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An integral part of Brazil’s public health system, psychiatric emergency services have been instrumental in improving qualified support for crisis situations involving mental disorders in an equitable, universally accessible, and humanized way. The purpose of this article is to present a systematic review and consensus on the infrastructure and the ideal team for psychiatric emergencies services in Brazil. The authors searched electronic databases including MEDLINE (PubMed), SciELO, and Cochrane, in addition to documents from the World Health Organization, the Brazilian Ministry of Health, and other authorities. Of the 6839 manuscripts found, 46 were included. The content analysis summarized consensus statements through the Delphi method, and, after a series of interactive versions, a final report was produced. Models for changing psychiatric emergency services are assessed. It was determined that the emergency care network must be supervised by qualified management, and all health equipment and units must be effectively integrated. Psychiatric emergency services need adequate infrastructure, qualified staff (including a psychiatrist), sufficient consultation and observation space, tools and resources for differential diagnosis, training for all staff members, and communication with the health care network to facilitate referrals following patient discharge. Standardized models should be available to public health managers to guide the development of new services and adjust existing ones, always seeking improvement. The authors propose a model of psychiatric emergency services.

In this paper, we propose a novel and enhanced approach for crowd counting within the domain of manatee monitoring, aiming to significantly improve efficiency and accuracy. The proposed model achieves state-of-the-art results in the challenging task of manatee counting, simplifying the work of scientists and experts in the field. Our model not only facilitates the identification and enumeration of manatees in images and videos but also excels in scenarios that pose considerable challenges for human observers. To enhance accurate counting of the manatee aggregation, we introduce a framework with three key innovations to tackle the challenge: a new approach to generate density maps during the training process, an augmented technique to balance the dataset, and a cross-domain solution to enhance overall performance. The proposed two-dimensional Gaussian kernel offers a refined method for creating density maps, providing a more robust foundation for the training phase. Additionally, we built a balanced and augmented dataset, ensuring that the model is exposed to diverse and representative instances, thus improving its generalization capabilities. Furthermore, we incorporate a cross-domain phase pretraining the model utilizing an image dataset of wild animals to initialize the weights and further improve performance. Experiments and comparisons, with respect to previously established CSRNET model presented in Wang et al. (2023), demonstrate noteworthy improvements. Remarkably, our model achieves a Mean Absolute Error (MAE) of nearly half compared to the rival approach, showcasing the substantial advancements achieved through our refined methodology. This progress boosts the reliability of manatee counting in conservation efforts and ecological research.

Age-associated sarcopenia, characterized by a progressive loss in muscle mass and strength, is the largest cause of frailty and disability in the elderly worldwide. Current treatments involve nonpharmacological guidelines that few subjects can abide by, highlighting the need for effective drugs. Preclinical models were employed to test the benefits of RJx-01, a combination drug composed of metformin and galantamine, on sarcopenia. In worms, RJx-01 treatment improved lifespan, locomotion, pharyngeal pumping, and muscle fiber organization. The synergistic effects of RJx-01 were recapitulated in a transgenic mouse model that displays an exacerbated aging phenotype (Opa1–/–). In these mice, RJx-01 ameliorated physical performance, muscle mass and force, neuromuscular junction stability, and systemic inflammation. RJx-01 also improved physical performance and muscle strength in 22-month-old WT mice and also improved skeletal muscle ultrastructure, mitochondrial morphology, autophagy, lysosomal function, and satellite cell content. Denervation and myofiber damage were decreased in RJx-01–treated animals compared with controls. RJx-01 improved muscle quality rather than quantity, indicating that the improvement in quality underlies the beneficial effects of the combination drug. The studies herein indicate synergistic beneficial effects of RJx-01 in the treatment of sarcopenia and support the pursuit of RJx-01 in a human clinical trial as a therapeutic intervention for sarcopenia.

Liver fibrosis is a common and reversible feature of liver damage associated with many chronic liver diseases, and its onset is influenced by sex. In this study, we investigated the mechanisms of liver fibrosis and regeneration, focusing on understanding the mechanistic gaps between females and males. We injected increasing doses of carbon tetrachloride into female and male mice and maintained them for a washout period of eight weeks to allow for liver regeneration. We found that male mice were more prone to developing severe liver fibrosis as a consequence of early chronic liver damage, supported by the recruitment of a large number of Ly6Chigh MoMφs and neutrophils. Although prolonged liver damage exacerbated the fibrosis in mice of both sexes, activated HSCs and Ly6Chigh MoMφs were more numerous and active in the livers of female mice than those of male mice. After eight weeks of washout, only fibrotic females reported no activated HSCs, and a phenotype switching of Ly6Chigh MoMφs to anti-fibrogenic Ly6Clow MoMφs. The early stages of liver fibrosis mostly affected males rather than females, while long-term chronic liver damage was not influenced by sex, at least for liver fibrosis. Liver repair and regeneration were more efficient in females than in males.

