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Introdução O Programa Farmácia Cuidar + foi implementado em 90% dos municípios do Rio Grande do Sul no ano de 2021, com o objetivo de ampliar, promover e qualificar os serviços farmacêuticos prestados nas Farmácias de Medicamentos Especiais (FME). O objetivo deste trabalho é descrever os resultados da fase inicial do eixo do cuidado farmacêutico do Programa Farmácia Cuidar+. Métodos Foi elaborada uma matriz de indicadores de avaliação de serviços clínicos farmacêuticos relacionados ao Componente Especializado da Assistência Farmacêutica (CEAF) e ao componente especial do estado que compõem os medicamentos da FME. A matriz foi validada por especialistas e os indicadores receberam um valor. A matriz foi aplicada por correio eletrônico na fase inicial do programa. A mesma matriz também será aplicada na fase intermediária e avançada do programa. O estudo foi aprovado pelo Comitê de Ética parecer número 5.235.955. Resultados A matriz final foi composta por oito dimensões e 22 indicadores que compõem uma nota de zero a cem e estão assim distribuídos nas dimensões: efetividade do tratamento de Asma (n=1), DPOC (n=1), Adesão (n=1), Atividades clínicas do farmacêutico(n=11), Consultório (n=1), Segurança (n=3), Educação em saúde (n=2) e Educação continuada (n=2). A nota média dos municípios que responderam o formulário (n=351) foi de 18,89 pontos, variando de 0,00 a 73,53 pontos. Efetividade do controle da Asma e da DPOC, Avaliação e monitoramento dos exames, Conciliação Medicamentosa, Avaliação de interação e Registro dos Efeitos Adversos foram os indicadores que menos pontuaram. Discussão e conclusões O instrumento proposto apresentou viabilidade de aplicação e os indicadores propostos foram capazes de identificar fragilidades relacionadas ao cuidado farmacêutico na dispensação de medicamentos para o controle de doenças crônicas que fazem parte do CEAF. O perfil longitudinal do estudo permitirá avaliar e acompanhar as melhorias nos serviços clínicos das Farmácias de Medicamentos Especiais e identificar quais fatores contribuem para a segurança do paciente, o uso adequado de medicamentos e o controle de doenças crônicas. O Programa Farmácia Cuidar+ é inovador ao alocar subsídios financeiros para ampliar os serviços clínicos farmacêuticos no Sistema Único de Saúde e por isso os indicadores para a avaliação de sua implantação são importantes como ferramentas de fortalecimento de políticas baseadas em evidências.

BackgroundPeople with severe or profound intellectual disability and visual impairment tend to have serious problems in orientation and mobility and need assistance for their indoor traveling. The use of technology solutions may be critically important to help them curb those problems and achieve a level of independence. ObjectiveThis study aimed to assess a new technology system to help people with severe to profound intellectual disability and blindness find room destinations during indoor traveling. MethodsA total of 7 adults were included in the study. The technology system entailed a barcode reader, a series of barcodes marking the room entrances, a smartphone, and a special app that controlled the presentation of different messages (instructions) for the participants. The messages varied depending on whether the participants were (1) in an area between room entrances, (2) in correspondence with a room entrance to bypass, or (3) in correspondence with a room entrance representing the destination to enter. The intervention with the technology system was implemented according to a nonconcurrent multiple baseline design across participants. Sessions included 7 traveling trials, in each of which the participants were to reach and enter a specific room (1 of the 7 or 9 available) to deliver an object they had carried (transported) during their traveling. ResultsThe participants’ mean frequency of traveling trials completed correctly was between zero and 2 per session during the baseline (without the system). Their mean frequency increased to between about 6 and nearly 7 per session during the intervention (with the system). ConclusionsThe findings suggest that the new technology system might be a useful support tool for people with severe to profound intellectual disability and blindness.

