Search

Abstract Background The application of semi-conductor detectors such as cadmium–zinc–telluride (CZT) in nuclear medicine improves extrinsic energy resolution and count sensitivity due to the direct conversion of gamma photons into electric signals. A 3D-ring pixelated CZT system named StarGuide was recently developed and implemented by GE HealthCare for SPECT acquisition. The system consists of 12 detector columns with seven modules of 16 × 16 CZT pixelated crystals, each with an integrated parallel-hole tungsten collimator. The axial coverage is 27.5 cm. The detector thickness is 7.25 mm, which allows acquisitions in the energy range [40–279] keV. Since there is currently no performance characterization specific to 3D-ring CZT SPECT systems, the National Electrical Manufacturers Association (NEMA) NU 1-2018 clinical standard can be tailored to these cameras. The aim of this study was to evaluate the performance of the SPECT/CT StarGuide system according to the NEMA NU 1-2018 clinical standard specifically adapted to characterize the new 3D-ring CZT. Results Due to the integrated collimator, the system geometry and the pixelated nature of the detector, some NEMA tests have been adapted to the features of the system. The extrinsic measured energy resolution was about 5–6% for the tested isotopes (99mTc, 123I and 57Co); the maximum count rate was 760 kcps and the observed count rate at 20% loss was 917 kcps. The system spatial resolution in air extrapolated at 10 cm with 99mTc was 7.2 mm, while the SPECT spatial resolutions with scatter were 4.2, 3.7 and 3.6 mm in a central, radial and tangential direction respectively. Single head sensitivity value for 99mTc was 97 cps/MBq; with 12 detector columns, the system volumetric sensitivity reached 520 kcps MBq−1 cc−1. Conclusions The performance tests of the StarGuide can be performed according to the NEMA NU 1-2018 standard with some adaptations. The system has shown promising results, particularly in terms of energy resolution, spatial resolution and volumetric sensitivity, potentially leading to higher quality clinical images.

Background Although clozapine is the most effective antipsychotic for people with treatment-resistant schizophrenia (TRS), only 40% of people with TRS respond, and there is limited evidence for augmentation agents. Cannabidiol (CBD) reduces positive symptoms in individuals with schizophrenia, but no trials have specifically examined its efficacy in those with clozapine-resistant schizophrenia. Aims To examine the clinical efficacy of CBD augmentation in people with clozapine-resistant schizophrenia. Method This is a 12-week randomised, placebo-controlled, double-blind, parallel-group trial (registration number: ACTRN12622001112752). We will recruit 88 individuals with clozapine-resistant schizophrenia, randomised (1:1) to 1000 mg daily CBD versus placebo. Eligible individuals will be aged between 18 and 64 years, fulfil DSM-IV criteria for schizophrenia or schizoaffective disorder, have a total PANSS (Positive and Negative Syndrome Scale) score ≥60, have received oral clozapine for at least 18 weeks and have a clozapine level of >350 ng/mL. Interim analyses will be conducted at 25, 50 and 75% recruitment; these will also provide an opportunity to reallocate participants dependent on conditional power. The primary endpoint will be the difference in PANSS positive scores at the end of week 12. Secondary endpoints include depression, anxiety, sleep, quality of life, alcohol consumption, change in weight and metabolic syndrome components, and neurocognitive measures, as well as safety and tolerability. Discussion Novel treatments for clozapine-resistant schizophrenia are urgently needed. If found to be effective, CBD may have a role as a novel and safe adjunct to clozapine.

O ensino da Língua de Sinais Italiana (LIS) está passando por uma profunda transformação na Itália. Desde o seu reconhecimento em 2021, como a língua natural da minoria surda, juntamente com o dos intérpretes de LIS como profissionais designados para mediar suas necessidades de comunicação em todos os ambientes públicos, o debate aumentou na tentativa de determinar o conteúdo e o(s) objetivo(s) dos cursos de formação de intérpretes (no ensino superior?). Enquanto a educação formal em língua de sinais (LS) esteja se tornando cada vez mais importante para o treinamento de intérpretes, e as universidades estão abrindo cursos experimentais para isso, a educação linguística de crianças surdas e o treinamento vocacional de adultos surdos como professores de LS estão ganhando nova atenção. À luz dessas mudanças, discuto o estado da arte da educação geral para surdos na Itália, observando as etapas levaram ao reconhecimento da LIS e ao treinamento de crianças bilíngues (surdas) bimodais na educação pública. O tópico será abordado a partir de uma perspectiva histórica e interdisciplinar, acompanhando a evolução das decisões sociais e políticas que influenciaram a educação de surdos.

