Predictors of mortality in critically ill patients with COVID-19 and diabetes.

The COVID-19 pandemic has challenged the entire world, and patients with diabetes mellitus (DM) have been particularly affected. We aimed to evaluate predictors of mortality during the first 30 days of hospitalization in critically ill patients with COVID-19 and comorbid DM. This prospective study included 110 critically ill patients admitted with COVID-19 infection. Thirty-two (29%) patients had a previous diagnosis of DM. Clinical variables, laboratory tests, and vascular biomarkers, such as VCAM-1, syndecan-1, ICAM-1, angiopoietin-1, and angiopoeitin-2, were evaluated after intensive care unit (ICU) admission. A comparison was made between patients with and without DM. No difference in mortality was observed between the groups (48.7 vs 46.9%, P=0.861). In the multivariate Cox regression analysis, VCAM-1 levels at ICU admission (HR: 1 [1-1.001], P<0.006) were associated with death in patients with DM. Among patients with DM, advanced age (HR 1.063 [1.031-1.096], P<0.001), increased Ang-2/Ang-1 ratio (HR: 4.515 [1.803-11.308] P=0.001), and need for dialysis (HR: 3.489 [1.409-8.642], P=0.007) were independent predictors of death. Higher levels of VCAM-1 in patients with DM was better at predicting death of patients with severe COVID-19 and comorbid DM, and their cut-off values were useful for stratifying patients with a worse prognosis. Vascular biomarkers VCAM-1 and Ang-2/Ang-1 ratio were predictors of death in patients with severe COVID-19 and comorbid DM and those without DM. Additionally, kidney injury was associated with an increased risk of death.

Predictors of mortality in critically ill patients with COVID-19 and diabetes

The COVID-19 pandemic has challenged the entire world, and patients with diabetes mellitus (DM) have been particularly affected. We aimed to evaluate predictors of mortality during the first 30 days of hospitalization in critically ill patients with COVID-19 and comorbid DM. This prospective study included 110 critically ill patients admitted with COVID-19 infection. Thirty-two (29%) patients had a previous diagnosis of DM. Clinical variables, laboratory tests, and vascular biomarkers, such as VCAM-1, syndecan-1, ICAM-1, angiopoietin-1, and angiopoeitin-2, were evaluated after intensive care unit (ICU) admission. A comparison was made between patients with and without DM. No difference in mortality was observed between the groups (48.7 vs 46.9%, P=0.861). In the multivariate Cox regression analysis, VCAM-1 levels at ICU admission (HR: 1 [1-1.001], P<0.006) were associated with death in patients with DM. Among patients with DM, advanced age (HR 1.063 [1.031-1.096], P<0.001), increased Ang-2/Ang-1 ratio (HR: 4.515 [1.803-11.308] P=0.001), and need for dialysis (HR: 3.489 [1.409-8.642], P=0.007) were independent predictors of death. Higher levels of VCAM-1 in patients with DM was better at predicting death of patients with severe COVID-19 and comorbid DM, and their cut-off values were useful for stratifying patients with a worse prognosis. Vascular biomarkers VCAM-1 and Ang-2/Ang-1 ratio were predictors of death in patients with severe COVID-19 and comorbid DM and those without DM. Additionally, kidney injury was associated with an increased risk of death.

N-Methyl-(2S, 4R)-trans-4-hydroxy-L-proline, the major bioactive compound from Sideroxylon obtusifolium, attenuates pilocarpine-induced injury in cultured astrocytes.

Glial cells have been implicated in temporal lobe epilepsy in humans and in its models. Astrocytes are lost in several brain regions after acute seizures induced by pilocarpine and may suffer hyperplasia at subsequent time points. This study investigated the effect of N-methyl-(2S,4R)-trans-4-hydroxy-L-proline (NMP) on astrocytes exposed to cytotoxic concentrations of pilocarpine. Astrocytes were incubated with pilocarpine (half maximal inhibitory concentration (IC50)=31.86 mM) for 24 h. Afterwards, they were treated with NMP at concentrations ranging from 3.12 to 100 µg/mL for 24 h. Cell viability was assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cytoplasmic reactive oxygen species (ROS) and mitochondrial transmembrane potential (ΔΨm) were analyzed by flow cytometry using 2',7'-dichlorofluorescein diacetate (DCFH-DA) and rhodamine-123 (Rho123), respectively. Expression of glial fibrillary acidic protein (GFAP) and voltage-dependent anion channel-1 (VDAC-1) were measured by western blot. Pilocarpine significantly decreased cell viability and mitochondrial potential and increased ROS concentration significantly by 6.7 times compared to the control. NMP concentrations ≥25 µg/mL protected astrocytes against pilocarpine-induced injury in a concentration-dependent manner. Concomitantly, NMP reduced cytoplasmic ROS accumulation to 27.3, 24.8, and 12.3% in the groups treated with 25, 50, and 100 µg/mL NMP, respectively. NMP also protected mitochondria from pilocarpine-induced depolarization. These effects were associated with improvement of pilocarpine-induced GFAP and VDAC-1 overexpression, which are important biomarkers of astrocyte dysfunction. In conclusion, the improvement of ROS accumulation, VDAC-1 overexpression, and mitochondrial depolarization are possible mechanisms of the NMP protective action on reactive astrocytes.

