Search

BackgroundAdvance care planning (ACP) is influenced by several factors (e.g., patient's readiness to engage, clinician's skills, and the cultural environment). Availability of reliable and valid self-reported measures of the ACP domains is crucial, including cross-cultural equivalence.AimTo culturally adapt into Italian the 19-item Quality of Communication (QOC) and the 4-item ACP Engagement (4-item ACP-E) questionnaires.MethodsWe translated and culturally adapted the two questionnaires and produced a significant other (SO) version of the QOC (QOC-SO). Each questionnaire was field tested via cognitive interviews with users: nine patients (QOC, 4-item ACP-E) and three SOs (QOC-SO) enrolled at three palliative care services.ResultsWe made minor changes to 5/19 QOC items, to improve clarity and internal consistency; we changed the response option 'didn't do' into 'not applicable'. Finally, we slightly revised the QOC to adapt it to the paper/electronic format. QOC debriefing revealed that the section on end of life was emotionally challenging for both patients and SOs. We simplified the 4-item ACP-E layout, added a sentence in the introduction, and revised the wording of one item, to improve coherence with the Italian ACP legislation. ACP-E debriefing did not reveal any major issue.ConclusionsResults were satisfactory in terms of semantic, conceptual and normative equivalence of both questionnaires. Acceptability was satisfactory for the 4-item ACP-E, while findings of the QOC cognitive debriefing informed a major amendment of a pilot trial protocol on ACP in multiple sclerosis (ConCure-SM): use of the interviewer version only, in an adaptive form. Psychometric testing of both questionnaires on a large, independent sample will follow.

The advent of deepfake technology has raised significant concerns regarding its impact on individuals' cognitive processes and beliefs, considering the pervasive relationships between technology and human cognition. This study delves into the psychological literature surrounding deepfakes, focusing on people's public representation of this emerging technology and highlighting prevailing themes, opinions, and emotions. Under the media framing, the theoretical framework is crucial in shaping individuals' cognitive schemas regarding technology. A qualitative method has been applied to unveil patterns, correlations, and recurring themes of beliefs about the main topic, deepfake, discussed on the forum Quora. The final extracted text corpus consisted of 166 answers to 17 questions. Analysis results highlighted the 20 most prevalent critical lemmas, and deepfake was the main one. Moreover, co-occurrence analysis identified words frequently appearing with the lemma deepfake, including video, create, and artificial intelligence-finally, thematic analysis identified eight main themes within the deepfake corpus. Cognitive processes rely on critical thinking skills in detecting anomalies in fake videos or discerning between the negative and positive impacts of deepfakes from an ethical point of view. Moreover, people adapt their beliefs and mental schemas concerning the representation of technology. Future studies should explore the role of media literacy in helping individuals to identify deepfake content since people may not be familiar with the concept of deepfakes or may not fully understand the negative or positive implications. Increased awareness and understanding of technology can empower individuals to evaluate critically the media related to Artificial Intelligence.

Technological innovation serves as the catalyst for the shift towards circular practices. Technologies not only address technical challenges, facilitating the transition to a more circular economy, but they also enhance business efficiency and profitability. Furthermore, they promote inclusivity and create job opportunities, ultimately yielding positive societal impacts. The research in this area tends to focus on digital technologies, neglecting other technological areas. Moreover, it heavily relies on literature reviews and expert opinions, potentially introducing biases. In this article we investigate the technological landscape of the circular economy through Natural Language Processing (NLP), examining key technologies used in this sector and the primary challenges in managing these technologies. The methodology is applied to more than 45,000 scientific publications and aims to extract technologies in the text of scientific articles with NLP. The findings of our analysis reveal a strong emphasis on emerging digital, life cycle assessment and biomaterials technologies. Furthermore, we identified seven distinct technological domains within the CE field. Finally, we provide advantages and problems arising in the adoption and implementation of these technologies in an industrial context.

Agent-based models of opinion formation are becoming increasingly complex, because of their size and of the embedding of several individual psychological traits of the agents, aimed at realistically capturing the multifaceted aspects of social interaction. Therefore, the characterisation of the model properties mostly relies on simulation-based numerical approaches: more techniques are needed to analyse, contrast, and compare the properties of different models. We propose a novel graphical technique, which relies on the Agreement Plot to visualise the evolution of opinion distributions over time, that allows us to unveil behavioural patterns and capabilities of agent-based opinion formation models. Our proposed approach can be used to characterise the relation between global properties of the model evolution and the model features (initial opinion distributions, agent parameters, underlying digraphs), and is here showcased through its application to both seminal and recently proposed opinion formation models.

Fibromyalgia (FM) is a central disorder characterized by chronic pain, fatigue, insomnia, depression, and other minor symptoms. Knowledge about pathogenesis is lacking, diagnosis difficult, clinical approach puzzling, and patient management disappointing. We conducted a theoretical study based on literature data and computational analysis, aimed at developing a comprehensive model of FM pathogenesis and addressing suitable therapeutic targets. We started from the evidence that FM must involve a dysregulation of central pain processing, is female prevalent, suggesting a role for the hypothalamus-pituitary-gonadal (HPG) axis, and is stress-related, suggesting a role for the HP-adrenocortical (HPA) axis. Central pathogenesis was supposed to involve a pain processing loop system including the thalamic ventroposterolateral nucleus (VPL), the primary somatosensory cortex (SSC), and the thalamic reticular nucleus (TRN). For decreasing GABAergic and/or increasing glutamatergic transmission, the loop system crosses a bifurcation point, switching from monostable to bistable, and converging on a high-firing-rate steady state supposed to be the pathogenic condition. Thereafter, we showed that GABAergic transmission is positively correlated with gonadal-hormone-derived neurosteroids, notably allopregnanolone, whereas glutamatergic transmission is positively correlated with stress-induced glucocorticoids, notably cortisol. Finally, we built a dynamic model describing a multistable, double-inhibitory loop between HPG and HPA axes. This system has a high-HPA/low-HPG steady state, allegedly reached in females under combined premenstrual/postpartum brain allopregnanolone withdrawal and stress condition, driving the thalamocortical loop to the high-firing-rate steady state, and explaining the connection between endocrine and neural mechanisms in FM pathogenesis. Our model accounts for FM female prevalence and stress correlation, suggesting the use of neurosteroid drugs as a possible solution to currently unsolved problems in the clinical treatment of the disease.

Feline chronic enteropathies (FCE), include food-responsive-enteropathy (FRE), inflammatory bowel disease (IBD), and low-grade intestinal T-cell lymphoma (LGITL), and are common causes of chronic gastrointestinal signs in cats. Distinguishing between different subgroups of FCE can be challenging due to the frequent overlap of anamnestic, clinical, and laboratory data. While dysregulation in lipid metabolism has been reported in humans and dogs with chronic IBD, similar changes in cats are not yet completely understood. Assessing the fatty acid (FA) profile of red blood cell (RBC) membranes offers a valuable method for evaluating the quantity and quality of structural and functional molecular components in the membranes. Therefore, this study aimed to examine the FA composition of RBC membranes in FCE in comparison to healthy cats (HC). Gas-chromatography was used to quantitatively analyze a cluster of 11 FA, and based on these results, parameters of lipid homeostasis and enzyme activity indexes were calculated. A total of 41 FCE cats (17 FRE, 15 IBD, 9 LGITL) and 43 HC were enrolled. In FCE cats, the values of docosapentaenoic acid (p = 0.0002) and docosahexaenoic acid (p = 0.0246), were significantly higher, resulting in an overall increase in ω-3 polyunsaturated fatty acids (PUFA) (p = 0.006), and that of linoleic acid (p = 0.0026) was significantly lower. Additionally, FCE cats exhibited an increased PUFA balance (p = 0.0019) and Δ6-desaturase index (p = 0.0151), along with a decreased ω-6/ω-3 ratio (p = 0.0019). No differences were observed among cats affected by FRE, IBD and LGITL. Like humans and dogs, the results of this study indicate that FCE cats also display changes in their FA lipid profile at the level of the RBC membrane. The non-invasive analysis of RBC membrane shows promise as a potential tool for gaining a better understanding of lipid imbalances in this disease.

