Intestinal phenotype in mice overexpressing a heparin-binding EGF-like growth factor transgene in enterocytes

Primary objective. Heparin-binding EGF-like growth factor (HB-EGF) protects the intestine from damage in animals. Future clinical trials of HB-EGF may involve administration of repeated doses of HB-EGF. Since HB-EGF activates EGF receptors which have been implicated in tumor development, we examined the effects of HB-EGF overexpression in the intestine.

Research design. We generated transgenic (TG) mice in which the human HB-EGF gene is driven by the villin promoter to overexpress HB-EGF along the crypt-villous axis from the duodenum to the colon.

Results. HB-EGF TG mice have increased enterocyte proliferation balanced by increased enterocyte apoptosis. Despite prolonged overexpression of HB-EGF, no evidence of intestinal hyperplasia or tumor formation occurs. Although HB-EGF TG mice have no significant phenotypic alterations under basal conditions, they have increased resistance to intestinal injury.

Conclusions. Prolonged intestinal HB-EGF overexpression results in no significant phenotypic alterations under basal conditions, but confers protection against intestinal injury.     

Abnormal motor surround inhibition associated with cortical and deep grey matter involvement in multiple sclerosis

ObjectiveMotor surround inhibition (mSI) is a physiological mechanism that contributes to hand movement control by focusing voluntary movement. Growing evidence suggests that hand movement control is impaired in multiple sclerosis. The aim of the study was to evaluate mSI in MS and to investigate the brain structures involved in mSI in multiple sclerosis.MethodsWe recruited 33 patients and 23 controls. To investigate mSI, we delivered transcranial magnetic single pulses during index finger flexion. Motor evoked potentials were recorded and first dorsal interosseous (“active muscle”) and from the abductor digiti minimi (“surround muscle”). mSI was expressed as the ratio between Motor evoked potentials recorded from the surround muscle during movement and at rest. Participants underwent a magnetic resonance study.ResultsPatients had impaired mSI as compared with controls. Magnetic resonance showed that basal ganglia had smaller volumes and higher mean diffusivity than controls. Impaired mSI correlated with primary motor cortex and basal ganglia involvement in multiple sclerosis.ConclusionAltered mSI in multiple sclerosis is related to cortical and subcortical grey matter involvement.SignificanceOur study provides the first demonstration of a pathophysiological mechanism underlying hand movement control dysfunction in multiple sclerosis. mSI represents a new therapeutic target of multiple sclerosis rehabilitative approaches.     

Starch digestibility modulation significantly improves glycemic variability in type 2 diabetic subjects: A pilot study

Background and aimsIn type 2 diabetes (T2D) patients, the reduction of glycemic variability and postprandial glucose excursions is essential to limit diabetes complications, beyond HbA1c level. This study aimed at determining whether increasing the content of Slowly Digestible Starch (SDS) in T2D patients’ diet could reduce postprandial hyperglycemia and glycemic variability compared with a conventional low-SDS diet.Methods and resultsFor this randomized cross-over pilot study, 8 subjects with T2D consumed a controlled diet for one week, containing starchy products high or low in SDS. Glycemic variability parameters were evaluated using a Continuous Glucose Monitoring System.Glycemic variability was significantly lower during High-SDS diet compared to Low-SDS diet for MAGE (Mean Amplitude of Glycemic Excursions, p < 0.01), SD (Standard Deviation, p < 0.05), and CV (Coefficient of Variation, p < 0.01). The TIR (Time In Range) [140–180 mg/dL[ was significantly higher during High-SDS diet (p < 0.0001) whereas TIRs ≥180 mg/dL were significantly lower during High-SDS diet. Post-meals tAUC (total Area Under the Curve) were significantly lower during High-SDS diet.ConclusionOne week of High-SDS Diet in T2D patients significantly improves glycemic variability and reduces postprandial glycemic excursions. Modulation of starch digestibility in the diet could be used as a simple nutritional tool in T2D patients to improve daily glycemic control.Registration numberin clinicaltrials.gov: NCT 03289494.     

