Myofibrillar myopathies: new developments

Purpose of review: Myofibrillar myopathies (MFMs) are a heterogeneous group of skeletal and cardiac muscle diseases. In this review, we highlight recent discoveries of new genes and disease mechanisms involved in this group of disorders.Recent findings: The advent of next-generation sequencing technology, laser microdissection and mass spectrometry-based proteomics has facilitated the discovery of new MFM causative genes and pathomechanisms. New mutations have also been discovered in older' genes, helping to find a classification niche for MFM-linked disorders showing variant phenotypes. Cell transfection experiments using primary cultured myoblasts and newer animal models provide insights into the pathogenesis of MFMs.Summary: An increasing number of genes are involved in the causation of variant subtypes of MFM. The application of modern technologies in combination with classical histopathological and ultrastructural studies is helping to establish the molecular diagnosis and reach a better understanding of the pathogenic mechanisms of each MFM subtype, thus putting an emphasis on the development of specific means for prevention and therapy of these incapacitating and frequently fatal diseases

Observation of slow light in the noise spectrum of a vertical external cavity surface emitting laser

The role of coherent population oscillations is evidenced in the noise spectrum of an ultra-low noise lasers. This effect is isolated in the intensity noise spectrum of an optimized single-frequency vertical external cavity surface emitting laser. The coherent population oscillations induced by the lasing mode manifest themselves through their associated dispersion that leads to slow light effects probed by the spontaneous emission present in the non-lasing side modes.Comment: accepted for publication in Phys. Rev. Let

Simultaneous bilateral or unilateral carpal tunnel release? A prospective cohort study of early outcomes and limitations

BACKGROUND: Over 60% of patients with carpal tunnel syndrome present with symptoms and findings of nerve compression in both hands. Our goal was to compare patient-rated difficulties in performing activities of daily living in the early postoperative period between those undergoing bilateral carpal tunnel release and those undergoing unilateral carpal tunnel release. METHODS: This prospective cohort study enrolled consecutive patients with bilateral carpal tunnel syndrome undergoing bilateral carpal tunnel release (n = 47) or unilateral carpal tunnel release (n = 41). Patient function and disease severity were measured by an abbreviated form of the Disabilities of the Arm, Shoulder and Hand questionnaire, QuickDASH, and the Boston Carpal Tunnel Questionnaire at baseline, at postoperative visit 1 at a mean time (and standard deviation) of 10 ± 3 days, and at postoperative visit 2 at a mean time (and standard deviation) of 30 ± 6 days. Patients rated their difficulty in completing fifteen activities of daily living each day for the first postoperative week. Patients reported the factors that influenced their choice of surgery. RESULTS: There was no difference in baseline function or disease severity between the two groups with regard to QuickDASH and the Boston Carpal Tunnel Questionnaire. Patients in both groups improved after carpal tunnel release with no difference between groups either at postoperative visit 1 for QuickDASH (p = 0.97) and the Boston Carpal Tunnel Questionnaire (p = 0.86) or at postoperative visit 2 for QuickDASH (p = 0.43) and the Boston Carpal Tunnel Questionnaire (p = 0.34). Patients undergoing bilateral carpal tunnel release had more difficulty only during postoperative days 1 to 2 in opening jars (p = 0.03), cooking (p = 0.008), and doing household chores (p = 0.02). Patients in the two groups did not differ (p > 0.05) in their abilities to perform activities of daily living necessary for personal hygiene or independence on any day during the first seven days following surgery with regard to using the bathroom, bathing, dressing, or eating. Although the most common reason why patients chose bilateral carpal tunnel release was to avoid two surgical procedures (42%), the most common reason why patients chose unilateral carpal tunnel release was concern for self-care (36%). CONCLUSIONS: Patients with bilateral carpal tunnel syndrome can anticipate more severe functional impairment during the first few postoperative days with bilateral carpal tunnel release compared with unilateral carpal tunnel release, but limitations beyond postoperative day 2 or 3 are similar for bilateral and unilateral carpal tunnel release. LEVEL OF EVIDENCE: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence

Improved cardiac management with a disease management program incorporating comprehensive lipid profiling.

