Confocal Laser Endomicroscopy in the Diagnosis of Biliary and Pancreatic Disorders: A Systematic Analysis

Background/Aims@#Endoscopic visualization of the microscopic anatomy can facilitate the real-time diagnosis of pancreatobiliary disorders and provide guidance for its treatment. This study aimed to review the technique, image classification, and diagnostic performance of confocal laser endomicroscopy (CLE). @*Methods@#We conducted a systematic review of CLE in pancreatic and biliary ducts of humans, and have provided a narrative of the technique, image classification, diagnostic performance, ongoing research, and limitations. @*Results@#Probe-based CLE differentiates malignant from benign biliary strictures (sensitivity, ≥89%; specificity, ≥61%). Needlebased CLE differentiates mucinous from non-mucinous pancreatic cysts (sensitivity, 59%; specificity, ≥94%) and identifies dysplasia. Pancreatitis may develop in 2-7% of pancreatic cyst cases. Needle-based CLE has potential applications in adenocarcinoma, neuroendocrine tumors, and pancreatitis (chronic or autoimmune). Costs, catheter lifespan, endoscopist training, and interobserver variability are challenges for routine utilization. @*Conclusions@#CLE reveals microscopic pancreatobiliary system anatomy with adequate specificity and sensitivity. Reducing costs and simplifying image interpretation will promote utilization by advanced endoscopists.

The maintenance ability and Ca²⁺ availability of skeletal muscle are enhanced by sildenafil

Sildenafil relaxes vascular smooth muscle cells and is used to treat pulmonary artery hypertension as well as erectile dysfunction. However, the effectiveness of sildenafil on skeletal muscle and the benefit of its clinical use have been controversial, and most studies focus primarily on tissues and organs from disease models without cellular examination. Here, the effects of sildenafil on skeletal muscle at the cellular level were examined using mouse primary skeletal myoblasts (the proliferative form of skeletal muscle stem cells) and myotubes, along with single-cell Ca2+ imaging experiments and cellular and biochemical studies. The proliferation of skeletal myoblasts was enhanced by sildenafil in a dose-independent manner. In skeletal myotubes, sildenafil enhanced the activity of ryanodine receptor 1, an internal Ca2+ channel, and Ca2+ movement that promotes skeletal muscle contraction, possibly due to an increase in the resting cytosolic Ca2+ level and a unique microscopic shape in the myotube membranes. Therefore, these results suggest that the maintenance ability of skeletal muscle mass and the contractility of skeletal muscle could be improved by sildenafil by enhancing the proliferation of skeletal myoblasts and increasing the Ca2+ availability of skeletal myotubes, respectively.

History of Alzheimer's Disease

As modern society ages rapidly, the number of people with dementia is sharply increasing. Direct medical costs and indirect social costs for dementia patients are also increasing exponentially. However, the lack of social awareness about dementia results in difficulties to dementia patients and their families. So, understanding dementia is the first step to remove or reduce the stigma of dementia patients and promote the health of our community. Alzheimer's disease is the most common form of dementia. The term, ‘Alzheimer's disease’ has been used for over 100 years since first used in 1910. With the remarkable growth of science and medical technologies, the techniques for diagnosis and treatment of dementia have also improved. Although the effects of the current symptomatic therapy are still limited, dramatic improvement is expected in the future through the continued research on disease modifying strategies at the earlier stage of disease. It is important to look at the past to understand the present and obtain an insight into the future. In this article, we review the etymology and history of dementia and previous modes of recognizing dementia. We also review the historical developments leading to the terminology of Alzheimer's disease.

Extracranial Carotid Artery Aneurysm With Thrombus: Usefulness of Carotid Duplex Ultrasonography

Extracranial carotid artery aneurysm is a rare disease. A 72-year-old man was admitted with a painful neck mass for 5 days. Neck CT angiography and carotid duplex ultrasonography revealed a fusiform aneurysm of the left carotid bifurcation with a thrombus. His symptoms improved after anticoagulation therapy. The thrombus decreased in size and ultimately disappeared, as evidenced by serial duplex examinations. Carotid duplex ultrasonography is a simple and useful tool for diagnosis and follow-up.

TRPC3 cation channel plays an important role in proliferation and differentiation of skeletal muscle myoblasts

During membrane depolarization associated with skeletal excitation-contraction (EC) coupling, dihydropyridine receptor [DHPR, a L-type Ca2+ channel in the transverse (t)-tubule membrane] undergoes conformational changes that are transmitted to ryanodine receptor 1 [RyR1, an internal Ca2+-release channel in the sarcoplasmic reticulum (SR) membrane] causing Ca2+ release from the SR. Canonical-type transient receptor potential cation channel 3 (TRPC3), an extracellular Ca2+-entry channel in the t-tubule and plasma membrane, is required for full-gain of skeletal EC coupling. To examine additional role(s) for TRPC3 in skeletal muscle other than mediation of EC coupling, in the present study, we created a stable myoblast line with reduced TRPC3 expression and without alpha1SDHPR (MDG/TRPC3 KD myoblast) by knock-down of TRPC3 in alpha1SDHPR-null muscular dysgenic (MDG) myoblasts using retrovirus-delivered small interference RNAs in order to eliminate any DHPR-associated EC coupling-related events. Unlike wild-type or alpha1SDHPR-null MDG myoblasts, MDG/TRPC3 KD myoblasts exhibited dramatic changes in cellular morphology (e.g., unusual expansion of both cell volume and the plasma membrane, and multi-nuclei) and failed to differentiate into myotubes possibly due to increased Ca2+ content in the SR. These results suggest that TRPC3 plays an important role in the maintenance of skeletal muscle myoblasts and myotubes.

Calcium Uptake and Release through Sarcoplasmic Reticulum in the Inferior Oblique Muscles of Patients with Inferior Oblique Overaction

We characterized and compared the characteristics of Ca2+ movements through the sarcoplasmic reticulum of inferior oblique muscles in the various conditions including primary inferior oblique overaction (IOOA), secondary IOOA, and controls, so as to further understand the pathogenesis of primary IOOA. Of 15 specimens obtained through inferior oblique myectomy, six were from primary IOOA, 6 from secondary IOOA, and the remaining 3 were controls from enucleated eyes. Ryanodine binding assays were performed, and Ca2+ uptake rates, calsequestrins and SERCA levels were determined. Ryanodine bindings and sarcoplasmic reticulum Ca2+ uptake rates were significantly decreased in primary IOOA (p < 0.05). Western blot analysis conducted to quantify calsequestrins and SERCA, found no significant difference between primary IOOA, secondary IOOA, and the controls. Increased intracellular Ca2+ concentration due to reduced sarcoplasmic reticulum Ca2+ uptake may play a role in primary IOOA.