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Summary: Human genetic studies of critical COVID-19 pneumonia have revealed the essential role of type I interferon-dependent innate immunity to SARS-CoV-2 infection. Conversely, an association between the HLA-B∗15:01 allele and asymptomatic SARS-CoV-2 infection in unvaccinated individuals was recently reported, suggesting a contribution of pre-existing T cell-dependent adaptive immunity. We report a lack of association of classical HLA alleles, including HLA-B∗15:01, with pre-omicron asymptomatic SARS-CoV-2 infection in unvaccinated participants in a prospective population-based study in the United States (191 asymptomatic vs. 945 symptomatic COVID-19 cases). Moreover, we found no such association in the international COVID Human Genetic Effort cohort (206 asymptomatic vs. 574 mild or moderate COVID-19 cases and 1,625 severe or critical COVID-19 cases). Finally, in the Human Challenge Characterisation study, the three HLA-B∗15:01 individuals infected with SARS-CoV-2 developed symptoms. As with other acute primary infections studied, no classical HLA alleles favoring an asymptomatic course of SARS-CoV-2 infection were identified.

Human activities are recognised as primarily responsible for global warming, with consequences such as biodiversity loss and extreme weather phenomena that impact human well-being. This study proposes a methodological approach for numerical simulation of the interactions between climate phenomena, the built environment, and the individual, based on the assumption that thoroughly understanding these connections will enable the development of more effective intervention strategies for climate mitigation and human comfort. The methodology is applied to three pilot cases in order to analyse the influence of different parameters of the urban built environment on physiological stress: the Quarticciolo neighbourhood (former borough) in Rome (Italy), the Westside San Antonio neighbourhood in Texas (USA), and the Shuangta Suzhou neighbourhood in China. Article info Received: 18/03/2024; Revised: 10/04/2024; Accepted: 19/04/2024

Background: The contour method for residual stress measurement has seen significant development, but an experimental reproducibility study utilizing physical samples has not been published. Objective: A double-blind reproducibly study is reported, having scope beginning with EDM cutting and ending with residual stress calculation. Methods: A reinforced I-beam sample geometry is identified for its unique residual stress profile when extracted from residual stress bearing quenched aluminum bar (7050-T74). Contour measurements are prescribed on a midplane of symmetry with dimensions 24.0 mm by 50.0 mm. Fourteen identically prepared samples are fabricated from a single long bar with well characterized and uniform residual stress. Five samples throughout the bar are identified for planning measurements to validate sample uniformity and overall suitability of the residual stress field. The planning measurements employ a range of techniques: contour method, neutron diffraction, and hole-drilling. Eight samples are distributed to an international group of participants to execute their standard measurement practice. A double-blind process is followed to provide anonymity. Results: Results are provided by eight participants: six being self-similar and two being quite different, the latter set aside as outliers. An average residual stress field is established from non-outlying results and the spatial distribution of reproducibility standard deviation is determined. The average stress field ranges from -60 to 70 MPa and the reproducibility standard deviation averages 8.1 MPa on the measurement plane. The average reproducibility standard deviation is about 3 × larger for points within 1.0 mm of plane boundaries (17.6 MPa) than for the remaining points (6.1 MPa). Conclusions: Reproducibility standard deviation (among different labs) for contour method residual stress measurement is found to be very similar to repeatability standard deviation (in a single lab) reported in prior work. The reproducibility observed here, for the entire measurement process, is also similar to that found in a prior reproducibility study limited to contour method data analysis.

Abstract No prospective data were available prior to 2021 to inform selection between combination BRAF and MEK inhibition versus dual blockade of programmed cell death protein-1 (PD-1) and cytotoxic T lymphocyte antigen-4 (CTLA-4) as first-line treatment options for BRAFV600-mutant melanoma. SECOMBIT (NCT02631447) was a randomized, three-arm, noncomparative phase II trial in which patients were randomized to one of two sequences with immunotherapy or targeted therapy first, with a third arm in which an 8-week induction course of targeted therapy followed by a planned switch to immunotherapy was the first treatment. BRAF/MEK inhibitors were encorafenib plus binimetinib and checkpoint inhibitors ipilimumab plus nivolumab. Primary outcome of overall survival was previously reported, demonstrating improved survival with immunotherapy administered until progression and followed by BRAF/MEK inhibition. Here we report 4-year survival outcomes, confirming long-term benefit with first-line immunotherapy. We also describe preliminary results of predefined biomarkers analyses that identify a trend toward improved 4-year overall survival and total progression-free survival in patients with loss-of-function mutations affecting JAK or low baseline levels of serum interferon gamma (IFNy). These long-term survival outcomes confirm immunotherapy as the preferred first-line treatment approach for most patients with BRAFV600-mutant metastatic melanoma, and the biomarker analyses are hypothesis-generating for future investigations of predictors of durable benefit with dual checkpoint blockade and targeted therapy.

