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Mutations in GBA1 encoding the lysosomal enzyme β-glucocerebrosidase (GCase) are among the most prevalent genetic susceptibility factors for Parkinsons disease (PD), with 10-30% of carriers developing the disease. To identify genetic modifiers contributing to the incomplete penetrance, we examined the effect of 1634 human transcription factors (TFs) on GCase activity in lysates of an engineered human glioblastoma line homozygous for the pathogenic GBA1 L444P variant. Using an arrayed CRISPR activation library, we uncovered 11 TFs as regulators of GCase activity. Among these, activation of MITF and TFEC increased lysosomal GCase activity in live cells, while activation of ONECUT2 and USF2 decreased it. While MITF, TFEC, and USF2 affected GBA1 transcription, ONECUT2 might control GCase trafficking. The effects of MITF, TFEC, and USF2 on lysosomal GCase activity were reproducible in iPSC-derived neurons from PD patients. Our study provides a systematic approach to identifying modulators of GCase activity and deepens our understanding of the mechanisms regulating GCase.

Although the first lasers invented operated in the visible, the first on-chip devices were optimized for near-infrared (IR) performance driven by demand in telecommunications. However, as the applications of integrated photonics has broadened, the wavelength demand has as well, and we are now returning to the visible (Vis) and pushing into the ultraviolet (UV). This shift has required innovations in device design and in materials as well as leveraging nonlinear behavior to reach these wavelengths. This review discusses the key nonlinear phenomena that can be used as well as presents several emerging material systems and devices that have reached the UV–Vis wavelength range.

Abstract Mutations in GBA1 encoding the lysosomal enzyme β-glucocerebrosidase (GCase) are among the most prevalent genetic susceptibility factors for Parkinson’s disease (PD), with 10–30% of carriers developing the disease. To identify genetic modifiers contributing to the incomplete penetrance, we examined the effect of 1634 human transcription factors (TFs) on GCase activity in lysates of an engineered human glioblastoma line homozygous for the pathogenic GBA1 L444P variant. Using an arrayed CRISPR activation library, we uncovered 11 TFs as regulators of GCase activity. Among these, activation of MITF and TFEC increased lysosomal GCase activity in live cells, while activation of ONECUT2 and USF2 decreased it. While MITF, TFEC, and USF2 affected GBA1 transcription, ONECUT2 might control GCase trafficking. The effects of MITF, TFEC, and USF2 on lysosomal GCase activity were reproducible in iPSC-derived neurons from PD patients. Our study provides a systematic approach to identifying modulators of GCase activity and deepens our understanding of the mechanisms regulating GCase.

Abstract Coronavirus disease (COVID)-19 had an impact on medical graduation, causing weaknesses arising from social isolation and remote emergency teaching, with an emphasis on deficits in the development of non-technical skills (soft skills). In this context, the interaction between a group of medical students and adolescents who develop activities at the Center for Learning and Mobilization for Citizenship in Campinas/SP, Brazil, was evaluated about the development of soft skills during the COVID-19 pandemic. The observational study was carried out using an electronic questionnaire based on a Likert scale on the feelings of undergraduate medical students regarding participation in project activities in the context of the development of social skills. The study demonstrated an important positive impact of student participation in a socio-educational project for the development of soft skills, emphasizing the ability to deal with adverse situations, decision-making, and the ability to deal with the fear of not corresponding. However, the existence of limitations and difficulties in the development of non-technical skills by students was revealed, further reinforced by the challenges brought by the COVID-19 pandemic. In this aspect, the study demonstrated participation in a voluntary social project as an important strategy to improve the teaching of these skills. Graphical Abstract

Breast cancer brain metastasis (BCBM) is a lethal disease with no effective treatments. Prior work has shown that brain cancers and metastases are densely infiltrated with anti-inflammatory, protumourigenic tumour-associated macrophages, but the role of brain-resident microglia remains controversial because they are challenging to discriminate from other tumour-associated macrophages. Using single-cell RNA sequencing, genetic and humanized mouse models, we specifically identify microglia and find that they play a distinct pro-inflammatory and tumour-suppressive role in BCBM. Animals lacking microglia show increased metastasis, decreased survival and reduced natural killer and T cell responses, showing that microglia are critical to promote anti-tumour immunity to suppress BCBM. We find that the pro-inflammatory response is conserved in human microglia, and markers of their response are associated with better prognosis in patients with BCBM. These findings establish an important role for microglia in anti-tumour immunity and highlight them as a potential immunotherapy target for brain metastasis.

Axillary surgery for breast cancer has continually evolved, with sentinel lymph node biopsy for clinically node-negative women with invasive breast cancer having long replaced axillary lymph node dissection. The information obtained from axillary staging has been important in providing prognostic information and guiding adjuvant treatment recommendations. However, recent studies suggest that sentinel lymph node biopsy should be omitted in select low-risk patients whose axillary surgery provides minimal prognostic value. This was highlighted by the Society of Surgical Oncology Choosing Wisely Guidelines, advocating against routine axillary staging in older women with early-stage hormone receptor-positive breast cancer. Since the guideline release, ongoing research has continued to identify the subset of low-risk patients who would benefit from the omission of axillary staging and improve adherence to Choosing Wisely to prevent overtreatment in older people.

