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Over the last years, the exponential progress of technology introduced a broader population of researchers and developers to the use of Virtual Reality (VR) devices in numerous contexts, e.g., gaming, simulations, and culture dissemination. Recently, cultural heritage has also been supported by motivational experiences and other improvements designed explicitly for specific users (visitors, researchers, and domain experts). In this context, we propose a protocol within a digital environment, using innovative, non-invasive, and non-destructive methods for the technological enhancement, education, and dissemination of ancient human remains. The presented case study is focused on sexual dimorphism in the human skull; several 3D models are digitally generated from female and male skull references exploiting an algorithmic approach with statistical analysis, e.g., Principal Component Analysis (PCA); then, the models are made available in a virtual environment with a Head Mounted Display (HMD) and can also be interacted with via a touchless approach (hands-free). Tests conducted with segmented populations provided promising results.

Abstract The aim of this study was to examine how running biomechanics (spatiotemporal and kinetic variables) adapt with exhaustion during treadmill runs at 90, 100, 110, and 120% of the peak aerobic speed (PS) of a maximal incremental aerobic test. Thirteen male runners performed a maximal incremental aerobic test on an instrumented treadmill to determine their PS. Biomechanical variables were evaluated at the start, mid, and end of each run until volitional exhaustion. The change of running biomechanics with fatigue was similar among the four tested speeds. Duty factor and contact and propulsion times increased with exhaustion (P ≤ 0.004; F ≥ 10.32) while flight time decreased (P = 0.02; F = 6.67) and stride frequency stayed unchanged (P = 0.97; F = 0.00). A decrease in vertical and propulsive peak forces were obtained with exhaustion (P ≤ 0.002; F ≥ 11.52). There was no change in the impact peak with exhaustion (P = 0.41; F = 1.05). For runners showing impact peaks, the number of impact peaks increased (P ≤ 0.04; $${\upchi }^{2}$$ χ 2 ≥ 6.40) together with the vertical loading rate (P = 0.005; F = 9.61). No changes in total, external, and internal positive mechanical work was reported with exhaustion (P ≥ 0.12; F ≤ 2.32). Results suggest a tendency towards a “smoother” vertical and horizontal running pattern with exhaustion. A smoother running pattern refers to the development of protective adjustments, leading to a reduction of the load applied to the musculoskeletal system at each running step. This transition seemed continuous between the start and end of the running trials and could be adopted by the runners to decrease the muscle force level during the propulsion phase. Despite these changes with exhaustion, there were no changes in either gesture speed (no alteration of stride frequency) or positive mechanical work, advocating that runners unconsciously organize themselves to maintain a constant whole-body mechanical work output.

This Editorial celebrates the 70th anniversary of the European Journal of Histochemistry since its foundation as Rivista di Istochimica Normale e Patologica, and introduces a Special Collection of selected articles on the application of the histochemical approach for investigating cell biological features and processes in animals and plants, and under diseased conditions. The year 2024 is a special one for histochemists, as 100 years ago J.W. Robert Feulgen and H. Rossenbeck introduced the histochemical procedure for the specific stoichiometric staining of DNA in histological samples: to commemorate this influential publication, three papers in the present issue are devoted to the application of the Feulgen reaction at light and electron microscopy, and in cytometry.

Este artículo trata acerca de la caracterización de la tecnología de un cielo raso de paja y barro denominada en lengua aymara como "caruna". El estudio se realizó en viviendas Aymaras a más de 4.000 metros sobre el nivel del mar en la localidad de Tacora, en la región de Arica y Parinacota, Chile. El estudio forma parte del proyecto 49204 financiado por el Servicio Nacional del Patrimonio Cultural. Su objetivo es rescatar esta técnica vernácula como alternativa a los materiales industrializados que han modificado la vivienda andina y la calidad de vida en climas extremos durante los últimos 25 años. Se recogieron muestras de los materiales utilizados en esta técnica, reproducida por un cultor local, y se analizaron en laboratorio para determinar sus propiedades térmicas y de trabajabilidad. Además, se monitoreó el desempeño energético de tres viviendas en el poblado de Tacora para comparar los resultados obtenidos con los de los laboratorios. Los hallazgos revelaron que la matriz de barro utilizada en esta técnica de encielado es predominantemente arcillosa con mediana compresibilidad y baja conductividad térmica, lo que la hace adecuada como aislante en climas desérticos fríos. El cielo de barro y paja alivianado se destacó por su presencia en la cultura local, la disponibilidad de recursos materiales y su facilidad de instalación. Este estudio subraya la importancia de preservar el conocimiento tradicional, respetando los saberes ancestrales y mejorando el desempeño térmico de las viviendas en la cordillera norte de Chile, Perú y Bolivia, destacando su relevancia para el desarrollo de soluciones habitacionales sostenibles y culturalmente pertinentes.

La plancha de barro y paja aligerada es una práctica constructiva que las comunidades andinas han empleado tradicionalmente en los cielos de sus viviendas. Según su ubicación geográfica se denomina con distintos nombres como “caruna, takta, t´ajta, p’ira, t’illi” y emplea en su elaboración la tierra y paja de su entorno altiplánico. Actualmente sufre el riesgo de desaparición, producto de los procesos socioculturales vividos en el territorio durante los últimos 50 años. Este artículo describe las acciones de rescate y puesta en valor del sistema, a través de un proyecto de investigación tecnológica con metodología de campo y laboratorio en la región de Arica y Parinacota, al norte de Chile. Los resultados obtenidos a través de esta investigación, han permitido caracterizar mecánica y físicamente el sistema, los hallazgos se han contrastado con los principios de salvaguardia para evaluar su potencialidad de reconocimiento en el sistema nacional de Patrimonio Inmaterial salvaguarda.

