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The influence of the geographical location on the chemical composition of commercial Sauvignon Blanc wines was investigated. The assay was carried out on Sauvignon Blanc wines from three cold-climate valleys in Central Chile, Casablanca, Leyda, and San Antonio. The analyses revealed clear variations in some chemical parameters, especially in titratable acidity, which was higher in the geographical areas closest to the Pacific Ocean, such as the Leyda and San Antonio valleys. Regarding the composition of low-molecular-weight phenolic compounds, 17 compounds were found, and the results show that the Casablanca valley exhibits a greater abundance of monomeric flavanols, such as (+)-catechin, whereas the Leyda valley shows a higher abundance in flavonols and phenolic acids esterified with tartaric acid. Concerning the aromatic compound profile, the wines from the Casablanca valley showed a greater abundance of esters, C13 norisoprenoids, and some terpenes. The PLS-DA analysis revealed some differences, especially between wines from Casablanca and Leyda, demonstrating that the difference in the chemical composition of the wines was influenced by the geographical area.

Abstract Neutrophils rely predominantly on glycolytic metabolism for their biological functions, including reactive oxygen species (ROS) production. Although pyruvate kinase M2 (PKM2) is a glycolytic enzyme known to be involved in metabolic reprogramming and gene transcription in many immune cell types, its role in neutrophils remains poorly understood. Here, we report that PKM2 regulates ROS production and microbial killing by neutrophils. Zymosan-activated neutrophils showed increased cytoplasmic expression of PKM2. Pharmacological inhibition or genetic deficiency of PKM2 in neutrophils reduced ROS production and Staphylococcus aureus killing in vitro. In addition, this also resulted in phosphoenolpyruvate (PEP) accumulation and decreased dihydroxyacetone phosphate (DHAP) production, which is required for de novo synthesis of diacylglycerol (DAG) from glycolysis. In vivo, PKM2 deficiency in myeloid cells impaired the control of infection with Staphylococcus aureus. Our results fill the gap in the current knowledge of the importance of lower glycolysis for ROS production in neutrophils, highlighting the role of PKM2 in regulating the DHAP and DAG synthesis to promote ROS production in neutrophils.

Abstract Background The human epidermal growth factor receptor 2 (HER2) and p53 pathways may be involved in chemotherapy sensitivity and/or resistance. We explore the value of HER2 and p53 status to foretell docetaxel sensitivity in advanced breast cancer. Methods HER2 and p53 expression was analysed in 36 (median age 55 yrs; range 37-87) metastatic breast cancer patients receiving docetaxel-based first-line chemotherapy. HER2 was determined by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH), p53 was tested by IHC. We correlate the expression of study parameters with pathologic parameters, RECIST response and survival. The standard cut-off value of 2 was used to determine HER2 overexpression while p53 mean expression level was used to divide low/high expressors tumors. Results Median time to progression and overall survival were 9 (range 2 - 54) and 20 (range 3 - 101) months. Overall response rate was 41.6%. Nine cases showed HER2 overexpression. HER2 was more frequently overexpressed in less differentiated (p = 0.05) and higher stage (p = 0.003) disease. Mean FISH-HER2 values were significantly higher in responder than in non-responder pts (8.53 ± 10.21 vs 2.50 ± 4.12, p = 0.027). Moreover, HER2 overexpression correlates with treatment response at cross-tabulation analysis (p = 0.046). p53 expression was only associated with higher stage disease (p = 0.02) but lack of any significant association with HER status or docetaxel response. No significant relation with survival was observed for any parameter. Conclusion Our data seem to indicate that FISH-determined HER2 status but not p53 is associated with docetaxel sensitivity in metastatic breast cancer.

Abstract Background There is conclusive evidence that human papillomavirus (HPV) infections of the cervix are a necessary cause of cervical cancer. In Italy there are consistent data of HPV prevalence in women aged 25 - 64 years, but there is limited data for younger women. The objective of this on-going 3-year prospective cohort study is to investigate the prevalence, acquisition, clearance and persistence of HPV infections in young Tuscan women and the risk factors correlated with such events. Methods One thousand and sixty-six women aged between 18 and 24 years were enrolled and received an initial HPV test. They were asked to return to the clinic over the study period for further tests every 12 months, if their HPV HR result was negative, or every 6 months, if positive. Additionally, women with an HPV positive result were given a cytological examination and if the cytological diagnosis was ASC-US or more severe, only women with HPV HR, were referred for colposcopy. Results We present here data for the enrolment phase of the study. At baseline, within the study sample, just under 30% of women were infected by HPV and 19.3% of women were infected with oncogenic types. A relationship was highlighted between HPV infection, number of sexual partners (in particularly in the last 3 years) and the lifetime number of partner's partners. Condom use showed a slight protective effect in univariate analysis but these data were not statistically significant in multivariate analysis. The association between HPV infection and demographic and behavioural variables were tested by crude odds ratio (OR). Multivariate logistic regression was applied to compute the adjusted odds ratios. Conclusions The prevalence of oncogenic HPV types was high in young Tuscan women. The 3-year follow-up of this cohort may provide a better understanding of the processes of acquisition, clearance and persistence of infection and the correlated risk factors.