BackgroundAs cannabis legalization continues to spread across the United States, average Δ9-tetrahydrocannabinol concentrations in recreational products have significantly increased, and no prior study has evaluated effective treatments to reduce cannabis use among high potency cannabis users. Some research has found that the non-intoxicating cannabinoid cannabidiol reduces cannabis use and cannabis use disorder-related symptoms, such as affective disturbance and withdrawal. Results of these studies are promising but limited to synthetic or isolated forms of cannabidiol.ObjectiveConduct a placebo-controlled randomized control trial comparing the effects of hemp-derived cannabidiol on reducing Δ9-tetrahydrocannabinol use in concentrate users with cannabis use disorder.MethodsDesign. Double-blind, three-arm randomized placebo-controlled trial. Setting. University in the Denver-Boulder, CO, USA area. Study population. Community members who are heavy, stable cannabis concentrate users that meet criteria for at least moderate cannabis use disorder and are seeking to decrease or stop cannabis use. Data. Self-report demographics, substance use, and mental health characteristics, blood and urine based biomarkers and anthropometrics. Outcomes. Affective, physiological, and physical withdrawal symptoms, Δ9-tetrahydrocannabinol use. Analysis. Three-group ANOVAs and χ2 tests will be used to compare baseline variables between groups. Characteristics that differ between groups will be evaluated as potential covariates in subsequent analyses. A multilevel modeling framework will be used for primary outcome analysis to account for the repeated observations nested within participants over time. Pairwise post-hoc simple effects tests will be conducted to confirm patterns of differences.Trial registrationClinicalTrials.gov NCT06107062.

BackgroundStereotactic radiosurgery (SRS) is an effective therapy for brain metastases. Response is assessed with serial 1H magnetic resonance imaging (MRI). Early markers for response are desirable to allow for individualized treatment adaption. Previous studies indicated that radiotherapy might have impact on tissue sodium concentration. Thus, 23Na MRI could provide early quantification of response to SRS.PurposeWe investigated whether longitudinal detection of tissue sodium concentration alteration within brain metastases and their peritumoral tissue after SRS with 23Na MRI was feasible.Study typeProspective.PopulationTwelve patients with a total of 14 brain metastases from various primary tumors.Assessment23Na MRI scans were acquired from patients 2 days before, 5 days after, and 40 days after SRS. Gross tumor volume (GTV) and healthy-appearing regions were manually segmented on the MPRAGE obtained 2 days before SRS, onto which all 23Na MR images were coregistered. Radiation isodose areas within the peritumoral tissue were calculated with the radiation planning system. Tissue sodium concentration before and after SRS within GTV, peritumoral tissue, and healthy-appearing regions as well as the routine follow-up with serial MRI were evaluated.Statistical testsResults were compared using Student's t-test and correlation was evaluated with Pearson's correlation coefficient.ResultsWe found a positive correlation between the tissue sodium concentration within the peritumoral tissue and radiation dosage. Two patients showed local progression and a differing tissue sodium concentration evolution within GTV and the peritumoral tissue compared to mean tissue sodium concentration of the other patients. No significant tissue sodium concentration changes were observed within healthy-appearing regions.ConclusionTissue sodium concentration assessment within brain metastases and peritumoral tissue after SRS with 23Na MRI is feasible and might be able to quantify tissue response to radiation.

The advent of deepfake technology has raised significant concerns regarding its impact on individuals' cognitive processes and beliefs, considering the pervasive relationships between technology and human cognition. This study delves into the psychological literature surrounding deepfakes, focusing on people's public representation of this emerging technology and highlighting prevailing themes, opinions, and emotions. Under the media framing, the theoretical framework is crucial in shaping individuals' cognitive schemas regarding technology. A qualitative method has been applied to unveil patterns, correlations, and recurring themes of beliefs about the main topic, deepfake, discussed on the forum Quora. The final extracted text corpus consisted of 166 answers to 17 questions. Analysis results highlighted the 20 most prevalent critical lemmas, and deepfake was the main one. Moreover, co-occurrence analysis identified words frequently appearing with the lemma deepfake, including video, create, and artificial intelligence—finally, thematic analysis identified eight main themes within the deepfake corpus. Cognitive processes rely on critical thinking skills in detecting anomalies in fake videos or discerning between the negative and positive impacts of deepfakes from an ethical point of view. Moreover, people adapt their beliefs and mental schemas concerning the representation of technology. Future studies should explore the role of media literacy in helping individuals to identify deepfake content since people may not be familiar with the concept of deepfakes or may not fully understand the negative or positive implications. Increased awareness and understanding of technology can empower individuals to evaluate critically the media related to Artificial Intelligence. [ABSTRACT FROM AUTHOR]

Technological innovation serves as the catalyst for the shift towards circular practices. Technologies not only address technical challenges, facilitating the transition to a more circular economy, but they also enhance business efficiency and profitability. Furthermore, they promote inclusivity and create job opportunities, ultimately yielding positive societal impacts. The research in this area tends to focus on digital technologies, neglecting other technological areas. Moreover, it heavily relies on literature reviews and expert opinions, potentially introducing biases. In this article we investigate the technological landscape of the circular economy through Natural Language Processing (NLP), examining key technologies used in this sector and the primary challenges in managing these technologies. The methodology is applied to more than 45,000 scientific publications and aims to extract technologies in the text of scientific articles with NLP. The findings of our analysis reveal a strong emphasis on emerging digital, life cycle assessment and biomaterials technologies. Furthermore, we identified seven distinct technological domains within the CE field. Finally, we provide advantages and problems arising in the adoption and implementation of these technologies in an industrial context. [ABSTRACT FROM AUTHOR]

This study aims to investigate how metformin (Met) affects muscle tissue by evaluating the drug effects on proliferating, differentiating, and differentiated C2C12 cells. Moreover, we also investigated the role of 5'-adenosine monophosphate-activated protein kinase (AMPK) in the mechanism of action of Met. C2C12 myoblasts were cultured in growth medium with or without Met (250μM, 1mM and 10mM) for different times. Cell proliferation was evaluated by MTT assay, while cell toxicity was assessed by Trypan Blue exclusion test and Lactate Dehydrogenase release. Fluorescence Activated Cell Sorting analysis was performed to study cell cycle. Differentiating myoblasts were incubated in differentiation medium (DM) with or without 10mM Met. For experiments on myotubes, C2C12 were induced to differentiate in DM, and then treated with Met at scalar concentrations and for different times. Western blotting was performed to evaluate the expression of proteins involved in myoblast differentiation, muscle function and metabolism. In differentiating C2C12, Met inhibited cell differentiation, arrested cell cycle progression in G2/M phase and reduced the expression of cyclin-dependent kinase inhibitor 1. These effects were accompanied by activation of AMPK and modulation of the myogenic regulatory factors. Comparable results were obtained in myotubes. The use of Compound C, a specific inhibitor of AMPK, counteracted the above-mentioned Met effects. We reported that Met inhibits C2C12 differentiation probably by blocking cell-cycle progression and preventing cells permanent exit from cell-cycle. Moreover, our study provides solid evidence that most of the effects of Met on myoblasts and myotubes are mediated by AMPK.

Background Advance care planning (ACP) is influenced by several factors (e.g., patient’s readiness to engage, clinician’s skills, and the cultural environment). Availability of reliable and valid self-reported measures of the ACP domains is crucial, including cross-cultural equivalence. Aim To culturally adapt into Italian the 19-item Quality of Communication (QOC) and the 4-item ACP Engagement (4-item ACP-E) questionnaires. Methods We translated and culturally adapted the two questionnaires and produced a significant other (SO) version of the QOC (QOC-SO). Each questionnaire was field tested via cognitive interviews with users: nine patients (QOC, 4-item ACP-E) and three SOs (QOC-SO) enrolled at three palliative care services. Results We made minor changes to 5/19 QOC items, to improve clarity and internal consistency; we changed the response option ‘didn’t do’ into ‘not applicable’. Finally, we slightly revised the QOC to adapt it to the paper/electronic format. QOC debriefing revealed that the section on end of life was emotionally challenging for both patients and SOs. We simplified the 4-item ACP-E layout, added a sentence in the introduction, and revised the wording of one item, to improve coherence with the Italian ACP legislation. ACP-E debriefing did not reveal any major issue. Conclusions Results were satisfactory in terms of semantic, conceptual and normative equivalence of both questionnaires. Acceptability was satisfactory for the 4-item ACP-E, while findings of the QOC cognitive debriefing informed a major amendment of a pilot trial protocol on ACP in multiple sclerosis (ConCure-SM): use of the interviewer version only, in an adaptive form. Psychometric testing of both questionnaires on a large, independent sample will follow.