Cytokines contribute to the pathogenesis of lupus nephritis (LN), yet their value as prognostic biomarkers is still debated. We aimed to describe the serum cytokines’ profiles and prospectively assess correlations with disease features and renal response in a multicentric cohort of consecutive adult patients with biopsy-proven active LN. Cytokine associations with clinical and serological data were performed at LN diagnosis (T0), and at 3 (T3) and 6 months (T6) of follow up. Renal response according to EULAR definition was assessed at T3, T6 and T12. BAFF and interleukin (IL)-37 were measured by ELISA; IL-2, IL-10, IL-17A and IL-18 by a bead-based multiplex cytokine assay (Luminex). Thirty-nine patients with active LN (age 40.5 ± 15.6 years; F 71.8%; 84.6% proliferative LN) were enrolled, of whom twenty-nine displayed complete longitudinal records. At T0, we observed higher levels of IL-37 and IL-17 in proliferative vs. non-proliferative LN (IL-37: 0.0510 (0.0110–0.2300) vs. 0.0000 (0.0000–0.0397) ng/mL, p = 0.0441; IL-17: 2.0920 (0.5125–17.9400) vs. 0.0000 (0.0000–0.6025) pg/mL, p = 0.0026, respectively), and positive correlations between IL-10 and 24 h proteinuria (r = 0.416, p = 0.0249) and anti-dsDNA levels (r = 0.639, p = 0.0003). BAFF was higher in patients with low complement (p < 0.0001). We observed a sustained correlation between BAFF and IL-10 throughout T6 (r = 0.654, p = 0.0210). Higher baseline IL-37 and BAFF levels were associated with renal response at T3 and T6, respectively, while baseline IL-18 levels were higher in patients achieving response at T12. Our study highlights the complexity of the cytokine network and its potential value as a marker of active LN and renal response.

This study aims to evaluate the potential of ERA5 precipitation and temperature reanalysis for snow water equivalent (SWE) simulation by considering the role of catchment spatial scale in controlling the errors obtained by comparison with corresponding SWE simulations from ground stations. This is obtained by exploiting a semi-distributed snowpack model (TOPMELT) implemented over the upper Adige River basin in the Eastern Italian Alps, where 16 sub-catchments of varying sizes are considered. The comparison is carried out from 1992 to 2019. The findings show that ERA5 precipitation overestimated low-intensity rainfall (drizzle problem) and underestimated high-intensity rainfall, while ERA5 temperature underestimated observations. The overestimation of low-intensity rainfall created fictitious low-intensity snowfall events, which, when combined with colder ERA5 temperature, resulted in delayed snowmelt and increased fictitious snow-cover days over the study area. The quantile mapping (QM) technique was used to remove errors in ERA5 variables. It was shown that ERA5 could struggle to resolve the orographic enhancement in precipitation, which may be particularly important during high-SWE years. This reduces the positive precipitation bias during those years, thus reducing comparatively the ability of the quantile mapping technique to correct for bias homogeneously during all years. This study highlighted the importance of temperature correction over precipitation correction in SWE simulation, particularly for smaller basins.

Esophageal adenocarcinoma (EAC) is the consequence of longstanding gastroesophageal reflux, which leads to inflammation and could cause Barrett’s esophagus (BE), the main risk factor for EAC development. The 5 year survival rate of EAC is poor since the diagnosis occurs at the late stage of the disease. To improve patient management, a better comprehension of the mechanism undergoing the evolution through to adenocarcinoma is needed. Within this scenario, the resident microbiome investigation was studied. This study aimed to explore the esophageal microbial profile in patients affected by non-dysplastic BE, low- and high-grade dysplastic BE, and EAC to identify parameters characterizing cancer progression and to develop a score suitable for clinical practice to stratify cancer risk. The microbiota was investigated through the 16S rRNA gene sequencing of esophageal biopsies. The microbial composition was evaluated at each different taxonomic level along the disease progression. To further investigate bacteria potentially associated with cancer development, non-dysplastic and dysplastic/cancer patients were compared. The presence of the six significant microbial features with multivariate analysis was used to develop a multiparametric score (Resident Esophageal Microbial Dysbiosis Test) to predict the risk of progression toward EAC. Finally, the diagnostic ability of the test and its discrimination threshold for its ability to identify dysplastic/cancer patients were demonstrated. Since EAC has been related to obesity, the relationship between these microbial parameters and patients’ diet/lifestyle habits was also investigated. Developing microbiome-based risk prediction models for esophageal adenocarcinoma onset could open new research avenues, demonstrating that the resident microbiome may be a valid cancer risk biomarker.

Solute transport in rivers is controlled by mixing processes that occur over a wide spectrum of spatial and temporal scales. Deviations from the classic advection–dispersion model observed in tracer test studies are known to be generated by the temporary trapping of solutes in storage zones where velocities and mixing rates are relatively small. In this work, the relation between the early and late-time behavior of solute breakthrough curves (BTCs) and the key parameters of the Transient Storage Model (TSM) is analyzed using non-asymptotic approximations of the model equations. Two main slopes are identified corresponding to the rising and decreasing limbs of the BTCs which are linked by specific relationships to transport and storage parameters. The validity of the proposed approximations is demonstrated with both synthetic and experimental data. Consistent with the TSM assumptions, the range of validity of the proposed approximations represents the limit of separability between surface dispersion and transient storage and can be expressed as a function of a nondimensional parameter. The results of this work can help environmental scientists identify solute transport and transient storage parameters and support the design of enhanced field tracer experiments.

Lomitapide, a drug for the treatment of homozygous familial hypercholesterolemia patients, reduced total and LDL cholesterol but no significant changes were observed on PCSK9 and Lp(a) plasma levels. Some changes of inflammatory mediators were also observed, including hsCRP, which may suggest an anti-inflammatory effect.

