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Although edible insects (EI) have been consumed for ages in many countries around the world, in most European countries, this is not a traditional practice. Still, it has been encouraged as a sustainable source of animal protein besides other nutrients. The Food and Agricultural Organization and the United Nations, recommend consuming EI as a way to contribute to the sustainable development goals. Hence, this research investigated how participants from Portugal and Romania perceive EI, and how these can be useful as a source of nutrients and other benefits for human health, as well as possible risks. For that, it was undertaken a questionnaire survey, with data collected online in the two countries. For the analysis of data, basis statistics and chi-square tests were used. Results showed significant differences between Portuguese and Romanian participants in six out of ten questions, namely regarding safety (p < 0.001), use in traditional medicine (p < 0.001), possible infection with parasites (p = 0.021), of pesticides (p = 0.031), their usage as therapeutics (p = 0.001) and being potential sources of allergens (p < 0.001) and aflatoxins (p < 0.001). Also, differences were tested for other sociodemographic variables. The results showed significant differences according to age for only three questions, gender for only two questions, and Education for most of the questions, i.e., six out of the ten. These results highlighted the greater influence of variables like country of origin and education in the perception of the effects of EI in human health.

We report on a 19-year-old female patient who was diagnosed with a complete suprapatellar plica syndrome. She underwent arthroscopic excision of the plica. Post-operatively, there was complete resolution of the symptoms, with return to sports activity. A complete suprapatellar plica is a rare condition that separates the suprapatellar pouch from the rest of the knee. Cases of symptomatic complete suprapatellar plica should be managed with conservative measures initially. If conservative therapy fails, surgical arthroscopic excision is required.

Artificial Intelligence (AI) simulates human intelligence in machines capable of rational response and actions. AI’s growth in healthcare, particularly in dentistry, has been remarkable in aiding clinical practices from appointment scheduling to treatment outcome predictions. In orthodontics, AI effectively handles tasks such as automated landmark detection, diagnosing orthodontic needs, assessing maxillary constriction, and selecting appliances. ChatGPT, an AI-based program by OpenAI, excels in generating human-like responses, making it useful across many applications, including those in dentistry. AI enhances personalised patient communication, supports diagnosis and decision-making, digitises patient data, and aids in disease prevention and treatment. In addition, ChatGPT offers support in personalised care, billing, and patient health monitoring. Patients benefit from its help in finding providers, scheduling initial appointments, accessing health information, improving healthcare access and service effectiveness. However, there are limitations. ChatGPT sometimes produces nonsensical responses and poses privacy risks associated with patient data. Generated medical advice might not therefore match professional expertise. Despite these issues, if trained properly, ChatGPT could significantly enhance medical knowledge dissemination. Future studies should weigh the benefits of AI against its risks, and users must verify AI-generated information with reliable sources to ensure effective patient care.

Abstract A universal newborn screening program for sickle cell disease (uNS‐SCD) was implemented in the province of Québec (Qc) in November 2013, close in time to the recommendation of early initiation of hydroxyurea (HU) therapy for children. This retrospective cohort study evaluated the impact of such a program on children first seen between January 2000 and December 2019. Cohorts pre‐SCD‐uNS in Qc (pre‐QcNS) (n = 253) and post‐QcNS (n = 157) for patients seen prior to or after Nov 2013 were compared. Kaplan‐Meier curves, Poisson regression, and logistic regressions were used for statistical analysis, using Software R version 4.2.1. Median age at first visit decreased significantly from 14.4 [interquartile range: 2.4–72.0] to 1.2 months [1.2–57.6] (p

Tommaso Costa,1,2 Mario Ferraro,1– 3 Jordi Manuello,1,2 Alessia Camasio,2,3 Andrea Nani,2 Lorenzo Mancuso,2 Franco Cauda,1,2 Peter T Fox,4,5 Donato Liloia1,2 1GCS-fMRI, Koelliker Hospital and Department of Psychology, University of Turin, Turin, Italy; 2FOCUS Laboratory, Department of Psychology, University of Turin, Turin, Italy; 3Department of Physics, University of Turin, Turin, Italy; 4Research Imaging Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA; 5Biggs Institute for Alzheimer’s and Neurodegenerative Diseases, University of Texas Health Science Center at San Antonio, San Antonio, TX, USACorrespondence: Jordi Manuello, FOCUS Laboratory, Department of Psychology, University of Turin, Via Giuseppe Verdi 10, Turin, 10124, Italy, Email jordi.manuello@unito.itAbstract: Over the past two decades, functional magnetic resonance imaging (fMRI) has become the primary tool for exploring neural correlates of emotion. To enhance the reliability of results in understanding the complex nature of emotional experiences, researchers combine findings from multiple fMRI studies using coordinate-based meta-analysis (CBMA). As one of the most widely employed CBMA methods worldwide, activation likelihood estimation (ALE) is of great importance in affective neuroscience and neuropsychology. This comprehensive review provides an introductory guide for implementing the ALE method in emotion research, outlining the experimental steps involved. By presenting a case study about the emotion of disgust, with regard to both its core and social processing, we offer insightful commentary as to how ALE can enable researchers to produce consistent results and, consequently, fruitfully investigate the neural mechanisms underpinning emotions, facilitating further progress in this field.Keywords: affective mapping, BrainMap, quantitative synthesis, coordinate-based meta-analysis, fMRI, affective neuroscience