Obtaining a Veterinary Surgeon degree relies on the acquisition of "Day One Competences" (DOCs), among which professional skills related to meat inspection are acquired during visits to abattoirs. In 2020, lockdown measures due to COVID-19 pandemic limited on-site practical training. The present study describes the creation of an e-learning course on bovine and swine slaughtering as an alternative tool for compulsory DOCs achievement within the course "Inspection and control of food of animal origin" during the fourth year of the Veterinary Medicine degree program (Department of Veterinary Sciences of the University of Pisa). Academics and external professionals took part on the planning and development of the learning material. Video pills, consisting of shooting of the slaughtering coupled with trainers' descriptive explanations, were produced. The perceived effectiveness of course contents, trainers' communication skills and technical quality were assessed with a questionnaire. The developed e-learning platform consisted of four main sections (Introduction, Swine slaughtering, Bovine slaughtering and Additional topics), integrated by multiple-choice questions for the student's self-assessment. According to students' assessment, the platform, of high technical quality, effectively condensed contents on meat inspection. Despite the unique and irreplaceable role of practical training in the achievement of the professional skills included in the veterinary curriculum, the e-learning course may concur in providing DOCs and is in line with the adoption of a modern teaching model where e-learning resources engage students in deeper learning approaches.

Background: Antimicrobial resistance (AMR) is increasing globally and poses a significant public health challenge. Community pharmacists, especially in primary care settings, play a pivotal role in mitigating the irrational use of antibiotics, a key driver of AMR. Objectives: This study aims to explore qualitative insights from community pharmacists regarding antibiotic supply and usage, analyze sentiments related to AMR, and highlight the crucial role of community pharmacists in AMR stewardship at the primary care/community level. Methods: This study engaged community pharmacists in Thailand through semi-structured interviews to obtain in-depth insights into the antibiotic supply and perceptions of AMR. Additionally, sentiment analysis, which evaluates the emotional tone of the pharmacists' responses, was conducted to enrich the findings. Results: Interviews with 23 community pharmacists highlighted the practices, challenges, and strategies related to antibiotic supply and use. Key findings include the identification of barriers such as patient demand and lack of awareness about antimicrobial resistance (AMR), alongside strategies for improvement such as public education and professional development. Sentiment analysis reveals a cautiously optimistic perspective toward enhancing rational antibiotic use, underscoring the importance of comprehensive approaches that combine education, ethics, and regulatory measures to address the complexities of antibiotic management at community pharmacies. Conclusion: This study underscores the necessity of public awareness, pharmacist–patient relationships, and regulatory reforms for the rational use of antibiotics in community pharmacies. These findings emphasize that pharmacist education and adherence to professional ethics are essential for mitigating antimicrobial resistance and promoting rational antibiotic use.

Introduction Pharmacogenomic testing (PGx) plays a crucial role in improving patient medication safety, yet ethical concerns and limitations impede its clinical implementation in the primary care settings.Aims To systematically review the current state of PGx in the primary care settings and determine the enablers and challenges of its implementation.Design A scoping review was carried out by adhering to Arksey and O’Malley’s 6-stage methodological framework and the 2020 Joanna Briggs Institute and Levac et al.Data sources Cochrane Library, EMBASE, Global Health, MEDLINE and PubMed were searched up to 17 July 2023.Eligibility criteria All peer-reviewed studies in English, reporting the enablers and the challenges of implementing PGx in the primary care settings were included.Date extraction and synthesis Two independent reviewers extracted the data. Information was synthesised based on the reported enablers and the challenges of implementing PGx testing in the primary care settings. Information was then presented to stakeholders for their inputs.Results 78 studies discussing the implementation of PGx testing are included, of which 57% were published between 2019 and 2023. 68% of the studies discussed PGx testing in the primary care setting as a disease-specific themes. Healthcare professionals were the major stakeholders, with primary care physicians (55%) being the most represented. Enablers encompassed various advantages such as diagnostic and therapeutic benefits, cost reduction and the empowerment of healthcare professionals. Challenges included the absence of sufficient scientific evidence, insufficient training for healthcare professionals, ethical and legal aspects of PGx data, low patient awareness and acceptance and the high costs linked to PGx testing.Conclusion PGx testing integration in primary care requires increased consumer awareness, comprehensive healthcare provider training on legal and ethical aspects and global feasibility studies to better understand its implementation challenges. Managing high costs entails streamlining processes, advocating for reimbursement policies and investing in research on innovation and affordability research to improve life expectancy.

Objectives Responding to prior research findings that lack of knowledge about their disease impacted patients’ quality of life, the objective of this study was to identify and prioritise information gaps about hypersensitivity pneumonitis (HP) from the perspective of patients living with the disease.Design This study used the nominal group technique, a semiquantitative and qualitative method to identify stakeholder priorities.Setting Virtual group sessions were conducted in an academic medical centre in the USA.Participants 21 patients diagnosed with HP participated in this study. Participants were eligible if they spoke English and had access to the internet and were excluded if they had cognitive impairment.Results The patient statements were grouped into seven themes that were prioritised by participants in the following order: (1) natural history and prognosis; (2) current treatment options and therapeutic research; (3) epidemiology and aetiology of HP; (4) living well with HP; (5) origin and management of symptoms; (6) identifying and mitigating exposures and (7) methods of educating patients, clinicians and others about HP.Conclusions This study provides an understanding of patients’ prioritisation of knowledge gaps in HP to inform targeted educational interventions and provide avenues for future research.