Introduction: A regular physical training is known to contribute to preserve muscle mass and strength, maintaining structure and function of neural and vascular compartments and preventing muscle insulin resistance and inflammation. However, physical activity is progressively reduced during aging causing mobility limitations and poor quality of life. Although physical exercise for rehabilitation purposes (e.g., after fractures or cardiovascular events) or simply aiming to counteract the development of sarcopenia is frequently advised by physicians, nevertheless few data are available on the targets and the global effects on the muscle organ of adapted exercise especially if started at old age.Methods: To contribute answering this question for medical translational purposes, the proteomic profile of the gastrocnemius muscle was analyzed in 24-month-old mice undergoing adapted physical training on a treadmill for 12 weeks or kept under a sedentary lifestyle condition. Proteomic data were implemented by morphological and morphometrical ultrastructural evaluations.Results and Discussion: Data demonstrate that muscles can respond to adapted physical training started at old age, positively modulating their morphology and the proteomic profile fostering protective and saving mechanisms either involving the extracellular compartment as well as muscle cell components and pathways (i.e., mitochondrial processes, cytoplasmic translation pathways, chaperone-dependent protein refolding, regulation of skeletal muscle contraction). Therefore, this study provides important insights on the targets of adapted physical training, which can be regarded as suitable benchmarks for future in vivo studies further exploring the effects of this type of physical activity by functional/metabolic approaches.

Summary: Phosphonates—compounds containing a direct C–P bond—represent an important source of phosphorus in some environments. The most common natural phosphonate is 2-aminoethylphosphonate (AEP). Many bacteria can break AEP down through specialized “hydrolytic” pathways, which start with the conversion of AEP into phosphonoacetaldehyde (PAA), catalyzed by the transaminase PhnW. However, the substrate scope of these pathways is very narrow, as PhnW cannot process other common AEP-related phosphonates, notably N-methyl AEP (M1AEP). Here, we describe a heterogeneous group of FAD-dependent oxidoreductases that efficiently oxidize M1AEP to directly generate PAA, thus expanding the versatility and usefulness of the hydrolytic AEP degradation pathways. Furthermore, some of these enzymes can also efficiently oxidize plain AEP. By doing so, they surrogate the role of PhnW in organisms that do not possess the transaminase and create novel versions of the AEP degradation pathways in which PAA is generated solely by oxidative deamination.

Abstract The study aimed to compare the ankle muscles activation, biomechanics and energetics of running in male runners during submaximal level run using minimalist (MinRS) and traditional cushioned (TrdRS) running shoes. During 45-min running in MinRS and TrdRS, the ankle muscles pre- and co-activation, biomechanics, and energetics of running of 16 male endurance runners (25.5 ± 3.5 yr) were assessed using surface electromyography (tibialis anterior and gastrocnemius lateralis), instrumented treadmill and indirect calorimetry, respectively. The net energy cost of running (Cr) was similar for both conditions (P = 0.25) with a significant increase over time (P

BackgroundLong non-coding RNAs (lncRNAs) exhibit highly cell type-specific expression and function, making this class of transcript attractive for targeted cancer therapy. However, the vast majority of lncRNAs have not been tested as potential therapeutic targets, particularly in the context of currently used cancer treatments. Malignant glioma is rapidly fatal, and ionizing radiation is part of the current standard-of-care used to slow tumor growth in both adult and pediatric patients.ResultsWe use CRISPR interference (CRISPRi) to screen 5689 lncRNA loci in human glioblastoma (GBM) cells, identifying 467 hits that modify cell growth in the presence of clinically relevant doses of fractionated radiation. Thirty-three of these lncRNA hits sensitize cells to radiation, and based on their expression in adult and pediatric gliomas, nine of these hits are prioritized as lncRNA Glioma Radiation Sensitizers (lncGRS). Knockdown of lncGRS-1, a primate-conserved, nuclear-enriched lncRNA, inhibits the growth and proliferation of primary adult and pediatric glioma cells, but not the viability of normal brain cells. Using human brain organoids comprised of mature neural cell types as a three-dimensional tissue substrate to model the invasive growth of glioma, we find that antisense oligonucleotides targeting lncGRS-1 selectively decrease tumor growth and sensitize glioma cells to radiation therapy.ConclusionsThese studies identify lncGRS-1 as a glioma-specific therapeutic target and establish a generalizable approach to rapidly identify novel therapeutic targets in the vast non-coding genome to enhance radiation therapy.

Background: A nudge intervention against Herpes Zoster, created and implemented in Italy, is presented in order to administer the Shingrix vaccine on a sample of frail patients, as required by the National Prevention Plan. Individual and contextual factors associated with vaccine adherence were investigated. Method: 300 frail adult subjects underwent a full vaccine cycle with recombinant-Shingrix vaccine (RZV vaccine). Hospital Presidia of the Salerno University Hospital Authority, a Hospital Presidium of the Salerno Local Health Authority, and the Public Health Laboratory of the University of Salerno (Campania) participated in the intervention. An ad hoc questionnaire was administered with the following scales: EQ-5D, PSS-10, MSPSS, and representations of HZ and its consequences. Results: Some variables, such as peer support, doctor–patient relationship, level of education, and perception of health, are important in vaccine adherence and information processing. The following factors emerged from the factor analysis: Trust in collective knowledge and collective responsibility (F1); beliefs about virus risk and vaccine function (F2); information about virus and symptomatology (F3); and vaccine distrust (F4). Factor 4 correlates negatively with social support indices (R = −0.363; p < 0.001). There is a significant relationship between factor 3 and satisfaction with national information campaigns (F = 3.376; gdl = 5; p-value = 0.006). Conclusions: Future vaccination campaigns should be built with the aim of personalizing information and developing contextualized strategies, starting from understanding the stakeholders involved, cultural contexts, and organizational settings.

