Somatic NRAS mutation in patient with generalized lymphatic anomaly

Generalized lymphatic anomaly (GLA or lymphangiomatosis) is a rare disease characterized by a diffuse proliferation of lymphatic vessels in skin and internal organs. It often leads to progressive respiratory failure and death, but its etiology is unknown. Here, we isolated lymphangiomatosis endothelial cells from GLA tissue. These cells were characterized by high proliferation and survival rates, but displayed impaired capacities for migration and tube formation. We employed whole exome sequencing to search for disease-causing genes and identified a somatic mutation in NRAS. We used mouse and zebrafish model systems to initially evaluate the role of this mutation in the development of the lymphatic system, and we studied the effect of drugs blocking the downstream effectors, mTOR and ERK, on this disease.     

Role of goblet cells and mucin layer in protecting maternal IgA in precocious birds

Immune protection of the gut in early life depends on provision of maternal antibodies, particularly that of IgA. In precocial birds (in this study Gallus gallus domesticus) the egg provides the only source of maternal antibodies, IgA inclusive. The gut-life of IgA in hatchlings is expected to be brief due to antigen binding and intestinal washout, and maternal IgA is likely to be depleted prior to immune independence at 7–10 days of age in the domestic fowl. We followed the track of maternal IgA in mucosal surfaces of the fowl and describe for the first time a mechanism that might provide the means to extend the active period of maternal IgA in the gut. Maternal IgA was located in the gut, lung, and cloacal bursa in embryos and hatchlings prior to the appearance of endogenic IgA positive plasma cells (D3 in the bursa or D7 in the gut and lung); the source of IgA was most probably the yolk, as the plasma was devoid of IgA till D7 post-hatch. The levels of maternal IgA decreased with time, but were still easily determined at the onset of endogenous IgA production following maturation of the adaptive immune system. Persistence of maternal IgA in the gut was enabled by goblet cell up-take by a yet un-described mechanism, and its consequent release in a mucin-like layer on enterocyte apical surfaces.     

Vemurafenib‐induced interface dermatitis manifesting as radiation‐recall and a keratosis pilaris‐like eruption

Vemurafenib is a specific inhibitor of the V600E mutated BRAF protein kinase used for the treatment of unresectable or metastatic melanoma harboring this mutation. Multiple predictable side effects have been described with use of this targeted therapy, and implicate BRAF and mitogen activated protein kinase (MAPK) signaling pathways in their pathogenesis. Herein, we report the novel finding of an interface dermatitis in radiation recall and a keratosis pilaris‐like clinical reaction in a patient treated with vemurafenib.     

Life on the Western Front of Israel Stressful Living Conditions and Adolescent Cannabis Use

Negative implications of exposure to violence on health and wellbeing of youth have been observed and studied worldwide, especially in Israel. Youth in the western Negev of the country have been exposed to missile and terror attacks for more than a decade. However, implications of such prolonged exposure have not been fully studied. This study is aimed at the implications of exposure to such conditions on youth in the town of Ofakim in the Negev. A focus group was conducted with youth following the Israeli Defense Forces’ “Protective Edge” response to continued attacks from Gaza (July–Aug. 2014). Focus group participants reported high stress levels during the operation that resulted in an increase of substance use including alcohol, tobacco, cannabis, synthetic cannabis-like substances (e.g., “Nice Guy,” “Spice” and “Black Mamba”) and changes in eating and sleeping behavior. The Ofakim resilience center served as a shelter for participants providing for them with physical and emotional comfort. Staying in the “shelter” used for protection against missile attack promoted youth resilience. Exposure to violence has a significant impact on the health and wellbeing of young people and others. A secure receptive facility that provides trust and support can serve as an important moderator of the negative impact of emergency conditions. From the results reported in this article, further research is needed to fully assess the long-term effects of stress conditions including the use of cannabis and synthetic cannabis-like substances among youth and other residents in the Western Negev.     

New RNA motifs suggest an expanded scope for riboswitches in bacterial genetic control

The expression of certain genes involved in fundamental metabolism is regulated by metabolite-binding "riboswitch" elements embedded within their corresponding mRNAs. We have identified at least six additional elements within the Bacillus subtilis genome that exhibit characteristics of riboswitch function (glmS, gcvT, ydaO/yuaA, ykkC/yxkD, ykoK, and yybP/ykoY). These motifs exhibit extensive sequence and secondary-structure conservation among many bacterial species and occur upstream of related genes. The element located upstream of the glmS gene in Gram-positive organisms functions as a metabolite-dependent ribozyme that responds to glucosamine-6-phosphate. Other motifs form complex folded structures when transcribed as RNA molecules and carry intrinsic terminator structures. These findings indicate that riboswitches serve as a major genetic regulatory mechanism for the control of metabolic genes in many microbial species.     

Alterations of heart rate variability in women with overactive bladder syndrome

Introduction and hypothesis

Our objective was to compare autonomic nervous system function between women with an overactive bladder (OAB) and control participants during regulated bladder filling.

Methods

Twenty-four women, nine with OAB and 15 without (control), were instructed to drink 1.5 l of water at a rate of 250?ml every 5?min during continuous electrocardiogram (ECG) monitoring. Participants were asked to indicate first sensations of filling (FSF), first desire to void (FDV), strong desire to void (SDV), and maximal bladder capacity (MC). ECG signals were used to assess heart rate variability, which were analyzed in time and frequency domains using the fast Fourier transform. The low-frequency (LF)and high-frequency (HF) spectral bands were used to asses sympathetic and parasympathetic pathways, respectively.

Results

During the bladder-filling phase, women with OAB had significantly lower LF values (at the MC phase 5.4?±?1.4?ms²/Hz vs. 6.4±?0.6?ms²/Hz in the control group, p?=?0.02). In the control group, LF increased continuously, whereas in the OAB group, LF increased until the sensation of SDV and then abruptly decreased to baseline values. MC was lower in women with OAB (372?±?153?ml vs. 592?±?298?ml, p?Conclusions Reduced sympathetic tone in women with OAB may explain their attainment of lower volumes of MC and their sensation of urgency. The rapid decrease in sympathetic neural activity that accompanies the sensation of an SDV may be related to the pathophysiology of the urgency symptom in these women.     

Unusual presentations of pediatric neurobrucellosis

Neurobrucellosis is an uncommon complication of pediatric brucellosis. Acute meningitis and encephalitis are the most common clinical manifestations, however symptoms may be protean and diagnosis requires a high index of suspicion in patients from endemic areas. Diagnosis is often based on neurological symptoms, serology, and suggestive brain imaging because cerebrospinal fluid culture yields are low. Two cases of pediatric neurobrucellosis with unusual clinical and radiologic findings are presented.