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Background In addition to the metabolic effects in diabetes, glucagon-like peptide 1 receptor (GLP-1R) agonists lead to a small but substantial increase in heart rate (HR). However, the GLP-1R actions on the autonomic nervous system (ANS) in diabetes remain debated. Therefore, this meta-analysis evaluates the effect of GLP-1R agonist on measures of ANS function in diabetes. Methods According to the Cochrane Collaboration and Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement, we conducted a meta-analysis considering clinical trials in which the autonomic function was evaluated in diabetic subjects chronically treated with GLP-1R agonists. The outcomes were the change of ANS function measured by heart rate variability (HRV) and cardiac autonomic reflex tests (CARTs). Results In the studies enrolled, HR significantly increased after treatment (P

Abstract Background Adolescence is a crucial period for body image formation. Weight misperception is the discrepancy between individuals’ body weight perception and their actual nutritional status. Both weight concerns and substance use are common among adolescents, and there is evidence of an associations between these two variables. Thus, the aim of this study was to assess the association between weight misperception and substance use (smoking and alcohol) in a national sample of normal weight Brazilian adolescents. Methods Data were obtained from the Brazilian Study of Cardiovascular Risks in Adolescents (ERICA), a cross-sectional, multicenter, national, school-based survey, carried out in 124 municipalities with more than 100,000 inhabitants from Brazil. The sample included adolescents aged 12–17 years, classified as normal weight by nutritional status evaluation. The following measures were collected: weight underestimation and overestimation (exposure); having tried cigarette smoking, current smoking, current alcohol consumption, binge drinking and current smoking and alcohol consumption(outcomes); macro-region, sex, type of school, and excessive screen time (confounders). The frequency of variables was calculated with 95% confidence intervals (CI). Poisson regression models were used to estimate prevalence ratios (PR). Results In total, data from 53,447 adolescents were analyzed. Weight misperception was present in a third of the adolescents, with similar prevalence of weight underestimation and overestimation. In adolescents aged 12–14 years, weight underestimation and overestimation were associated with having tried cigarette smoking (PR: 1.18 and 1.43, respectively), current alcohol consumption (PR: 1.33 for both weight misperception categories), and binge drinking (PR: 1.96 and 2.01, respectively). Weight underestimation was associated with both having tried cigarette smoking and current alcohol consumption in boys (PR: 1.14 and 1.16, respectively) and girls (PR: 1.32 and 1.15, respectively). In girls, weight overestimation was associated with all substance use variables (PR between 1.19 and 1.41). Conclusions Our results showed an association between weight misperception and having tried cigarette smoking, alcohol consumption, and binge drinking in younger adolescents. In addition, weight overestimation was associated with all substance use indicators in girls. Based on our findings, interventions aimed to improve weight perception in normal weight adolescents may contribute to the reduction of substance use in this population.

Multifunctional scaffolds with host defense peptides designed for regenerative endodontics are desirable nanobiotechnological tools for dentistry. Here, different scaffolds were tested for use during the pulp revascularization process, including poly(vinyl alcohol)-PVA hydrogels or resins, collagen hydrogels and poly(vinyl alcohol) PVA/Chitosan (PVA/CS) nanofibers. Based on time to degradation (21 days), nanofibers were chosen to be incorporated with ciprofloxacin and IDR-1002 (each at 50 mg/g). Nanofibers containing ciprofloxacin and IDR-1002 had anti-biofilm activity against Enterococcus faecalis, Staphylococcus aureus and a multispecies oral biofilm, besides anti-inflammatory activities. The in vivo subcutaneous tissue response to tooth fragments filled with nanofibers demonstrated a pulp-like tissue formation, when compared to empty teeth fragments. Thus, we designed a strong antimicrobial, immunomodulatory and regenerative candidate for pulp revascularization and regeneration procedures.

Abstract Background Biologics have demonstrated efficacy in PsA in randomized clinical trials. More evidence is needed on their effectiveness under real clinical practice conditions. The aim of the present work is to provide real-world evidence of the effectiveness of biologics for PsA in the daily clinical practice. Methods CHRONOS was a multicenter, non-interventional, cohort study conducted in 20 Italian hospital rheumatology clinics. Results 399 patients were eligible (56.9% females, mean (SD) age: 52.4 (11.6) years). The mean (SD) duration of PsA and psoriasis was 7.2 (6.9) and 15.3 (12.2) years, respectively. The mean (SD) duration of the biologic treatment under analysis was 18.6 (6.5) months. The most frequently prescribed biologic was secukinumab (40.4%), followed by adalimumab (17.8%) and etanercept (16.5%). The proportion of overall responders according to EULAR DAS28 criteria was 71.8% (95% CI: 66.7–76.8%) out of 308 patients at 6 months and 68.0% (95% CI: 62.7–73.3%) out of 297 patients at 1 year. Overall, ACR20/50/70 responses at 6 months were 41.2% (80/194), 29.4% (57/194), 17.1% (34/199) and at 1-year were 34.9% (66/189), 26.7% (51/191), 18.4% (36/196), respectively. Secondary outcome measures improved rapidly already at 6 months: mean (SD) PASI, available for 87 patients, decreased from 3.2 (5.1) to 0.6 (1.3), the proportion of patients with dactylitis from 23.6% (35/148) to 3.5% (5/142) and those with enthesitis from 33.3% (49/147) to 9.0% (12/133). Conclusions The CHRONOS study provides real-world evidence of the effectiveness of biologics in PsA in the Italian rheumatological practice, confirming the efficacy reported in RCTs across various outcome measures.