Hyaluronic acid (HA) is a linear, anionic, non-sulfated glycosaminoglycan occurring in almost all body tissues and fluids of vertebrates including humans. It is a main component of the extracellular matrix and, thanks to its high water-holding capacity, plays a major role in tissue hydration and osmotic pressure maintenance, but it is also involved in cell proliferation, differentiation and migration, inflammation, immunomodulation, and angiogenesis. Based on multiple physiological effects on tissue repair and reconstruction processes, HA has found extensive application in regenerative medicine. In recent years, nanotechnological research has been applied to HA in order to improve its regenerative potential, developing nanomedical formulations containing HA as the main component of multifunctional hydrogels systems, or as core component or coating/functionalizing element of nanoconstructs. This review offers an overview of the various uses of HA in regenerative medicine aimed at designing innovative nanostructured devices to be applied in various fields such as orthopedics, dermatology, and neurology.

Hereditary breast and ovarian cancer (HBOC) syndrome is responsible for approximately 10% of breast cancers (BCs). The HBOC gene panel includes both high-risk genes, i.e., a four times higher risk of BC (BRCA1, BRCA2, PALB2, CDH1, PTEN, STK11 and TP53), and moderate-risk genes, i.e., a two to four times higher risk of BC (BARD1, CHEK2, RAD51C, RAD51D and ATM). Pathogenic germline variants (PGVs) in HBOC genes confer an absolute risk of BC that changes according to the gene considered. We illustrate and compare different BC risk estimation models, also describing their limitations. These models allow us to identify women eligible for genetic testing and possibly to offer surgical strategies for primary prevention, i.e., risk-reducing mastectomies and salpingo-oophorectomies.

Background: The impact of non-vitamin K antagonist oral anticoagulants (NOACs) on platelet function is still unclear. We conducted a comprehensive ex vivo study aimed at assessing the effect of the four currently marketed NOACs on platelet function. Methods: We incubated blood samples from healthy donors with concentrations of NOACs (50, 150 and 250 ng/mL), in the range of those achieved in the plasma of patients during therapy. We evaluated generation of thrombin; light transmittance platelet aggregation (LTA) in response to adenosine diphosphate (ADP), thrombin receptor-activating peptide (TRAP), human γ-thrombin (THR) and tissue factor (TF); generation of thromboxane (TX)B2; and expression of protease-activated receptor (PAR)-1 and P-selectin on the platelet surface. Results: All NOACs concentration-dependently reduced thrombin generation compared with control. THR-induced LTA was suppressed by the addition of dabigatran at any concentration, while TF-induced LTA was reduced by factor-Xa inhibitors. ADP- and TRAP-induced LTA was not modified by NOACs. TXB2 generation was reduced by all NOACs, particularly at the highest concentrations. We found a concentration-dependent increase in PAR-1 expression after incubation with dabigatran, mainly at the highest concentrations, but not with FXa inhibitors; P-selectin expression was not changed by any drugs. Conclusions: Treatment with the NOACs is associated with measurable ex vivo changes in platelet function, arguing for antiplatelet effects beyond the well-known anticoagulant activities of these drugs. There are differences, however, among the NOACs, especially between dabigatran and the FXa inhibitors.

Aging is accompanied by a progressive loss of skeletal muscle mass and strength. The mechanisms underlying this phenomenon are certainly multifactorial and still remain to be fully elucidated. Changes in the cell nucleus structure and function have been considered among the possible contributing causes. This review offers an overview of the current knowledge on skeletal muscle nuclei in aging, focusing on the impairment of nuclear pathways potentially involved in age-related muscle decline. In skeletal muscle two types of cells are present: fiber cells, constituting the contractile muscle mass and containing hundreds of myonuclei, and the satellite cells, i.e., the myogenic mononuclear stem cells occurring at the periphery of the fibers and responsible for muscle growth and repair. Research conducted on different experimental models and with different methodological approaches demonstrated that both the myonuclei and satellite cell nuclei of aged skeletal muscles undergo several structural and molecular alterations, affecting chromatin organization, gene expression, and transcriptional and post-transcriptional activities. These alterations play a key role in the impairment of muscle fiber homeostasis and regeneration, thus contributing to the age-related decrease in skeletal muscle mass and function.

