Sarcomeric deficits underlie MYBPC1-associated myopathy with myogenic tremor.

Myosin binding protein-C slow (sMyBP-C) comprises a subfamily of cytoskeletal proteins encoded by MYBPC1 that is expressed in skeletal muscles where it contributes to myosin thick filament stabilization and actomyosin cross-bridge regulation. Recently, our group described the causal association of dominant missense pathogenic variants in MYBPC1 with an early-onset myopathy characterized by generalized muscle weakness, hypotonia, dysmorphia, skeletal deformities, and myogenic tremor, occurring in the absence of neuropathy. To mechanistically interrogate the etiologies of this MYBPC1-associated myopathy in vivo, we generated a knock-in mouse model carrying the E248K pathogenic variant.

Endoplasmic reticulum maintains ion homeostasis required for plasma membrane repair.

Of the many crucial functions of the ER, homeostasis of physiological calcium increase is critical for signaling. Plasma membrane (PM) injury causes a pathological calcium influx. Here, we show that the ER helps clear this surge in cytoplasmic calcium through an ER-resident calcium pump, SERCA, and a calcium-activated ion channel, Anoctamin 5 (ANO5).

Ryanodine channel complex stabilizer compound S48168/ARM210 as a disease modifier in dystrophin-deficient mdx mice: proof-of-concept study and independent validation of efficacy.

Muscle fibers lacking dystrophin undergo a long-term alteration of Ca homeostasis, partially caused by a leaky Ca release ryanodine (RyR) channel. S48168/ARM210, an RyR calcium release channel stabilizer (a Rycal compound), is expected to enhance the rebinding of calstabin to the RyR channel complex and possibly alleviate the pathologic Ca leakage in dystrophin-deficient skeletal and cardiac muscle. This study systematically investigated the effect of S48168/ARM210 on the phenotype of mdx mice by means of a first proof-of-concept, short (4 wk), phase 1 treatment, followed by a 12-wk treatment (phase 2) performed in parallel by 2 independent laboratories.

Müllerian Agenesis in Cat Eye Syndrome and 22q11 Chromosome Abnormalities: A Case Report and Literature Review.

Background: Although Müllerian agenesis is the second most common cause of primary amenorrhea the underlying etiology in most cases is unknown. Müllerian agenesis has been reported as a rare finding associated with chromosomal aberrations of the 22q11 chromosomal region including at least 1 individual with cat eye syndrome (CES) and 10 individuals with deletions or duplications of the 22q11.2 region.

Impact of hepatobiliary service centralization on treatment and outcomes in patients with colorectal cancer and liver metastases.

Background: Centralization of specialist surgical services can improve patient outcomes. The aim of this cohort study was to compare liver resection rates and survival in patients with primary colorectal cancer and synchronous metastases limited to the liver diagnosed at hepatobiliary surgical units (hubs) with those diagnosed at hospital Trusts without hepatobiliary services (spokes).

Methods: The study included patients from the National Bowel Cancer Audit diagnosed with primary colorectal cancer between 1 April 2010 and 31 March 2014 who underwent colorectal cancer resection in the English National Health Service.