Objetivo: Relatar três casos clínicos de Hemoglobinúria Paroxística Noturna (HPN) debatendo suas formas de apresentação clínica, clonalidade, cenário diagnóstico e tratamento. Série de casos: C.M.S, feminina, 34 anos, deu entrada no serviço com cefaleia e exames laboratoriais evidenciando hemólise. Apresentava coombs direto positivo, poliespecifico e presença de crioaglutininas. Inicialmente refrataria a corticoesteroides e então a pesquisa de clone HPN foi solicitado. Devido a gravidade do quadro e as informações até o momento, iniciado rituximab. O resultado de clone HPN revelou 46.3% clone tipo III e 20.4% clone tipo II em hemácias. Iniciado tratamento com eculizumab endovenoso apresentando resolução completa da anemia. A.C.S, masculino, 63 anos, com diagnóstico em 2016 de aplasia medular não grave e clone HPN 5%. Em 2018, iniciou tratamento com ciclosporina, que foi suspensa em 2020 devido à nefrotoxicidade e níveis hematimétricos estáveis. Em 2023, apresentou piora da anemia com critérios de hemólise, coombs direto negativo, esplenomegalia e dificuldade de ereção. Repetida pesquisa de clone HPN com achado de 32% clone tipo II e 1% clone tipo III. Estabelecimento diagnóstico de HPN sobreposto à aplasia de medula óssea (MO), iniciou eculizumab com remissão completa dos sintomas e normalização da hemoglobina após 3 semanas. F.A.F, masculino, 24 anos, com anemia aplástica grave diagnosticada em 2019 com imuno-histoquímica de MO acusando 6% de clone HPN. Realizada terapia com prednisona, timoglobulina de coelho e ciclosporina, com boa resposta ao tratamento. Após redução gradativa da dose de ciclosporina, sem citopenias importantes ou necessidade transfusional, foi optado por suspender medicação em 2023 e paciente manteve sem piora da anemia. Durante segmento, apresentava clone HPN de 7.7% em hemácias, sendo 4.16% tipo III e clones acometidos em neutrófilos e monócitos próximos a 30%. Mantem sem necessidade de tratamento com eculizumabe. Discussão: A HPN é condição rara e adquirida onde as células-tronco hematopoiéticas e seus clones possuem mutação no gene PIGA, responsável pela biossíntese de glicosilfosfatidilinositol (GPI) o que causa redução ou ausência de inibidores do sistema complemento na superfície das hemácias (CD55 e CD59). Resulta em hemólise intravascular crônica, trombose arterial e venosa, distonia dos músculos lisos e MO hipocelular ou displásica. Clones tipo I são normais, tipo II apresentam deficiência parcial e tipo III deficiência completa desses inibidores. Embora os clones possam surgir em diversas linhagens celulares os sintomas clássicos se relacionam ao acometimento da linhagem eritrocítica, que resulta em hemólise. Sendo assim hipótese diagnóstica nos casos de anemias hemolíticas em aplasias e outras falências medulares ou em eventos trombóticos sem outra explicação. É caracterizada como anemia hemolítica coombs negativo, mas pode apresentar padrões positivos principalmente em hemólises graves. A distribuição do clone e a diversidade na apresentação clínica podem resultar em atraso no diagnóstico. Conclusão: A variabilidade das expressões clonais assim como a falta do teste de coombs monoespecifico no SUS, tornam o diagnóstico da HPN desafiador. É necessário reforçar a importância do conhecimento clínico sobre a doença para obter o diagnóstico preciso.

Objetivo: Avaliar a relação entre as reservas de hemocomponentes (HCP) feitas ao banco de sangue (BS) do Hospital de Clínicas da Universidade Federal do Triângulo Mineiro (HC-UFTM), a utilização desses recursos e a adesão de especialidades médico-cirúrgicas ao Protocolo Institucional de Reserva Pré-operatória de Hemocomponentes (PRH). Materiais e métodos: Trata-se de estudo retrospectivo realizado por meio da análise de dados de janeiro a junho de 2024, relativos a procedimentos cirúrgicos eletivos realizados no HC-UFTM, sendo incluídos todos aqueles com reservas de HCP e excluídos aqueles sem especificação de procedimento ou sem referência no PRH. Foram avaliados: a quantidade e o tipo de HCP reservados para cirurgias e a quantidade utilizada. Além disso, analisou-se a conformidade da quantidade de reserva com aquela estabelecida no PRH, bem como a relação das variáveis de acordo com as especialidades médicas demandantes. Resultados: Em 402 cirurgias eletivas analisadas, foram reservadas 3194 bolsas de HCP e somente 2,72% foram utilizadas. Maior montante de reserva foi de concentrado de plaquetas - CP (40,23%), seguido de concentrado de hemácias - CH (31,12%), plasma fresco congelado - PFC (18,13%) e crioprecipitado - CRIO (10,52%). A relação entre reserva/uso, que demonstra o número de reserva para cada bolsa de HCP realmente utilizada, foi de 116,8, 67,2, 30,4 e 19,1, respectivamente, para CP, CRIO, PFC e CH. Em média, foram reservadas cerca de 3,17 bolsas de CP a mais que o utilizado por cirurgia, 2,34 de CH, 1,39 de PFC e 0,83 de CRIO. Apenas 0,5% das cirurgias com reserva de CH seguiram as recomendações do PRH. As 994 bolsas de CH reservadas representaram reserva 6,29 vezes maior que a prevista no PRH (158). Em média, foram solicitados 2,08 CH além do recomendado por cirurgia, todavia, do total reservado somente 12,9% foi utilizado. As especialidades médico-cirúrgicas com menor adesão ao PRH foram Cirurgia Cardíaca e Cirurgia Vascular, com média de reserva de 2,6 CH acima do recomendado por cirurgia. Em relação ao uso efetivo, a especialidade com média de utilização mais próxima ao reservado foi Ginecologia e Obstetrícia. Para as reservas de CP, CRIO e PFC, não previstas em PRH, das 2200 bolsas reservadas (68,9% das reservas) apenas 1,59% foram utilizadas. Discussão: Os dados demonstram grande discrepância entre a quantidade e o tipo de HCP reservados e a utilização efetiva, bem como, a insignificante adesão das especialidades médico-cirúrgicas demandantes das reservas quanto ao montante e ao tipo de HCP previstos no PRH. O cenário descrito revela possíveis falhas no processo de Educação Médica e nos mecanismos de controle interno para validação e efetivação de reservas. Ainda, a reserva excessiva implica em riscos no gerenciamento de estoques de HCP pela indisponibilidade temporária dos HCP durante período de reserva e custos desnecessários através da realização também exagerada de testes imuno-hematológicos. Conclusão: O estudo aponta falhas na reserva de HCP pelas especialidades médico-cirúrgicas, que não aderiram às recomendações do PRH, o que gera riscos potenciais para a organização dos estoques de HCP e aumento de custos. Melhoria dos processos de Educação Médica e do gerenciamento de estoques de HCP faz-se necessária.