Introdução: A Constituição Federal de 1988, no seu artigo 5º, subseção VI, garante a liberdade de crença religiosa como um dos pilares fundamentais de uma sociedade democrática. No entanto, a atual conjuntura da prática médica no Brasil em relação às Testemunhas de Jeová (TJ), grupo religioso cristão que rejeita Transfusão Sanguínea (TS), constitui um dilema entre a autonomia do paciente de recusar tratamentos que transgridem os preceitos de suas crenças, mas são essenciais para a sua sobrevivência, e o papel do médico de honrar seus princípios, ainda que isso possa afetar a condução clínica do caso. A complexidade dessa interação entre fé, ciência e direitos fundamentais exige uma avaliação das implicações, tanto no âmbito individual quanto coletivo. É essencial considerar não somente os aspectos médicos e legais, mas também as dimensões psicológicas e sociais envolvidas. Portanto, a análise do conflito entre a liberdade religiosa e a prática médica, como exemplificado pelas TJ e a recusa de TS, lança uma luz crítica sobre as interseções entre valores individuais e responsabilidades profissionais. Objetivos: Contribuir para uma abordagem, que respeite as crenças pessoais sem comprometer a integridade da prática médica e a busca pela preservação da vida. Metodologia: É uma análise bibliográfica envolvendo o complexo dilema da “Hemotransfusão em Testemunhas de Jeová”e surgiu a partir de trabalhos acadêmicos do curso de medicina e da recente decisão de um Desembargador do Tribunal Justiça de Minas Gerais (TJMG). Discussão: Em contextos em que o paciente recusa a TS, o médico deve equilibrar o respeito à autonomia do indivíduo com a urgência de preservar vidas. Diante dessa dicotomia, emergem esforços jurídicos em busca de soluções que permitam a intervenção médica respeitando as crenças.Exemplo dessa interação entre medicina e jurisdição é a recente atuação do desembargador Leonardo de Faria Beraldo, do TJMG, ao suspender uma decisão que autorizava o Hospital Santa Casa de Montes Claros a realizar uma TS em uma TJ que recusava tal procedimento. Sob um viés social, as crenças determinam a qualidade de vida de um indivíduo. A transgressão dos princípios bíblicos descritos em Gênesis (9:4) e Levítico (17:10), que proíbem a TS, acarreta a exclusão das TJ das atividades religiosas. Logo, muitos indivíduos decidem arriscar a própria vida, a fim de manter a integridade de sua crença.Esse contexto levanta questões acerca dos limites da autonomia do paciente, os deveres éticos e legais do corpo médico e a necessidade do estudo científico de alternativas terapêuticas. Destarte, uma abordagem que considere a saúde física e mental dos pacientes é crucial para guiar as decisões médicas e jurídicas. A interseção entre sistemas legais e cuidados de saúde é fundamental para encontrar soluções humanitárias e científicas que respeitem a diversidade das crenças religiosas e defendem outras opções de tratamento. Avançando a discussão e estudos de novos tratamentos que respeitem a fé do paciente. Conclusão: Em suma, os princípios bioéticos devem auxiliar os médicos em sua rotina, ajudando a respeitar o paciente com suas crenças e tratando-o de maneira integral. O respeito deve estar ancorado em todas as situações junto com o paciente, percebendo a comunicação, o relacionamento interpessoal e o acesso à informação, como fatores facilitadores para esse ancoramento.

Introdução: A anemia falciforme (AF) é uma doença hereditária causada por uma mutação nos genes da cadeia beta-globina e detectada pela presença da hemoglobina S nas hemácias. No Brasil, ela compõe a condição genética crônica mais prevalente, sendo um relevante assunto de Saúde Pública, visto que os aspectos psicossociais da hemoglobinopatia influenciam a autoestima, imagem corporal, bem-estar emocional, formação da personalidade e relações pessoais do indivíduo afetado. Objetivos: Fornecer uma síntese acerca das informações existentes sobre os impactos psicossociais desse tipo de doença falciforme (DF), de forma a ressaltar a importância desses aspectos na doença hematológica em questão e ampliar a compreensão acerca da condição dos pacientes. Metodologia: O trabalho em questão trata-se de uma revisão integrativa com base no banco de dados das plataformas SciELO, PubMed e Portal Regional da Biblioteca Virtual em Saúde. A pesquisa utilizou os descritores “‘sickle cell anemia’ AND psychosocial”, selecionando artigos dos últimos dez anos, completos e em português e inglês. Excluíram-se os estudos que não abordavam a temática desta pesquisa em seus resumos. Resultados e discussão: Portadores da AF convivem com recorrentes quadros de crises e lesões de órgãos-alvo. A sintomatologia pode apresentar-se com crises vaso-oclusivas; dores agudas e crônicas; úlceras nos membros; manifestações pulmonares, neurológicas, genitourinárias, ósseas, cardiovasculares, hepatobiliares, oftálmicas e esplênicas. Essas alterações físicas cursam com distúrbios cognitivos e emocionais, os quais interferem no desenvolvimento psicossocial da população falciforme, com manifestações de tristeza, indiferença, angústia, impotência, falta de perspectiva e sensação de inutilidade, marcadas por quadros que restringem o cotidiano desses indivíduos. Dessarte, a impotência em que se encontram os pacientes culmina em quadros de transtornos mentais, como depressão, ansiedade, distimia e bipolaridade. Tal contexto desencadeia comportamentos de esquiva social, bem como problemas severos de baixo rendimento escolar e baixa autoestima, subsequentes das hospitalizações frequentes. Para além disso, a hemoglobinopatia não deixa de exercer a sua influência sobre os genitores do indivíduo afetado, incitando uma preocupação incessante diante das exigências cuidadosas que a condição requer. Nessa jornada, entrelaça-se uma teia de desafios financeiros decorrentes do tratamento médico, bem como restringe as atividades familiares, potencialmente dando origem a sentimentos de frustração e isolamento que permeiam a vida de todos os membros da família. Assim, constrói-se uma relação bidirecional entre a doença e as variadas desordens psicológicas, em que as complicações físicas da AF agravam o quadro psicológico do paciente, e vice-versa. Conclusão: Logo, diante da variedade de complicações causadas pela doença, faz-se necessária a constante atenção familiar e multiprofissional, com destaque para os psicólogos, com o objetivo de mitigar os sintomas e melhorar a qualidade de vida do paciente. Dessa maneira, o núcleo familiar no qual a hemoglobinopatia se faz presente é guiado pelas vicissitudes da doença, que reverberam no desenvolvimento psicossocial do indivíduo afetado. Ademais, fica claro que a avaliação específica de depressão em pacientes com anemia falciforme ainda é objeto de poucos estudos e seu diagnóstico é subestimado pelos profissionais de saúde.