Abstract The AS04-adjuvanted human papillomavirus (HPV)16/18 vaccine, an L1-based vaccine, provides strong vaccine efficacy (VE) against vaccine-targeted type infections, and partial cross-protection to phylogenetically-related types, which may be affected by variant-level heterogeneity. We compared VE against incident HPV31, 33, 35, and 45 detections between lineages and SNPs in the L1 region among 2846 HPV-vaccinated and 5465 HPV-unvaccinated women through 11-years of follow-up in the Costa Rica HPV Vaccine Trial. VE was lower against HPV31-lineage-B (VE=60.7%;95%CI = 23.4%,82.8%) compared to HPV31-lineage-A (VE=94.3%;95%CI = 83.7%,100.0%) (VE-ratio = 0.64;95%CI = 0.25,0.90). Differential VE was observed at several lineage-associated HPV31-L1-SNPs, including a nonsynonymous substitution at position 6372 on the FG-loop, an important neutralization domain. For HPV35, the only SNP-level difference was at position 5939 on the DE-loop, with significant VE against nucleotide-G (VE=65.0%;95%CI = 28.0,87.8) but not for more the common nucleotide-A (VE=7.4%;95%CI = −34.1,36.7). Because of the known heterogeneity in precancer/cancer risk across cross-protected HPV genotype variants by race and region, our results of differential variant-level AS04-adjuvanted HPV16/18 vaccine efficacy has global health implications.

Polianne Angella Oliveira Figueiredo,1 Tâmara Stéphanie Lucena de Medeiros Costa,2 Mateus Dantas de Azevedo Lima,2 Adriana Gomes Magalhães,2 Ingrid Fonsêca Damasceno Bezerra,3 Patricia Driusso,4 Vanessa Patrícia Soares de Sousa2 1Faculty of Health Sciences of Trairi, Federal University of Rio Grande do Norte, Santa Cruz, Rio Grande do Norte, Brazil; 2Multicampus School of Medical Sciences, Federal University of Rio Grande do Norte, Caicó, Rio Grande do Norte, Brazil; 3Brazilian Hospital Services Company (Ebserh), Natal, Rio Grande do Norte, Brazil; 4Federal University of São Carlos, São Carlos, São Paulo, BrazilCorrespondence: Vanessa Patrícia Soares de Sousa, Tel +55 84 98702-7110, Email vanessa.sousa@ufrn.brIntroduction: Sexual dysfunction (SD) comprises disorders in sexual desire, arousal, orgasm, and lubrication. The importance of self-perceived SD relies on its relation to personal values, sex education, and partnership. We aimed to analyze the association between self-perceived SD and the Female Sexual Function Index (FSFI) in adult women of reproductive age and the correlation between age and sexual function.Material and Methods: This analytical cross-sectional study included 285 women aged 18 to 49 years, sexually active for at least four weeks, cisgender and heterosexual, and with Internet access. Women were divided into control (CG, control group; without SD) or study group (SG, study group; with SD) and responded to a self-applicable online survey containing a sociodemographic characterization, an interview about SD knowledge, and the FSFI test. The Chi-square test of independence (χ2) analyzed the association between self-perceived SD and FSFI-assessed SD. Pearson’s correlation coefficient investigated the correlation between age and FSFI.Results: Included women had a mean age of 29.57 years ± 7.11 years. Self-perceived SD showed a moderate association (Cramer’s V = 0.590) with the FSFI score (χ2 [2] = 91.500; p < 0.001). A weak, negative, and significant correlation was observed between age and the FSFI desire domain (r = − 0.120; p = 0.030; r2 = 1.440).Conclusion: Women with self-perceived SD were 68% more likely to present FSFI-assessed SD. Regarding the FSFI desire domain, sexual function decreased with age.Keywords: sexual dysfunction, physiological, sexuality, women

Background and Aims: We aimed to characterize the epidemiologic and comorbidities profiles of patients with chronic Hepatitis D (CHD) followed in clinical practice in Italy and explored their interferon (IFN) eligibility. Methods: This was a cross-sectional study of the PITER cohort consisting of consecutive HBsAg-positive patients from 59 centers over the period 2019-2023. Multivariable analysis was performed by logistic regression model. Results: Of 5492 HBsAg-positive enrolled patients, 4152 (75.6%) were screened for HDV, 422 (10.2%) were anti-HDV positive. Compared with HBsAg mono-infected, anti-HDV positive patients were more often younger, non-Italians, with a history of drug use, had elevated alanine transaminase (ALT), cirrhosis, or hepatocellular carcinoma (HCC). Compared with Italians, anti-HDV positive non-Italians were younger (42.2% age ≤ 40 years vs. 2.1%; P < 0.001), more often females (males 43.0% vs. 68.6%; P < 0.001) with less frequent cirrhosis and HCC. HDV-RNA was detected in 63.2% of anti-HDV-positive patients, who were more likely to have elevated ALT, cirrhosis, and HCC. Extrahepatic comorbidities were present in 47.4% of anti-HDV positive patients and could affect the eligibility of IFN-containing therapies in at least 53.0% of patients in care. Conclusions: CHD affects young, foreign-born patients and older Italians, of whom two-thirds had cirrhosis or HCC. Comorbidities were frequent in both Italians and non-Italians and impacted eligibility for IFN.

