Mutation spectrum in the large GTPase dynamin 2, and genotype-phenotype correlation in autosomal dominant centronuclear myopathy

Centronuclear myopathy (CNM) is a genetically heterogeneous disorder associated with general skeletal muscle weakness, type I fiber predominance and atrophy, and abnormally centralized nuclei. Autosomal dominant CNM is due to mutations in the large GTPase dynamin 2 (DNM2), a mechanochemical enzyme regulating cytoskeleton and membrane trafficking in cells. To date, 40 families with CNM-related DNM2 mutations have been described, and here we report 60 additional families encompassing a broad genotypic and phenotypic spectrum. In total, 18 different mutations are reported in 100 families and our cohort harbors nine known and four new mutations, including the first splice-site mutation. Genotype-phenotype correlation hypotheses are drawn from the published and new data, and allow an efficient screening strategy for molecular diagnosis. In addition to CNM, dissimilar DNM2 mutations are associated with Charcot-Marie-Tooth (CMT) peripheral neuropathy (CMTD1B and CMT2M), suggesting a tissue-specific impact of the mutations. In this study, we discuss the possible clinical overlap of CNM and CMT, and the biological significance of the respective mutations based on the known functions of dynamin 2 and its protein structure. Defects in membrane trafficking due to DNM2 mutations potentially represent a common pathological mechanism in CNM and CMT.     

Creatine supplementation does not augment muscle carnosine content in type 2 diabetic patients

We examined whether creatine supplementation affects muscle carnosine content in type 2 diabetic patients. Subjects were randomly assigned to receive either creatine (5 g·day(-1)) or placebo in a double-blind fashion. At baseline and after 12 weeks, carnosine content was evaluated in gastrocnemius and soleus muscles by using a 1H-MRS technique. No changes were found in gastrocnemius (p = 0.81) and soleus (p = 0.85). We concluded that creatine supplementation does not augment muscle carnosine content in type 2 diabetic patients.     

Isolation of Candida dubliniensis in denture stomatitis

Objective

To describe the isolation of Candida dubliniensis from a patient with denture stomatitis and to compare with the presence of yeasts in the oral cavities of denture wearers.

Design

One hundred and fifty-two Candida isolates were recovered through oral swabs from denture as well as the underlying mucosa from 100 patients wearing denture. For detection and identification of fungal isolates, standard phenotypic and genotypic methods were used.

Results

Forty-five of 100 denture wearers suffered from denture stomatitis. Seventy-three Candida isolates were recovered from 38 denture wearers without denture stomatitis. In this group, Candida albicans was the predominant species (58.9%), followed by Candida tropicalis (15.1%), Candida guilliermondii (13.7%), Candida glabrata (9.6%), and Candida parapsilosis (2.7%).Seventy-nine isolates were yielded from 40 patients suffering from denture stomatitis. C. albicans was also the most frequently isolated species (58 isolates, 73.4%), followed by C. glabrata and C. tropicalis (7 isolates each, 8.9%), and Saccharomyces cerevisiae (2 isolates, 2.5%). One isolate was yielded of the following species: Candida famata, Candida krusei, C. parapsilosis and C. guilliermondii. Moreover 1 isolate was phenotypic and genotypic identified as C. dubliniensis genotype 1.

Conclusions

C. albicans is the predominant fungal species isolated from denture wearers. C. dubliniensis could be isolated from adults with denture stomatitis.     

Creatine supplementation does not impair kidney function in type 2 diabetic patients: a randomized, double-blind, placebo-controlled, clinical trial

Creatine supplementation may have a therapeutic role in diabetes, but it is uncertain whether this supplement is safe for kidney function. The aim of this study was to investigate the effects of creatine supplementation on kidney function in type 2 diabetic patients. A randomized, double-blind, placebo-controlled trial was performed. The patients were randomly allocated to receive either creatine or placebo for 12?weeks. All the patients underwent exercise training throughout the trial. Subjects were assessed at baseline and after the intervention. Blood samples and 24-h urine samples were obtained for kidney function assessments. Additionally, (51)Cr-EDTA clearance was performed. To ensure the compliance with creatine intake, we also assessed muscle phosphorylcreatine content. The creatine group presented higher muscle phosphorylcreatine content when compared to placebo group (CR Pre 44?±?10, Post 70?±?18?mmol/kg/wt; PL Pre 52?±?13, Post 46?±?13?mmol/kg/wt; p?=?0.03; estimated difference between means 23.6; 95% confidence interval 1.42-45.8). No significant differences were observed for (51)Cr-EDTA clearance (CR Pre 90.4?±?16.9, Post 96.1?±?15.0?mL/min/1.73?m(2); PL Pre 97.9?±?21.6, Post 96.4?±?26.8?mL/min/1.73?m(2); p?=?0.58; estimated difference between means -0.3; 95% confidence interval -24.9 to 24.2). Creatinine clearance, serum and urinary urea, electrolytes, proteinuria, and albuminuria were unchanged. CR supplementation does not affect kidney function in type 2 diabetic patients, opening a window of opportunities to explore its promising therapeutic role in this population. ClinicalTrials.gov registration number: NCT00992043.     