Introdução: A doença crônica (DC), segundo a Organização Mundial da Saúde, se manifesta através de um processo gradual e de longa duração, acompanhando o indivíduo ao longo de sua existência. Neste contexto, as hemoglobinopatias e as demais DC hematológicas demandam um vínculo especial entre o paciente e o cuidador, tornando essencial que o profissional de saúde, seja ele um hematologista ou psicólogo, compreenda a subjetividade da experiência de adoecimento para cada pessoa, conforme a trajetória de vida e o histórico pessoal, o que torna este assunto de grande relevância nos campos referentes à saúde. Objetivos: Compreender as vicissitudes do adoecimento e da relação médico-paciente nos casos de doenças crônicas hematológicas, como anemia falciforme, talassemia, hemofilia e outros importantes diagnósticos relacionados. Métodso: Este trabalho foi produzido através de uma revisão bibliográfica sobre o tema, a partir de artigos em português e inglês, presentes nas plataformas SciELO e PubMed. Ademais, ele surgiu a partir da procura de acadêmicos de Medicina da Universidade Federal de Juiz de Fora pelo setor de psicologia da Fundação Hemominas/JFO para uma “Roda de Conversa”. Resultados e discussão: As pessoas com doenças crônicas vivenciam revolta pela limitação provocada, pois a vida se transforma juntamente com o corpo doente. A enfermidade pode parecer uma admissão de fraqueza e inferioridade, o que ocasiona o afastamento do convívio social para ocultar a doença, de forma que os pacientes se considerem vítimas de injustiças. Na esfera familiar, o responsável pelo cuidado dedica mais tempo ao membro que adoeceu, relegando os demais integrantes da família e as tarefas, fato que pode comprometer tanto o convívio familiar quanto o vínculo trabalhista do cuidador, em decorrência das frequentes idas a médicos, laboratórios e hospitais. No âmbito do profissional de saúde, deve-se ressaltar que os pacientes com DCs hematológicas demandam mais atenção e cuidado, devido à longitudinalidade do tratamento. Assim, o especialista é protagonista na transmissão de notícias e saberes técnicos, através da fala, de expressões corporais e emoções. De acordo com Freud, em “A Questão da Análise Leiga”, a palavra pode transmitir emoções e influenciar outras pessoas, de forma benéfica ou maléfica, o que reforça a necessidade de cautela na interação com pacientes crônicos. Por isso, Robert Buckman propõe, no livro “How to Break Bad News”, o protocolo SPIKES, um acrônimo que demonstra as etapas ideais para comunicar notícias ruins, com base na preparação, percepção, convite, conhecimento, emoções, estratégia e resumo, permitindo o aprimoramento das habilidades comunicativas. Todavia, a depender do estado de saúde do paciente, pode ser necessário que o especialista contente-se apenas em assisti-lo e em promover, na medida do possível, uma vida digna e confortável. Conclusão: Em suma, a conduta do profissional de saúde diante das doenças crônicas hematológicas deve ser pautada na sensibilidade, no respeito, na paciência, na flexibilidade para lidar com o imprevisto e na compreensão das diferentes formas de vivenciar a condição. Ao aliar conhecimento técnico e humanidade, os cuidadores tornam-se essenciais na jornada do paciente, auxiliando-os a enfrentar os desafios e a construir um caminho de superação e adaptação às novas circunstâncias. Assim, juntos, podem vislumbrar um horizonte de esperança e qualidade de vida, mesmo diante das adversidades impostas.

Introdução: Nas últimas décadas, a espiritualidade mostrou-se valiosa na prática clínica, principalmente na área dos cuidados paliativos. Nesse contexto, a realidade dos pacientes crônicos hematológicos é trazida à tona, devido à relevância dos aspectos psicossociais na eficácia e na adesão ao tratamento, visto que tais fatores influenciam a autoestima, o bem-estar emocional, a formação de personalidade e a manutenção das relações pessoais. Dessa forma, a adoção de uma abordagem integral que incorpora aspectos físicos, emocionais e espirituais pode contribuir para um melhor enfrentamento das adversidades e para uma consequente evolução do prognóstico. Objetivos: Compreender os benefícios da espiritualidade no tratamento e no suporte a pacientes hematológicos crônicos e discutir como os profissionais de saúde podem abordá-la de forma sensível e integrativa, visando enriquecer a compreensão acerca da condição desses pacientes. Métodos: O presente trabalho é uma revisão bibliográfica baseada no banco de dados das plataformas SciELO e PubMed. Para seleção do material, foram utilizados os descritores “spirituality”e “chronic disease”, selecionando artigos completos dos últimos dez anos, em português e inglês. Os estudos que não tratavam da temática desta pesquisa em seus resumos foram descartados. Resultados e discussão: Enquanto a religião é definida por um sistema de crenças e práticas de uma comunidade, a espiritualidade transcende a experiência humana, sendo fonte de apoio psicossocial, através da oferta de um propósito e significado em meio aos desafios impostos pela enfermidade. Enfrentar uma doença crônica, como leucemia, linfoma ou anemia aplásica, é uma jornada exaustiva e emocionalmente desafiadora, tanto para os pacientes quanto para os familiares. Nesse cenário, a espiritualidade permite a expressão de angústias e incertezas, proporcionando alívio emocional, conforto e esperança, o que fortalece a resiliência durante o processo. Além disso, a prática de meditação, oração ou outras formas de conexão espiritual pode auxiliar na redução do estresse e da ansiedade, frequentemente associados à experiência da dor crônica. Outrossim, a adesão ao tratamento pode ser favorecida, tendo em vista que pacientes que confiam na recuperação tendem a seguir as orientações médicas de forma mais diligente. Atualmente, a abordagem da espiritualidade é baseada nos questionários FICA e HOPE, que tratam a temática de forma ampla, a fim de traçar uma conduta que seja benéfica ao paciente. Contudo, vale ressaltar que a prática espiritual não substitui os tratamentos médicos tradicionais e que a psicoterapia deve ser empregada no acompanhamento desse paciente pelo psicólogo. Conclusão: Conclui-se que a espiritualidade é benéfica para os pacientes crônicos hematológicos e para o cuidado integral desses indivíduos. É fundamental que os profissionais da saúde estejam abertos a escutar questões espirituais de seus pacientes, respeitando a diversidade de crenças, a fim de garantir que a abordagem seja bem recebida. Ao adotar o tratamento holístico, cria-se um ambiente de cuidado mais empático, facilitando o enfrentamento dos desafios impostos pela doença e o alcance de uma melhor qualidade de vida e bem-estar emocional. Por fim, são necessárias pesquisas futuras para aprofundar os conhecimentos existentes e desenvolver intervenções mais eficazes que integrem a espiritualidade no cuidado em saúde.

