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The construction sector, also thanks to digital implementation, can contribute significantly to the control and reduction of the environmental impacts of building products and components. This article presents an open and inclusive workflow to assess environmental sustainability starting from Building Information Modelling in IFC format integrated with data on environmental impacts. By simplifying the readability of the data and exploiting the BIM model to highlight strengths and weaknesses in the life cycle of a window, a prototype software application has been developed, aiming to encourage not only conscious choices by clients but also sustainable innovations by manufacturers of building materials and components.

Successfully integrating transcriptomic experiments is a challenging task with the ultimate goal of analyzing gene expression data in the broader context of all available measurements, all from a single point of access. In its second major release VESPUCCI, the integrated database of gene expression data for grapevine, has been updated to be FAIR-compliant, employing standards and created with open-source technologies. It includes all public grapevine gene expression experiments from both microarray and RNA-seq platforms. Transcriptomic data can be accessed in multiple ways through the newly developed COMPASS GraphQL interface, while the expression values are normalized using different methodologies to flexibly satisfy different analysis requirements. Sample annotations are manually curated and use standard formats and ontologies. The updated version of VESPUCCI provides easy querying and analyzing of integrated grapevine gene expression (meta)data and can be seamlessly embedded in any analysis workflow or tools. VESPUCCI is freely accessible and offers several ways of interaction, depending on the specific goals and purposes and/or user expertise; an overview can be found at https://vespucci.readthedocs.io/.

Manifestações neurológicas ocorrem em aproximadamente 30% dos pacientes com endocardite infecciosa, sendo a meningite bacteriana responsável por 7% destas, com isolamento do microorganismo em cultura de liquor ainda mais raro. Complicações neurológicas adicionais podem ocorrer, como acidente vascular cerebral isquêmico, hemorragia intracraniana, abscesso cerebral e aneurisma micótico. Staphylococcus aureus e Streptococcus pneumoniae são os isolados mais frequentes. O relato de caso envolve a análise do diagnóstico e condutas adotadas em paciente atendida no São Bernardo Apart Hospital, Colatina-ES, Brasil, durante os meses de outubro e novembro de 2019. O caso clínico relata paciente de 88 anos, feminino, que deu entrada em unidade de terapia intensiva com sinais de acometimento do sistema nervoso central, disfasia, delirium e ausência de febre. Além disso apresentava insuficiência cardíaca descompensada e insuficiência renal crônica agudizada. Para descartar diagnósticos diferenciais foram solicitados exames de imagem (ecocardiografia transesofágica, ressonância magnética e tomografia computadorizada de crânio e abdome), exames laboratoriais (hemograma, hemocultura e cultura de líquor). Aos exames foram verificados os seguintes diagnósticos: vegetações em valva aórtica sugestivas de endocardite infecciosa, evoluindo com embolização séptica para sistema nervoso central, sendo quatro hemoculturas e duas culturas de líquor positivas para Staphylococcus aureus sensíveis a meticilina. A presença de imagens compatíveis com a embolização micótica na ressonância magnética de encéfalo, de acordo com as diretrizes, infere na necessidade de tratamento cirúrgico, porém, devido ao elevado risco perioperatório, optou-se apenas pelo tratamento conservador com antibioticoterapia, tendo inicialmente realizado ceftriaxone empírico e após resultados das culturas foi substituído por oxaciclina. Meningite bacteriana isolada como manifestação de endocardite é raro e é uma difícil suspeita diagnóstica. A paciente continuou com culturas positivas para S. aureus por tempo prolongado. O quadro evoluiu com dissecção de aorta por êmbolos micóticos, o que a levou ao óbito. A suspeita clínica precoce associada aos exames laboratoriais e de imagem foram importantes para o diagnóstico rápido e para início da terapia correta. Entretanto, devido à alta morbi-motalidade do quadro apresentado, a paciente evoluiu a óbito devido complicações.

Background Italy records very alarming levels antimicrobial resistance (AMR), so a National Action Plan on Antimicrobial resistance (PNCAR) was developed, adopting the AMR European Union’s recommendations based on the results of the ECDC site visit of January 2017. For achieving PNCAR objectives, it is necessary to support and harmonize the implementation of recommendations in all the different healthcare levels (regional authorities and local trusts), so the SPiNCAR project was launched to create a tool for reaching this goal. Methods We developed a framework based on a scientific literature and national and international guidelines. Firstly, we identified the major intervention areas for tackling AMR, then, for each area, we built a set of standards, both for regional authorities than for local trusts. Every standard is composed by a set of essential and additional criteria, which refer to a minimum or supplemental performance level respectively. The contents were firstly discussed by the project’s team during face-to-face kick-off meetings, then confirmed with Delphi methodology and finally validated through a pilot study. Results The final framework consists of seven different areas that reflect the PNCAR structure: Governance, Surveillance and Monitoring, Appropriate Use of antimicrobials, Healthcare-associated Infections (HAIs) control and prevention, Education and Training, Alliance among Stakeholders, Implementation. The total number of standards for the regional framework was 34 with 264 criteria and for the local version 36 criteria with 279 standards. Conclusion The ongoing use of this tool, developed on international evidences and recommendations that were tailored on the Italian specific context, allows monitoring the improvement achieved over time and plan the next steps.