The agrifood industry shows one of the widest ranges of possible end products from crops, such as fruits, legumes, cereals, and tubers. The raw material is generally collected and processed industrially, producing a significant amount of organic waste. The overall picture is made more complex by the wide variety of nature and composition, and by the difficulty identifying the possible uses of the wastes coming from the processing industry. Such wastes are often disposed of in landfills or treated in waste-to-energy plants depending on the area where they are produced. The circular economy approach has suggested numerous possible generic strategies to improve waste management, involving the exploitation of waste to obtain new value-added products. The use of fibers from legume waste from the canning industry in the bioplastics production sector is a promising and relatively little explored line, particularly for the fibers of beans and green beans. With this in mind, in this article, green bean and borlotti bean fibers obtained from the treatment of wastes were used as reinforcing material for polycaprolactone (PCL)-based biocomposites by melt blending. Analyses were carried out about the morphological, spectroscopic, thermal, and mechanical properties of the starting and the obtained materials.

The Cape Verde palm tree, Phoenix atlantica, holds significant ecological and cultural importance within the Cape Verde archipelago. However, its genetic distinctiveness has been questioned due to its close relationship and morphological similarity to the date palm (Phoenix dactylifera). In this study, we used an expanded sample set, 18 simple sequence repeat (SSR) markers, and a plastid minisatellite to characterize P. atlantica in Cape Verde and investigate its relationship with other Phoenix species. Our findings identify genetic markers that differentiate the P. atlantica genetic pool, including a unique fixed allele. We also provide evidence of the recent divergence of P. atlantica from Northern African date palm populations, suggesting a relatively recent colonization of Cape Verde by palm trees. Additionally, we characterized the genetic composition of palm tree populations across three Cape Verde islands, concluding that wild samples from certain populations in Boavista and Sal are best suited for establishing a seed and/or germplasm bank for replantation efforts, representing a crucial step for the conservation of Cape Verde’s natural heritage. Overall, our results enhance the understanding of the historical trajectories and genetic characterization of palm trees in Africa, offering valuable insights for conservation strategies.

Pancreatic cancer is a very aggressive disease with a dismal prognosis. The tumor microenvironment exerts immunosuppressive activities through the secretion of several cytokines, including interleukin (IL)-1. The IL-1/IL-1 receptor (IL-1R) axis is a key regulator in tumor-promoting T helper (Th)2- and Th17-type inflammation. Th2 cells are differentiated by dendritic cells endowed with Th2-polarizing capability by the thymic stromal lymphopoietin (TSLP) that is secreted by IL-1-activated cancer-associated fibroblasts (CAFs). Th17 cells are differentiated in the presence of IL-1 and other IL-1-regulated cytokines. In pancreatic cancer, the use of a recombinant IL-1R antagonist (IL1RA, anakinra, ANK) in in vitro and in vivo models has shown efficacy in targeting the IL-1/IL-1R pathway. In this study, we have developed sphingomyelin nanosystems (SNs) loaded with ANK (ANK-SNs) to compare their ability to inhibit Th2- and Th17-type inflammation with that of the free drug in vitro. We found that ANK-SNs inhibited TSLP and other pro-tumor cytokines released by CAFs at levels similar to ANK. Importantly, inhibition of IL-17 secretion by Th17 cells, but not of interferon-γ, was significantly higher, and at lower concentrations, with ANK-SNs compared to ANK. Collectively, the use of ANK-SNs might be beneficial in reducing the effective dose of the drug and its toxic effects.