Background: Echocardiographic myocardial work is a new load-independent echocardiographic technique to quantify left ventricle (LV) systolic performance. Our aim was to establish normal values for echocardiographic myocardial work in a large population of healthy children. Methods: For all the subjects 4-, 2-, and 3-chamber-view videos were stored. The following parameters were obtained by offline analysis: the global myocardial work (GMW), the global myocardial constructive work (GCW), the global myocardial wasted work (GWW), and the global myocardial work efficiency (GWE). Age, weight, height, heart rate, and body surface area (BSA) were used as independent variables in the statistical analysis. Results: In all, 516 healthy subjects (age range, 1 day—18 years; median age, 8.2 ± 5.3 years; 55.8% male; body surface area (BSA) range, 0.16 to 2.12 m2) were included. GWI, GCW, and GWW increased with weight, height, and BSA (ρ ranging from 0.635 to 0.226, p all < 0.01); GWI and GCW positively correlated with age (ρ 0.653 and 0.507). After adjusting for BSA differences, females showed higher mean GWI (p = 0.002) and GCW values (p < 0.001), thus Z-score equations for gender have been presented. Conclusions: We provided MW values in a large population of healthy pediatric subjects including lower ages. MW values increased with age and body size and, interestingly, were higher in females than in men. These data cover a gap in current nomograms and may serve as a baseline for the evaluation of MW analysis in children with congenital and acquired heart diseases.

Background: Although coronary artery nomograms in children have been published, data on Caucasian children are lacking. The aim of this study is to provide: (i) a full dataset of coronary artery diameters in healthy children and (ii) a comparison among major previous nomograms. Materials and Methods: We prospectively evaluated 606 healthy subjects (age range, 1 days–2 scores, were logarithmic (ln[y] = a + b*ln[x]). Predicted values and Z-score boundaries by BSA are provided. Our ranges of normality are slightly lower than those, diverging from −0.22 to −0.59 Z-scores for the left main coronary artery and from −0.23 to −0.3 Z-scores for the right coronary artery. Conclusions: We report a complete dataset of normal echocardiography coronary artery diameter (including new measures of the proximal origin) values in a large population of healthy children. Our data were statistically like those of north American nomograms.

Resumo Em 2009, a Frente Nacional de Prefeitos (FNP) denominou g100 um grupo de municípios caracterizados por possuir mais de 80 mil habitantes, baixos níveis de receita pública per capita e alta vulnerabilidade socioeconômica. Este estudo buscou descrever o g100 a partir da posição comparativa segundo três medidas de vulnerabilidade socioeconômica aplicadas aos municípios com mais de 80 mil habitantes, discutindo a pertinência do uso da proposta da FNP como critério de priorização em políticas sociais. Comparou-se a listagem dos 100 primeiros municípios g100 com aquelas do Índice do Desenvolvimento Humano Municipal (IDHM), Índice de Vulnerabilidade Social (IVS) e Índice Brasileiro de Privação (IBP). Identificou-se que 25 municípios classificados como g100 não estavam entre os 100 primeiros nos demais índices; mas 46 municípios g100 encontravam-se entre os mais vulneráveis nas três medidas. Discute-se a necessidade de amplo debate e consenso sobre as medidas de vulnerabilidade socioeconômica empregadas no planejamento e execução de políticas públicas. Esta reflexão está ancorada na defesa de que as ações e políticas públicas sejam intrinsicamente planejadas para garantia de maior equidade geográfica e alocativa em face da efetividade de resposta às demandas da população.

Background: Guidelines recommend targeting decongestion in management of decompensated HF, with lower extremity edema often serving as the clinical target. LECW are seldom used in the acute setting, with a paucity of data on efficacy in HF, despite serving as a cornerstone of chronic lymphedema management. Primary objective: Study the efficacy and safety of LECW in acute decompensated HF. Methods: Open-label, randomized, parallel-group clinical trial. Primary outcomes: Days on intravenous (IV) diuretic therapy, total hospital length of stay (LOS), and 30-day all-cause readmission. Results: 32 patients were enrolled, with 29 patients completing the study. Enrollment was suspended due to the COVID-19 pandemic. Overall LOS was shorter in the intervention group (3.5 vs 6 days, p = 0.05), with no significant difference in total days on IV diuresis or 30-day readmission rate with use of LECW. Fewer patients required continuous diuretic infusion after treatment with LECW (0 vs 7 patients, p = 0.027). The intervention group scored significantly better on the MLWHF (55.5 vs 65, p = 0.021), including both the physical and emotional dimension scores. No adverse events were reported with use of LECW, including a significantly lower incidence of AKI (1 vs 13 patients, p = 0.005). Conclusion: The use of LECW resulted in reduced hospital LOS compared to standard therapy, with no difference in days of IV diuresis administration or 30-day readmission. Treatment with LECW also resulted in less continuous IV diuretic therapy, fewer incidence of AKI, and improved quality of life. Trends toward less escalation of diuresis, and greater reduction in edema were also observed.

Background: The decision to perform biventricular repair (BVR) in neonates and infants presenting with either single or multiple left ventricle outflow obstructions (LVOTOs) and a borderline left ventricle (BLV) is subject to extensive discussion, and limited information is known regarding the long-term outcomes. As a result, the objective of this study is to critically assess and summarize the available data regarding the prognosis of neonates and infants with LVOTO and BLV who underwent BVR. Methods: In February 2023, we conducted a review study with three different medical search engines (the National Library of Medicine, Science Direct, and Cochrane Library) for Medical Subject Headings and free text terms including “congenital heart disease”, “outcome”, and “borderline left ventricle”. The search was refined by adding keywords for “Shone’s complex”, “complex LVOT obstruction”, “hypoplastic left heart syndrome/complex”, and “critical aortic stenosis”. Results: Out of a total of 51 studies, 15 studies were included in the final analysis. The authors utilized heterogeneous definitions to characterize BLV, resulting in considerable variation in inclusion criteria among studies. Three distinct categories of studies were identified, encompassing those specifically designed to evaluate BLV, those focused on Shone’s complex, and finally those on aortic stenosis. Despite the challenges associated with comparing data originating from slightly different cardiac defects and from different eras, our results indicate a favorable survival rate and clinical outcome following BVR. However, the incidence of reintervention remains high, and concerns persist regarding residual pulmonary hypertension, which has been inadequately investigated. Conclusions: The available data concerning neonates and infants with LVOTO and BLV who undergo BVR are inadequate and fragmented. Consequently, large-scale studies are necessary to fully ascertain the long-term outcome of these complex defects.