In this study, we aimed to assess the accuracy of the proposed novel, noninvasive serum DSC test in predicting the risk of gastric cancer before the use of upper endoscopy. To validate the DSC test, we enrolled two series of individuals living in Veneto and Friuli-Venezia Giulia, Italy (n = 53 and n = 113, respectively), who were referred for an endoscopy. The classification used for the DSC test to predict gastric cancer risk combines the coefficient of the patient’s age and sex and serum pepsinogen I and II, gastrin 17, and anti-Helicobacter pylori immunoglobulin G concentrations in two equations: Y1 and Y2. The coefficient of variables and the Y1 and Y2 cutoff points (>0.385 and >0.294, respectively) were extrapolated using regression analysis and an ROC curve analysis of two retrospective datasets (300 cases for the Y1 equation and 200 cases for the Y2 equation). The first dataset included individuals with autoimmune atrophic gastritis and first-degree relatives with gastric cancer; the second dataset included blood donors. Demographic data were collected; serum pepsinogen, gastrin G17, and anti-Helicobacter pylori IgG concentrations were assayed using an automatic Maglumi system. Gastroscopies were performed by gastroenterologists using an Olympus video endoscope with detailed photographic documentation during examinations. Biopsies were taken at five standardized mucosa sites and were assessed by a pathologist for diagnosis. The accuracy of the DSC test in predicting neoplastic gastric lesions was estimated to be 74.657% (65%CI; 67.333% to 81.079%). The DSC test was found to be a useful, noninvasive, and simple approach to predicting gastric cancer risk in a population with a medium risk of developing gastric cancer.

Enhanced temperature-index distributed models for snowpack simulation, incorporating air temperature and a term for clear sky potential solar radiation, are increasingly used to simulate the spatial variability of the snow water equivalent. This paper presents a new snowpack model (termed TOPMELT) which integrates an enhanced temperature-index model into the ICHYMOD semi-distributed basin-scale hydrological model by exploiting a statistical representation of the distribution of clear sky potential solar radiation. This is obtained by discretizing the full spatial distribution of clear sky potential solar radiation into a number of radiation classes. The computation required to generate a spatially distributed water equivalent reduces to a single calculation for each radiation class. This turns into a potentially significant advantage when parameter sensitivity and uncertainty estimation procedures are carried out. The radiation index may be also averaged in time over given time periods. Thus, the model resembles a classical temperature-index model when only one radiation class for each elevation band and a temporal aggregation of 1 year is used, whereas it approximates a fully distributed model by increasing the number of the radiation classes and decreasing the temporal aggregation. TOPMELT is integrated within the semi-distributed ICHYMOD model and is applied at an hourly time step over the Aurino Basin (also known as the Ahr River) at San Giorgio (San Giorgio Aurino), a 614 km2 catchment in the Upper Adige River basin (eastern Alps, Italy) to examine the sensitivity of the snowpack and runoff model results to the spatial and temporal aggregation of the radiation fluxes. It is shown that the spatial simulation of the snow water equivalent is strongly affected by the aggregation scales. However, limited degradation of the snow simulations is achieved when using 10 radiation classes and 4 weeks as spatial and temporal aggregation scales respectively. Results highlight that the effects of space–time aggregation of the solar radiation patterns on the runoff response are scale dependent. They are minimal at the scale of the whole Aurino Basin, while considerable impact is seen at a basin scale of 5 km2.

Recently, some preclinical and clinical studies have demonstrated the ability of brown seaweeds in reducing the risk factors for metabolic syndrome. Here, we analyzed the beneficial effect of a nutraceutical formulation containing a phytocomplex extracted from seaweeds and chromium picolinate in animal models of liver steatosis of differing severities (rats with non-alcoholic fatty liver disease (NAFLD) and its complication, non-alcoholic steatohepatitis (NASH)). This treatment led to a significant drop in hepatic fat deposition in both models (p < 0.01 vs. untreated animals), accompanied by a reduction in plasma inflammatory cytokines, such as interleukin 6, tumor necrosis factor α, and C reactive protein, and myeloperoxidase expression in liver tissue. Furthermore, a modulation of the molecular pathways involved in lipid metabolism and storage was demonstrated, since we observed the significant reduction of the mRNA levels of fatty acid synthase, diacylglycerol acyltransferases, the sterol-binding protein SREBP-1, and the lipid transporter perilipin-2, in both treated NAFLD and NASH rats in comparison to untreated ones. In conclusion, this nutraceutical product was effective in reducing liver steatosis and showed further beneficial effects on hepatic inflammation and glycemic control, which were particularly evident in rats characterized by a more severe condition, thus representing a therapeutic option for the treatment of NAFLD and NASH patients.