Torpor is a state used by several mammals to survive harsh winters and avoid predation, characterized by a drastic reduction in metabolic rate followed by a decrease in body temperature, heart rate, and many physiological variables. During torpor, all organs and systems must adapt to the new low-energy expenditure conditions to preserve physiological homeostasis. These adaptations may be exploited in a translational perspective in several fields. Recently, many features of torpor were shown to be mimicked in non-hibernators by the inhibition of neurons within the brainstem region of the Raphe Pallidus. The physiological resemblance of this artificial state, called synthetic torpor, with natural torpor has so far been described only in physiological terms, but no data have been shown regarding the induced morphological changes. Here, we show the first description of the ultrastructural changes in the liver, kidney, lung, skeletal muscle, and testis induced by a 6-hours inhibition of Raphe Pallidus neurons in a non-hibernating species, the rat.

IntroductionNon-invasive evaluation of myocardial tissue is a major goal of cardiac imaging. This is the case of myocardial fibrosis which is crucial in many myocardial diseases. Cardiac extracellular volume (ECV) was shown to indicate myocardial fibrosis and early cardiac involvement. With this study, our objective is to evaluate ECV measured with cardiac magnetic resonance (CMR) in patients with myotonic dystrophy type 1 (DM1) and 2 (DM2) as potential imaging biomarkers of subclinical cardiac pathology, and its relationship with demographic and clinical parameters, ECG-derived measures of cardiac conduction, and neuromuscular performance status.Materials and methodsWe retrospectively analyzed 18 DM1 patients and 4 DM2 patients without apparent cardiac disease who had CMR at our center. Differences between independent distributions were evaluated using Mann–Whitney U test, while correlations were evaluated using Spearman’s ρ.ResultsGlobal ECV in DM1 patients (median 28.36; IQR 24.81–29.77) was significantly higher (p = 0.0141) than in DM2 patients (median 22.93; IQR 21.25–24.35), and than that reported in literature in healthy subjects (p = 0.0374; median 25.60; IQR 19.90–31.90). Septal ECV was significantly higher (p = 0.0074) in DM1 (median 27.37; IQR 25.97–29.74) than in DM2 patients (median 22.46; 21.57–23.19). Global ECV showed a strong, positive correlation with septal ECV (ρ = 0.9282, p

Many patients with cancer experience cancer-related cognitive decline (CRCD). Previous studies have shown that elevated S100β, a calcium-binding protein commonly found in glial cells, can exhibit neurotoxic effects, including disruption of the blood-brain barrier (BBB). We studied changes in S100β levels in patients with breast cancer receiving chemotherapy, and the relationship to changes in cognitive function. A total of 505 women with breast cancer (mean (sd) age; 53.4 (53.6)) and 336 age-matched controls without cancer (52.8 (10.3)) were included from a nationwide study as part of the National Cancer Institute Community Oncology Research Program (NCORP). Both groups provided blood samples and completed neurocognitive assessments within 7 days before the patients with breast cancer received their first chemotherapy dose (pre-chemotherapy; T1) and within 1 month of their last chemotherapy administration (post-chemotherapy; T2). Utilizing a linear mixed model, multivariate linear regressions, and Spearman rank correlations (rs), we investigated longitudinal changes in serum S100β concentrations and their relationships to changes in neurocognitive outcomes over time. We observed an increase in S100β for patients with breast cancer (p = 0.002), but not for controls without cancer over time (p = 0.683). Additionally, we identified subtle relationships between increases in serum S100β and worsening in cognitive performance on the Backward Counting test (rs = 0.11, p = 0.041) and self-reported FACT-Cog Perceived Cognitive Abilities (rs = −0.10, p = 0.025). Regression analyses adjusted for age, race, body-mass index (BMI), education, menopausal status, anxiety, and depression revealed a trend remained for the relationship of S100β with Backward Counting. In conclusion, we found that patients with breast cancer experience a significant increase in concentration of serum S100β over the course of chemotherapy. This increase is correlated with worsening in some neurocognitive outcomes from pre-to post-chemotherapy, with trending results remaining following adjustment for covariates.

