Decreased differentiation of erythroid cells exacerbates ineffective erythropoiesis in beta-thalassemia

In β-thalassemia, the mechanism driving ineffective erythropoiesis (IE) is insufficiently understood. We analyzed mice affected by β-thalassemia and observed, unexpectedly, a relatively small increase in apoptosis of their erythroid cells compared with healthy mice. Therefore, we sought to determine whether IE could also be characterized by limited erythroid cell differentiation. In thalassemic mice, we observed that a greater than normal percentage of erythroid cells was in S-phase, exhibiting an erythroblast-like morphology. Thalassemic cells were associated with expression of cell cycle–promoting genes such as EpoR, Jak2, Cyclin-A, Cdk2, and Ki-67 and the antiapoptotic protein Bcl-X_L. The cells also differentiated less than normal erythroid ones in vitro. To investigate whether Jak2 could be responsible for the limited cell differentiation, we administered a Jak2 inhibitor, TG101209, to healthy and thalassemic mice. Exposure to TG101209 dramatically decreased the spleen size but also affected anemia. Although our data do not exclude a role for apoptosis in IE, we propose that expansion of the erythroid pool followed by limited cell differentiation exacerbates IE in thalassemia. In addition, these results suggest that use of Jak2 inhibitors has the potential to profoundly change the management of this disorder.     

Host- and microbe-related risk factors for and pathophysiology of fatal Rickettsia conorii infection in Portuguese patients

BACKGROUND: The pathophysiologic mechanisms that determine the severity of Mediterranean spotted fever (MSF) and the host-related and microbe-related risk factors for a fatal outcome are incompletely understood. METHODS: This prospective study used univariate and multivariate analyses to determine the risk factors for a fatal outcome for 140 patients with Rickettsia conorii infection admitted to 13 Portuguese hospitals during 1994-2006 with documented identification of the rickettsial strain causing their infection. RESULTS: A total of 71 patients (51%) were infected with the Malish strain of Rickettsia conorii, and 69 (49%) were infected with the Israeli spotted fever (ISF) strain. Patients were admitted to the intensive care unit (40 [29%]), hospitalized as routine inpatients (95[67%]), or managed as outpatients (5[4%]). Death occurred in 29 adults (21%). A fatal outcome was significantly more likely for patients infected with the ISF strain, and alcoholism was a risk factor. The pathophysiology of a fatal outcome involved significantly greater incidence of petechial rash, gastrointestinal symptoms, obtundation and/or confusion, dehydration, tachypnea, hepatomegaly, leukocytosis, coagulopathy, azotemia, hyperbilirubinemia, and elevated levels of hepatic enzymes and creatine kinase. Some, but not all, of these findings were observed more often in ISF strain-infected patients. CONCLUSIONS: Although fatalities and similar clinical manifestations occurred among both groups of patients, the ISF strain was more virulent than the Malish strain. Multivariate analysis revealed that acute renal failure and hyperbilirubinemia were most strongly associated with a fatal outcome.     

Função Diastólica e Biomarcadores de Participantes de Caminhada de Longa Distância

Background:The effects of long-distance walking on the cardiovascular system have been little studied.Objectives:The general objective of this study was to verify these effects on the behavior of diastolic function and the cardiac biomarkers CK-MB (mass), troponin T, and NT-proBNP, in amateur athletes.Method:This longitudinal study, conducted in 2015, evaluated participants during the following 5 stages: E0 (baseline) before starting the trajectory and the others, E1, E2, E3, and E4, at the end of each day, totaling 244.7 km. At all stages, the biomarkers NT-proBNP, CK-MB (mass), and troponin T were measured. Echocardiogram was performed to analyze the E, A and E'' waves. P < 0.05 was adopted as significant.Results:The study evaluated 25 participants, with an average age of 46 ± 10.5 years and body mass index of 20.2 ± 2.3 kg/m2. Increased values were found for NT-proBNP from E0 to E1, E2, E3, and E4 (p < 0.001), CK-MB (mass) from E0 to E2 (p < 0.001), and E'' wave from E0 to E1, E2, E3, and E4 (p < 0.001). Positive correlations were identified between the following: CK-MB (mass) and troponin T (E1: r = 0.524, p = 0.010; E4: r = 0.413, p = 0.044); CK-MB (mass) and NT-proBNP (E4: r = 0.539, p = 0.006); and E/A and E'' (E0: r = 0.603, p < 0.001; E1: r = 0.639, p < 0.001; E4: r = 0.593, p = 0.002). A negative correlation was found between CK-MB (mass) and E/A (E1: r = −0.428, p = 0.041).Conclusion:The effects of intense, prolonged, and interspersed physical activity were verified based on significant variations in the behavior of CK-MB (mass), NT-proBNP, and the E'' wave. Notwithstanding the alterations found, there were no criteria suggestive of myocardial damagePalavras-chave: Walking, Biomarkers, Biological, Blood Pressure, Troponin-T, Natriuretic Peptide Brain, Athletes, Echocardiography, Doppler/methods     

Unsafe Drug Use and Arrhythmic Events in Brugada Patients with ICD: Results of a Long-Term Follow-Up

Purpose

Brugada syndrome is a hereditary disease linked with an increased risk of sudden death that may require an implantable cardioverter-defibrillator (ICD) in order to halt the arrhythmic events. The aim of this study was to identify possible triggers for appropriate ICD therapies in patients with Brugada syndrome, focusing on their past and current therapeutic profiles.

Methods

Thirty patients with high-risk Brugada syndrome, with ICD implanted at the Coimbra Hospital and University Center, were enrolled. Patients were questioned about their Brugada syndrome history, previous cardiac events, comorbidities, present and past medications, and physical activity. Patients were followed up during 5.8?±?5.3 years. The ICD was interrogated, and arrhythmic events and device therapies were recorded. The cohort who received appropriate ICD therapies was compared with the remaining patients to determine the potential link between clinical variables and potentially fatal arrhythmic events.

Results

More than half of the patients (53.3%) took at least one non-recommended drug, and 16.7% received appropriate ICD therapies, with a long-term rate of 4.0%/year. There was a tendency for more appropriate ICD therapies in patients who took unsafe drugs (85.7 versus 45.5%, p?=?0.062), and the mean time between unsafe drug intake and appropriate ICD therapies was 3.8?±?7.5 days.

Conclusions

This study revealed that the medical community is still unaware of the pharmacological restrictions imposed by Brugada syndrome. Patients who took non-recommended drugs seem to have a higher risk of ventricular arrhythmic events.

     

Computer-Aided Methodology for Syndromic Strabismus Diagnosis

Strabismus is a pathology that affects approximately 4 % of the population, causing aesthetic problems reversible at any age and irreversible sensory alterations that modify the vision mechanism. The Hirschberg test is one type of examination for detecting this pathology. Computer-aided detection/diagnosis is being used with relative success to aid health professionals. Nevertheless, the routine use of high-tech devices for aiding ophthalmological diagnosis and therapy is not a reality within the subspecialty of strabismus. Thus, this work presents a methodology to aid in diagnosis of syndromic strabismus through digital imaging. Two hundred images belonging to 40 patients previously diagnosed by an specialist were tested. The method was demonstrated to be 88 % accurate in esotropias identification (ET), 100 % for exotropias (XT), 80.33 % for hypertropias (HT), and 83.33 % for hypotropias (HoT). The overall average error was 5.6Δ and 3.83Δ for horizontal and vertical deviations, respectively, against the measures presented by the specialist.