BackgroundThe lack of empathy is associated with several psychological and behavioral disorders, and it is important to assess this construct broadly, through multi-methods.ObjectiveTo conduct a psychometric analysis of the Brazilian version of the Multifaceted Empathy Test (MET), a computerized task that assesses emotional and cognitive empathy.MethodsThe samples were recruited from the community using the snowball method (phase 1: face-to-face; N = 142) and through social media (phase 2: online; N = 519). The participants completed the MET and the Interpersonal Reactivity Index (IRI) to assess the convergent validity between the instruments. To assess validity with correlated constructs (resilient coping and stress), the Brief Resilient Coping Scale and Perceived Stress Scale were used. A task was also implemented in the face-to-face application to assess facial emotions. The retest was applied 25 days later to a portion of the sample (face-to-face: N = 31; online: N = 102).ResultsIt was observed adequate test-retest reliability for most items (ICC = 0.49-0.98), satisfactory infit and outfit indexes, discriminatory ability between sexes, weak convergent validity with empathy measures (r = 0.17-0.36), and correlate constructs (r = 0.12-0.46). MET presented good psychometric indicators, confirming its use in face-to-face/computer-based and online formats in clinical and research contexts. However, weaknesses were found regarding the cognitive subscale, demanding future studies to address larger samples to enable more robust conclusions concerning its adequacy. Further research on the instrument's internal structure can also contribute to its improvement.

BackgroundThe primary objective of this study was to retrospectively compare short-term outcomes of intracorporeal versus extracorporeal anastomosis for minimally invasive laparoscopic and robotic-assisted right colectomies for benign and malignant disease. Recent studies suggest potential short-term outcomes advantages for the intracorporeal anastomosis technique.MethodsThis is a multicenter retrospective propensity score-matched comparison of intracorporeal and extracorporeal anastomosis techniques for laparoscopic and robotic-assisted right colectomy between January 11, 2010, and July 21, 2016.ResultsAfter propensity score-matching, there were a total of 1029 minimal invasive surgery cases for analysis-379 right colectomies (335 robotic-assisted and 44 laparoscopic) done with an intracorporeal anastomosis and 650 right colectomies (253 robotic-assisted and 397 laparoscopic) done with an extracorporeal anastomosis. There were no significant differences in any preoperative patient characteristics between groups. The minimally invasive intracorporeal anastomosis group had significantly longer operative times (p

Background: Stereotactic radiosurgery (SRS) is an effective therapy for brain metastases. Response is assessed with serial 1H magnetic resonance imaging (MRI). Early markers for response are desirable to allow for individualized treatment adaption. Previous studies indicated that radiotherapy might have impact on tissue sodium concentration. Thus, 23Na MRI could provide early quantification of response to SRS. Purpose: We investigated whether longitudinal detection of tissue sodium concentration alteration within brain metastases and their peritumoral tissue after SRS with 23Na MRI was feasible. Study type: Prospective. Population: Twelve patients with a total of 14 brain metastases from various primary tumors. Assessment: 23Na MRI scans were acquired from patients 2 days before, 5 days after, and 40 days after SRS. Gross tumor volume (GTV) and healthy-appearing regions were manually segmented on the MPRAGE obtained 2 days before SRS, onto which all 23Na MR images were coregistered. Radiation isodose areas within the peritumoral tissue were calculated with the radiation planning system. Tissue sodium concentration before and after SRS within GTV, peritumoral tissue, and healthy-appearing regions as well as the routine follow-up with serial MRI were evaluated. Statistical tests: Results were compared using Student's t-test and correlation was evaluated with Pearson's correlation coefficient. Results: We found a positive correlation between the tissue sodium concentration within the peritumoral tissue and radiation dosage. Two patients showed local progression and a differing tissue sodium concentration evolution within GTV and the peritumoral tissue compared to mean tissue sodium concentration of the other patients. No significant tissue sodium concentration changes were observed within healthy-appearing regions. Conclusion: Tissue sodium concentration assessment within brain metastases and peritumoral tissue after SRS with 23Na MRI is feasible and might be able to quantify tissue response to radiation. [ABSTRACT FROM AUTHOR]

How landscape composition and configuration impact the distribution of multi-vector and multi-host mosquito vector-borne disease systems, such as West Nile virus (WNV), remains challenging because of complex habitat and resource requirements by hosts and vectors that affect transmission opportunities. We examined correlations between landscape composition and configuration and 2018 WNV sentinel chicken seroconversion in Florida, USA across the state and within five National Oceanic Atmospheric Administration (NOAA) bioclimatic regions to understand strength and variation of landscape effects during an elevated transmission year. Although few landscape studies have examined WNV in Florida, we expected higher percentages of residential or medium-developed landscapes and more fragmented landscapes would be positively correlated with WNV seroconversion owing to the main mosquito vector habitats and avian host distributions. However, we expected to find variation in the importance of forest, wetland, and agriculture landscapes across bioclimatic regions in the state. WNV seroconversion rates were calculated using Florida 2018 Department of Health WNV sentinel chicken seroconversion data from 187 flocks maintained by mosquito control programs. Percent land cover and edge density metrics were calculated for multiple land cover classes and within multiple buffer distances from chicken coops using 2019 National Land Cover Data. We used binomial generalized linear mixed effects models to calculate the importance of landscape metrics to WNV seroconversion. We found no statewide predictors of seroconversion, but as expected, the importance of landscape varied across regions. In the north-central part of the state, we found higher seroconversion in less populated suburban areas while higher seroconversion in south-central Florida was correlated with fragmented forested areas within 0.5 km of coops and intact woody wetland areas within 2 km of coops. This work corroborates previous findings that consistent landscape predictors of WNV are difficult to identify across broader geographic areas and sets the stage for additional work that incorporates climate and landscapes interactions for a greater understanding of WNV ecology in this geographic region. [ABSTRACT FROM AUTHOR]

Background: As cannabis legalization continues to spread across the United States, average Δ9-tetrahydrocannabinol concentrations in recreational products have significantly increased, and no prior study has evaluated effective treatments to reduce cannabis use among high potency cannabis users. Some research has found that the non-intoxicating cannabinoid cannabidiol reduces cannabis use and cannabis use disorder-related symptoms, such as affective disturbance and withdrawal. Results of these studies are promising but limited to synthetic or isolated forms of cannabidiol. Objective: Conduct a placebo-controlled randomized control trial comparing the effects of hemp-derived cannabidiol on reducing Δ9-tetrahydrocannabinol use in concentrate users with cannabis use disorder. Methods: Design. Double-blind, three-arm randomized placebo-controlled trial. Setting. University in the Denver-Boulder, CO, USA area. Study population. Community members who are heavy, stable cannabis concentrate users that meet criteria for at least moderate cannabis use disorder and are seeking to decrease or stop cannabis use. Data. Self-report demographics, substance use, and mental health characteristics, blood and urine based biomarkers and anthropometrics. Outcomes. Affective, physiological, and physical withdrawal symptoms, Δ9-tetrahydrocannabinol use. Analysis. Three-group ANOVAs and χ2 tests will be used to compare baseline variables between groups. Characteristics that differ between groups will be evaluated as potential covariates in subsequent analyses. A multilevel modeling framework will be used for primary outcome analysis to account for the repeated observations nested within participants over time. Pairwise post-hoc simple effects tests will be conducted to confirm patterns of differences. Trial registration: ClinicalTrials.gov NCT06107062. [ABSTRACT FROM AUTHOR]

