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Este artículo identifica, con base en la teoría de Ecosistemas de Emprendimiento (EE), los factores que promueven los Ecosistemas de Emprendimiento Social (EES) en el estado de Querétaro, México. Dicha teoría explica que los EES se desarrollan en EE fortalecidos y que estos últimos prosperan en regiones con recursos. Desde una metodología cualitativa, se analizan los factores para el desarrollo de EES en Querétaro, los principales hallazgos los muestran como incipientes y con necesidad de implementar medidas holísticas para emerger adecuadamente. Este estudio es relevante porque profundiza el conocimiento de los EE regionales y los EES en México y América Latina.

The neutrophil-to-lymphocyte ratio (NLR) in the diagnosis of sepsis has been found to be higher in non-survivors than in survivors, and that is associated with mortality. A higher NLR in non-survivors than in survivors has been reported in two studies during patient follow-up; however, NLR was not controlled for sepsis severity. Thus, the objective of this study was to determine whether there is an association between NLR in the first seven days and mortality controlling for sepsis severity.This observational study, which included septic patients, was conducted in the Intensive Care Units of 3 Spanish hospitals. NLR was recorded on the first, fourth, and eighth day of sepsis. Multiple logistic regression analyses were carried out to determine the association between NLR during the first 7 days of sepsis diagnosis and mortality controlling for sepsis severity.Thirty-day non-surviving patients (n=68) compared to surviving patients (n=135) showed higher NLR on the first (p0.001), fourth (p0.001), and eighth (p0.001) day of sepsis diagnosis. Multiple logistic regression analysis found an association between NLR at days first (p0.001), fourth (p=0.004), and eighth (p=0.01) of sepsis diagnosis and mortality controlling for SOFA and lactic acid in those days.The new finding of our study was the association between NLR in the first seven days of sepsis and mortality controlling for sepsis severity.

Safe and effective severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines have been crucial to fight against the coronavirus disease 2019 pandemic. Most vaccines are based on a mutated version of the Spike glycoprotein [K986P/V987P (S-2P)] with improved stability, yield and immunogenicity. However, S-2P is still produced at low levels. Here, we described a novel V987H mutation that increases by two-fold the production of the recombinant Spike and the exposure of the receptor binding domain (RBD). S-V987H immunogenicity was similar to S-2P in K18-hACE2 mice and golden Syrian hamsters, and superior to a monomeric RBD. Immunization with S-V987H, but not with S-2P or RBD, conferred full protection against severe disease in both animal models after SARS-CoV-2 challenge (D614G and B.1.351 variants). Furthermore, S-V987H immunized K18-hACE2 mice showed a faster tissue viral clearance than RBD- or S-2P-vaccinated animals. Thus, S-V987H protein provides an alternative to S-2P for future SARS-CoV-2 vaccines development.

Neoantigens are tumor-specific antigens that are mostly particular for each patient. Since the immune system is able to mount a specific immune response against these neoantigens, they are a promising tool for the development of therapeutic personalized cancer vaccines. Neoantigens must be presented to T cells by Antigen Presenting Cells (APC) in the context of MHC-I or MHC-II molecules. Therefore, the strategy of vaccine delivery may have a major impact on the magnitude and quality of T cell responses. Neoantigen vaccines are frequently administered as a pool of individual synthetic peptides that induce mainly CD4+ T cell responses. MHC-I-mediated presentation and the elicitation of CD8+ T cell responses may be improved using DNA or RNA sequences that code for a unique long polypeptide that concatenates the different neoantigens spaced by linker sequences. When administered this way, the selection of the spacer between neoantigens is of special interest, as it might influence the processing and presentation of the right peptides by APCs. Here, we evaluate the impact of such linker regions on the MHC-I-dependent antigen presentation using an in vitro assay that assesses the MHC-I presentation of SIINFEKL, a H-2Kb-restricted OVA peptide. Our results show that spacers used to generate epitope concatenates have a large impact on the efficiency of neoantigen processing and presentation by MHC-I molecules; in contrast, the peptide position and the flanking regions have a minimal impact. Moreover, linkers based on alanine residues promote a more efficient peptide presentation than the commonly used GGGS linker.

There are not data on blood B-cell lymphoma 2 (Bcl-2) concentrations (one of the antiapoptotic molecules of the Bcl-2 family in the intrinsic apoptosis pathway) in septic patients. Therefore, this study was carried with the aims to explore whether blood Bcl-2 concentrations at diagnosis of sepsis are different in survivor and non-survivor septic patients, are associated with mortality, and are useful for the mortality prediction.Intensive Care Units from 3 Spanish hospitals participated in this observational and prospective study with septic patients and serum Bcl-2 concentrations at diagnosis of sepsis were determined. Mortality at 30 days was as outcome variable.We found that 30-day non-surviving patients (n=81) showed lower serum Bcl-2 levels (p=0.003) than surviving patients (n=140). We found that serum concentrations of Bcl-24.4ng/mL were associated with mortality (OR=3.228; 95% CI=1.406-7.415; p=0.006) in the multiple logistic regression analysis, and that showed an area under the curve for mortality prediction of 62% (95% CI=55-68%; p=0.003).In our study appears novel findings such as higher blood Bcl-2 concentrations in survivor than in non-survivor septic patients, the association between low blood Bcl-2 concentrations and mortality of septic patients, and the ability of blood Bcl-2 concentrations for the prediction of septic patient mortality.

The work (titled) “The meaning of the alternative in the solidarity economy: The experience of Yomol A'tel” aims to provide- from a qualitative approach- a deeper understanding of the case of the solidarity enterprise Yomol A'tel; an organization that has worked for several years with an excluded group in Chiapas, Mexico. This academic effort focusses on the project team members, from a narrative perspective that captures and conveys their perceptions, and allows us to analyze the impact of Yomol A'tel project in terms of social transformation.

