from different health units. The interviews were recorded, transcribed and analyzed according to the analysis protocol of the IRaMuTeQ software (Interface de R pour les Analyses Multidimensionnelles de Textes et de Questionnaires) version 0.7 alpha 2. Results In total, 43 interviews were conducted between February and April 2024. Interviews revealed that local focal points face various challenges in combating violence against health workers. The lack of specific training, the scarcity of security resources and the culture of underreporting were some of the obstacles identified. However, participants also stressed the importance of teamwork, effective communication and institutional support in dealing with this problem. Conclusions Violence against health professionals is a worrying reality that requires effective measures to prevent and combat it, requiring a coordinated and multifaceted response. Local focal points play a key role in this process, but they need adequate training, resources and institutional support. Comprehensive and regular training programs on violence, interpersonal communication and conflict management, and investment in security resources, including physical and technological measures, should be implemented in health facilities. Clear protocols should be created for dealing with situations of violence and a culture of reporting situations of violence to health professionals should be promoted, as well as the monitoring of victims by the authorities involved in cases of violence. Ongoing training and the simulation of real-life scenarios are crucial for preparing professionals to effectively manage situations of violence.

Abstract Long Covid results from the damage caused by SARS-CoV-2, involving the release of cytokines and the continuous activation of immune cells. This cross-sectional study investigates leukocyte and cytokine profiles in Long Covid patients in the Amazon, a region where such studies are limited. Blood samples were analysed for differential leukocyte counts and cytokine levels. We suggest elevated lymphocyte counts in hospitalised patients and those with severe COVID-19. Higher eosinophil counts were observed in patients with up to three months of Long Covid, and increased monocyte counts in those with up to six months. IL-2 levels were higher in patients with fewer symptoms and Long Covid duration of more than three months, whereas IL-10 may remain elevated for up to 12 months. We suggest positive correlations between neutrophils, monocytes, eosinophils, and lymphocytes with different cytokines (IFN-γ, IL-6, IL-4, IL-17a, IL-2). Women were associated with lower hospitalisation rates and longer durations of Long Covid; increased lymphocyte counts were linked to hospitalisation due to COVID-19, while higher monocyte counts were associated with Long Covid durations of up to six months. We suggest that Long Covid patients may exhibit alterations in inflammatory markers, indicating a persistently pro-inflammatory microenvironment that tends to diminish after 12 months of Long Covid.

Abstract The Cyprus Biobank collects biosamples, medical and lifestyle information with the aim of reaching 16,500 Cypriots aged ≥ 18-years, by year 2027, as part of a multitasked EU funded project. Volunteers are both from the general population and from disease cohorts of focused research projects, who amongst others will contribute to canvas the architecture of the Cyprus human genome and study the healthy and morbid anatomy of Cypriots. The Cyprus Biobank is a research infrastructure pillar of the biobank.cy Center of Excellence in Biobanking and Biomedical Research. Within 3-years (November 2019–October 2022), 1348 participants of the general population who represent a subset of the Cyprus Biobank recruited individuals, were enrolled in the pilot study. The study did not include individuals from separate disease-specific cohorts. Extensive information was collected from each participant, including biochemistry, complete blood count, physiological, anthropometric, socio-demographic, diet, and lifestyle characteristics. Prevalent health conditions along with medication use and family history were recorded, including 58 biomarkers based on blood and urine samples. With a systematic recruitment campaign, the Biobank is continuously increasing the number of individuals in the general population cohort and is developing separate disease cohorts of the Cypriot population. The pilot study enrolled 579 men and 769 women, aged between 18 and 85 years (median 48-years). The enrollment takes 40 min on average, including the collection of biological samples and phenotypic information. More than half (n = 733, 55%) of the participants are educated to college level or above. Statistically significant differences were found between men and women regarding their education level (p

Abstract Background In Yemen, effective early detection and a comprehensive grasp of breast cancer symptoms and risk factors are vital in preventing its potentially deadly spread. However, challenges arise in combating breast cancer in Yemen due to the lack of patient registries, national strategies, and structured cancer treatment plans. Objective This research sought to evaluate the awareness levels of breast cancer and the perceived obstacles to breast cancer screening among adult Yemeni women. Methods A community-based cross-sectional questionnaire study was conducted from September 2023 to January 2024 from two teaching and largest hospitals in the capital municipality, Sana’a, Yemen, where 533 women (≥ 18 years old) were conveniently selected in this study. Data were analyzed using SPSS software (version 23).. The Chi-square test was used to test associations. The factors associated with breast cancer awareness and barriers to breast cancer screening were analyzed separately, using multivariable logistic regression. Results The study revealed that 88.6% of women were familiar with breast cancer, and 61.9% being knowledgeable about screening methods such as clinical breast examination (CBE) or mammography. The primary hindrance to screening (84.1%, n = 53) was the absence of symptoms or pain. The second most common reason for not undergoing screening was a lack of understanding about breast cancer and its treatment (61.9%, n = 39). Conclusion To enhance breast cancer screening rates among Yemeni women consistently, targeted educational programs emphasizing the benefits of early detection and dispelling misconceptions and barriers related to the disease are essential.

Objetivo: Identificar as características dos distúrbios miofuncionais orofaciais em idosos institucionalizados. Métodos: A amostra foi constituída por 7 indivíduos do sexo feminino e 6 do sexo masculino, com idades entre 60 e 74 anos, abrigados na Casa de Longa Permanência Ieda Lucena, na cidade de Recife, Pernambuco, no período de setembro a novembro de 2009. Foi aplicado o Protocolo de Avaliação Miofuncional Orofacial. Também foram realizadas a avaliação das estruturas orofaciais, por meio da observação, palpação e movimentos dos órgãos fonoarticulatórios; observação do processo de mastigação e deglutição e avaliação global da fala. Resultados: Foram constatadas alterações estruturais quanto a postura, tonicidade e mobilidade dos órgãos fonoarticulatórios e desempenho das funções estomatognáticas, interferindo na comunicação oral e na alimentação dos idosos. Observou-se um número significativo de idosos desdentados (8 pessoas), condição que afeta a mastigação, alimentação, comunicação e interação social, com impacto negativo na qualidade de vida do idoso. Conclusão: As alterações no sistema estomatognático são frequentes no idoso e podem trazer consequências que interferem na melhoria das condições de vida desses indivíduos, especialmente nos idosos institucionalizados, que se apresentam fragilizados, por aspectos de ordem psicológica (solidão provocada pelo isolamento social, falta do convívio familiar) e precariedade econômica. Diante dessa realidade, conclui-se que a atuação fonoaudiológica configura-se como instrumento fundamental no diagnóstico e atendimento dessa clientela.

Abstract Membrane contact sites (MCSs) are hubs allowing various cell organelles to coordinate their activities. The dynamic nature of these sites and their small size hinder analysis by current imaging techniques. To overcome these limitations, we here design a series of reversible chemogenetic reporters incorporating improved, low-affinity variants of splitFAST, and study the dynamics of different MCSs at high spatiotemporal resolution, both in vitro and in vivo. We demonstrate that these versatile reporters suit different experimental setups well, allowing one to address challenging biological questions. Using these probes, we identify a pathway in which calcium (Ca2+) signalling dynamically regulates endoplasmic reticulum-mitochondria juxtaposition, characterizing the underlying mechanism. Finally, by integrating Ca2+-sensing capabilities into the splitFAST technology, we introduce PRINCESS (PRobe for INterorganelle Ca2+-Exchange Sites based on SplitFAST), a class of reporters to simultaneously detect MCSs and measure the associated Ca2+ dynamics using a single biosensor.

Abstract Peptidylarginine deiminase IV (PADI4, PAD4) deregulation promotes the development of autoimmunity, cancer, atherosclerosis and age-related tissue fibrosis. PADI4 additionally mediates immune responses and cellular reprogramming, although the full extent of its physiological roles is unexplored. Despite detailed molecular knowledge of PADI4 activation in vitro, we lack understanding of its regulation within cells, largely due to a lack of appropriate systems and tools. Here, we develop and apply a set of potent and selective PADI4 modulators. Using the mRNA-display-based RaPID system, we screen >1012 cyclic peptides for high-affinity, conformation-selective binders. We report PADI4_3, a cell-active inhibitor specific for the active conformation of PADI4; PADI4_7, an inert binder, which we functionalise for the isolation and study of cellular PADI4; and PADI4_11, a cell-active PADI4 activator. Structural studies with PADI4_11 reveal an allosteric binding mode that may reflect the mechanism that promotes cellular PADI4 activation. This work contributes to our understanding of PADI4 regulation and provides a toolkit for the study and modulation of PADI4 across (patho)physiological contexts.