Palbociclib is in early-stage clinical testing in advanced hepatocellular carcinoma (HCC). Here, we investigated whether the anti-tumor activity of palbociclib, which prevents the CDK4/6-mediated phosphorylation of RB1 but simultaneously activates AKT signaling, could be improved by its combination with a PI3K/AKT/mTOR inhibitor in liver cancer models. The selective pan-AKT inhibitor, MK-2206, or the microRNA-199a-3p were tested in combination with palbociclib in HCC cell lines and in the TG221 HCC transgenic mouse model. The combination palbociclib/MK-2206 was highly effective, but too toxic to be tolerated by mice. Conversely, the combination miR-199a-3p mimics/palbociclib not only induced a complete or partial regression of tumor lesions, but was also well tolerated. After 3 weeks of treatment, the combination produced a significant reduction in number and size of tumor nodules in comparison with palbociclib or miR-199a-3p mimics used as single agents. Moreover, we also reported the efficacy of this combination against sorafenib-resistant cells in vitro and in vivo. At the molecular level, the combination caused the simultaneous decrease of the phosphorylation of both RB1 and of AKT. Our findings provide pre-clinical evidence for the efficacy of the combination miR-199a-3p/palbociclib as anti-HCC treatment or as a new approach to overcome sorafenib resistance.

BackgroundBreathing pattern disorders (BPDs) and inducible laryngeal obstruction (ILO) cause similar symptoms to asthma, including dyspnea and chest tightness, with an estimated prevalence of up to one-fifth of patients with asthma. Both conditions can be comorbid with asthma, and there is evidence that they are misdiagnosed and mistreated as asthma. ObjectiveThis study aims to explore whether the symptoms of ILO and BPD were topics of discussion in a UK asthma online health community and patient experiences of diagnosis and treatment, in particular their use of reliever inhalers. MethodsA qualitative thematic analysis was performed with posts from an asthma community between 2018 and 2022. A list of key ILO or BPD symptoms was created from the literature. Posts were identified using the search terms “blue inhaler” and “breath” and included if describing key symptoms. Discussion threads of included posts were also analyzed. ResultsThe search retrieved a total of 1127 relevant posts: 1069 written by 302 users and 58 posted anonymously. All participants were adults, except 2 who were parents writing about their children. Sex and age were only available for 1.66% (5/302; 3 females and 2 males) and 9.93% (30/302) of participants (27 to 73 years old), respectively. The average number of posts written by each participant was 3.54 (range 1-63). Seven participants wrote >20 posts each. Participants experiencing undiagnosed ILO or BPD symptoms, whether or not comorbid with asthma, expressed frustration with the “one-size-fits-all” approach to diagnosis, as many felt that their asthma diagnosis did not fully explain symptoms. Some suspected or were formally diagnosed with BPD or ILO, the latter reporting relief on receiving a diagnosis and appropriate management. Participants showed awareness of their inappropriate salbutamol use or overuse due to lack of effect on symptoms. BPD and ILO symptoms were frequently comorbid with asthma. The asthma online community was a valuable resource: engagement with peers not only brought comfort but also prompted action with some going back to their clinicians and reaching a diagnosis and appropriate management. ConclusionsUndiagnosed ILO and BPD symptoms and lack of effects of asthma treatment were topics of discussion in an asthma online community, caused distress and frustration in participants, and affected their relationship with health care professionals, showing that patients experiencing BPD and ILO have unmet needs. Clinicians’ education on BPD and ILO diagnosis and management, as well as increased access to appropriate management options, such as respiratory physiotherapy and speech and language therapy, are warranted particularly in primary care. Qualitative evidence that engagement with the online community resulted in patients taking action going back to their clinicians and reaching a diagnosis of ILO and BPD prompts future research on online peer support from an established online health community as a self-management resource for patients.

A construção de um Projeto Político Pedagógico (PPP) é essencial para orientar as atividades da comunidade escolar proporcionando uma base sólida para a organização e o desenvolvimento da educação. Nesse sentido, o objetivo deste artigo consiste em investigar a compreensão de docentes que atuam no município de Cairu-BA sobre o PPP. Fundamentado na perspectiva de Paulo Freire e em alguns estudos que discutem a construção de um PPP, foi realizado um questionário relativo à construção do PPP, sua importância e suas bases democráticas. As informações foram obtidas por um questionário desenvolvido no Google Forms e enviado via link pelo aplicativo Whatsapp e foram analisadas por meio da Análise Textual Discursiva, com base nas seguintes categorias: i) Orientar/Nortear o fazer pedagógico; ii) Identidade Escolar; iii) A importância da Comunidade e a democratização do PPP. Dentre os resultados apresentados, destaca-se a importância da participação da comunidade escolar na elaboração do PPP como caminho para transformação da realidade e democratização do processo educacional. Ademais, o estudo indica a relação entre o entendimento do professor acerca do PPP como um dos elementos norteadores para sua construção, visto que, está intrinsecamente ligado à participação dos docentes no processo de discussão, elaboração e execução do PPP.

Este artigo tem por objetivo refletir sobre história, usos e valores místicos do café, tendo como âncora as religiões de matriz africana (com ênfase na Umbanda e no Afro-catolicismo) e os saberes tradicionais quilombolas. O artigo é resultado de estudos desenvolvidos no âmbito da disciplina de História da Alimentação, porém, respaldado em pesquisas e vivências de campo em um terreiro de Umbanda e em memórias familiares quilombolas. Assim, aqui são trazidas as primeiras percepções dessa pesquisa, que tem a pretensão de mapear as principais ervas utilizadas nos terreiros de matriz africana da Cidade de Goiás. Um trabalho de cunho bibliográfico, mas também vivencial, pautado na metodologia da história oral, fundamentado em teóricos como Abimbola (1976), Ribeiro (1996), Bourdieu (2007), Eliade (1996), Rafael Marque de Bivar (2011), Rezende (2017), Ferrão (1993), Negrão (1983-1986), Otto (2005), Polain (2006), Moreira (2010), Simoni (2015), entre outros. O contexto social marcado pela diversidade direciona múltiplos olhares para as religiões de matriz africana e o uso das plantas nesse contexto é um elemento que precisa ser melhor pesquisado. Dentre todas as plantas utilizadas nos rituais, o café é considerado uma planta sagrada na Umbanda, utilizado por parteiras e benzedeiras desde Brasil colônia. Ele é uma planta considerada como instrumento místico de cura e fortalecimento pelos umbandistas, e este artigo traz as primeiras percepções suscitadas pelas pesquisas que o embasam. Essas pesquisas nos levam a pensar que os rituais de práticas terapêuticas desenvolvidos na Umbanda caminham em sintonia com a medicina tradicional.

