Microscopy with ultraviolet surface excitation (MUSE): A novel approach to real‐time inexpensive slide‐free dermatopathology

Traditional histology relies on processing and physically sectioning either frozen or formalin‐fixed paraffin‐embedded (FFPE) tissue into thin slices (typically 4‐6 μm) prior to staining and viewing on a standard wide‐field microscope. Microscopy using ultraviolet (UV) surface excitation (MUSE) represents a novel alternative microscopy method that works with UV excitation using oblique cis‐illumination, which can generate high‐quality images from the cut surface of fresh or fixed tissue after brief staining, with no requirement for fixation, embedding and histological sectioning of tissue specimens. We examined its potential utility in dermatopathology. Concordance between MUSE images and hematoxylin and eosin (H&E) slides was assessed by the scoring of MUSE images on their suitability for identifying 10 selected epidermal and dermal structures obtained from minimally fixed tissue, including stratum corneum, stratum granulosum, stratum spinosum, stratum basale, nerve, vasculature, collagen and elastin, sweat glands, adipose tissue and inflammatory cells, as well as 4 cases of basal cell carcinoma and 1 case of pseudoxanthoma elasticum deparaffinized out of histology blocks. Our results indicate that MUSE can identify nearly all normal skin structures seen on routine H&E as well as some histopathologic features, and appears promising as a fast, reliable and cost‐effective diagnostic approach in dermatopathology.     

Fasting glucose cutoff point: where does the risk terminate? Tehran lipid and glucose study

The aim of this study is to determine safe fasting plasma glucose (FPG) levels. We included data on 5,960 individuals aged ≥20?years at baseline with at least one follow-up examination. Diabetes was ascertained in accordance with American Diabetes Association criteria, using standard 2-h post-challenge plasma glucose test. Multivariate restricted cubic splines Weibull regression was implemented for interval-censored survival data on incident diabetes. We used Harrell’s C statistic for discrimination, Nam-D’Agostino χ² for calibration, and Royston’s R ² for variations in the outcome explained by models. During a 6-year median follow-up, 369 incident cases of diabetes were ascertained. Family history of diabetes, systolic blood pressure, waist-to-height ratio, and triglyceride-to-high-density lipoprotein cholesterol ratio, independent of FPG and each other remained associated with incident diabetes. The cubic splines model achieved good calibration (χ²?=?12.1) and discrimination (C?=?0.828) and explained 75% of variation in the time until incident diabetes. A J-shaped FPG-diabetes relationship was observed. Descending arm of the dose–response relationship curve corresponded to increasing FPG levels up to 4.0?mmol?l^?1, where it started increasing. The risk of incident diabetes decreased with decreasing levels of FPG down to 4.0?mmol?l^?1, where the risk stopped decreasing. Multivariate-adjusted risk of incident diabetes was zero at FPG?=?5.05?mmol?l^?1. Although currently there is no firm evidence to show that early intervention among individuals with the elevated FPG levels could prevent or delay onset of diabetes, individuals with FPG levels below 5.05?mmol?l^?1 could be safely reassured about their near-term risk of developing incident diabetes and screened on a less frequent basis.     

Evaluation of Apoptotic and Antileishmanial Activities of Artemisinin on Promastigotes and BALB/C Mice Infected with Leishmania major

Background:

In leishmaniasis, some drugs prescribed for treatment have toxic effects and there are reports about drug resistance in some countries. Due to this fact, using herbal drugs such as artemisinin with good efficacy and low toxic effect might be suitable.

Methods:

We evaluated the apoptotic effect of artemisinin on Leishmania major in vitro and the antileishmanial activities of artemisinin on leishmaniasis in BALB/c mice and at the end INF-γ and IL-4 cytokines levels were detected by ELISA in spleen cell culture supernatants. During treatment the lesion size and survival rate were measured each four and ten days, respectively.

Results:

Percentage of early and late apoptosis in promastigotes of control group and promastigotes treated with 10, 25, 50 and 100 μg/ml of artemisinin after 48 h were 0.13, 16.04, 41.23, 49.03 and 81.83, respectively. The IFN-γ in ointment treated group were higher than those of other groups (P<0.05). The in vivo results showed that ointment compounds healed the lesions more effectively rather than intraperitoneal injection method (P<0.05). The survival rate of mice 150 days after challenge in treated group with ointment of artemisinin was 66% while all mice in control groups were died.