Abstract Chronic limb-threatening ischemia (CLTI) significantly increases the risk of major adverse limb events (MALE) and major adverse cardiac events (MACE) after lower extremity revascularization (LER). This study aims to identify novel biomarkers that help to further reduce the risk of postoperative cardiovascular complications. In this prospective, nonrandomized, observational study, baseline serum levels of sirtuin 1 (SIRT1) were assessed in 147 diabetic patients scheduled for LER due to CLTI, and participants were followed for the occurrence of MALE and MACE over 12 months. Fifty-three patients experienced MALE, and 33 experienced MACE within the follow-up period. Lower baseline SIRT1 levels were significantly associated with an increased risk of MALE and MACE, independent of other risk factors. The ROC curve analysis identified a SIRT1 cutoff of 3.79 ng/mL for predicting the risk of MALE. Moreover, incorporating SIRT1 into predictive models significantly enhanced the accuracy of predicting adverse outcomes. Results suggest serum SIRT1 is a potential independent marker for predicting MALE and MACE in diabetic patients with CLTI undergoing LER. Further research is needed to clarify the mechanistic pathways in which SIRT1 may influence cardiovascular outcomes, and the role of this novel biomarker in the management of PAD and CLTI among patients with diabetes.

Abstract Clinical pathway recommendations (CPR) are based on existing guidelines and deliver a short overview on how to deal with a specific diagnosis, resulting therapy and follow-up. In this paper we propose a methodology for developing CPRs for Pompe disease, a metabolic myopathy caused by deficiency of lysosomal acid alpha-glucosidase. The CPR document was developed within the activities of the MetabERN, a non-profit European Reference Network for Metabolic Diseases established by the European Union. A working group was selected among members of the MetabERN lysosomal storage disease subnetwork, with specific expertise in the care of Pompe disease, and patient support group representatives. The working strategy was based on a systematic literature search to develop a database, followed by quality assessment of the studies selected from the literature, and by the development of the CPR document according to a matrix provided by MetabERN. Quality assessment of the literature and collection of citations was conducted according to the AGREE II criteria and Grading of Recommendations, Assessment, Development and Evaluation methodology. General aspects were addressed in the document, including pathophysiology, genetics, frequency, classification, manifestations and clinical approach, laboratory diagnosis and multidisciplinary evaluation, therapy and supportive measures, follow-up, monitoring, and pregnancy. The CPR document that was developed was intended to be a concise and easy-to-use tool for standardization of care for patients among the healthcare providers that are members of the network or are involved in the care for Pompe disease patients.

Selective conversion of biomass into targeted molecules like polyols, especially, from cellulosic compounds, is being widely investigated as a sustainable process to produce biodiesel and bio-additives. The known process involves two steps, namely hydrolysis and hydrogenation. Thus, it requires two different catalytic materials or bifunctional catalysts. In this context, the present work reports a new catalytic approach based on the use of tandem catalysts, consisting of the combination of an acid solid catalyst (active for hydrolysis) and a supported metal catalyst (active for hydrogenation). Two different functionalized activated carbons and the resin Amberlyst 15 have been tested as solid acid catalysts, and Ru nanoparticles supported on the original activated carbon (SA) are the metal catalyst part of the tandem. All the tested tandem catalysts exhibited higher activity than the supported Ru catalyst did. The highest cellulose conversion and selectivity to sorbitol (70% and 86%, respectively) have been obtained over a novel tandem catalyst, which resulted from a physical mixture between a sulfuric acid modified SA carbon (SASu) and Ru loaded SA (Ru/SA), leading to a tandem catalyst (Ru/SA+SASu). This novel-designed tandem catalyst is reusable. Based on tandem catalysts with a solid-solid system combination, the adopted novel-designed catalytic approach is cost-efficient and sustainable, and can be considered promising for the green production of high-added-value chemicals.

Summary. Along with traditional research on psychiatric stigma, there has recently been increasing interest in the neurobiological factors associated with stigmatization.Aim: to study the most common research methods in the studies of the neurobiological correlates of stigmatization phenomenon and its components, as well as to systematize their results, taking into account their methodological limitations.Materials and Methods: The review was conducted in accordance with the PRISMA-ScR extension. Studies were searched in MEDLINE, EMBASE, PsycINFO using the Ovid platform. After evaluating 2358 articles according to inclusion, non-inclusion, and exclusion criteria, 20 articles were included in the final analysis.Results: The most of the studies were conducted on samples of healthy respondents without a control group (14 articles). The mean age of respondents ranged from 18.8 [1.0] to 42.7 [14.7] years. Psychiatric stigma was studied in 2 studies; in the remaining articles, various components of stigma were studied, among which social rejection sensitivity was most often studied (13 articles). Among fMRI paradigm the Cyberball social exclusion task was used more often (10 articles). Changes in neural activity, correlating with the severity of stigma and its constituent constructs, were found in the anterior cingulate cortex, prefrontal cortex, insula, thalamus, hypothalamus, hippocampus, parahippocampal gyrus, ventral region of the striatum, putamen, amygdala.Conclusion: Functional magnetic resonance studies can be an effective tool for verifying and assessing the dynamics of the psychological state of people experiencing the phenomenon of stigmatization.

Abstract Background Crohn’s disease (CD) is characterized by chronic intestinal inflammation. Diet is a key modifiable factor influencing the gut microbiome (GM) and a risk factor for CD. However, the impact of diet modulation on GM function in CD patients is understudied. Herein, we evaluated the effect of a high-fiber, low-fat diet (the Mi-IBD diet) on GM function in CD patients. All participants were instructed to follow the Mi-IBD diet for 8 weeks. One group of CD patients received one-time diet counseling only (Gr1); catered food was supplied for the other three groups, including CD patients (Gr2) and dyads of CD patients and healthy household controls (HHCs) residing within the same household (Gr3-HHC dyads). Stool samples were collected at baseline, week 8, and week 36, and analyzed by liquid chromatography-tandem mass spectrometry. Results At baseline, the metaproteomic profiles of CD patients and HHCs differed. The Mi-IBD diet significantly increased carbohydrate and iron transport and metabolism. The predicted microbial composition underlying the metaproteomic changes differed between patients with ileal only disease (ICD) or colonic involvement: ICD was characterized by decreased Faecalibacterium abundance. Even on the Mi-IBD diet, the CD patient metaproteome displayed significant underrepresentation of carbohydrate and purine/pyrimidine synthesis pathways compared to that of HHCs. Human immune-related proteins were upregulated in CD patients compared to HHCs. Conclusions The Mi-IBD diet changed the microbial function of CD patients and enhanced carbohydrate metabolism. Our metaproteomic results highlight functional differences in the microbiome according to disease location. Notably, our dietary intervention yielded the most benefit for CD patients with colonic involvement compared to ileal-only disease. Video Abstract

The case study of the monumental complex of San Francesco le Moniche, built in the ancient Norman county Aversa, in northern Campania (Italy), is analyzed here. The cultural heritage of the complex and the additional value associated with geoheritage (building stones and underground extraction cavities) have been highlighted. The building stratification of the complex was reconstructed based on documentary sources, including historical cartography and photographic documentation of postcards from the early 1900s. It began around 1200 and ended in the 20th century; part of the original citadel was dismantled and incorporated into the urban fabric in the Fascist era. The building stratification of the complex was also read from the distribution and architecture of the existing underground cavities from which the building stones were extracted. The subsoil, reconstructed on the basis of geological and geophysical data, is made up of a tuff substrate, starting from approximately 5–6 m from the ground level, which represents the main building stone as well as being an important testimony to the long volcanological history of northern Campania. Laser scanner surveys of the known and accessible cavities were carried out to obtain a three-dimensional view of the entire monumental complex and its underground spaces. The results provide a clear example of a geoheritage–cultural heritage interface which reminds us of the importance of an integrated approach in their valorization, specifically in urban areas. Additionally, the results of the study allowed us to improve the knowledge of the complex and the site, and provide useful tools for the planning of future targeted investigations.