BackgroundHispanic and Latinx gay, bisexual, and other sexual minority men (SMM) are disproportionately affected by HIV in the United States. With the availability of self-testing services, HIV and sexually transmitted infection (STI) testing may be more accessible for Latinx immigrant SMM who face obstacles to obtaining HIV-related services. Combining the potential of self-testing kits and the influence of peer educators may present an opportunity to increase HIV and STI testing and preexposure prophylaxis (PrEP) uptake or linkage to HIV care among Latinx immigrant SMM. ObjectiveThis study aimed to develop and pilot a peer intervention to distribute HIV and STI self-testing kits and provide peer counseling based on the information-motivation-behavioral skills model to increase PrEP uptake and HIV and STI testing among Latinx immigrant SMM. Our evaluation focused on determining the differences in HIV testing, STI testing, and PrEP uptake outcomes between the intervention and control groups. MethodsWe conducted semistructured interviews with community stakeholders to elicit factors to consider for training and intervention. The interview findings informed the development of the intervention and peer training protocols. We piloted the intervention with Latinx immigrant SMM and randomly assigned participants to the intervention group, who received peer counseling and HIV and STI self-testing kits, or the control group, who only received peer counseling. We administered baseline, 1-week, 6-week, and 12-week follow-up surveys to assess behaviors related to HIV testing, STI testing, and PrEP uptake. Owing to the COVID-19 pandemic, the intervention components were delivered via web-based modalities. Chi-square tests were performed to examine the associations between HIV testing, STI testing, and PrEP motivation and behaviors across the study arms (intervention vs control). We conducted Cramer V test to determine the strength of the association between study arm and each of the outcome variables. We also assessed the impact of the COVID-19 pandemic on participants. ResultsOverall, 50 (intervention, n=30 and control, n=20) Latinx immigrant SMM participated in the program. Participants reported life disruptions owing to COVID-19, with 68% (34/50) reporting job loss after the declaration of the pandemic. After intervention participation, a higher proportion of participants in the intervention group reported having been tested for STIs (76% vs 36.8%; P=.01; Cramer V=0.394). Among the participants in the intervention group, 91% (21/23) reported being motivated to use PrEP compared with 59% (10/17) in the control group (P=.02; Cramer V=0.385). ConclusionsBy facilitating access to HIV and STI testing through peer-delivered information, motivational support, and behavioral skills training as well as the provision of self-testing kits, our intervention demonstrated the potential to increase HIV prevention behaviors in Latinx immigrant SMM. Peer-based programs that offer self-testing and internet-based modes of accessing information may be a feasible strategy for reaching Latinx immigrant SMM. Trial RegistrationClinicalTrials.gov NCT03922126; https://clinicaltrials.gov/ct2/show/NCT03922126

Objectives The objectives of this systematic review are to identify studies that assess the effectiveness of patient-directed financial incentive interventions to improve asthma management behaviours, determine overall effectiveness of financial incentives, identify design characteristics of effective interventions and assess the impact on longer-term outcomes in the context of asthma.Design Systematic review with narrative synthesis.Data sources Electronic databases (MEDLINE, Embase, Global Health, PsycINFO, CINAHL, PubMed and Web of Science) and grey literature sources (NHS Digital, CORE, ProQuest, Clinical Trials Register and EU Clinical Trials Register) were searched in November 2021 and updated March 2023.Eligiblity criteria Eligible articles assessed financial incentives to improve asthma management behaviours (attendance at appointments, medication adherence, tobacco smoke/allergen exposure, inhaler technique and asthma education) for patients with asthma or parents/guardians of children with asthma. Eligible study design included randomised controlled, controlled or quasi-randomised trials and retrospective/prospective cohort, case-controlled or pilot/feasibility studies.Synthesis A narrative synthesis was conducted; eligible studies were grouped by asthma management behaviours and financial incentive framework domains.Results We identified 4268 articles; 8 met the inclusion criteria. The studies were from the USA (n=7) and the UK (n=1). Asthma management behaviours included attendance at appointments (n=4), reduction in smoke exposure (n=1) and medication adherence (n=3). Five studies demonstrated positive behaviour change, four of which were significant (attendance at appointments (n=3) showed significant differences between intervention and control: 73% and 49% in one study, 46.3% and 28.9% in another, and 35.7% and 18.9%, respectively; medication adherence (n=1) showed significant change from 80% during intervention to 33% post intervention). These four significant studies used ‘positive gain’, ‘certain’, ‘fixed’ financial incentives of smaller magnitude, given for ‘all’ instances of behaviour.Conclusion There is some evidence that patient-directed financial incentives improve asthma management behaviours. However, in view of the wide heterogeneity in study design and measured outcomes, determining overall effectiveness was challenging.PROSPERO registration number CRD42021266679.