Burden of phenylketonuria in Latin American patients: a systematic review and meta-analysis of observational studies.

BACKGROUND: Phenylketonuria (PKU) is an inborn error of metabolism caused by a deficiency of the enzyme phenylalanine hydroxylase. If untreated, the complications of PKU lead to significant neucognitive and neuropsychiatric impairments, placing a burden on both the individual's quality of life and on the healthcare system. We conducted a systematic literature review to characterize the impact of PKU on affected individuals and on healthcare resources in Latin American (LATAM) countries. METHODS: Searches of the global medical literature as well as regional and local medical literature up to September 2021. Observational studies on patients with PKU from any LATAM country. Pairs of reviewers independently screened eligible articles, extracted data from included studies, and assessed their risk of bias. RESULTS: 79 unique studies (47 cross-sectional studies, 18 case series, 12 case reports, and two cohort studies) with a total of 4090 patients were eligible. Of these studies, 20 had data available evaluating early-diagnosed PKU patients for meta-analysis of burden outcomes. Intellectual disability in the pooled studies was 18% [95% Confidence Interval (CI) 0.04-0.38; I2 = 83.7%, p = 0.0133; two studies; n = 114]. Motor delay was 15% [95% CI 0.04-0.30; I2 = 74.5%, p = 0.0083; four studies; n = 132]. Speech deficit was 35% [95% CI 0.08-0.68; I2 = 93.9%, p < 0.0001; five studies; n = 162]. CONCLUSIONS: There is currently evidence of high clinical burden in PKU patients in LATAM countries. Recognition that there are many unmet neuropsychological needs and socioeconomic challenges faced in the LATAM countries is the first step in planning cost-effective interventions.

Kidney injury molecule-1 and urinary gamma-glutamyl transferase as biomarkers of acute kidney injury in cats.

OBJECTIVES: To evaluate the concentration of kidney injury molecule-1 and activity of urinary gamma-glutamyl transferase in cats with urethral obstruction and healthy cats. MATERIALS AND METHODS: Blood and urine samples were collected from a group of 15 healthy cats (control group) and a group of 20 cats with urethral obstruction at presentation, and 24 hours and 7 days after unblocking the obstruction. The serum creatinine, urinary creatinine and urinary gamma-glutamyl transferase were measured by spectrophotometry and kidney injury molecule-1 by the sandwich enzyme-linked immunosorbent assay. RESULTS: On presentation, cats with obstruction had serum creatinine concentration and urinary gamma-glutamyl transferase index higher than healthy cats (mean difference 544 µmol/L, 95% confidence intervals 222 to 865 µmol/L, and 0.0022 U/µmol-uCre, 0.00043 to 0.0039 U/µmol-uCre, respectively), urine creatinine concentration lower (mean difference 25,624 µmol/L, 17,329 to 33,919 µmol/L), and no significant difference in the kidney injury molecule-1/urinary creatinine ratio (mean difference 13 pg/µmol-uCre, -33 to 59 pg/µmol-uCre). In the group of cats with urinary obstruction, over time serum creatinine decreased, urine creatinine increased, urinary gamma-glutamyl transferase index did not change significantly, and kidney injury molecule-1/urinary creatinine ratio increased. CLINICAL SIGNIFICANCE: Cats with post-renal obstruction and potential intrinsic renal damage had higher urinary gamma-glutamyl transferase index than healthy cats at the time of presentation and showed increase in kidney injury molecule-1/urinary creatinine ratio over time.

N-Methyl-(2S, 4R)-trans-4-hydroxy-L-proline, the major bioactive compound from Sideroxylon obtusifolium, attenuates pilocarpine-induced injury in cultured astrocytes