Platelet-rich plasma (PRP) is gaining more and more attention in regenerative medicine as an innovative and efficient therapeutic approach. The regenerative properties of PRP rely on the numerous bioactive molecules released by the platelets: growth factors are involved in proliferation and differentiation of endothelial cells and fibroblasts, angiogenesis and extracellular matrix formation, while cytokines are mainly involved in immune cell recruitment and inflammation modulation. Attempts are ongoing to improve the therapeutic potential of PRP by combining it with agents able to promote regenerative processes. Two interesting candidates are ozone, administered at low doses as gaseous oxygen-ozone mixtures, and procaine. In the present study, we investigated the effects induced on platelets by the in vitro treatment of PRP with ozone or procaine, or both. We combined transmission electron microscopy to obtain information on platelet modifications and bioanalytical assays to quantify the secreted factors. The results demonstrate that, although platelets were already activated by the procedure to prepare PRP, both ozone and procaine induced differential morpho-functional modifications in platelets resulting in an increased release of factors. In detail, ozone induced an increase in surface protrusions and open canalicular system dilation suggestive of a marked α-granule release, while procaine caused a decrease in surface protrusions and open canalicular system dilation but a remarkable increase in microvesicle release suggestive of high secretory activity. Consistently, nine of the thirteen platelet-derived factors analysed in the PRP serum significantly increased after treatment with ozone and/or procaine. Therefore, ozone and procaine proved to have a remarkable stimulating potential without causing any damage to platelets, probably because they act through physiological, although different, secretory pathways.

Glioblastoma is a devastating form of brain cancer. To identify aspects of tumor heterogeneity that may illuminate drivers of tumor invasion, we created a glioblastoma tumor cell atlas with single-cell transcriptomics of cancer cells mapped onto a reference framework of the developing and adult human brain. We find that multiple GSC subtypes exist within a single tumor. Within these GSCs, we identify an invasive cell population similar to outer radial glia (oRG), a fetal cell type that expands the stem cell niche in normal human cortex. Using live time-lapse imaging of primary resected tumors, we discover that tumor-derived oRG-like cells undergo characteristic mitotic somal translocation behavior previously only observed in human development, suggesting a reactivation of developmental programs. In addition, we show that PTPRZ1 mediates both mitotic somal translocation and glioblastoma tumor invasion. These data suggest that the presence of heterogeneous GSCs may underlie glioblastoma's rapid progression and invasion.

Abstract Background The occurrence and timing of mycobacterial culture conversion is used as a proxy for tuberculosis treatment response. When researchers serially sample sputum during tuberculosis studies, contamination or missed visits leads to missing data points. Traditionally, this is managed by ignoring missing data or simple carry-forward techniques. Statistically advanced multiple imputation methods potentially decrease bias and retain sample size and statistical power. Methods We analyzed data from 261 participants who provided weekly sputa for the first 12 weeks of tuberculosis treatment. We compared methods for handling missing data points in a longitudinal study with a time-to-event outcome. Our primary outcome was time to culture conversion, defined as two consecutive weeks with no Mycobacterium tuberculosis growth. Methods used to address missing data included: 1) available case analysis, 2) last observation carried forward, and 3) multiple imputation by fully conditional specification. For each method, we calculated the proportion culture converted and used survival analysis to estimate Kaplan-Meier curves, hazard ratios, and restricted mean survival times. We compared methods based on point estimates, confidence intervals, and conclusions to specific research questions. Results The three missing data methods lead to differences in the number of participants achieving conversion; 78 (32.8%) participants converted with available case analysis, 154 (64.7%) converted with last observation carried forward, and 184 (77.1%) converted with multiple imputation. Multiple imputation resulted in smaller point estimates than simple approaches with narrower confidence intervals. The adjusted hazard ratio for smear negative participants was 3.4 (95% CI 2.3, 5.1) using multiple imputation compared to 5.2 (95% CI 3.1, 8.7) using last observation carried forward and 5.0 (95% CI 2.4, 10.6) using available case analysis. Conclusion We showed that accounting for missing sputum data through multiple imputation, a statistically valid approach under certain conditions, can lead to different conclusions than naïve methods. Careful consideration for how to handle missing data must be taken and be pre-specified prior to analysis. We used data from a TB study to demonstrate these concepts, however, the methods we described are broadly applicable to longitudinal missing data. We provide valuable statistical guidance and code for researchers to appropriately handle missing data in longitudinal studies.

In a trans-scalar perspective, the Bicocca district extends from the local NIL (Nucleo di Identità Locale) to part of Municipality 9, Sesto San Giovanni and Cinisello Balsamo. Recently, the University of Milan-Bicocca, as regards to the so-called ‘terza missione’, has remarked its role as a key-pole for the surrounding area by proposing research, educational (and orientation) activities, as well as institutional initiatives based in this post-industrial area of Milan. Within this scenario, our group was in charge of design-ing a project leading to an artistic image representing the district users’ sense of place. By combining geography of perception, urban sociology, participatory design and the flânerie approaches, we planned a working process starting from the ‘subjective production of images’ by the district’s users and inhabitants. The project was structured in two phases: (1) December 2020 – January 2021: we organised two workshops by inviting groups of students, teachers and shop owners and working on their mental maps to construct a final image resulting from the two teams’ negotiation processes. The reading of the maps was initially inspired by the categories identified by Kevin Lynch (1962) and then moved on to a process of co-construction of a collective image; (2) March 2021: we shared the visual body with a professional illustrator (Carlo Stanga) entrusted with the mandate to translate the images into an artistic product. The essay discusses the visual representation of users’ sense of place and the potential legacy upon communication strategies, way-findings tools and education projects.

