Gyrification, cortical and subcortical morphometry in neurofibromatosis type 1: an uneven profile of developmental abnormalities.

Background: Neurofibromatosis type 1 (NF1) is a monogenic disorder associated with cognitive impairments. In order to understand how mutations in the NF1 gene impact brain structure it is essential to characterize in detail the brain structural abnormalities in patients with NF1. Previous studies have reported contradictory findings and have focused only on volumetric measurements. Here, we investigated the volumes of subcortical structures and the composite dimensions of the cortex through analysis of cortical volume, cortical thickness, cortical surface area and gyrification. Methods: We studied 14 children with NF1 and 14 typically developing children matched for age, gender, IQ and right/left-handedness. Regional subcortical volumes and cortical gyral measurements were obtained using the FreeSurfer software. Between-group differences were evaluated while controlling for the increase in total intracranial volume observed in NF1. Results: Subcortical analysis revealed disproportionately larger thalami, right caudate and middle corpus callosum in patients with NF1. Cortical analyses on volume, thickness and surface area were however not indicative of significant alterations in patients. Interestingly, patients with NF1 had significantly lower gyrification indices than typically developing children primarily in the frontal and temporal lobes, but also affecting the insula, cingulate cortex, parietal and occipital regions. Conclusions: The neuroanatomic abnormalities observed were localized to specific brain regions, indicating that particular areas might constitute selective targets for NF1 gene mutations. Furthermore, the lower gyrification indices were accompanied by a disproportionate increase in brain size without the corresponding increase in folding in patients with NF1. Taken together these findings suggest that specific neurodevelopmental processes, such as gyrification, are more vulnerable to NF1 dysfunction than others. The identified changes in brain organization are consistent with the patterns of cognitive dysfunction in the NF1 phenotype. © 2013 Violante et al

Characterization of B cells in healthy pregnant women from late pregnancy to post-partum: a prospective observational study

BACKGROUND: B cells play a role in pregnancy due to their humoral and regulatory activities. To our knowledge, different maturational stages (from transitional to memory) of circulating B cell subsets have not yet been characterized (cell quantification and phenotype identification) in healthy pregnant women. Thus, the objective of our study was to characterize these subsets (as well as regulatory B cells) from late pregnancy to post-partum and to compare them with the circulating B cells of non-pregnant women. METHODS: In all of the enrolled women, flow cytometry was used to characterize the circulating B cell subsets according to the expression of IgD and CD38 (Bm1-Bm5 classification system). Regulatory B cells were characterized based on the expression of surface antigens (CD24, CD27, and CD38) and the production of IL-10 after lipopolysaccharide stimulation. RESULTS: Compared to the absolute counts of B cells in the non-pregnant women (n = 35), those in the pregnant women (n = 43) were significantly lower (p < 0.05) during the 3rd trimester of pregnancy and on delivery day (immediately after delivery). The percentages of these cells on delivery day and at post-partum were significantly lower than those in the non-pregnant women. In general, the absolute counts and percentages of the majority of the B cell subsets were significantly lower in the 3rd trimester of pregnancy and on delivery day than in the non-pregnant women. However, these counts and percentages did not differ significantly between the post-partum and the non-pregnant women. The most notable exceptions to the above were the percentages of naïve B cells (which were significantly higher in the 3rd trimester and on delivery day than in the non-pregnant women) and of CD24(hi)CD38(hi) regulatory B cells (which were significantly higher in the post-partum than in the non-pregnant women). CONCLUSION: According to our study, the peripheral B cell compartment undergoes quantitative changes during normal late pregnancy and post-partum. Such findings may allow us to better understand immunomodulation during human pregnancy and provide evidence that could aid in the development of new strategies to diagnose and treat pregnancy-associated disturbances. Our findings could also be useful for studies of the mechanisms of maternal responses to vaccination and infection

Long-term follow-up of asymptomatic or mildly symptomatic patients with severe degenerative mitral regurgitation and preserved left ventricular function