Background: There is a need for prospective studies investigating substance use variations in mild COVID-19 patients. These individuals represent the majority of patients affected by the disease and are routinely treated at home, facing periods of quarantine.Methods: This was a retrospective cohort study. All people who tested positive for COVID-19 and classified as mild cases (i.e., no alarm sign/symptom, no need for in-person consultation) during the treatment in the public health system of a Brazilian city with around 160,000 inhabitants were monitored by phone for all the COVID-19 symptoms listed by the Centers for Disease Control and Prevention (CDC) during the active phase of the disease (i.e., no longer experiencing symptoms, up to 14 days in mild cases). After this phase (median = 108 days after intake, IQR = 76–137), we asked these patients who were classified as experiencing mild COVID-19 (n = 993) about last-month substance use in three time-points: pre-COVID, just after COVID-19 acute phase (post-COVID acute phase) and in the period before survey (post-COVID follow-up phase).Results: The number of COVID-19 symptoms was not associated with pre- or post-infection substance use. Pre-COVID alcohol and non-medical benzodiazepine use were associated with specific COVID-19 symptoms. However, sensitivity analyses showed that such associations could be explained by previous psychiatric and medical profiles. Alcohol and tobacco use decreased and non-medical analgesics increased in the post-COVID acute phase. However, just alcohol use remained lower in the post-COVID follow-up period. Higher pre-COVID levels of tobacco and alcohol were associated with post-COVID follow-up cannabis and non-medical analgesic use, respectively. Non-medical benzodiazepine use had positive and negative bi-directional associations with cannabis and non-medical analgesic use, respectively.Conclusion: We were not able to find specific associations between substance use and COVID-19 symptomatology in the present study. Patients with mild COVID-19 should be monitored for substance use in the post-COVID-19 period, and preventive interventions for non-medical analgesic use should be implemented. Focused preventive interventions increasing the perceived risks of cannabis and non-medical benzodiazepine and analgesic use among people experiencing mild COVID-19 that reported previous substance use could be useful.

Anemia is highgly prevalent among elderly and few previous studies have focused on hospitalized medical patients aged ≥ 75 years. During a four-months period of this single center prospective cohort study, 508 patients were admitted and studied with a standardized set of blood tests. Anemia, defined as by WHO, was present in 277 (54.5%) and in the majority of cases was mild (71.8%), normocytic (82.8%), hypoproliferative (90.5%). Most frequent diagnosis was multifactorial anemia (47.7%); anemia of chronic disease was the most frequent single cause (28.5%) and the most frequent etiologic co-factor among multifactorial anemia. Iron deficiency was found in 22.7% of cases; vitamin B12 and folate deficiency were found in 7.5% and 26.1% respectively; chronic kidney disease in 16.2%; overt bleeding anemias in 4.8% and clonal hemopathies in 3.2%. Unexplained anemia was diagnosed only in 5.1% of cases. The finding of a very high frequency of anemia of chronic disease and multifactorial anemia has implications on both the diagnostic and therapeutic grounds.

Este estudo teve como objetivo principal descrever o processo de internacionalização e as adaptações no composto mercadológico da Holz. Em termos específicos, pretendeu-se atingir os seguintes objetivos: (1) Identificar as estratégias de internacionalização da Holz; (2) Identificar as adaptações no composto mercadológico da Holz. A revisão da literatura contempla os modelos gradual e Born Global de internacionalização, as principais estratégias de internacionalização (exportação, contrato e investimento direto no exterior) e os elementos do composto mercadológico (produto, preço, praça e promoção). Esta pesquisa pode ser classificada como qualitativa; a estratégia utilizada foi o estudo de caso. Os dados primários foram obtidos por meio de entrevista semiestruturada e os secundários col etados no website da empresa. Foi realizada uma entrevista com o proprietário da Holz, a qual durou aproximadament e uma hor a, foi gravada e transcrita e posteriormente analisada por meio da técnica de análise de conteúdo. O processo de internacionalização da Holz é caracterizado como Born global, pois a empresa foi criada para exportar madeira. A empresa utilizou-se d a estratégia de exportação i n direta, por meio de agentes comissionados no país de o r i g em. O mix de marketing da Holz é adaptado conforme as necessidades do mercado consumidor: o produto recebe alterações de acordo com a necessidade e costume de cada país; as modificações de preço são limitadas, pois os preços são uniformes; o método de distribuição é indireto; a promoção é inexistente.

Obesity and associated insulin resistance (Ins-R) have been identified as important risk factors for esophageal adenocarcinoma development. Elevated calories and protein consumption are also associated with Ins-R and glucose intolerance. We investigated the effect of a 24-month moderate calorie and protein restriction program on overweight or obese patients affected by Barrett’s esophagus (BE), as no similar dietary approach has been attempted to date in this disease context. Anthropometric parameters, levels of serum analytes related to obesity and Ins-R, and the esophageal insulin/IGF-1 signaling pathway were analyzed. This study is registered with ClinicalTrials.gov, number NCT03813381. Insulin, C-peptide, IGF-1, IGF-binding protein 3 (IGFBP3), adipokines, and esophageal expression of the main proteins involved in insulin/IGF-1 signal transduction were quantified using Luminex-XMAP® technology in 46 patients who followed the restriction program (IA) and in 54 controls (CA). Body mass index and waist circumference significantly decreased in 76.1% of IA and 35.2% of CA. IGF-1 levels were reduced in 71.7% of IA and 51.8% of CA. The simultaneous reduction of glycaemia, IGF-1, the IGF-1/IGFBP3 ratio, and the improvement in weight loss-dependent insulin sensitivity, were associated with the downregulation of the insulin/IGF-1 signal on BE tissue. The proposed intervention program was an effective approach to counteract obesity-associated cancer risk factors. The improvement in metabolic condition resulted in a downregulation of the ERK-mediated mitogenic signal in 43.5% of patients, probably affecting the molecular mechanism driving adenocarcinoma development in BE lesions.