Abstract RadioLab is an Italian project, addressed to school-age people, and designed for the dissemination of scientific culture on the theme of environmental radioactivity, with particular regards to the importance of knowledge of radon gas exposure. The project is a nationwide initiative promoted by the National Institute of Nuclear Physics- INFN. First tool used by the project, and of immediate impact to assess the public awareness on radon, is the administration of the survey “do you know the radon gas?”. In the survey, together with the knowledge of radon and of its sources, information on personal, cultural and territorial details regarding the interviewees are also taken. Reasonably, the survey invests not only young people, but also their relatives, school workers and, gradually, the public. The survey is administrated during exhibitions or outreach events devoted to schools, but also open to the public. The survey is in dual form: printed and online. The online mode clearly leads RadioLab project even outside the school environment. Based on the results of the survey, several statistical analyses have been performed and many conclusions are drawn about the knowledge of the population on the radon risk. The RadioLab benefit and the requirement to carry on the project goals, spreading awareness of environmental radioactivity from radon, emerge. The dataset involves all twenty Italian regions and consists of 28,612 entries covering the 5-year period 2018–2022.

Manganese dioxide-multiwall carbon nanotube (MnO2-MWCNT) nanocomposites were synthesized via one-pot synthesis method with varying concentrations of 1 mg/ml, 4 mg/ml, and 10 mg/ml MWCNT. The synthesized nanocomposites were characterized using x-ray diffraction (XRD), transmission electron microscopy (TEM), and electrochemical measurements. The intent of studying different concentrations is, ultimately, to correlate the effect of the concentration of multiwall carbon nanotube on the electrochemical performance of the MnO2-MWCNT nanocomposites. Two primary phenomena were observed as CNT concentration increased. First, less crystalline MnO2 adsorption onto individual CNTs occurred. Subsequently, CNT agglomeration became the primary feature of the nanostructures of high CNT concentration. The electrochemical studies reveal that the specific capacitance of MnO2 increases from 124 F/g to 145 F/g by the addition of 1 mg/ml MWCNTs and decreases to 102 F/g for MnO2-10 mg/ml MWCNT nanocomposite.

Cutaneous bacillary angiomatosis (cBA) is a vascular proliferative disorder due to Bartonella henselae or Bartonella quintana that has been mostly described in people living with HIV. Since cBA is considered to be rare in hosts not affected by major immunosuppression, it could be underdiagnosed in this population. Moreover, antimicrobial treatment of cBA has been poorly validated, thus reporting experiences on this clinical entity is important. We reported a challenging and well-characterized case of an Italian 67-year-old gentleman without a history of major immunocompromizing conditions, although he was affected by conditions that can be associated with impaired immune function. The patient reported herein was diagnosed after a long time since the initiation of symptoms and was successfully treated with combined antibiotic therapy including macrolides and quinolones under the guidance of molecular test results. Physicians should consider cBA as a possible manifestation of Bartonella spp. Infection in patients not suffering from major immunocompromizing conditions. Until evidence-based guidelines are available, molecular tests together with severity and extension of the disease can be useful to personalize the type of treatment and its duration.