Abstract The D-aspartate oxidase (DDO) gene encodes the enzyme responsible for the catabolism of D-aspartate, an atypical amino acid enriched in the mammalian brain and acting as an endogenous NMDA receptor agonist. Considering the key role of NMDA receptors in neurodevelopmental disorders, recent findings suggest a link between D-aspartate dysmetabolism and schizophrenia. To clarify the role of D-aspartate on brain development and functioning, we used a mouse model with constitutive Ddo overexpression and D-aspartate depletion. In these mice, we found reduced number of BrdU-positive dorsal pallium neurons during corticogenesis, and decreased cortical and striatal gray matter volume at adulthood. Brain abnormalities were associated with social recognition memory deficit at juvenile phase, suggesting that early D-aspartate occurrence influences neurodevelopmental related phenotypes. We corroborated this hypothesis by reporting the first clinical case of a young patient with severe intellectual disability, thought disorders and autism spectrum disorder symptomatology, harboring a duplication of a chromosome 6 region, including the entire DDO gene.

The Socotra Archipelago (Yemen) is an interesting biodiversity hotspot, with a significant proportion of endemic species that have evolved to survive in an arid subtropical environment, inscribed as a World Heritage Site by UNESCO. The terrestrial ecosystems of Socotra face several threats, including climate change, overgrazing and soil degradation. Socotra Island has four endemic species of the genus Commiphora (Burseraceae). Little is known about their local distribution and ecology, yet these trees could be useful indicator species. Our study focuses on the distribution and niche characterisation of the four endemic Commiphora species of Socotra and how climate change may affect them. The aim is to improve insights into their habitats and to provide an essential basis for future local management plans and ecological restoration. We compared the current distribution with the forecasted potential distribution under a CMIP6 (Coupled Model Intercomparison Project) climate scenario, allowing us to define target conservation areas and assess potential local extinction risks. To achieve this, we collected distribution data in the field throughout Socotra Island, covering the current distribution ranges of the four species. To assess the potential distribution of these species, we applied three models (GAM, MaxEnt, RandomForest) using bioclimatic, topographic and soil variables. Forecasts under a climate change scenario were made using bioclimatic variables from the CMCC-CESM2 climate model for two different socioeconomic pathways. The distribution of three endemic Socotran Commiphora is mainly correlated to clay content in the soil and winter precipitation, while C. socotrana is affected by seasonal precipitation and temperature. Under different potential future climate scenarios, the distribution of C. ornifolia is predicted to remain stable or increase, while C. parvifolia distribution could increase, yet C. planifrons and C. socotrana are predicted to undergo a strong reduction of suitable areas and an upward shift in the mountains. Our results highlight that it is essential to conserve the unique terrestrial ecosystems in Socotra and to preserve these endemic trees which have a wide range of ecosystem services. Updates on the predicted extinction risk assessment are fundamental to understand conservation priorities and strategize future actions to ensure the persistence of Socotran myrrh trees and other endangered endemic tree taxa on the island.

Allergic contact dermatitis (ACD) is a common inflammatory skin disease that, especially when the condition becomes chronic, has a high impact on the quality of life and represents a significant disease burden. ACD represents a type IV delayed-type hypersensitivity reaction that is triggered by contact with an allergen in previously sensitized individuals through the activation of allergen-specific T cells. In the acute phase, it is characterized by eczematous dermatitis, which presents with erythema, edema, vesicles, scaling, and intense itch. Non-eczematous clinical forms are also described (lichenoid, bullous, and lymphomatosis). Lichenification is the most common clinical picture in the chronic phase if the culprit allergen is not found or eliminated. ACD can be associated with both occupational and non-occupational exposure to allergens, representing approximately 90% of occupational skin disorders along with irritant contact dermatitis. Patch testing with suspected allergens is required for a diagnosis. Metals, especially nickel, fragrance mix, isothiazolinones, and para-phenylenediamine, are the most commonly positive allergens in patients patch tested for suspected ACD. The treatment goal is to avoid contact with the culprit agent and use topical and/or systemic corticosteroid therapy.

Recent works demonstrated the existence of a double-descent phenomenon for the generalization error of neural networks, where highly overparameterized models escape overfitting and achieve good test performance, at odds with the standard bias-variance trade-off described by statistical learning theory. In the present work, we explore a link between this phenomenon and the increase of complexity and sensitivity of the function represented by neural networks. In particular, we study the Boolean mean dimension (BMD), a metric developed in the context of Boolean function analysis. Focusing on a simple teacher-student setting for the random feature model, we derive a theoretical analysis based on the replica method that yields an interpretable expression for the BMD, in the high dimensional regime where the number of data points, the number of features, and the input size grow to infinity. We find that, as the degree of overparameterization of the network is increased, the BMD reaches an evident peak at the interpolation threshold, in correspondence with the generalization error peak, and then slowly approaches a low asymptotic value. The same phenomenology is then traced in numerical experiments with different model classes and training setups. Moreover, we find empirically that adversarially initialized models tend to show higher BMD values, and that models that are more robust to adversarial attacks exhibit a lower BMD.