Abstract Morphology‐based taxonomic research frequently applies linear morphometrics (LMM) in skulls to quantify species distinctions. The choice of which measurements to collect generally relies on the expertise of the investigators or a set of standard measurements, but this practice may ignore less obvious or common discriminatory characteristics. In addition, taxonomic analyses often ignore the potential for subgroups of an otherwise cohesive population to differ in shape purely due to size differences (or allometry). Geometric morphometrics (GMM) is more complicated as an acquisition technique but can offer a more holistic characterization of shape and provides a rigorous toolkit for accounting for allometry. In this study, we used linear discriminant analysis (LDA) to assess the discriminatory performance of four published LMM protocols and a 3D GMM dataset for three clades of antechinus known to differ subtly in shape. We assessed discrimination of raw data (which are frequently used by taxonomists); data with isometry (i.e., overall size) removed; and data after allometric correction (i.e., with nonuniform effects of size removed). When we visualized the principal component analysis (PCA) plots, we found that group discrimination among raw data was high for LMM. However, LMM datasets may inflate PC variance accounted in the first two PCs, relative to GMM. GMM discriminated groups better after isometry and allometry were removed in both PCA and LDA. Although LMM can be a powerful tool to discriminate taxonomic groups, we show that there is substantial risk that this discrimination comes from variation in size, rather than shape. This suggests that taxonomic measurement protocols might benefit from GMM‐based pilot studies, because this offers the option of differentiating allometric and nonallometric shape differences between species, which can then inform on the development of the easier‐to‐apply LMM protocols.

Abstract Background In the pharmaceutical industry, competing for few validated drug targets there is a drive to identify new ways of therapeutic intervention. Here, we attempted to define guidelines to evaluate a target’s ‘fitness’ based on its node characteristics within annotated protein functional networks to complement contingent therapeutic hypotheses. Results We observed that targets of approved, selective small molecule drugs exhibit high node centrality within protein networks relative to a broader set of investigational targets spanning various development stages. Targets of approved drugs also exhibit higher centrality than other proteins within their respective functional class. These findings expand on previous reports of drug targets’ network centrality by suggesting some centrality metrics such as low topological coefficient as inherent characteristics of a ‘good’ target, relative to other exploratory targets and regardless of its functional class. These centrality metrics could thus be indicators of an individual protein’s ‘fitness’ as potential drug target. Correlations between protein nodes’ network centrality and number of associated publications underscored the possibility of knowledge bias as an inherent limitation to such predictions. Conclusions Despite some entanglement with knowledge bias, like structure-oriented ‘druggability’ assessments of new protein targets, centrality metrics could assist early pharmaceutical discovery teams in evaluating potential targets with limited experimental proof of concept and help allocate resources for an effective drug discovery pipeline.

Abstract There is currently a need for adaptation in higher education due to the new demands of society. In this context, two factors are noteworthy: academic engagement and entrepreneurial education. This study aimed to examine whether entrepreneurship education influences academic engagement and entrepreneurial potential in college students participating and not participating in entrepreneurship education programs. It is a quantitative, exploratory, and correlational study on a 563-student sample, using the Entrepreneurial Potential Identification Scale - Escala para Identificar Potencial Empreendedor, the Utrecht Work Engagement Scale-Students, and a sociodemographic questionnaire. The results showed that students who entered an entrepreneurial training program had significantly higher rates of academic engagement and entrepreneurial potential, when compared with academics from institutions that did not have a program designed for this purpose. It is concluded that investing in entrepreneurial education can foster the generation of more engaged students with greater entrepreneurial potential.

Purpose – This research aims to investigate the different impacts of easy (fluency) and difficult (disfluency) business relationship evaluations on future purchase intentions. In addition, it seeks to investigate the mediating role of confidence in these evaluations and present a new form of fluency manipulation performed directly by satisfaction evaluations. Design/methodology/approach – This research includes a first experiment with a 3 (fluency: easy vs difficult vs control) x 2 (hypothetical scenario of satisfaction vs dissatisfaction) factorial design, using 180 undergraduate students, and a second single factor experiment (fluency: easy vs difficult vs control) with 326 consumers evaluating their financial services provider. Both used a between-subject design with the individuals being randomly distributed between the scenarios. Findings – Dissatisfied consumers who perceived ease in evaluating commercial relationships have increased confidence in these evaluations, negatively influencing their purchase intentions. Meanwhile, satisfied consumers are generally overconfident, being equally affected by perceived difficulty or ease due to a direct bias from the evaluation, which increases purchase intentions. Originality/value – The results demonstrate that fluency (perceived ease or difficulty) depends on the valence of the evaluations, directly affecting (positive valence) or indirectly affecting (negative valence) subsequent decisions. We also present a new, faster, and more practical way to manipulate fluency. Furthermore, we raise some ethical questions as these effects result in biased decisions.