Background: This study uses a randomized controlled trial (RCT) to test the health benefits of expressive writing that is culturally adapted for Chinese immigrant breast cancer survivors (BCSs) and to characterize how acculturation moderates the effects of expressive writing interventions. Methods: We will recruit Chinese immigrant BCSs (N = 240) diagnosed with stage 0-III breast cancer and within 5 years of completion of primary treatment. Recruitment will occur primarily through community-based organizations and cancer registries. Participants will be randomly assigned either to a control condition to write about neutral topics or to one of two intervention conditions, self-regulation or self-cultivation, both of which aim to promote adaptive cognitive processes but differ in how they achieve this goal. The self-regulation intervention culturally adapts a Western expressive writing paradigm and incorporates emotional disclosure, whereas the self-cultivation intervention originates from Asian cultural values without disclosing emotions. Participants in all three conditions will be asked to write in their preferred language for three 30-minute sessions. The primary outcome will be quality of life (QOL) at the 6- and 12-month follow-ups, and the secondary outcomes will be perceived stress, stress biomarkers, and medical appointments for cancer-related morbidities. Discussion: This project will be the first large RCT to test culturally based brief interventions to improve QOL and reduce stress among Chinese immigrant BCSs. This project is expected to address two important needs of Chinese immigrant BCSs: their unmet psychological needs and the lack of culturally competent mental health care for Chinese immigrant BCSs. The immediate product of this line of research will be empirically evaluated, culturally responsive interventions ready for dissemination to Chinese immigrant BCSs across the United States. ClinicalTrials.gov identifier: NCT04754412. [ABSTRACT FROM AUTHOR]

Understanding the effect of anthropogenic disturbance, and its interaction with carnivores and their prey, is crucial to support the conservation of threatened carnivores, particularly in rapidly changing landscapes. Based on systematic camera-trap sampling of four protected areas in Riau Province of central Sumatra, we assessed the habitat occupancy and spatiotemporal overlap between people, potential carnivore prey, and four threatened species of medium-sized or large carnivores: Sumatran tigers (Panthera tigris sumatrae), Malayan sun bears (Helarctos malayanus), dholes (Cuon alpinus), and Sunda clouded leopards (Neofelis diardi). To assess spatial overlap of target species, we used single-species occupancy models and applied a Species Interaction Factor (SIF) to conditional two-species occupancy models. We also used kernel density estimation (KDE) to assess temporal overlap among these species. Our habitat use models showed that altitude (elevation) strongly influenced the occupancy of all large carnivores and potential prey species. Except for Sunda clouded leopards, the occurrence of large carnivore species was positively related to the spatial co-occurrence of humans (SIF > 1). In addition, we found that sun bears and dholes both exhibited high spatial overlap with tigers, and that sun bears alone exhibited high temporal overlap with people. Our findings contribute to an improved understanding of the contemporary ecology of carnivores and their prey in rapidly changing, southeast Asian landscapes. Such knowledge is important to the conservation and recovery of large carnivores in conservation hotspots that are increasingly dominated by humans across Sumatra, as well as globally.

Background Teams caring for people living with cancer face many difficult clinical situations that are compounded by the pandemic and can have serious consequences on professional and personal life. This study aims to better understand how a multi-component intervention builds resilience in oncology teams. The intervention is based on a salutogenic approach, theories and empirical research on team resilience at work. This intervention research involves partnership between researchers and stakeholders in defining situations of adversity and solutions appropriate to context. Methods The principles of realist evaluation are used to develop context-mechanism-outcome configurations of a multi-component intervention developed by researchers and field partners concerned with the resilience of oncology teams. The multiple case study involves oncology teams in natural contexts in four healthcare establishments in Québec (Canada). Qualitative and quantitative methods are employed. Qualitative data from individual interviews, group interviews and observation are analyzed using thematic content analysis. Quantitative data are collected through validated questionnaires measuring team resilience at work and its effect on teaming processes and cost-effectiveness. Integration of these data enables the elucidation of associations between intervention, context, mechanism and outcome. Discussion The study will provide original data on contextual factors and mechanisms that promote team resilience in oncology settings. It suggests courses of action to better manage difficult situations that arise in a specialized care sector, minimize their negative effects and learn from them, during and after the waves of the pandemic. The mechanisms for problem resolution and arriving at realistic solutions to professional workforce and team effectiveness challenges can help improve practices in other settings.

Perinatal asphyxia (PA) still occurs in about three to five per 1,000 deliveries in developed countries; 20% of these infants show hypoxic-ischemic encephalopathy (HIE) on brain magnetic resonance imaging (MRI). The aim of our study was to apply metabolomic analysis to newborns undergoing therapeutic hypothermia (TH) after PA to identify a distinct metabotype associated with the development of HIE on brain MRI. We enrolled 53 infants born at >35 weeks of gestation with PA: 21 of them showed HIE on brain MRI (the "HIE" group), and 32 did not (the "no HIE" group). Urine samples were collected at 24, 48 and 72 hours of TH. Metabolomic data were acquired using high-resolution mass spectrometry and analyzed with univariate and multivariate methods. Considering the first urines collected during TH, untargeted analysis found 111 relevant predictors capable of discriminating between the two groups. Of 35 metabolites showing independent discriminatory power, four have been well characterized: L-alanine, Creatine, L-3-methylhistidine, and L-lysine. The first three relate to cellular energy metabolism; their involvement suggests a multimodal derangement of cellular energy metabolism during PA/HIE. In addition, seven other metabolites with a lower annotation level (proline betaine, L-prolyl-L-phenylalanine, 2-methyl-dodecanedioic acid, S-(2-methylpropionyl)-dihydrolipoamide-E, 2,6 dimethylheptanoyl carnitine, Octanoylglucuronide, 19-hydroxyandrost-4-ene-3,17-dione) showed biological consistency with the clinical picture of PA. Moreover, 4 annotated metabolites (L-lysine, L-3-methylhistidine, 2-methyl-dodecanedioic acid, S-(2-methylpropionyl)-dihydrolipoamide-E) retained a significant difference between the "HIE" and "no HIE" groups during all the TH treatment. Our analysis identified a distinct urinary metabotype associated with pathological findings on MRI, and discovered 2 putative markers (L-lysine, L-3-methylhistidine) which may be useful for identifying neonates at risk of developing HIE after PA.

ObjectivesThis study sought to evaluate advanced psychometric properties of the 15-item Economic Strain and Resilience in Cancer (ENRICh) measure of financial toxicity for cancer patients.MethodsWe surveyed 515 cancer patients in the greater Houston metropolitan area using ENRICh from March 2019 to March 2020. We conducted a series of factor analyses alongside parametric and non-parametric item response theory (IRT) assessments using Mokken analysis and the graded response model (GRM). We utilized parameters derived from the GRM to run a simulated computerized adaptive test (CAT) assessment.ResultsAmong participants, mean age was 58.49 years and 278 (54%) were female. The initial round factor analysis results suggested a one-factor scale structure. Negligible levels of differential item functioning (DIF) were evident between eight items. Three items were removed due to local interdependence (Q3>+0.4). The original 11-point numerical rating scale did not function well, and a new 3-point scoring system was implemented. The final 12-item ENRICh had acceptable fit to the GRM (pConclusionThese CAT and 4-item versions provide options for quick screening in clinical practice and low-burden assessment in research.

IntroductionThe detection of atherosclerotic plaques at risk for disruption will be greatly enhanced by molecular probes that target vessel wall biomarkers. Here, we test if fluorescently-labeled Activatable Cell Penetrating Peptides (ACPPs) could differentiate stable plaques from vulnerable plaques that disrupt, forming a luminal thrombus. Additionally, we test the efficacy of a combined ACPP and MRI technique for identifying plaques at high risk of rupture.Methods and resultsIn an atherothrombotic rabbit model, disrupted plaques were identified with in vivo MRI and co-registered in the same rabbit aorta with the in vivo uptake of ACPPs, cleaved by matrix metalloproteinases (MMPs) or thrombin. ACPP uptake, mapped ex vivo in whole aortas, was higher in disrupted compared to non-disrupted plaques. Specifically, disrupted plaques demonstrated a 4.5~5.0 fold increase in fluorescence enhancement, while non-disrupted plaques showed only a 2.2~2.5 fold signal increase. Receiver operating characteristic (ROC) analysis indicates that both ACPPs (MMP and thrombin) show high specificity (84.2% and 83.2%) and sensitivity (80.0% and 85.7%) in detecting disrupted plaques. The detection power of ACPPs was improved when combined with the MRI derived measure, outward remodeling ratio.ConclusionsOur targeted fluorescence ACPP probes distinguished disrupted plaques from stable plaques with high sensitivity and specificity. The combination of anatomic, MRI-derived predictors for disruption and ACPP uptake can further improve the power for identification of high-risk plaques and suggests future development of ACPPs with molecular MRI as a readout.