Glial cells have been implicated in temporal lobe epilepsy in humans and in its models. Astrocytes are lost in several brain regions after acute seizures induced by pilocarpine and may suffer hyperplasia at subsequent time points. This study investigated the effect of N-methyl-(2S,4R)-trans-4-hydroxy-L-proline (NMP) on astrocytes exposed to cytotoxic concentrations of pilocarpine. Astrocytes were incubated with pilocarpine (half maximal inhibitory concentration (IC50)=31.86 mM) for 24 h. Afterwards, they were treated with NMP at concentrations ranging from 3.12 to 100 μg/mL for 24 h. Cell viability was assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cytoplasmic reactive oxygen species (ROS) and mitochondrial transmembrane potential (ΔΨm) were analyzed by flow cytometry using 2',7'-dichlorofluorescein diacetate (DCFH-DA) and rhodamine-123 (Rho123), respectively. Expression of glial fibrillary acidic protein (GFAP) and voltage-dependent anion channel-1 (VDAC-1) were measured by western blot. Pilocarpine significantly decreased cell viability and mitochondrial potential and increased ROS concentration significantly by 6.7 times compared to the control. NMP concentrations ≥25 µg/mL protected astrocytes against pilocarpine-induced injury in a concentration-dependent manner. Concomitantly, NMP reduced cytoplasmic ROS accumulation to 27.3, 24.8, and 12.3% in the groups treated with 25, 50, and 100 µg/mL NMP, respectively. NMP also protected mitochondria from pilocarpine-induced depolarization. These effects were associated with improvement of pilocarpine-induced GFAP and VDAC-1 overexpression, which are important biomarkers of astrocyte dysfunction. In conclusion, the improvement of ROS accumulation, VDAC-1 overexpression, and mitochondrial depolarization are possible mechanisms of the NMP protective action on reactive astrocytes.

Interleukin-6 and adhesion molecules VCAM-1 and ICAM-1 as biomarkers of post-acute myocardial infarction heart failure.

Acute coronary syndromes are associated with a high prevalence of complications including heart failure (HF). The aim of this study was to investigate the association of novel biomarkers with the occurrence of post-acute myocardial infarction (AMI) HF. A prospective study was conducted with patients admitted to the emergency department with ST-segment elevation myocardial infarction (STEMI). Blood and urine samples were collected for analysis of traditional and novel biomarkers, including interleukin-6, vascular cell adhesion molecule 1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1). We compared the levels of these biomarkers between patients with and without post-STEMI HF. A total of 48 patients were assessed, with a prevalence of males. Fifteen patients (31.2%) had post-STEMI HF. Patients with HF had higher mean values of IL-6, VCAM-1, and ICAM-1 compared to those who did not develop HF (57.06 vs 14.03 pg/mL, P=0.001; 1719.58 vs 1304.34 ng/mL, P=0.001; and 1594.20 vs 1158.74 ng/mL, P<0.001, respectively). The three biomarkers were shown to be good predictors of post-STEMI HF (IL-6: AUC 0.786, P=0.002; VCAM-1: AUC 0.797, P=0.001; and ICAM-1: AUC 0.825, P<0.0001), with the respective cutoff points being calculated based on the best sensitivity and specificity indexes (IL-6: 8.67 pg/mL; VCAM-1: 1501.42 ng/mL; and ICAM-1: 1262.38 ng/mL). Of the three biomarkers, only VCAM-1 and ICAM-1 had a direct linear association between them (r=0.470, P<0.0001). IL-6, VCAM-1, and ICAM-1 were associated with the development of new post-AMI HF symptoms, but only VCAM-1 and ICAM-1 correlated with each other, possibly because they have the same pathophysiological mechanism of action.

Bothrops alternatus Snake Venom Induces Cytokine Expression and Oxidative Stress on Renal Function.

BACKGROUND: Envenomation caused by Bothrops alternatus is common in Southern Brazil. Acute Kidney Injury occurs after Bothrops snakebite and more information is necessaryrequired to understand its mechanism. OBJECTIVE: The objective was to evaluate the effect of Bothrops alternatus venom (BaV) on renal cells and rat isolated kidney function. METHODS: Wistar rats (n = 6, weighing 260-320 g) were perfused with a Krebs-Henseleit solution containing 6 g 100 mL-1 of bovine serum albumin. After 30 minutes, the kidneys were perfused with BaV to a final concentration of 1 and 3 µgmL-1; and subsequently were evaluated for Perfusion Pressure (PP), Renal Vascular Resistance (RVR), Urinary Flow (UF), Glomerular Filtration Rate (GFR), and percentage of electrolyte tubular transport. Renal histological analysis, cytokine release, oxidative stress and cytotoxicity in renal proximal tubular cells were assessed. RESULTS: BaV reduced PP, RVR, GFR, UF, total and proximal sodium transport (%TNa+), and chloride (%TCl-) in the isolated kidney perfusion model. Histological analysis of perfused kidneys disclosed the presence of proteinaceous material in the glomeruli and renal tubules, vacuolar tubular epithelial cell degeneration, Bowman's capsule degeneration, swelling of glomerular epithelial cells, glomerular atrophy and degeneration, and the presence of intratubular protein. Cytokine release (TNF-α, IL-1ß, IL-10) and oxidative stress were increased in the kidneys. The viability of LLC-MK2 cells (IC50: 221.3 µg/mL) was decreased by BaV and necrosis was involved in cell death. CONCLUSION: These findings indicate that BaV modifies functional parameters in an isolated perfused kidney model and has cytotoxic effects on renal lineage cells.