The analgesic specificity of navicular bursa (NB) anesthetic infiltration is still questionable. The study aimed to determine the mechanical nociceptive threshold of non-specific analgesia in the dorsal lamellar stratum, as well as in the sole, coronary band, and heel bulbs of the hoof, after navicular bursa anesthetic infiltration. Six healthy horses with no clinical or radiographic changes of the digits and no communication between the NB and the distal interphalangeal joint, were used. After random selection, the NB of one of the forelimbs was infiltrated with 2% lidocaine and the contralateral one with lactated ringer’s solution. Contrast was added to confirm radiographic infiltration. The mechanical nociceptive threshold was determined using a portable pressure dynamometer, before and at various times after the infiltration, in 10 points of the hoof. The effects of time and treatment were verified by ANOVA (P0.05) in all regions evaluated. However, in one of the six hooves that receives lidocaine, complete absence of response to the painful stimulus (maximum force of 6 Kg over an area of 38.46 mm2, for a maximum of 4 seconds) was observed in the dorsal lamellae between 30 and 60 min after infiltration. In conclusion, lidocaine infiltration of NB did not promote significant increases in the nociceptive threshold of the sole, coronary band, bulbs of the heel and dorsal lamellae clinically healthy horses. However, the occurrence of analgesia in one of the six hooves subjected to NB anesthesia indicates that the technique may not be fully specific in few horses.

The digitalization of the process for building permit (involving the use of 3D information systems) is seen as a priority in a wide part of the world. Since it is a very multidisciplinary use case, involving a variety of stakeholders tackling complex issues and topics, some of them joined their efforts and skills in the European Network for Digital Building Permit. The initial activity of the network, after a review of on-going experiences, was a workshop to share knowledge about the topics involved and to identify the main ambitions of the network with respect to three pillars (i.e. Process – Rules and Requirements – Technology) and the related requirements. It was achieved through a collective brainstorming activity guided by digital tools, whose results were further analysed in a post-processing phase. Such results are presented in this paper and will be the base for planning the future network activity.

Predicting accurate remaining useful life (RUL) of components plays a crucial role in making optimal decision for maintenance management. As sensor technology developed, multiple heterogeneous sensors are being used to collect information for monitoring the condition of components. Deep learning architectures, such as convolutional neural network (CNN) and long short term memory (LSTM), can be considered as a successful end-to-end framework to predict RUL from the multivariate time series collected by those sensors. For that, we employ an architecture combining the parallel branch of CNN in series with LSTM which is referred as multi-head CNN-LSTM. Furthermore, we propose a combination of the network with time series prediction error analysis (PEA). The prediction errors at entire time cycles of each time series are estimated by recursive least squares (RLS) and single exponential smoothing (SES) respectively. We analyze each of the two sequences of prediction errors with exponentially weighted moving average (EWMA) and combine them with Fisher's method. Finally, the output of the PEA is fed into the CNN-LSTM network as the additional input. We evaluate the performance of our methods on widely used C-MAPSS dataset. The experimental results suggest that using the PEA improves the performance of the deep learning-based RUL prediction model. Compared to other methods in recent literature, the proposed method achieves the state-of-the-art result on one sub-dataset and very competitive results on the others. In addition, the proposed method shows promising results in the consecutive RUL prediction following the degradation process of components.

Abstract Background The coverage for influenza vaccination among healthcare workers (HCWs) is inadequate in many countries despite strong recommendations; is there evidence that influenza vaccination is effective in preventing absenteeism? Aim of the study is to evaluate the influenza vaccination coverage and its effects on absences from work among HCWs of an Italian academic healthcare trust during the 2017–2018 influenza season. Methods We performed a retrospective study to identify predictive characteristics for vaccination, and a retrospective cohort study to establish the effect of vaccination on absences among the vaccinated and non-vaccinated cohorts between December 2017 and May 2018. Overall absence rates over the whole observation period and sub-rates over 14-days intervals were calculated; then comparison between the two groups were conducted applying Chi-square test. Results Influenza vaccination coverage among 4419 HCWs was 14.5%. Age, university degree, medical care area and physician profile were positively associated with vaccine uptake. Globally during influenza season non-vaccinated HCWs lost 2.47/100 person-days of work compared to 1.92/100 person-days of work among vaccinated HCWs (p

Abstract Background Silver-Russell Syndrome (SRS) is a genetic disorder characterized by intrauterine and postnatal growth restriction and normal head circumference with consequent relative macrocephaly. Addictional findings are protruding forehead in early life, body asymmetry (of upper and lower limbs) and substantial feeding difficulties. Although several genetic mechanisms that cause the syndrome are known, more than 40% of patients with a SRS-like phenotype remain without an etiological diagnosis. In the last few years, different clinical reports have suggested that mutations or deletions of the HMGA2 gene can be responsible for a SRS-like phenotype in patients with negative results of the common diagnostic tests for this syndrome. Case presentation We present a 3-year-old male patient with clinical diagnosis of Silver-Russell Syndrome (SRS) associated with a de novo heterozygous deletion of the long arm of the chromosome 12 (12q14.3) encompassing the HMGA2 gene. Conclusions Our report confirms the etiological role of HMGA2 as a disease gene in the development of a SRS-like phenotype.