Feline chronic enteropathies (FCE), include food-responsive-enteropathy (FRE), inflammatory bowel disease (IBD), and low-grade intestinal T-cell lymphoma (LGITL), and are common causes of chronic gastrointestinal signs in cats. Distinguishing between different subgroups of FCE can be challenging due to the frequent overlap of anamnestic, clinical, and laboratory data. While dysregulation in lipid metabolism has been reported in humans and dogs with chronic IBD, similar changes in cats are not yet completely understood. Assessing the fatty acid (FA) profile of red blood cell (RBC) membranes offers a valuable method for evaluating the quantity and quality of structural and functional molecular components in the membranes. Therefore, this study aimed to examine the FA composition of RBC membranes in FCE in comparison to healthy cats (HC). Gas-chromatography was used to quantitatively analyze a cluster of 11 FA, and based on these results, parameters of lipid homeostasis and enzyme activity indexes were calculated. A total of 41 FCE cats (17 FRE, 15 IBD, 9 LGITL) and 43 HC were enrolled. In FCE cats, the values of docosapentaenoic acid (p = 0.0002) and docosahexaenoic acid (p = 0.0246), were significantly higher, resulting in an overall increase in ω-3 polyunsaturated fatty acids (PUFA) (p = 0.006), and that of linoleic acid (p = 0.0026) was significantly lower. Additionally, FCE cats exhibited an increased PUFA balance (p = 0.0019) and Δ6-desaturase index (p = 0.0151), along with a decreased ω-6/ω-3 ratio (p = 0.0019). No differences were observed among cats affected by FRE, IBD and LGITL. Like humans and dogs, the results of this study indicate that FCE cats also display changes in their FA lipid profile at the level of the RBC membrane. The non-invasive analysis of RBC membrane shows promise as a potential tool for gaining a better understanding of lipid imbalances in this disease. [ABSTRACT FROM AUTHOR]

Fibromyalgia (FM) is a central disorder characterized by chronic pain, fatigue, insomnia, depression, and other minor symptoms. Knowledge about pathogenesis is lacking, diagnosis difficult, clinical approach puzzling, and patient management disappointing. We conducted a theoretical study based on literature data and computational analysis, aimed at developing a comprehensive model of FM pathogenesis and addressing suitable therapeutic targets. We started from the evidence that FM must involve a dysregulation of central pain processing, is female prevalent, suggesting a role for the hypothalamus-pituitary-gonadal (HPG) axis, and is stress-related, suggesting a role for the HP-adrenocortical (HPA) axis. Central pathogenesis was supposed to involve a pain processing loop system including the thalamic ventroposterolateral nucleus (VPL), the primary somatosensory cortex (SSC), and the thalamic reticular nucleus (TRN). For decreasing GABAergic and/or increasing glutamatergic transmission, the loop system crosses a bifurcation point, switching from monostable to bistable, and converging on a high-firing-rate steady state supposed to be the pathogenic condition. Thereafter, we showed that GABAergic transmission is positively correlated with gonadal-hormone-derived neurosteroids, notably allopregnanolone, whereas glutamatergic transmission is positively correlated with stress-induced glucocorticoids, notably cortisol. Finally, we built a dynamic model describing a multistable, double-inhibitory loop between HPG and HPA axes. This system has a high-HPA/low-HPG steady state, allegedly reached in females under combined premenstrual/postpartum brain allopregnanolone withdrawal and stress condition, driving the thalamocortical loop to the high-firing-rate steady state, and explaining the connection between endocrine and neural mechanisms in FM pathogenesis. Our model accounts for FM female prevalence and stress correlation, suggesting the use of neurosteroid drugs as a possible solution to currently unsolved problems in the clinical treatment of the disease. [ABSTRACT FROM AUTHOR]

Evidence supports that people identifying as a sexual or gender minority (SGMs) experience minority-related stress resulting from discrimination or expectations of prejudice, and that this is associated with increased mental and physical health problems compared to cisgender heterosexuals. However, the biological mechanisms driving minority-related stress impacts remain unknown, including the role of the gut microbiome. Thus, the aim of this study was to determine the relationship between SGM status and gut microbiome health among young adults attending a 4-year university. To this end, a prospective pilot study was completed in the fall and spring semesters of 2021–22. Self-identified SGMs (N = 22) and cisgender-heterosexuals (CIS-HET, N = 43) completed in-person interviews to provide mental health data and demographic information. Nail and saliva samples were collected at the time of interview to quantify chronic and acute cortisol. Stool samples were collected within 48 hours of interview for microbiome analysis. Assessment of the gut microbiota identified a significant reduction in alpha diversity among the SGM group, even when adjusting for mental health outcome. SGM group showed trends for higher abundance of microbes in phylum Bacteroidetes and lower abundance of microbes in phyla Firmicutes, Actinobacteria, and Proteobacteria compared to the CIS-HET group. These findings support that the gut microbiome could be contributing to negative health effects among the SGM community. [ABSTRACT FROM AUTHOR]

Aim The aim of this study was to analyze changes in the incidence, management and mortality of DFU in Sicilian Type 2 diabetic patients hospitalized between two eras, i.e. 2008–2013 and 2014–2019. Methods We compared the two eras, era1: 2008–13, era2: 2014–19. In era 1, n = 149, and in era 2, n = 181 patients were retrospectively enrolled. Results In the population hospitalized for DFU in 2008–2013, 59.1% of males and 40.9% of females died, whilst in 2014–2019 65.9% of males and 34.1% of females died. Moderate chronic kidney disease (CKD) was significantly higher in patients that had died than in ones that were alive (33% vs. 43%, p < 0.001), just as CKD was severe (14.5% vs. 4%, p < 0.001). Considering all together the risk factors associated with mortality, at Cox regression multivariate analysis only moderate-severe CKD (OR 1.61, 95% CI 1.07–2.42, p 0.021), age of onset greater than 69 years (OR 2.01, 95% CI 1.37–2.95, p Conclusions Patients with DFU have high mortality and reduced life expectancy. Age at onset of diabetic foot ulcer, eGFR values and CKD are the principal risk factors for mortality.

Mice lacking B cells are more susceptible to S. typhimurium infection. How B cells contribute to protective immunity against Salmonella and what signals drive their activation are still unclear. Neutrophils (Nphs), monocytes (MOs), and dendritic cells (DCs) are involved in early immune responses to control the initial replication of S. typhimurium. These cells can produce B cell activating factor (BAFF) required for mature B cell survival and may help regulate B cell responses during Salmonella infection. Using BAFF reporter mice (BAFF-RFP+/-), we discovered that an i.p. infection with a virulent strain of S. typhimurium increased BAFF expression in splenic conventional DCs (cDC) and inflammatory Ly6Chi MOs/DCs four days post-infection. S. typhimurium infection induced the release of BAFF from Nphs, a decrease of BAFF-RFP expression and expansion of BAFF-RFP+ Nphs in the spleen and peritoneal cavity. After S. typhimurium infection, serum BAFF levels and immature and mature B cell subsets and plasma cells increased substantially. Conditional knockout (cKO) mice lacking BAFF in either Nphs or cDCs compared to control Bafffl/fl mice had reduced up-regulation of systemic BAFF levels and reduced expansion of mature and germinal center B cell subsets after infection. Importantly, the cKO mice lacking BAFF from either Nphs or cDCs had impaired induction of Salmonella-specific IgM Abs, and were more susceptible to S. typhimurium infection. Thus, Nphs and cDCs are major cellular sources of BAFF driving B cell responses, required for mounting optimal protective immunity against lethal Salmonella infection.

ObjectiveTo investigate the durability of the first integrase inhibitor-based regimen in a HIV geriatric multicentric prospective cohort and to explore the reasons of regimen discontinuation.DesignThis is an analysis conducted on the Geriatric Patients Living with HIV/AIDS (GEPPO) cohort, an Italian prospective observational multicentre cohort of people living with HIV with 65 years of age or more.MethodsThe analysis was performed using R (version 4.0.2). The tests performed were two sided assuming a 5% significance level (Kruskal-Wallis test, Chi-squared test, log-rank test and a Cox Proportional Hazard model). The proportion of participants discontinuing the three regimens was displayed using cumulative curves.ResultsAmong 1531 patients enrolled between 2017 and 2019 in the GEPPO cohort, we included 822 participants in this analysis. At baseline, median age was 69.8, the immunovirological profile good, multimorbidity was present in 42.3% of participants, while 27.4% were on polypharmacy. Overall, 483, 243 and 96 participants received DTG, RAL and EVG/c respectively as first InSTI. At the end of the follow up 6.4%, 21.1% and 22.9% participants discontinued DTG, RAL and EVG/c respectively. Using a log-rank test, EVG showed a significantly lower durability than DTG (pConclusionsThe three integrase inhibitors considered showed a good durability and no virological failures in geriatric patients such as those enrolled in the GEPPO cohort when used in a two or three drug regimen.