AIM:The study aimed to establish how granulocytes, monocytes and macrophages contribute to the development of bronchopulmonary dysplasia (BPD). MATERIALS AND METHODS:Study A: samples of blood and tracheal aspirates (TAs) collected from preterm newborn infants during the first 3 days of life were investigated by flow cytometry, and testing for white blood cells (WBCs), neutrophils and neutrophil extracellular traps (NETs). Maternal blood samples were also collected. Study B: data from previously-tested samples of TAs collected from preterm newborn infants were re-analyzed in the light of the findings in the new cohort. RESULTS:Study A: 39 preterm newborn infants were studied. A moderate correlation emerged between maternal WBCs and neutrophils and those of their newborn in the first 3 days of life. WBCs and neutrophils correlated in the newborn during the first 8 days of life. Decision rules based on birth weight (BW) and gestational age (GA) can be used to predict bronchopulmonary dysplasia (BPD). Neutrophil levels were lower in the TAs from the newborn with the lowest GAs and BWs. Study B: after removing the effect of GA on BPD development, previously-tested newborn were matched by GA. Monocyte phenotype 1 (Mon1) levels were lower in the blood of newborn with BPD, associated with a higher ratio of Monocyte phenotype 3 (Mon3) to Mon1. Newborn infants from mothers with histological chorioamnionitis (HCA) had lower levels of classically-activated macrophages (M1) and higher levels of alternatively-activated macrophages (M2) in their TAs than newborn infants from healthy mothers. CONCLUSION:Immune cell behavior in preterm newborn infants was examined in detail. Surprisingly, neutrophil levels were lower in TAs from the newborn with the lowest GA and BW, and no correlation emerged between the neutrophil and NET levels in TAs and the other variables measured. Interestingly, monocyte phenotype seemed to influence the onset of BPD. The rise in the ratio of Mon 3 to Mon 1 could contribute to endothelial dysfunction in BPD.

Combined heat and power systems (CHP) produce heat and electricity simultaneously. Their resulting high efficiency makes them more attractive from the energy managers’ perspective than other conventional thermal systems. Although heat is a by-product of the electricity generation process, system operators usually operate CHP systems to satisfy heat demand. Electricity generation from CHP is thus driven by the heat demand, which follows the variability of seasonal temperature, and thus is not always correlated with the fluctuation of electricity demand. Consequently, from the perspective of the electricity grid operator, CHP systems can be seen as a non-controllable energy source similar to other renewable energy sources such as solar, wind or hydro. In this study, we investigate how ‘non-controllable’ electricity generation from CHP systems combines with ‘non-controllable’ electricity generation from solar photovoltaic panels (PV) and run-of-the river (RoR) hydropower at a district level. Only these three energy sources are considered within a 100% renewable mix scenario. Energy mixes with different shares of CHP, solar and RoR are evaluated regarding their contribution to total energy supply and their capacity to reduce generation variability. This analysis is carried out over an ensemble of seventeen catchments in North Eastern Italy located along a climate transect ranging from high elevation and snow dominated head-water catchments to rain-fed and wet basins at lower elevations. Results show that at a district scale, integration of CHP systems with solar photovoltaic and RoR hydropower leads to higher demand satisfaction and lower variability of the electricity balance. Results also show that including CHP in the energy mix modifies the optimal relative share between solar and RoR power generation. Results are consistent across the climate transect. For some districts, using the electricity from CHP might also be a better solution than building energy storage for solar PV.

Moderate resolution imaging spectroradiometry (MODIS) snow cover accuracy has been assessed in the past at different scales, with various approaches and in relation to the many factors influencing the remote observation of snow-covered areas (SCA). However, the challenge of fully characterizing MODIS accuracy over forest sites is still open. In this study, we exploit 5 years of data from the upper river Adige basin at Ponte Adige (Eastern Italian Alps) to condition an enhanced temperature index snowpack model accounting for model parameter uncertainty by using the Generalized Likelihood Uncertainty Estimation (GLUE) methodology. The simulated SCA is then compared with MODIS retrievals through a range of different statistical metrics to investigate how land use and solar illumination conditions affect such comparison. In particular, the Overall Accuracy index (OA) is used to quantify the agreement between satellite-derived and simulated SCA on a pixel-by-pixel basis. Analyzing the spatial variability either of the median OA and its range shows that illumination conditions over forested canopies represent a major source of uncertainty in MODIS SCA. Exploiting this finding, we identify the minimum level of incoming short-wave radiation for accurate use of MODIS SCA in forest areas.

Mário de Andrade identifies rhythm as the common structural underpinning between poetry and song. Rhythm is also the apple of discord between them, since it is with rhythm that we are able to note the fundamental distinction between the sung and the spoken word. As well as differentiating language by means of its use, popular song also fluctuates rhythmically; that is, it has another ‘wave’ (or mood) which varies depending on a series of other factors, which Andrade calls to mind. By considering 'canto' (chant) in psycho-physical terms, this essay offers an interpretation of Andrade’s reading of the masses present at one political event in 1930 described in “Dinamogenias políticas.” Moreover, this paper connects the political with the religious practices introduced in Brazil by the Jesuits, focusing above all on the Gregorian chant. I propose that with his “Crítica do gregoriano” Andrade offers a counterpoint by which to understand popular music in Brazil.