Forests play a crucial role in storing much of the world's carbon (C). Accurately estimating C sequestration is essential for addressing and mitigating the impacts of global warming. While many studies have used machine learning models to estimate carbon storage (CS) in forests based on remote sensing data, this research further examines C sequestration (i.e., the annual carbon uptake by trees; CSE). The objectives of this study are two-fold: firstly, to identify the best models for estimating CSE and CS by testing various methods, and secondly, to examine the effect of climatic data and the canopy height model (CHM) on the estimation of CSE. To achieve the first objective, we will compare the performance of fourteen models, including twelve machine learning models, one deep learning model, and an ensemble model that combines the top four independent models. For the second objective, we study the effect of four input configurations: the first is a baseline configuration based solely on attributes extracted from satellite images (Sentinel-2) and geomorphology; the second combines satellite features with climatic data; the third uses a CHM derived from LiDAR instead of climatic data; and the fourth combines all available features: satellite images, climatic data, and CHM. The results show that adding climatic data does not improve the estimation of CSE and CS. However, adding CHM features significantly improves the models' performance for both targets. The implemented ensemble model demonstrated the best performance across all configurations.

ABSTRACT Given that the Atlantic Forest is one of the most threatened biomes in the world, this study aims to compare alpha and beta diversity of the bee assemblage sampled in a site covered by remnants of the Atlantic Forest, in the municipality of Colombo, Paraná State, with those from ten other sites along the Curitiba Metropolitan Region, previously sampled under similar methodology. Our objective is to analyze if species diversity and composition are influenced by spatial gradients and vegetation cover. The study site’s bee assemblage is composed of 91 species, including Apis mellifera. The assemblage consists of 42 Apinae, 33 Halictinae, eight Megachilinae, five Colletinae, and three Andreninae species. Compared to the other sites, 11 species were sampled exclusively in Colombo, including Bombus brasiliensis Lepeletier, 1836, Centris proxima Friese, 1899, and Trichocerapis mirabilis (Smith, 1865). The most abundant native species were Trigona spinipes (Fabricius, 1793) (204 individuals), Paratrigona subnuda Moure, 1947 (176) and Scaptotrigona bipunctata (Lepeletier, 1836) (113). Despite its high vegetation cover, Colombo exhibited intermediate values of species richness and diversity when compared to other sites, with a high dominance of Meliponini species. The sites could be separated based on beta diversity and the north–south gradient and vegetation cover were significantly related to species composition at this study’s spatial scale. Understanding the regional communities and the factors that influence species composition is essential for planning effective biodiversity conservation actions.

It is well established that several Homo sapiens populations experienced admixture with extinct human species during their evolutionary history. Sometimes, such a gene flow could have played a role in modulating their capability to cope with a variety of selective pressures, thus resulting in archaic adaptive introgression events. A paradigmatic example of this evolutionary mechanism is offered by the EPAS1 gene, whose most frequent haplotype in Himalayan highlanders was proved to reduce their susceptibility to chronic mountain sickness and to be introduced in the gene pool of their ancestors by admixture with Denisovans. In this study, we aimed at further expanding the investigation of the impact of archaic introgression on more complex adaptive responses to hypobaric hypoxia evolved by populations of Tibetan/Sherpa ancestry, which have been plausibly mediated by soft selective sweeps and/or polygenic adaptations rather than by hard selective sweeps. For this purpose, we used a combination of composite-likelihood and gene network-based methods to detect adaptive loci in introgressed chromosomal segments from Tibetan WGS data and to shortlist those presenting Denisovan-like derived alleles that participate to the same functional pathways and are absent in populations of African ancestry, which are supposed to do not have experienced Denisovan admixture. According to this approach, we identified multiple genes putatively involved in archaic introgression events and that, especially as regards TBC1D1, RASGRF2, PRKAG2, and KRAS, have plausibly contributed to shape the adaptive modulation of angiogenesis and of certain cardiovascular traits in high-altitude Himalayan peoples. These findings provided unprecedented evidence about the complexity of the adaptive phenotype evolved by these human groups to cope with challenges imposed by hypobaric hypoxia, offering new insights into the tangled interplay of genetic determinants that mediates the physiological adjustments crucial for human adaptation to the high-altitude environment.