Introdução: As ligas acadêmicas são oportunidades singulares para o desenvolvimento de atividades extracurriculares focadas no tripé ensino, pesquisa e extensão, colaborando positivamente na formação dos acadêmicos. A Liga Acadêmica de Hematologia e Hemoterapia da UFTM (LAHH-UFTM) tem essa proposta, com atividades direcionadas à educação em saúde, pesquisa científica e promoção da saúde na comunidade. Ademais, oferece aos alunos um contato com a prática de Hematologia e Hemoterapia, já nos anos iniciais de sua formação, possibilitando experiências multidisciplinares com diferentes profissionais. Objetivos: Relatar as atividades da LAHH-UFTM entre os anos de 2012 e 2024 e destacar sua importância para o meio acadêmico e comunitário. Materiais e métodos: Trata-se de um relato de experiência das ações desenvolvidas pelos membros da LAHH desde sua implantação. Atualmente, a liga é composta por 9 coordenadores discentes e 24 ligantes dos cursos de Biomedicina, Enfermagem e Medicina. O programa é desenvolvido em reuniões quinzenais, abordando módulos como Hemoterapia, Anemias, Hemostasia e Onco-Hematologia. Durante os encontros, são realizadas aulas teóricas e práticas e elabora-se temas para projetos comunitários. Discussão: Anualmente, a LAHH-UFTM realiza um simpósio aberto à comunidade acadêmica para informar sobre temas importantes em hematologia e hemoterapia e selecionar futuros ligantes. Entre 2012 e 2020, os principais projetos foram “Doadores do Futuro”, realizado em escolas de primeiro e segundo grau para conscientização sobre a doação de sangue, e “Anemia Ferropriva”, também com caráter de conscientização em escolas. Em março de 2020, as atividades da liga foram paralisadas devido à pandemia da Covid-19 e à suspensão das atividades acadêmicas. Em 2021, iniciou-se um plano de retomada das ações com uma nova coordenação, e um novo ciclo de aulas começou em abril de 2022. Desde então, a LAHH participou de eventos em parceria com Centros Acadêmicos dos cursos da área da saúde e com a universidade, incluindo a campanha “SUS todo dia, em todo lugar: 34 anos em defesa da vida”, na qual expôs a importância da doação de sangue e medula à população local, e um stand na Feira de Profissões da UFTM, onde apresentou suas atividades a alunos da educação básica de Uberaba e região. Em outubro de 2023, membros da coordenação da liga compareceram ao Congresso Nacional de Hematologia, Hemoterapia e Terapia Celular (HEMO) em São Paulo. Participaram de uma competição promovida pelo Sangue Jovem sobre inovações em saúde na terapia celular. Conclusão: A LAHH-UFTM, entre 2012 e 2024, mostrou-se essencial para a formação dos alunos, oferecendo experiências práticas e multidisciplinares. Suas atividades, desde projetos em escolas até a participação em congressos, destacam seu impacto positivo na comunidade e na educação em saúde. A retomada das ações pós-pandemia reafirma seu compromisso com a educação, pesquisa e extensão. Em suma, a LAHH tem sido uma plataforma eficaz para o desenvolvimento profissional dos estudantes e a promoção da saúde na comunidade.

Introdução: Mieloma múltiplo é uma doença que afeta as células da medula óssea, particularmente os plasmócitos. A idade média de diagnóstico varia entre 65 e 74 anos. Esta condição é caracterizada por alta morbidade e mortalidade. As manifestações extramedulares são raras, ocorrendo em cerca de 5% dos casos, enquanto o acometimento do sistema nervoso central (SNC) é uma complicação rara, afetando 1% dos pacientes. Neste estudo, é relatado um caso de mieloma múltiplo com infiltração no SNC e seu desfecho clínico. Objetivo: Relatar o caso clínico de Mieloma múltiplo com acometimento do sistema nervoso central de paciente em seguimento no Hospital Estadual Mário Covas (HEMC). Relato de caso: JSM, um paciente masculino de 58 anos, hipertenso, com diagnóstico de mieloma múltiplo de cadeia leve Kappa, apresentou manifestações neurológicas (despertar patológico). Um EEG revelou alentecimento difuso bilateral, enquanto a tomografia computadorizada do crânio não mostrou alterações. A análise do líquor revelou níveis de proteína de 51,8, glicose de 63 e celularidade de 5. A imunofenotipagem do líquor indicou a presença de 0,31% de plasmócitos. Materiais e métodos: Revisão do prontuário do paciente, do acesso ao laudo dos métodos diagnósticos aos quais o paciente foi submetido e de uma revisão de literatura. Discussão: Os sintomas em pacientes com mieloma múltiplo são inespecíficos e cursam com anemia, hipercalcemia, lesão lítica e renal. O acometimento do SNC é raro, mas pode ocorrer por contiguidade ou por via hematogênica. O tratamento da doença, apesar de não curativo e apresentar sobrevida de 5 anos em menos de 60% dos casos, consiste na associação de quimioterapia e corticosteroide. No entanto, em casos de infiltração do SNC, a literatura ainda é escassa em evidências para guiar o tratamento. Conclusão: A apresentação deste caso de mieloma múltiplo com envolvimento do sistema nervoso central destaca a complexidade e gravidade da doença. A rápida progressão e os desafios terapêuticos ressaltam a necessidade de abordagens integradas e vigilância contínua para melhorar os desfechos clínicos. Este relato sublinha a importância da detecção precoce e manejo multidisciplinar para enfrentar os múltiplos aspectos dessa doença.