Coeliac disease is a common condition for which the only current treatment is a gluten-free diet. Adherence to this diet is not always easy and is associated with a reduction in quality of life for the patient and their family. Non-adherence is associated with complications of varying severity. The lack of control at the outpatient care level in a high percentage of these patients evinces the need to improve follow-up protocols and the approach to care delivery with coordination of paediatric gastroenterology units (PGU) and primary care paediatricians. With this aim in mind, the present document was developed by consensus to offer a set of recommendations adapted to our region, based on the recent recommendations published by the European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN), and with participation of the pertinent scientific societies, including those concerning the adult population, for the management and follow-up of adolescents and the transition to adult care. Resumen: La enfermedad celíaca es una patología frecuente y cuyo único tratamiento en el momento actual es la dieta sin gluten. El seguimiento de esta dieta no siempre es fácil e implica limitaciones en la calidad de vida del paciente y su familia. La no adherencia se asociaría a complicaciones de distinta gravedad. La falta de control de estos pacientes en consultas en un alto porcentaje de casos plantea la necesidad de mejorar los protocolos de seguimiento y de abordarlos de forma coordinada entre las Unidades de Gastroenterología Pediátrica (UGP) y los pediatras de Atención Primaria. Con ese objetivo se han consensuado en este documento, basándose en las recomendaciones recientemente publicadas por la Sociedad Europea de Gastroenterología, Hepatología y Nutrición Pediátrica (ESPGHAN), un conjunto de recomendaciones adaptadas a nuestro entorno y contando con la participación de las Sociedades Científicas implicadas, incluyendo a las Sociedades de adultos para el abordaje del seguimiento del adolescente y de la transición de cuidados a los profesionales de adultos.

Abstract Background Cormus domestica (L.) is a monophyletic wild fruit tree belonging to the Rosaceae family, with well-documented use in the Mediterranean region. Traditionally, these fruits are harvested and stored for at least 2 weeks before consumption. During this period, the fruit reaches its well-known and peculiar organoleptic and texture characteristics. However, the spread of more profitable fruit tree species, resulted in its progressive erosion. In this work we performed proteomic and metabolomic fruit analyses at three times after harvesting, to characterise postharvest physiological and molecular changes, it related to nutritional and organoleptic properties at consumption. Results Proteomics and metabolomics analysis were performed on fruits harvested at different time points: freshly harvested fruit (T0), fruit two weeks after harvest (T1) and fruit four weeks after harvest (T2). Proteomic analysis (Shotgun Proteomic in LC-MS/MS) resulted in 643 proteins identified. Most of the differentially abundant proteins between the three phases observed were involved in the softening process, carbohydrate metabolism and stress responses. Enzymes, such as xyloglucan endotransglucosylase/hydrolase, pectin acetylesterase, beta-galactosidase and pectinesterase, accumulated during fruit ripening and could explain the pulp breakdown observed in C. domestica. At the same time, enzymes abundant in the early stages (T0), such as sucrose synthase and malic enzyme, explain the accumulation of sugars and the lowering of acidity during the process. The metabolites extraction from C. domestica fruits enabled the identification of 606 statistically significant differentially abundant metabolites. Some compounds such as piptamine and resorcinol, well-known for their antimicrobial and antifungal properties, and several bioactive compounds such as endocannabinoids, usually described in the leaves, accumulate in C. domestica fruit during the post-harvest process. Conclusions The metabolomic and proteomic profiling of the C. domestica fruit during the postharvest process, evaluated in the study, provides a considerable contribution to filling the existing information gap, enabling the molecular and phytochemical characterisation of this erosion-endangered fruit. Data show biochemical changes that transform the harvested fruit into palatable consumable product.

Abstract Background SARS-CoV-2 infection has become a major international issue, not only from a medical point of view, but also social, economic and political. Most of the available information comes from the United States, Europe, and China, where the population and the socioeconomic status are very different from Latin American countries. This study evaluates the effect of regional socioeconomic characteristics on mortality due SARS-CoV-2 infection in patients with immune-mediated rheumatic diseases (IMRD) from Argentina, Mexico and Brazil. Methods Data from three national registries, SAR-COVID (Argentina), CMR-COVID (Mexico) and ReumaCoV-Brasil (Brazil), were combined. Adult IMRD patients with SARS-CoV-2 infection were recruited. National data for each province/state, including population density, number of physicians per inhabitant, income, unemployment, GINI index, Municipal Human Development Index (MHDI), stringency index, vaccination rate and most frequent viral strains per period were assessed as risk factors for mortality due to COVID-19. Results A total of 4744 patients were included, 2534 (53.4%) from SAR-COVID, 1166 (24.6%) from CMRCOVID and 1044 (22.0%) from ReumaCoV-Brasil. Mortality due to COVID-19 was 5.4%. In the multivariable analysis, higher number of physicians per 1000 inhabitants and being infected during the vaccination period of each country were associated with lower mortality. After adjustment for socioeconomic factors, there was no association with country of residence and mortality. Conclusion These findings corroborate the complex interplay between socioeconomic factors, rheumatic disease activity, and regional disparities as determinants of death due to COVID-19 in Argentina, Brazil and Mexico. Thus, this research provides valuable insights for guiding public health policies and clinical practice in the ongoing fight against the COVID-19 pandemic.

Abstract We describe the geographical variation in tree species composition across Amazonian forests and show how environmental conditions are associated with species turnover. Our analyses are based on 2023 forest inventory plots (1 ha) that provide abundance data for a total of 5188 tree species. Within-plot species composition reflected both local environmental conditions (especially soil nutrients and hydrology) and geographical regions. A broader-scale view of species turnover was obtained by interpolating the relative tree species abundances over Amazonia into 47,441 0.1-degree grid cells. Two main dimensions of spatial change in tree species composition were identified. The first was a gradient between western Amazonia at the Andean forelands (with young geology and relatively nutrient-rich soils) and central–eastern Amazonia associated with the Guiana and Brazilian Shields (with more ancient geology and poor soils). The second gradient was between the wet forests of the northwest and the drier forests in southern Amazonia. Isolines linking cells of similar composition crossed major Amazonian rivers, suggesting that tree species distributions are not limited by rivers. Even though some areas of relatively sharp species turnover were identified, mostly the tree species composition changed gradually over large extents, which does not support delimiting clear discrete biogeographic regions within Amazonia.

This study was conducted to identify and characterize the Bacillus strain from Goat’s milk in Algeria and to evaluate the prebiotic effect of H. scoparia aqueous extract and ZnO-NPs on the isolated Bacillus strain. Potentially probiotic bacteria were isolated and identified based on phenotypic characteristics, including the morphological, physiological (growth temperature, salt tolerance), biochemical (API 10S strip kits), and confirmed by 16S rDNA gene sequencing. Bacillus pumilus specie of lactic acid bacteria were identified. The base pair length of amplified DNA for the isolate was 1500 Bp. The isolates could not grow at 10°C and 45°C and tolerate up to 6% salt. H. scoparia extract and ZnO-NPs have a beneficial effect on the Bacillus pumilus strain for acid tolerance, bile tolerance, and cell surface hydrophobicity respectively; H. scoparia extract and ZnO-NPs results are high comparing to the control group’s results. As the concentration of the tested samples increases, the percentage of probiotic characteristics of Bacillus pumilus increases, in contrast to the control sample. Therefore, they could be useful tools to define adequate combinations in colonic foods development and health benefits. The beneficial physiological and biochemical properties of isolated Bacillus pumilus space from Goat’s milk with the H. scoparia aqueous extract and ZnO-NPs revealed their potential applications in the food industry.

