Novel de novo heterozygous loss-of-function variants in MED13L and further delineation of the MED13L haploinsufficiency syndrome

MED13L haploinsufficiency has recently been described as responsible for syndromic intellectual disability. We planned a search for causative gene variants in seven subjects with intellectual disability and overlapping dysmorphic facial features such as bulbous nasal tip, short mouth and straight eyebrows. We found two de novo frameshift variants in MED13L, consisting in single-nucleotide deletion (c.3765delC) and duplication (c.607dupT). A de novo nonsense variant (c.4420A>T) in MED13L was detected in a further subject in the course of routine whole-exome sequencing. By analyzing the clinical data of our patients along with those recently described in the literature, we confirm that there is a common, recognizable phenotype associated with MED13L haploinsufficiency, which includes intellectual disability and a distinctive facial appearance. Congenital heart diseases are found in some subjects with various degree of severity. Our observation of cleft palate, ataxia, epilepsy and childhood leukemia observed in single cases broadens the known clinical spectrum. Haploinsufficiency for MED13L should be considered in the differential diagnosis of the 1p36 microdeletion syndrome, due to overlapping dysmorphic facial features in some patients. The introduction of massive parallel-sequencing techniques into clinical practice is expected to allow for detection of other causative point variants in MED13L. Analysis of genomic data in connection with deep clinical evaluation of patients could elucidate genetic heterogeneity of the MED13L haploinsufficiency phenotype.     

Dermatological manifestations in onchocerciasis: A retrospective study of 400 imported cases

Introduction

Onchocerciasis is caused by Onchocerca volvulus and mainly leads to pruritus and skin and visual disorders, including blindness. Seventeen million people are infected in 38 countries; 31 of these are in sub-Saharan Africa, six in Latin America and one on the Arabian Peninsula. More than 99% of cases occur in sub-Saharan Africa where 120 million people are at risk of infection. Eye disorders have been well-documented; however, skin disorders have not been described accurately. The objective of our study was to describe the epidemiology, main skin manifestations and treatment of imported onchocerciasis.

Peyer's Patches Epithelium in the Rat

The epithelial layer covering lymphoid follicles of Peyer's patches consists of cells with a different surface morphology. Some of these cells have been described as a distinct cytotype, the so-called M cells. In order to resolve the controversy on the specific morphological and biochemical markers of M cells, structural, ultrastructural, and morphometrical study of the epithelium covering the rat Peyer's patches were performed. Peyer's patches from healthy rats were processed for light microscopy, immunohistochemistry, in situ nick-end labeling (TUNEL), and scanning and transmission electron microscopy. A morphometric study was also performed to evaluate microvillus density, length, and number of lysosomes in different areas of the epithelium. Peyer's patches were covered by simple columnar/cubical dome epithelium (DE). Scarce goblet cells and a large number of enterocytes were observed. Ultrastructural observations revealed that the DE showed cells with different morphology. The density and length of microvilli and the lysosome number varied along the whole dome without significant differences. The DE cells characterized by short and disorganized microvilli appeared always in close spatial relationship with lymphocytes. In conclusion, the concept that distinct cell types (enterocytes and M cells) can be identified in the rat DE does not appear to be valid based on morphological criteria. It seems correct to consider that in rat Peyer's patches the presence of scarce goblet cells and a large number of enterocytes showing dynamic morphofunctional modifications is related to the functional state and/or to cell cycle.     

Intramyocardial dissecting hematoma in anterior wall ST elevation myocardial infarction: impact on left ventricular remodeling and prognosis