Objective Different genetic polymorphisms of human leukocyte antigen (HLA) have been associated with the risk and prognosis of autoimmune and infectious diseases. The objectives of this study were to determine whether there is an association between HLA genetic polymorphisms and the susceptibility to and mortality of coronavirus disease 2019 (COVID-19) patients. Design Observational and prospective study. Setting Eight Intensive Care Units (ICU) from 6 hospitals of Canary Islands (Spain). Patients COVID-19 patients admitted in ICU and healthy subjects. Interventions Determination of HLA genetic polymorphisms. Main variable of interest Mortality at 30 days. Results A total of 3886 healthy controls and 72 COVID-19 patients (10 non-survivors and 62 survivor patients at 30 days) were included. We found a trend to a higher rate of the alleles HLA-A*32 (p = 0.004) in healthy controls than in COVID-19 patients, and of the alleles HLA-B*39 (p = 0.02) and HLA-C*16 (p = 0.02) in COVID-19 patients than in healthy controls; however, all these p-values were not significant after correction for multiple comparisons. Logistic regression analysis showed that the presence of certain alleles was associated with higher mortality, such as the allele HLA-A*11 after controlling for SOFA (OR = 7.693; 95% CI = 1.063–55.650; p = 0.04) or APACHE-II (OR = 11.858; 95% CI = 1.524–92.273; p = 0.02), the allele HLA-C*01 after controlling for SOFA (OR = 11.182; 95% CI = 1.053–118.700; p = 0.04) or APACHE-II (OR = 17.604; 95% CI = 1.629–190.211; p = 0.02), and the allele HLA-DQB1*04 after controlling for SOFA (OR = 9.963; 95% CI = 1.235–80.358; p = 0.03). Conclusions The new finding from our preliminary study of small sample size was that HLA genetic polymorphisms could be associated with COVID-19 mortality; however, studies with a larger sample size before definitive conclusions can be drawn.

Feline leukemia virus (FeLV) is one of the most prevalent infectious diseases in domestic cats. Although different commercial vaccines are available, none of them provides full protection. Thus, efforts to design a more efficient vaccine are needed. Our group has successfully engineered HIV-1 Gag-based VLPs that induce a potent and functional immune response against the HIV-1 transmembrane protein gp41. Here, we propose to use this concept to generate FeLV-Gag-based VLPs as a novel vaccine strategy against this retrovirus. By analogy to our HIV-1 platform, a fragment of the FeLV transmembrane p15E protein was exposed on FeLV-Gag-based VLPs. After optimization of Gag sequences, the immunogenicity of the selected candidates was evaluated in C57BL/6 and BALB/c mice, showing strong cellular and humoral responses to Gag but failing to generate anti-p15E antibodies. Altogether, this study not only tests the versatility of the enveloped VLP-based vaccine platform but also sheds light on FeLV vaccine research.

Aim: To determine whether blood concentrations of Bcl-2 during the 1st week of sepsis could help predict mortality. Methods: Serum Bcl-2 concentrations were determined at the 1st, 4th and 8th days of sepsis diagnosis. Results: Thirty-day surviving patients (n = 168) showed higher serum Bcl-2 levels at the 1st (p = 0.002), 4th (p

There are few data on caspase‑9 (intrinsic apoptosis pathway initiating caspase) in septic patients. Higher serum caspase‑9 levels in septic patients than in healthy subjects have been found. However, there are no data on the prognosis of septic patients and blood caspase‑9 concentrations. Therefore, the objective of this study was to analyze the potential association between blood caspase‑9 concentrations and prognosis in septic patients.Three Spanish hospitals participated in the recruitment of septic patients admitted to intensive care units in this observational and prospective study. Serum caspase‑9 concentrations were determined at the time of sepsis diagnosis. The 30-day mortality was the outcome variable.Higher Acute Phisiology and Chronic Health Evaluation(APACHE)-II (p 0.001), Sepsis-related Organ Failure Assessment score (SOFA) (p 0.001), serum lactic acid levels (p = 0.001), serum caspase‑9 levels (p 0.001), age (p 0.001), International normalized ratio (INR) (p = 0.001), rate of septic shock (p = 0.001), Activated partial thromboplastin time (aPTT) (p = 0.03), rate of diabetes mellitus (p = 0.04), and lower platelet counts (p = 0.01) were found in non-surviving (n = 80) than in surviving patients (n = 134). Multiple logistic regression analysis showed an association between serum caspase‑9 concentrations and mortality (Odds Ratio (OR) = 1.985; 95% Confidence Interval (CI) = 1.359-2.900; p 0.001) regardless of age, SOFA, lactic acid and septic shock and history of diabetes mellitus. No significant differences were found when we compared area under ROC curves of serum caspase‑9 with SOFA (p = 0.92) and with lactic acid (p = 0.59).The main novel finding of our study was the association between blood caspase‑9 concentrations and septic patient prognosis. However, our study showed some limitations (for example, the absence of data in respect to execution of Surviving Sepsis Campaign bundles); thus, more research could be interesting to confirm our preliminary findings.