Abstract The objective of this study was to evaluate the improved effectiveness of a disease management treatment protocol incorporating comprehensive lipid profiling and targeted lipid care based on lipid profile findings in patients with ischemic heart disease (IHD) or congestive heart failure (CHF) enrolled in a managed care plan. This retrospective cohort study, conducted over a 2-year period, compared outcomes between patients with a standard lipid profile to those evaluated with a comprehensive lipid profile. All adult members of the WellMed Medical Management, Inc. managed care health plan diagnosed with IHD or CHF, and continuously enrolled between July 1, 2006 and June 30, 2008, were included in the study. Cases were defined as those who had at least 1 comprehensive lipid test (the VAP [vertical auto profile] ultracentrifuge test) during this period (n=1767); they were compared to those who had no lipid testing or traditional standard lipid testing only (controls, n=289). Univariate statistics were analyzed to describe the groups, and bivariate t tests or chi-squares examined differences between the 2 cohorts. Multivariate regression analyses were performed to control for potential confounders. The results show that the case group had lower total costs ($4852.62 vs.$7413.18; P=0.0255), fewer inpatient stays (13.1% vs. 18.3% of controls; P=0.0175) and emergency department visits (11.9% vs. 15.6% of controls; P=0.0832). Prescription use and frequency of lipid measurement suggested improved control resulting from a targeted approach to managing specific dyslipidemias. A treatment protocol incorporating a comprehensive lipid profile appears to improve care and reduce utilization and costs in a disease management program for cardiac patients. (Population Health Management 2012;15:46-51)

Prepyramid-to-pyramid transition of SiGe islands on Si(001)

The morphology of the first three-dimensional islands appearing during strained growth of SiGe alloys on Si(001) was investigated by scanning tunneling microscopy. High resolution images of individual islands and a statistical analysis of island shapes were used to reconstruct the evolution of the island shape as a function of size. As they grow, islands undergo a transition from completely unfacetted rough mounds (prepyramids) to partially {105} facetted islands and then they gradually evolve to {105} facetted pyramids. The results are in good agreement with the predictions of a recently proposed theoretical model

Trapeziectomy with ligament reconstruction/ suspensionplasty compared to suture tape suspensionplasty for the surgical treatment of advanced thumb carpometacarpal osteoarthritis

PURPOSE: Trapeziectomy with tendon reconstruction/suspensionplasty (TRS) is the most commonly performed surgical procedure in the United States for treatment of thumb carpometacarpal (CMC) osteoarthritis (OA). Trapeziectomy with suture tape suspensionplasty (STS) has been used recently at the study institution as an alternative surgical treatment option with perceived benefits of earlier return to function and reduced operative time. The purpose of this study was to compare patient outcomes following TRS versus STS for treatment of thumb CMC OA. METHODS: All patients who underwent primary, isolated TRS or STS for treatment of thumb CMC OA between 1/1/2014 and 9/1/2020 were analyzed. We assessed demographics and preoperative and postoperative patient-rated outcome scores including Patient-reported outcomes measurement information system scores as well as pain outcomes, satisfaction, and appearance at a mean of 2.6 years after surgery (minimum 6 months). Time to return to work and activities was compared between groups. Bivariate statistics compared outcomes between groups. RESULTS: Ninety-four patients were included in the final study cohort, of which 53 underwent TRS and 41 underwent STS. There were no differences in preoperative, postoperative, or final patient-rated outcome scores between groups. Patients reported high global and appearance satisfaction scores at final follow-up in both groups. Mean tourniquet time was 15 minutes (26%) shorter and return to work was on average 3 weeks faster for the STS group. CONCLUSIONS: There were no differences in postoperative patient-rated outcome scores between the STS and TRS groups. The STS group had a shorter surgical time and faster return-to-work after surgery. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic III