Objective: Determine the prevalence and risk factors for anxiety, stress and depression among higher education students in a sample from Portugal and Brazil. Methods: Students from Portugal (n = 709) and Brazil (n = 487) answered the Depression, Anxiety and Stress Scale (DASS-21) and demographic and academic characteristics questions. Results: Rates of anxiety, stress, and depression were 55.3 %, 55.9 % and 56.3 % for Portuguese students and 71.5 %, 75.6 % and 68.2 % for Brazilian students, respectively. In the total sample, being Brazilian was found to predict anxiety, stress and depression. In both samples, being female was found to predict anxiety and stress. Being displaced was also found to affect mental health: anxiety for the Portuguese sample; stress for the Brazilian sample. Furthermore, in the Portuguese sample, fields of study were found to affect mental health: Education and Human Motricity protected from anxiety, stress and depression; Psychology protected from anxiety and depression; Medicine protected from depression. Non-working status was also found to predict depression in this sample. Limitations: The cross-sectional design prevents the establishment of causal relationships; self-report measures may be susceptible to response bias; the recruitment of participants may be susceptible to selection bias; cultural factors and institutional differences between these countries may affect mental health. Conclusions: Country, gender, displacement, field of study, and working status were found to affect higher education students’ mental health. From a clinical perspective, specific programs addressing anxiety, stress and depression in university students should be tested, as these disorders have a noteworthy prevalence in this population.

Considering gastronomy as a source of expression of local culture, its use in tourism can contribute to enhancing and adding value to the destination, as well as encourage the pride of the local community, stimulating its production and consumption, and its dissemination outside the region. Bucho Raiano is a gastronomic product of identity and representativeness for the inland border region of Portugal (Riba Côa), for which its confraternity seeks the dissemination, the promotion of its consumption, and enhancement as a cultural resource. In this context, we seek to frame the Bucho Raiano gastronomic product, its identity, and the role of the confreres in its promotion and dissemination. Thus, this research aims to contextualize the Confraria do Bucho Raiano as a case study, evaluate the confreres’ perception of the confraternity’s mission, its strategies and contributions to the promotion and enhancement of this gastronomic product. The aim is to find out whether Bucho can be an important tourist product for this region and, consequently, strengthen the link between traditional local gastronomy and the tourist destination, according to the confreres’ perception.

Daniela Oliveira Werneck Rodrigues,1,2 Roberta Wolp Diniz,2 Leonardo Cunha Dentz,1 Monica de Albuquerque Costa,3 Roberto Heleno Lopes,2 Lucas Fernandes Suassuna,4 Jane Rocha Duarte Cintra,2 Christian Domenge2 1Department of Medicine, Centro Universitário Presidente Antônio Carlos, Juiz de Fora, MG, Brazil; 2Department of Oncohematology, Hospital 9 de Julho/ Instituto Oncológico de Juiz de Fora, Juiz de Fora, MG, Brazil; 3Department of Dematology, Secretaria de Saúde da Prefeitura Municipal de Juiz de Fora, Juiz de Fora, MG, Brazil; 4Department of Medicine, Universidade Federal de Juiz de Fora (UFJF), Juiz de Fora, MG, BrazilCorrespondence: Daniela Oliveira Werneck Rodrigues, Instituto Oncológico de Juiz de Fora, R. Santos Dumont, 56 - Granbery, Juiz de Fora, MG, 36010-510, Brazil, Tel +553232573126, Email danielawerneckhemato@hotmail.comAbstract: Rosai-Dorfman Disease (RDD) is a rare non-Langerhans histiocytosis, usually self-limited and presenting with massive, painless, bilateral cervical lymphadenopathy, with or without constitutional symptoms. Extranodal disease is frequently present, and may happen in the absence of lymph node involvement, symptomatology and differential diagnosis will depend on the site affected and fatal cases may occur. The authors present two cases of Rosai-Dorfman disease (RDD), diagnosed through immunohistochemistry, with different progressions, one with complete remission and one culminating in death, highlighting the variety of presentations and the diagnostic difficulty. RDD is a rare condition with clinical presentations similar to several diseases, and should be considered in the differential diagnosis of lymphadenopathy with extranodal lesions.Keywords: Rosai Dorfman disease, immunohistochemistry, diagnosis, differential diagnosis (MeSH-NCBI)

Abstract Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is one of the leading causes of admission to the intensive care unit, often triggered by a respiratory tract infection of bacterial or viral aetiology. Managing antibiotic therapy in this context remains a challenge. Respiratory panel molecular tests allow identifying viral aetiologies of AECOPD. We hypothesized that the systematic use of a respiratory multiplex PCR (mPCR) would help antibiotics saving in severe AECOPD. Our objectives were to describe the spectrum of infectious aetiologies of severe AECOPD, using a diagnostic approach combining conventional diagnostic tests and mPCR, and to measure antibiotics exposure. The study was bicentric, prospective, observational, and included 105 critically ill patients with a severe AECOPD of presumed infectious aetiology, in whom a respiratory mPCR with a viral panel was performed in addition to conventional microbiological tests. Altogether, the microbiological documentation rate was 50%, including bacteria alone (19%), respiratory viruses alone (16%), and mixed viruses and bacterial species (16%). The duration of antibiotic therapy was shorter in patients without documented bacterial infection (5.6 vs. 9 days; P = 0.0006). This pilot study suggests that molecular tests may help for the proper use of anti-infective treatments in critically ill patients with severe AECOPD.

An 11-year-old male dog presenting exophthalmia and perforation of the cornea of the left eye was seen at the veterinary hospital of the State University of Maranhão. Upon physical examination, irregularly shaped granulomas of crumbly appearance were observed on the dog’s tongue. The dog was sent for ocular enucleation surgery. The following tests were requested: complete blood count, serum biochemistry, hemoparasite investigation, chest X-Ray, echocardiogram, electrocardiogram, cytology and nodule histopathology. The blood count revealed neutrophilia, signs of anemia, increased total plasma protein and thrombocytopenia. Serum biochemistry and the imaging examinations showed normal results. The cytological examination on the tongue nodules showed microfilariae and the histopathological examination showed chronic glossitis. Polymerase chain reaction (PCR) and genetic sequencing were performed on a blood sample, which made it possible to identify the species Acanthocheilonema reconditum. This is the first record worldwide of the occurrence of microfilariae of A. reconditum on tongue nodules. This finding serves to alert dermatologists and dentists regarding the need for a differential diagnosis for types of oral cavity lesions of unknown etiological origin.