Abstract Introduction Cancer patients are frail individuals, thus the prevention of SARS‐CoV‐2 infection is essential. To date, vaccination is the most effective tool to prevent COVID‐19. In a previous study, we evaluated the immunogenicity of two doses of mRNA‐based vaccines (BNT162b2 or mRNA‐1273) in solid cancer patients. We found that seroconversion rate in cancer patients without a previous exposure to SARS‐CoV‐2 was lower than in healthy controls (66.7% vs. 95%, p = 0.0020). The present study aimed to evaluate the clinical efficacy of the vaccination in the same population. Methods This is a single‐institution, prospective observational study. Data were collected through a predefined questionnaire through phone call in the period between the second and third vaccine dose. The primary objective was to describe the clinical efficacy of the vaccination, defined as the percentage of vaccinated subjects who did not develop symptomatic COVID‐19 within 6 months after the second dose. The secondary objective was to describe the clinical features of patients who developed COVID‐19. Results From January to June 2021, 195 cancer patients were enrolled. Considering that 7 (3.59%) patients tested positive for SARS‐CoV‐2 and 5 developed symptomatic disease, the clinical efficacy of the vaccination was 97.4%. COVID‐19 disease in most patients was mild and managed at home; only one hospitalization was recorded and no patient required hospitalization in the intensive care unit. Discussion Our study suggests that increasing vaccination coverage, including booster doses, could improve the prevention of infection, hospitalization, serious illness, and death in the frail population of cancer patients.

BackgroundCognitive impairment is common with schizophrenia spectrum disorders. Cognitive remediation (CR) is effective in improving global cognition, but not all individuals benefit from this type of intervention. A better understanding of the potential mechanism of action of CR is needed. One proposed mechanism is reward learning (RL), the cognitive processes responsible for adapting behavior following positive or negative feedback. It is proposed that the structure of CR enhances RL and motivation to engage in increasingly challenging tasks, and this is a potential mechanism by which CR improves cognitive functioning in schizophrenia. ObjectiveOur primary objective is to examine reward processing in individuals with schizophrenia before and after completing CR and to compare this with a group of matched clinical controls. We will assess whether RL mediates the relationship between CR and improved cognitive function and reduced negative symptoms. Potential differences in social RL and nonsocial RL in individuals with schizophrenia will also be investigated and compared with a healthy matched control group. MethodsWe propose a clinical, nonrandomized, pre-post pilot study comparing the impact of CR on RL and neurocognitive outcomes. The study will use a combination of objective and subjective measures to assess neurocognitive, psychiatric symptoms, and neurophysiological domains. A total of 40 individuals with schizophrenia spectrum disorders (aged 18-35 years) will receive 12 weeks of CR therapy (n=20) or treatment as usual (n=20). Reward processing will be evaluated using a reinforcement learning task with 2 conditions (social reward vs nonsocial reward) at baseline and the 12-week follow-up. Functional magnetic resonance imaging responses will be measured during this task. To validate the reinforcement learning task, RL will also be assessed in 20 healthy controls, matched for age, sex, and premorbid functioning. Mixed-factorial ANOVAs will be conducted to evaluate treatment group differences. For the functional magnetic resonance imaging analysis, computational modeling will allow the estimation of learning parameters at each point in time, during each task condition, for each participant. We will use a variational Bayesian framework to measure how learning occurred during the experimental task and the subprocesses that underlie this learning. Second-level group analyses will examine how learning in patients differs from that observed in control participants and how CR alters learning efficiency and the underlying neural activity. ResultsAs of September 2023, this study has enrolled 15 participants in the CR group, 1 participant in the treatment-as-usual group, and 11 participants in the healthy control group. Recruitment is expected to be completed by September 2024. Data analysis is expected to be completed and published in early 2025. ConclusionsThe results of this study will contribute to the knowledge of CR and RL processes in severe mental illness and the understanding of the systems that impact negative symptoms and cognitive impairments within this population. International Registered Report Identifier (IRRID)DERR1-10.2196/52505

ObjectiveThe urgent transfer of an intensive care unit (ICU) is particularly challenging because it carries a high clinical and infectious risk and is a critical node in a hospital’s patient flow. In early 2017, exceptional rainfall damaged the roof of the tertiary hospital in Udine, necessitating the relocation of one of the three ICUs for six months. We decided to assess the impact of this transfer on quality of care and patient safety using a set of indicators, primarily considering the incidence of healthcare-associated infections (HAIs) and mortality rates.MethodsWe performed a retrospective, observational analysis of structural, process, and outcome indicators comparing the pre- and posttransfer phases. Specifically, we analyzed data between July 2016 and June 2017 for the transferred ICU and examined mortality and the incidence of HAI.ResultsDespite significant changes in structural and organizational aspects of the unit, no differences in mortality rates or cumulative incidence of HAIs were observed before/after transfer. We collected data for all 393 patients (133 women, 260 men) admitted to the ICU before (49.4%) and after transfer (50.6%). The mortality rate for 100 days in the ICU was 1.90 (34/1791) before and 2.88 (37/1258) after transfer (p = 0.063). The evaluation of the occurrence of at least one HAI included 304 patients (102 women and 202 men), as 89 of them were excluded due to a length of stay in the ICU of less than 48 h; again, there was no statistical difference between the two cumulative incidences (13.1% vs. 6.9%, p = 0.075).ConclusionIn the case studied, no adverse effects on patient outcomes were observed after urgent transfer of the injured ICU. The indicators used in this study may be an initial suggestion for further discussion.