Degenerative processes of the intervertebral disc (IVD) and cartilaginous endplate lead to chronic spine pathologies. Several studies speculated on the intrinsic regenerative capacity of degenerated IVD related to the presence of local mesenchymal progenitors. However, a complete characterisation of the resident IVD cell populations, particularly that isolated from the endplate, is lacking. The purpose of the present study was to characterise the gene expression profiles of human nucleus pulposus (NPCs), annulus fibrosus (AFCs) and endplate (EPCs) cells, setting the basis for future studies aimed at identifying the most promising cells for regenerative purposes. Cells isolated from NP, AF and EP were analysed after in vitro expansion for their stemness ability, immunophenotype and gene profiles by large-scale microarray analysis. The three cell populations shared a similar clonogenic, adipogenic and osteogenic potential, as well as an immunophenotype with a pattern resembling that of mesenchymal stem cells. NPCs maintained the greatest chondrogenic potential and shared with EPCs the loss of proliferation capability during expansion. The largest number of selectively highly expressed stemness, chondrogenic/tissue-specific and surface genes was found in AFCs, thus representing the most promising source of tissue-specific expanded cells for the treatment of IVD degeneration.

The aim of the present study is to investigate the effect of κ-casein B content in milk on the yield of high-moisture mozzarella cheese. The study was carried out by monitoring the production of eight mozzarella cheese batches at four cheesemaking factories. At each factory, two cheesemaking trials were performed in parallel: one using bulk milk from Italian Brown cattle and the other using bulk milk from Italian Friesian cattle. The average κ-casein B content was 0.04 g per 100 g in the Italian Friesian cows’ milk, whereas it was four times higher in the Italian Brown cows’ milk, reaching values of 0.16 g per 100 g. Both the κ-casein B content and κ-casein B to casein ratio were positively correlated with actual cheese yield. Both parameters showed correlation coefficient values over 0.9, higher than for any other protein fraction. The influence of the level of κ-casein on the increase of the yield is probably due to smaller and more homogeneous micelles, with more efficient rennet coagulation. Consequently, milk with higher κ-casein B content produces a more elastic curd that withstands better the technological treatments and limits losses during curd mincing and stretching. In conclusion, the Italian Brown cows’ milk, characterized by higher κ-casein content than the Italian Friesian’s one, allowed a yield increase of about 2.65 %, which is a very relevant result for both farms and cheesemaking factories.

A presente investigação compreende a análise de conteúdos de História da Ciência em livros didáticos de Ciências utilizados em escolas do Ensino Fundamental, anos iniciais. Especificamente, constituíram-se objeto de estudo os livros didáticos dos 5os anos selecionados para uso em sala de aula pelos municípios de Cascavel, Paraná (BR) e de Kaohsiung (高雄), Taiwan(台灣). Norteados pelas seguintes problemáticas: “quais são os conteúdos de História das Ciências e como eles são abordados nesses livros didáticos”. Embasados no instrumento analítico elaborado por Laurinda Leite, procedemos a argumentação a respeito de três dimensões categóricas: tipo e organização da informação histórica; propostas de atividades envolvendo a História da Ciência; e status do conteúdo histórico. Os resultados, emanados da pesquisa qualitativa dos livros de dois países, indicaram a presença de conteúdos sobre a História das Ciências em todos os livros analisados, tendo, no entanto, especificidades quanto à apresentação desses conteúdos. No estudo foi possível ainda tecer considerações sobre o potencial dos estudos comparativos para compreensão das concepções sobre o ensino de Ciência assumido nesses países.

Abstract Background Hirschsprung Disease (HSCR) is a congenital defect of the intestinal innervations characterized by complex inheritance. Many susceptibility genes including RET, the major HSCR gene, and several linked regions and associated loci have been shown to contribute to disease pathogenesis. Nonetheless, a proportion of patients still remains unexplained. Copy Number Variations (CNVs) have already been involved in HSCR, and for this reason we performed Comparative Genomic Hybridization (CGH), using a custom array with high density probes. Results A total of 20 HSCR candidate regions/genes was tested in 55 sporadic patients and four patients with already known chromosomal aberrations. Among 83 calls, 12 variants were experimentally validated, three of which involving the HSCR crucial genes SEMA3A/3D, NRG1, and PHOX2B. Conversely RET involvement in HSCR does not seem to rely on the presence of CNVs while, interestingly, several gains and losses did co-occur with another RET defect, thus confirming that more than one predisposing event is necessary for HSCR to develop. New loci were also shown to be involved, such as ALDH1A2, already found to play a major role in the enteric nervous system. Finally, all the inherited CNVs were of maternal origin. Conclusions Our results confirm a wide genetic heterogeneity in HSCR occurrence and support a role of candidate genes in expression regulation and cell signaling, thus contributing to depict further the molecular complexity of the genomic regions involved in the Enteric Nervous System development. The observed maternal transmission bias for HSCR associated CNVs supports the hypothesis that in females these variants might be more tolerated, requiring additional alterations to develop HSCR disease.

