What's the best way to treat Achilles tendonopathy?

Rest and ice are considered first-line therapy for acute Achilles tendonopathy (strength of recommendation [SOR]: C, expert opinion), as is nonsteroidal anti- inflammatory drugs (NSAIDs) (SOR: B, systematic review). Chronic noninsertional Achilles tendonopathy should be treated with eccentric calf-muscle training (ECMT) (SOR: B, 3 randomized controlled trials [RCTs])

Deletion of periostin reduces muscular dystrophy and fibrosis in mice by modulating the transforming growth factor-β pathway

The muscular dystrophies are broadly classified as muscle wasting diseases with myofiber dropout due to cellular necrosis, inflammation, alterations in extracellular matrix composition, and fatty cell replacement. These events transpire and progress despite ongoing myofiber regeneration from endogenous satellite cells. The degeneration/regeneration response to muscle injury/disease is modulated by the proinflammatory cytokine transforming growth factor-β (TGF-β), which can also profoundly influence extracellular matrix composition through increased secretion of profibrotic proteins, such as the matricellular protein periostin. Here we show that up-regulation and secretion of periostin is pathological and enhances disease in the δ-sarcoglycan null (Sgcd(−/−)) mouse model of muscular dystrophy (MD). Indeed, MD mice lacking the Postn gene showed dramatic improvement in skeletal muscle structure and function. Mechanistically, Postn gene deletion altered TGF-β signaling so that it now enhanced tissue regeneration with reduced levels of fibrosis. Systemic antagonism of TGF-β with a neutralizing monoclonal antibody mitigated the beneficial effects of Postn deletion in vivo. These data suggest that periostin functions as a disease determinant in MD by promoting/allowing the pathological effects of TGF-β, suggesting that inhibition of periostin could represent a unique treatment approach

Recurrent Primary Intrasellar Paraganglioma

We describe a case of an 81-year-old male presenting with bitemporal visual field defects and blurry vision in the right eye. The patient was found to have a recurrent primary paraganglioma in the sellar and suprasellar region requiring a repeat transsphenoidal endoscopic resection. Immunohistochemical examination confirmed paraganglioma with the classic zellballen appearance which stained positive for chromogranin, synaptophysin, and S-100 in the periphery. Paragangliomas (PGLs) in the sella turcica are a rare entity; only 19 cases have ever been reported in the literature. PGLs in the sellar region are often misdiagnosed or diagnosed in a delayed fashion. Earlier diagnosis of this locally aggressive tumor and meticulous debulking can prevent morbidity secondary to the tumor's compressive effects. This report highlights the effectiveness of surgical interventions in treatment of paragangliomas. More research is still needed to determine the need for adjuvant therapies such as radiation

Marine bird aggregations associated with the tidally-driven plume and plume fronts of the Columbia River

Freshwater discharge from large rivers into the coastal ocean creates tidally-driven frontal systems known to enhance mixing, primary production, and secondary production. Many authors suggest that tidal plume fronts increase energy flow to fish-eating predators by attracting planktivorous fishes to feed on plankton aggregated by the fronts. However, few studies of plume fronts directly examine piscivorous predator response to plume fronts. Our work examined densities of piscivorous seabirds relative to the plume region and plume fronts of the Columbia River, USA. Common murres (Uria aalge) and sooty shearwaters (Puffinus griseus) composed 83% of all birds detected on mesoscale surveys of the Washington and Oregon coasts (June 2003-2006), and 91.3% of all birds detected on fine scale surveys of the plume region less than 40 km from the river mouth (May 2003 and 2006). Mesoscale comparisons showed consistently more predators in the central plume area compared to the surrounding marine area (murres: 10.1-21.5 vs. 3.4-8.2 birds km⁻²; shearwaters: 24.2-75.1 vs. 11.8-25.9 birds km⁻²). Fine scale comparisons showed that murre density in 2003 and shearwater density in both 2003 and 2006 were significantly elevated in the tidal plume region composed of the most recently discharged river water. Murres tended to be more abundant on the north face of the plume. In May 2003, more murres and shearwaters were found within 3 km of the front on any given transect, although maximum bird density was not necessarily found in the same location as the front itself. Predator density on a given transect was not correlated with frontal strength in either year. The high bird densities we observed associated with the tidal plume demonstrate that the turbid Columbia River plume does not necessarily provide fish with refuge from visual predators. Bird predation in the plume region may therefore impact early marine survival of Pacific salmon (Oncorhynchus spp.), which must migrate through the tidal plume and plume front to enter the ocean. Because murres and shearwaters eat primarily planktivorous fish such as the northern anchovy (Engraulis mordax), aggregation of these birds in the plume supports the hypothesis that it is the plume region as a whole, and not just the plume fronts, which enhances trophic transfer to piscivorous predators via planktivorous fishes.Keywords: Marine birds, River plumes, USA, Tidal fronts, Columbia River, Predator prey interactions, Forage fish, Salmon, Washington, Orego

Intrathecal enzyme replacement for Hurler syndrome: biomarker association with neurocognitive outcomes.