The use of "belly scoring" can offer a novel, non-invasive objective management tool to gauge food intake between individuals, groups, and populations, and thus, population fitness. As food availability is increasingly affected by predation, ecological competition, climate change, habitat modification, and other human activities, an accurate belly scoring tool can facilitate comparisons among wildlife populations, serving as an early warning indicator of threats to wildlife population health and potential population collapse. In social species, belly scores can also be a tool to understand social behavior and ranking. We developed and applied the first rigorous quantitative photogrammetric methodology to measure belly scores of wild painted dogs (Lycaon pictus). Our methodology involves: (1) Rigorous selection of photographs of the dorso/lateral profile of individuals at a right angle to the camera, (2) photogrammetrically measuring belly chord length and "belly drop" in pixels, (3) adjusting belly chord length as a departure from a standardized leg angle, and (4) converting pixel measurements to ratios to eliminate the need to introduce distance from the camera. To highlight a practical application, this belly score method was applied to 631 suitable photographs of 15 painted dog packs that included 186 individuals, all collected between 2004-2015 from allopatric painted dog populations in and around Hwange (n = 462) and Mana Pools National Parks (n = 169) in Zimbabwe. Variation in mean belly scores exhibited a cyclical pattern throughout the year, corresponding to biologically significant patterns to include denning demand and prey availability. Our results show significant differences between belly scores of the two different populations we assessed, thus highlighting food stress in the Hwange population. In the face of growing direct and indirect anthropogenic disturbances, this standardised methodology can provide a rapid, species-specific non-invasive management tool that can be applied across studies to rapidly detect emergent threats.

IntroductionSince the start of the pandemic, millions of people have been infected, with thousands of deaths. Many foci worldwide have been identified in retirement nursing homes, with a high number of deaths. Our study aims were to evaluate the spread of SARS-CoV-2 in the retirement nursing homes, the predictors to develop symptoms, and death.Methods and findingsWe conducted a retrospective study enrolling all people living in retirement nursing homes (PLRNH), where at least one SARS-CoV-2 infected person was present. Medical and clinical data were collected. Variables were compared with Student's t-test or Pearson chi-square test as appropriate. Uni- and multivariate analyses were conducted to evaluate variables' influence on infection and symptoms development. Cox proportional-hazards model was used to evaluate 30 days mortality predictors, considering death as the dependent variable. We enrolled 382 subjects. The mean age was 81.15±10.97 years, and males were 140(36.7%). At the multivariate analysis, mental disorders, malignancies, and angiotensin II receptor blockers were predictors of SARS-CoV-2 infection while having a neurological syndrome was associated with a lower risk. Only half of the people with SARS-CoV-2 infection developed symptoms. Chronic obstructive pulmonary disease and neurological syndrome were correlated with an increased risk of developing SARS-CoV-2 related symptoms. Fifty-six (21.2%) people with SARS-CoV-2 infection died; of these, 53 died in the first 30 days after the swab's positivity. Significant factors associated with 30-days mortality were male gender, hypokinetic disease, and the presence of fever and dyspnea. Patients' autonomy and early heparin treatment were related to lower mortality risk.ConclusionsWe evidenced factors associated with infection's risk and death in a setting with high mortality such as retirement nursing homes, that should be carefully considered in the management of PLRNH.

Stress exposure during perinatal period may lead to maternal cortisol increase that negatively affects the offspring development. In recent years, the interest on non-invasive sampling methods to measure cortisol as a marker of stress is increasing in both humans and animals. Indeed, discomfort due to blood collection may compromise the diagnostic outcome, mainly in uncooperative patients. So far, some alternative matrices but not milk have been explored in adult dogs, while no data are available on the neonate and paediatric live pups. This study aimed to measure cortisol concentration in different biological substrates in both dams (blood, saliva, hair and milk) and pups (saliva and hair) at established times from proestrus up to two months after parturition. For this purpose, five female German shepherd bitches and their 22 pups were enrolled. Cortisol concentration was assessed using the enzyme immunoassay kit (Salivary Cortisol ELISA kit, Salimetrics) after matrices appropriate preparation if required. Cortisol was measurable in all the substrates, except some milk samples below the detection limit. Maternal cortisol concentrations differed among the matrices (P

Agent-based models of opinion formation are becoming increasingly complex, because of their size and of the embedding of several individual psychological traits of the agents, aimed at realistically capturing the multifaceted aspects of social interaction. Therefore, the characterisation of the model properties mostly relies on simulation-based numerical approaches: more techniques are needed to analyse, contrast, and compare the properties of different models. We propose a novel graphical technique, which relies on the Agreement Plot to visualise the evolution of opinion distributions over time, that allows us to unveil behavioural patterns and capabilities of agent-based opinion formation models. Our proposed approach can be used to characterise the relation between global properties of the model evolution and the model features (initial opinion distributions, agent parameters, underlying digraphs), and is here showcased through its application to both seminal and recently proposed opinion formation models. [ABSTRACT FROM AUTHOR]

Mapping brain functions is crucial for neurosurgical planning in patients with drug-resistant seizures. However, presurgical language mapping using either functional or structural networks can be challenging, especially in children. In fact, most of the evidence on this topic derives from cross-sectional or retrospective studies in adults submitted to anterior temporal lobectomy. In this prospective study, we used fMRI and DTI to explore patterns of language representation, their predictors and impact on cognitive performances in 29 children and young adults (mean age at surgery: 14.6 ± 4.5 years) with focal lesional epilepsy. In 20 of them, we also assessed the influence of epilepsy surgery on language lateralization. All patients were consecutively enrolled at a single epilepsy surgery center between 2009 and 2015 and assessed with preoperative structural and functional 3T brain MRI during three language tasks: Word Generation (WG), Rhyme Generation (RG) and a comprehension task. We also acquired DTI data on arcuate fasciculus in 24 patients. We first assessed patterns of language representation (relationship of activations with the epileptogenic lesion and Laterality Index (LI)) and then hypothesized a causal model to test whether selected clinical variables would influence the patterns of language representation and the ensuing impact of the latter on cognitive performances. Twenty out of 29 patients also underwent postoperative language fMRI. We analyzed possible changes of fMRI and DTI LIs and their clinical predictors. Preoperatively, we found atypical language lateralization in four patients during WG task, in one patient during RG task and in seven patients during the comprehension task. Diffuse interictal EEG abnormalities predicted a more atypical language representation on fMRI (p = 0.012), which in turn correlated with lower attention (p = 0.036) and IQ/GDQ scores (p = 0.014). Postoperative language reorganization implied shifting towards atypical language representation. Abnormal postoperative EEG (p = 0.003) and surgical failures (p = 0.015) were associated with more atypical language lateralization, in turn correlating with worsened fluency. Neither preoperative asymmetry nor postoperative DTI LI changes in the arcuate fasciculus were observed. Focal lesional epilepsy associated with diffuse EEG abnormalities may favor atypical language lateralization and worse cognitive performances, which are potentially reversible after successful surgery.

The objective of this study was to evaluate the effects of the association of cottonseed processing method with chitosan on carcass traits and meat quality of lambs finished in feedlot. Eighty lambs with an average body weight of 20.6 kg, with 04 months of age, were distributed in a completely randomized design, in a 2 x 2 factorial arrangement. The factors were represented by two cottonseed processing method (whole or ground) and two levels of chitosan (0 and 136 mg/kg BW). The association of cottonseed processing method with chitosan in the lamb diet did not affect (P>0.05) carcasses traits. The pH, color, cooking losses, shear force, and proximate composition of meat were also not affected (P>0.05) by the processing method of cottonseed or its association with chitosan in the lamb diets. There was an increase in palmitoleic (c9-C16:1; P = 0.01) and conjugated linoleic (P = 0.02) fatty acids when ground cottonseed was associated with chitosan. Ground cottonseed associated with chitosan increases the concentration of unsaturated fatty acids in the meat of feedlot lambs.