Pietro Quaglino,1 Paolo A Ascierto,2 Francesca Consoli,3 Paola Queirolo,4 Francesco Spagnolo,5 Maria Francesca Morelli,6 Rossana Berardi,7 Vanna Chiarion-Sileni,8 Marco Tucci,9 Teresa Troiani,10 Barbara Melotti,11 Ernesto Rossi,12 Mario Mandala,13 Gaetana Rinaldi,14 Ilaria Gioia Marcon,15 Matteo Pizzuti,15 Michele Del Vecchio16 1Department of Medical Sciences, Dermatologic Clinic, University of Turin, Turin, Italy; 2Department of Melanoma, Cancer Immunotherapy and Development Therapeutics, Istituto Nazionale Tumori IRCCS Fondazione Pascale, Naples, Italy; 3Department of Oncology, ASST Spedali Civili, Brescia, Italy; 4Oncology Division, Policlinico San Martino IRCCS, Genova, Italy, and Division of Medical Oncology for Melanoma, Sarcoma, and Rare Tumors, IEO, European Institute of Oncology IRCCS, Milan, Italy; 5Skin Cancer Unit, IRCCS Ospedale Policlinico San Martino, Genova, Italy; 6Department of Oncology and Dermatological Oncology, Istituto Dermopatico dell’Immacola, Rome, Italy; 7Università Politecnica delle Marche – Azienda Ospedaliero-Universitaria delle Marche, Ancona, Italy; 8Melanoma Oncology Unit, Veneto Institute of Oncology IOV-IRCCS, Padova, Italy; 9Medical Oncology Unit, Department of Interdisciplinary Medicine, University of Bari ‘Aldo Moro’, Bari, Italy; 10Faculty of Medicine, Second University of Naples, Naples, Italy; 11Medical Oncology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy; 12Medical Oncology, Fondazione Policlinico Universitario A.Gemelli IRCCS, Rome, Italy; 13Division of Oncology, Papa Giovanni XXIII Hospital, Bergamo, Italy, and University of Perugia, Perugia, Italy; 14UOC Oncologia Medica Aoup Paolo Giaccone, Palermo, Italy; 15Novartis Farma S.p.A, Milan, Italy; 16Unit of Melanoma Medical Oncology, Department of Medical Oncology and Hematology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, ItalyCorrespondence: Michele Del Vecchio, Unit of Melanoma Medical Oncology, Department of Medical Oncology and Hematology, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Giacomo Venezian, 1 20133, Milano, Italy, Tel +39 2.23902557, Email Michele.DelVecchio@istitutotumori.mi.itPurpose: Real-world data from patients with BRAFV600-mutated, resected, stage III melanoma treated with dabrafenib plus trametinib as adjuvant targeted therapy are limited, and it is important to gain an understanding of the characteristics of this patient population, as well as of the patient journey. Here we aimed to describe the characteristics, dosage reductions and discontinuations in patients with BRAFV600E/K-mutated melanoma receiving adjuvant dabrafenib plus trametinib after surgical resection through an Italian managed access program (MAP).Patients and Methods: Eligible patients had completely resected cutaneous melanoma with confirmed BRAF V600E or V600K mutation, or initially resectable lymph node recurrence after a diagnosis of stage I or II melanoma. The starting dose of dabrafenib and trametinib was 150 mg twice daily and 2 mg once daily, respectively.Results: A total of 557 patients received dabrafenib plus trametinib through the MAP (stage III resected disease at inclusion, 554). Median age was 54.0 years, and 40.2% of patients were female. The proportion of all treated patients who required a dose reduction was low (10.8%) as was the proportion of patients who discontinued treatment (13.5%). The main reason for treatment discontinuation was adverse events (36.0%).Conclusion: New treatments, including BRAF-targeted therapies and immunotherapy, have transformed the natural history of melanoma. This is the largest study to date describing patients treated with dabrafenib plus trametinib in routine clinical practice in Italy between 2018 and 2019. Results highlight the characteristics of the patients treated and their journey, as well as the tolerable safety profile of dabrafenib plus trametinib in a real-world patient population.Keywords: BRAF mutation, dabrafenib, melanoma, real-world, trametinib, managed access program

More consumers are replacing cow’s milk (CM) with plant-based drinks (PBD), but data indicating the nutritional impact are limited. This theoretical study aims to assess the effect of substituting CM with PBD sold in Italy on nutrient intake within two dietary patterns: one aligned with the EAT-Lancet Commission reference diet adapted to Italian food habits (EAT-IT) and another one in line with the Italian Dietary Guidelines (IDG). Nutrition information from 368 PBD were collected and categorized according to their descriptive name and their fortification or not with calcium (Ca- and nCa-fortified). The substitution of CM with each PBD category in both dietary patterns was conducted, and an analysis of nutrient content and adequacy was performed. Substituting CM with all PBD resulted in reduced protein intake, except for nCa-fortified soy drinks, decreased saturated fat and vitamins B2 and B12, and increased fiber intake. Replacing CM with nCa-fortified PBD within both diets decreased Ca intake. Following the substitution of CM with Ca-fortified PBD, variations in vitamin D intake depended on the PBD category. The main risk of nutritional inadequacy was observed in Ca and vitamin D levels, which may even be amplified considering the different bioavailability based on the source of nutrients. This study highlighted the important role of CM in meeting calcium requirements and the potential unintended consequences of substituting CM with PBD without considering their nutritional differences.