Podolian cattle is an autochthonous breed well adapted to the harsh semi-arid environments of the Southern Italy regions; the extensive rearing system used for these indigenous animals is based on grazing on spontaneous pastures, such as grasslands or wood pastures These grazing systems respect animal welfare and enrich animal products with characteristics closely related to the feeding system and the farming environment. The aim of the present study was to characterize the nutritional value of a forage crop and a wood-pasture and to evaluate the effects of grazing by Podolian young bulls on the performances and meat quality in relation to the age at slaughter (14 or 18 months) and to the ageing time of meat (3, 9 or 14 days). The metabolizable energy and the gas production were greater in April and June for both pasture systems. Young bulls raised on the grassland showed greater slaughter weights (p

Introduction The use of novel adjuvants in human vaccines continues to expand as their contribution to preventing disease in challenging populations and caused by complex pathogens is increasingly understood. AS01 is a family of liposome-based vaccine Adjuvant Systems containing two immunostimulants: 3-O-desacyl-4’-monophosphoryl lipid A and the saponin QS-21. AS01-containing vaccines have been approved and administered to millions of individuals worldwide.Areas covered Here, we report advances in our understanding of the mode of action of AS01 that contributed to the development of efficacious vaccines preventing disease due to malaria, herpes zoster, and respiratory syncytial virus. AS01 induces early innate immune activation that induces T cell-mediated and antibody-mediated responses with optimized functional characteristics and induction of immune memory. AS01-containing vaccines appear relatively impervious to baseline immune status translating into high efficacy across populations. Currently licensed AS01-containing vaccines have shown acceptable safety profiles in clinical trials and post-marketing settings.Expert opinion Initial expectations that adjuvantation with AS01 could support effective vaccine responses and contribute to disease control have been realized. Investigation of the utility of AS01 in vaccines to prevent other challenging diseases, such as tuberculosis, is ongoing, together with efforts to fully define its mechanisms of action in different vaccine settings.

P-glycoprotein (P-gp) plays a crucial role in cellular detoxification and drug efflux processes, transitioning between inward-facing (IF) open, occluded, and outward-facing (OF) states to facilitate substrate transport. Its role is critical in cancer therapy, where P-gp contributes to the multidrug resistance phenotype. In our study, classical and enhanced molecular dynamics (MD) simulations were conducted to dissect the structural and functional features of the P-gp conformational states. Our advanced MD simulations, including kinetically excited targeted MD (ketMD) and adiabatic biasing MD (ABMD), provided deeper insights into state transition and translocation mechanisms. Our findings suggest that the unkinking of TM4 and TM10 helices is a prerequisite for correctly achieving the outward conformation. Simulations of the IF-occluded conformations, characterized by kinked TM4 and TM10 helices, consistently demonstrated altered communication between the transmembrane domains (TMDs) and nucleotide binding domain 2 (NBD2), suggesting the implication of this interface in inhibiting P-gp's efflux function. A particular emphasis was placed on the unstructured linker segment connecting the NBD1 to TMD2 and its role in the transporter's dynamics. With the linker present, we specifically noticed a potential entrance of cholesterol (CHOL) through the TM4-TM6 portal, shedding light on crucial residues involved in accommodating CHOL. We therefore suggest that this entry mechanism could be employed for some P-gp substrates or inhibitors. Our results provide critical data for understanding P-gp functioning and developing new P-gp inhibitors for establishing more effective strategies against multidrug resistance.

Background: Extensive-stage small-cell lung cancer (ES-SCLC) treatment has recently been revolutionized by the advent of immune checkpoint inhibitors. This survey was conducted to evaluate the current pattern of care among Italian clinicians, in particular about the integration with radiation therapy (RT). Methods: In June 2023, 225 Italian cancer care professionals were invited to complete a 21-question web-based survey about ES-SCLC management through personal contacts and the Italian Association for Radiotherapy and Clinical Oncology (AIRO) network. Results: We received 90 responses; the majority were radiation oncologists (89%) with more than 10 years of experience (51%). The preferred management of ES-SCLC in patients with a good performance status was concomitant chemo-immunotherapy (84%). Almost all respondents recommended prophylactic cranial irradiation (PCI) (85%), taking into account age and thoracic response; PCI was performed mainly between the end of chemotherapy and before starting immunotherapy (37%), with a three-dimensional conformal technique (46%). Furthermore, 83% of respondents choose to deliver thoracic RT in the case of both an intrathoracic and extrathoracic response, with an RT schedule of 30 Gy/10 fractions. Stereotactic RT is increasingly being used in oligoprogressions. Conclusions: Our analysis showed the variability of real-world management of ES-SCLC. Future clinical trials and developments are needed to improve the multidisciplinary treatment of these patients.

Introduction: Genetic polymorphisms who disturb the mineral homeostasis during tooth development and eruption are candidate to clarify the molecular mechanisms involved in changes in the tooth eruption chronology. In this study, we evaluate whether the FokI (rs2228570) and BglI (rs739837) polymorphisms in the Vitamin D receptor (VDR) gene are associated with changes in the chronology of eruption of permanent teeth. Material & method: This cross-sectional study randomly included 353 biologically unrelated children, both sexes, without systemic impairment or syndromes and history of trauma during the primary dentition. One operator perform the oral clinical examination. The tooth was considered erupted if there was a visible minimum of any tooth surface emerging from the mucosa. Genomic DNA was extracted from buccal epithelial cells from saliva samples. Genotyping was performed by Real-Time Polymerase Chain Reactions using TaqMan® technology. The average of the total number of erupted permanent teeth between the genotypes was compared by the Mann-Whitney test and multivariate Generalized Linear Models (GLM) (α = 5 %). β values with Confidence Interval (CI) 95 % were calculated. Results: The heterozygous adenine-guanine genotype of the FokI significantly decreases the number of erupted permanent teeth (β = −1.15; CI 95 % = −2.22 to −0.07; p = 0.036). In the stratified analysis for maxillary and mandibular teeth, this genotype was associated with a decrease in the number of erupted maxillary permanent teeth (β = −0.65; CI 95 % = −1.22 to −0.09; p = 0.023). BglI was not associated with permanent teeth eruption. Conclusion: The FokI, but not BglI, in the VDR may delay the eruption of permanent teeth.

Abstract Background To determine whether obesity and markers of lipid metabolism are associated with radiological hand osteoarthritis (OA) in the Halland County Osteoarthritis (HALLOA) cohort. Methods In this cross-sectional study, we included 231 participants aged 30–65 from the HALLOA cohort, which began in 2017 and is ongoing. Hand OA was defined as ≥ 2 joint groups (distal interphalangeal, proximal interphalangeal, and carpometacarpal I) with Kellgren-Lawrence grade ≥ 2. The severity of hand OA was classified in terms of the number of affected joint groups (moderate hand OA 2–4 joint groups, severe hand OA 5–6 joint groups). Metabolic profile, including body mass index (BMI), bioimpedance, waist circumference, blood pressure, serum leptin, total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides, were obtained. Multicollinearity was assessed with Pearson’s correlation and associations with logistic regression analyses adjusting for age, HDL-cholesterol, and central obesity. Results Two-thirds of the participants were women, and 91 (39%) had hand OA. We found a relationship between LDL-cholesterol and prevalent hand OA in women with an odds ratio of 1.7 (95% CI 1.1–2.6) and an association between LDL-cholesterol and severity of hand OA in women; odds ratio for no hand OA vs. moderate hand OA was 1.6 (95% CI 1.0-2.4) and for no hand OA vs. severe hand OA 2.5 (95% CI 1.2–4.9). There were no significant relationships between hand OA and obesity or serum leptin levels. Conclusion Circulating LDL-cholesterol levels were associated with the prevalence and severity of hand OA in women but not men. Trial registration ClinicalTrials. Gov (NCT04928170), Date of registration: 2017-12-20.

Abstract The evaluation of white matter lesions (WMLs) showing the central vein sign (CVS) and paramagnetic rim lesions (PRLs) has been suggested to enhance the diagnostic work‐up of adult multiple sclerosis (MS). We aimed to evaluate the fulfillment of different CVS criteria and the added value of PRLs in 22 pediatric MS patients. Eleven patients (50%) fulfilled the 40%‐rule threshold. Nineteen (86%) patients had ≥3 CVS+ WMLs or ≥1 PRL, whereas 17 (77%) had ≥6 CVS+ WMLs or ≥1 PRL. A simplified CVS‐based approach, with the combined evaluation of ≥1 PRL in patients with ≥6 CVS+ WMLs, may improve MS diagnosis in pediatric patients.