Abstract Background Simulation in laparoscopic surgery is nowadays recognized as a valid instrument for learning and training surgeons in different procedures. However, its role as evaluation test and self-assessment tool to verify basic surgical skills is still under discussion. Methods Thirty-three residents in obstetrics and gynecology at University of Pisa, Italy were recruited, and they received a simulation program consisting of 5 tasks. They had to perform basic laparoscopic surgery maneuvers as creating pneumoperitoneum, positioning trocars under vision, demonstrating the appropriate use of dominant and non-dominant hand and making single stitch and knot. They were evaluated with a modified OSATs scale. Results Senior trainees had better score than junior trainees (p value

The Amazon rainforest has 90% of Brazil's total kaolin reserves, and its mining is of great economic interest. However, the intense kaolin activity produces large quantities of deposited waste in tailing dams, generating a tremendous environmental and local economic liability. Such wastes have no economic value, but their high kaolinite composition can be interesting for the cement industry. Thus, this study aimed to valorize such material as a potential Supplementary Cementitious Material (SCM) in low-carbon cements. The calcined kaolin waste (KAW) was used with limestone and gypsum as clinker substitutes. Its performance was compared with calcined pure kaolin (KA) and an inert material (quartz powder, QP). The cements were evaluated regarding their setting times, water demand, rheological behavior, hydration and compressive strength at different ages. The most important results of the KAW are related to its better rheological behavior compared to KA and closer to QP when used in cement formulations. The kaolinite clay content played a significant role in the fresh properties assessed as well. The microstructural and mechanical performance of KAW cement is similar to KA, which highlights comparable reactivity. This study brings a new insight into the potential use of kaolinite-rich waste from the mining sector as SCM to be used in the local infrastructure of the Amazon region.

This study aims to evaluate the influence of low-grade local materials as clinker substitute in ternary cements, with calcined clay (30 wt%) and limestone (15 wt%), also known as LC³ cements. A coal mining waste (based on 35 wt% kaolinite content, AR) and a dolomitic limestone (LLS) were compared to more pure materials such as natural clay (constituted by 83% kaolinite content, NC) and high-grade limestone (HLS), respectively. LC³ cements were compared to reference system (45 wt% quartz filler instead of limestone and calcined clays), as well as a fly ash blended cement (40 wt% fly ash, 40FA). Hydration kinetics, water demand, plastic viscosity, and yield stress were evaluated in a fresh state. The fineness of the calcined clays and limestone had a greater impact on the water demand and thixotropy of the pastes than their mineralogical compositions. However, the higher kaolinite content of NC led to higher pozzolanic activity, greater formation of carboaluminate type phases, and compressive strength than LC3 cements with AR. The HLS and LLS had similar impact on the proprieties assessed despite their different mineralogical composition. Thus, both low-grade materials are feasible as raw materials for the production of LC³ type cements with similar performance when compared to conventional cements.

SARS-CoV-2 management in Emergency Department: risk stratification and care setting identification proposal based on first pandemic wave in Pisa University Hospital Background: COVID-19 patients require early treatment and admission to an appropriate care setting, considering possible rapid and unpredictable to Severe Acute Respiratory Syndrome. Objective: A flow-chart was developed by a multidisciplinary team of Emergency Department (ED) clinicians, intensivists and radiologists aiming to provide tools for disease severity stratification, appropriate ventilation strategy and hospitalization setting identification. Methods: We conducted a retrospective application of our model on 313 hospitalized patients at Pisa University Hospital including 222 patients admitted to ED for respiratory failure between March and April 2020. Risk stratification score was based on respiratory and chest imaging parameters, while management strategy on comorbidities and age. Results: Age, comorbidities, clinical respiratory and arterial blood gas parameters, semi-quantitative chest computed tomography score were significant predictors of mortality (p

RESUMO O objetivo deste trabalho foi verificar se a oferta de disciplinas voltadas à Saúde Coletiva se faz presente, ou não, nos cursos de Educação Física das Universidades Públicas do Rio de Janeiro, bem como, a abordagem de “saúde” na formação destas instituições. Para tanto, utilizou-se a análise crítico-documental das ementas que compõem as matrizes dos cursos. Observou-se a predominância de disciplinas biológicas associadas à saúde e, no que tange às demandas coletivas, as poucas disciplinas e seus respectivos conteúdos não se aprofundam nestas temáticas, negligenciando temas como o Sistema Único de Saúde, a Educação para a Saúde e a atuação em equipes multidisciplinares.

Resumo Introdução A utilização dos bens e serviços de saúde é considerada uma expressão positiva de acesso, influenciada por diversos fatores. Objetivo Analisar o acesso aos serviços e bens em saúde bucal, com seus fatores determinantes, entre escolares de 7-10 anos. Material e método Estudo seccional realizado com escolares de amostra probabilística por conglomerado. Os dados foram coletados através de formulário aplicado às crianças e questionário enviado aos pais/responsáveis. O desfecho de interesse foi o acesso aos bens e serviços de saúde odontológicos, a partir das variáveis “primeira consulta odontológica” e “posse de escova dental própria”. As variáveis independentes (características infantis, maternas e socioeconômicas) que apresentaram significância estatística ≤0,10, na análise bivariada, foram incluídas no modelo de Regressão Logística Multivariada. O nível de significância adotado no modelo final foi de 5%. Resultado Associaram à posse de escova dental: idades de 8 (OR=3,303; IC95%= 1,135 – 9,610), 9 (OR=3,452; IC95% = 1,176 - 10,137) e 10 anos (OR= 6,901; IC95% = 1,468 – 32,434); tabagismo materno (OR=4,509; IC95% = 2,021-10,060). Associados à primeira consulta odontológica: idades de 9 (OR=2,321; IC95% = 1,340 – 4,022) e 10 anos (OR= 3,155; IC95% = 1,687 – 5,899); escola privada (OR=3,691; IC95% = 1,343-10,145); dois ou mais quartos na residência (OR: 3,691; IC95% = 1,343 – 10,145) e posse de escova dental própria (OR=2,065; IC95% = 1,009 – 4,226). Conclusão Os resultados apontam para desigualdade no acesso à saúde odontológica. Crianças mais velhas, com mães não fumantes e melhores condições socioeconômicas apresentam maior acesso aos serviços e bens em saúde bucal.