Bacillus spp. as direct-fed microbial antibiotic alternatives to enhance growth,immunity, and gut health in poultry

The increasing occurrence of antibiotic-resistant bacteria combined with regulatory pressure and consumer demands for foods produced without antibiotics has caused the agricultural industry to restrict its practice of using antibiotic growth promoters (AGP) in food animals. The poultry industry is not immune to this trend, and has been actively seeking natural alternatives to AGP that will improve the health and growth performance of commercial poultry flocks. Bacillus probiotics have been gaining in popularity in recent years as an AGP alternative because of their health-promoting benefits and ability to survive the harsh manufacturing conditions of chicken feed production. This review provides an overview of several modes of action of some Bacillus direct-fed microbials as probiotics. Among the benefits of these direct-fed microbials are their production of naturally synthesized antimicrobial peptides, gut flora modulation to promote beneficial microbiota along the gastrointestinal tract, and various immunological and gut morphological alterations. The modes of action for increased performance are not well defined, and growth promotion is not equal across all Bacillus species or within strains. Appropriate screening and characterization of Bacillus isolates prior to commercialization are necessary to maximize poultry growth to meet the ultimate goal of eliminating AGP usage in animal husbandry.     

Photodynamic therapy effective for the treatment of actinic keratosis and basal cell carcinoma in bullous pemphigoid patients

Treating skin cancers and extensive actinic keratosis in patients with bullous pemphigoid (BP) can be challenging. Treatment options pose unique risks in these patients as surgical wounds can have delayed wound healing and photodynamic therapy (PDT) may exacerbate their blistering disease. We report the successful use of PDT to treat actinic keratosis and skin cancers in two patients with BP, both of whom had excellent response to PDT and tolerated treatment without any bullous disease flares. Carefully selected patients with skin cancers and stable, well controlled BP can be safely considered for treatment using PDT.     

Musical Alexia for Rhythm Notation: A Discrepancy Between Pitch and Rhythm

In the process of reading music, the reading of rhythm and pitch might be differentiated, although there is no evidence of this to date. There have been cases of disorders restricted to the reading of pitch, but none in which the disorder has been restricted to the reading of rhythm. We present a case of musical alexia and agraphia with Wernicke’s aphasia. An in-depth assessment of the subject’s musical reading ability showed that her musical alexia was restricted to unfamiliar melodies. When a melody was divided into rhythm elements and pitch elements, pitch reading was preserved, but rhythm reading was severely disturbed. This is the first case reported of a disorder restricted to rhythm reading, and suggests the independence of rhythm reading and pitch reading.     

Adjustments in the force–frequency relationship during passive and exercise‐induced hyperthermia

Introduction: We examined the extent to which fatiguing cycling exercise in the heat influences contractile function in modulating the force–frequency relationship. Methods: Before (∽37.0°C) and after (∽38.5°C) exercise (ExH) and passive (PaH) hyperthermia, an 8‐s train of stimulation at 10, 20, 50, and 100 Hz (2 s per frequency) and a potentiated twitch were evoked on the relaxed knee extensors using percutaneous stimulation. Results: ExH and PaH produced a decrease in the 20:50 Hz force ratio, indicative of low‐frequency fatigue (P < 0.01). This adjustment was more pronounced after ExH than PaH (P < 0.01). A rightward displacement in the force–frequency relationship occurred after ExH and PaH (P < 0.05) and was exacerbated by ExH (P < 0.05). Peak twitch force also decreased after ExH (P < 0.05). Conclusions: ExH reduces force summation due to development of skeletal muscle fatigue, exacerbating the shift in force–frequency to the right relative to PaH. Muscle Nerve 50 : 822–829, 2014     

Perceptions of Home Dialysis Training and Experience Among US Nephrology Fellows

1. Download : Download high-res image (397KB)
2. Download : Download full-size image