Abstract Voltage-gated potassium channels play a crucial role in cellular repolarization and are potential therapeutic targets in neuroinflammatory disorders and neurodegenerative diseases. This study explores Tityus bahiensis scorpion venom for neuroactive peptides. We identified the αKtx12 peptide as a potent neuroprotective agent. In SH-SY5Y cells, αKtx12 significantly enhances viability, validating its pharmacological potential. And in the animal model, we elucidate central nervous system (CNS) mechanism of αKtx12 through neuroproteomic analyses highlighting αKtx12 as a valuable tool for characterizing neuroplasticity and neurotropism, revealing its ability to elicit more physiological responses. The peptide’s potential to promote cell proliferation and neuroprotection suggests a role in functional recovery from nervous system injury or disease. This research unveils the neuroactive potential of scorpion venom-derived αKtx12’s, offering insights into its pharmacological utility. The peptide’s impact on neuronal processes suggests a promising avenue for therapeutic development, particularly in neurodegenerative conditions.

Abstract BerryPortraits (Phenotyping of Ripening Traits) is open source Python-based image-analysis software that rapidly detects and segments berries and extracts morphometric data on fruit quality traits such as berry color, size, shape, and uniformity. Utilizing the YOLOv8 framework and community-developed, actively-maintained Python libraries such as OpenCV, BerryPortraits software was trained on 512 postharvest images (taken under controlled lighting conditions) of phenotypically diverse cranberry populations (Vaccinium macrocarpon Ait.) from the two largest public cranberry breeding programs in the U.S. The implementation of CIELAB, an intuitive and perceptually uniform color space, enables differentiation between berry color and berry brightness, which are confounded in classic RGB color channel measurements. Furthermore, computer vision enables precise and quantifiable color phenotyping, thus facilitating inclusion of researchers and data analysts with color vision deficiency. BerryPortraits is a phenotyping tool for researchers in plant breeding, plant genetics, horticulture, food science, plant physiology, plant pathology, and related fields. BerryPortraits has strong potential applications for other specialty crops such as blueberry, lingonberry, caneberry, grape, and more. As an open source phenotyping tool based on widely-used python libraries, BerryPortraits allows anyone to use, fork, modify, optimize, and embed this software into other tools or pipelines.

Abstract Background Clowning has been used in many hospitals, particularly for children. Studies suggest the effectiveness of this methodology, but more evidence is needed. The aim of this study was to evaluate the impact of a humour therapy intervention on biological markers, pain and anxiety levels in paediatric patients. Methods Three different clinical contexts were chosen to assess the effect of clowning interventions: patients who were subjected to venepuncture (group 1), patients undergoing general anesthesia for any cause (group 2)and patients hospitalized in the pediatric ward without distinction of their disease (group 3). Groups 1 and 2 were divided into control (C) and intervention (I) subgroups. A saliva sample was taken from all the children to measure oxytocin and cortisol levels by ELISAs. Validated scales and crying time were used to determine pain, stress, and anxiety levels. Children in group 3 were assessed before and after the intervention, employing the same methods. Results A total of 272 patients were included. The children in group 1 (n = 125) were 7.7 ± 3.2 years old, and 53.6% were females. 48% were in the I group, which showed decreased cortisol levels and increased oxytocin levels. The I group exhibited a decrease in perceived pain and crying time. The children in group 2 (n = 69) were aged 7.1 ± 3.5 years, and 36% were females. 51% were in the I group, which showed increased oxytocin levels and decreased cortisol levels, acute stress levels, perceived pain, and crying time. The children in group 3 (n = 78) were 8.6 ± 3.3 years old, and 54% of the children were females. There was an increase in oxytocin levels and a decrease in cortisol levels, stress levels and perceived pain following the intervention. Conclusions This study suggested that an intervention based on clowning is an effective strategy for decreasing pain, stress, and anxiety levels in paediatric patients in different clinical contexts. These findings support the implementation of humour therapy programs in paediatric units.

The social category ‘borrowers’ is heterogeneous in a number of indicators. The article raises the problem of differences in the psychological characteristics of borrowers who prefer formal loans and loans from private individuals. The purpose of the study is to analyze the psychological characteristics of consumers of various types of loans. Based on previous research, the authors identified for analysis variables such as time perspective and long-term orientation of the individual, consideration of the consequences of one’s behavior, level of generalized trust, moral foundations, social beliefs and attitudes towards debt, which were presumably associated with people’s preferred type of borrowing. The sample consisted of users of financial services with various types of loans ( N = 1974); they were divided into three groups, homogeneous by type of loans: (1) the respondents who had only loans received from relatives, friends or acquaintances ( N = 97), (2) the respondents who had only loans from microfinance organizations (MFO) ( N = 97), and (3) the respondents who had only consumer loans ( N = 103). The analysis was carried out using the following methods and techniques: The Moral Foundations Questionnaire (MFQ) by J. Haidt (adapted by O.A. Sychev), The Long-Term Orientation of Personality (LTOP) by T.A. Nestik, The Consideration for Future Consequences (CFC) by A. Strathman (adapted by T.A. Nestik), a short version of The Dual Process Model Scales by J. Duckitt (adapted by D.S. Grigoriev), a short version of The Zimbardo Time Perspective Inventory (ZTPI) , The World Value Survey (WVS) , The Personal Belief in a Just World Scale by K. Dalbert with two subscales: belief in the justice of the world and belief in the justice of the world in relation to oneself (adapted by S.K. Nartova-Bochaver), and The Debt Behavior Express Inventory . In each group of the respondents, significant differences were found in the structure of relationships among the studied parameters. The results showed that the respondents who had only non-institutional loans, in contrast to those who had exclusively bank or MFO loans, were less loyal to their group (low traditionalism), which in their perceptions was associated with reduced trust in (regional) authorities. This may indicate the autonomy of these borrowers in social terms. The limitations of the study were also noted. Finally, the prospects for further research were outlined and the possibilities of practical use of the results obtained were determined.

The article presents approaches to defining quality criteria for pedagogical experimental research. Particular attention is paid to the evidence-based approach in pedagogy. It is argued that pedagogical research today is an integral part of the educational process and dissertations on pedagogical sciences. However, it should be noted that there are problems with the quality of such studies, which constitute a significant share of the total number of defended dissertations, and this causes an urgent need to develop methodological principles and criteria for assessing their quality. But it is not every pedagogical research that is the subject of this paper: its focus is on the methodological foundations of experimental pedagogical research or simply experimental research in pedagogy, which often do not meet the requirements of the scientific method. The authors analyzed the main topics of pedagogical research in Russia and abroad. The key results and conclusions of the study are the complex requirements for dissertations as a scientific product and pedagogical research, which determine the algorithm for obtaining proven, reliable data used in science. It is concluded that experimental research in the field of pedagogy should be carried out in accordance with the requirements for all empirical research. In particular, special attention is paid to ethical issues of pedagogical research and procedures for implementing the experimental method.

Introdução: Os idosos representam uma população crescente no Brasil e no mundo. As alterações fisiológicas decorrentes da idade, as comorbidades e a necessidade de polifarmacoterapia os tornam altamente susceptíveis à ocorrência de eventos adversos relacionados a medicamentos. A conciliação medicamentosa mostra-se estratégia útil para reduzir esses eventos, quando o paciente transita entre diferentes níveis de cuidado à saúde. Objetivo: Realizar uma revisão de literatura sobre conciliação medicamentosa em idosos na transição do cuidado à saúde. Metodologia: Trata-se de revisão da literatura realizada na base de dados PubMed. Os critérios de inclusão foram: Enfoque na população idosa; idioma inglês, espanhol ou português; publicação nos últimos 5 anos. Dois revisores examinaram títulos e resumos e procederam à leitura integral e à inclusão dos artigos relevantes. Resultados: Doze estudos foram incluídos, dentre os quais a metade descreveu as discrepâncias de medicamentos nos pontos de transição, revelando como principal a omissão de algum fármaco; 3 avaliaram a contribuição do farmacêutico para o processo, evidenciando maior qualidade com o envolvimento desse profissional; e 5 analisaram a consistência das informações prestadas na continuidade do cuidado e o impacto da conciliação de medicamentos sobre os erros de medicação, demonstrando a importância da coleta de uma história medicamentosa inicial precisa para redução de eventos adversos, polifarmácia e erros de medicação. Conclusão: A conciliação medicamentosa revelou-se importante para a segurança do paciente idoso na transição do cuidado à saúde. A atuação do farmacêutico e a integridade da história farmacoterápica relacionaram-se a uma melhoria no processo, aprimorando a assistência prestada ao paciente.