Hybrid powertrains represent a potential solution to reduce the emissions of agricultural machineries and meet the restrictive standards introduced by the different governments with the aim to achieve Climate Neutrality. This study investigates a hybrid powertrain in the series architecture as it potentially better suits the requirements of agricultural applications, even though it has not yet been fully investigated in literature. A series hybrid powertrain model was built, then its control and components size were optimized for a vineyard/orchard tractor using real on-field data and a two level optimization procedure. This last is based on Dynamic Programming and the exhaustive search approach. Both environmental and economical aspects were taken into account in the optimization goals; in addition, powertrain volume constraints were introduced as they represent a key limiting factor for tractor hybridization. The average efficiency of the hybrid powertrain is higher than that of the conventional configuration. A sensitivity analysis was performed to understand the impact of different design parameters. This analysis showed that hybrid powertrains have enormous potential in the agricultural market, as this type of configuration was simulated in several scenarios for different European countries showing to be the most convenient. Moreover, this trend is expected to intensify with the upcoming emissions regulations and the increase in fuel prices through emission taxes.

The Raphe Pallidus (RPa) is a brainstem nucleus containing sympathetic premotor neurons that control thermogenesis and modulate cardiovascular function. It receives inputs from various hypothalamic areas, including the Lateral Hypothalamus (LH), a heterogeneous region intricately involved in several autonomic and behavioral functions. A key subpopulation of neurons in the LH expresses orexin/hypocretin, a neuropeptide which is crucially involved in the regulation of the wake–sleep states and feeding behavior. The RPa receives orexinergic projections from the LH and orexinergic signalling in the RPa has been shown to enhance thermogenesis in the anaesthetized rat, but only in the presence of an already existing thermogenic drive, without significantly affecting cardiovascular function. The present work was aimed at exploring the effects on thermoregulation and autonomic function and the possible role in the modulation of the wake–sleep states and feeding behavior of orexin injection in the RPa in the free-behaving rat. In order to assess the influence of an already present thermogenic drive on orexinergic signalling in the RPa, animals were studied at three different ambient temperatures (Ta, 10°C, 24°C, and 32°C). We found that orexin injection into the RPa variably affected the wake–sleep states, autonomic functions, motor activity, and feeding behavior, at the different Tas. In particular, in the first post-injection hour, we observed an increase in wakefulness, which was large at Ta 24°C and Ta 10°C and rather mild at Ta 32°C. Deep brain temperature was increased by orexin injection at Ta 10°C, but not at either Ta 24°C or Ta 32°C. Moreover, an increase in mean arterial blood pressure occurred at Ta 24°C, which was probably masked by the high baseline levels at Ta 10°C and was completely absent at Ta 32°C. Finally, an enhancement in feeding behavior was observed at Ta 24°C and 10°C only. In accordance with what observed in anaesthetized rats, orexinergic signalling in the RPa seems to be ineffective in the absence of any thermogenic drive. Moreover, the effects observed on the wake–sleep states and feeding behavior introduce the RPa as a novel player in the central neural network promoting wakefulness and feeding.

Abstract The objective of this work was to evaluate the effect of temperature on disks and rings for seeders and the consequences for the performance of seed distribution. The treatments consisted of the heating of three types of disks and rings for seeders at 30, 40, 50, 60, 70, 80, 90, and 100°C, with four replicates. The evaluated variables were: fitting to the base of the seeder, thickness, diameter, and quality of seed distribution (failed, multiple, and acceptable spacings). There is no significant deformation in the disks and rings for the analyzed variables, and the performance of the longitudinal seed distribution is maintained at all temperatures.

Abstract Synthetic cocaine analogs are designer drugs that recently emerged as non‐controlled substitutes for their parent drug. Among them, nitracaine is of particular concern for its psychoactive effect. In this work, we present a thorough characterization of the electrochemical behavior of nitracaine, with a final quantification performed by differential pulse voltammetry (DPV) in ethanol/lithium perchlorate 0.1 M. The selectivity of the method and reproducibility of results were assessed. LOQ of 0.3 μg mL−1 and a linear dynamic range of up to 400 μg mL−1 were obtained. In addition, recoveries from 85 % to 101 % were achieved on both simulated and real samples. For nitracaine analysis in urine, a clean‐up and a preconcentration step by solid phase extraction (SPE) using the adsorbent Florisil have been developed and optimized through the Design of Experiments (DoE) strategy, thus achieving an enrichment factor of 20.