Candidemia is an emerging problem among patients hospitalized in Internal Medicine Wards (IMW). We performed a retrospective study to assess the epidemiology, species distribution, antifungal susceptibility and outcome of candidaemia recorded over a 3-year period (2010-2012) among IMW of community hospitals of Udine province in Italy: forty-eight patients were identified, with an overall incidence of 1.44 cases/1000 hospital admissions/year. Candida albicans was the most frequent species, followed by Candida parapsilosis that accounted for 42.9% of Tolmezzo cases. All isolates were susceptible to amphotericin and caspofungin, while 11.4% of strains were not-susceptible to voriconazole and 14.3% to fluconazole. Crude mortality was 41.7%. In conclusion, in community hospitals overall incidence of candidemia is similar to tertiary care hospitals, but 80% of cases are detected in IMW. Candida species distribution is overlapping, but differences in local epidemiology were found and should be taken into consideration. No resistance to amphotericin and caspofungin was found while resistance to azoles was observed. Knowledge of this data might be useful when planning the best therapeutic strategy.

The majority of acutely ill medical patients are elderly with some degree of renal impairment. In this setting, venous thromboembolism (VTE) is one of the leading causes of morbidity and mortality and, to reduce this risk, a correct thromboprophylaxis is needed. The aim of this single center retrospective study was to assess the safety and efficacy of fondaparinux in elderly acutely ill medical patients with renal impairment. All patients aged 60 years or over, bedridden for at least four days, with a creatinine clearance (CrCl) of 50 mL/min or under, and who had received fondaparinux during hospitalization were evaluated and followed for up to 90 days after discharge. A total of 125 patients were evaluated (34.4% males); median age was 83.0 years. Median duration of thromboprophylaxis was 9.0 days. Forty-one (32.8%) patients were treated with fondaparinux 1.5 mg daily, 84 (67.2%) with 2.5 mg daily. Inappropriately high doses of fondaparinux were used in 77 patients with CrCl 20-50 mL/min, in 12 patients with CrCl below 20 mL/min, in 14 patients with prothrombin time (PT) ratio over 1.2, in 8 patients with PT ratio over 1.5, and in 3 patients with thrombocytopenia. No episodes of VTE or of major bleeding were recorded while there were 6 episodes (2.4%) of minor bleeding. Both dosages of fondaparinux showed similar safety and efficacy. Twenty-six patients (20.8%) died; no cause of death was related to fondaparinux. In conclusion, in elderly acutely ill hospitalized medical patients with renal impairment, prophylaxis with fondaparinux 2.5 or 1.5 mg daily is safe and effective in preventing VTE without increasing bleeding risk.

Histidine-containing peptides self-assemble on the surface of monolayer protected gold nanoparticles to form a catalytic system for transesterification reactions. Self-assembly is a prerequisite for catalysis, since the isolated peptides do not display catalytic activity by themselves. A series of catalytic peptides and substrates are studied in order to understand the structural parameters that are of relevance to the catalytic efficiency of the system. It is shown that the distance between the His-residue and the anionic tail does not affect the catalytic activity. On the other hand, the catalytic His-residue is sensitive to the chemical nature of the flanking amino acid residues. In particular, the presence of polar Ser-residues causes a significant increase in activity. Finally, kinetic studies of a series of substrates reveal that substrates with a hydrophobic component are very suitable for this catalytic system.

Bronchopulmonary dysplasia (BPD) is a serious complication associated with preterm birth. A growing body of evidence suggests a role for prenatal factors in its pathogenesis. Metabolomics allows simultaneous characterization of low molecular weight compounds and may provide a picture of such a complex condition. The aim of this study was to evaluate whether an unbiased metabolomic analysis of amniotic fluid (AF) can be used to investigate the risk of spontaneous preterm delivery (PTD) and BPD development in the offspring.We conducted an exploratory study on 32 infants born from mothers who had undergone an amniocentesis between 21 and 28 gestational weeks because of spontaneous preterm labor with intact membranes. The AF samples underwent untargeted metabolomic analysis using mass spectrometry combined with ultra-performance liquid chromatography. The data obtained were analyzed using multivariate and univariate statistical data analysis tools.Orthogonally Constrained Projection to Latent Structures-Discriminant Analysis (oCPLS2-DA) excluded effects on data modelling of crucial clinical variables. oCPLS2-DA was able to find unique differences in select metabolites between term (n = 11) and preterm (n = 13) deliveries (negative ionization data set: R2 = 0.47, mean AUC ROC in prediction = 0.65; positive ionization data set: R2 = 0.47, mean AUC ROC in prediction = 0.70), and between PTD followed by the development of BPD (n = 10), and PTD without BPD (n = 11) (negative data set: R2 = 0.48, mean AUC ROC in prediction = 0.73; positive data set: R2 = 0.55, mean AUC ROC in prediction = 0.71).This study suggests that amniotic fluid metabolic profiling may be promising for identifying spontaneous preterm birth and fetuses at risk for developing BPD. These findings support the hypothesis that some prenatal metabolic dysregulations may play a key role in the pathogenesis of PTD and the development of BPD.