ABSTRACT The objective of the current study was to investigate the effects of different levels of andiroba oil (AO) in a bioproduct based on andiroba oil (BBAO) on the physical quality, bacteriological concentration, chemical composition, yolk lipid oxidation, and sensory characteristics when coating eggs and storing them for seven days at room temperature. The eggs were arranged in a completely randomized design, in which treatments consisted of a control group (eggs stored for seven days without the application of BBAO) and eggs covered with biofilms produced with BBAO with different levels of AO (1%, 5%, 10%, and 15%). Each treatment contained 50 eggs, and each egg was considered a replicate. Data collected were subjected to Tukey test and linear or polynomial regression at 0.05 statistical significance. The results indicate that the application of BBAO on eggs stored for 7 days at room temperature resulted in better (p

ABSTRACT Avian mycoplasmosis is a disease of significant economic impact, potentially leading to restrictions on the international trade of poultry products. Mycoplasma synoviae (MS) and Mycoplasma gallisepticum (MG) are well-established as pathogenic, while Mycoplasma gallinaceum (Mgc) is considered commensal. Nevertheless, the latter can exacerbate clinical conditions in cases of co-infections with other pathogens. Due to the slow growth rates of MS and MG, they are susceptible to being outpaced by fast growing mycoplasmas, thereby complicating cultivation, and potentially yielding false-negative results. Thus, this study aimed to report a mixed infection of Mgc and MS in commercial laying hens and the compromised isolation of MS caused by this non-pathogenic mycoplasma. Twenty tracheal samples from chickens were collected, subjected to PCR, and cultured in a modified Frey’s medium. Samples displaying colonies compatible with mycoplasmas underwent three passages to obtain pure cultures. PCR-positive samples for the Mycoplasma spp., and negative ones for MS and MG, were subsequently subjected to DNA sequencing. All clinical samples tested via PCR were positive for MS (20/20) and negative for MG (0/20). During isolation, only five samples exhibited colonies with characteristic mycoplasma growth. However, PCR analysis of these cultures produced negative results for MS and MG, but were positive for Mycoplasma spp. DNA sequencing confirmed that all isolated strains were Mgc. Mgc displayed rapid growth, posing challenges to obtaining MS strains for isolation. The coexistence of MS and Mgc in the respiratory tract of commercial laying hens has the potential of inducing a synergistic effect on respiratory manifestations.

Gabriel Iudy Yamaguchi Rocha,1 Jonathas Eduardo Miranda Gomes,1 Michel Lopes Leite,1,2 Nicolau B da Cunha,1,3,4 Fabricio F Costa1,5,6 1Genomic Sciences and Biotechnology Program, Catholic University of Brasilia, Brasília, DF, Brazil; 2Department of Cell Biology, Institute of Biological Sciences, Campus Darcy Ribeiro, University of Brasilia (UnB), Brasília, DF, Brazil; 3Faculty of Agronomy and Veterinary Medicine (FAV), Campus Darcy Ribeiro, University of Brasilia (UnB), Brasília, DF, Brazil; 4Graduate Program in Agronomy, Campus Darcy Ribeiro, University of Brasilia (UnB), Brasília, DF, Brazil; 5Cancer Biology and Epigenomics Program, Northwestern University’s Feinberg School of Medicine, Chicago, IL, USA; 6Genomic Enterprise, San Francisco CA, USACorrespondence: Fabricio F Costa, Genomic Sciences and Biotechnology Program, UCB SGAN 916 Modulo B, Bloco C, Brasília, DF, 70790-160, Brazil, Email fcosta@genomicenterprise.com Nicolau B da Cunha, Faculty of Agronomy and Veterinary Medicine (FAV), University of Brasília (UnB), Campus Darcy Ribeiro, Brasília, DF, 70910-900, Brazil, Email nicolau.cunha@unb.brAbstract: Fighting cancer remains one of the greatest challenges for science in the 21st century. Advances in immunotherapy against different types of cancer have greatly contributed to the treatment, remission, and cure of patients. In this context, knowledge of epigenetic phenomena, their relationship with tumor cells and how the immune system can be epigenetically modulated represent some of the greatest advances in the development of anticancer therapies. Epigenetics is a rapidly growing field that studies how environmental factors can affect gene expression without altering DNA sequence. Epigenomic changes include DNA methylation, histone modifications, and non-coding RNA regulation, which impact cellular function. Epigenetics has shown promise in developing cancer therapies, such as immunotherapy, which aims to stimulate the immune system to attack cancer cells. For example, PD-1 and PD-L1 are biomarkers that regulate the immune response to cancer cells and recent studies have shown that epigenetic modifications can affect their expression, potentially influencing the efficacy of immunotherapy. New therapies targeting epigenetic modifications, such as histone deacetylases and DNA methyltransferases, are being developed for cancer treatment, and some have shown promise in preclinical studies and clinical trials. With growing understanding of epigenetic regulation, we can expect more personalized and effective cancer immunotherapies in the future. This review highlights key advances in the use of epigenetic and epigenomic tools and modern immuno-oncology strategies to treat several types of tumors.Keywords: epigenetics, epigenomics, PD-1, PD-L1, epigenetic biomarkers, oncology, immunotherapy

