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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