Com o advento da pandemia do novo coronavírus, dentre os meios de comunicação com a população destacam-se as redes sociais. Assim, o objetivo deste artigo foi analisar as publicações do Instagram® do Conselho Federal de Educação Física do Brasil durante a pandemia, enfatizando as atividades de comunicação com os profissionais de educação física e a população geral no combate ao coronavírus. Realizou-se uma investigação netnográfica, com análise qualitativa das publicações. Entre 11 de março de 2020 a 01 de julho de 2021, 96 postagens foram feitas na rede social. Dessas, 53 estavam vinculadas à pandemia. Percebeu-se um forte discurso biomédico envolvendo a saúde, especialmente nos episódios de uma websérie lançada para reforçar a importância da atividade física durante a pandemia. Além disso, a cobrança dos profissionais de Educação Física por assistência do conselho foi recorrente. Ademais, houve reduções significativas de publicações envolvendo a pandemia no período em que o país atingiu o maior número de mortos. Embora existam vastas informações nas publicações reforçando a importância dos exercícios físicos para a saúde, esperava-se do Conselho abordagens mais coletivas e intensificação da divulgação sobre os cuidados necessários para o enfrentamento da pandemia, como, por exemplo, a vacinação

Purpose: The goal of this study on Spinal Cord Injury (SCI) patients with cervical or thoracic lesion was to assess whether disturbances of ANS control, according to location, might differently affect vagal and sympatho-vagal markers during sleep and orthostatic challenge. We analyzed with linear and nonlinear techniques beat-by-beat RR and arterial pressure (and respiration) variability signals, extracted from a polysomnographic study and a rest–tilt test. We considered spontaneous or induced sympathetic excitation, as obtained shifting from non-REM to REM sleep or from rest to passive tilt. We obtained evidence of ANS cardiac (dys)regulation, of greater importance for gradually proximal location (i.e., cervical) SCI, compatible with a progressive loss of modulatory role of sympathetic afferents to the spinal cord. Furthermore, in accordance with the dual, vagal and sympathetic bidirectional innervation, the results suggest that vagally mediated negative feedback baroreflexes were substantially maintained in all cases. Conversely, the LF and HF balance (expressed specifically by normalized units) appeared to be negatively affected by SCI, particularly in the case of cervical lesion (group p = 0.006, interaction p = 0.011). Multivariate analysis of cardiovascular variability may be a convenient technique to assess autonomic responsiveness and alteration of functionality in patients with SCI addressing selectively vagal or sympathetic alterations and injury location. This contention requires confirmatory studies with a larger population.

Background: Turner syndrome is a rare genetic condition in which a female is partly or completely missing an X chromosome. Signs and symptoms vary among those affected. In fetuses that survive at birth and without congenital malformations, the prognosis is usually positive, but it has high lethality in utero, especially in the first trimester of pregnancy. Methods: We report a case of monosomy X detected during a prenatal diagnosis for beta thalassemia on coelomic fluid (CF) at the VIII week of gestation. Beta globin gene analysis, whole genome amplification (WGA), quantitative fluorescent PCR and array comparative genomic hybridization (array-CGH) were performed on DNA extracted from CF. Results: A monoallelic pattern of all Short Tandem Repeats mapped on the X chromosome was found and array-CGH performed on WGA from a few fetal erythroblasts confirmed monosomy X. Conclusion: This report underlines the importance of an early prenatal diagnosis and the countless potentialities of array-CGH that could make definition of molecular karyotype possible from a few fetal cells, unlike conventional cytogenetic techniques that require a greater cellular content. This is the first report of a molecular karyotype obtained from two cells selected by micromanipulation of CF and defined at such an early gestational age.

Several limitations, including dark toxicity, reduced tumor tissue selectivity, low photostability and poor biocompatibility hamper the clinical use of Photodynamic therapy (PDT) in cancer treatment. To overcome these limitations, new PSs have been synthetized, and often combined with drug delivery systems, to improve selectivity and reduce toxicity. In this context, BODIPYs (4,4-difluoro-4-bora-3a,4a-diaza-s-indacene) have recently emerged as promising and easy-to-handle scaffolds for the preparation of effective PDT antitumor agents. In this study, the anticancer photodynamic effect of newly prepared negatively charged polymethyl methacrylate (nPMMA)-bounded BODIPYs (3@nPMMA and 6@nPMMA) was evaluated on a panel of 2D- and 3D-cultured cancer cell lines and compared with free BODIPYs. In particular, the effect on cell viability was evaluated, along with their ability to accumulate into the cells, induce apoptotic and/or necrotic cell death, and inhibit cellular migration. Our results indicated that 3@nPMMA and 6@nPMMA reduce cancer cell viability in 3D models of HC116 and MCF7 cells more effectively than the corresponding free compounds. Importantly, we demonstrated that MDA-MB231 and SKOV3 cell migration ability was significantly impaired by the PDT treatment mediated by 3@nPMMA and 6@nPMMA nanoparticles, likely indicating the capability of this approach to reduce metastatic tumor potential.