The article provided insights into why local government and service delivery must be rethought in light of digital transformation. It exposed the significance of digital transformation in solving local government and service delivery challenges. The article followed a qualitative research approach. It employed document analysis and literature review as data collection instruments. It argued that digital transformation can help local governments in South Africa fulfil constitutional obligations and meet policy goals. It demonstrated how digitally transformed local government can solve service delivery problems through the deployment of digital technologies that improve decision-making, cut costs, streamline operations, and offer efficient services. The article revealed that the digital divide, lack of technical expertise, data security concerns and resource constraints are some of the challenges that can affect the digital transformation of local government and service delivery in South Africa. These challenges must be resolved for digital transformation to play a significant role in improving the effectiveness of local government in service delivery. The article recommended that local governments in South Africa digitally transform in ways that foster equality and deliver local government services to all citizens. The article contributes to scholarship advocating for public sector innovation broadly, and specifically, illustrates the criticality of embracing digital transformation of local government and service delivery.

Matteo Megna,1 Luca Potestio,1 Angelo Ruggiero,1 Sara Cacciapuoti,1 Francesco Maione,2 Marco Tasso,3 Francesco Caso,3,&ast; Luisa Costa3,&ast; 1Section of Dermatology, Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy; 2Immunopharmalab, Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, Naples, Italy; 3Rheumatology Research Unit, Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy&ast;These authors contributed equally to this workCorrespondence: Angelo Ruggiero, Section of Dermatology, Department of Clinical Medicine and Surgery, University of Naples Federico II, Via Pansini 5, Napoli, 80131, Italy, Tel +39 - 081 – 7462457, Fax +39 - 081 – 7462442, Email angeloruggiero1993@libero.itAbstract: Psoriasis is now considered to be the cutaneous phenotype of a systemic inflammatory condition, recognized under the term Psoriatic Disease (PsD). PsD has several extracutaneous manifestations, such as inflammatory articular and entheseal involvement, leading to psoriatic arthritis (PsA), and the less frequent intestinal and ocular manifestations with colitis/inflammatory bowel disease and uveitis, respectively. There have also been several reports of an increased frequency of comorbidities such as hypertension, diabetes, dyslipidemia, obesity, metabolic syndrome and cardiovascular manifestations during the course of PsD. The link between psoriasis and related comorbidities is considered a long-term disease sequela, often characterized by an unhealthy lifestyle and a consequence of systemic inflammation; hence, psoriasis requires adequate and prompt treatment, with the aim of controlling not only cutaneous manifestations but also extracutaneous manifestations and systemic inflammation. Pharmacological strategies for PsD have significantly increased over recent years. Recently, the targeted synthetic DMARDs, Janus kinase (JAK) inhibitors, tofacitinib and upadacitinib, were added to the therapeutic armamentarium for treating PsA, and deucravacitinib for psoriasis. These oral agents act directly on inflammatory mechanisms underlining the disease, as antagonists of the intracellular JAK signal pathway and, by STAT phosphorylation, inhibit gene proinflammatory cytokine transcription. JAK inhibitors represent a recent additional treatment strategy for PsD management and, among these, tofacitinib and upadacitinib have recently been approved for PsA, and deucravacitinib for psoriasis. In this review we describe ongoing and recent phase II and III randomized controlled trials (RCTs) evaluating the efficacy and safety of investigational JAK inhibitors in psoriasis and PsA.Keywords: JAK inhibitors, plaque psoriasis, psoriatic arthritis, TYK2 inhibitors

Pedro Henrique Dias Moura Prazeres,1,2 Heloísa Ferreira,2 Pedro Augusto Carvalho Costa,2 Walison da Silva,2 Marco Túllio Alves,2 Marshall Padilla,3 Ajay Thatte,3 Anderson Kenedy Santos,4,5 Anderson Oliveira Lobo,6 Adriano Sabino,7 Helen Lima Del Puerto,1 Michael J Mitchell,3 Pedro Pires Goulart Guimaraes1,2 1Department of Pathology, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil; 2Department of Physiology and Biophysics, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil; 3Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA; 4Department of Pediatrics/Gastroenterology and Hepatology, Yale School of Medicine, New Haven, CT, USA; 5Department of Genetics, Yale School of Medicine, New Haven, CT, USA; 6Department of Materials Engineering, Federal University of Piauí, Teresina, PI, Brazil; 7Department of Clinical and Toxicological Analysis, Federal University of Minas Gerais, Belo Horizonte, MG, BrazilCorrespondence: Pedro Pires Goulart Guimaraes, Department of Physiology and Biophysics, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil, Email ppiresgo@reitoria.ufmg.brIntroduction: Chimeric antigen receptor (CAR) cell therapy represents a hallmark in cancer immunotherapy, with significant clinical results in the treatment of hematological tumors. However, current approved methods to engineer T cells to express CAR use viral vectors, which are integrative and have been associated with severe adverse effects due to constitutive expression of CAR. In this context, non-viral vectors such as ionizable lipid nanoparticles (LNPs) arise as an alternative to engineer CAR T cells with transient expression of CAR.Methods: Here, we formulated a mini-library of LNPs to deliver pDNA to T cells by varying the molar ratios of excipient lipids in each formulation. LNPs were characterized and screened in vitro using a T cell line (Jurkat). The optimized formulation was used ex vivo to engineer T cells derived from human peripheral blood mononuclear cells (PBMCs) for the expression of an anti-CD19 CAR (CAR-CD19BBz). The effectiveness of these CAR T cells was assessed in vitro against Raji (CD19+) cells.Results: LNPs formulated with different molar ratios of excipient lipids efficiently delivered pDNA to Jurkat cells with low cytotoxicity compared to conventional transfection methods, such as electroporation and lipofectamine. We show that CAR-CD19BBz expression in T cells was transient after transfection with LNPs. Jurkat cells transfected with our top-performing LNPs underwent activation when exposed to CD19+ target cells. Using our top-performing LNP-9-CAR, we were able to engineer human primary T cells to express CAR-CD19BBz, which elicited significant specific killing of CD19+ target cells in vitro.Conclusion: Collectively, our results show that LNP-mediated delivery of pDNA is a suitable method to engineer human T cells to express CAR, which holds promise for improving the production methods and broader application of this therapy in the future.Keywords: lipid nanoparticles, pDNA delivery, CAR T cells, cell engineering, cancer immunotherapy