Introduction In the UK, approximately 4.3 million adults have asthma, with one-third experiencing poor asthma control, affecting their quality of life, and increasing their healthcare use. Interventions promoting emotional/behavioural self-management can improve asthma control and reduce comorbidities and mortality. Integration of online peer support into primary care services to foster self-management is a novel strategy. We aim to co-design and evaluate an intervention for primary care clinicians to promote engagement with an asthma online health community (OHC). Our protocol describes a ‘survey leading to a trial’ design as part of a mixed-methods, non-randomised feasibility study to test the feasibility and acceptability of the intervention.Methods and analysis Adults on the asthma registers of six London general practices (~3000 patients) will be invited to an online survey, via text messages. The survey will collect data on attitudes towards seeking online peer support, asthma control, anxiety, depression, quality of life, information on the network of people providing support with asthma and demographics. Regression analyses of the survey data will identify correlates/predictors of attitudes/receptiveness towards online peer support. Patients with troublesome asthma, who (in the survey) expressed interest in online peer support, will be invited to receive the intervention, aiming to reach a recruitment target of 50 patients. Intervention will involve a one-off, face-to-face consultation with a practice clinician to introduce online peer support, sign patients up to an established asthma OHC, and encourage OHC engagement. Outcome measures will be collected at baseline and 3 months post intervention and analysed with primary care and OHC engagement data. Recruitment, intervention uptake, retention, collection of outcomes, and OHC engagement will be assessed. Interviews with clinicians and patients will explore experiences of the intervention.Ethics and dissemination Ethical approval was obtained from a National Health Service Research Ethics Committee (reference: 22/NE/0182). Written consent will be obtained before intervention receipt and interview participation. Findings will be shared via dissemination to general practices, conference presentations and peer-reviewed publications.Trial registration number NCT05829265.

Abstract Introduction Recent advances in long‐acting antiretroviral therapy (LA‐ART) could provide new options for HIV treatment and reduce adherence barriers, if regimens are acceptable to patients. We elicited preferences for key attributes of potential LA‐ART regimens among people with HIV (PWH) in the United States, focusing on four treatment modes (oral tablets, subcutaneous injections, intramuscular injections, and implants), product characteristics and location of administration. Methods A discrete choice experiment was conducted among PWH aged ≥18 years recruited from HIV clinics in Washington State and Atlanta, Georgia from March 2021 to June 2022. Participants responded to 17 choice scenarios, each with three options: two systematically generated hypothetical LA‐ART regimens and a constant opt‐out (their current daily oral treatment). LA‐ART regimen descriptions included treatment mode, pain, dosing frequency, location, pre‐treatment time with undetectable viral load, pre‐treatment negative reaction testing and “late‐dose leeway” (i.e. flexibility or forgiveness in timing the next dose). We used conditional logistic regression, with an interaction between treatment mode and pain, to estimate preference weights for all attribute levels. Results Seven hundred participants (350 at each site) enrolled, with median age 51 years (range 18–73); 70% identified as cisgender male, 24% as cisgender female and 6% as non‐binary or transgender. LA oral tablets were the only mode preferred over current daily oral treatment, with annual implants and injections the next most preferred LA‐ART option. Longer time between doses was preferred, and administration at home was preferred to clinics, which were preferred to pharmacies. Attributes with less impact on preferences included oral lead‐in treatment to achieve viral suppression or test for negative reactions and late‐dose leeway around the prescribed dosing interval. Participants in Atlanta were more likely to prefer their current daily oral ART than participants from Seattle. Conclusions PWH in the United States may soon have several options for LA‐ART. Our results suggest that LA oral tablets will be preferred by many patients over their current daily oral treatment, while implants and injections with longer duration may be acceptable to some. Future research should investigate sources of preference heterogeneity and actual uptake of and adherence to LA‐ART products, when available.

The treatment of deep-seated tumours with electrons of very high energies (VHEE, 70–150 MeV) has already been explored in the past, suggesting that a dosimetric coverage comparable with state-of-the-art proton (PT) or photon radiotherapy (RT) could be achieved with a large (> 10) number of fields and high electron energy. The technical and economical challenges posed by the deployment of such beams in treatment centres, together with the expected small therapeutic gain, prevented the development of such technique. This scenario could radically change in the light of recent developments that occurred in the compact, high-gradient, electron acceleration technology and, additionally, of the experimental evidence of the sparing of organs at risk achieved in ultra-high dose rate irradiation, also referred to as FLASH. Electrons with the energy required to treat intracranial lesions could be provided, at dose rates compatible with what is needed to trigger the FLASH effect, by accelerators that are a few metres long, and the organ sparing could be exploited to significantly simplify the irradiation geometry, decreasing the number of fields needed to treat a patient. In this paper, the case of two patients affected by a chordoma and a meningioma, respectively, treated with protons in Trento (IT) is presented. The proton plans have been compared with VHEE plans and X-ray intensity-modulated radiotherapy (IMRT) plans. The VHEE plans were first evaluated in terms of physical dose distribution and then assuming that the FLASH regimen can be achieved. VHEE beams demonstrated their potential in obtaining plans that have comparable tumour coverage and organs at risk sparing when benchmarked against current state-of-the-art IMRT and PT. These results were obtained with a number of explored fields that was in the range between 3 and 7, consistent with what is routinely performed in IMRT and PT conventional irradiations. The FLASH regimen, in all cases, showed its potential in reducing damage to the organs placed nearby the target volume, allowing, particularly in the chordoma case where the irradiation geometry is more challenging, a better tumour coverage with respect to the conventional treatments.

RESUMO: A pesquisa tem como objetivo identificar e analisar estudos latino-americanos, que se pautam em aspectos como a participação social no desenvolvimento científico-tecnológico e a concepção de agendas de pesquisa no contexto da Educação em Ciências, no contexto da perspectiva do Pensamento Latino-Americano em Ciência, Tecnologia e Sociedade (PLACTS) e da Tecnologia Social. Para isso, localizamos pesquisas publicadas em periódicos nos países da América Latina, nas seguintes bases de dados: Scielo e Redalyc. Os estudos foram analisados com base na Análise Textual Discursiva, tendo como categorias a Participação Social e a Ressignificação de agendas de pesquisa. Dentre os resultados, evidenciamos nos estudos que a Participação Social potencializa a reconstrução de relações sociais coletivas e tem contribuído para a mudança de postura de atores sociais no fazer ciência e tecnologia; e a Ressignificação de agendas de pesquisa propiciaram o direcionamento para o desenvolvimento científico-tecnológico, latino-americano, aderente às especificidades locais, contribuindo para uma Educação em Ciências crítica e emancipatória.