Skeletal muscle mass is reduced during many diseases or physiological situations (disuse, aging), which results in decreased strength and increased mortality. Muscle mass is mainly controlled by the ubiquitin-proteasome system (UPS), involving hundreds of ubiquitinating enzymes (E2s and E3s) that target their dedicated substrates for subsequent degradation. We recently demonstrated that MuRF1, an E3 ubiquitin ligase known to bind to sarcomeric proteins (telethonin, α-actin, myosins) during catabolic situations, interacts with 5 different E2 enzymes and that these E2-MuRF1 couples are able to target telethonin, a small sarcomeric protein, for degradation. Amongst the E2s interacting with MuRF1, E2E1 was peculiar as the presence of the substrate was necessary for optimal MuRF1-E2E1 interaction. In this work, we focused on the putative role of E2E1 during skeletal muscle atrophy. We found that E2E1 expression was restricted to type I and type IIA muscle fibers and was not detectable in type IIB fibers. This strongly suggests that E2E1 targets are fiber-specific and may be strongly linked to the contractile and metabolic properties of the skeletal muscle. However, E2E1 knockdown was not sufficient for preserving the protein content in C2C12 myotubes subjected to a catabolic state (dexamethasone treatment), suggesting that E2E1 is not involved in the development of muscle atrophy. By contrast, E2E1 knockdown aggravated the atrophying process in both catabolic C2C12 myotubes and the Tibialis anterior muscle of mice, suggesting that E2E1 has a protective effect on muscle mass.

A retrospective analysis on human anisakiasis in Italy since its first description in 1996 was performed by conducting a literature search. Inclusion criteria based on the presence of a larva and on parasite identification were applied. Epidemiological data and clinical features were analysed. Particular attention was paid to the source of infection. In total, 73 cases were included in the analysis, while 34 were excluded. Cases were reported from eight Italian regions, most frequently Abruzzo, Apulia and Latium. The parasite was detected by endoscopy (51.4%) or laparotomy (48.6%). The site of infection was intestinal (42.5%), gastric (43.8%), oesophageal (1.4%) or ectopic (12.3%). Most of the parasites (71.0%) were identified as Anisakis sp. or A. simplex (s.l.). However, when molecular methods were used (21 cases), A. pegreffii was always identified. In most of the patients (65.7%), the source of infection was raw or undercooked anchovies, followed by “anchovies or sardines” (15.1%), generic “raw seafood” (15.1%), and sardines (1.4%). In only 2 cases (2.7%), the source was not available. This is the first systematic analysis of Italian cases of anisakiasis. The main conclusions derived from the results are: i) attention should be given to the history, in particular when raw marinated anchovies, proven to be the main source of human anisakiasis in Italy, are consumed; ii) in order to assess correct epidemiological data, a confirmed and specific etiological identification should always be sought.

High-temperature (470-1170 K) properties of CdTe:P single crystals, grown by Bridgman technique, with an initial concentration of impurities in the melt 1×1019 at/cm3, were investigated by measuring of the Hall effect. Experimental results indicate that up to the temperature of ~700 K samples had p-type conductivity and above ~940 K – n-type one. Character of isothermal dependences of Hall constant strongly differs from the dependence of the undoped material due to the influence of impurities. Acceptor effect of phosphorus is observed up to 1170 K, it shows a high content of acceptor impurity form (PTe). The low-temperature electric measurements data confirm the fact of phosphorus high solubility in CdTe. The results of IR microscopy indicate that the introduction of phosphorus into CdTe crystal resulted in almost complete elimination of second phase inclusions with size ≥1 μm, which are usually present in such material.

Radical and quick transformations towards sustainability will be fundamental to achieving a more sustainable future. However, deliberate interventions to reconfigure systems will result in winners and losers, with the potential for greater or lesser equity and justice outcomes. Positive tipping points (PTPs) have been proposed as interventions in complex systems with the aim to (a) reduce the likelihood of negative Earth system tipping points and/or (b) increase the likelihood of achieving just social foundations. However, many narratives around PTPs often do not take into account the entire spectrum of impacts the proposed alternatives could have or still rely on narratives that maintain current unsustainable behaviours and marginalize many people (i.e. do not take “b” into account). One such example is the move from petrol-based to electric vehicles. An energy transition that remains based on natural resource inputs from the Global South must be unpacked with an equity and justice lens to understand the true cost of this transition. There are two arguments why a critical engagement with these and other similar proposals needs to be made. First, the idea of transitioning through a substitution (e.g. of fuel) while maintaining the system structure (e.g. of private vehicles) may not necessarily be conceived as the kind of radical transformation being called for by global scientific bodies like the Intergovernmental Panel on Climate Change (IPCC) and Intergovernmental Science-Policy Platform on Biodiversity and Ecosystem Services (IPBES). Second, and probably more importantly, the question of positive for whom, positive where, and positive how must be considered. In this paper, we unpack these narratives using a critical decolonial view from the south and outline their implications for the concept of tipping points.