Stress shielding is a problem for traditional metal bone fixation plates made of magnesium and titanium alloys. This problem can be solved by using composite materials with a low elastic modulus. This study analyzed the effect of carbon fiber reinforced PEEK (CFRP) composites on stress shielding under static loading using finite element simulations. Callus formation times relative to the healing period were gradually imposed according to the elapsed time, considering 1% and 75% as healing stages. The Inventor© 3D CAD 2024 software was used for modeling, and the ANSYS© FEA R2023 software was used for analysis. The results showed that metal fixation plates made of titanium and magnesium alloys transferred less stress to the bone than the CFRP fixation plate. In particular, the use of the CFRP fixation plate resulted in a higher peak stress and a more uniform stress field in the bone, especially in the bone-plate contact area, where the risk of stress shielding is higher in the 1% and 75% healing phases.

Neuroendocrine differentiation (NED) represents a possible androgen receptor pathway inhibitors (ARPI) resistance mechanism in metastatic castration resistance prostate cancer (mCRPC). As mCRPC with NED has been excluded from clinical trials evaluating ARPI efficacy, this study investigates the prognostic impact of NED in mCRPC patients treated with ARPIs. Methods: We retrospectively analyzed 327 mCRPC patient data treated with Enzalutamide or Abiraterone in the first and second or successive lines of treatment. NED was assessed using prostate biopsy samples through immunohistochemical staining. Results: NED was confirmed in 32/327 (9.8%) mCRPC patients. In the overall population, mCRPC with NED showed worse PFS (4.38 vs. 11.48 months HR 2.505 [1.71–3.68] p < 0.05), disease control rate (DCR), and PSA response. In the first line setting, mCRPC with NED demonstrated worse PFS (8.5 vs. 14.9 months HR 2.13 [1.18–3.88], p < 0.05). Similarly, in the second or successive lines, mCRPC with NED showed worse PFS (4.0 vs. 7.5 months HR 2.43 [1.45–4.05] p < 0.05), DCR, PSA response and OS (12.53 vs. 18.03 months HR 1.86 [1.12–3.10] p < 0.05). The adverse impact of NED on PFS was consistence across all subgroups; we also noted a trend of worse PFS in patients with high vs. low NED. Conclusions: In our study, mCRPC with NED treated with Enzalutamide or Abiraterone showed worse clinical outcomes. NED assessment should be considered to optimize treatment decisions in the mCRPC setting.

A ZnO-Graphene oxide nanocomposite (Z-G) was prepared in order to exploit the biomedical features of each component in a single anticancer material. This was achieved by means of an environmentally friendly synthesis, taking place at a low temperature and without the involvement of toxic reagents. The product was physicochemically characterized. The ZnO-to-GO ratio was determined through thermogravimetric analysis, while scanning electron microscopy and transmission electron microscopy were used to provide insight into the morphology of the nanocomposite. Using energy-dispersive X-ray spectroscopy, it was possible to confirm that the graphene flakes were homogeneously coated with ZnO. The crystallite size of the ZnO nanoparticles in the new composite was determined using X-ray powder diffraction. The capacity of Z-G to enhance the toxicity of the anticancer drug Paclitaxel towards breast cancer cells was assessed via a cell viability study, showing the remarkable anticancer activity of the obtained system. Such results support the potential use of Z-G as an anticancer agent in combination with a common chemotherapeutic like Paclitaxel, leading to new chemotherapeutic formulations.

Use of artificial intelligence (AI) is a burgeoning field in otolaryngology and the communication sciences. A virtual symposium on the topic was convened from Duke University on October 26, 2020, and was attended by more than 170 participants worldwide. This review presents summaries of all but one of the talks presented during the symposium; recordings of all the talks, along with the discussions for the talks, are available at https://www.youtube.com/watch?v=ktfewrXvEFg and https://www.youtube.com/watch?v=-gQ5qX2v3rg . Each of the summaries is about 2500 words in length and each summary includes two figures. This level of detail far exceeds the brief summaries presented in traditional reviews and thus provides a more-informed glimpse into the power and diversity of current AI applications in otolaryngology and the communication sciences and how to harness that power for future applications.

Purpose: The purpose of this study was to conduct a scoping review of literature focused on the effects of developmental language disorder (DLD) on writing skills across the life span to highlight gaps in our knowledge of how to support writing for this population. Method: We adopted the five-step framework for conducting scoping reviews outlined by Arksey and O'Malley (2005) to identify literature focused on writing outcomes for individuals with DLD in childhood, adolescence, and adulthood. Results: Seventy-two studies from 1991 to 2022 met review criteria. Results indicated that spelling may be an area of relative weakness for individuals with DLD across the life span. Children and adolescents with DLD also may have relative difficulty with grammar, organization, cohesion, and length of written output. Research on the writing skills of adults with DLD is too sparse to draw broad conclusions about the writing skills of this subset of the population with DLD. Conclusions: Overall, research into the writing skills of individuals with DLD is limited, and more information is needed to inform functional evidence-based approaches to assessment and intervention of writing for those with DLD from childhood through adulthood. Additionally, more focus on electronic writing in research is needed, as only two studies included in this review examined typed writing in any form. Results of this review also indicate a need for systematic, uniform approaches to defining and measuring writing skills for those who experience language difficulties.