Abstract Networks can help implement the United Nations Sustainable Development Goals (SDGs) in a variety of ways. They can facilitate the sharing of best practices and resources among organisations, enabling them to more effectively implement the SDGs. They can also help spread awareness on the SDGs and encourage people to take action. Networks can also assist coordinate collaborations between different organisations to support the SDGs implementation, especially in the academic sector. This study aims to fill the literature gap in assessing the transformative power of sustainability networking and reports on a worldwide analysis of the international networks which are believed to have been playing a significant role in the implementation of the SDGs in higher education. A concise online questionnaire was designed and administered to experts via an expert database mailing list and social networks, and collected 153 responses from 37 countries. This was complemented by an assessment of a set of case studies, where 5 major sustainability networks—ESSSR, IUSDRP, SDSN, AASHE and Copernicus Alliance—were evaluated in respect of their scope, target groups, types of activities and contributions to the SDGs. The results have highlighted the fact that, whereas assessed networks are very active, there is still a perceived need for more concerted actions to allow these networks to become more engaged in the implementation of the SDGs. This study suggests some specific actions which may foster a greater collaboration among networks in order to maximise the impact of their sustainability initiatives. The process of networking contributes to the advancement of sustainability and is closely related with contributions to policy, economic development and society, as well as particularly to SDG 17—Partnerships for the Goals. This study supports the role of networking, while indicating the need for greater collaboration among networks in order to maximise the impact of their initiatives and their transformative power.

Abstract Fumarate hydratase (FH) mutated papillary renal cell carcinoma is an aggressive variant of kidney cancer that poorly responds to conventional targeted therapies and immunotherapy. Here, we present the 10-year follow-up of a heavily pre-treated patient with several lines of therapy, achieving a remarkable complete response to anti-PD-1 rechallenge. In addition, we highlight a common immune-related adverse event of anti-PD-1, eosinophilia, as a possible biomarker of response and using TCGA data analysis, provide proof-of-concept for tumor expression of the eosinophil-related gene SIGLEC8, as a promising powerful predictor of prognosis for papillary renal cell carcinoma patients.

Abstract Background Worldwide, rural populations are recognized to be exposed to increased health challenges due to their living and working environment, socioeconomic status, and access to health services. According to the Romanian Country Health Profile 2023, approximately 46% of all deaths recorded in Romania in 2019 could be attributed to behavioral risk factors such as tobacco smoking, dietary risks, alcohol consumption and low physical activity. No data on rural versus urban areas are available to date, and research is needed to document health inequalities, identify barriers to health services, and explore solutions. Methods This study is an analysis of data collected during the Health Evaluation Survey carried out by the National Institute of Public Health in 2022 and aimed to reveal differences in health risk factors between rural and urban areas. The analysis was carried out under the methodological framework of the Health Evaluation Survey 2022, which is coordinated by the National Institute of Public Health. Results Our study’s objectively measured data revealed that the overall health profile of rural communities is characterized by lower education levels, lower incomes, and higher binge drinking rates than those of their urban counterparts. Additionally, rural inhabitants more often have high blood pressure, are more overweight and obese (per body mass index measurements) and have higher fasting plasma glucose. The health profile of the urban population revealed higher education levels and greater proportions of people with adequate monthly income, people with daily alcohol consumption, people who smoke, and people with hypercholesterolemia. Access to primary health care evaluated through proxy indicators was lower in rural areas but was relatively good overall. Conclusions Our analysis of the health profile of rural communities revealed a greater prevalence of obesity and overweight, especially among women, and an increased prevalence of heavy drinking among men. Access to primary health care evaluated through proxy indicators is lower in rural areas but is relatively good overall. Lower education levels and the possibility of lower health literacy underpin the need for targeted health education campaigns. Sustainable strategies for rural health need to be identified, especially in the field of health promotion and disease prevention programs. Trial registration This study is observational research involving human participants where no interventions were applied to the study population.

Abstract Background It is challenging for mothers who give birth very preterm to produce sufficient breast milk by expressing for weeks before their baby is able to feed from the breast, and then to transition from tube feeding to breastfeeding. Lactation is most successful when stimulated shortly after birth, established within 72 h, and maintained by expressing 6–8 times a day. This study explored mothers’ experiences of how breast milk feeding and breastfeeding for very preterm babies can be supported by staff and the facilities of a neonatal unit. Methods Twenty-three mothers of very preterm babies were interviewed, from four neonatal units in England with high or low rates of breast milk feeding at discharge. Interviews were analysed using the COM-B framework to consider how mothers’ behaviour (breast milk feeding and breastfeeding) is affected by capability, opportunity and motivation. Results Mothers’ motivation in the traumatic situation of very preterm birth was strongly affected by information from staff about the benefits of breast milk for their baby, the importance of early and frequent expressing, and how to assess the effectiveness of direct breastfeeding. It was maintained through positive feedback about their efforts which built their confidence, and reassurance about what is ‘normal’ growth when a baby begins direct breastfeeding. Motivation needed to be supported by opportunity, including access to equipment for expressing and facilities to stay near the neonatal unit, and also by capability, which required proactive and skilled information and support from staff. Specialist support and facilities varied between units, and some mothers were not given necessary information or had their motivation undermined by staff comments. Conclusions Interventions to increase breast milk feeding and breastfeeding for very preterm babies should address mothers’ motivation, capability and opportunity, aiming for systematic elimination of obstacles. Mothers value personalised and skilled specialist support, but also need other staff to be able to give consistent information and affirmation focused on their efforts rather than their success, with a trauma-informed approach. Investing in rooming-in facilities that minimise the separation of mothers and babies is likely to overcome a key obstacle.

Abstract Several bacterial strains have developed resistance against commercial antibiotics, and interestingly, supramolecular nanomaterials have shown considerable advantages for antibacterial applications. However, the main challenges in adopting nanotechnology for antibacterial studies are random aggregation, compromised toxicity, multi-step preparation approaches, and unclear structure-function properties. Herein, we designed the amphiphilic tripeptide that acts as a reducing and capping agent for silver metal to form silver-peptide colloidal nanohybrids with the mild assistance of UV light (254 nm) through the photochemical reduction method. The nanohybrids are characterized by different spectroscopic and microscopic techniques, and non-covalent molecular interactions between metal and peptide building blocks confirm their central role in the formation of nanohybrids. The tripeptide is biocompatible and can reduce the toxicity of silver ions (Ag+) by reducing to Ag0. These colloidal nanohybrids showed antibacterial activity against gram-negative and gram-positive bacterial strains, and the possible mechanism of killing bacterial cells could be membrane disruption. This synthetic strategy is facile and green, which helps avoid using toxic chemicals or reagents and complicated methods for colloidal nanohybrid preparation for biomedical applications.

Abstract Background Dysregulation of the complement system is involved in development of age-related macular degeneration (AMD). The complement cascade is regulated by membrane bound complement regulatory proteins (Cregs) on mononuclear leukocytes among others. This study aims to investigate systemic complement proteins and Cregs in AMD stages and their association with treatment response in neovascular AMD (nAMD). Methods In this clinical prospective study, treatment-naïve patients with nAMD, intermediate AMD (iAMD) and healthy controls were recruited and systemic complement proteins C3, C3a and C5a were investigated with electrochemiluminescence immunoassays, and Creg expression (CD35, CD46 and CD59) on T cells (CD4 + and CD8+) and monocytes (classical, intermediate and non-classical) investigated with flow cytometry. Treatment response in nAMD patients was evaluated after loading dose and after one year, and categorized as good, partial or poor. Complement proteins and Creg expression levels were compared between healthy controls, iAMD and nAMD, as well as between good, partial and poor nAMD treatment response groups. Polymorphisms in the CFH and ARMS2 genes were analyzed and compared to complement proteins and Creg expression levels in nAMD patients. Results One hundred patients with nAMD, 34 patients with iAMD and 61 healthy controls were included. 94 nAMD patients completed the 1-year follow-up. Distribution of treatment response in nAMD was 61 (65%) good, 26 (28%) partial, and 7 (7%) poor responders. The distribution of 1-year treatment response was 50 (53%) good, 33 (36%) partial, and 11 (11%) poor responders. The concentrations of systemic C3, C3a, and the C3a/C3-ratio were significantly increased in patients with nAMD compared to healthy controls (P