Intramyocardial dissecting hematoma is an uncommon complication of myocardial infarction potentially leading to cardiac rupture. The aim of the present study was to investigate coronary reperfusion results, left ventricular (LV) function recovery and remodeling and clinical outcomes in patients with anterior STEMI complicated by intramyocardial hematoma. We prospectively studied 87 patients (mean age 59?±?10 years; 88% male) with anterior STEMI (42 with intramyocardial hematoma) in order to evaluate coronary reperfusion results, LV remodeling (≥15% increase in end-systolic volume) and clinical outcomes (cardiac death, non-fatal reinfarction, and hospitalization for congestive heart failure) at 24 months. Thrombolysis in myocardial infarction (TIMI) flow score and myocardial blush grade (MBG) were assessed both pre- and post-percutaneous coronary intervention (PCI) and speckle-tracking echocardiography was performed post PCI and at 6-month follow-up. Patients with hematoma had lower post-PCI TIMI score and MBG, higher heart rate, worse LV ejection fraction and longitudinal or rotational function than their counterparts. LV remodeling occurred in 33 (78.6%) patients with hematoma and 11 (24.4%) patients without (p?<?0.001). Independent predictors of LV remodeling were heart rate (p?=?0.018), MBG (p?=?0.036) and presence of hematoma (p?<?0.001). Hematoma (log-rank test, χ²?=?9.849; p?=?0.002) and LV remodeling (log-rank test, χ²?=?13.770; p?<?0.001) were associated to a higher rate of adverse events. Cox analysis identified LV remodeling as the only independent predictor of adverse events (hazard ratio?=?3.912; 95% confidence interval, 1.429–10.714; p?=?0.008). Intramyocardial dissecting hematoma complicating anterior STEMI is an independent determinant of LV remodeling and is associated to poor prognosis.     

Population-Based Study of Trachoma in Guatemala

Abstract

Purpose: A prevalence survey for active trachoma in children aged under 10 years and trichiasis in women aged 40 years and older was carried out in four districts in the Sololá region in Guatemala, which is suspected of still having a trachoma problem.

Methods: Population-based surveys were undertaken in three districts, within 15 randomly selected communities in each district. In addition, in a fourth district that borders the third district chosen, we surveyed the small northern sub-district, by randomly selecting three communities in each community, 100 children aged under 10 years were randomly selected, and all females over 40 years. Five survey teams were trained and standardized. Trachoma was graded using the World Health Organization simplified grading scheme and ocular swabs were taken in cases of clinical follicular or inflammatory trachoma. Prevalence estimates were calculated at district and sub-district level.

Results: Trachoma rates at district level varied from 0–5.1%. There were only two sub-districts where active trachoma approached 10% (Nahualá Costa, 8.1%, and Santa Catarina Costa, 7.3%). Trichiasis rates in females aged 40 years and older varied from 0–3%. Trachoma was likely a problem in the past.

Conclusions: Trachoma is disappearing in the Sololá region in Guatemala. Health leadership may consider further mapping of villages around the areas with an especially high rate of trachoma and infection, and instituting trichiasis surgery and active trachoma intervention where needed.     

Effect of Parasympathetic Stimulation on Brain Activity During Appraisal of Fearful Expressions

Autonomic nervous system activity is an important component of human emotion. Mental processes influence bodily physiology, which in turn feeds back to influence thoughts and feelings. Afferent cardiovascular signals from arterial baroreceptors in the carotid sinuses are processed within the brain and contribute to this two-way communication with the body. These carotid baroreceptors can be stimulated non-invasively by externally applying focal negative pressure bilaterally to the neck. In an experiment combining functional neuroimaging (fMRI) with carotid stimulation in healthy participants, we tested the hypothesis that manipulating afferent cardiovascular signals alters the central processing of emotional information (fearful and neutral facial expressions). Carotid stimulation, compared with sham stimulation, broadly attenuated activity across cortical and brainstem regions. Modulation of emotional processing was apparent as a significant expression-by-stimulation interaction within left amygdala, where responses during appraisal of fearful faces were selectively reduced by carotid stimulation. Moreover, activity reductions within insula, amygdala, and hippocampus correlated with the degree of stimulation-evoked change in the explicit emotional ratings of fearful faces. Across participants, individual differences in autonomic state (heart rate variability, a proxy measure of autonomic balance toward parasympathetic activity) predicted the extent to which carotid stimulation influenced neural (amygdala) responses during appraisal and subjective rating of fearful faces. Together our results provide mechanistic insight into the visceral component of emotion by identifying the neural substrates mediating cardiovascular influences on the processing of fear signals, potentially implicating central baroreflex mechanisms for anxiolytic treatment targets.     

Postpartum depression in Mexican women with autoimmune rheumatic diseases

Clinical Rheumatology -     

Doppler enthesitis: a potential useful outcome in the assessment of axial spondyloarthritis and psoriatic arthritis

Clinical Rheumatology - To analyse the frequency of power Doppler (PD) enthesitis in active axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA) patients and its potential usefulness in...