INFN has been running a distributed infrastructure (the Tier-1 at Bologna-CNAF and 9 Tier-2 centres) for more than 20 years which currently offers about 150000 CPU cores and 120 PB of space both in tape and disk storage, serving more than 40 international scientific collaborations. This Grid-based infrastructure was augmented in 2019 with the INFN Cloud: a production quality multi-site federated Cloud infrastructure, composed by a core backbone, and which is able to integrate other INFN sites and public or private Clouds as well. The INFN Cloud provides a customizable and extensible portfolio offering computing and storage services spanning the IaaS, PaaS and SaaS layers, with dedicated solutions to serve special purposes, such as ISO-certified regions for the handling of sensitive data. INFN is now revising and expanding its infrastructure to tackle the challenges expected in the next 10 years of scientific computing adopting a “cloud-first” approach, through which all the INFN data centres will be federated via the INFN Cloud middleware and integrated with key HPC centres, such as the pre-exascale Leonardo machine at CINECA. In such a process, which involves both the infrastructures and the higher level services, initiatives and projects such as the "Italian National Centre on HPC, Big Data and Quantum Computing" (funded in the context of the Italian "National Recovery and Resilience Plan") and the Bologna Technopole are precious opportunities that will be exploited to offer advanced resources and services to universities, research institutions and industry. In this paper we describe how INFN is evolving its computing infrastructure, with the ambition to create and operate a national vendorneutral, open, scalable, and flexible "datalake" able to serve much more than just INFN users and experiments.

During future space missions, astronauts will be exposed to cosmic radiation and microgravity (μG), which are known to be health risk factors. To examine the differentially expressed genes (DEG) and their prevalent biological processes and pathways as a response to these two risk factors simultaneously, 1BR-hTERT human fibroblast cells were cultured under 1 gravity (1G) or simulated μG for 48 h in total and collected at 0 (sham irradiated), 3 or 24 h after 1 Gy of X-ray or Carbon-ion (C-ion) irradiation. A three-dimensional clinostat was used for the simulation of μG and the simultaneous radiation exposure of the samples. The RNA-seq method was used to produce lists of differentially expressed genes between different environmental conditions. Over-representation analyses were performed and the enriched biological pathways and targeting transcription factors were identified. Comparing sham-irradiated cells under simulated μG and 1G conditions, terms related to response to oxygen levels and muscle contraction were identified. After irradiation with X-rays or C-ions under 1G, identified DEGs were found to be involved in DNA damage repair, signal transduction by p53 class mediator, cell cycle arrest and apoptosis pathways. The same enriched pathways emerged when cells were irradiated under simulated μG condition. Nevertheless, the combined effect attenuated the transcriptional response to irradiation which may pose a subtle risk in space flights.

The ex vivo treatment of a limited volume of blood with gaseous oxygen–ozone (O2–O3) mixtures and its rapid reinfusion into the patient is a widespread medical procedure. O3 instantly reacts with the blood’s antioxidant systems, disappearing before reinfusion, although the molecules formed act as messengers in the organism, inducing multiple antioxidant and anti-inflammatory responses. An appropriate dose of O3 is obviously essential to ensure both safety and therapeutic efficacy, and in recent years, the low-dose O3 concept has led to a significant reduction in the administered O3 concentrations. However, the molecular events triggered by such low concentrations in the blood still need to be fully elucidated. In this basic study, we analysed the molecular modifications induced ex vivo in sheep blood by 5 and 10 µg O3/mL O2 by means of a powerful metabolomics analysis in association with haemogas, light microscopy and bioanalytical assays. This combined approach revealed increased oxygenation and an increased antioxidant capacity in the O3-treated blood, which accorded with the literature. Moreover, original information was obtained on the impact of these low O3 concentrations on the metabolic pathways of amino acids, carbohydrates, lipids and nucleotides, with the modified metabolites being mostly involved in the preservation of the oxidant–antioxidant balance and in energy production.

Dietary consumption of olive oil represents a key pillar of the Mediterranean diet, which has been shown to exert beneficial effects on human health, such as the prevention of chronic non-communicable diseases like cancers and neurodegenerative diseases, among others. These health benefits are partly mediated by the high-quality extra virgin olive oil (EVOO), which is produced mostly in Mediterranean countries and is directly made from olives, the fruit of the olive tree (Olea europaea L.). Preclinical evidence supports the existence of antioxidant and anti-inflammatory properties exerted by the polyphenol oleocanthal, which belongs to the EVOO minor polar compound subclass of secoiridoids (like oleuropein). This narrative review aims to describe the antioxidant and anti-inflammatory properties of oleocanthal, as well as the potential anticancer and neuroprotective actions of this polyphenol. Based on recent evidence, we also discuss the reasons underlying the need to include the concentrations of oleocanthal and other polyphenols in the EVOO’s nutrition facts label. Finally, we report our personal experience in the production of a certified organic EVOO with a “Protected Designation of Origin” (PDO), which was obtained from olives of three different cultivars (Rotondella, Frantoio, and Leccino) harvested in geographical areas located a short distance from one another (villages’ names: Gorga and Camella) within the Southern Italy “Cilento, Vallo di Diano and Alburni National Park” of the Campania Region (Province of Salerno, Italy).

Abstract Runners were classified using their duty factor (DF) and using their foot-strike pattern (FSP; rearfoot, midfoot, or forefoot strikers), determined from their foot-strike angle (FSA). High and low DF runners showed different FSPs but DF was assumed to not only reflect what happens at initial contact with the ground (more global than FSP/FSA). Hence, FSP and DF groups should not necessarily be constituted by the same runners. However, the relation between FSP and DF groups has never been investigated, leading to the aim of this study. One hundred runners ran at 9, 11, and 13 km/h. Force data (1000 Hz) and whole-body kinematics (200 Hz) were acquired by an instrumented treadmill and optoelectronic system and were used to classify runners according to their FSA and DF. Weak correlations were obtained between FSA and DF values and a sensitivity of 50% was reported between FSP and DF groups, i.e., only one in two runners was attributed to the DF group supposedly corresponding to the FSP group. Therefore, ‘local’ FSP/FSA and DF do not represent similar running pattern information when investigated at the individual level and DF should be preferred to FSP/FSA when evaluating the global running pattern of a runner.