Abstract The biogeographic distribution of diversity among populations of threatened mammalian species is generally investigated using population genetics. However, intraspecific phenotypic diversity is rarely assessed beyond taxonomy‐focused linear measurements or qualitative descriptions. Here, we use a technique widely used in the evolutionary sciences—geometric morphometrics—to characterize shape diversity in the skull of an endangered marsupial, the northern quoll, across its 5,000 km distribution range along Northern Australia. Skull shape is a proxy for feeding, behavior, and phenotypic differentiation, allowing us to ask whether populations can be distinguished and whether patterns of variation indicate adaptability to changing environmental conditions. We analyzed skull shape in 101 individuals across four mainland populations and several islands. We assessed the contribution of population, size, sex, rainfall, temperature, and geography to skull shape variation using principal component analysis, Procrustes ANOVA, and variation partitioning analyses. The populations harbor similar amounts of broadly overlapping skull shape variation, with relatively low geographic effects. Size predicted skull shape best, coinciding with braincase size variation and differences in zygomatic arches. Size‐adjusted differences in populations explained less variation with far smaller effect sizes, relating to changes in the insertion areas of masticatory muscles, as well as the upper muzzle and incisor region. Climatic and geographic variables contributed little. Strikingly, the vast majority of shape variation—76%—remained unexplained. Our results suggest a uniform intraspecific scope for shape variation, possibly due to allometric constraints or phenotypic plasticity beyond the relatively strong allometric effect. The lack of local adaptation indicates that cross‐breeding between populations will not reduce local morphological skull (and probably general musculoskeletal) adaptation because none exists. However, the potential for heritable morphological variation (e.g., specialization to local diets) seems exceedingly limited. We conclude that 3D geometric morphometrics can provide a comprehensive, statistically rigorous phenomic contribution to genetic‐based conservation studies.

Background: Echocardiographic screening of anomalous coronary artery origin is of increasing interest for children participating in sport activities. However, criteria to define normal coronary artery origins in children are poorly defined. Thus, the aim of the present investigation is to define the normal origin and angle of emergence of coronary arteries by echocardiography in healthy children. Materials and methods: The distances of the left main and right coronary artery (LMCA, RCA) origins from the aortic annulus were measured in the parasternal long-axis view (LAX). The angle of coronary artery emergence was measured in the parasternal short-axis view (SAX). Results: A total of 700 healthy subjects (mean age: 9.53 ± 5.95 years; range: 1 day–17.98 years) were prospectively enrolled. The distance of the RCA and LMCA from the aortic annulus correlated with body surface area, and nomograms (Z-scores) were generated. The RCA origin was below the sinotubular junction (STJ) in 605 patients (86.43%), at the STJ in 66 patients (9.43%), and above the STJ in 29 patients (4.14%). The LMCA origin was below the STJ in 671 patients (95.86%), at the STJ in 12 patients (1.71%), and above the STJ in 17 patients (2.43%). With respect to the RCA, an emergence angle < 18.5° in the SAX predicted a high take-off. with a sensitivity of 98.3% and a specificity of 93.1% (AUC 0.998). With respect to the LMCA, an emergence angle > 119.5° in the SAX predicted a high take-off, with a sensitivity of 70.6% and a specificity of 82.4% (AUC 0.799). Conclusion: This study establishes nomograms for LMCA and RCA origin in standard echocardiographic projections in healthy children.

A very rare variant of MPD is the Pigmented Mammary Paget Disease (PMPD), first described by Culberson et al. in 1956. It is very difficult to distinguish this variant from melanoma both clinically and dermoscopically. The diagnosis is confirmed by histopathology and immunohistochemistry. Correct diagnosis is crucial for surgical treatment, which is different for these two diseases. We report the case of a 92-year-old woman, who presented an asymptomatic pigmented lesion of the right nipple and areola. The lesion was arisen for about 6 months and was suspected for melanoma because of clinical and dersmoscopic characteristics. Incisional biopsy revealed tumor cells, that proliferate in the major mammary ducts, and tumor cells in the overlying epidermis of the nipple, thus diagnosing pigmented mammary Paget disease (PMPD). The patient underwent radical mastectomy.

This article examines the Uruguayan state approach to the teaching of writing in public elementary education during the 1830s, and is an attempt to explain why state officials advanced new pedagogical methods aimed at increasing rationalisation and standardisation. While many different handwriting styles existed in the past, the school system simplified and standardised public education under a single cursive style, the English round-hand. Notwithstanding the state's standardising directives, Uruguayan teachers combined the pedagogical innovations of Lancaster's monitorial system with the calligraphic traditions of the old writing masters. According to personal preference and necessity, teachers devised a hybrid system, which implemented new dictation exercises and the use of the writing slate, but preserved the writing masters' imitation of "muestras," and the use of quill, ink, and paper. The government arranged an inventive procedure to accurately measure students' handwriting performance. The "planas," or samples of students' handwriting, were useful tools in the standardisation and evaluation of public education. Elementary schools from all over the country forwarded handwriting samples to the central state, or exhibited them in public examination ceremonies, as teachers publicised pedagogical success, and state officials confirmed the general advancement of public education. This study is also an attempt to show that the teaching of writing was part of a greater pedagogical mission and nation-building project: the intentional departure from colonial corporate identities, and the construction of a national community conceived as the sum of its individual citizens.