Conclusion:

All of in vitro results represented that this drug had antileishmanial effects and these results were confirmed by evaluation effects in vivo condition of leishmaniasis. Interestingly, according to these results it can be concluded that this drug has antileishmanial effects in vitro and in vivo conditions. Artemisinin induces cytotoxic effect on L. major via apoptosis-related mechanism.     

Update on the efficacy of statins in primary and secondary prevention of atrial fibrillation

Atrial fibrillation is the most common arrhythmia in adults and its prevalence is growing rapidly. It has been shown that AF is associated with increased risk of heart failure, ischemic and hemorrhagic stroke, and mortality. Hence, there is growing interest among researchers in seeking preventive and therapeutic interventions regarding AF. In recent decades, it has been suggested that statins may decrease the incidence of AF and may also decrease its recurrence after cardioversion and catheter ablation. These effects are thought to be mediated by different mechanisms such as modulating inflammation, altering the properties of transmembrane ion channels, interfering with activation of matrix metalloproteinases, and acting on endothelial function. In this article, we review and update current knowledge about the role of statins in primary and secondary prevention of AF in general and specific populations.     

Androgen receptor gene and sex-specific Alzheimer's disease

Women are at a 2-fold risk of developing late-onset Alzheimer's disease (AD) (onset at 65 years of age or older) compared with men. During perimenopausal years, women undergo hormonal changes that are accompanied by metabolic, cardiovascular, and inflammatory changes. These all together have been suggested as risk factors for late-onset AD. However, not all perimenopausal women develop AD; we hypothesize that certain genetic factors might underlie the increased susceptibility for developing AD in postmenopausal women. We investigated the Androgen Receptor gene (AR) in a clinical cohort of male and female AD patients and normal control subjects by sequencing all coding exons and evaluating the length and distribution of the CAG repeat in exon 1. We could not establish a correlation between the repeat length, sex, and the disease status, nor did we identify possible pathogenic variants. AR is located on the X chromosome; to assess its role in AD, X-inactivation patterns will need to be studied to directly correlate the actual expressed repeat length to a possible sex-specific phenotypic effect.     

Effects of Hybridized Synthetic Fibers on the Shear Properties of Cement Composites

The use of fibers in cementitious composites yields numerous benefits due to their fiber-bridging capabilities in resisting cracks. Therefore, this study aimed to improve the shear-resisting capabilities of conventional concrete through the hybridization of multiple synthetic fibers, specifically on reinforced concrete structures in seismic-prone regions. For this study, 16 hybrid fiber-reinforced concretes (HyFRC) were developed from the different combinations of Ferro macro-synthetic fibers with the Ultra-Net, Super-Net, Econo-Net, and Nylo-Mono microfibers. These hybrids were tested under direct shear, resulting in improved shear strength of controlled specimens by Ferro-Ultra (32%), Ferro-Super (24%), Ferro-Econo (44%), and Ferro-Nylo (24%). Shear energy was further assessed to comprehend the effectiveness of the fiber interactions according to the mechanical properties, dosage, bonding power, manufactured material, and form of fibers. Conclusively, all fiber combinations used in this study produced positive synergistic effects under direct shear at large crack deformations.     

Task-specific stability in muscle activation space during unintentional movements

We used robot-generated perturbations applied during position-holding tasks to explore stability of induced unintentional movements in a multidimensional space of muscle activations. Healthy subjects held the handle of a robot against a constant bias force and were instructed not to interfere with hand movements produced by changes in the external force. Transient force changes were applied leading to handle displacement away from the initial position and then back toward the initial position. Intertrial variance in the space of muscle modes (eigenvectors in the muscle activations space) was quantified within two subspaces, corresponding to unchanged handle coordinate and to changes in the handle coordinate. Most variance was confined to the former subspace in each of the three phases of movement, the initial steady state, the intermediate position, and the final steady state. The same result was found when the changes in muscle activation were analyzed between the initial and final steady states. Changes in the dwell time between the perturbation force application and removal led to different final hand locations undershooting the initial position. The magnitude of the undershot scaled with the dwell time, while the structure of variance in the muscle activation space did not depend on the dwell time. We conclude that stability of the hand coordinate is ensured during both intentional and unintentional actions via similar mechanisms. Relative equifinality in the external space after transient perturbations may be associated with varying states in the redundant space of muscle activations. The results fit a hierarchical scheme for the control of voluntary movements with referent configurations and redundant mapping between the levels of the hierarchy.