O presente estudo explora o comportamento ecoempreendedor no contexto da Covid-19, analisando a influência da obrigação moral e do engajamento ambiental na percepção de empatia, autoeficácia ecoempreendedora e criação de valor ambiental. Dados primários foram coletados de 130 participantes do Projeto Conexão Mata Atlântica. A análise dos dados foi realizada usando o PLS-SEM. Seis das oito hipóteses de pesquisa foram suportadas. O estudo confirmou que a percepção de empatia e autoeficácia é influenciada por níveis mais elevados de obrigação moral. Os resultados indicam que os ecoempreendedores mais engajados com o meio ambiente têm níveis mais altos de autoeficácia e criação de valor ambiental. Foi contrariada a premissa de que um sentimento de moralidade poderia impactar positivamente a criação de valor ambiental decorrente do negócio. A hipótese de que o engajamento ambiental influencia positivamente a empatia ecoempreendedora não foi confirmada. Os resultados demonstram a complexidade das relações entre as variáveis que medem o comportamento ecoempreendedor e a necessidade de explorar esses determinantes de características-chave. Assim, a pesquisa representa um avanço na temática do ecoempreendedorismo, abrindo-se uma nova direção para invetigações ao testar o poder explicativo de variáveis até então não testadas. Ela também oferece percepções práticas para formuladores de políticas e educadores envolvidos com o ecoempreendedorismo. Por fim, fazemos algumas reflexões à luz dos produtores rurais e das atividades rurais. Além disso, apresentamos contribuições diretamente relacionadas à Agenda dos Objetivos de Desenvolvimento Sustentável (ODS) da ONU.

Rangel de Sousa Costa,1 Luiz Celso Hygino da Cruz Jr,2 Simone Rachid de Souza,3 Nina Ventura,1 Diogo Goulart Corrêa2 1Department of Radiology, Paulo Niemeyer State Brain Institute, Rio de Janeiro, RJ, Brazil; 2Department of Radiology, Clínica de Diagnóstico por Imagem (CDPI)/DASA, Rio de Janeiro, RJ, Brazil; 3Department of Pathology, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, BrazilCorrespondence: Diogo Goulart Corrêa, Department of Radiology, Clínica de Diagnóstico por Imagem (CDPI)/DASA, Avenida das Américas, 4666, 302A, 303, 307, 325, 326, Rio de Janeiro, RJ, Brazil, Tel +55 21 993843617, Email diogogoulartcorrea@yahoo.com.brAbstract: Paracoccidioidomycosis (PCM) is a infection caused by the thermodimorphic fungus Paracoccidioides spp. (P. lutzii and, mainly, P. brasiliensis). This infection predominantly affects rural male workers aged between 30 and 50 years old who deal with soil on daily activities. Clinically, the disease is classified as acute/subacute phase, which evolves rapidly, secondary to dissemination of the fungus through to the phagocytic-mononuclear system, leading to fever, weight loss, and anorexia, associated with hepatosplenomegaly and lymphadenopathy, which can be complicated with suppuration and fistulization; and chronic phase, which corresponds to 74% to 95% of symptomatic cases, with a common pulmonary involvement. Central nervous system involvement is almost always a characteristic of the chronic form. Inhalation is the most common route of primary infection, usually affecting the lungs, forming the primary complex. From the primary complex, hematogenic dissemination can occur to any organ, including the brain and spinal cord. Although PCM of the central nervous system diagnosis is usually based on histopathological analysis and the imaging features are not specific for PCM, computed tomography and magnetic resonance imaging can demonstrate evidences of granuloma, abscess, meningitis, or a combination of these lesions, contributing to a preoperative diagnosis, especially when considered in conjunction with epidemiology. In this article, we review the pathophysiology, clinical manifestations and imaging aspects of neuro-PCM.Keywords: paracoccidioidomycosis, neuro-PCM, magnetic resonance imaging, granuloma, meningitis

Marta Barba,1 Alice Cola,2 Clarissa Costa,1 Antonio Liberatore,3 Matteo Frigerio2 1Obstetric and Gynecology Department - University of Milano-Bicocca, Monza, Italy; 2Gynecology Department, Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy; 3School of Medicine, University of Milano-Bicocca, Monza, ItalyCorrespondence: Marta Barba, University of Milano-Bicocca, Via Pergolesi, 33, Monza, Italy, Tel +39 233 9434, Email m.barba8792@gmail.comObjective: Single-incision slings (SISs) are not considered the first surgical choice for stress urinary incontinence due to few data about long-term results. Our aim was to evaluate the outcomes of SISs 12 years after implantation and to search for consequences such as deterioration after a certain amount of time.Methods: We included women with stress urinary incontinence both clinically and urodynamically proven who underwent SISs procedure. Objective and subjective cure rates were compared to short-term outcomes to detect possible deterioration over time.Results: A total of 85 patients were analysed with a median follow-up of 12.0 (IQR 10.4– 12.8) years. Objective and subjective cure rates were 81.0% and 82.1%, respectively. Median (IQR) PGI-I scores and ICIQ-SF, respectively, were 1 (1– 2) and 0 (0– 6.8). No significant deterioration of outcomes over time was shown after comparison between short-term and long-term follow-ups (objective cure rate 84.5% vs 81.0%, p=0.684; subjective cure rates 92.9% vs 82.1%, p=0.060). Also, voiding symptoms and overactive bladder did not differ over time (20.2% vs 21.4%, p=1.000; 20.2% vs 33.3%, p=0.080, respectively).Conclusion: SISs were shown to be a procedure with a great efficacy and safety profile at very long-term follow-up.Keywords: complications, functional outcomes, long-term follow-up, quality of life, single-incision sling, stress urinary incontinence