Summary: Background: Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis and it is characterized by predominant pro-tumor Th2-type inflammation. T follicular helper (Tfh) cells are relevant immunoregulators in cancer, and often correlate with better survival. How the Th2-skewed microenvironment in PDAC modulates the differentiation of Tfh cells and their immunoregulatory function is unknown. Methods: We carried out high-dimensional flow cytometry and T-cell receptor- and RNA-sequencing, as well as bioinformatics, immunohistochemistry and in vitro mechanistic studies. Findings: We identified Tfh1-, Tfh2-, and Tfh17-like cell clusters in the blood, tumors and tumor-draining lymph-nodes (TDLNs) of chemo-naïve PDAC patients and showed that high percentages of Tfh2 cells within the tumor tissue and TDLNs correlated with reduced patient survival. Moreover, only Tfh2 cells were highly activated and were reduced in frequency in patients who responded to neoadjuvant chemotherapy. RNA-sequencing analysis of immunoglobulin expression showed that tumor and TDLN samples expressed all immunoglobulin (IGH) isotypes apart from IGHE. Consistent with these findings, Tfh2 cells differentiated in vitro by tumor microenvironment-conditioned dendritic cells promoted the production of anti-inflammatory IgG4 antibodies by co-cultured B cells, dependent on IL-13. Moreover, unexpectedly, Tfh2 cells inhibited the secretion of pro-inflammatory IgE, dependent on prostaglandin E2. Interpretation: Our results indicate that in PDAC, highly activated pro-tumor Tfh2 favor anti-inflammatory IgG4 production, while inhibit pro-inflammatory IgE. Thus, targeting the circuits that drive Tfh2 cells, in combination with chemotherapy, may re-establish beneficial anti-tumor Tfh–B cell interactions and facilitate more effective treatment. Funding: Research grants from the Italian Association for Cancer Research (AIRC) IG-19119 to MPP and the AIRC Special Program in Metastatic disease: the key unmet need in oncology, 5 per Mille no. 22737 to CB, MF, CD, MR and MPP; the ERA-NET EuroNanoMed III (a collaborative european grant financed by the Italian Ministry of Health, Italy) project PANIPAC (JTC2018/041) to MPP; the Fondazione Valsecchi to SC.

In ecology, stable‐isotope ratios are widely used to determine diets of organisms and reconstruct food webs. This is usually done by analyzing the stable‐isotope ratios of nitrogen (δ15N), which increase with increasing trophic level, and those of carbon (δ13C), which correlate with the δ13C value of food source(s) and generally differ between terrestrial and marine food sources. Assimilation of food changes stable‐isotope ratios, resulting in different values between the food source and its consumer. These differences are known as isotope trophic discrimination factors and, if known, can be used to determine from the stable‐isotope ratios in the consumer's tissue what the consumer has been eating. What is often ignored is that discrimination factors can differ between consumer's food sources and also between tissue types. Therefore, we performed a controlled feeding study in red knots Calidris canutus to determine discrimination factors between different food sources and red knot tissues. We kept two groups of red knots in captivity on a stable diet, one group feeding on mudsnails and the other on Trouvit pellets, for several months, during which the birds molted their feathers. We analyzed δ13C and δ15N in both food sources and in five red knot tissues (blood cells, blood plasma and three feather types) and subsequently calculated the isotope discrimination factors. We confirmed that the discrimination factors differed between tissues, and also between diets. Our values deviated from general averages reported in reviews on a wide range of animals/birds, but were very similar to values from previous red knot and dunlin studies. We therefore think that our discrimination factors can be used in future stable isotope studies, not only on red knots, but also on other marine shorebird species and plea for careful consideration of using the right discrimination factors. Keywords: δ13C, δ15N, discrimination factor, red knot, shorebird, stable isotope