Hyperinsulinemia could have a role in the growing incidence of esophageal adenocarcinoma (EAC) and its pre-cancerous lesion, Barrett’s Esophagus, a possible consequence of Gastro-Esophageal Reflux Disease. Obesity is known to mediate esophageal carcinogenesis through different mechanisms including insulin-resistance leading to hyperinsulinemia, which may mediate cancer progression via the insulin/insulin-like growth factor axis. We used the hyperinsulinemic non-obese FVB/N (Friend leukemia virus B strain) MKR (muscle (M)-IGF1R-lysine (K)-arginine (R) mouse model to evaluate the exclusive role of hyperinsulinemia in the pathogenesis of EAC related to duodeno-esophageal reflux. FVB/N wild-type (WT) and MKR mice underwent jejunum-esophageal anastomosis side—to end with the exclusion of the stomach. Thirty weeks after surgery, the esophagus was processed for histological, immunological and insulin/Insulin-like growth factor 1 (IGF1) signal transduction analyses. Most of the WT mice (63.1%) developed dysplasia, whereas most of the MKR mice (74.3%) developed squamous cell and adenosquamous carcinomas, both expressing Human Epidermal growth factor receptor 2 (HER2). Hyperinsulinemia significantly increased esophageal cancer incidence in the presence of duodenal-reflux. Insulin receptor (IR) and IGF1 receptor (IGF1R) were overexpressed in the hyperinsulinemic condition. IGF1R, through ERK1/2 mitogenic pattern activation, seems to be involved in cancer onset. Hyperinsulinemia-induced IGF1R and HER2 up-regulation could also increase the possibility of forming of IGF1R/HER2 heterodimers to support cell growth/proliferation/progression in esophageal carcinogenesis.

Abstract Aim The aim of this report is to present a brief review of the current literature on the management of EEC. Case Report A term male neonate presented at birth with classic bladder exstrophy, a variant of the exstrophy-epispadias complex (EEC). The defect was covered with sterile silicon gauzes and waterproof dressing; at 72 hours of life, primary closure without osteotomy of bladder, pelvis, and abdominal wall was successfully performed. Discussion EEC incidence is approximately 2.15 per 1,00,000 live births; several urological, musculocutaneous, spinal, orthopedic, gastrointestinal, and gynecological anomalies may be associated to EEC. Initial medical management includes use of occlusive dressings to prevent air contact and dehydration of the open bladder template. Umbilical catheters should not be positioned. Surgical repair stages include initial closure of the bladder and abdominal wall with or without osteotomy, followed by epispadias repair at 6 to 12 months, and bladder neck repair around 5 years of life. Those who fail to attain continence eventually undergo bladder augmentation and placement of a catheterizable conduit. Conclusion Modern-staged repair of EEC guarantees socially acceptable urinary continence in up to 80% of cases; sexual function can be an issue in the long term, but overall quality of life can be good.

PURPOSE: The aim of the present study was to evaluate the alterations of surface microhardness and wear caused by the sodium bicarbonate jet on bovine enamel and the further remineralizing effect of artificial saliva. METHODS: Fifteen enamel samples (4,0mm x 4,0mm) were used, which constituted the groups: no treatment (MI); treatment with sodium bicarbonate jet (MII and DI); treatment with sodium bicarbonate jet and immersion in saliva for one hour (MIII and DII), 24 hours (MIV and DIII) and 7 days (MV and DIV). Microhardness tests were carried out using a microdurometer in groups M and wear tests by a rugosimeter in groups D. The data were assessed by the one criterion variance analysis and Tukey test. RESULTS: The mean value of microhardness, in KHN, in groups MI, MII, MIII, MIV and MV were 359,80; 335,46; 369,20; 377,73 and 341,86, respectively, whereas the mean values in µm, of wear for group DI, DII, DIII and DIV were 0,564; 0,519; 0,441 and 0,428, respectively. CONCLUSIONS: The sodium bicarbonate jet caused a wear and a reduction in microhardness on the enamel surface; saliva promoted the recovery of initial condition surface microhardness and reduced the wear; the repairing effect of saliva on the surface microhardness alterations occurred within one hour of treatment, having no significant statistical difference from the effect obtained in 24 hours; the best saliva repairing effect on the wear occurred with treatment of 24 hours.OBJETIVO: A finalidade do trabalho foi avaliar as alterações da microdureza e o desgaste provocado pelo jato de bicarbonato de sódio em esmalte bovino e o posterior efeito remineralizador da saliva artificial. MÉTODOS: Utilizaram-se 15 espécimes de esmalte (4,0mm x 4,0mm) que constituíram os grupos: sem tratamento (MI); tratamento com jato de bicarbonato de sódio (MII e DI); tratamento com jato de bicarbonato de sódio e imersão em saliva artificial por uma hora (MIII e DII), 24 horas (MIV e DIII) e sete dias (MV e DIV). Foram realizados testes de microdureza com um microdurômetro nos grupos M e testes de desgaste com um rugosímetro nos grupos D. RESULTADOS: Os dados foram avaliados pela Análise de Variância a um critério e pelo Teste de Tukey. O valor das médias da microdureza, em KHN, nos grupos MI, MII, MIII, MIV e MV foram 359,80; 335,46; 369,20; 377,73 e 341,86; respectivamente, enquanto que os valores médios, em µm, do desgaste para o grupo DI, DII, DIII e DIV foram 0,564; 0,519; 0,441 e 0,428, respectivamente. CONCLUSÕES: o jato de bicarbonato de sódio causou desgaste e diminuição da microdureza superficial; a saliva promoveu o retorno da microdureza superficial à condição inicial e reduziu o desgaste; o efeito reparador da saliva sobre as alterações na microdureza superficial já ocorreu com uma hora de tratamento, não havendo diferença estatisticamente significante do efeito obtido com 24 horas; o melhor efeito reparador da saliva sobre o desgaste ocorreu com 24 horas de tratamento.