The myocyte enhancer factor 2 (MEF2) gene family play fundamental roles in the genetic programs that control cell differentiation, morphogenesis, proliferation, and survival in a wide range of cell types. More recently, these genes have also been implicated as drivers of carcinogenesis, by acting as oncogenes or tumor suppressors depending on the biological context. Nonetheless, the molecular programs they regulate and their roles in tumor development and progression remain incompletely understood. The present study evaluated whether the MEF2D transcription factor functions as a tumor suppressor in breast cancer. The knockout of the MEF2D gene in mouse mammary epithelial cells resulted in phenotypic changes characteristic of neoplastic transformation. These changes included enhanced cell proliferation, a loss of contact inhibition, and anchorage-independent growth in soft agar, as well as the capacity for tumor development in mice. Mechanistically, the knockout of MEF2D induced the epithelial-to-mesenchymal transition (EMT) and activated several oncogenic signaling pathways, including AKT, ERK, and Hippo-YAP. Correspondingly, a reduced expression of MEF2D was observed in human triple-negative breast cancer cell lines, and a low MEF2D expression in tissue samples was found to be correlated with a worse overall survival and relapse-free survival in breast cancer patients. MEF2D may, thus, be a putative tumor suppressor, acting through selective gene regulatory programs that have clinical and therapeutic significance.

This paper describes the structural and textural characteristics of silicon oxycarbide ceramics obtained from three different hybrid polymers by varying pyrolysis temperature. The first polymer was prepared by hydrosilylation between poly(hydromethylsiloxane) and divinylbenzene in stoichiometric proportions; the second was similarly obtained, but with excess of divinylbenzene (60 wt.%) and the third was also synthesized with 60 wt.% divinylbenzene, involving simultaneously hydrosilylation and radical reactions. Precursors were pyrolysed under argon at 1000, 1200 and 1500°C to produce silicon oxycarbide-based ceramics. Silicon carbide phase development and devitrification resistance were influenced by the disordered and ordered residual carbon fraction, which was directly related to the polymer structure. High specific surface area and pore volume values were obtained in C-richer ceramics at 1500°C derived from poly(divinylbenzene) network-containing precursor. Silicon oxycarbide matrices, derived from hybrid polymers containing graphitic carbon and silicon carbide phases together with different amount of porosity, revealed desirable features for electrochemical applications and adsorbent systems.

This study explores the use of Moringa leaves and tapioca flour as additives in chicken nuggets, a popular processed chicken meat product. Moringa leaves are known for their high nutritional content, including vitamins, minerals, and antioxidants. The research aims to determine the optimal dosages of Moringa leaves and tapioca flour for chicken nugget production, providing guidance for producers to enhance product formulations and nutritional value. The study investigates how variations in the doses of Moringa leaves and tapioca flour impact the physicochemical and organoleptic properties of chicken nuggets. An experimental design involving two factors (Moringa leaves and tapioca flour) with multiple levels is utilized. Each treatment combination is repeated to obtain reliable results. The findings indicate significant interactions between the doses of Moringa leaves and tapioca flour, particularly related to water content. The addition of 300g tapioca flour and 200g Moringa leaves resulted in the lowest water content compared to other dose combinations. However, there was no significant interaction observed on ash content, although higher doses of Moringa leaves and tapioca flour tended to increase the ash content in the chicken nuggets. Crude protein levels showed an interaction effect, with the addition of 100g Moringa leaves and increased tapioca flour contributing positively to the crude protein content. Additional doses of Moringa leaves and tapioca flour affected the crude fat content, with the addition of 100g Moringa leaves and increased tapioca flour resulting in increased crude fat. However, higher doses in specific combinations led to varied effects on crude fat content. The addition of Moringa leaves and tapioca flour influenced the crude fiber content in chicken nuggets. Within a certain range, the addition of Moringa leaves positively increased the crude fiber content, while higher doses of tapioca flour also contributed to increased crude fiber. Overall, this research provides insights into the effects of Moringa leaves and tapioca flour on the physicochemical properties and organoleptic qualities of chicken nuggets. The findings offer valuable information for the development of more efficient product formulations with enhanced nutritional value.