The identification of genes that confer either extension of life span or accelerate age-related decline was a step forward in understanding the mechanisms of aging and revealed that it is partially controlled by genetics and transcriptional programs. Here, we discovered that the human DNA sequence C16ORF70 encodes a protein, named MYTHO (macroautophagy and youth optimizer), which controls life span and health span. MYTHO protein is conserved from Caenorhabditis elegans to humans and its mRNA was upregulated in aged mice and elderly people. Deletion of the orthologous myt-1 gene in C. elegans dramatically shortened life span and decreased animal survival upon exposure to oxidative stress. Mechanistically, MYTHO is required for autophagy likely because it acts as a scaffold that binds WIPI2 and BCAS3 to recruit and assemble the conjugation system at the phagophore, the nascent autophagosome. We conclude that MYTHO is a transcriptionally regulated initiator of autophagy that is central in promoting stress resistance and healthy aging., Introduction In nature, organisms are continuously exposed to environmental stresses that challenge their survival. The species that quickly and efficiently adapt to hostile conditions are positively selected. This response is [...]

IntroductionThis study investigates the interplay between body composition, dietary patterns, and physical activity across genders, focusing on gender-specific differences in food preferences and eating behaviors. Understanding these interactions is crucial for developing targeted nutritional and lifestyle interventions.MethodsA cross-sectional study was conducted with 1,333 participants (58.7% female, 41.3% male), aged 18–65 years. Participants were categorized into tertiles based on their fat mass to fat-free mass (FM-to-FFM) ratio. Data on dietary choices, eating behaviors, and physical activity were collected and analyzed to identify gender-specific trends.ResultsSignificant gender-specific differences were observed in food preferences and eating behaviors. Males experienced greater hunger in the late afternoon, while females felt more hunger in the morning. Males showed a preference for processed and red meats, whereas females preferred cooked vegetables. Eating behaviors such as meal skipping, uncontrolled eating, nocturnal eating, and taste preferences (sweet or salty) varied distinctly between FM-to-FFM tertiles and genders. Higher FM-to-FFM ratios correlated with lower physical activity levels, particularly in strength training and general sports engagement.DiscussionThese findings highlight the complex interactions between body composition, dietary habits, and lifestyle factors, emphasizing gender-specific differences. The results suggest that body composition and BMI significantly impact health-related behaviors, necessitating tailored interventions to address these differences and promote healthier lifestyles.

BackgroundUltrasound-guided percutaneous cryoneurolysis is an analgesic technique in which a percutaneous probe is used to reversibly ablate a peripheral nerve(s) using exceptionally low temperature, and has yet to be evaluated with randomized, controlled trials. Pain after mastectomy can be difficult to treat, and the authors hypothesized that the severity of surgically related pain would be lower on postoperative day 2 with the addition of cryoanalgesia compared with patients receiving solely standard-of-care treatment.MethodsPreoperatively, participants at one enrolling center received a single injection of ropivacaine, 0.5%, paravertebral nerve block at T3 or T4, and perineural catheter. Participants subsequently underwent an active or sham ultrasound-guided percutaneous cryoneurolysis procedure of the ipsilateral T2 to T5 intercostal nerves in a randomized, patient- and observer-masked fashion. Participants all received a continuous paravertebral block with ropivacaine, 0.2%, until the early morning of discharge (usually postoperative day 2). The primary endpoint was the average pain level measured using a 0 to 10 numeric rating scale the afternoon of postoperative day 2. Participants were followed for 1 yr.ResultsOn postoperative day 2, participants who had received active cryoneurolysis (n = 31) had a median [interquartile range] pain score of 0 [0 to 1.4] versus 3.0 [2.0 to 5.0] in patients given sham (n = 29): difference -2.5 (97.5% CI, -3.5 to -1.5), P < 0.001. There was evidence of superior analgesia through month 12. During the first 3 weeks, cryoneurolysis lowered cumulative opioid use by 98%, with the active group using 1.5 [0 to 14] mg of oxycodone compared with 72 [20 to 120] mg in the sham group (P < 0.001). No oral analgesics were required by any patient between months 1 and 12. After 1 yr chronic pain had developed in 1 (3%) active compared with 5 (17%) sham participants (P < 0.001).ConclusionsPercutaneous cryoneurolysis markedly improved analgesia without systemic side effects or complications after mastectomy.Editor’s perspective

Background Phantom limb pain (PLP) occurs after amputations and can persist in a chronic and debilitating way. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive neuromodulation method capable of influencing brain function and modulating cortical excitability. Its effectiveness in treating chronic pain is promising.

Abstract Generation of high-speed laser pulses is essential for sustaining today’s global, hyper-connected society. One approach for achieving high spectral and temporal purity is to combine optical nonlinear materials with spectral filtering devices. In this work, a graphene-coated microresonator integrates a nonlinear material and a spectral filtering platform into a single device, creating a tunable GHz repetition rate mode-locked fiber laser. The graphene is directly synthesized on the non-planar surface of microresonator, resulting in a uniform, conformal coating with minimal optical loss in the device. The whispering gallery modes of the resonator filter the propagating modes, and the remaining modes from the interaction with graphene lock their relative phases to form short pulses at an elevated repetition rate relying on inter-modal spectral distance. Additionally, by leveraging the photo-thermal effect, all-optical tuning of the repetition rate is demonstrated. With optimized device parameters, repetition rates of 150 GHz and tuning of 6.1 GHz are achieved.