BACKGROUND:Conversion to secondary progressive multiple sclerosis (SPMS) is associated with a relatively poor prognosis, and SPMS is responsible for the majority of the social and economic costs associated with MS. Managing the Transition to SPMS (ManTra) is a mixed methods project conducted in Italy and Germany aimed to set up a user-led resource to empower and improve the quality of life of newly diagnosed SPMS patients. AIMS:To assess the experiences and the needs of Italian people who recently converted to SPMS, patient significant others (SOs), neurologists and other health professionals (HPs). METHODS:We conducted 15 personal semistructured interviews (PSIs) with SPMS patients who transitioned up to five years, and three focus group meetings (FGMs), one of SPMS SOs, one of neurologists, and one of other HPs. Participants were purposely selected from the three geographic areas of Italy, and varied in terms of gender, education and (for patients) disease severity. PSIs and FGMs were audiorecorded, transcribed and analyzed by two researchers using the framework analysis. RESULTS:One hundred sub-categories were identified, grouped into 13 categories and four themes: 'awareness of the transition', 'communication of the transition', 'dealing with symptoms worsening', and 'needs'. The major unmet needs were collected in four dimensions 'organization and management; 'empowerment training'; 'information'; and 'policies'. CONCLUSIONS:Two are the main findings: first, the widespread lack of awareness around the transition; second, the need to improve the quality of the care pathway in the Italian context. It was particularly stressed the need for a holistic and multidisciplinary approach (with patients and SOs as members of the team), the development of an ad hoc plan of follow up visits with easy access to MS specialists' consultation/treatment; specialized training for each stakeholders; more information on SPMS, daily management and changes at policy level.

INTRODUCTION:An Australian case series study demonstrated the effectiveness of the REsilience and Activities for every DaY for people with multiple sclerosis (READY for MS), a resilience group training program based on Acceptance and Commitment Therapy, in improving quality of life in people with MS. This study aimed to evaluate the feasibility and acceptability of the Italian READY for MS program, and to preliminary assess its efficacy when compared to an active control intervention (group relaxation). METHODS:Single-blind phase II randomized controlled trial (RCT) and nested qualitative study (ISRCTN registration number: 38971970). Health-related quality of life (primary study outcome), mood, resilience, psychological flexibility and its protective factors were measured at baseline, after seven, 12 and 24 weeks. READY participants completed the purpose-built satisfaction questionnaire after 12 weeks. After trial completion, the control group also received READY. One-to-one participant interviews were conducted within three months of finishing the READY groups. RESULTS:Four intervention groups were conducted with 39 participants (20 READY, 19 relaxation). Two patients (READY) withdrew before beginning the intervention due to unexpected work commitments. Feasibility and acceptability of READY were good, with high participant engagement and satisfaction. No statistical effects of READY were detected vs relaxation. Thirty participants were interviewed (18 READY; 12 relaxation + READY). Content data analysis revealed seven overarching themes: "Attitudes towards participation"; "Perceptions of program composition"; "Program impacts on life domains"; "Program active elements"; "Program improvement trajectories"; "Program differences and similarities"; "Suggested READY improvements". CONCLUSION:READY was well accepted by MS patients with varied socio-demographic and clinical characteristics. Qualitative (but not quantitative) data provided evidence in favour of READY. Our findings will inform methodological and intervention refinements for the multi-centre RCT that will follow.

AimSubclasses of different glycaemic disturbances could explain the variation in characteristics of individuals with type 2 diabetes (T2D). We aimed to examine the association between subgroups based on their glucose curves during a five-point mixed-meal tolerance test (MMT) and metabolic traits at baseline and glycaemic deterioration in individuals with T2D.MethodsThe study included 787 individuals with newly diagnosed T2D from the Diabetes Research on Patient Stratification (IMI-DIRECT) Study. Latent class trajectory analysis (LCTA) was used to identify distinct glucose curve subgroups during a five-point MMT. Using general linear models, these subgroups were associated with metabolic traits at baseline and after 18 months of follow up, adjusted for potential confounders.ResultsAt baseline, we identified three glucose curve subgroups, labelled in order of increasing glucose peak levels as subgroup 1-3. Individuals in subgroup 2 and 3 were more likely to have higher levels of HbA1c, triglycerides and BMI at baseline, compared to those in subgroup 1. At 18 months (n = 651), the beta coefficients (95% CI) for change in HbA1c (mmol/mol) increased across subgroups with 0.37 (-0.18-1.92) for subgroup 2 and 1.88 (-0.08-3.85) for subgroup 3, relative to subgroup 1. The same trend was observed for change in levels of triglycerides and fasting glucose.ConclusionsDifferent glycaemic profiles with different metabolic traits and different degrees of subsequent glycaemic deterioration can be identified using data from a frequently sampled mixed-meal tolerance test in individuals with T2D. Subgroups with the highest peaks had greater metabolic risk.

Amyotrophic lateral sclerosis (ALS) is a poor-prognosis disease with puzzling pathogenesis and inconclusive treatments. We develop a mathematical model of ALS based on a system of interactive feedback loops, focusing on the mutant SOD1G93A mouse. Misfolded mutant SOD1 aggregates in motor neuron (MN) mitochondria and triggers a first loop characterized by oxidative phosphorylation impairment, AMP kinase over-activation, 6-phosphofructo-2-kinase (PFK3) rise, glucose metabolism shift from pentose phosphate pathway (PPP) to glycolysis, cell redox unbalance, and further worsening of mitochondrial dysfunction. Oxidative stress then triggers a second loop, involving the excitotoxic glutamatergic cascade, with cytosolic Ca2+ overload, increase of PFK3 expression, and further metabolic shift from PPP to glycolysis. Finally, cytosolic Ca2+ rise is also detrimental to mitochondria and oxidative phosphorylation, thus closing a third loop. These three loops are overlapped and positive (including an even number of inhibitory steps), hence they form a candidate multistationary (bistable) system. To describe the system dynamics, we model the interactions among the functional agents with differential equations. The system turns out to admit two stable equilibria: the healthy state, with high oxidative phosphorylation and preferential PPP, and the pathological state, with AMP kinase activation, PFK3 over expression, oxidative stress, excitotoxicity and MN degeneration. We demonstrate that the loop system is monotone: all functional agents consistently act toward the healthy or pathological condition, depending on low or high mutant SOD1 input. We also highlight that molecular interactions involving PFK3 are crucial, as their deletion disrupts the system's bistability leading to a single healthy equilibrium point. Hence, our mathematical model unveils that promising ALS management strategies should be targeted to mechanisms that keep low PFK3 expression and activity within MNs.

BackgroundPeople with HIV with co-occurring substance use and mental health diagnoses who are unstably housed have poorer outcomes for retention in care and viral suppression. Navigation models are a potential strategy to help this vulnerable population obtain the necessary medical and non-medical services across multiple service systems. The Health Resources and Services Administration's Special Projects of National Significance: "Building a Medical Home for Multiply-Diagnosed HIV-positive Homeless Populations initiative 2012-2017 found that navigation models may be an effective intervention to support people with HIV with unstable housing improve HIV health outcomes. However, there is limited information about the mechanisms by which this intervention works. In this article, we explore the participant and program factors for achieving stable housing at 6 months and how these factors influence HIV health outcomes.Methods and findingsThis was a prospective study of 471 unstably housed people with HIV enrolled in a navigation intervention across nine sites in the United Stated from 2013-2017. All sites provided HIV primary medical care. Eight sites were located in urban areas and one site served a predominantly rural population. Two sites were federally qualified health centers, three were city or county health departments, one site was a comprehensive HIV/AIDS service organization, and three sites were outpatient or mobile clinics affiliated with a university -based or hospital system. Data were collected via interview and medical chart review at baseline, post 6 and 12 months. Type and dose of navigation activities were collected via a standardized encounter form. We used a path analysis model with housing stability at 6 months as the mediator to examine the direct and indirect effects of participant's socio-demographics and risk factors and navigation on viral suppression and retention in care at 12 months. Housing stability at 6 months was associated with male gender, younger age, viral suppression at baseline, having a lower risk for opiate use, recent homelessness, lower risk of food insecurity, and a longer length of time living with HIV. Participants who increased self-efficacy with obtaining help by 6 months had significantly higher odds of achieving housing stability. Stable housing, fewer unmet needs, moderate to high risk for opiate use, and viral suppression at baseline had a direct effect on viral suppression at 12 months. The intensity of navigation contact had no direct effect on housing stability and a mixed direct effect on viral suppression. Recent diagnosis with HIV, women, greater social support, increased self-efficacy and higher intensity of navigation contact had a direct effect on improved retention in HIV primary care at 12 months.ConclusionsIn this sample of people with HIV who are experiencing homelessness, housing stability had a significant direct path to viral suppression. Navigation activities did not have a direct effect on the path to housing stability but were directly related to retention in care. These results identify key populations and factors to target resources and policies for addressing the health and social unmet needs of people with HIV to achieve housing stability and HIV health outcomes.