In questo testo viene presentata l’antologia Nulla che non possano i versi – Antologia de poesia italiana entre o Brasil e a Itália (2018), in cui sono presentati dei poeti, uomini e donne, nati/e, vissuti o attualmente residenti in Brasile, che tra il XVIII ed il XXI secolo hanno adottato l’italiano come lingua di poesia. Ognuno/a a suo modo, si sono impegnati/e nella valorizzazione della lingua italiana e nella possibilità di stabilire proficui dialoghi tra l’Italia e il Brasile. S’intravede, nell’insieme della loro opera, una possibile tradizione di scrittura in lingua italiana in Brasile

Affinity matured self-reactive antibodies are found in autoimmune diseases like systemic lupus erythematous. Here, we used fate-mapping reporter mice and single-cell transcriptomics coupled to antibody repertoire analysis to characterize the post-germinal center (GC) B cell compartment in a new mouse model of autoimmunity. Antibody-secreting cells (ASCs) and memory B cells (MemBs) from spontaneous GCs grouped into multiple subclusters. ASCs matured into two terminal clusters, with distinct secretion, antibody repertoire and metabolic profiles. MemBs contained FCRL5+ and CD23+ subsets, with different in vivo localization in the spleen. GC-derived FCRL5+ MemBs share transcriptomic and repertoire properties with atypical B cells found in aging and infection and localize to the marginal zone, suggesting a similar contribution to recall responses. While transcriptomically diverse, ASC and MemB subsets maintained an underlying clonal redundancy. Therefore, self-reactive clones could escape subset-targeting therapy by perpetuation of self-reactivity in distinct subsets.

Background: Overprescription of short-acting beta-agonist (SABA) inhalers and blood eosinophil count have strong associations with exacerbation risk in asthma. However, in the authors' recent publication only a minority of patients overprescribed SABA (≥6 inhalers in 12 months) were eosinophilic (≥0.3 x 109 cells/l). Aim: To compare the characteristics of eosinophilic and non-eosinophilic patients with asthma overprescribed SABA inhalers, and identify latent classes using clinical variables available in primary care. Design & setting: Cross-sectional analysis of patients with asthma in North East London, England, using primary care electronic health record data. Method: Unadjusted and adjusted multi-variate regression models and latent class analysis. Results: Eosinophilia was significantly less likely in female patients (P = 0.004), those with multiple mental health comorbidities (P

ABSTRACT Objective: This two-centre cross-sectional study aimed to evaluate whether xerostomia occurrence is associated with oral health-related quality of life (OHRQoL) in patients with end-stage renal disease (ESRD) after the adjustment for potential confounders. Methods: Oral examinations were performed by calibrated examiners for untreated dental caries, periodontitis and tooth loss in 180 adults with ESRD. The presence of xerostomia was determined using the global question “How often does your mouth feel dry?”. OHRQoL was evaluated by the simplified version of the Oral Health Impact Profile (OHIP14) questionnaire. Multivariate zero-inflated negative binomial regression analysis was used to calculate the incidence rate ratios (IRR) for the nonzero scores and odds ratios (OR) of having no impact in OHIP14 scores according to the presence of exposure. Results: In the adjusted model, xerostomia (IRR = 1.57; 95% CI: 1.12 to 2.20) was associated with poorer OHRQoL. The adjusted domain-specific analysis revealed that xerostomia occurrence significantly impacted the psychological disability and social disability, and the chance of having no impact was lower for the psychological discomfort domain (OR = 0.84; 95% CI: 0.12 to 0.98). Conclusion: Xerostomia exert an impact on OHRQoL in patients with ESRD, mainly in the psychological and social disabilities constructs.

The catfishes Brachyplatystoma filamentosum (Kumakuma), Brachyplatystoma vaillantii (Laulao catfish), and Brachyplatystoma rousseauxii (gilded catfish) are important fishery resources in Brazil, where they are sold both fresh and in the form of fillets or steaks. These species have morphological similarities, thus, they can be easily misidentified or substituted, especially after processed. Therefore, accurate, sensitive, and reliable methods are needed for the identification of these species to avoid commercial fraud. In the present study, we develop two multiplex PCR assays for the identification of the three catfish species. Each multiplex protocol combined three species-specific forward primers and a universal reverse primer to produce banding patterns able to discriminate the target species unequivocally. The length of the cytochrome C oxidase subunit I (COI) fragments was approximately 254 bp for B. rousseauxii, 405 bp for B. vaillantii, and 466 bp for B. filamentosum, while the control region (CR) assay produced fragments of approximately 290 bp for B. filamentosum, 451 bp for B. vaillantii, and 580 bp for B. rousseauxii. The protocols were sensitive enough to detect the target species at a DNA concentration of 1 ng/µL, with the exception of the CR of B. vaillantii, in which the fragment was only detectable at 10 ng/µL. Therefore, the multiplex assays developed in the present study were sensitive, accurate, efficient, rapid, and cost-effective for the unequivocal identification of the target species of Brachyplatystoma. They can be utilized by fish processing industries to certify their products, or by government agencies to authenticate products and prevent fraudulent commercial substitutions.