Studies highlight that although the spiritual/religious dimension is commonly used as a resource for coping with stress and suffering, sometimes this dimension can also be a locus of struggles. The Religious and Spiritual Struggles (RSS) Scale, composed of 26 items (extended version), is an instrument that assesses the presence of six types of spiritual struggles, categorized into three major categories: Intrapersonal, Interpersonal, and Supernatural. More recently, studies have presented a leaner version, with 14 items (short version), also suitable for evaluating religious/spiritual struggles. This study aimed to validate the RSS Scale, in its two versions, in the Brazilian cultural context and was able to attest to its quality and reliability, albeit with small variations. The Brazilian extended version presented six components (similar to the original version) explaining 68.48% of variance and 0.907 of KMO. Two items were withdrawn due to low loadings, but the psychometric qualities of both versions in two different samples (one wide sample and one with LGBTQIA+ individuals) were maintained. The reliability (Cronbach’s alpha) for each one of the six components ranged from 0.78 to 0.88 (24 items) and from 0.73 to 0.83 (14 items). The TLI and CFI were, respectively, 0.934 and 0.945 (24 items) and 0.982 and 0.988 for the short version (14 items). Furthermore, convergent validity tests indicated correlations with the Satisfaction with Life Scale. The RSS Scale (the Brazilian versions with 24 and 14 items), demonstrated reliability in the studied sample and can be applied in clinical and research contexts.

Non-alcoholic fatty liver disease (NAFLD) is one of the most common forms of liver disease, which is associated with several etiological factors, including stress and dysfunction in oxidative metabolism. However, studies showed that aerobic exercise training (AET) can combat the oxidative stress (OS) and improves mitochondrial functionality in the NAFLD. To test the hypothesis that AET improves oxidative metabolism and antioxidant defense in the liver of ob/ob mice. Male ob/ob mice with eight weeks old were separated into two groups: the sedentary group (S), n=7, and the trained group (T), n=7. The T mice were submitted to an 8-week protocol of AET at 60% of the maximum velocity achieved in the running capacity test. Before AET, no difference was observed in running test between the groups (S=10.4 ± 0.7 min vs. T= 13 ± 0.47 min). However, after AET, the running capacity was increased in the T group (12.8 ± 0.87 min) compared to the S group (7.2 ± 0.63 min). In skeletal muscle, the T group (26.91 ± 1.12 U/mg of protein) showed higher citrate synthase activity compared with the S group (19.28 ± 0.88 U/mg of protein) (p =0.006). In the analysis of BW evolution, significant reductions were seen in the T group as of the fourth week when compared to the S group. In addition, food intake was not significant different between the groups. Significant increases were observed in the activity of enzymes citrate synthase (p=0.004) and β-HAD (p=0.01) as well as in PGC-1α gene expression (p=0.002) in the liver of T group. The levels of TBARs and carbonyls, as well as SOD, CAT and GST were not different between the groups. However, in the nonenzymatic antioxidant system, we found that the T group had higher sulfhydryl (p = 0.02), GSH (p=0.001) and GSH/GSSG (p=0.02) activity. In conclusion, the AET improved body weight evolution and the aerobic capacity, increased the response of oxidative metabolism markers in the liver such as PGC-1α gene expression and citrate synthase and β-HAD enzyme activities in ob/ob mice. In addition, AET improved the non-enzymatic antioxidant defense and did not change the enzymatic defense.

Background Previous data have reported that the growth of established tumors may be facilitated by postsepsis disorder through changes in the microenvironment and immune dysfunction. However, the influence of postsepsis disorder in initial carcinogenesis remains elusive.Methods In the present work, the effect of postsepsis on inflammation-induced early carcinogenesis was evaluated in an experimental model of colitis-associated colorectal cancer (CAC). We also analyzed the frequency and role of intestinal T regulatory cells (Treg) in CAC carcinogenesis.Results The colitis grade and the tumor development rate were evaluated postmortem or in vivo through serial colonoscopies. Sepsis-surviving mice (SSM) presented with a lower colonic DNA damage, polyp incidence, reduced tumor load, and milder colitis than their sham-operated counterparts. Ablating Treg led to restoration of the ability to develop colitis and tumor polyps in the SSM, in a similar fashion to that in the sham-operated mice. On the other hand, the growth of subcutaneously inoculated MC38luc colorectal cancer cells or previously established chemical CAC tumors was increased in SSM.Conclusion Our results provide evidence that postsepsis disorder has a dual effect in cancer development, inhibiting inflammation-induced early carcinogenesis in a Treg-dependent manner, while increasing the growth of previously established tumors.

Overweight and obesity are a worldwide pandemic with geographic differences. Possible explanations include variable access to food and its quality, dietary habits of the populations, behavioral patterns, and characteristics of the food markets. This study aimed to examine the acquisition of food in the different regions of Brazil and to relate it with the geography of Brazilian obesity. We used data provided by a Brazilian official organ, which gathers periodic data on the household food acquisition. Descriptive statistics and multidimensional scaling techniques were used to ascertain the similarity of food acquisition among populations in the Brazilian states. High levels of overweight and obesity occur in all states (>44%), especially in the southern half of the country (>54%). We found differences in the food acquisition patterns throughout the country. Furthermore, we identify that states with similar dietary patterns have similar population levels of overweight and obesity, demonstrating a possible relationship between the food supply models and these food insecurity manifestations as expressed in the individual health. However, the occurrence of regional singularities suggests that the food supply model constitutes only one of the multiple variables that compete for diversity in the Brazilian regional distribution of obesity and overweight. We found that socioeconomic conditions influence nutritional misalignment in the geography of Brazil. Our results show that overweight and obesity have a higher occurrence in middle age (35–79 years), and it is more present in females. Moreover, women with lower education and lower incomes have higher levels of overweight and obesity, an association of unhealthy food intake with poverty. In men, obesity is more frequent in those with more schooling and higher incomes. Based on the widely variable geographical characteristics of the distant states of Brazil, we conclude that overweight and obesity go beyond an individual lifestyle and access to quality food, and is more related to a complex framing of factors, like schooling, age, sex, income, feeding patterns, food markets, and anthropological circumstances.