Renal Alterations Induced by the Venom of Colombian Scorpion Centruroides Margaritatus.

BACKGROUND: Scorpion venom causes renal injury and affects vascular ion-channels function. Centruroides margaritatus scorpion is found in Colombia and is frequently the cause of envenomation accidents; however, its renal impact has never been investigated. OBJECTIVE: To evaluate the effects of C. margaritatus venom (CmV) on renal parameters using isolated rat kidney and renal cell culture models. METHODS: Wistar rats (n = 5, weighing 240-300 g) were first perfused with Krebs-Henseleit solution containing 6 g 100 mL-1 bovine serum albumin. After 30 minutes, the kidneys were perfused with CmV to a final concentration of 10 µgmL-1; evaluation was performed by measuring Perfusion Pressure (PP), Renal Vascular Resistance (RVR), Urinary Flow (UF), Glomerular Filtration Rate (GFR), and percentage of electrolyte tubular transport. Moreover, kidney histological analyses and cell cytotoxicity in renal tubule epithelial cells (MDCK) and proximal tubular cells (LLC-MK2) were assessed. RESULTS: CmV increased PP and RVR 60 min after perfusion. On the other hand, UF, GFR, and the percentages of sodium, potassium and chloride tubular transport decreased after experimental envenomation. UF dropped after 120 min, while GFR and percentage of electrolyte tubular transport diminished after 60, 90 and 120 min. CmV was not toxic to MDCK cell line but reduced the viability of LLC-MK2 cells at concentrations ranging from 6.25 to 200 µgmL-1. Histological analyses disclosed hydropic degeneration, edema, and protein deposits. Flow cytometry disclosed that cell death occurred predominantly by necrosis. CONCLUSION: Our results suggest that C. margaritatus venom can trigger renal impairment, mainly in the proximal kidney tubule.

Antichagasic effect of violacein from Chromobacterium violaceum.

AIMS: Violacein (VIO), a bacterial pigment produced by Chromobacterium violaceum, was examined to evaluate the antichagasic activity and its action mechanism against Trypanosoma cruzi Y strain. METHODS AND RESULTS: Violacein was tested against the epimastigote, trypomastigote and amastigote forms of T. cruzi Y strain (benznidazole-resistant strain). VIO inhibited all T. cruzi developmental forms, including amastigotes, which is implicated in the burden of infection in the chronic phase of Chagas disease (CD). VIO induced cell death in T. cruzi through apoptosis, as determined by flow cytometry analyses with specific molecular probes and morphological alterations, such as involvement of reactive oxygen species and changes in mitochondrial membrane potential and cell shrinkage. CONCLUSION: The results suggest antichagasic activity of VIO against T. cruzi Y strain with apoptotic involvement. SIGNIFICANCE AND IMPACT OF THE STUDY: The treatment of CD has limited efficacy and side effects that restrict patient tolerability and compliance. The VIO molecule could be used as a model for therapeutic alternatives for this disease.

Applicability of the Platelia EIA® Aspergillus test for the diagnosis of aspergilosis in penguins / Aplicabilidade do Platelia EIA® Aspergillus como teste diagnostico da aspergilose em pinguins

Abstract Even today, an effective diagnostic test for aspergillosis in penguins is unknown, being the gold standard post-mortem examinations. The fungal antigen galactomannan (GM) has been used as a biomarker of disease in humans and is detected by the Platelia Aspergillus EIA (BioRad)®, a commercial kit based on the sandwich ELISA technique. It is standardized for use in neutropenic patients, however studies have demonstrated its usefulness also possible for birds. The aim of our study was to evaluate the effectiveness of Platelia Aspergillus EIA® test (BioRad-US) in the diagnosis of aspergillosis in Magellanic penguins, determining sensitivity, specificity, and positive and negative predictive values for different cut-off points. Were included in the study, blood serum samples (n = 29) Magellanic penguins in captivity that died by aspergillosis. Detection of GM was performed following manufacturer's instructions and the GM index was obtained by dividing the average value of OD of the duplicate of the clinical sample by duplicate OD of the average value of the cut-off sample provided by the kit. Through information database results were obtained for the presence of anti-Aspergillus fumigatus antibodies detected by agar gel immunodiffusion (AGID) for all serum samples. Results were analyzed using chi-square test and Kruskal-Wallis from SPSS 20.0, IBM®. ROC curve was obtained and from this, rates of sensitivity, specificity, positive and negative predictive values were also calculated based on four different cutoff points (0.5, 1.0, 1.5 and 2.0). The serum GM index did not differ between animals of the case and control group (pkw =0.097). In determining the ROC curve for serum GM detection the value of area under the curve was 0.635. From the values ​​determined by the coordinate of the curve, four different cut points (0.5, 1.0, 1.5 and 2.0) were analyzed, resulting in sensitivity rates ranging from 86.2 to 34.5% % and specificity between 87% and 26.1%. By comparing the serum GM index in group case as the presence or absence of antibodies detected by AGID was found p=0.503. The detection of GM the Platelia Aspergillus EIA® test seems is not be useful for the diagnosis of aspergillosis in naturally infected penguins.