OBJECTIVES: The timing for mitral valve surgery in asymptomatic patients with severe mitral regurgitation and preserved left ventricular function remains controversial. We analyzed the immediate and long-term outcomes of these patients after surgery. METHODS: From January 1992 to December 2012, 382 consecutive patients with severe chronic degenerative mitral regurgitation, with no or mild symptoms, and preserved left ventricular function (ejection fraction ≥ 60%) were submitted to surgery and followed for up to 22 years (3209 patient-years). Patients with associated surgeries, other than tricuspid valve repair, were excluded. Cox proportional-hazard survival analysis was performed to determine predictors of late mortality and mitral reoperation. Subgroup analysis involved patients with atrial fibrillation or pulmonary hypertension. RESULTS: Mitral valvuloplasty was performed in 98.2% of cases. Thirty-day mortality was 0.8%. Overall survival at 5, 10, and 20 years was 96.3% ± 1.0%, 89.7% ± 2.0%, and 72.4% ± 5.8%, respectively, and similar to the expected age- and gender-adjusted general population. Patients with atrial fibrillation/pulmonary hypertension had a 2-fold risk of late mortality compared with the remaining patients (hazard ratio, 2.54; 95% confidence interval, 1.17-4.80; P = .018). Benefit was age-dependent only in younger patients (<65 years; P = .016). Patients with atrial fibrillation/pulmonary hypertension (hazard ratio, 4.20, confidence interval, 1.10-11.20; P = .037) and patients with chordal shortening were at increased risk for reoperation, whereas patients with P2 prolapse (hazard ratio, 0.06; confidence interval, 0.008-0.51; P = .037) and patients with myxomatous valves (hazard ratio, 0.072; confidence interval, 0.008-0.624; P = .017) were at decreased risk. CONCLUSIONS: Mitral valve repair can be achieved in the majority of patients with low mortality (<1%) and excellent long-term survival. Patients with atrial fibrillation/pulmonary hypertension had compromised long-term survival, particularly younger patients (aged <65 years), and are at increased risk of mitral reoperation.info:eu-repo/semantics/publishedVersio

Left Ventricular Diastolic Function in Type 2 Diabetes Mellitus and the Association With Coronary Artery Calcium Score: A Cardiac MRI Study

OBJECTIVE: The purpose of this study was to compare cardiac MRI-derived parameters of left ventricular (LV) diastolic function between uncomplicated type 2 diabetes mellitus (DM2) and normoglycemic control subjects and to evaluate whether these parameters of LV diastolic function are related to coronary atherosclerosis. SUBJECTS AND METHODS: We prospectively studied 41 subjects with DM2 and 21 normoglycemic control subjects (30 women and 32 men; mean age, 57.2 ± 7.1 [SD] years) with no evidence of overt cardiovascular disease. We used cardiac MRI to measure LV volumes, LV peak filling rate (PFR), and transmitral flow and CT to determine coronary artery calcium scores. RESULTS: Absolute values of the peak filling rate (PFR) were significantly lower in DM2 patients than in control subjects (mean ± SD, 293.2 ± 51.7 vs 375.7 ± 102.8 mL/s, respectively; p < 0.001). Mitral peak E velocities (mean ± SD, 42.8 ± 10.7 vs 48.8 ± 10.4 cm/s; p = 0.040) and peak E velocity-to-peak A velocity ratios (0.88 ± 0.3 vs 1.1 ± 0.3; p = 0.002) were also lower in DM2 patients compared with control subjects. DM2 patients with coronary artery calcification showed a lower PFR normalized to stroke volume (SV) (mean ± SD, 4.4 ± 1.0 vs 5.3 ± 1.4, respectively; p = 0.038) and lower mitral peak E velocities (40.1 ± 11.3 vs 48.0 ± 7.3 cm/s; p = 0.024) than DM2 patients without coronary calcification. PFR normalized to SV was independently associated with the presence of coronary artery calcification (β = -1.5, p = 0.005). CONCLUSION: DM2 decreases cardiovascular MRI-derived parameters of LV diastolic function. Patients with DM2 and coronary atherosclerosis show a more impaired LV diastolic function than patients without coronary atherosclerosis

Ketogenic Diet and Drug-Induced Hepatotoxicity During Tuberculosis Treatment

When therapy with hepatotoxic drugs is being considered, all other possible contributing agents of liver damage should be held to account. While not generally considered a risk factor, we present 2 cases in which ketogenic diet (KD) may have played a role in liver injury due to antituberculosis drugs. Ketogenic diet has been linked to liver injury, and while its pathophysiology remains obscure, carnitine depletion could play a role, as it is a mechanism of liver damage common to KD and antituberculosis drug regimens.info:eu-repo/semantics/publishedVersio

Compreender a Recorrência dos Mixomas Cardíacos. Um Caso Clínico

Recurrence of cardiac myxoma is a rare condition, observed in about 3% of patients in sporadic cases, although it is more frequent in familial ones. Several mechanisms have been proposed to explain such recurrence, and the importance of increased vascularization as a facilitating feature is the subject of debate. The authors report the case of a non-familial right atrial myxoma, unusual for both its histopathology and recurrence