Remote sensing techniques, namely Unmanned Aerial Vehicle (UAV) photogrammetry and t-LiDAR (terrestrial Light Detection and Ranging), two well-established techniques, were applied for seven years in a mountainous Mediterranean catchment in Greece (Ilioupoli test site, Athens), following a wildfire event in 2015. The goal was to monitor and quantify soil erosion and sedimentation rates with cm accuracy. As the frequency of wildfires in the Mediterranean has increased, this study aims to present a methodological approach for monitoring and quantifying soil erosion and sedimentation rates in post-fire conditions, through high spatial resolution field measurements acquired using a UAV survey and a t-LiDAR (or TLS—Terrestrial Laser Scanning), in combination with georadar profiles (Ground Penetration Radar—GPR) and GNSS. This test site revealed that 40 m3 of sediment was deposited following the first intense autumn rainfall events, a value that was decreased by 50% over the next six months (20 m3). The UAV–SfM technique revealed only 2 m3 of sediment deposition during the 2018–2019 analysis, highlighting the decrease in soil erosion rates three years after the wildfire event. In the following years (2017–2021), erosion and sedimentation decreased further, confirming the theoretical pattern, whereas sedimentation over the first year after the fire was very high and then sharply lessened as vegetation regenerated. The methodology proposed in this research can serve as a valuable guide for achieving high-precision sediment yield deposition measurements based on a detailed analysis of 3D modeling and a point cloud comparison, specifically leveraging the dense data collection facilitated by UAV–SfM and TLS technology. The resulting point clouds effectively replicate the fine details of the topsoil microtopography within the upland dam basin, as highlighted by the profile analysis. Overall, this research clearly demonstrates that after monitoring the upland area in post-fire conditions, the UAV–SfM method and LiDAR cm-scale data offer a realistic assessment of the retention dam’s life expectancy and management planning. These observations are especially crucial for assessing the impacts in the wildfire-affected areas, the implementation of mitigation strategies, and the construction and maintenance of retention dams.

The EU steel industry accounts for a crude steel production of 140 Mt/y, provided by the integrated (57%) and electric (43%) routes, which respectively require up to 6.0 and 0.6 MWh/tCrudeSteel of energy input, and emits on average 1.85 and 0.4 tCO2/tCrudeSteel. The mitigation of such CO2 emissions is crucial, and would involve the direct avoidance of carbon, improvement of energy efficiency, and carbon capture. However, the environmental burden of the steel industry cannot be limited to this, given the very large amount (approximately 5 Mt) of residues landfilled every year in the EU. This practice cannot be sustained anymore, since it represents a detrimental waste of resources and burden to the environment. These aspects require prompt action to meet the Green Deal goals envisioned for 2030. This review paper aims to provide an overview of the main state-of-the-art technologies commercially (and not) available for the effective treatment of a wide variety of residues. To enrich this overview with further potential candidates towards a more sustainable steel manufacturing process, the combined application of two technologies (a plasma reactor and a RecoDust unit for the recovery of metals and minerals, respectively) at TRL 5-6 is also investigated here.

Stevia rebaudiana (Bertoni) is a highly valuable crop for the steviol glycoside content in its leaves, which are no-calorie sweeteners hundreds of times more potent than sucrose. The presence of health-promoting phenolic compounds, particularly flavonoids, in the leaf of S. rebaudiana adds further nutritional value to this crop. Although all these secondary metabolites are highly desirable in S. rebaudiana leaves, the genes regulating the biosynthesis of phenolic compounds and the shared gene network between the regulation of biosynthesis of steviol glycosides and phenolic compounds still need to be investigated in this species. To identify putative candidate genes involved in the synergistic regulation of steviol glycosides and phenolic compounds, four genotypes with different contents of these compounds were selected for a pairwise comparison RNA-seq analysis, yielding 1136 differentially expressed genes. Genes that highly correlate with both steviol glycosides and phenolic compound accumulation in the four genotypes of S. rebaudiana were identified using the weighted gene co-expression network analysis. The presence of UDP-glycosyltransferases 76G1, 76H1, 85C1, and 91A1, and several genes associated with the phenylpropanoid pathway, including peroxidase, caffeoyl-CoA O-methyltransferase, and malonyl-coenzyme A:anthocyanin 3-O-glucoside-6″-O-malonyltransferase, along with 21 transcription factors like SCL3, WRK11, and MYB111, implied an extensive and synergistic regulatory network involved in enhancing the production of such compounds in S. rebaudiana leaves. In conclusion, this work identified a variety of putative candidate genes involved in the biosynthesis and regulation of particular steviol glycosides and phenolic compounds that will be useful in gene editing strategies for increasing and steering the production of such compounds in S. rebaudiana as well as in other species.

The worldwide agricultural system confronts a significant challenge represented by the increasing demand for food in the face of a growing global population. This challenge is exacerbated by a reduction in cultivable land and the adverse effects of climate change on crop yield quantity and quality. Breeders actively embrace cutting-edge omics technologies to pursue resilient genotypes in response to these pressing issues. In this global context, new breeding techniques (NBTs) are emerging as the future of agriculture, offering a solution to introduce resilient crops that can ensure food security, particularly against challenging climate events. Indeed, the search for domestication genes as well as the genetic modification of these loci in wild species using genome editing tools are crucial steps in carrying out de novo domestication of wild plants without compromising their genetic background. Current knowledge allows us to take different paths from those taken by early Neolithic farmers, where crop domestication has opposed natural selection. In this process traits and alleles negatively correlated with high resource environment performance are probably eradicated through artificial selection, while others may have been lost randomly due to domestication and genetic bottlenecks. Thus, domestication led to highly productive plants with little genetic diversity, owing to the loss of valuable alleles that had evolved to tolerate biotic and abiotic stresses. Recent technological advances have increased the feasibility of de novo domestication of wild plants as a promising approach for crafting optimal crops while ensuring food security and using a more sustainable, low-input agriculture. Here, we explore what crucial domestication genes are, coupled with the advancement of technologies enabling the precise manipulation of target sequences, pointing out de novo domestication as a promising application for future crop development.