Spectrometer manager: A versatile control software for pulse EPR spectrometers

A versatile control software for pulse EPR spectrometers is introduced. Common and task-specific problems are discussed and their solutions are described. The software provides the full spectrum of possibilities needed to perform arbitrary multidimensional pulse experiments. It allows for an easy interfacing of commonly used hardware components and enables straightforward modifications of the spectrometer. Good performance, configurability, and a number of unique features turn this software into an excellent tool for the operation of modern EPR spectrometers and upgrading old ones. © 2005 Wiley Periodicals, Inc

Filamin C-related myopathies: pathology and mechanisms

The term filaminopathy was introduced after a truncating mutation in the dimerization domain of filamin C (FLNc) was shown to be responsible for a devastating muscle disease. Subsequently, the same mutation was found in patients from diverse ethnical origins, indicating that this specific alteration is a mutational hot spot. Patients initially present with proximal muscle weakness, while distal and respiratory muscles become affected with disease progression. Muscle biopsies of these patients show typical signs of myofibrillar myopathy, including disintegration of myofibrils and aggregation of several proteins into distinct intracellular deposits. Highly similar phenotypes were observed in patients with other mutations in Ig-like domains of FLNc that result in expression of a noxious protein. Biochemical and biophysical studies showed that the mutated domains acquire an abnormal structure causing decreased stability and eventually becoming a seed for abnormal aggregation with other proteins. The disease usually presents only after the fourth decade of life possibly as a result of ageing-related impairments in the machinery that is responsible for disposal of damaged proteins. This is confirmed by mutations in components of this machinery that cause a highly similar phenotype. Transfection studies of cultured muscle cells reflect the events observed in patient muscles and, therefore, may provide a helpful model for testing future dedicated therapeutic strategies. More recently, FLNC mutations were also found in families with a distal myopathy phenotype, caused either by mutations in the actin-binding domain of FLNc that result in increased actin-binding and non-specific myopathic abnormalities without myofibrillar myopathy pathology, or a nonsense mutation in the rod domain that leads to RNA instability, haploinsufficiency with decreased expression levels of FLNc in the muscle fibers and myofibrillar abnormalities, but not to the formation of desmin-positive protein aggregates required for the diagnosis of myofibrillar myopathy

An AC susceptometer for the characterization of large, bulk superconducting samples

The main purpose of this work was to design, develop and construct a simple, low-cost AC susceptometer to measure large, bulk superconducting samples (up to 32 mm in diameter) in the temperature range 78-120 K. The design incorporates a double heating system that enables a high heating rate (25 K/hour) while maintaining a small temperature gradient (< 0.2 K) across the sample. The apparatus can be calibrated precisely using a copper coil connected in series with the primary coil. The system has been used successfully to measure the temperature dependence of the AC magnetic properties of entire RE-Ba-Cu-O [(RE)BCO] bulk superconducting domains. A typical AC susceptibility measurement run from 78 K to 95 K takes about 2 hours, with excellent temperature resolution (temperature step ~ 4 mK) around the critical temperature, in particular.Comment: 25 pages, 7 figures. Accepted for publication in Measurement Science and Technolog

Mammalian Adaptation of an Avian Influenza A Virus Involves Stepwise Changes in NS1

Influenza A viruses (IAVs) are common pathogens of birds that occasionally establish endemic infections in mammals. The processes and mechanisms that result in IAV mammalian adaptation are poorly understood. The viral non-structural 1 (NS1) protein counteracts the interferon (IFN) response, a central component of the host-species barrier. We characterised the NS1 proteins of equine influenza virus (EIV), a mammalian IAV lineage of avian origin. We showed that evolutionary distinct NS1s counteract the IFN response using different and mutually exclusive mechanisms: while the NS1s of early EIVs block general gene expression by binding to the cellular polyadenylation specific factor 30 (CPSF30), NS1s from more evolved EIVs specifically block the induction of IFN-stimulated genes by interfering with the JAK/STAT pathway. These contrasting anti-IFN strategies are associated with two mutations that appeared sequentially and became rapidly selected during EIV evolution, highlighting the importance of evolutionary processes on immune evasion mechanisms during IAV adaptation