Peripheral Attentional Targets under Covert Attention Lead to Paradoxically Enhanced Alpha Desynchronization in Neurofibromatosis Type 1

The limited capacity of the human brain to process the full extent of visual information reaching the visual cortex requires the recruitment of mechanisms of information selection through attention. Neurofibromatosis type-1 (NF1) is a neurodevelopmental disease often exhibiting attentional deficits and learning disabilities, and is considered to model similar impairments common in other neurodevelopmental disorders such as autism. In a previous study, we found that patients with NF1 are more prone to miss targets under overt attention conditions. This finding was interpreted as a result of increased occipito-parietal alpha oscillations. In the present study, we used electroencephalography (EEG) to study alpha power modulations and the performance of patients with NF1 in a covert attention task. Covert attention was required in order to perceive changes (target offset) of a peripherally presented stimulus. Interestingly, alpha oscillations were found to undergo greater desynchronization under this task in the NF1 group compared with control subjects. A similar pattern of desynchronization was found for beta frequencies while no changes in gamma oscillations could be identified. These results are consistent with the notion that different attentional states and task demands generate different patterns of abnormal modulation of alpha oscillatory processes in NF1. Under covert attention conditions and while target offset was reported with relatively high accuracy (over 90% correct responses), excessive desynchronization was found. These findings suggest an abnormal modulation of oscillatory activity and attentional processes in NF1. Given the known role of alpha in modulating attention, we suggest that alpha patterns can show both abnormal increases and decreases that are task and performance dependent, in a way that enhanced alpha desynchronization may reflect a compensatory mechanism to keep performance at normal levels. These results suggest that dysregulation of alpha oscillations may occur in NF1 both in terms of excessive or diminished activation patterns

Coronary artery bypass surgery without cardioplegia: hospital results in 8515 patients†

OBJECTIVES: Cardioplegic myocardial protection is used in most cardiac surgical procedures. However, other alternatives have proved useful. We analysed the perioperative results in a large series of patients undergoing coronary artery bypass (CABG) using cardiopulmonary bypass (CPB) and non-cardioplegic methods. METHODS: From January 1992 to October 2013, 8515 consecutive patients underwent isolated CABG with CPB without cardioplegia, under hypothermic ventricular fibrillation and/or an empty beating heart. The mean age was 61.9 ± 9.5 years, 12.4% were women, 26.3% diabetic, 64% hypertensive; and 9.6% had peripheral vascular disease, 7.8% cerebrovascular disease and 54.3% previous acute myocardial infarction (AMI). One-third of patients were in Canadian Cardiovascular Society Class III/IV. Three-vessel disease was present in 76.5% of the cases and 10.9% had moderate/severe left ventricle (LV) dysfunction (ejection fraction <40%). A multivariate analysis was made of risk factors associated to in-hospital mortality and three major morbidity complications [cerebrovascular accident, mediastinitis and acute kidney injury (AKI)], as well as for prolonged hospital stay. RESULTS: The mean CPB time was 58.2 ± 20.7 min. The mean number of grafts per patient was 2.7 ± 0.8 (arterial: 1.2 ± 0.5). The left internal thoracic artery (ITA) was used in 99.4% of patients and both ITAs in 23.1%. The in-hospital mortality rate was 0.7% (61 patients), inotropic support was required in 6.6% and mechanical support in 0.8, and 2.0% were re-explored for bleeding and 1.3% for sternal complications (mediastinitis, 0.8%). AKI, the majority transient, occurred in 1595 patients (18.9%). The incidence rates of stroke/transient ischemic attack (TIA) and acute myocardial infarction (AMI) were 2.6 and 2.5%, respectively, and atrial fibrillation/flutter occurred in 22.6% of cases. Age, LV dysfunction, non-elective surgery, previous cardiac surgery, peripheral vascular disease and CPB time were independent risk factors for mortality and major morbidity. The mean hospital stay was 7.2 ± 5.7 days. CONCLUSIONS: Isolated CABG with CPB using non-cardioplegic methods proved very safe, with low mortality and morbidity. These methods are simple and expeditious and remain as very useful alternative techniques of myocardial preservation.info:eu-repo/semantics/publishedVersio

Genome-wide distribution of 5-formylcytosine in embryonic stem cells is associated with transcription and depends on thymine DNA glycosylase

This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.EAR is a Herchel Smith Fellow. MB and HB are supported by the Centre for Trophoblast Research, MB is a Next Generation Research Fellow. MJB is supported by a BBSRC studentship. The WR lab is supported by BBSRC, MRC, the Wellcome Trust, EU EpiGeneSys and BLUEPRINT. The SB lab is supported by core funding from Cancer Research UK