Chronic wound healing represents an impactful financial burden on healthcare systems. In this context, the use of natural products as an alternative therapy reduces costs and maintains effectiveness. Phytotherapeutic gels applied in photodynamic therapy (PDT) have been developed to act as topical healing medicines and antibiotics. The bioactive system is composed of Spirulina sp. (source of chlorophylls) and Copaifera reticulata oil microdroplets, both incorporated into a polymeric blend constituted by kappa-carrageenan (k-car) and F127 copolymer, constituting a system in which all components are bioactive agents. The flow behavior and viscoelasticity of the formulations were investigated. The photodynamic activity was accessed from studies of the inactivation of Staphylococcus aureus bacteria, the main pathogen of hospital relevance. Furthermore, in vivo studies were conducted using eighteen rabbits with dermatitis (grade III and IV) in both paws. The gels showed significant antibiotic potential in vitro, eliminating up to 100% of S. aureus colonies in the presence or absence of light. The k-car reduced 41% of the viable cells; however, its benefits were enhanced by adding chlorophyll and copaiba oil. The animals treated with the phytotherapeutic medicine showed a reduction in lesion size, with healing and re-epithelialization verified in the histological analyses. The animals submitted to PDT displayed noticeable improvement, indicating this therapy’s viability for ulcerative and infected wounds. This behavior was not observed in the iodine control treatment, which worsened the animals’ condition. Therefore, gel formulations were a viable alternative for future pharmaceutical applications, aiming at topical healing.

Background: Vertical transmission of Zika Virus (ZIKV) can be associated with several clinical features in newborn infants. The goal of the present review was to analyze the current state of knowledge regarding clinical repercussions following perinatal exposure to ZIKV in children up to 3 years of age.Methods: A systematic review of published studies was carried out, without the restriction of language or date of publication, identified in the databases PubMed, Virtual Health Library (BVS), Scopus, and Web of Science and the catalog for CAPES theses and dissertations. According to the proposed flowchart, the bibliographic search resulted in 1,563 papers. Of these, according to the eligibility criteria, 70 were selected for systematic review; all were published between 2016 and 2021.Results: Regarding clinical findings, 19 papers evaluated clinical imaging alterations, 21 ophthalmic manifestations, and 39 evaluated the central nervous system; of these, 15 analyzed neuro-psychomotor development. The remainder evaluated audiological (n = 14), nutritional (n = 14), orthopedic (n = 7), cardiorespiratory (n = 5), genitourinary (n = 3) or endocrinological (n = 1) manifestations.Conclusion: It is critical for studies to continue monitoring children with antenatal ZIKV exposure as they grow, given the unknown long-term repercussions of ZIKV and the recognized postnatal complications of this infection during pregnancy. Broader descriptions of observed clinical findings are also important in order to characterize the entire spectrum of disease in children.Systematic Review Registration: PROSPERO REGISTER: CRD42020205947.

Athletic performance is determined by many factors, such as cardiorespiratory fitness, muscular strength and psychological features, which all interact simultaneously. The large Italian National Olympic Committee database of Olympic athletes offers a unique healthy population to verify the strength of the interplay among a number of major elements of training, including autonomic nervous system (ANS) modulation, biochemical indicators and body composition, in a system medicine approach. This observational, retrospective study involved 583 individuals. As part of the yearly precompetitive examination, cardiac autonomic (heart rate variability), psychological, physical (cycloergometer stress test), biochemical and body composition (BOD POD) evaluations were performed. In subsequent analysis, we first considered the relationship between body composition and single individual variables in a simple correlation matrix, including a multitude of variables; then, Exploratory Factor Analysis (EFA) restricted the information to six latent domains, each combining congruent information in relation to body composition. Finally, we employed a multiple quantile regression model to evaluate possible relationships between ANSIs (index capable of synthetizing ANS regulation) and the latent domains indicated by EFA reflecting body composition. We observed a clear relationship between ANS and body mass composition parameters, as indicated by both bivariate correlations and the quantile regression result of ANSIs versus the latent domain aggregating mainly body composition data expressed in % (p = 0.002). In conclusion, these results suggest that specific training may elicit parallel adaptation of ANS control and body composition. The analysis of Olympic athletes’ data allowed us to obtain a better understanding of the complex, multidimensional factors involved in determining sport performance. The latter appears to be determined by the simultaneous interaction not only of cardiorespiratory fitness, muscular strength and psychological features, but also of ANS cardiovascular modulation and body composition.