The understanding of HIV-1 pathogenesis and clinical progression is incomplete due to the variable contribution of host, immune, and viral factors. The involvement of viral factors has been investigated in extreme clinical phenotypes from rapid progressors to long-term non-progressors (LTNPs). Among HIV-1 proteins, the envelope glycoprotein complex (Env) has been concentrated on in many studies for its important role in the immune response and in the first steps of viral replication. In this study, we analyzed the contribution of 41 Envs from 24 patients with different clinical progression rates and viral loads (VLs), LTNP-Elite Controllers (LTNP-ECs); Viremic LTNPs (vLTNPs), and non-controller individuals contemporary to LTNPs or recent, named Old and Modern progressors. We studied the Env expression, the fusion and cell-to-cell transfer capacities, as well as viral infectivity. The sequence and phylogenetic analysis of Envs were also performed. In every functional characteristic, the Envs from subjects with viral control (LTNP-ECs and vLTNPs) showed significant lower performance compared to those from the progressor individuals (Old and Modern). Regarding sequence analysis, the variable loops of the gp120 subunit of the Env (i.e., V2, V4, and mainly V5) of the progressor individuals showed longer and more glycosylated sequences than controller subjects. Therefore, HIV-1 Envs from virus of patients presenting viremic control and the non-progressor clinical phenotype showed poor viral functions and shorter sequences, whereas functional Envs were associated with virus of patients lacking virological control and with progressor clinical phenotypes. These correlations support the role of Env genotypic and phenotypic characteristics in the in vivo HIV-1 infection and pathogenesis. This work is supported by Spanish AIDS network “Red Temática Cooperativa de Investigación en SIDA” RD12/0017/0002, RD12/0017/0028, RD12/0017/0034, RD16/0025/0011, RDCIII16/0002/0005, and RD16/0025/0041 as part of the Plan Nacional R + D + I and cofunded by Spanish “Instituto de Salud Carlos III (ISCIII)-Subdirección General de Evaluación y el Fondo Europeo de Desarrollo Regional (FEDER).” JB is a researcher from “Fundació Institut de Recerca en Ciències de la Salut Germans Trias i Pujol” supported by the Health Department of the Catalan Government/Generalitat de Catalunya and ISCIII grant numbers PI17/01318 and PI20/00093 (to JB). Work in CL-G and CC lab was supported by grants SAF (2010-17226) and (2016-77894-R) from MINECO (Spain) and FIS (PI 13/02269 and PI20/00093, ISCIII). AV-F’s Lab is supported by the European Regional Development Fund (ERDF), RTI2018-093747-B-100 (“Ministerio de Ciencia e Innovación,” Spain), “Ministerio de Ciencia, Innovación y Universidades” (Spain), ProID2020010093 (“Agencia Canaria de Investigación, Innovación y Sociedad de la Información” and European Social Fund), UNLL10-3E-783 (ERDF and “Fundación CajaCanarias”) and “SEGAI-ULL.” SP-Y is funded by “Fundación Doctor Manuel Morales” (La Palma, Spain) and “Contrato Predoctoral Ministerio-ULL Formación de Doctores” (2019 Program; “Ministerio de Ciencia, Innovación y Universidades,” Spain). RC-R is funded by RD16/0025/0011 and ProID2020010093 (“Agencia Canaria de Investigación, Innovación y Sociedad de la Información” and European Social Fund). JE-H is funded by the Cabildo Tenerife “Agustin de Betancourt” 2017 Program. Sí

Since the genetic sequence of SARS-CoV-2 became available in January 2020, new vaccines have been developed at an unprecedented speed. The current vaccines have been directly associated with a decline in new infection rates, prevention of severe disease and an outstanding decrease in mortality rates. However, the pandemic is still far from being over. New Variants of Concern (VoCs) are continuously evolving. Thus, it is essential to develop accessible second-generation COVID-19 vaccines against known and future VoCs to mitigate the current pandemic. Here, we provide preclinical data showing the immunogenicity, efficacy, and safety results in mice of a receptor-binding domain (RBD)-based recombinant protein vaccine candidate (PHH-1V) which consists of a novel RBD fusion heterodimer containing the B.1.1.7 (alpha) and B.1.351 (beta) variants of SARS-CoV-2, formulated with an oil-based adjuvant equivalent to MF59C.1. BALB/c and K18-hACE2 mice were immunized with different doses of recombinant RBD fusion heterodimer, following a two-dose prime-and-boost schedule. Upon 20 μg RBD fusion heterodimer/dose immunization, BALB/c mice produced RBD-binding antibodies with neutralising activity against the alpha, beta, gamma, and delta variants. Furthermore, vaccination elicited robust activation of CD4+ and CD8+ T cells with early expression of Th1 cytokines upon in vitro restimulation, along with a good tolerability profile. Importantly, vaccination with 10 μg or 20 μg RBD fusion heterodimer/dose conferred 100% efficacy preventing mortality and bodyweight loss upon SARS-CoV-2 challenge in K18-hACE2 mice. These findings demonstrate the feasibility of this novel recombinant vaccine strategy, allowing the inclusion of up to 2 different RBD proteins in the same vaccine. Most importantly, this new platform is easy to adapt to future VoCs and has a good stability profile, thus ensuring its global distribution.

We have not found data about blood caspase-8 concentrations (initiator caspase in the extrinsic pathway of apoptosis) during follow-up of sepsis and this was the objective of our study. We included septic patients. Serum caspase-8 concentrations were determined at days 1, 4, and 8 of sepsis diagnosis. We registered mortality at 30 days. Nonsurviving patients (n = 89) in respect to surviving patients (n = 160) showed higher serum caspase-8 levels at days 1 (P0.001), 4 (P0.001), and 8 (P0.001) of sepsis diagnosis. Serum caspase-8 levels on day 1, day 4, and day 8 had an area under curve for the prediction of 30-day mortality of 68% (60%-75%, P0.001), 72% (62%-82%, P0.001), and 81% (73%-90%, P0.001). Thus, that blood caspase-8 concentrations at any time during the first week of sepsis were higher in non-survivor than in survivor patients and that were able to predict mortality were new findings in our study.