This quantitative study examined the characteristics of the developmental networks of young South Korean self-initiated expatriates (SIEs) in Vietnam and the effects of the network characteristics on developmental functions and career growth. Based on a literature review, a hypothesized model was developed and examined using a path analysis. The results demonstrated that organizational, cultural, and program diversity and network strength influenced different types of developmental functions (career, psychosocial, and cultural support). The findings also demonstrated that cultural support did not have a direct relationship with perceived career growth opportunities, while it indirectly influenced career growth through career and psychosocial functions of developmental networks. This study provides a comprehensive understanding of SIEs' developmental networks and their effect on career development with empirical evidence. The results of this study will inform career counselors and educators on how to support SIEs' career development and career-related relationship building.

IntroductionB cells play a pivotal role in adaptive immunity which has been extensively characterised primarily via flow cytometry-based gating strategies. This study addresses the discrepancies between flow cytometry-defined B cell subsets and their high-confidence molecular signatures using single-cell multi-omics approaches.MethodsBy analysing multi-omics single-cell data from healthy individuals and patients across diseases, we characterised the level and nature of cellular contamination within standard flow cytometric-based gating, resolved some of the ambiguities in the literature surrounding unconventional B cell subsets, and demonstrated the variable effects of flow cytometric-based gating cellular heterogeneity across diseases.ResultsWe showed that flow cytometric-defined B cell populations are heterogenous, and the composition varies significantly between disease states thus affecting the implications of functional studies performed on these populations. Importantly, this paper draws caution on findings about B cell selection and function of flow cytometric-sorted populations, and their roles in disease. As a solution, we developed a simple tool to identify additional markers that can be used to increase the purity of flow-cytometric gated immune cell populations based on multi-omics data (AlliGateR). Here, we demonstrate that additional non-linear CD20, CD21 and CD24 gating can increase the purity of both naïve and memory populations.DiscussionThese findings underscore the need to reconsider B cell subset definitions within the literature and propose leveraging single-cell multi-omics data for refined characterisation. We show that single-cell multi-omics technologies represent a powerful tool to bridge the gap between surface marker-based annotations and the intricate molecular characteristics of B cell subsets.

A “green breakthough” at the table due to consumer demand for healthy and sustainable foods, which aligns with the typical Mediterranean diet, has recently led to an increase in the consumption of products such as extra virgin olive oil. In fact, Italian olive cultivation, which contributes an average of 15% of world production, has seen the production of extra virgin olive oil with a value of exports that have doubled in the last 20 years. In this context, the olive oil sector of the Emilia-Romagna region (Italy), and in particular the PDO Brisighella, could achieve greater success with consumers by proposing a product obtained through sustainable agriculture that enhances the content of bioactive compounds. For these reasons, in this study, different agronomic variables are investigated in order to optimize the presence of bioactive components in extra virgin olive oil made from monovarietal Nostrana di Brisighella, namely phenolic and positive volatile compounds, thus naturally enriching this product both from health and sensory points of view. The study focuses on the volatile and phenolic fractions (derivatives of hydroxytyrosol and tyrosol) of olive oil and the positive sensory attributes (fruity, bitter and pungent) that are known to be associated with these molecules. The phenolic content is of particular interest due to the potential to support health claims. Extra virgin olive oil samples were produced from olives of the Nostrana di Brisighella cultivar; fruits were obtained through integrated pest management or organic farming and picked at four increasing indices of maturity, corresponding to four successive weeks of harvesting. These agronomic variables influenced the compositional and sensory characteristics of the extra virgin olive oils assessed, highlighting differences that likely derive from the effect of the agronomic system used, i.e., integrated pest management or organic farming.

Several studies have been conducted that show the crucial role of active participation in music in health promotion (e.g. Dingle et al., 2021; Sheppard & Broughton, 2020); however, little research has focused on the biopsychosocial effects of choral singing. The present study aims to evaluate the effectiveness, in terms of improving physiological and psychosocial factors, of a choral program for middle-aged and older individuals. We integrated our study with qualitative observations of the atmosphere and flow state experienced by the choristers. The data were collected before and after 12 weeks of training, with 23 participants took part in the study. They experienced significant improvements in weight, oxygen saturation, heart rate, and satisfaction of psychological needs. A beneficial trend, although not statistically significant, were observed for blood pressure, cholesterol, triglycerides, stress, psychological needs, and mental health. The observations progressively revealed a more cohesive and focused group. Our findings support the potential for cross-disciplinary collaboration between healthcare and arts policy to promote and enhance health and well-being throughout the lifespan.