BackgroundCurrently, patients with cystic fibrosis do not routinely monitor their respiratory function at home. ObjectiveThis study aims to assess the clinical validity of using different connected health devices at home to measure 5 physiological parameters to help prevent exacerbations on a personalized basis from the perspective of patient empowerment. MethodsA multicenter interventional pilot study including 36 patients was conducted. Statistical process control—the cumulative sum control chart (CUSUM)—was used with connected health device measures with the objective of sending patients alerts at a relevant time in order to identify their individual risk of exacerbations. Associated patient education was delivered. Quantitative and qualitative data were collected. ResultsOne-half (18/36) of the patients completed the protocol through the end of the study. During the 12-month intervention, 6162 measures were collected with connected health devices, 387 alerts were sent, and 33 exacerbations were reported. The precision of alerts to detect exacerbations was weak for all parameters, which may be partly related to the low compliance of patients with the measurements. However, a decrease in the median number of exacerbations from 12 months before the study to after the 12-month intervention was observed for patients. ConclusionsThe use of connected health devices associated with statistical process control showed that it was not acceptable for all patients, especially because of the burden related to measurements. However, the results suggest that it may be promising, after adaptations, for early identification and better management of exacerbations. Trial RegistrationClinicalTrials.gov NCT03304028; https://clinicaltrials.gov/study/NCT03304028

Objetivo: Demostrar la seguridad de realizar estudios tomográficos con contraste endovenoso en sujetos sin ayuno. Método: Estudio retrospectivo que analizó estudios tomográficos de abdomen con uso de contraste endovenoso. Se dividieron según la presencia/ausencia de ayuno y se registraron los eventos adversos. Resultados: Se analizaron 542 tomografías donde el 40.2% cumplió con ayuno. En todos los casos se completó el estudio. La distribución por sexo fue similar y la mediana de edad de 47 años (RIC: 33-60). En ninguno de los grupos se presentaron eventos adversos o complicaciones. Conclusiones: El ayuno previo a un estudio tomográfico con uso de medio de contraste endovenoso no influye en la aparición de efectos adversos o complicaciones.

Microplastics (MPs) accumulate in tissues, including kidney tissue, while Bisphenol A (BPA) is a plasticizer of particular concern. At present, the combined effects of MPs and BPA are unexplored in human renal cells. Therefore, we exposed a proximal tubular cell line (PTECs) to polyethylene (PE)-MPs and BPA, both separately and in combination. When co-exposed, cells showed a significantly reduced cell viability (MTT test) and a pronounced pro-oxidant (MDA levels, NRF2 and NOX4 expression by Western blot) and pro-inflammatory response (IL1β, CCL/CCR2 and CCL/CCR5 mRNAs by RT-PCR), compared to those treated with a single compound. In addition, heat shock protein (HSP90), a chaperone involved in multiple cellular functions, was reduced (by Western Blot and immunocytochemistry), while aryl hydrocarbon receptor (AHR) expression, a transcription factor which binds environmental ligands, was increased (RT-PCR and immunofluorescence). Our research can contribute to the study of the nephrotoxic effects of pollutants and MPs and shed new light on the combined effects of BPA and PE-MPs.

Summary: Intra-tumor heterogeneity, i.e., the presence of diverse cell types and subpopulations within tumors, presents a significant obstacle in cancer treatment due to its negative consequences for resistance to therapy and disease recurrence. However, the mechanisms that underlie intra-tumor heterogeneity and result in the plethora of different cancer cells within a single lesion remain poorly understood. Here, we leverage the SW480 cell line as a model system to investigate the molecular and functional diversity of colon cancer cells. Through a combination of fluorescence-activated cell sorting (FACS) analysis and transcriptomic profiling, we identified three distinct subpopulations, namely resident cancer stem cells (rCSCs), migratory CSCs (mCSCs), and high-relapse cells (HRCs). These subpopulations show varying Wnt signaling levels and gene expression profiles mirroring their stem-like and functional properties. Examination of publicly available spatial transcriptomic data confirms the presence of these subpopulations in patient-derived cancers and reveals their distinct spatial distribution relative to the tumor microenvironment.