Bovine tuberculosis (bTB) is a zoonotic disease with consequences for public health as well as the economy. In the EU, compulsory eradication programmes have been applied, and most territories in Italy have been reported as disease-free (FTs). However, outbreaks (OBs), i.e., an officially confirmed occurrence of bTB in one or more animals in an establishment, have continued to be reported. In this study we provide an overview of bTB in terms of OB numbers in cattle from Italian FTs. Legislative sources were collected to find the FTs, the relevant declaration of free status year (FSY), and regional control and surveillance plans. Then, descriptive and statistical analyses were applied to the collected OBs. A total of 12 regions and 19 provinces were declared FTs in the 20 years from 2003 to 2023. Differences in regional plans were observed with respect to the percentages of herds that were annually controlled (control frequency). Overall, 370 OBs were recorded. A non-statistically significant decrease in the OB incidence rate after the FSY was declared. However, a notable increase in OBs detected at slaughterhouses after the FSY suggests that control systems (serological tests) at the herd level are not completely effective. Differences in the herds’ control frequencies among FTs seem to not have had a significant influence on the observed OB number. The Tuscany region was the most affected FT based on the OB numbers after the FSY (especially in the last year). Epidemiologically relevant primary determinants seem to be the farming system (semi-extensive and adjacent herds) and the cattle movements from positive incidence areas (trade and animal fairs). The role of wild boars in the disease maintenance cannot be excluded. The results of this study stress the need to revise bTB eradication and surveillance plans based on risk analysis.

In the present study, in order to expand the knowledge on the distribution of parasites of the genus Eustrongylides in never investigated Italian lacustrine areas of Tuscany and Latium, fish specimens from four Tuscan lakes (Bilancino, Chiusi, Montedoglio and San Cipriano) and two Latium lakes (Bolsena and Bracciano) were collected and analyzed. The parasitological analysis, consisting of a visual inspection followed by a chloro-peptic digestion, was performed on 1650 specimens belonging to 17 species: European perch (Perca fluviatilis), Pumpkinseed (Lepomis gibbosus), Pike-perch (Sander lucioperca), Largemouth black bass (Micropterus salmoides), Pike (Esox lucius), Big-scale sand smelt (Atherina boyeri), Tench (Tinca), European Whitefish (Coregonus lavaretus), Channel catfish (Ictalurus punctatus), Chub (Squalius cephalus), Rudd (Scardinius erythrophthalmus), Common bleak (Alburnus alborella), South European roach (Sarmarutilus rubilio), South European nase (Protochondrostoma genei), Italian riffle dace (Telestes muticellus), Goldfish (Carassius auratus), and Freshwater bream (Abramis brama). Eustrongylides spp. larvae were only found in one specimen of European perch caught in Bracciano Lake and purchased from a local fishmonger (P = 3.3%; MI = 1; MA = 0.03). The only isolated Eustrongylides spp. larva was submitted to molecular analysis of the ITS gene region and identified as E. excisus. This finding adds Bracciano Lake to the list of the several Italian lakes in which nematodes belonging to this genus have been reported. Even if the observed prevalence is currently low, the presence of the parasite in this local freshwater fish supply chain requires FBOs to adopt risk management measures to prevent contaminated products from reaching final consumer. Moreover, future investigations will show if the parasite expands in these areas.

Gene expression profiling is a powerful tool that has been extensively used to investigate the underlying biology and etiology of diseases, including cancer. Microarray gene expression analysis enables simultaneous measurement of thousands of mRNA levels. Sophisticated computational approaches have evolved in parallel with the rapid progress in bioassay technologies, enabling more effective analysis of the large and complex datasets that these technologies produce.In this study, we utilized systems biology approaches to examine gene expression profiles across different grades of breast cancer progression. We conducted a meta-analysis of publicly available microarray data to elucidate the molecular mechanisms underlying breast cancer grade classification.Our results suggest that while grade index is commonly used for evaluating cancer progression status in the clinic, the complexity of molecular mechanisms, histological characteristics, and other factors related to patient outcomes raises doubts about the utility of breast cancer grades as a foundation for formulating treatment protocols.Our study underscores the importance of advancing personalized strategies for breast cancer classification and management. More research is crucial to refine diagnostic tools and treatment modalities, aiming for greater precision and tailored care in patient outcomes.

To standardize control activities, it is necessary to introduce checklists to support the control of consignments entering the European Union through border control posts (BCPs). This study aimed to develop a pilot checklist for the control of fishery consignments, preliminarily identified as the predominant group of goods entering the Livorno (Italy) BCP. The design of the pilot checklist was preceded by i) a revision of the current European and national legislation on the general and specific objectives of border control activities on fishery products and ii) a comparative analysis of two checklists (one of the Ministry of Health and one of the former Livorno border inspection post) developed on the basis of the repealed legislation. This comparison aimed to define the pilot checklist structure, verification objectives, and selection of assessment scores to be included in defining consignment compliance and acceptability. Once developed, the clarity and ease of use of the first draft of the pilot checklist were verified through its use in a field test during the control of 64 fishery product consignments. 22 regulatory sources (18 European and 4 national) were selected as reference legislation. The pilot checklist was structured as a dynamic “read-do” document based on the workflow of control activities described in the current legislation. The field test was useful in improving the clarity of the verification objectives within the documentary, identity, and physical control sections and in facilitating the use of the checklist and the collection of evidence during the control activity. This study, which focused on fishery products, can provide a practical approach for the development of checklists for all the other goods categories under the responsibility of BCPs.