The planetary crisis regarding water resources means that new methods are needed to monitor large areas of water basins that are threatened by chemical and natural pollutants, together with climate change. With the aim to detect oil spill, we applied an algorithm, which could consistently and reliably confirm the presence of oil in four polluted lake waters analyzed. Combined algorithm application and metagenomic analysis from the spill areas that had been detected by the satellite identified drivers of the microbial response to oil pollution. Based on ortholog abundances, metabolic pathway reconstruction carried out in PICRUSt2 highlighted the degradative capacity of these microorganism. These microorganisms could be suitable candidates for treatment of crude oil, aromatic hydrocarbons and the desulfurization of persistent petroleum substances like dibenzothiophene.Environmental changes have been analysed with the combination of satellite monitoring and metagenomic in other studies. Red snow phenomenon, in Franz Josef Land's Arctic observed by satellite, is the result of a microbial succession dominated by Chlamydomonas nivalis, a unicellular, red-colored photosynthetic green algae. Similarly, satellite monitoring and metagenomic monitoring were used to assess the impact on coral reefs of a huge quantity of mud spill from iron ore mining on the Abrolhos Bank reef in Brazil.In our study, the combination of satellite sensing and metagenomics analyses offer useful tools for the real-time monitoring of water bodies threatened by oil spills, as well as for the design of recovery strategies based on the use of valuable hydrocarbonoclastic microorganisms.

This case report describes the identification of Ochrobactrum anthropi (O.a.), from a positive blood culture using MALDI-TOF spectrometry system. According to the information availed this is the first case in AORN Sant’Anna and San Sebastiano, Caserta, Campania, Italy. This microbe is moderately pathogenic and hazardous, with the potential to cause hospital-acquired infections. It is recommended that it be included in hospital “germ alerts”.

A Lei N° 14.026/2020 instituiu um novo marco legal do saneamento básico no Brasil. Esta lei apresentou mudanças a fim de impulsionar melhorias na prestação dos serviços do setor, e definindo metas de universalização para abastecimento de água potável e esgotamento sanitário. Especificamente para a drenagem e manejo de águas pluviais urbanas (DMAPU) a referida legislação não especificou os resultados desejados. O cenário brasileiro de DMAPU, no entanto, é diverso e repleto de desafios que precisam ser vencidos em busca de um ambiente urbano integrado e sustentável que promova saúde e bem-estar social. Neste artigo é apresentado um panorama do setor de DMAPU no país, identificando os principais problemas e soluções a partir de uma análise de estrutura institucional, técnica, da regulação, do financiamento, planejamento e gestão dos serviços públicos. Esta análise é também realizada a partir da aplicação de estudos de caso à municípios brasileiros que representassem as diferenças e dimensões continentais do país.

ObjectivesPrimary objective is to determine if transfusion of short storage RBCs compared with standard issue RBCs reduced risk of delirium/coma in critically ill children. Secondary objective is to assess if RBC transfusion was independently associated with delirium/coma.DesignThis study was performed in two stages. First, we compared patients receiving either short storage or standard RBCs in a multi-institutional prospective randomized controlled trial. Then, we compared all transfused patients in the randomized controlled trial with a single-center cohort of nontransfused patients matched for confounders of delirium/coma.SettingTwenty academic PICUs who participated in the Age of Transfused Blood in Critically Ill Children trial.PatientsChildren 3 days to 16 years old who were transfused RBCs within the first 7 days of admission.InterventionsSubjects were randomized to either short storage RBC study arm (defined as RBCs stored for up to seven days) or standard issue RBC study arm. In addition, subjects were screened for delirium prior to transfusion and every 12 hours after transfusion for up to 3 days.Measurements and main resultsPrimary outcome measure was development of delirium/coma within 3 days of initial transfusion. Additional outcome measures were dose-response relationship between volume of RBCs transfused and delirium/coma, and comparison of delirium/coma rates between transfused patients and individually matched nontransfused patients. We included 146 subjects in the stage I analysis; 69 were randomized to short storage RBCs and 77 to standard issue. There was no significant difference in delirium/coma development between study arms (79.5% vs 70.1%; p = 0.184). In the stage II analysis, adjusted odds for delirium in the transfused cohort was more than eight-fold higher than in the nontransfused matched cohort, even after controlling for hemoglobin (adjusted odds ratio, 8.9; CI, 2.8-28.4; p < 0.001).ConclusionsRBC transfusions (and not anemia) are independently associated with increased odds of subsequent delirium/coma. However, storage age of RBCs does not affect delirium risk.