BackgroundEfficacy and safety of treatments for hospitalized COVID-19 are uncertain. We systematically reviewed efficacy and safety of remdesivir for the treatment of COVID-19.MethodsStudies evaluating remdesivir in adults with hospitalized COVID-19 were searched in several engines until August 21, 2020. Primary outcomes included all-cause mortality, clinical improvement or recovery, need for invasive ventilation, and serious adverse events (SAEs). Inverse variance random effects meta-analyses were performed.ResultsWe included four randomized controlled trials (RCTs) (n = 2296) [two vs. placebo (n = 1299) and two comparing 5-day vs. 10-day regimens (n = 997)], and two case series (n = 88). Studies used intravenous remdesivir 200mg the first day and 100mg for four or nine more days. One RCT (n = 236) was stopped early due to AEs; the other three RCTs reported outcomes between 11 and 15 days. Time to recovery was decreased by 4 days with remdesivir vs. placebo in one RCT (n = 1063), and by 0.8 days with 5-days vs. 10-days of therapy in another RCT (n = 397). Clinical improvement was better for 5-days regimen vs. standard of care in one RCT (n = 600). Remdesivir did not decrease all-cause mortality (RR 0.71, 95%CI 0.39 to 1.28, I2 = 43%) and need for invasive ventilation (RR 0.57, 95%CI 0.23 to 1.42, I2 = 60%) vs. placebo at 14 days but had fewer SAEs; 5-day decreased need for invasive ventilation and SAEs vs. 10-day in one RCT (n = 397). No differences in all-cause mortality or SAEs were seen among 5-day, 10-day and standard of care. There were some concerns of bias to high risk of bias in RCTs. Heterogeneity between studies could be due to different severities of disease, days of therapy before outcome determination, and how ordinal data was analyzed.ConclusionsThere is paucity of adequately powered and fully reported RCTs evaluating effects of remdesivir in hospitalized COVID-19 patients. Until stronger evidence emerges, we cannot conclude that remdesivir is efficacious for treating COVID-19.

Mass-vaccination against COVID-19 is still a distant goal for most low-to-middle income countries. The experience gained through decades producing polyclonal immunotherapeutics (such as antivenoms) in many of those countries is being redirected to develop similar products able to neutralize SARS-CoV-2 infection. In this study we analyzed the biological activity (viral neutralization or NtAb) and immunochemical properties of hyperimmune horses’ sera (HHS) obtained during initial immunization (I) and posterior re-immunization (R) cycles using the RBD domain of the SARS-CoV-2 spike protein as antigen. HHS at the end of the R cycle showed higher NtAb titers when compared to those after the I cycle (35,585 vs. 7000 mean NtAb, respectively). Moreover, this increase paralleled an increase in avidity (95.2% to 65.2% mean avidity units, respectively). The results presented herein are relevant for manufacturers of these therapeutic tools against COVID-19.

Background: Speckle-tracking echocardiography (STE) has gained increasing value in the evaluation of congenital heart diseases (CHD); however, its use in pediatric cardiac surgery is limited. Aim: To evaluate left ventricular (LV) systolic impairment after biventricular pediatric cardiac surgery by STE strain (ε) analysis. Methods: We prospectively enrolled 117 children undergoing cardiac surgery for CHD. Echocardiography was performed at four different times: pre-operatively, 12–36 h (Time 1), 3–5 days (Time 2), and 6–8 days (Time 3). Images were obtained in the 4-2-and 3 apical chamber’s views to derive LV global and regional (basal/mid/apical) ε values. Results: At different postoperative times, we performed 320 examinations in 117 children (mean age: 2.4 ± 3.9, range: 0–16 years); 117 age-matched healthy children served as controls. All global, basal, and mid LVε values decreased after surgery; the lowest values being at Time 1 (p < 0.0001), which increased thereafter. At discharge, all global, basal, and mid LVε values remained lower than in pre-operative and healthy children (p < 0.05). Instead, apical segments (lowest at baseline) increased after surgery (p < 0.0001) but remained lower compared to controls. LV ejection fraction (LVEF) decreased at Time 1 (p = 0.0004) but promptly recovered to Time 2 and normalized at Time 3. Conclusions: STE ε analysis revealed a significant LV systolic impairment after surgery with amelioration thereafter but incomplete normalization at discharge. Base-apex differences emerged with apical segments that, contrary to all the other regions, showed relative hypercontractility after surgery. The slower recovery of LVε values compared to LVEF suggests that STE ε analysis may be more accurate for the follow-up of mild LV post-surgical impairment.

Resumo: O objetivo foi analisar as barreiras de acesso aos serviços de saúde existentes em cinco Regiões de Saúde do Brasil. Foram analisadas as respostas obtidas a partir da aplicação de questionários semiestruturados a gestores, prestadores e, em número mais restrito, a profissionais de saúde do Sistema Único de Saúde, tendo como referência as dimensões: Acessibilidade Geográfica, Disponibilidade e Aceitabilidade. Foram verificadas as especificidades em relação às barreiras de acesso nas regiões consideradas, já outras como a localização e tempo gasto no trajeto foram barreiras em quase todas elas quando foi considerado o cuidado ao acidente vascular cerebral. Quando à Disponibilidade, foram observadas questões relacionadas à insuficiência de médicos, tempo de espera prolongado e problemas relativos à integração, em todas as regiões. Quanto à Aceitabilidade, destacou-se a crença dos usuários de não possuir problemas de saúde. As Regiões de Saúde situadas no Sul e Sudeste do país registraram menor quantidade e diversidade de barreiras, revelando a persistência de desigualdades regionais. Embora os resultados não representem o conjunto do Brasil, permitem apontar questões relevantes sobre o processo de regionalização do sistema de saúde no país.