The original notifications (n=1355) managed by the Rapid Alert System for Food and Feed of the Tuscany region in the seven-year period 2015-2021 were analyzed. 68.9% of them were classified as alert notifications, and they mostly originated (56.3%) from official controls on the market, followed by the company's own checks (29.1%). Italy was the most represented notifying country (73.3%) and the most represented country of origin of the notified products (64.5%). Out of the 28 considered food categories, “fish and products thereof” (F), “cereals and bakery products” (C), “bivalve mollusks and products thereof” (B), and “meat and meat products (other than poultry)” (M) were the most notified. F were especially notified for the presence of heavy metals (45.7%), C for undeclared allergens (32.1%), B for microbial contaminants (Escherichia coli, 49.6%), and M for pathogenic microorganisms (55.9%), mostly Salmonella spp. and Listeria monocytogenes. This study provides an updated framework for the main food safety issues at the regional level. The Rapid Alert System for Food and Feed should be periodically analyzed to evaluate historical trends and emerging or poorly known hazards. This is especially important for the planning of official control activities and the prevention of risks through the food supply chain.

Abstract Mesalazine (5-ASA) is a medication utilized to treat inflammatory bowel diseases involving ulcerative colitis and Crohn’s disease. Mesalazine has fewer side effects but the low solubility and bioavailability of it is responsible for its delayed onset of action. Hence, the goal of this study is to determine the molar solubility of 5-ASA in aqueous pseudo-binary mixtures containing low toxic biocompatible choline chloride/ethylene glycol deep eutectic solvent (ChCl/EG DES) with DES mass fraction of 0.0–1.0 using a shake-flask technique at 293.2–313.2 K and approximately 85 kPa. The experimental results indicated that the solubility of 5-ASA enhanced by addition of DES mass fraction and also increasing temperature. The molarity values of 5-ASA were then modelled by some traditional cosolvency models, and regressed each model parameters. The back-computed molarity of 5-ASA using the selected cosolvency models presented a good consistency with the experimental data (lower mean percentage deviation than 5.14%). Moreover, the Gibbs and van’t Hoff equations were employed to compute the thermodynamic functions of 5-ASA dissolution process in ChCl/EG DES + water from the temperature dependency of solubility data. This analysis presented an endothermic and entropy-driven process of 5-ASA dissolution in ChCl/EG DES + water. Furthermore, enthalpy-entropy compensation analysis represented non-linear enthalpy dissolution vs. Gibbs free energy compensation plots with positive and negative slopes for 5-ASA whereas the positive and negative slopes were probably due to the enhance in solvation of 5-ASA by ChCl/EG DES molecules and the solvent-structure loosing, respectively.

Abstract Background Migraine is the second world’s cause of disability. Among non-pharmacological treatments, nutritional intervention, particularly ketogenic diet, represents one of the most promising approaches. Methods This a prospective, single center, randomized, controlled study aimed at evaluating the efficacy of a very low-calorie ketogenic diet (VLCKD) compared to a hypocaloric balanced diet (HBD) in migraine prophylaxis in patients affected by high-frequency episodic migraine (HFEM) with a Body Mass Index (BMI) > 27 kg/m2. Fifty-seven patients were randomly assigned to a VLCKD (group 1) or HBD (group 2). Group 1 patients followed a VLCKD for 8 weeks, followed by a low calorie diet (LCD, weeks 9–12), and a HBD (weeks 13–24), whereas group 2 patients followed a HBD from week 0 to 24. Anthropometric indexes, urine and blood chemistry were assessed at enrollment, baseline, weeks 4, 8, 12, and 24. Migraine characteristics were evaluated at baseline, weeks 8, 12 and 24. Change in monthly migraine days (MMDs) at weeks 5–8 compared to baseline was the primary endpoint. Secondary endpoints encompassed changes in visual analogue scale (VAS), Headache Impact Test-6 (HIT-6) and Short Form Health Survey-36 (SF-36) scores. We also studied effects on circulating lymphocytes and markers of inflammation, changes in plasma aldosterone and renin levels before and after VLCKD or HBD treatment. Results Reduction from baseline in MMDs was greater in VLCKD compared to HBD group at week 8 (p = 0.008), at week 12 (p = 0.007), when ketosis had been interrupted by carbohydrates reintroduction, and at week 24 (p = 0.042), when all patients were following the same dietary regimen. Quality of life scores (SF-36) were improved in VLCKD group at week 8 and 12, and were also improved in HBD group, but only at week 12. Weight-loss was significantly higher in VLCKD group at week 8 (p = 0.002) and week 12 (p = 0.020). At the end of the study weight loss was maintained in VLCKD group whereas a slight weight regain was observed in HBD group. Inflammatory indexes, namely C reactive protein (CRP), neutrophil to lymphocyte ratio (NLR) and total white blood cell count (WBC) were significantly reduced (p

Diversos setores da economia, sejam públicos ou privados, têm obtido sucesso na aplicação de métodos integrados para a melhoria de seus processos, a partir da gestão de processos de negócio associada às novas tecnologias da Indústria 4.0 (I4.0). Tal fato tem despertado interesse de profissionais e pesquisadores, que buscam, na literatura científica, abordagens sob diferentes aspectos relacionadas a esses temas. Assim, o objetivo deste artigo é apresentar uma revisão sistemática da literatura que responda à seguinte questão de pesquisa: “Quais práticas de BPM são aplicadas no contexto das tecnologias da Indústria 4.0 no segmento industrial?”. As análises efetuadas em 26 estudos apresentaram as tendências atuais de pesquisas relacionadas ao tema abordado, assim como os principais periódicos que publicam essas pesquisas. Os resultados apontaram uma relação das práticas de BPM ao tipo de tecnologia da Indústria 4.0, assim como o segmento industrial de aplicação. A partir dos resultados obtidos, foi possível identificar uma forte tendência de pesquisa associada à Análise e Modelagem de Processo a partir da utilização da Internet das Coisas (IoT).