BackgroundUnderstanding the determinants of long-term immune responses to SARS-CoV-2 and the concurrent impact of vaccination and emerging variants of concern will guide optimal strategies to achieve global protection against the COVID-19 pandemic.MethodsA prospective cohort of 332 COVID-19 patients was followed beyond one year. Plasma neutralizing activity was evaluated using HIV-based reporter pseudoviruses expressing different SARS-CoV-2 spikes and was longitudinally analyzed using mixed-effects models.FindingsLong-term neutralizing activity was stable beyond one year after infection in mild/asymptomatic and hospitalized participants. However, longitudinal models suggest that hospitalized individuals generate both short- and long-lived memory B cells, while outpatient responses were dominated by long-lived B cells. In both groups, vaccination boosted responses to natural infection, although viral variants, mainly B.1.351, reduced the efficacy of neutralization. Importantly, despite showing higher neutralization titers, hospitalized patients showed lower cross-neutralization of B.1.351 variant compared to outpatients. Multivariate analysis identified severity of primary infection as the factor that independently determines both the magnitude and the inferior cross-neutralization activity of long-term neutralizing responses.ConclusionsNeutralizing response induced by SARS-CoV-2 is heterogeneous in magnitude but stable beyond one year after infection. Vaccination boosts these long-lasting natural neutralizing responses, counteracting the significant resistance to neutralization of new viral variants. Severity of primary infection determines higher magnitude but poorer quality of long-term neutralizing responses.

The understanding of HIV-1 pathogenesis and clinical progression is incomplete because of the variable contribution of host, immune and viral factors. The involvement of viral factors has been investigated in extreme clinical phenotypes from rapid progressors to long-term non-progressors (LTNPs). Among HIV-1 proteins, the envelope glycoprotein complex (Env) has concentrated many studies for its important role in the immune response and in the first steps of viral replication. In this study, we analyzed the contribution of 41 Envs from 24 patients with different clinical progression rates and viral loads (VLs), LTNP-Elite Controllers (LTNP-ECs); Viremic LTNPs (vLTNPs), and non-controller’s individuals contemporary to LTNPs or recent, named Old and Modern progressors. We analyzed the Env expression, the fusion and cell-to-cell transfer capacities as well as viral infectivity. The sequence and phylogenetic analysis of Envs were also performed. In every functional characteristic, the Envs from subjects with viral control (LTNP-ECs and vLTNPs) showed significant lower performance compared to those from the progressor individuals (Old and Modern). Regarding sequence analysis, the variable loops of the gp120 subunit of the Env (i.e., V2, V4 and mainly V5) of the progressor individuals showed longer and more glycosylated sequences than controller subjects. Therefore, HIV-1 Envs presenting poor viral functions and shorter sequences were associated with viremic control and the non-progressor clinical phenotype, whereas functional Envs were associated with the lack of virological control and progressor clinical phenotypes. These correlations support the central role of Env genotypic and phenotypic characteristics in the in vivo HIV-1 infection and pathogenesis.IMPORTANCEThe role of the virus in the pathogenesis of HIV-1 infection has not been investigated in isolates from individuals with different progression rates. In this work, we studied the properties of the envelope glycoprotein complex (Env) in individuals with different progression rates to elucidate its role in pathogenesis. We estimated the Env expression, the CD4 binding, the fusion and cell-to-cell viral transfer capacities that affect the infectivity of the viral Envs in recombinant viruses. The Envs from individuals which control viral replication and lack clinical progression (LTNP-ECs and vLTNPs) showed lower functional capacities than from subjects with clinical progression (Old and Modern). The functional increase of the Envs characteristics was associated with an increase in viral infectivity and in increased length of variable loops and the number of glycosylation sites of the Env (gp120/SU). These results support the concept that viral characteristics contribute to viral infection and pathogenesis.

To the Editor,In this journal we recently reported our study on serum levels of soluble Fas Ligand (sFasL), a ligand that activates extrinsic apoptosis pathway, in septic patients [1]. At diagnosis...

To assess the potential impact of predominant circulating SARS-CoV-2 variants on neutralizing activity of infected and/or vaccinated individuals, we analyzed neutralization of pseudoviruses expressing the spike of the original Wuhan strain, the D614G and B.1.1.7 variants. Our data show that parameters of natural infection (time from infection and infecting variant) determined cross-neutralization. Importantly, upon vaccination, previously infected individuals developed equivalent B.1.1.7 and Wuhan neutralizing responses. In contrast, uninfected vaccinees showed reduced neutralization against B.1.1.7.FundingThis study was funded by Grifols, the Departament de Salut of the Generalitat de Catalunya, the Spanish Health Institute Carlos III, CERCA Programme/Generalitat de Catalunya, and the crowdfunding initiatives #joemcorono, BonPreu/Esclat and Correos.