Resumo Ainda hoje, um teste diagnóstico eficaz para aspergilose em pinguins não é conhecido, sendo o padrão-ouro os exames post-mortem. O antígeno fúngico galactomanana (GM) tem sido utilizado como biomarcador da doença em humanos, sendo detectado pelo Platelia Aspergillus EIA (BioRad)®, um kit comercial que se baseia na técnica ELISA sanduíche. É padronizado para utilização em pacientes neutropênicos, no entanto estudos tem demonstrado sua possível utilidade também para aves.O objetivo de nosso estudo foi avaliar a eficácia do teste Platelia Aspergillus EIA® (BioRad-US) no diagnóstico da aspergilose em pinguins-de-Magalhães, determinando sensibilidade, especificidade e valores preditivos positivos e negativos em diferentes pontos de corte. Foram incluídas no estudo, amostras de soro sanguíneo (n=29) de pinguins-de-Magalhães em cativeiro que vieram a óbito por aspergilose. A detecção de GM foi realizada seguindo instruções do fabricante e o índice de GM foi obtido dividindo o valor da média da DO da duplicata da amostra clínica pelo valor da média da DO da duplicata da amostra de cut-off fornecida pelo kit. Através de informações em banco de dados foram obtidos resultados sobre a presença de anticorpos anti-Aspergillus fumigatus, detectada por Imunodifusão em gel de ágar (IDGA) em todas as amostras séricas. Os resultados foram analisados utilizando-se teste de qui-quadrado e Kruskal-Wallis a partir do programa estatístico SPSS 20.0, IBM®. Curva ROC foi obtida e a partir desta, taxas de sensibilidade, especificidade, valores preditivo positivo e negativo foram igualmente calculados considerando quatro diferentes pontos de corte (0.5, 1.0, 1.5 e 2.0). O índice de GM sérica não diferiu entre os animais do grupo caso e controle (pKW = 0.097). Na determinação da curva ROC para detecção de GM sérica o valor da área sobre a curva foi de 0.635. A partir dos valores determinados pelas coordenadas da curva, quatro diferentes pontos de corte (0.5, 1.0, 1.5 e 2.0) foram analisados, resultando em taxas de sensibilidade variando de 86.2% a 34.5%, e de especificidade entre 87% e 26.1%. Ao comparar o índice de GM sérica nos animais do grupo caso quanto a presença ou não de anticorpos detectados pela IDGA foi encontrado p=0.503. A detecção de GM pelo teste Platelia Aspergillus EIA® não parece ser útil para o diagnóstico da aspergilose em pinguins naturalmente infectados.

Applicability of the Platelia EIA® Aspergillus test for the diagnosis of aspergilosis in penguins.

Even today, an effective diagnostic test for aspergillosis in penguins is unknown, being the gold standard post-mortem examinations. The fungal antigen galactomannan (GM) has been used as a biomarker of disease in humans and is detected by the Platelia Aspergillus EIA (BioRad)®, a commercial kit based on the sandwich ELISA technique. It is standardized for use in neutropenic patients, however studies have demonstrated its usefulness also possible for birds. The aim of our study was to evaluate the effectiveness of Platelia Aspergillus EIA® test (BioRad-US) in the diagnosis of aspergillosis in Magellanic penguins, determining sensitivity, specificity, and positive and negative predictive values for different cut-off points. Were included in the study, blood serum samples (n = 29) Magellanic penguins in captivity that died by aspergillosis. Detection of GM was performed following manufacturer's instructions and the GM index was obtained by dividing the average value of OD of the duplicate of the clinical sample by duplicate OD of the average value of the cut-off sample provided by the kit. Through information database results were obtained for the presence of anti-Aspergillus fumigatus antibodies detected by agar gel immunodiffusion (AGID) for all serum samples. Results were analyzed using chi-square test and Kruskal-Wallis from SPSS 20.0, IBM®. ROC curve was obtained and from this, rates of sensitivity, specificity, positive and negative predictive values were also calculated based on four different cutoff points (0.5, 1.0, 1.5 and 2.0). The serum GM index did not differ between animals of the case and control group (pkw =0.097). In determining the ROC curve for serum GM detection the value of area under the curve was 0.635. From the values ​​determined by the coordinate of the curve, four different cut points (0.5, 1.0, 1.5 and 2.0) were analyzed, resulting in sensitivity rates ranging from 86.2 to 34.5% % and specificity between 87% and 26.1%. By comparing the serum GM index in group case as the presence or absence of antibodies detected by AGID was found p=0.503. The detection of GM the Platelia Aspergillus EIA® test seems is not be useful for the diagnosis of aspergillosis in naturally infected penguins.