Clinical and molecular characterization by Whole Exome Sequencing (WES) is reported in 35 COVID-19 patients attending the University Hospital in Siena, Italy, from April 7 to May 7, 2020. Eighty percent of patients required respiratory assistance, half of them being on mechanical ventilation. Fiftyone percent had hepatic involvement and hyposmia was ascertained in 3 patients. Searching for common genes by collapsing methods against 150 WES of controls of the Italian population failed to give straightforward statistically significant results with the exception of two genes. This result is not unexpected since we are facing the most challenging common disorder triggered by environmental factors with a strong underlying heritability (50%). The lesson learned from Autism-Spectrum-Disorders prompted us to re-analyse the cohort treating each patient as an independent case, following a Mendelian-like model. We identified for each patient an average of 2.5 pathogenic mutations involved in virus infection susceptibility and pinpointing to one or more rare disorder(s). To our knowledge, this is the first report on WES and COVID-19. Our results suggest a combined model for COVID-19 susceptibility with a number of common susceptibility genes which represent the favorite background in which additional host private mutations may determine disease progression.

Detecting the ultrastructure of brain tissue in human archaeological remains is a rare event that can offer unique insights into the structure of the ancient central nervous system (CNS). Yet ancient brains reported in the literature show only poor preservation of neuronal structures. Using scanning electron microscopy (SEM) and advanced image processing tools, we describe the direct visualization of neuronal tissue in vitrified brain and spinal cord remains which we discovered in a male victim of the AD 79 eruption in Herculaneum. We show exceptionally well preserved ancient neurons from different regions of the human CNS at unprecedented resolution. This tissue typically consists of organic matter, as detected using energy-dispersive X-ray spectroscopy. By means of a self-developed neural image processing network, we also show specific details of the neuronal nanomorphology, like the typical myelin periodicity evidenced in the brain axons. The perfect state of preservation of these structures is due to the unique process of vitrification which occurred at Herculaneum. The discovery of proteins whose genes are expressed in the different region of the human adult brain further agree with the neuronal origin of the unusual archaeological find. The conversion of human tissue into glass is the result of sudden exposure to scorching volcanic ash and the concomitant rapid drop in temperature. The eruptive-induced process of natural vitrification, locking the cellular structure of the CNS, allowed us to study possibly the best known example in archaeology of extraordinarily well-preserved human neuronal tissue from the brain and spinal cord.

Within triple negative breast cancer, several molecular subtypes have been identified, underlying the heterogeneity of such an aggressive disease. The basal-like subtype is characterized by mutations in the TP53 gene, and is associated with a low pathologic complete response rate following neoadjuvant chemotherapy. In a genome-scale short hairpin RNA (shRNA) screen of breast cancer cells, polo-like kinase 1 (Plk1) was a frequent and strong hit in the basal breast cancer cell lines indicating its importance for growth and survival of these breast cancer cells. Plk1 regulates progression of cells through the G2-M phase of the cell cycle. We assessed the activity of two ATP-competitive Plk1 inhibitors, GSK461364 and onvansertib, alone and with a taxane in a set of triple negative breast cancer cell lines and in vivo. GSK461364 showed synergism with docetaxel in SUM149 (Combination Index 0.70) and SUM159 (CI, 0.62). GSK461364 in combination with docetaxel decreased the clonogenic potential (interaction test for SUM149 and SUM159, p

Candida bloodstream infection (BSI) represents a growing infective problem frequently associated to biofilm production due to the utilization of intravascular devices. Candida species distribution (n = 612 strains), their biofilm production and hospital antifungal drug consumption were evaluated in different wards of a tertiary care academic hospital in Italy during the years 2011-2016. In the considered time window, an increasing number of Candida BSI (p = 0.005) and of biofilm producing strains were observed (p

BACKGROUND:Word comprehension across semantic categories is a key area of language development. Using online automated eye-tracking technology to reduce response demands during a word comprehension test may be advantageous in children with autism spectrum disorder (ASD). OBJECTIVES:To measure online accuracy of word recognition across eleven semantic categories in preschool children with ASD and in typically developing (TD) children matched for gender and developmental age. METHODS:Using eye-tracker methodology we measured the relative number of fixations on a target image as compared to a foil of the same category shown simultaneously on screen. This online accuracy measure was considered a measure of word understanding. We tested the relationship between online accuracy and offline word recognition and the effects of clinical variables on online accuracy. Twenty-four children with ASD and 21 TD control children underwent the eye-tracking task. RESULTS:On average, children with ASD were significantly less accurate at fixating on the target image than the TD children. After multiple comparison correction, no significant differences were found across the eleven semantic categories of the experiment between preschool children with ASD and younger TD children matched for developmental age. The ASD group showed higher intragroup variability consistent with greater variation in vocabulary growth rates. Direct effects of non-verbal cognitive levels, vocabulary levels and gesture productions on online word recognition in both groups support a dimensional view of language abilities in ASD. CONCLUSIONS:Online measures of word comprehension across different semantic categories show higher interindividual variability in children with ASD and may be useful for objectively monitor gains on targeted language interventions.

BackgroundThe purpose of this study was to evaluate the role of a non-locking plate applied to the anteromedial surface of the proximal humerus on loads at the implant-bone interface of non-locking and locking lateral plate fixation of proximal humeral fractures with a medial gap.MethodsTwenty synthetic humeri models were used. In fifteen, the proximal portion of the humerus was osteotomized to create a two-part surgical neck fracture, with a 10-mm medial gap and a 5-mm lateral gap; five models were controls. In the osteotomized humeri, five models were stabilized with a locking lateral plate (group L), five with a locking lateral plate and an anteromedial non-locking plate (group L+T), and five with a non-locking lateral plate and a non-locking anteromedial plate (group T+T). All humeri were tested under axial loading until catastrophic failure, which was characterized as complete closure of the medial gap. Stiffness was calculated using force vs. displacement curves. The data were analyzed via descriptive and inferential studies, at a 5% significance level.ResultsStatistically significant differences were seen among all the constructions. The combination of a lateral locking plate with an anteromedial non-locking plate (group L+T) was the stiffest construction, while the combination of a non-locking lateral plate with a non-locking anteromedial plate (group T+T) was the least stiff, even in comparison with a single locking lateral plate (p = 0.01). When the two groups which utilized a lateral locking plate (groups L+T and L) were compared, the group with additional anteromedial support demonstrated greater stiffness (p = 0.03), and stiffness values for the control group comprised of intact humeri models were even higher (p = 0.01).ConclusionCombining a lateral locking plate with a non-locking anteromedial plate provides a stiffer construction for fixation of unstable two-part proximal humerus fractures with a medial gap. Mechanical benefits of medial support with a second non-locking antero-medial plate seems to be related with better construct stability in terms of strength and fatigue, potentially reducing the risk of varus collapse of the humerus head and fracture healing disturbances.

Clostridium difficile (Cd) infection (CDI) typically occurs after antibiotic usage perturbs the gut microbiota. Mucosa-associated invariant T cells (MAIT) are found in the gut and their development is dependent on Major histocompatibility complex-related protein 1 (MR1) and the host microbiome. Here we were interested in determining whether the absence of MR1 impacts resistance to CDI. To this end, wild-type (WT) and MR1-/- mice were treated with antibiotics and then infected with Cd spores. Surprisingly, MR1-/- mice exhibited resistance to Cd colonization. 16S rRNA gene sequencing of feces revealed inherent differences in microbial composition. This colonization resistance was transferred from MR1-/- to WT mice via fecal microbiota transplantation, suggesting that MR1-dependent factors influence the microbiota, leading to CDI susceptibility.