The protective effect of neutralizing antibodies in SARS-CoV-2 infected individuals is not yet well defined. To address this issue, we have analyzed the kinetics of neutralizing antibody responses and their association with disease severity. Between March and May 2020, the prospective KING study enrolled 72 COVID-19+ participants grouped according to disease severity. SARS-CoV-2 infection was diagnosed by serological and virological tests. Plasma neutralizing responses were assessed against replicative virus and pseudoviral particles. Multiple regression and non-parametric tests were used to analyze dependence of parameters. The magnitude of neutralizing titers significantly increased with disease severity. Hospitalized individuals developed higher titers compared to mild-symptomatic and asymptomatic individuals, which together showed titers below the detection limit in 50% of cases. Longitudinal analysis confirmed the strong differences in neutralizing titers between non-hospitalized and hospitalized participants and showed rapid kinetics of appearance of neutralizing antibodies (50% and 80% of maximal activity reached after 11 and 17 days after symptoms onset, respectively) in hospitalized patients. No significant impact of age, gender or treatment on the neutralizing titers was observed in this limited cohort. These data identify a clear association of humoral immunity with disease severity and point to immune mechanisms other than antibodies as relevant players in COVID-19 protection. This work was partially funded by Grifols, the Departament de Salut of the Generalitat de Catalunya (Grant DSL0016 to JB and Grant DSL015 to JC), the Spanish Health Institute Carlos III (Grant PI17/01518 and PI18/01332 to JC) and the crowdfunding initiatives #joemcorono, BonPreu/Esclat and Correos. The funders had no role in study design, data collection and analysis, the decision to publish, or the preparation of the manuscript. EP was supported by a doctoral grant from National Agency for Research and Development (ANID)—Formation of Advanced Human Capital Program, Becas Chile: Grant 72180406. We are deeply grateful to all participant and to the technical staff of IrsiCaixa for sample processing. We also thank Daniel Pérez-Zsolt and Jordana Muñoz-Basagoiti for assistance with ACE-2 expressing 293T cell culture. Peer Reviewed "Article signat per 26 autors/es: Benjamin Trinité, Ferran Tarrés-Freixas, Jordi Rodon, Edwards Pradenas, Víctor Urrea, Silvia Marfil, María Luisa Rodríguez de la Concepción, Carlos Ávila-Nieto, Carmen Aguilar-Gurrieri, Ana Barajas, Raquel Ortiz, Roger Paredes, Lourdes Mateu, Alfonso Valencia, Víctor Guallar, Lidia Ruiz, Eulàlia Grau, Marta Massanella, Jordi Puig, Anna Chamorro, Nuria Izquierdo-Useros, Joaquim Segalés, Bonaventura Clotet, Jorge Carrillo, Júlia Vergara-Alert & Julià Blanco"

Altres ajuts: This work was partially funded by Grifols, the Departament de Salut of the Generalitat de Catalunya (grant SLD016 to J.B. and Grant SLD015 to J.C.), and the crowdfunding initiatives #joemcorono, BonPreu/Esclat and Correos. With the spread of new variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), there is a need to assess the protection conferred by both previous infections and current vaccination. Here we tested the neutralizing activity of infected and/or vaccinated individuals against pseudoviruses expressing the spike of the original SARS-CoV-2 isolate Wuhan-Hu-1 (WH1), the D614G mutant and the B.1.1.7 variant. Our data show that parameters of natural infection (time from infection and nature of the infecting variant) determined cross-neutralization. Uninfected vaccinees showed a small reduction in neutralization against the B.1.1.7 variant compared to both the WH1 strain and the D614G mutant. Interestingly, upon vaccination, previously infected individuals developed more robust neutralizing responses against B.1.1.7, suggesting that vaccines can boost the neutralization breadth conferred by natural infection.

The ideal treatment of pelvis bone metastases may be complex and involve multimodality treatment approaches to achieve optimal outcomes. The chapter describes the treatments indications of these patients. It is described from nonoperative treatments, through minimally invasive palliative procedures until reaching the surgical treatment, emphasizing types of pelvis resection and indications for surgical reconstruction of the acetabulum.

There are scarce data on soluble Fas Ligand (sFasL), one of the main ligands that activate the apoptosis extrinsic pathway, in septic patients. In a small study of septic children were found higher plasma sFasL levels in non-survivors compared with survivors; however, an association between blood sFasL levels and mortality controlling for sepsis severity was not stablished due to the small sample size of the study. Therefore, the main objective of this study was to determine whether there is an association between blood sFasL concentrations and mortality in septic patients controlling for sepsis severity.Thirty-day non-surviving patients (The main new finding from our study was that serum sFasL concentrations were associated with mortality in septic patients controlling for sepsis severity. Highlights Blood sFasL concentrations were higher in non-survivor than in survivor patients. There is an association between blood sFasL concentrations and mortality in septic patients. Blood sFasL concentrations could predict mortality of septic patients.

Scarce data on Fas, one of the main receptors that activates the apoptosis extrinsic pathway, in septic patients exists. Higher blood soluble Fas (sFas) concentrations in non-survivor septic patients compared with survivors have been found in small studies; however, the association of blood sFas concentrations with mortality controlling for sepsis severity has not been stablished due to this small sample size in those studies. Thus, our main objective study was to determine whether an association between blood sFas concentrations and sepsis mortality controlling for sepsis severity exists.We included septic patients in this observational and prospective study carried out in three Spanish Intensive Care Units. We obtained serum samples at sepsis diagnosis sepsis for sFas levels determination.Thirty-day non-surviving patients (n=85) compared to surviving patients (n=151) had higher serum sFas levels (p0.001). We found in multiple logistic regression analysis an association of serum sFas levels with mortality controlling for age and SOFA (OR=1.004; 95% CI=1.002-1.006; p0.001), and for age and APACHE-II (OR=1.004; 95% CI=1.002-1.006; p0.001). Serum sFas levels showed and area under the curve for mortality prediction of 71% (95% CI=65-71%; p0.001). Kaplan-Meier analysis showed higher mortality rate in patients with serum sFas levels83.5ng/mL (Hazard ratio=3.2; 95% CI=2.1-5.0; p0.001).That an association between blood sFas concentrations and sepsis mortality controlling for sepsis severity exists was our main new finding study.