Statistical analysis of properties of single microparticles, such as cells, bacteria or plastic slivers, has attracted increasing interest in recent years. In this field flow cytometry is considered the gold standard technique, but commercially available instruments are bulky, expensive, and not suitable for use in Point-of-Care (PoC) testing. Microfluidic flow cytometers, on the other hand, are small, cheap and can be used for on-site analysis. However, in order to detect small particles, they require complex geometries and the aid of external optical components. To overcome these limitations here we present an opto-fluidic flow cytometer with an integrated 3D in-plane spherical mirror for enhanced optical signal collection. As result the signal-to-noise ratio is increased by a factor of 6, enabling the detection of particle sizes down to 1.5μm. The proposed optofluidic detection scheme allows the simultaneous collection of particles fluorescence and scattering - using a single optical fiber - which is crucial to easily distinguish particle populations with different optical properties. The devices have been fully characterized using fluorescent polystyrene beads of different sizes. As a proof of concept for potential real-world applications, signals from fluorescent HEK cells and Escherichia coli bacteria were analyzed.

The bursting phenomenon consists in the switch of a laminar separation bubble from a short to a long configuration. In the former case, reduced effects on profile pressure distribution are typically observed with respect to the attached condition. On the contrary, long bubbles provoke significant variations in the loading coefficient upstream of the separation position, with increased risk of stall of the lifting surfaces. The present work presents an experimental database describing separated boundary layers evolving under different Reynolds numbers, adverse pressure gradients and free-stream turbulence levels. Overall, more than 80 flow conditions were tested concerning short and long bubbles for the characterization of separated flows under turbine-like conditions. Measurements were performed on a flat plate geometry using a fast-response Particle Image Velocimetry (PIV) system. For each flow case, two sets of 6000 flow records were acquired with an acquisition frequency equal to 300 and 1000 Hz. Based on existing criteria for the identification of the bursting phenomenon, the flow cases were clustered in terms of short and long bubble states. Additionally, the kind of instability (i.e., convective or absolute) developing into the separated boundary layer was identified based on flow statistics. The present data captures the existing link between the bursting of a laminar separation bubble and the onset of the absolute instability of the separated shear layer, with stationary vortices forming in the dead air region.

Transposable elements (TEs) significantly drive dynamic changes that characterize genome evolution. However, understanding the variability associated with TE insertions among different cultivars remains challenging. The pomegranate (Punica granatum L.) has yet to be extensively studied regarding the roles of TEs in the diversification of cultivars. Herein, we explored the genome distribution of TEs and its potential functional implications among four pomegranate cultivars, ‘Bhagwa’, ‘Dabenzi’, ‘Taishanhong’ and ‘Tunisia’, whose genome sequences are available. A total of 8404 full-length TEs were isolated. The content of TEs varied among the cultivars, ranging from 41.67% of ‘Taishanhong’ to 52.45% of ‘Bhagwa’. In all cultivars, the Gypsy superfamily of retrotransposons accounted for a larger genome proportion than the Copia superfamily. Seventy-three full-length TEs were found at the same genomic loci in all four cultivars. By contrast, 947, 297, 311, and 874 TEs were found exclusively in ‘Bhagwa’, ‘Dabenzi’, ‘Taishanhong’, and ‘Tunisia’ cultivars, respectively. Phylogenetic clustering based on the presence of TE insertions in specific loci reflected the geographic origins of the cultivars. The insertion time profiles of LTR-REs were studied in the four cultivars. Shared elements across the four cultivars exhibited, on average, a more ancient insertion date than those exclusive to three, two, or one cultivars. The majority of TEs were located within 1000 bp from the nearest gene. This localization was observed for 57% of DNA TEs and 55% of long-terminal repeat retrotransposons (LTR-RE). More than 10% of TEs resulted inserted within genes. Concerning DNA TEs, 3.91% of insertions occurred in introns, while 2.42% occurred in exons. As to LTR-REs, 4% of insertions occurred in exons and 1.98% in introns. Functional analysis of the genes lying close to TEs was performed to infer if differences in TE insertion can affect the fruit quality. Two TE insertions were found close to two genes encoding 4-coumarate--CoA ligase, an enzyme involved in the phenylpropanoid pathway. Moreover, a TIR/Mariner element was found within the exon of a gene encoding anthocyanidin reductase in the ‘Tunisia’ genotype, crucial in the biosynthesis of flavan-3-ols and proanthocyanidins, strictly correlated with the nutraceutical properties of pomegranate. Although functional and metabolomic studies are essential to elucidate the consequences of TE insertions, these results contribute to advancing our comprehension of the role of TEs in pomegranate genomics, providing insights for crop breeding.

Renal failure is relatively common in children presenting to the emergency department, suggesting that the assumption of normal renal function is not always valid. Although some computed tomography (CT) scans necessitate the use of intravenous contrast, one should probably consider whether a blood test is necessary to assess the patient’s renal function and possibly consider other imaging modalities before proceeding. With no pediatric-specific guidelines and no validated pediatric prevention strategies, further research is needed to establish clear recommendations for contrast-enhanced exams in stable and unstable pediatric patients with unknown renal function.

Robotic Total Stations (RTS) are fully automated theodolites with electronic distance measurement (EDM) that include a number of additional tools (e.g., camera, laser rangefinder, onboard computer, and tracking software, etc.) enabling them to work autonomously. The added tools make RTSs able to track mobile targets on civil structures thus opening to the use of RTSs in structural monitoring. Unfortunately, the available RTSs are able to track a target up to a motion rate of 3 Hz. Reducing mobile masses is a viable design strategy for extending this frequency border. Such a strategy is pursued in this study by proposing the use of parallel pointing systems (PPS) as basic mechanical architectures for RTSs. The literature on PPSs is reviewed and the applicable PPS architectures are selected. Successively, the selected architectures are sized according to RTSs’ functional requirements, and the positioning precision of the sized mechanisms is evaluated. The result of this study is that there are three PPS architectures suitable for RTSs, whose detailed comparison is also presented.