BackgroundBladder cancer (BC) is the 9th most common cancer diagnosis worldwide. Low grade (LG) represents 70% of all BCs, characterized by recurrence and rare ability (10-15%) to progress to high grade (HG) and invade. The remaining 30% is high grade (HG), fast invasive BC, which is resistant to therapy. Identifying biomarkers for predicting those tumors able to progress is a key goal for patient outcome improvement. This study focuses on the most promising prognostic markers.Materials and methodsTP53 and FGFR3 mutational status, Survivin, CK19, CK20, E-cadherin and CD44 gene expression analysis were performed on 66 BCs.ResultsSurvivin was found associated to tumor grade (pConclusionWe suggest Survivin, both as a biomarker associated to G3 BCs but negatively related to TP53 mutational status, and as a potential novel therapeutic target.

In this study, the effects of static and multi-pulsed mild-intensity high hydrostatic pressure (HHP) treatments (60 or 100 MPa, ~23 °C) on the extractability and accumulation of phenolics and carotenoids in whole carrots were evaluated. HHP treatments were applied for the time needed to reach the desired pressure (come-up-time, CUT) either as a single pulse or multi-pulse (2P, 3P, and 4P). Likewise, a single sustained treatment (5 min) applied at 60 or 100 MPa was evaluated. Individual carotenoids, free and bound phenolics were quantified after HHP treatment and subsequent storage (48 h, 15 °C). As an immediate HHP response, phenolic extractability increased by 66.65% and 80.77% in carrots treated with 3P 100 MPa and 4P 60 MPa, respectively. After storage, CUT 60 MPa treatment accumulated free (163.05%) and bound (36.95%) phenolics. Regarding carotenoids, total xanthophylls increased by 27.16% after CUT 60 MPa treatment, whereas no changes were observed after storage. Results indicate that HHP processing of whole carrots at mild conditions is a feasible innovative tool to enhance the nutraceutical properties of whole carrots by increasing their free and bound phenolic content while maintaining carotenoid levels. HHP treated carrots can be used as a new functional food or as raw material for the production of food and beverages with enhanced levels of nutraceuticals.

Introduction: Attentional bias, the tendency that a person has to drive or maintain attention to a specific class of stimuli, may play an important role in the etiology and persistence of mental disorders. Attentional bias modification has been studied as a form of additional treatment related to automatic processing. Objectives: This systematic literature review compared and discussed methods, evidence of success and potential clinical applications of studies about attentional bias modification (ABM) using a visual probe task. Methods: The Web of Knowledge, PubMed and PsycInfo were searched using the keywords attentional bias modification, attentional bias manipulation and attentional bias training. We selected empirical studies about ABM training using a visual probe task written in English and published between 2002 and 2014. Results: Fifty-seven studies met inclusion criteria. Most (78%) succeeded in training attention in the predicted direction, and in 71% results were generalized to other measures correlated with the symptoms. Conclusions: ABM has potential clinical utility, but to standardize methods and maximize applicability, future studies should include clinical samples and be based on findings of studies about its effectiveness.

Fibre-reinforced concrete (FRC) has been used in numerous types of precast elements around the world, as has been shown that reductions in production costs and time can be obtained; however, there is little experience of this material in Uruguay. Therefore, our study analysed the feasibility of its utilisation in this country. This paper reports on the development of a simple analysis model that is useful for the design of FRC precast elements. The model efficiency was evaluated through its application to a practical case study—vertical precast concrete sandwich panel systems tested by bending. Three different types of reinforcement were analysed: synthetic fibres, metal fibres, and steel mesh. With the developed model, the cost-efficiency of different panel geometries and amounts of reinforcement were evaluated. The model allowed consideration of the contribution of the fibres to withstand internal tensile forces of the panels and therefore be able to substitute for the steel mesh in the panel wythes. It was found that it was possible to optimise panel reinforcement and geometry, thereby reducing wythe thickness. Besides the reduction in production time, it was possible to achieve cost savings of up to 10% by replacing steel mesh with fibres and of more than 20% if the geometry was also modified.

Objetivo: avaliar a adequação do cuidado no desempenho dos serviços de saúde na atenção básica, de média e alta complexidade nas regiões e unidades federadas brasileiras no período de 1998 a 2010. Métodos: dados dos sistemas nacionais de informação em saúde de nascidos vivos, doenças de notificação compulsória, atendimento ambulatorial e hospitalar e dados demográficos do Instituto Brasileiro de Geografia e Estatística foram utilizados para o cálculo de taxas padronizadas, médias, razões e proporções para o Brasil, regiões e unidades federativas no período de 1998 a 2010. Resultados: melhor adequação dos serviços de saúde foi observada na área básica e na alta complexidade identificadas pela evolução positiva do número de consultas de pré-natal em todas as regiões e do percentual de tomografias realizadas em pacientes com acidente vascular cerebral que usaram tomografia computadorizada que alcançam, respectivamente, valores em torno de 61% e 33% em 2010. Conclusão: uma melhor avaliação da adequação depende tanto da implementação de políticas e práticas de saúde mais equitativas quanto de mudanças nos registros administrativos.