Highlights • Non-surviving showed higher RDW than surviving patients. • There is an association between RDW and mortality. • RDW could be used as mortality biomarker., Purpose We have previously reported an association between high red blood cell distribution width (RDW) and mortality in septic and brain infarction patients. However, no association between RDW and mortality in coronavirus disease 2019 (COVID-19) patients has been reported so far; thus, the objective of this study was to determine if that association exists. Methods Prospective and observational study carried out in 8 Intensive Care Units from 6 hospitals of Canary Islands (Spain) including COVID-19 patients. We recorded RDW at ICU admission and 30-day survival. Results We found that patients who did not survive (n = 25) compared to surviving patients (n = 118) were older (p = 0.004), showed higher RDW (p = 0.001), urea (p

OBJETIVO: Estimar a prevalência de quedas acidentais em mulheres e identificar possíveis associações de variáveis sociodemográficas, clínicas e de hábitos de vida com as quedas, em 2007 e 2014. MÉTODOS: Foram realizados dois estudos transversais, em 2007 e 2014, dentro do Projeto de Saúde de Pindamonhangaba (PROSAPIN), com mulheres com idades variando de 35 a 75 anos. As amostras probabilísticas foram selecionadas dentre as mulheres residentes no município e participantes da Estratégia Saúde da Família. A coleta de dados incluiu: entrevista face a face, exame antropométrico e exame sanguíneo. A variável de desfecho “Sofreu queda nos últimos seis meses?” foi levantada durante a entrevista. Foram estimadas as prevalências de quedas em 2007 e 2014 por ponto e intervalo de confiança de 95% (IC95%). Modelos de regressão logística múltipla foram construídos para identificar a associação das variáveis independentes e a ocorrência de quedas para cada ano a partir da odds ratio (OR). Utilizou-se o software Stata 14.0 para análise estatística. RESULTADOS: A s p revalências d e q uedas a cidentais f oram: 17,6% ( IC95% 14,9–20,5) e m 2007 e 17,2% (IC95% 14,8–19,8) em 2014. Em 2007 os fatores associados a quedas foram: idade de 50–64 anos (OR = 1,81; IC95% 1,17–2,80), ensino médio (OR = 1,76; IC95% 1,06–2,93), hiperuricemia (OR = 3,74; IC95% 2,17–6,44), depressão (OR = 2,07; IC95% 1,31–3,27), sono ruim (OR = 1,78; IC95% 1,12–2,82) e sonolência diurna (OR = 1,86; IC95% 1,16–2,99). Em 2014 permaneceram: idade de 50–64 anos (OR = 1,64; IC95% 1,04–2,58), hiperuricemia (OR = 1,91; IC95% 1,07–3,43) e depressão (OR = 1,56; IC95% 1,02–2,38), acrescidos da síndrome metabólica (OR = 1,60; IC95% 1,03–2,47) e da dor musculoesquelética (OR = 1,81; IC95% 1,03–3,18). CONCLUSÕES: As quedas ocorrem de maneira importante em mulheres a partir dos 50 anos, indicando que não são restritas a idosos e que há necessidade de iniciar medidas preventivas mais precocemente. Os dois estudos mostraram magnitudes semelhantes de ocorrência de quedas acidentais e reforçaram sua multifatorialidade. Além disso, a hiperuricemia pode ser um potencial novo fator associado a quedas.

Abusive head trauma (AHT) is an extreme form of physical abuse that is produced by abruptly shaking an infant or toddler.To describe the direct economic cost of care during hospitalization of 14 children with confirmed diagnosis of AHT in a pediatric hospital.Analysis of the cost of disease in patients with AHT attended to between 2001 and 2010. Partial direct economic cost of medical care (days of hospital stay, laboratory tests and imaging studies, surgical procedures and subspecialist consultations) was calculated adjusting for inflation, with year 2001 taken as base year. Patients were classified in three groups (moderate, severe and fatal AHT). Descriptive and sensitivity analysis was carried out.Patients with severe AHT generated higher medical care costs ($105,794.88 ± 33,201.91) in comparison with the group of moderate ($37,012.95, ± 7,154.87) and fatal AHT ($18,595.04 ± 6424.47) (p0.05). Total cost was $665,467.98 Mexican pesos ($71,249.25 international dollars).Total cost for the 14 patients was an elevated figure, as in other parts of the world. The direct economic cost is closely related to the severity of the clinical presentation.El trauma craneal no accidental (TCNA) es una forma extrema de abuso físico que se produce por la sacudida brusca de un lactante o preescolar.Describir el costo económico directo de la atención durante la hospitalización de 14 niños con diagnóstico confirmado de TCNA en un hospital pediátrico.Análisis del costo de la enfermedad en pacientes con TCNA, atendidos entre 2001 y 2010. Se realizó análisis descriptivo y de sensibilidad. Se calculó costo económico directo parcial de la atención médica (días de estancia hospitalaria, exámenes de laboratorio y gabinete, procedimientos quirúrgicos y consultas por subespecialista), ajustado por la inflación, se tomó como año base 2001. Los pacientes se clasificaron en tres grupos: TCNA moderado, severo y fatal.Los pacientes con TCNA severo generaron mayor costo en la atención médica ($105 794.88 ± 33 201.91), en comparación con el grupo con TCNA moderado ($37 012.95 ± 7154.87) y fatal ($18 595.04 ± 6424.47) (p0.05). El costo total fue de 665 467.98 pesos mexicanos (71 249.25 dólares internacionales).El costo total de los 14 pacientes fue una cifra elevada como en otras partes del mundo. El costo económico directo se relaciona estrechamente con la gravedad del cuadro clínico.