Interleukin-6 and adhesion molecules VCAM-1 and ICAM-1 as biomarkers of post-acute myocardial infarction heart failure

Acute coronary syndromes are associated with a high prevalence of complications including heart failure (HF). The aim of this study was to investigate the association of novel biomarkers with the occurrence of post-acute myocardial infarction (AMI) HF. A prospective study was conducted with patients admitted to the emergency department with ST-segment elevation myocardial infarction (STEMI). Blood and urine samples were collected for analysis of traditional and novel biomarkers, including interleukin-6, vascular cell adhesion molecule 1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1). We compared the levels of these biomarkers between patients with and without post-STEMI HF. A total of 48 patients were assessed, with a prevalence of males. Fifteen patients (31.2%) had post-STEMI HF. Patients with HF had higher mean values of IL-6, VCAM-1, and ICAM-1 compared to those who did not develop HF (57.06 vs 14.03 pg/mL, P=0.001; 1719.58 vs 1304.34 ng/mL, P=0.001; and 1594.20 vs 1158.74 ng/mL, P<0.001, respectively). The three biomarkers were shown to be good predictors of post-STEMI HF (IL-6: AUC 0.786, P=0.002; VCAM-1: AUC 0.797, P=0.001; and ICAM-1: AUC 0.825, P<0.0001), with the respective cutoff points being calculated based on the best sensitivity and specificity indexes (IL-6: 8.67 pg/mL; VCAM-1: 1501.42 ng/mL; and ICAM-1: 1262.38 ng/mL). Of the three biomarkers, only VCAM-1 and ICAM-1 had a direct linear association between them (r=0.470, P<0.0001). IL-6, VCAM-1, and ICAM-1 were associated with the development of new post-AMI HF symptoms, but only VCAM-1 and ICAM-1 correlated with each other, possibly because they have the same pathophysiological mechanism of action.

Proteomic landscape of seminal plasma associated with dairy bull fertility.

Male fertility is the ability of sperm to fertilize the egg and sustain embryo development. Several factors determine the fertilizing capacity of mammalian sperm, including those intrinsic to sperm and components of the seminal plasma. The present study analyzed the seminal fluid proteome of Bos taurus and potential associations between proteins and fertility scores. Mass spectrometry coupled with nano HPLC allowed the identification of 1,159 proteins in the dairy bull seminal plasma. There were 50 and 29 seminal proteins more abundant in high (HF) low fertility (LF) bulls, respectively. Based on multivariate analysis, C-type natriuretic peptide, TIMP-2, BSP5 and sulfhydryl oxidase indicated relationship with HF bulls. Clusterin, tissue factor pathway inhibitor 2, galectin-3-binding protein and 5'-nucleotidase were associated with LF bulls. Abundance of NAD(P)(+)-arginine ADP-ribosyltransferase, prosaposin and transmembrane protein 2 proteins had the highest positive correlations with fertility ranking. Quantities of vitamin D-binding protein, nucleotide exchange factor SIL1 and galectin-3-binding protein showed the highest negative correlations with fertility ranking. A fertility ranking score was calculated and the relationship with these proteins was significant (Spearman's rho = 0.94). The present findings represent a major and novel contribution to the study of bovine seminal proteins. Indicators of fertility can be used to improve reproductive biotechnologies.

WITHDRAWN: Recommendations for evaluation and management of pain in patients with mucopolysaccharidosis in Latin America.

The Publisher regrets that this article is an accidental duplication of an article that has already been published, https://doi.org/10.1016/j.jpainsymman.2018.03.023. The duplicate article has therefore been withdrawn. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.

Association between syndecan-1 and renal function in adolescents with excess weight: evidence of subclinical kidney disease and endothelial dysfunction.

Excess weight (overweight and obesity) is associated with kidney and cardiovascular disease. The aim of this study was to investigate the association between syndecan-1 and renal function among adolescents with excess weight. A total of 56 students from a public school at Fortaleza, CE, Brazil, were investigated. The adolescents were submitted to anthropometric evaluation, including weight, height, blood pressure and body mass index. Blood and urine samples were collected for the determination of serum lipids (total cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol, triglycerides), and the endothelial injury biomarker syndecan-1. Participants' mean age was 16±1 years (range 14-19 years), and 68% were females. Overweight was observed in 4 cases (7.1%) and obesity in 7 (12.5%). Changes in serum lipid levels were more frequent in the overweight group. A positive correlation between syndecan-1 and serum creatinine (r=0.5, P=0.001) and triglycerides (r=0.37, P=0.004), and a negative correlation with glomerular filtration rate (r=-0.33, P=0.02) were found. These findings suggest that adolescents with excess weight present incipient changes at the cellular level that make them more vulnerable to the development of kidney and cardiovascular diseases.