This study investigates a novel approach toward enhancing the efficacy of Lutetium-177 (Lu-177) radiopharmaceutical therapy by combining it with gold nanoparticles (AuNPs) in the HepG2 hepatic cancer cell line. Lu-177, known for its effective β radiation, also emits gamma rays at energies (113 keV and 208 keV) near the photoelectric absorption range, suggesting potential for targeted and localized radiation enhancement when used in conjunction with AuNPs. Thus, HepG2 cells were treated at two different activity levels (74 MBq and 148 MBq), with Lu-177 alone, with a combination of Lu-177 and AuNPs in two sizes (10 nm and 50 nm), while some received no treatment. Treatment efficacy was assessed by quantifying the radiation enhancement ratio (RER) and the apoptosis levels. The results reveal that combining Lu-177 with AuNPs significantly increases cell death and apoptosis compared to Lu-177 alone, with 10 nm AuNPs demonstrating superior effectiveness. Additionally, varying Lu-177 activity levels influenced the treatment outcomes, with higher activity levels further augmenting the therapeutic impact of combined therapy. These findings underscore the potential of utilizing Lu-177’s beta, but also gamma, emissions, traditionally considered non-therapeutic, for localized radiation enhancement when combined with AuNPs. This novel strategy leverages Lu-177 as an internal irradiator to exploit gamma radiation for a targeted therapeutic advantage without requiring nanoparticle functionalization. The study provides a promising approach to improving radionuclide therapy and sets the stage for future research aimed at optimizing cancer treatments through the combined use of Lu-177 and AuNPs.

Abstract Introduction Appropriate oral antibiotic therapy for the treatment of acute bacterial skin and skin structure infections (ABSSSI) is a challenge, as current oral treatment guidelines do not fully cover the most common skin pathogens. Both linezolid and omadacycline are available as intravenous or bioequivalent oral formulations. Materials and methods This post hoc analysis of the OASIS-1 (ClinicalTrials.gov identifier NCT02378480) and OASIS-2 (ClinicalTrials.gov identifier NCT02877927) phase 3 trials assessed safety and clinical efficacy of intravenous (IV)-start versus oral (PO)-start therapy in patients treated with omadacycline or linezolid for ABSSSI. In OASIS-1, patients were randomized to IV omadacycline or linezolid, with optional switch to oral therapy, while patients in OASIS-2 received oral omadacycline or linezolid. Treatment was provided for 7–14 days in both studies. The primary endpoint was an early clinical response (ECR) at 48 to 72 h, defined as survival and ≥ 20% reduction in lesion size, without rescue antibacterial therapy. Results A total of 645 IV-start inpatients and 735 PO-start outpatients were assessed. Median age was 47 years for the IV-start group and 44 years for the PO-start group. Most patients had solely gram-positive infections (97% in each group; ECR [85.2% IV-start and 85.0% PO-start]), and the incidence of treatment-emergent adverse events (AEs) was similar between the groups. The most frequent AEs observed were nausea (11.2% [IV-start] versus 18.9% [PO-start]) and subcutaneous abscess (5.6% [IV-start] versus 1.9% [PO-start]). Discontinuation due to AEs was infrequent in both groups (2% [IV-start] versus 1.2% [PO-start]). Conclusion Oral therapy is equally efficacious to IV therapy when omadacycline or linezolid is used to treat ABSSSIs. These data strengthen the evidence for oral omadacycline as a therapeutic option for ABSSSI, particularly for patients who have experienced treatment failure because of the limitations of other therapies. Trial registration Clinicaltrials.gov, NCT02378480 and NCT02877927.

Abstract Tubulointerstitial fibrosis associated with chronic kidney disease (CKD) represents a global health care problem. We previously reported that short and dysfunctional telomeres lead to interstitial renal fibrosis; however, the cell-of-origin of kidney fibrosis associated with telomere dysfunction is currently unknown. We induced telomere dysfunction by deleting the Trf1 gene encoding a telomere-binding factor specifically in renal fibroblasts in both short-term and long-term life-long experiments in mice to identify the role of fibroblasts in renal fibrosis. Short-term Trf1 deletion in renal fibroblasts was not sufficient to trigger kidney fibrosis but was sufficient to induce inflammatory responses, ECM deposition, cell cycle arrest, fibrogenesis, and vascular rarefaction. However, long-term persistent deletion of Trf1 in fibroblasts resulted in kidney fibrosis accompanied by an elevated urinary albumin-to-creatinine ratio (uACR) and a decrease in mouse survival. These cellular responses lead to the macrophage-to-myofibroblast transition (MMT), endothelial-to-mesenchymal transition (EndMT), and partial epithelial-to-mesenchymal transition (EMT), ultimately causing kidney fibrosis at the humane endpoint (HEP) when the deletion of Trf1 in fibroblasts is maintained throughout the lifespan of mice. Our findings contribute to a better understanding of the role of dysfunctional telomeres in the onset of the profibrotic alterations that lead to kidney fibrosis.

Background.The issue of diarrheal diseases remains relevant for modern health care in all countries. Campylobacteriosis is the most common infectious disease with foodborne transmission and poultry meat is a transmission factor.Materials and methods.724 items of faeces sampled from patients with diarrheal syndrome and 283 samples of faeces of chickens raised on private farms and five poultry farms in the province were studied. For bacteriological method were used selective media. Traditional routine tests (cell morphology, cytochrome oxidase, catalase, hydrolysis of sodium hippurate and indoxyl acetate) and MALDI-ToF mass spectrometry was performed for identification. The susceptibility of strains to antibiotics was analysed using the disc-diffusion method. Results were interpreted according to the EUCAST criteria, versions 2019–2022.Results.Campylobacterspp. was cultured in 65 out of 724 faecal samples from patients with acute diarrhoea, of them 83.08% were identified asC. jejuni, and 16.92% asC. coli. Of the 237Campylobacterstrains from chicken were identified asC. jejuni(54.0%), asC. coli(46.0%).Campylobacterspp. strains from humans were resistant to tetracycline (40.0%), to erythromycin (6.15%), to ciprofloxacin (12.31%). The strains from chickens kept on farms, were resistant to tetracycline in 42.55%, to ciprofloxacin — in 22.70% and to erythromycin — in 11.35%. The strains from chickens kept on private farms were resistant to tetracycline in 4.17%, to ciprofloxacin — in 1.04%, all strains were sensitive to erythromycin.Conclusion.Thus, due to the widespread prevalence ofCampylobacterspp., infectious diseases they cause remain a topical issue. Studying the resistance to antibiotics inCampylobacterspp. among poultry could allow to develop new approaches to confirming the significance of their foodborne nature and to improve the national disease prevention system.

An enduring debate in research revolves around the association between elevated endogenous testosterone levels and prostate cancer. This systematic review is intended to assess the present understanding of the role of endogenous testosterone in the diagnosis and treatment of low- and intermediate-risk prostate cancer. Our search strategy was the following: (endogenous testosterone) AND (((low risk) OR (intermediate risk)) AND ((diagnosis) OR (treatment))) AND (prostate cancer); that was applied to PubMed, Web of Science, and Scopus databases to identify pertinent articles. Two investigators performed an independent selection following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The preliminary investigation detected 105 records, and 81 records remained after eliminating duplicates. Following the review of titles and abstracts, 71 articles were excluded. A comprehensive examination of the full text was conducted for 10 articles, excluding 3 of them. After revising the references of eligible articles, other 3 articles were included. We finally identified 10 suitable studies, including three main topics: (1) association between endogenous testosterone and European Association of Urology (EAU) risk classes; (2) association between endogenous testosterone density and the tumor load; and (3) association of endogenous testosterone with tumor upgrading and tumor upstaging. Actual literature about the impact of endogenous testosterone on low- and intermediate-risk prostate cancer is not numerous, but appears to be still conflicting. More investigations are needed to increase the consistency of the literature’s results.