Sentinel lymph node biopsy is a crucial step in the management of patients affected by melanoma. The decision whether to perform it or not is based on different histological parameters, but the mitotic rate is no longer considered a prognostic variable after the release of the 8th edition of the American Joint Committee on Cancer (AJCC) guidelines. Our objective was to investigate the risk factors that increase the chance for sentinel lymph node positivity in melanomas with a Breslow thickness of less than 2.00 mm, including the mitotic count. A retrospective single-center study was performed on a homogenous cohort of 408 patients treated for cutaneous melanoma. Histological and clinical features were gathered and correlated with the increased risk for sentinel lymph node positivity by means of univariate and multivariate analyses. A statistically significant correlation between a high mitotic index and a positive sentinel lymph node was found in pT1 and pT2 patients, suggesting that in the case of pT1a melanoma with a high number of mitoses, a discussion about whether a sentinel lymph node biopsy is required should be done. [ABSTRACT FROM AUTHOR]

Resumen INTRODUCCIÓN La incidencia de insuficiencia renal aguda a nivel mundial es 18% y la mortalidad intrahospitalaria puede alcanzar más del 50%. En Perú, existen escasos estudios acerca de la mortalidad en pacientes con insuficiencia renal aguda en hemodiálisis. OBJETIVOS Identificar los factores de riesgo asociados a mortalidad intrahospitalaria en pacientes con insuficiencia renal aguda en hemodiálisis. MÉTODOS Es una cohorte retrospectiva, en la cual se estudió a los pacientes con insuficiencia renal aguda en hemodiálisis en el Hospital Nacional Edgardo Rebagliati Martins entre enero de 2013 y diciembre de 2015. Se halló un tamaño de muestra de 154 pacientes con una potencia de 80%, y un intervalo de confianza de 95%. Se utilizaron los códigos de la Clasificación Internacional de Enfermedades-10 para identificar las historias clínicas de pacientes con insuficiencia renal aguda (N.17) y hemodiálisis (Z.49). La variable independiente fue oliguria y la variable dependiente fue mortalidad intrahospitalaria. Para el análisis multivariado, se utilizó regresión de Poisson. RESULTADOS El universo fue de 285 pacientes. Se revisaron 212 historias clínicas y se excluyeron 44. De las 168 historias clínicas estudiadas, 129 pertenecían a pacientes vivos y 39 a fallecidos. La incidencia de mortalidad fue de 17,2%. Las principales causas de insuficiencia renal aguda en hemodiálisis fueron sepsis (39,2%) y deshidratación severa (10,8%). En el modelo ajustado, los factores de riesgo asociados a mortalidad intrahospitalaria de insuficiencia renal aguda en hemodiálisis fueron lactato (riesgo relativo 1,09), potasio (riesgo relativo 0,93), y presión arterial media (riesgo relativo 0,97). CONCLUSIONES El lactato es un parámetro objetivo que permite predecir el pronóstico y contribuye a un mejor manejo de los pacientes con insuficiencia renal aguda en hemodiálisis.

Purpose: The purpose of this paper is to identify the number of courses related to sustainability offered in bachelor degree programs of business administration in Brazilian federal universities. Design/methodology/approach: An exploratory research was carried out based on a descriptive scope. The process of mapping federal universities in Brazil was carried out using data available in the Cadastro das Instituicoes de Educacao Superior (General Register of Undergraduate Institutions), on the Instituto Nacional de Estudos e Pesquisas Educacionais--INEPE (National Institute for Educational Studies and Research) web site. Then, researchers collected business administration curricula from the universities' web sites. The present study was based on 40 of the 45 universities first considered, which represents 89 percent of the programs offered in Brazil. After data collection: performed from July to August 2009--a qualitative analysis of the curriculum was carried out. Findings: The inclusion of new courses that involve sustainability in business administration programs is still irregular and slow. Of the 40 universities investigated, only 13 (around 33 percent) offered courses related to the topic. Research limitations/implications: The nature of the research does not allow generalizations regarding other public or private undergraduate institutions. Practical implications: Results denote a deficiency in relation to the adoption of required courses on sustainability. This gap in the curriculum may compromise the ability of business administration students: who are the future managers and strategists: to reflect on the role of organizations in society. Originality/value: The present study is the first to examine the teaching of sustainability in Brazilian business education. It also contributes to monitoring the performance of Brazilian federal universities in the teaching of sustainability in business administration programs. (Contains 1 table and 2 figures.)

The centrality of religiosity scale (CRS), available in three versions (with 5, 10 and 15 items), is a measuring instrument that identifies the central importance of religiosity in the psychological construction and in the behavior of an individual. According to the literature, five components together express the centrality of religion in life: Public practice, private practice, ideological, intellectual, and religious experience. These components are the ground on which religious constructs are formed and activated. For the validation of the scale in the Brazilian cultural context, two versions were tested (CRS-10BR and CRS-5BR) with data collected from a general population (N = 687). Exploratory Factor Analysis (N = 334) resulted in a five-factor solution congruent to CRS-10BR. Confirmatory Factor Analysis (N = 353) demonstrated that a five-factor solution (Intellect, Ideology, Private Practice, Public Practice and Religious Experience) indicated better fit indexes than the single-factor solution of five items (CRS-5BR). Thus, CRS-10BR is recommended to capture CRS full construct. However, the CRS-5BR version can be considered suitable for use in the Brazilian population when the context is demanding simpler and faster data collection.