Nitrogen content in urine plays a crucial role in assessing the environmental impact of dairy farming. Urine acidifications avoid urine nitrogen volatilization, but potentially lead to a degradation of creatinine, the most dependable marker for quantifying total urine excretion volume, affecting its measurement. This study aimed to assess how acidifying urine samples affects the concentration and detection of creatinine in dairy cattle. In this trial, individual urine samples from 20 Holstein lactating dairy cows were divided into three subsamples, allocated to 1 of 3 groups consisting of 20 samples each. Samples were immediately treated as follows: acidification with H2SO4 (1 mL of acid in 30 mL of sample) to achieve a pH < 2 (Group 1)); addition of an equal volume of distilled water (1 mL of distilled water in 30 mL of sample) to investigate dilution effects (Group 2); or storage without any acid or water treatment (Group 3). An analysis of creatinine levels was carried out using the Jaffe method. The Friedman test was employed to compare urine groups across treatments, and the Bland–Altman test was used to assess the agreement between measurements in Group 1 and Group 3. Urinary creatinine values were statistically different (p < 0.001) between Group 1 (median 48.5 mg/dL; range 36.9–83 mg/dL), Group 2 (median 47.5 mg/dL; range 36.5–80.7 mg/dL), and Group 3 (median 48.9 mg/dL, range 37.2–84). Bland–Altman analysis demonstrates agreement between Group 3 and Group 1. The measurement of urinary creatinine using the Jaffe method is affected by sample acidification, but the use of creatinine as a marker for total urine output could remain a viable tool when urine samples are acidified.

The presence of microbial pathogens in foods compromises their safety resulting in foodborne illnesses, public health disorders, product recalls, and economic losses. In this work, 60 samples of chilled raw chicken meat and 40 samples of packaged ready-to-eat (RTE) fresh leafy greens salads, sold in Greek retail stores (butchers and supermarkets), were analyzed for the presence of three important foodborne pathogenic bacteria, i.e., Campylobacter spp., Salmonella spp., and Listeria monocytogenes, following the detection protocols of the International Organization for Standardization (ISO). In parallel, the total aerobic plate count (APC), Enterobacteriaceae, total coliforms, Escherichia coli, and staphylococci were also enumerated as hygiene (safety) indicator organisms. When present, representative typical colonies for each pathogen were biochemically verified, following the ISO guidelines. At the same time, all the Campylobacter isolates from chicken (n = 120) were identified to the species level and further phylogenetically discriminated through multiplex and repetitive sequence-based (rep) polymerase chain reaction (PCR) methods, respectively. Concerning raw chicken, Campylobacter spp. were recovered from 54 samples (90.0%) and Salmonella spp. were recovered from 9 samples (15.0%), while L. monocytogenes was present in 35 samples (58.3%). No Campylobacter was recovered from salads, and Salmonella was present in only one sample (2.5%), while three salads were found to be contaminated with L. monocytogenes (7.5%). The 65% of the Campylobacter chicken isolates belonged to C. jejuni, whereas the rest, 35%, belonged to C. coli. Alarmingly, APC was equal to or above 106 CFU/g in 53.3% and 95.0% of chicken and salad samples, respectively, while the populations of some of the other safety indicators were in some cases also high. In sum, this study unravels high occurrence percentages for some pathogenic and food safety indicator microorganisms in raw chicken meat and RTE fresh leafy greens salads sold in Greek retail, highlighting the need for more extensive microbiological control throughout the food production chain (from the farm/field to the market).

Alcohol-related liver disease (ALD) encompasses a range of pathological conditions that are complex to study at the clinical and preclinical levels. Despite the global burden of ALD, there is a lack of effective treatments, and mortality is high. One of the reasons for the unsuccessful development of novel therapies is that experimental studies are hindered by the challenge of recapitulating this multifactorial disorder in vitro, including the contributions of hepatotoxicity, impaired lipid metabolism, fibrosis and inflammatory cytokine storm, which are critical drivers in the pathogenesis of ALD in patients and primary targets for drug development. Here, we present the unique characteristics of the culture of human precision-cut liver slices (PCLS) to replicate key disease processes in ALD. PCLS were prepared from human liver specimens and treated with ethanol alone or in combination with fatty acids and lipopolysaccharide (FA + LPS) for up to 5 days to induce hepatotoxic, inflammatory and fibrotic events associated with ALD. Alcohol insult induced hepatocyte death which was more pronounced with the addition of FA + LPS. This mixture showed a significant increase in the cytokines conventionally associated with the prototypical inflammatory response observed in severe ALD, and interestingly, alcohol alone exhibited a different effect. Profibrogenic activation was also observed in the slices and investigated in the context of slice preparation. These results support the versatility of this organotypic model to study different pathways involved in alcohol-induced liver damage and ALD progression and highlight the applicability of the PCLS for drug discovery, confirming their relevance as a bridge between preclinical and clinical studies.

Induction of fetal hemoglobin (HbF) is highly beneficial for patients carrying β-thalassemia, and novel HbF inducers are highly needed. Here, we describe a new class of promising HbF inducers characterized by an isoxazole chemical skeleton and obtained through modification of two natural molecules, geldanamycin and radicicol. After preliminary biological assays based on benzidine staining and RT-qPCR conducted on human erythroleukemic K562 cells, we employed erythroid precursors cells (ErPCs) isolated from β-thalassemic patients. ErPCs weretreated with appropriate concentrations of isoxazole derivatives. The accumulation of globin mRNAs was studied by RT-qPCR, and hemoglobin production by HPLC. We demonstrated the high efficacy of isozaxoles in inducing HbF. Most of these derivatives displayed an activity similar to that observed using known HbF inducers, such as hydroxyurea (HU) or rapamycin; some of the analyzed compounds were able to induce HbF with more efficiency than HU. All the compounds were active in reducing the excess of free α-globin in treated ErPCs. All the compounds displayed a lack of genotoxicity. These novel isoxazoles deserve further pre-clinical study aimed at verifying whether they are suitable for the development of therapeutic protocols for β-thalassemia.