Objective To review the chemistry, pharmacology, microbiology, pharmacokinetics, pharmacodynamics, clinical efficacy, safety, dosing, and administration of ceftazidime/avibactam (CAZ/AVI). Data sources A search of PubMed using the terms "ceftazidime," "avibactam," "NXL104," and "AVE1330A" was performed. The manufacturer's website was also reviewed to further identify relevant information. Study selection All English-language articles from 2004 to May 2015 appearing in these searches were reviewed for relevance to this paper. In addition, their bibliographies were reviewed to identify any articles not identified in the searches. Data synthesis CAZ/AVI is a new cephalosporin β-lactamase inhibitor combination with a spectrum of activity targeted against Gram-negative organisms including Enterobacteriaceae and Pseudomonas aeruginosa. The dosing regimen is 2.5 g every eight hours administered via IV infusion over two hours for 5 to 14 days. The dosing regimen should be adjusted based on renal function. A phase II trial has demonstrated that clinical cure rates with CAZ/AVI plus metronidazole are comparable to those with meropenem in the treatment of adults with complicated intra-abdominal infections. Another phase II clinical trial has demonstrated that clinical cure rates with CAZ/AVI are comparable to those with imipenem/cilastatin for the treatment of adults with complicated urinary tract infections (cUTIs). CAZ/AVI has a side effect profile similar to that of cephalosporins and carbapenems. Conclusion CAZ/AVI has a favorable efficacy and safety profile in the treatment of adults with complicated intra-abdominal infections or cUTIs. Further research is needed to refine its role, particularly for the treatment of multi-drug-resistant Gram-negative infections.

This paper reviews the potential of stilbenoids as nutraceuticals. Stilbenoid compounds in wine are considered key factors in health-promoting benefits. Resveratrol and resveratrol-related compounds are found in a large diversity of vegetal products. The stilbene composition varies from wine to wine and from one season to another. Therefore, the article also reviews how food science and technology and wine industry may help in providing wines and/or food supplements with efficacious concentrations of stilbenes. The review also presents results from clinical trials and those derived from genomic/transcriptomic studies. The most studied stilbenoid, resveratrol, is a very safe compound. On the other hand, the potential benefits of stilbene intake are multiple and are apparently due to downregulation more than upregulation of gene expression. The field may take advantage from identifying the mechanism of action(s) and from providing useful data to show evidence for specific health benefits in a given tissue or for combating a given disease.

Objective: To analyze the influence of a kinesiotherapeutic program for the prevention of falls on the cardiovascular function in the elderly. Materials and Methods: The sample consisted of 18 community-living elderly with a mean age of 73.5 ± 8.8 years (14 women; 4 men) who participated in an exercise program for flexibility, strength, balance and proprioception. We measured systolic (SBP) and diastolic (DBP) blood pressure, heart rate (HR) and double product (DP) before and after exercise. The coefficient of variation (CV) of the measures was used, as well as paired t test and Wilcoxon test for comparison between baseline and endpoint after exercise. Results: In 10 sessions, there was an average CV lower than 10% for SBP, DBP and HR. As an acute effect of exercise, there was a significant increase in SBP and DBP and a significant decrease in HR. Comparing the data of the 1st session of exercise to those of the 10th session, we observed that the values of the variables tended to be reduced (except the initial DBP), but with significance only for the final DP. There was a greater reduction in SBP, HR and DP over 20 sessions compared to 10 sessions. Conclusion: The program for the prevention of falls provided chronic effects that are beneficial to cardiovascular function in the elderly, which may also be indicated for the management of cardiovascular diseases. DESCRIPTORS: Aged. Exercises. Arterial Pressure. Heart Rate.

Objetivo: Relatar a experiencia vivenciada por estudantes do Programa de Educacao pelo Trabalho para Saude, Rede de Cuidados a Pessoa com Deficiencia (PET Rede PCD), numa unidade de saude da familia, na construcao e execucao de um Projeto Terapeutico Singular (PTS). Configurando-se como uma proposta interdisciplinar e multiprofissional potencializadora dos diferentes saberes do cuidado. Relato da Experiencia: a ideia de se construir um PTS, uma iniciativa dos estudantes do PET junto a equipe de saude, surgiu diante da necessidade de atender a um maior numero de pessoas da comunidade com deficiencia fisica e que vivem num contexto biopsicossocial de extrema vulnerabilidade. Apos a realizacao de visitas domiciliares e a de identificacao dos criterios de elegibilidade - possibilidades de melhoria da qualidade de vida, complexo contexto familiar, identificacao de necessidades e, principalmente, a necessidade particular de superar dificuldades - o sujeito eleito possui 15 anos de idade, tendo como diagnostico Diplegia Espastica. Comentarios: a realizacao desse PTS junto a equipe de Saude da Familia foi uma experiencia desafiadora e muito proveitosa, possibilitando a troca de saberes entre diversas areas e profissionais, se constituindo como instrumento para a formacao academica dos graduandos envolvidos, alem de estimular a equipe para a educacao permanente. Nao podemos esquecer que a natureza do PTS e ser um processo continuo de planejamento, acompanhamento e avaliacao. Varias metas foram alcancadas, porem ha muito por ser feito. Acreditamos que devemos ser multiplicadores de propostas como essa, valorizando-as para que ocorram mudancas na realidade e no cenario de pratica onde estao sendo formados os profissionais de saude. DESCRITORES Paralisia Cerebral. Espastica. Infantil. Saude Publica.