Liposomes as a Promising Ultrasound-Triggered Drug Delivery System in Cancer Treatment.

The initial uses of ultrasound waves in the medical field were limited to the thermal ablation of solid tumors and as a diagnostic tool. Recent advances at the preclinical stage have allowed the use of ultrasound as a powerful tool to improve drug delivery when the agent is administered encapsulated inside a nanoparticle. This spatial and temporal control of drug release, using a non-invasive modality, is a promising approach to decrease the side effects of conventional chemotherapy in cancer treatments, as it reduces the interaction of the anti-neoplastic agent with healthy tissues. In this review, we explain the physics of ultrasound, introduce and discuss several examples on the use of nanoparticles as drug carriers, with a focus on liposomes. Examples of in vitro and in vivo studies are presented and discussed.

Influence of ßS-Globin Haplotypes and Hydroxyurea on Arginase I Levels in Sickle Cell Disease.

Introduction. Sickle cell disease (SCD) is characterized by hemoglobin S homozygosity, leading to hemolysis and vasoocclusion. The hemolysis releases arginase I, an enzyme that decreases the bioavailability of nitric oxide, worsening the symptoms. The different SCD haplotypes are related to clinical symptoms and varied hemoglobin F (HbF) concentration. The aim of this study was to evaluate the impact of the ßS gene haplotypes and HbF concentration on arginase I levels in SCD patients. Methods. Fifty SCD adult patients were enrolled in the study and 20 blood donors composed the control group. Arginase I was measured by ELISA. The ßS haplotypes were identified by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Statistical analyses were performed with GraphPad Prism program and the significance level was p < 0.05. Results. Significant increase was observed in the arginase I levels in SCD patients compared to the control group (p < 0.0001). The comparison between the levels of arginase I in three haplotypes groups showed a difference between the Bantu/Bantu × Bantu/Benin groups; Bantu/Bantu × Benin/Benin, independent of HU dosage. An inverse correlation with the arginase I levels and HbF concentration was observed. Conclusion. The results support the hypothesis that arginase I is associated with HbF concentration, also measured indirectly by the association with haplotypes.

Blood parameters and measurements of weight in the rehabilitation of Magellanic penguins (Spheniscus magellanicus, Foster 1781) / Parâmetros sanguíneos e medidas de peso na reabilitação de pinguins-de-Magalhães (Spheniscus magellanicus, Foster 1781)

During the austral winter the appearance of the Magellanic penguin (Spheniscus magellanicus) is common on the southern coast of Brazil. The oil pollution constitutes a major cause of death of these birds. The monitoring of the weight and blood variables is important to make decisions during the rehabilitation and release of these animals. Thus, the aim of this study was to evaluate the relationship between the penguins' survival during rehabilitation and the values of hematocrit (Hct), total plasma protein (TPP) and body weight (BW) of the birds received at Centro de Recuperação de Animais Marinhos (Recovery Centre for Sea Animals) between 2006 and 2009. The analysis took place weekly, and penguins were classified according to the outcome of the rehabilitation process, when 101 specimens were rehabilitated and released, and 67 died. Released animals showed a decrease in the Hct in the second and third weeks (41±6% and 40±5% respectively) followed by recovery of the values in the fourth and fifth week (41±4% and 43±4% respectively). TPP levels increased steadily over the collections, stabilizing at 7.3±0.8g/dL in the fourth week. On the other hand, animals that died, although following the same response for TPP, showed no significant difference in Hct between collections, and showed a tendency for loss of BW in the last weeks of rehabilitation. The curves of BW and Hct during rehabilitation were considered a potential prognostic indicator of penguins in rehabilitation. Animals that arrived at the recovery centre with BW, Hct and TPP above 2.700g, 45% and 5.6 g / dL, respectively, have a greater chance of recovery, making these parameters crucial points in decision making regarding the treatment to be conducted during rehabilitation.

Durante o inverno austral, é comum o aparecimento do pinguim-de-Magalhães (Spheniscus magellanicus) no litoral sul do Brasil. A poluição por petróleo constitui a maior causa de morte dessas aves. O acompanhamento do peso e de variáveis sanguíneas é importante para a tomada de decisões durante a reabilitação e liberação desses animais. O objetivo deste estudo foi avaliar a relação entre a sobrevivência dos pinguins durante a reabilitação e os valores de hematócrito (Ht), proteínas plasmáticas totais (PPT) e peso corpóreo (PC) das aves recebidas no Centro de Recuperação de Animais Marinhos entre 2006 e 2009. As análises ocorreram semanalmente, e os pinguins foram classificados em função do desfecho do processo de reabilitação, quando 101 espécimes foram reabilitados e liberados e 67 foram a óbito. Animais liberados apresentaram queda no Ht na segunda e terceira semanas (41±6% e 40±5%, respectivamente), seguida de recuperação dos valores na quarta e quinta semanas (41±4% e 43±4%, respectivamente). Os níveis de PPT aumentaram progressivamente ao longo das coletas, estabilizando na quarta semana em 7,3±0,8g/dL. Em contrapartida, animais que foram a óbito, apesar de seguirem a mesma resposta para as PPT, não apresentaram diferença significativa do Ht, entre as coletas, e demonstraram tendência à perda de PC nas últimas semanas de reabilitação. As curvas de PC e Ht foram consideradas indicadoras potenciais de prognóstico durante a reabilitação dos pinguins. Animais que chegaram ao centro de recuperação com PC, Ht e PPT acima de 2.700g, 45% e 5,6g/dL, respectivamente, apresentaram maior chance de recuperação, fazendo desses parâmetros pontos críticos na tomada de decisão quanto ao tratamento a ser conduzido durante a reabilitação.