Abstract Tracking animal movement is important for understanding how animals interact with their (changing) environment, and crucial for predicting and explaining how animals are affected by anthropogenic activities. The Wadden Sea is a UNESCO World Heritage Site and a region of global importance for millions of shorebirds. Due to climate change and anthropogenic activity, understanding and predicting movement and space-use in areas like the Wadden Sea is increasingly important. Monitoring and predicting animal movement, however, requires high-resolution tracking of many individuals. While high-resolution tracking has been made possible through GPS, trade-offs between tag weight and battery life limit its use to larger species. Here, we introduce WATLAS (the Wadden Sea deployment of the ATLAS tracking system) capable of monitoring the movements of hundreds of (small) birds simultaneously in the Dutch Wadden Sea. WATLAS employs an array of receiver stations that can detect and localize small, low-cost tags at fine spatial (metres) and temporal resolution (seconds). From 2017 to 2021, we tracked red knots, sanderlings, bar-tailed godwits, and common terns. We use parts of these data to give four use-cases revealing its performance and demonstrating how WATLAS can be used to study numerous aspects of animal behaviour, such as, space-use (both intra- and inter-specific), among-individual variation, and social networks across levels of organization: from individuals, to species, to populations, and even communities. After describing the WATLAS system, we first illustrate space-use of red knots across the study area and how the tidal environment affects their movement. Secondly, we show large among-individual differences in distances travelled per day, and thirdly illustrate how high-throughput WATLAS data allows calculating a proximity-based social network. Finally, we demonstrate that using WATLAS to monitor multiple species can reveal differential space use. For example, despite sanderlings and red knots roosting together, they foraged in different areas of the mudflats. The high-resolution tracking data collected by WATLAS offers many possibilities for research into the drivers of bird movement in the Wadden Sea. WATLAS could provide a tool for impact assessment, and thus aid nature conservation and management of the globally important Wadden Sea ecosystem.

Summary: In Dictyostelium chimeras, “cheaters” are strains that positively bias their contribution to the pool of spores, i.e., the reproductive cells resulting from development. On evolutionary time scales, the selective advantage; thus, gained by cheaters is predicted to undermine collective functions whenever social behaviors are genetically determined. Genotypes; however, are not the sole determinant of spore bias, but the relative role of genetic and plastic differences in evolutionary success is unclear. Here, we study chimeras composed of cells harvested in different phases of population growth. We show that such heterogeneity induces frequency-dependent, plastic variation in spore bias. In genetic chimeras, the magnitude of such variation is not negligible and can even reverse the classification of a strain’s social behavior. Our results suggest that differential cell mechanical properties can underpin, through biases emerging during aggregation, a “lottery” in strains’ reproductive success that may counter the evolution of cheating.

Background Mental health services are encouraged to use language consistent with principles of recovery-oriented practice. This study presents a novel approach for identifying whether clinical documentation contains recovery-oriented rehabilitation language, and evaluates an intervention to improve the language used within a community-based rehabilitation team. Aims This is a pilot study of training to enhance recovery-oriented rehabilitation language written in care review summaries, as measured through a text-based analysis of language used in mental health clinical documentation. Method Eleven case managers participated in a programme that included instruction in recovery-oriented rehabilitation principles. Outcomes were measured with automated textual analysis of clinical documentation, using a custom-built dictionary of rehabilitation-consistent, person-centred and pejorative terms. Automated analyses were run on Konstanz Information Miner (KNIME), an open-source data analytics platform. Differences in the frequency of term categories in 50 pre-training and 77 post-training documents were analysed with inferential statistics. Results The average percentage of sentences with recovery-oriented rehabilitation terms increased from 37% before the intervention to 48% afterward, a relative increase of 28% (P < 0.001). There was no significant change in use of person-centred or pejorative terms, possibly because of a relatively high frequency of person-centred language (22% of sentences) and low use of pejorative language (2.3% of sentences) at baseline. Conclusions This computer-driven textual analysis method identified improvements in recovery-oriented rehabilitation language following training. Our study suggests that brief interventions can affect the language of clinical documentation, and that automated text-analysis may represent a promising approach for rapidly assessing recovery-oriented rehabilitation language in mental health services.