Summary: Heat shock (HS) coincides with the assembly of translationally arrested heat shock messenger ribonucleoprotein particles (HS-mRNPs) and condensates. Here, we present a protocol to reconstitute HS-mRNPs and HS condensates with eIF4G, eIF4E, Pab1p, and mRNA in vitro. In addition, we describe the necessary steps to measure the effect of HS-mRNPs and HS condensates on translation in yeast extracts. The protocol can be modified to study mRNPs and condensates assembled with other proteins and to study translation in extracts prepared from different cells.For complete details on the use and execution of this protocol, please refer to Desroches Altamirano et al.1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

This review paper examines the hydrogeological characteristics and challenges of urban groundwater management in ten major Italian cities: Turin, Milano, Padova, Bologna, Roma, Pescara, Napoli, Bari, Catania, and Cagliari. Urbanization has placed significant pressure on groundwater systems, highlighting the need for sustainable management. The study categorizes the cities based on their hydrogeological settings and groundwater uses, identifying key issues such as salinization, industrial contamination, and land subsidence. The findings emphasize the importance of urban local aquifers (ULAs) for drinking water, industry, and ecological support, advocating for integrated urban water management and governance to enhance resilience against future water shortages and climate change impacts.

PurposeWe undertook a study to evaluate the current state of pedagogy on antiracism, including barriers to implementation and strengths of existing curricula, in undergraduate medical education (UME) and graduate medical education (GME) programs in US academic health centers.MethodsWe conducted a cross-sectional study with an exploratory qualitative approach using semistructured interviews. Participants were leaders of UME and GME programs at 5 institutions participating in the Academic Units for Primary Care Training and Enhancement program and 6 affiliated sites from November 2021 to April 2022.ResultsA total of 29 program leaders from the 11 academic health centers participated in this study. Three participants from 2 institutions reported the implementation of robust, intentional, and longitudinal antiracism curricula. Nine participants from 7 institutions described race and antiracism-related topics integrated into health equity curricula. Only 9 participants reported having "adequately trained" faculty. Participants mentioned individual, systemic, and structural barriers to implementing antiracism-related training in medical education such as institutional inertia and insufficient resources. Fear related to introducing an antiracism curriculum and undervaluing of this curriculum relative to other content were identified. Through learners and faculty feedback, antiracism content was evaluated and included in UME and GME curricula. Most participants identified learners as a stronger voice for transformation than faculty; antiracism content was mainly included in health equity curricula.ConclusionsInclusion of antiracism in medical education requires intentional training, focused institutional policies, enhanced foundational awareness of the impact of racism on patients and communities, and changes at the level of institutions and accreditation bodies.

Abstract: Aim: To determine the relationships between the functional trait composition of forest communities and environmental gradients across scales and biomes and the role of species relative abundances in these relationships. Location: Global. Time period: Recent. Major taxa studied: Trees. Methods: We integrated species abundance records from worldwide forest inventories and associated functional traits (wood density, specific leaf area and seed mass) to obtain a data set of 99,953 to 149,285 plots (depending on the trait) spanning all forested continents. We computed community‐weighted and unweighted means of trait values for each plot and related them to three broad environmental gradients and their interactions (energy availability, precipitation and soil properties) at two scales (global and biomes). Results: Our models explained up to 60% of the variance in trait distribution. At global scale, the energy gradient had the strongest influence on traits. However, within‐biome models revealed different relationships among biomes. Notably, the functional composition of tropical forests was more influenced by precipitation and soil properties than energy availability, whereas temperate forests showed the opposite pattern. Depending on the trait studied, response to gradients was more variable and proportionally weaker in boreal forests. Community unweighted means were better predicted than weighted means for almost all models. Main conclusions: Worldwide, trees require a large amount of energy (following latitude) to produce dense wood and seeds, while leaves with large surface to weight ratios are concentrated in temperate forests. However, patterns of functional composition within‐biome differ from global patterns due to biome specificities such as the presence of conifers or unique combinations of climatic and soil properties. We recommend assessing the sensitivity of tree functional traits to environmental changes in their geographic context. Furthermore, at a given site, the distribution of tree functional traits appears to be driven more by species presence than species abundance.