Over the past 30 years, photodynamic therapy (PDT) has shown great development. In the clinical setting the few approved molecules belong almost exclusively to the porphyrin family; but in the scientific field, in recent years many researchers have been interested in other families of photosensitizers, among which BODIPY has shown particular interest. BODIPY is the acronym for 4,4-difluoro-4-bora-3a, 4a-diaza-s-indacene, and is a family of molecules well-known for their properties in the field of imaging. In order for these molecules to be used in PDT, a structural modification is necessary which involves the introduction of heavy atoms, such as bromine and iodine, in the beta positions of the pyrrole ring; this change favors the intersystem crossing, and increases the 1O2 yield. This mini review focused on a series of structural changes made to BODIPYs to further increase 1O2 production and bioavailability by improving cell targeting or photoactivity efficiency.

Obesity is associated with an increased risk of several chronic comorbidities, which may also be determined by dysfunctional autonomic nervous system (ANS). The influence of bariatric surgery (BS) on ANS balance was explored in previous studies, but with high heterogeneity in both the assessment timing and methods employed. In the present observational study, we applied a clinical protocol which considers two subsequent phases. Twenty-nine non-diabetic obese subjects were studied at baseline (T0), after one month of lifestyle modification (prehabilitation) (phase 1-T1), and after eight months following BS (phase 2-T2). ANS regulation was assessed across the three study epochs by means of ANSI, a single composite percent-ranked proxy of autonomic balance, being free of gender and age bias, economical and simple to apply in a clinical setting. The aim of the present study was to investigate the effects of the clinical protocol based on prehabilitation and subsequent BS on the ANS regulation by means of ANSI. Potential intertwined correlations with metabolic parameters were also investigated. Notably, we observed a progressive improvement in ANS control, even by employing ANSI. Moreover, the reduction in the markers of sympathetic overactivity was found to significantly correlate with the amelioration in some metabolic parameters (fasting glucose, insulin levels, and waist circumference), as well as in stress and tiredness perception. In conclusion, this study provides convincing evidence that a unitary proxy of cardiac autonomic regulation (CAR) may reflect the progressive improvement in autonomic regulation following behavioral and surgical interventions in obese patients. Intriguingly, this might contribute to reducing cardiovascular and metabolic risk.

An increasing amount of evidence indicates the critical role of the NSD1 gene in Sotos syndrome (SoS), a rare genetic disease, and in tumors. Molecular mechanisms affected by NSD1 mutations are largely uncharacterized. In order to assess the impact of NSD1 haploinsufficiency in the pathogenesis of SoS, we analyzed the gene expression profile of fibroblasts isolated from the skin samples of 15 SoS patients and of 5 healthy parents. We identified seven differentially expressed genes and five differentially expressed noncoding RNAs. The most upregulated mRNA was stratifin (SFN) (fold change, 3.9, Benjamini–Hochberg corrected p < 0.05), and the most downregulated mRNA was goosecoid homeobox (GSC) (fold change, 3.9, Benjamini–Hochberg corrected p < 0.05). The most upregulated lncRNA was lnc-C2orf84-1 (fold change, 4.28, Benjamini–Hochberg corrected p < 0.001), and the most downregulated lncRNA was Inc-C15orf57 (fold change, −0.7, Benjamini–Hochberg corrected p < 0.05). A gene set enrichment analysis reported the enrichment of genes involved in the KRAS and E2F signaling pathways, splicing regulation and cell cycle G2/M checkpoints. Our results suggest that NSD1 is involved in cell cycle regulation and that its mutation can induce the down-expression of genes involved in tumoral and neoplastic differentiation. The results contribute to defining the role of NSD1 in fibroblasts for the prevention, diagnosis and control of SoS.

Purpose To assess the urodynamic findings in patients with Parkinson disease (PD) with overactive bladder symptoms. Methods We performed a retrospective chart review of all PD patients who were seen in an outpatient clinic for lower urinary tract symptoms (LUTS) between 2010 and 2017 in a single-institution. Only patients who complained of overactive bladder (OAB) symptoms and underwent a video-urodynamic study for these symptoms were included. We excluded patients with neurological disorders other than PD and patients with voiding LUTS but without OAB symptoms. Results We included 42 patients (29 men, 13 women, 74.5±8.1 years old). Seven patients (16.7%) had a postvoid residual (PVR) bladder volume >100 mL and only one reported incomplete bladder emptying. Detrusor overactivity (DO) was found in all 42 patients (100%) and was terminal in 19 (45.2%) and phasic in 22 patients (52.4%). Eighteen patients had detrusor underactivity (DU) (42.3%). Later age of PD diagnosis was the only parameter associated with DU (P=0.02). Patients with bladder outlet obstruction (BOO) were younger than patients without BOO (70.1 years vs. 76.5 years, P=0.004), had later first sensation of bladder filling (173.5 mL vs. 120.3 mL, P=0.02) and first involuntary detrusor contraction (226.4 mL vs. 130.4 mL, P=0.009). Conclusions DO is almost universal in all patients with PD complaining of OAB symptoms (97.1%). However, a significant percentage of patients also had BOO (36.8%), DU (47%), and increased PVR (16.7%) indicating that neurogenic DO may not be the only cause of OAB symptoms in PD patients.