Prevalence and etiology of buffalo mastitis and milk somatic cell count in dry and rainy seasons in a buffalo herd from Analândia, São Paulo State, Brazil / Prevalência e etiologia da mastite bubalina e contagem de células somáticas no leite, nas estações seca e chuvosa, em um rebanho bubalino do município de Analândia, Estado de São Paulo, Brasil

The aim of this study was to evaluate somatic cell count (SCC), prevalence and etiology of mastitis in a dairy buffalo herd from Analândia, São Paulo State, Brazil, in the dry and rainy seasons. Additionally, antimicrobial susceptibility profile of microorganisms isolated from milk samples was also evaluated. 1,042 milk samples from female Murrah buffaloes in a dairy farm located in Analândia, São Paulo State, Brazil, collected between May 2011 and November 2012 were analyzed. After the mammary gland physical examination, strip cup test and California Mastitis Test (CMT) were performed. Afterwards, 50mL of milk samples from each mammary quarter were collected aseptically for SCC in automatic equipment and microbiological examination. The antimicrobial sensitivity profile to ampicillin, cefoperazone, ceftiofur, enrofloxacin, gentamicin, neomycin, oxacillin, penicillin, and sulfamethoxazole/trimethoprim was evaluated by disk diffusion method. The monthly average temperature and pluviometric index were obtained from "Centro Integrado de Informações Agrometeorológicas" (CIIAGRO) of "Instituto Agronômico de Campinas" (IAC). Milk samples with positive results in the microbiological test showed average SCC of 137,720 cells/mL in the dry period and 190,309 cells/mL in the rainy period. Although a higher number of isolated microorganisms was observed in buffalo milk samples during the rainy period (69/600) compared to the dry period (50/442), the season had no significant effect on the frequency of isolation of microorganisms. The main genera of microorganisms isolated were coagulase-negative Staphylococcus (38.4%), Streptococcus agalactiae (28.8%), and Bacillus spp. (7.56%) during the dry season and Corynebacterium sp. (23.5%), Streptococcus spp. (32.3%), and Streptococcus agalactiae (9.24%) during the rainy period. Multidrug resistance was observed in 30.1% of the isolated microorganisms...

O objetivo do presente estudo foi avaliar a contagem de células somáticas, a prevalência e a etiologia da mastite bubalina nas estações seca e chuvosa em um rebanho de bubalinos do município de Analândia, estado de São Paulo, Brasil. Adicionalmente, verificou-se o perfil de sensibilidade antimicrobiana dos micro-organismos isolados nas amostras de leite das búfalas. Foram avaliadas 1.042 amostras de leite de búfalas da raça Murrah pertencentes a uma propriedade rural localizada no município de Analândia-SP, obtidas no período de maio de 2011 e novembro de 2012. Após o exame físico da glândula mamária, foram realizados o teste da caneca de fundo escuro e o California Mastits Test (CMT); em seguida, foram colhidas, de forma asséptica, amostras de 50mL de leite de cada quarto mamário, para a contagem de células somáticas (CCS) em aparelho automático e exame microbiológico. Também, foi avaliado o perfil de sensibilidade antimicrobiana a ampicilina, cefoperazona, ceftiofur, enrofloxacina, gentamicina, neomicina, oxacilina, penicilina e sulfametoxazol/trimetoprim, pelo método de difusão em disco. A temperatura média e o índice pluviométrico mensais foram obtidos no Centro Integrado de Informações Agrometeorológicas (CIIAGRO) do Instituto Agronômico de Campinas (IAC). Notou-se que as amostras de leite com resultado positivo no exame microbiológico apresentaram CCS média de 137.720 células/mL, no período seco, e 190.309 células/mL, no período chuvoso. Embora tenha se constatado maior índice de isolamentos de micro-organismos nas amostras de leite obtidas no período chuvoso (69/600) do que no período seco (50/442), a frequência de isolamentos não foi influenciada significativamente pela estação do ano...