The study aimed to test if Briganti’s 2012 nomogram could be associated with the risk of prostate cancer (PCa) progression in European Association of Urology (EAU) intermediate-risk patients treated with robotic surgery. From January 2013 to December 2021, 527 consecutive patients belonging to the EAU intermediate-risk class were selected. Briganti’s 2012 nomogram, which predicts the risk of pelvic lymph node invasion (PLNI), was assessed as a continuous and dichotomous variable that categorized up to the median of 3.0%. Disease progression defined as biochemical recurrence and/or metastatic progression was evaluated by Cox proportional hazards (univariate and multivariate analysis). After a median follow-up of 95.0 months (95% confidence interval [CI]: 78.5–111.4), PCa progression occurred in 108 (20.5%) patients who were more likely to present with an unfavorable nomogram risk score, independently by the occurrence of unfavorable pathology including tumor upgrading and upstaging as well as PLNI. Accordingly, as Briganti’s 2012 risk score increased, patients were more likely to experience disease progression (hazard ratio [HR] = 1.060; 95% CI: 1.021–1.100; P = 0.002); moreover, it also remained significant when dichotomized above a risk score of 3.0% (HR = 2.052; 95% CI: 1.298–3.243; P < 0.0001) after adjustment for clinical factors. In the studied risk population, PCa progression was independently predicted by Briganti’s 2012 nomogram. Specifically, we found that patients were more likely to experience disease progression as their risk score increased. Because of the significant association between risk score and tumor behavior, the nomogram can further stratify intermediate-risk PCa patients, who represent a heterogeneous risk category for which different treatment paradigms exist.

Abstract The role of universities in addressing climate change is often discussed, but one crucial aspect tends to be overlooked: their potential contribution to carbon sequestration. Many universities around the world possess significant tracts of land, often featuring substantial forested areas. These landscapes represent an underutilised opportunity for nature-based solutions that facilitate carbon sequestration. This paper discusses the current trends and status of university-owned forests, highlighting some of the largest and most ecologically significant forests managed by academic institutions across different regions worldwide. It explores their capacity for carbon sequestration, their biodiversity value, and the potential they hold for contributing to global climate change mitigation efforts. Furthermore, the article examines how these university forests can serve as dynamic, living laboratories for research, education, and conservation, as well as spaces for community engagement. In addition to their environmental benefits, these green spaces can enhance human health and well-being. Based on this analysis, the paper offers recommendations for universities on how to optimise their forested lands as carbon sinks and enhance their role in advancing sustainable practices, research, and education. Graphical abstract

Abstract Background Intragastric botulinum neurotoxin injections (IBNI) are offered off-label in the private medical sector in a few European countries as a safe and effective weight-loss measure. In February and March 2023, an outbreak of iatrogenic botulism occurred in several European countries following IBNI treatment in Turkey. This case series describes the clinical features of severe iatrogenic botulism after IBNI. Methods We retrospectively summarize the clinical course and emergency department and intensive care unit interventions in ten cases of severe iatrogenic botulism that occurred after receiving IBNI in this sudden outbreak in Austria and Germany. Results Seven out of ten cases initially showed characteristic symptoms of botulism with diplopia, dysphagia, dysarthria, dysarthrophonia, and descending paralysis. All patients were hospitalized, six in an intensive care unit and partially requiring mechanical ventilation. All patients recovered and were discharged without relevant permanent deficits. Conclusion Our study highlights ten clinical cases in this iatrogenic botulism outbreak, representing the largest reported outbreak worldwide. Clinicians should be aware of the risks associated with medical procedures involving botulinum neurotoxins and ensure measures to minimize the risk of iatrogenic botulism.

Introduction. Anxiety and depression have an increased prevalence in cancer patients, especially in those in an advanced stage of the disease. These disorders have a major impact on the social life, existential concerns and quality of life of cancer patients. Materials and Methods. A number of 114 consecutive patients were included in the study (in a period of 2 weeks) who were screened for anxiety, depression and for other common symptoms, using Hospital Anxiety and Depression Scale (HADS) and Edmonton Symptom Assessment System (ESAS). Results. Regarding the age - the abnormal level of anxiety and depression: the percentage of patients over 65 years was higher than the percentage of patients under 64 years, both in terms of anxiety and depression. Regarding the Performance status ECOG - abnormal level of anxiety and depression: the percentage of patients with ECOG = 3-4 is higher than that of patients with ECOG = 0-2. Results. The increased prevalence of anxiety and depression requires psychological counseling and treatment. It is important for these symptoms to be identified as soon as possible, in order to provide a good quality of life. Conclusions. The model we propose is for the HADS to be a screening tool on admission to a palliative care ward, for certain categories of patients.

Abstract China’s global infrastructure financing flagship, the Belt and Road Initiative (BRI) encompasses countries hosting over 60% of the global population and one-third of worldwide GDP. It is based mainly on long-term loans that will mature decades into the future, and timely repayments are only possible if they remain commercially viable. But despite its vast global scope, little is known about the climate risks that could imperil the operations of BRI projects over the next few decades, and, consequently, threaten their long-term sustainability. We narrow this gap by estimating the impacts of future climate change on 217 BRI projects across 70 countries and 9 sectors in two dimensions. First, the effects of increased heat stress on human physical work capacity are calculated using the wet bulb globe temperature and an assessment of the workload for each selected BRI project. Second, the potential structural damages from more frequent flooding incidents are measured by return period (RP), where a shorter RP signals heightened risk. Both have direct impacts on human productivity and infrastructural integrity, which are essential to maintaining the operational viability and financial stability of BRI projects. We compared projected changes on both measures for the mid- and late-twentieth centuries (2041–2060 and 2081–2100) to the historical baseline (1981–2010). We found that BRI projects face escalating vulnerability to climatic risks on both counts. The results underscore a broad variance across different future carbon emission scenarios measured under the Shared Socioeconomic Pathways (including SSP1-2.6, SSP2-4.5, SSP3-7.0, and SSP5-8.5). BRI’s aggregated climatic risks are substantially elevated under a high carbon emission scenario compared to a low emission scenario. By the end of the twentieth century, labor workability under SSP3-7.0 (31%) could potentially decrease three times more compared to SSP1-2.6 (10%). Under an intermediate-emission scenario (SSP2-4.5), floods with a historical return period of 10 years could have a return period of 5 years in the future. Significantly hampering the utilization and economic return generation potential of infrastructure projects. In addition, regional geography contributes to risk heterogeneity, with 100-year floods occurring every 15 years in South Asia and every 24 years in Sub-Saharan Africa. Such climate risk implications, potentially overlooked by development financiers, represent significant risks to the sustenance of the BRI, estimated to be worth $1 trillion.

Abstract Controlling crystal growth alignment in low-dimensional perovskites (LDPs) for solar cells has been a persistent challenge, especially for low-n LDPs (n 1.7 eV) impeding charge flow. Here we overcome such transport limits by inducing vertical crystal growth through the addition of chlorine to the precursor solution. In contrast to 3D halide perovskites (APbX3), we find that Cl substitutes I in the equatorial position of the unit cell, inducing a vertical strain in the perovskite octahedra, and is critical for initiating vertical growth. Atomistic modelling demonstrates the thermodynamic stability and miscibility of Cl/I structures indicating the preferential arrangement for Cl-incorporation at I-sites. Vertical alignment persists at the solar cell level, giving rise to a record 9.4% power conversion efficiency with a 1.4 V open circuit voltage, the highest reported for a 2 eV wide band gap device. This study demonstrates an atomic-level understanding of crystal tunability in low-n LDPs and unlocks new device possibilities for smart solar facades and indoor energy generation.

Abstract After traumatic events, simple cue-threat associative memories strengthen while episodic memories become incoherent. However, how the brain prioritises cue associations over episodic coding of traumatic events remains unclear. Here, we developed an original episodic threat conditioning paradigm in which participants concurrently form two memory representations: cue associations and episodic cue sequence. We discovered that these two distinct memories compete for physiological fear expression, reorganising overnight from an overgeneralised cue-based to a precise sequence-based expression. With multivariate fMRI, we track inter-area communication of the memory representations to reveal that a rebalancing between hippocampal- and prefrontal control of the fear regulatory circuit governs this memory maturation. Critically, this overnight re-organisation is altered with heightened trait anxiety. Together, we show the brain prioritises generalisable associative memories under recent traumatic stress but resorts to selective episodic memories 24 h later. Time-dependent memory competition may provide a unifying account for memory dysfunctions in post-traumatic stress disorders.