William Jackson,1 Emily L Zale,2 Stanley J Berman,3 Alberto Malacarne,1 Amy Lapidow,4 Michael E Schatman,5,6 Ronald Kulich,1,7,* Ana-Maria Vranceanu2,* 1Department of Diagnostic Sciences, Tufts University School of Dental Medicine, Boston, MA, USA; 2Department of Psychiatry, Massachusetts General Hospital, Harvard School of Medicine, MA, USA; 3Department of Clinical Health Psychology, William James College, MA, USA; 4Department of Health Sciences Library, Tufts University School of Dental Medicine, Boston, MA, USA; 5Department of Public Health and Community Medicine, Tufts University School of Medicine, Boston, MA, USA; 6Research and Network Development, Boston PainCare, Waltham, MA, USA; 7Department of Anesthesia, Massachusetts General Hospital, Harvard School of Medicine, MA, USA *These authors contributed equally to this work Purpose: The importance of improved physical function as a primary outcome in the treatment of chronic pain is widely accepted. There have been limited attempts to assess the effects mindfulness skills training (MST) has on objective outcomes in chronic pain care. Methods: This systematic review evaluated published reports of original randomized controlled trials that described physical function outcomes after MST in the chronic pain population and met methodological quality according to a list of predefined criteria. PRISMA criteria were used to identify and select studies, and assess their eligibility for inclusion. The established guidelines for best practice of systematic reviews were followed to report the results. Results: Of the 2,818 articles identified from the original search of four electronic databases, inclusionary criteria were met by 15 studies published as of August 10, 2015, totaling 1,199 patients. All included studies used self-report measures of physical function, and only two studies also employed performance-based measures of function. There were wide variations in how physical function was conceptualized and measured. Although the quality of the studies was rated as high, there was inconclusive evidence for improvement in physical function assessed by self-report due to contradiction in individual study findings and the measures used to assess function. Strong evidence for lack of improvement in physical function assessed via performance-based measures was found. Conclusion: This review draws attention to the importance of having a unified approach to how physical function is conceptualized and assessed, as well as the importance of using quality performance-based measures in addition to subjective self-reports that appropriately assess the physical function construct within MSTs for chronic pain. Keywords: mindfulness, chronic pain, physical functioning, systematic review, outcome measures, activity trackers

Epoxyeicosatrienoic acids (EETs) are signaling lipids produced by the cytochrome P450-(CYP450)-mediated epoxygenation of arachidonic acid. EETs have numerous biological effects on the vascular system, but aspects including their species specificity make their effects on vascular tone controversial. CYP450 enzymes require the 450-reductase (POR) for their activity. We set out to determine the contribution of endothelial CYP450 to murine vascular function using isolated aortic ring preparations from tamoxifen-inducible endothelial cell-specific POR knockout mice (ecPOR−/−). Constrictor responses to phenylephrine were similar between control (CTR) and ecPOR−/− mice. Contrastingly, sensitivity to the thromboxane receptor agonist U46619 and prostaglandin E2 (PGE2) was increased following the deletion of POR. Ex vivo incubation with a non-hydrolyzable EET (14,15-EE-8(Z)-E, EEZE) reversed the increased sensitivity to U46619 to the levels of CTR. EETs had no effect on vascular tone in phenylephrine-preconstricted vessels, but dilated vessels contracted with U46619 or PGE2. As U46619 acts through RhoA-dependent kinase, this system was analyzed. The deletion of POR affected the expression of genes in this pathway and the inhibition of Rho-GTPase with SAR407899 decreased sensitivity to U46619. These data suggest that EET and prostanoid crosstalk at the receptor level and that lack of EET production sensitizes vessels to vasoconstriction via the induction of the Rho kinase system.

Modern agriculture is an extremely energy-intensive process [...]

Interstitial deletions of the long arm of chromosome 12 are rare, with a dozen patients carrying a deletion in 12q21 being reported. Recently a critical region (CR) has been delimited and could be responsible for the more commonly described clinical features, such as developmental delay/intellectual disability, congenital genitourinary and brain malformations. Other, less frequent, clinical signs do not seem to be correlated to the proposed CR. We present seven new patients harboring non-recurrent deletions ranging from 1 to 18.5 Mb differentially scattered across 12q21. Alongside more common clinical signs, some patients have rarer features such as heart defects, hearing loss, hypotonia and dysmorphisms. The correlation of haploinsufficiency of genes outside the CR to specific signs contributes to our knowledge of the effect of the deletion of this gene-poor region of chromosome 12q. This work underlines the still important role of copy number variations in the diagnostic setting of syndromic patients and the positive reflection on management and family genetic counseling.

This data article associated with the manuscript “A high glucose levels is associated with decreased aspirin-mediated acetylation of platelet cyclooxygenase (COX)-1 at serine 529: a pilot study” (Finamore et al., 2018) refers to the shotgun proteomics approach carried out on platelet protein extracts from diabetic patients and healthy controls. Platelet proteins were in vitro incubated with 500 µM aspirin for 30 min at 37 °C to enhance the acetylation process. After protein digestion with trypsin, DDA data were acquired on a Thermo QExactive plus using 3 technical replicate injections per sample. Here, we were able to elucidate the preferential sites of aspirin-induced acetylation on a significant fraction of the platelet proteome and to quantify the impact of diabetes on the effect of aspirin on several platelet proteins. Data are available via ProteomeXchange with identifier PXD011582.