Selectivity for spectral motion as a neural computation for encoding natural communication signals in bat inferior colliculus

This study examines the neural computations performed by neurons in the auditory system to be selective for the direction and velocity of signals sweeping upward or downward in frequency, termed spectral motion. We show that neurons in the auditory midbrain of Mexican free-tailed bats encode multiple spectrotemporal features of natural communication sounds. These features to which each neuron is tuned are nonlinearly combined to produce selectivity for spectral motion cues present in their conspecific calls, such as direction and velocity. We find that the neural computations resulting in selectivity for spectral motion are analogous to models of motion selectivity studied in vision. Our analysis revealed that auditory neurons in the inferior colliculus (IC) are avoiding spectrotemporal modulations that are redundant across different bat communication signals and are specifically tuned for modulations that distinguish each call from another by their frequency-modulated direction and velocity, suggesting that spectral motion is the neural computation through which IC neurons are encoding specific features of conspecific vocalizations.     

From numbers to letters: Feedback regularization in visual word recognition

Word reading in alphabetic languages involves letter identification, independently of the format in which these letters are written. This process of letter ‘regularization’ is sensitive to word context, leading to the recognition of a word even when numbers that resemble letters are inserted among other real letters (e.g., M4TERI4L). The present study investigates the electrophysiological correlates of number-to-letter regularization by means of the masked priming paradigm: target words (MATERIAL) were preceded by fully alphabetic primes (MATERIAL), primes with letter-like numbers (M4T3R14L), or primes with unrelated numbers (M7T6R28L). ERPs revealed three subsequent effects. Around 150 ms the unrelated numbers condition elicited a positive effect, compared to the other two conditions, in the occipital electrodes. Then, target words preceded by primes with numbers elicited a more negative N200 in the same electrodes compared to the fully alphabetic condition. Finally, both alphabetic primes and letter-like numbers elicited a posterior positive component peaking around 260 ms compared to unrelated numbers. Source analysis for each electrophysiological effect revealed a similar early increase of activity in the left occipito-temporal pathway for alphabetic primes and primes with letter-like numbers. Around 200 ms, the orthographic interference due to the numerical values correlated with an increase of activity in parietal areas; finally, a recursive effect in the left occipital cortex was found, reflecting abstract letter activation. These results indicate that direct feedback interaction from word units strongly influences the activation of the letter units at a format-independent abstract level.     

CT metal artefact reduction of total knee prostheses using angled gantry multiplanar reformation

This study was designed to determine whether or not acquiring CT images of total knee prostheses by using an angled gantry and multiplanar reformation can reduce beam hardening artefact. A CT phantom was created with a total knee prosthesis suspended in gelatine with a known attenuation. CT data was acquired with a gantry angled at 0°, 5°, 10° and 15° in both craniocaudal oblique planes. Axial images where then reformatted from these datasets. Two independent observers selected regions of interest to measure the mean and standard deviation (SD) of attenuation in the gelatine for all reformatted axial images. Artefact was measured as SD of the background attenuation and areas under the curve of SD for each gantry angle acquisition were compared. Inter-observer reliability was excellent (ICC = 0.89, CI 0.875–0.908). The most accurate mean attenuation values for tissues around a TKR were obtained with a CT gantry using 10° to 15° anteroinferior to posterosuperior angulation. The smallest area under the curve for SD of attenuation for the whole prosthesis, and the femoral component in isolation, was obtained with a 5° gantry angle in the same direction. The smallest area under the curve for the tibial component in isolation occurred with a gantry angle of 15°. We conclude that acquiring CT data with a gantry angle can reduce metal artefact around a TKR. Optimal overall metal artefact reduction can be achieved with a small angle from anteroinferior to posterosuperior. Further selective artefact reduction around the tibial component can be achieved with larger angles.     

Changes in the Gut Bacteria Composition of Healthy Men with the Same Nutritional Profile Undergoing 10-Week Aerobic Exercise Training: A Randomized Controlled Trial

Nutrient consumption and body mass index (BMI) are closely related to the gut microbiota, and exercise effects on gut bacteria composition may be related to those variables. Thus, we aimed to investigate the effect of 10-week moderate aerobic exercise on the cardiorespiratory fitness and gut bacteria composition of non-obese men with the same nutritional profile. Twenty-four previously sedentary men (age 25.18 [SD 4.66] years, BMI 24.5 [SD 3.72] kg/m²) were randomly assigned into Control (CG; n = 12) or Exercise Groups (EG; n = 12). Body composition, cardiorespiratory parameters, blood markers, dietary habits and gut bacteria composition were evaluated. EG performed 150 min per week of supervised moderate (60–65% of VO₂peak) aerobic exercise, while CG maintained their daily routine. The V4 16S rRNA gene was sequenced and treated using QIIME software. Only EG demonstrated marked improvements in cardiorespiratory fitness (VO₂peak, p < 0.05; Effect Size = 0.971) without changes in other gut bacteria-affecting variables. Exercise did not promote clustering based on diversity indices (p > 0.05), although significant variations in an unclassified genus from Clostridiales order and in Streptococcus genus were observed (p < 0.05). Moreover, α-diversity was correlated with VO₂peak (Pearson’s R: 0.47; R² 0.23: 95%CI: 0.09 to 0.74, p = 0.02) and BMI (Pearson’s R: −0.50; R² 0.25: 95%CI: −0.75 to −0.12, p = 0.01). Roseburia, Sutterella and Odoribacter genera were associated with VO₂peak, while Desulfovibrio and Faecalibacterium genera were associated with body composition (p < 0.05). Our study indicates that aerobic exercise at moderate intensity improved VO₂peak and affected gut bacteria composition of non-obese men who maintained a balanced consumption of nutrients.