Ritmos, acentos, formas, armonías y contrapuntos son algunas de las geografías musicales con las que se interpreta el Contrapunteo cubano del tabaco y el azúcar. Gracias a ellas, es posible abrir la noción antropológica de transculturación con la cual se ha desarrollado el estudio de la identidad latinoamericana desde la década de 1940. Al llamar la atención alrededor de una postura analítica basada en la escucha, este artículo invita a reflexionar sobre una serie de herramientas con las que se busca concienciar lo letrado e identificar, en los límites que demarcan la estructura del ensayo de Ortiz, un replanteamiento crítico para el análisis de la cultura.

The history of protein kinase CK2 is crowded with paradoxes and unanticipated findings. Named after a protein (casein) that is not among its physiological substrates, CK2 remained in search of its targets for more than two decades after its discovery in 1954, but it later came to be one of the most pleiotropic protein kinases. Being active in the absence of phosphorylation and/or specific stimuli, it looks unsuitable to participate in signaling cascades, but its “lateral” implication in a variety of signaling pathways is now soundly documented. At variance with many “onco-kinases”, CK2 is constitutively active, and no oncogenic CK2 mutant is known; still high CK2 activity correlates to neoplasia. Its pleiotropy and essential role may cast doubts on the actual “druggability” of CK2; however, a CK2 inhibitor is now in Phase II clinical trials for the treatment of cancer, and cell clones viable in the absence of CK2 are providing information about the mechanism by which cancer becomes addicted to high CK2 levels. A phosphoproteomics analysis of these CK2 null cells suggests that CK2 pleiotropy may be less pronounced than expected and supports the idea that the phosphoproteome generated by this kinase is flexible and not rigidly pre-determined.

Premature newborns are frequently exposed to hyperoxic conditions and experimental data indicate modulation of liver metabolism by hyperoxia in the first postnatal period. Conversely, nothing is known about possible modulation of growth factors and signaling molecules involved in other hyperoxic responses and no data are available about the effects of hyperoxia in postnatal liver haematopoiesis. The aim of the study was to analyse the effects of hyperoxia in the liver tissue (hepatocytes and haemopoietic cells) and to investigate possible changes in the expression of Vascular Endothelial Growth Factor (VEGF), Matrix Metalloproteinase 9 (MMP-9), Hypoxia-Inducible Factor-1α (HIF-1α), endothelial Nitric Oxide Synthase (eNOS), and Nuclear Factor-kB (NF-kB). Experimental design of the study involved exposure of newborn rats to room air (controls), 60% O2 (moderate hyperoxia), or 95% O2 (severe hyperoxia) for the first two postnatal weeks. Immunohistochemical and Western blot analyses were performed. Severe hyperoxia increased hepatocyte apoptosis and MMP-9 expression and decreased VEGF expression. Reduced content in reticular fibers was found in moderate and severe hyperoxia. Some other changes were specifically produced in hepatocytes by moderate hyperoxia, i.e., upregulation of HIF-1α and downregulation of eNOS and NF-kB. Postnatal severe hyperoxia exposure increased liver haemopoiesis and upregulated the expression of VEGF (both moderate and severe hyperoxia) and eNOS (severe hyperoxia) in haemopoietic cells. In conclusion, our study showed different effects of hyperoxia on hepatocytes and haemopoietic cells and differential involvement of the above factors. The involvement of VEGF and eNOS in the liver haemopoietic response to hyperoxia may be hypothesized.

The chemical modification of synthetic oligonucleotides has recently been investigated to improve their pharmacological utilization. In addition to chemical alterations of the backbone and of the heterocyclic bases, their conjugation with amphiphylic moieties, such as the polyethylene glycol has been proposed. The large scale production of these molecules as demanded for commercial purposes is hampered by the heterogeneity of the solid-phase processes and by the low reactivity of high-molecular weight PEGs in solution. A new synthetic procedure based on the recently developed liquid-phase method (HELP), has been set up to overcome these limitations.

Anemia is highly prevalent among the elderly, and few previous studies have focused on hospitalized medical patients aged ≥75 years. During the four months of this single-center prospective cohort study, 508 patients were admitted and studied with a standardized set of blood tests. Anemia, as defined by the World Health Organization, was present in 277 (54.5%) patients; in the majority of cases it was mild (71.8%), normocytic (82.8%), and hypoproliferative (90.5%). The most frequent diagnosis was multifactorial anemia (47.7%); anemia of chronic disease was the most frequent single cause (28.5%) and the most frequent etiologic co-factor among multifactorial anemia. Iron deficiency was found in 22.7% of cases; vitamin B12 and folate deficiencies were found in 7.5% and 26.1%, respectively; chronic kidney disease in 16.2%; overt bleeding anemias in 4.8% and clonal hemopathies in 3.2%. Unexplained anemia was diagnosed only in 5.1% of cases. The finding of a very high frequency of anemia of chronic disease and multifactorial anemia has implications on both the diagnostic and therapeutic grounds. [ABSTRACT FROM AUTHOR]