Angelo Di Vincenzo,1 Marnie Granzotto,1 Marika Crescenzi,1 Camilla Costa,1 Stefano Piaserico,2 Vincenzo Vindigni,3 Roberto Vettor,1 Marco Rossato1 1Department of Medicine – DIMED, Clinica Medica 3, University - Hospital of Padova, Padova, Italy; 2Department of Medicine - DIMED, Section of Dermatology, University - Hospital of Padova, Padova, Italy; 3Department of Neurosciences, Clinic of Plastic Reconstructive and Aesthetic Surgery, University – Hospital of Padova, Padova, ItalyCorrespondence: Marco Rossato, Department of Medicine – DIMED, Clinica Medica 3, University Hospital of Padova, Via Giustiniani 2, Padova, 35128, Italy, Tel +39 49 8218746, Fax +39 49 8213332, Email marco.rossato@unipd.itPurpose: Psoriasis is a chronic systemic inflammatory disease involving the production of many pro-inflammatory cytokines derived from immune cells and interacting with different tissues leading to the typical skin lesions. Psoriasis shows a higher prevalence and a worse progression in obese than in lean subjects. The IL-23/IL-17 immune axis has a pivotal role in the pathogenesis of psoriasis and anti-IL-23 monoclonal antibodies are highly effective in its treatment. Since obesity in frequently associated with elevated insulin plasma levels, we have investigated the ability of in vitro differentiated human adipocytes to produce IL-23 at basal conditions and after insulin stimulation.Material and Methods: In vitro differentiated human adipocytes were incubated in the absence and presence of different insulin concentrations and the expression of IL-23 was analyzed by real-time PCR and Western blotting.Results: The results of this study show that in vitro differentiated human adipocytes spontaneously express IL-23 mRNA and protein being stimulated by insulin in a dose-dependent manner. The stimulatory effects of insulin on IL-23 expression were specific since it did not stimulate the expression of other well-known cytokines involved in psoriasis pathogenesis such as Il-22 nor LL-37. Furthermore, lipopolysaccharide did not stimulate IL-23 expression in human adipocytes, thus highlightening the specific effects of insulin in the stimulation of IL-23 expression in human adipocytes.Conclusion: Here we show that human adipocytes spontaneously express IL-23 and that insulin stimulates IL-23 production by these cells in a specific manner as other stimuli, known to be involved in psoriasis pathophysiology, are ineffective. These observations could explain the association between psoriasis and obesity, a condition frequently characterized by a state of insulin hypersecretion.Keywords: adipocyte, human, IL-23, insulin, obesity, psoriasis

Ana Teresa Melo,1,2,&ast; Eduardo Dourado,1,2,&ast; Raquel Campanilho-Marques,1,2,&ast; Matilde Bandeira,1,2 Sofia C Barreira,1,2 José Costa,3 Rita Pimenta,4 Sofia Antunes-Duarte,4 Inês Cordeiro,1,2 João E Fonseca1,2 1Rheumatology Department, Hospital de Santa Maria, Centro Hospitalar Universitário Lisboa Norte, Centro Académico de Medicina de Lisboa, Lisbon, Portugal; 2Rheumatology Investigation Unit, Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Centro Académico de Medicina de Lisboa, Lisbon, Portugal; 3Physical Medicine and Rehabilitation Department, Hospital de Santa Maria, Centro Hospitalar Universitário Lisboa Norte, Centro Académico de Medicina de Lisboa, Lisbon, Portugal; 4Dermatology Department, Hospital de Santa Maria, Centro Hospitalar Universitário Lisboa Norte, Centro Académico de Medicina de Lisboa, Lisbon, Portugal&ast;These authors contributed equally to this workCorrespondence: Ana Teresa Melo, Serviço de Reumatologia, Centro Hospitalar Universitário Lisboa Norte, Hospital de Santa Maria, EPE, R. Prof. Egas Moniz, Lisboa, 1700, Portugal, Tel +351 217805139, Email anateresamelo@campus.ul.ptBackground: Idiopathic inflammatory myopathies (IIM) are a rare heterogeneous group of diseases characterised by chronic skeletal muscle inflammation, but other organs are also frequently involved. IMM represent a diagnostic challenge and a multidisciplinary approach is important to ensure successful diagnosis and adequate follow-up of these patients.Objective: To describe the general functioning of our multidisciplinary myositis clinic, highlighting the benefits of multidisciplinary team management in patients with confirmed or suspected IIM and to characterise our clinical experience.Methods: Description of the organization of a dedicated multidisciplinary myositis outpatient clinic, supported by IMM specific electronic assessment tools and protocols based on our Portuguese Register - Reuma.pt. In addition, an overview of our activity between 2017 and 2022 is provided.Results: An IIM multidisciplinary care clinic, based on a close collaboration between Rheumatologists, Dermatologists and Physiatrist is detailed in this paper. One hundred and eighty-five patients were assessed in our myositis clinic; 138 (75%) of those were female, with a median age of 58 [45– 70] years. At the last appointment, 130 patients had a confirmed IIM diagnosis, and the mean disease duration was 4 [2– 6] years. The most frequent diagnosis was dermatomyositis (n = 34, 26.2%), followed by antisynthetase syndrome (n = 27, 20.8%) and clinically amyopathic/paucimyopathic dermatomyositis (n = 18, 13.8%). Twenty-four patients (18.5%) were on monotherapy and 94 (72.3%) were on combination therapy.Conclusion: A multidisciplinary approach is important to ensure the correct diagnosis and follow-up of these patients. A myositis clinic, with a standardised practice at a tertiary hospital level, contributes to a standardization of care and opens research opportunities.Keywords: inflammatory myopathies, rheumatology, dermatology, rehabilitation medicine, multidisciplinary clinic

The forestry sector in Italy is facing issues related to the need to make the most of environmental, territorial and socio-economic opportunities. The research is called upon to translate technological advances into practical applications, even in the field of geomatics and information and communication technologies. The exploitation of precision technologies can foster innovation and the improvement of management processes as well as the development of new products useful for forest owners, entrepreneurs, forest technicians and citizens, with benefits for the quality of forest production, the reduction of production costs and the reduction of environmental and social impacts. This note provides a brief overview of precision technologies applied to forest farm-scale monitoring, silviculture management, logging, poplar farming, forest nursery and forest product traceability.