Objetivo: Relatar experiencias vividas por dois estudantes inseridos na Rede de Servicos a Pessoa com Deficiencia, atraves do Programa de Educacao pelo Trabalho para a Saude (PET SAUDE). Relato de Experiencia: Suas acoes foram desenvolvidas em um centro de media complexidade, referencia em atencao a saude das pessoas com deficiencia no estado da Paraiba, a FUNAD. As acoes visaram primeiramente diagnosticar as necessidades do servico e consequentemente sugerir acoes que favorecam o dialogo entre os usuarios e o servico, bem como a melhoria na qualidade dos servicos prestados. Assim, realizou-se um diagnostico situacional da FUNAD, onde se constatou pontos positivos e fragilidades. Para tal, foi tomado como base o instrutivo CER IV que estabelece Normas Gerais de Funcionamento dos Servicos Especializados em Reabilitacao, entao ao compara-lo com a realidade apresentada pelo servico se identificou a necessidade de desenvolver um projeto de pesquisa que avaliasse a qualidade do servico prestado. Tal necessidade foi discutida com parte da gestao e dos proprios profissionais que se posicionaram de acordo, como tambem se demonstraram estimulados para colaborarem, uma vez que consideraram tal acao uma oportunidade real de mudanca positiva na qualidade das condicoes de trabalho como tambem dos servicos prestados. Conclusao: E de suma importância, para aquisicao de resultados fidedignos, considerar tambem a opiniao dos usuarios, uma vez que sao eles que recebem os servicos prestados e assim sabem as suas reais necessidades. De tal modo, apos a avaliacao da qualidade, serao propostas acoes de melhoria na qualidade dos servicos prestados pela FUNAD. DESCRITORES Deficiencia. Avaliacao em Saude. Servicos de Saude.

Objetivo: O presente artigo tem como proposta realizar um relato de experiencia das atividades vivenciadas no Projeto Pet – Redes de Cuidados a Pessoa com Deficiencia, com enfoque nas acoes desenvolvidas no cenario de praticas da Secretaria Estadual da Saude da Paraiba – Area Tecnica de Saude da Pessoa com Deficiencia, produzindo uma reflexao critica sob a otica dos alunos bolsistas inseridos neste campo de pratica. Material e Metodos: Trata-se de um relato de experiencia que toma como procedimento a analise feita a partir das vivencias pautadas no tripe: Ensino, Pesquisa e Extensao do Programa de Educacao pelo Trabalho em Saude (PET). Resultados: Com isto, pudemos observar a dinâmica de construcao do Plano Estadual da Pessoa com Deficiencia e participar de experiencias para a nossa formacao profissional tais como: Encontro Regional da Economia da Saude do Nordeste 2014: “Avancos e Eficiencias nas Politicas de Saude para o SUS”, Reunioes com o Grupo Condutor Estadual da Paraiba, Oficina PET, dentre outros. Conclusao: Por fim, concluimos que o PET desenvolve e proporciona experiencias impares para a nossa formacao, fazendo com que se obtenha um olhar diferenciado sobre a realidade e o processo de construcao de projetos dentro da gestao. DESCRITORES Gestao em Saude. Pessoas com Deficiencia. Educacao Superior.

INTRODUÇÃO: A população idosa apresenta-se em um acelerado processo de crescimento associado ao aumento da expectativa de vida. As alterações no envelhecimento podem comprometer o padrão de marcha e equilíbrio dos idosos, predispondo-os a quedas. Como estratégia de prevenção, indica-se a atividade física regular direcionada para ganho de força, equilíbrio, propriocepção e melhoria da marcha. OBJETIVO: Verificar os efeitos de um programa de exercícios físicos na marcha e na mobilidade funcional de idosos. MATERIAIS E MÉTODOS: Participaram do estudo oito idosos com mais de 60 anos (três homens e cinco mulheres). Os participantes realizaram duas avaliações antes e após a intervenção de seis meses: (1) marcha, pelo método de marcação de passarelas e (2) equilíbrio, por meio do Time Up and Go Test (TUGT). Para análise dos dados utilizou-se o software R (2.9.0). Para comparação dos dados, foi utilizado o teste t de Student pareado e o teste de correlação de Pearson, com p < 0,05. RESULTADOS: Verificou-se aumento no comprimento dos passos E (de 0,71 ± 0,19 para 0,80 ± 0,19 cm) e D (de 0,73 ± 0,17 para 0,81 ± 0,17 cm), e das passadas E (de 1,44 ± 0,36 para 1,59 ± 0,32 cm). Para o TUGT, além de forte correlação entre idade e velocidade da marcha e base de suporte, observou-se diminuição no tempo de realização do teste (de 13,92 ± 3,84 para 9,46 ± 1,68 segundos). CONCLUSÃO: O programa de exercícios físicos direcionados para a prevenção de quedas melhorou o desempenho funcional de idosos e alterou positivamente as variáveis da marcha. INTRODUCTION: The elderly population is presented in an accelerated growth associated with increased life expectancy. The changes in aging can affect the pattern of gait and balance in the elderly may predispose them to falls. As prevention strategy, regular physical activity is indicated to gain strength, balance, proprioception and gait improvement. OBJECTIVE: To investigate the effects of an exercise program on gait and mobility of elderly. MATERIALS ANS METHODS: Eight subjects (three men and five women) over 60 years old participated in the study. They underwent two assessments: 1) march, by the method of marking walkways, and balance through the Time Up and Go Test (TUGT) before and after the six months intervention. For data analysis, we used R software (2.9.0). To compare the data we used the Student's "t" test paired and Pearson correlation, p < 0.05. RESULTS: An increase in stride length and (0.71 ± 0.19 to 0.80 ± 0.19 cm) and D (0.73 ± 0.17 to 0.81 ± 0.17 cm), and stride E (1.44 ± 0.36 to 1.59 ± 0.32 cm). For TUGT observed reduction in the time of the test (of 13.92 ± 3.84 to 9.46 ± 1.68 seconds), and a strong correlation between age and gait speed and support base. CONCLUSION: The exercise program targeted to prevention of falls improved the performance of elderly and positively affected the gait variables.