Objective: This study aimed to determine whether or not transfusion of fresh red blood cells (RBCs) reduced the incidence of new or progressive multiple organ dysfunction syndrome compared with standard-issue RBCs in pediatric patients undergoing cardiac surgery. Methods: Preplanned secondary analysis of the Age of Blood in Children in Pediatric Intensive Care Unit study, an international randomized controlled trial. This study included children enrolled in the Age of Blood in Children in Pediatric Intensive Care Unit trial and admitted to a pediatric intensive care unit after cardiac surgery with cardiopulmonary bypass. Patients were randomized to receive either fresh (stored ≤7 days) or standard-issue RBCs. The primary outcome measure was new or progressive multiple organ dysfunction syndrome, measured up to 28 days postrandomization or at pediatric intensive care unit discharge, or death. Results: One hundred seventy-eight patients (median age, 0.6 years; interquartile range, 0.3-2.6 years) were included with 89 patients randomized to the fresh RBCs group (median length of storage, 5 days; interquartile range, 4-6 days) and 89 to the standard-issue RBCs group (median length of storage, 18 days; interquartile range, 13-22 days). There were no statistically significant differences in new or progressive multiple organ dysfunction syndrome between fresh (43 out of 89 [48.3%]) and standard-issue RBCs groups (38 out of 88 [43.2%]), with a relative risk of 1.12 (95% CI, 0.81 to 1.54; P = .49) and an unadjusted absolute risk difference of 5.1% (95% CI, −9.5% to 19.8%; P = .49). Conclusions: In neonates and children undergoing cardiac surgery with cardiopulmonary bypass, the use of fresh RBCs did not reduce the incidence of new or progressive multiple organ dysfunction syndrome compared with the standard-issue RBCs. A larger trial is needed to confirm these results.

Abstract Background Pomegranate is known for its beneficial properties due to its high content in antioxidants and might constitute a natural option for preventing and treatment of different pathologies including cancer. Since mitochondria are involved in tumorigenesis through ROS production and modulation of oxidative metabolism, we investigated the biological effects of pomegranate on cellular redox state, proliferation and metabolism in the breast cancer cell line MDA-MB-231 (MDA). Methods MDA were treated for 24 h with graded concentration of filtered Pomegranate juice (PJ) and tested for metabolic Flux Analysis with XFe96 Extracellular Flux Analyzer, for proliferation using the xCELLigence System Real-Time Cell Analyzer and for intracellular ROS content by Confocal Microscopy Imaging. Results Cells-treatment with freshly prepared pomegranate juice (PJ) resulted in a significant reduction of the intracellular ROS content already at the lower concentration of PJ tested. Additionally, it enhanced mitochondria respiration, and decreased glycolysis at high concentrations, inhibiting at the same time cell proliferation. As pomegranate is a seasonal fruit, assessment of optimum storage conditions preserving its bio-active properties was investigated. Our results indicated that storage conditions under controlled atmosphere for 30 days was able to enhance mitochondrial respiration at the same extent than freshly extracted PJ. Conversely, freezing procedure, though retaining the antioxidant and cell-growth inhibitory property, elicited an opposite effect on the metabolic profile as compared with fresh extract. Conclusion Overall, the results of our study, on the one hand, confirms the preventive/therapeutic potential of PJ, as well as of its post-harvested processing, for cancer management. On the other hand, it highlights the intrinsic difficulties in attaining mechanistic insights when a multiplicity of effects is elicited by a crude mixture of bio-active compounds.

Prior criteria for organ dysfunction in critically ill children were based mainly on expert opinion. We convened the Pediatric Organ Dysfunction Information Update Mandate (PODIUM) expert panel to summarize data characterizing single and multiple organ dysfunction and to derive contemporary criteria for pediatric organ dysfunction. The panel was composed of 88 members representing 47 institutions and 7 countries. We conducted systematic reviews of the literature to derive evidence-based criteria for single organ dysfunction for neurologic, cardiovascular, respiratory, gastrointestinal, acute liver, renal, hematologic, coagulation, endocrine, endothelial, and immune system dysfunction. We searched PubMed and Embase from January 1992 to January 2020. Study identification was accomplished using a combination of medical subject headings terms and keywords related to concepts of pediatric organ dysfunction. Electronic searches were performed by medical librarians. Studies were eligible for inclusion if the authors reported original data collected in critically ill children; evaluated performance characteristics of scoring tools or clinical assessments for organ dysfunction; and assessed a patient-centered, clinically meaningful outcome. Data were abstracted from each included study into an electronic data extraction form. Risk of bias was assessed using the Quality in Prognosis Studies tool. Consensus was achieved for a final set of 43 criteria for pediatric organ dysfunction through iterative voting and discussion. Although the PODIUM criteria for organ dysfunction were limited by available evidence and will require validation, they provide a contemporary foundation for researchers to identify and study single and multiple organ dysfunction in critically ill children.

ObjectivesCritically ill children frequently receive plasma and platelet transfusions. We sought to determine evidence-based recommendations, and when evidence was insufficient, we developed expert-based consensus statements about decision-making for plasma and platelet transfusions in critically ill pediatric patients.DesignSystematic review and consensus conference series involving multidisciplinary international experts in hemostasis, and plasma/platelet transfusion in critically ill infants and children (Transfusion and Anemia EXpertise Initiative-Control/Avoidance of Bleeding [TAXI-CAB]).SettingNot applicable.PatientsChildren admitted to a PICU at risk of bleeding and receipt of plasma and/or platelet transfusions.InterventionsNone.Measurements and main resultsA panel of 29 experts in methodology, transfusion, and implementation science from five countries and nine pediatric subspecialties completed a systematic review and participated in a virtual consensus conference series to develop recommendations. The search included MEDLINE, EMBASE, and Cochrane Library databases, from inception to December 2020, using a combination of subject heading terms and text words for concepts of plasma and platelet transfusion in critically ill children. Four graded recommendations and 49 consensus expert statements were developed using modified Research and Development/UCLA and Grading of Recommendations, Assessment, Development, and Evaluation methodology. We focused on eight subpopulations of critical illness (1, severe trauma, intracranial hemorrhage, or traumatic brain injury; 2, cardiopulmonary bypass surgery; 3, extracorporeal membrane oxygenation; 4, oncologic diagnosis or hematopoietic stem cell transplantation; 5, acute liver failure or liver transplantation; 6, noncardiac surgery; 7, invasive procedures outside the operating room; 8, sepsis and/or disseminated intravascular coagulation) as well as laboratory assays and selection/processing of plasma and platelet components. In total, we came to consensus on four recommendations, five good practice statements, and 44 consensus-based statements. These results were further developed into consensus-based clinical decision trees for plasma and platelet transfusion in critically ill pediatric patients.ConclusionsThe TAXI-CAB program provides expert-based consensus for pediatric intensivists for the administration of plasma and/or platelet transfusions in critically ill pediatric patients. There is a pressing need for primary research to provide more evidence to guide practitioners.

Desert strains of the genus Chroococcidiopsis are among the most desiccation-resistant cyanobacteria capable of anhydrobiosis. The accumulation of two sugars, sucrose and trehalose, facilitates the entrance of anhydrobiotes into a reversible state of dormancy by stabilizing cellular components upon water removal. This study aimed to evaluate, at the atomistic level, the role of trehalose in desiccation resistance by using as a model system the 30S ribosomal subunit of the desert cyanobacterium Chroococcidiopsis sp. 029. Molecular dynamic simulations provided atomistic evidence regarding its protective role on the 30S molecular structure. Trehalose forms an enveloping shell around the ribosomal subunit and stabilizes the structures through a network of direct interactions. The simulation confirmed that trehalose actively interacts with the 30S ribosomal subunit and that, by replacing water molecules, it ensures ribosomal structural integrity during desiccation, thus enabling protein synthesis to be carried out upon rehydration.

The growing drive towards more sustainable dietary patterns has led to an increased demand for and availability of plant-based meat analogues (PBMAs). This systematic review aims to summarize the currently available evidence from human intervention studies investigating the impact of substituting animal meat (AM) with PBMAs in adults. A total of 19 studies were included. Overall, an increase in satiety following PBMA intake was reported, albeit to different extents and not always accompanied by changes in leptin and ghrelin. PBMAs generally resulted in lower protein bioavailability and a smaller increase in plasma essential amino acids in comparison to AM. However, muscle protein synthesis and physical performance were not affected. Finally, conflicting results have been reported for other outcomes, such as pancreatic and gastrointestinal hormones, oxidative stress and inflammation, vascular function, and microbiota composition. In conclusion, we documented that the impact of substituting AM with PBMA products has been scarcely investigated. In addition, the heterogeneity found in terms of study design, population, outcomes, and findings suggests the need for additional high-quality intervention trials, particularly long-term ones, to better clarify the advantages and potential critical issues of such substitutions within sustainable healthy diets.