PurposeAbnormalities in cerebrospinal fluid (CSF) have been reported in Hurler syndrome, a fatal neurodegenerative lysosomal disorder. While no biomarker has predicted neurocognitive response to treatment, one of these abnormalities, glycosaminoglycan nonreducing ends (NREs), holds promise to monitor therapeutic efficacy. A trial of intrathecal enzyme replacement therapy (ERT) added to standard treatment enabled tracking of CSF abnormalities, including NREs. We evaluated safety, biomarker response, and neurocognitive correlates of change.MethodsIn addition to intravenous ERT and hematopoietic cell transplantation, patients (N = 24) received intrathecal ERT at four peritransplant time points; CSF was evaluated at each point. Neurocognitive functioning was quantified at baseline, 1 year, and 2 years posttransplant. Changes in CSF biomarkers and neurocognitive function were evaluated for an association.ResultsOver treatment, there were significant decreases in CSF opening pressure, biomarkers of disease activity, and markers of inflammation. Percent decrease in NRE from pretreatment to final intrathecal dose posttransplant was positively associated with percent change in neurocognitive score from pretreatment to 2 years posttransplant.ConclusionIntrathecal ERT was safe and, in combination with standard treatment, was associated with reductions in CSF abnormalities. Critically, we report evidence of a link between a biomarker treatment response and neurocognitive outcome in Hurler syndrome

Vitamin D Status Is Not Associated with Risk of Early Menopause

Background: Early natural menopause, the cessation of ovarian function before age 45 y, is positively associated with cardiovascular disease and other conditions. Dietary vitamin D intake has been inversely associated with early menopause; however, no previous studies have evaluated risk with regard to plasma 25-hydroxyvitamin D [25(OH)D] concentrations. Objective: We prospectively evaluated associations of total and free 25(OH)D and vitamin D–binding protein (VDBP) concentrations and the risk of early menopause in a case-control study nested within the Nurses’ Health Study II (NHS2). We also considered associations of 25(OH)D and VDBP with anti-Müllerian hormone (AMH) concentrations. Methods: The NHS2 is a prospective study in 116,430 nurses, aged 25–42 y at baseline (1989). Premenopausal plasma blood samples were collected between 1996 and 1999, from which total 25(OH)D and VDBP concentrations were measured and free 25(OH)D concentrations were calculated. Cases experienced menopause between blood collection and age 45 y (n = 328) and were matched 1:1 by age and other factors to controls who experienced menopause after age 48 y (n = 328). Conditional logistic regression models were used to estimate ORs and 95% CIs for early menopause according to each biomarker. Generalized linear models were used to estimate AMH geometric means according to each biomarker. Results: After adjusting for smoking and other factors, total and free 25(OH)D were not associated with early menopause. Quartile 4 compared with quartile 1 ORs were 1.04 (95% CI: 0.60, 1.81) for total 25(OH)D and 0.70 (95% CI: 0.41, 1.20) for free 25(OH)D. 25(OH)D was unrelated to AMH concentrations. VDBP was positively associated with early menopause; the OR comparing the highest with the lowest quartile of VDBP was 1.80 (95% CI: 1.09, 2.98). Conclusions: Our findings suggest that total and free 25(OH)D are not importantly related to the risk of early menopause. VDBP may be associated with increased risk, but replication is warranted

De novo assembly of the cattle reference genome with single-molecule sequencing.

BackgroundMajor advances in selection progress for cattle have been made following the introduction of genomic tools over the past 10-12 years. These tools depend upon the Bos taurus reference genome (UMD3.1.1), which was created using now-outdated technologies and is hindered by a variety of deficiencies and inaccuracies.ResultsWe present the new reference genome for cattle, ARS-UCD1.2, based on the same animal as the original to facilitate transfer and interpretation of results obtained from the earlier version, but applying a combination of modern technologies in a de novo assembly to increase continuity, accuracy, and completeness. The assembly includes 2.7 Gb and is >250× more continuous than the original assembly, with contig N50 >25 Mb and L50 of 32. We also greatly expanded supporting RNA-based data for annotation that identifies 30,396 total genes (21,039 protein coding). The new reference assembly is accessible in annotated form for public use.ConclusionsWe demonstrate that improved continuity of assembled sequence warrants the adoption of ARS-UCD1.2 as the new cattle reference genome and that increased assembly accuracy will benefit future research on this species

Multiple Optimal Phenotypes Overcome Redox and Glycolytic Intermediate Metabolite Imbalances in <i>Escherichia coli pgi</i> Knockout Evolutions

A mechanistic understanding of how new phenotypes develop to overcome the loss of a gene product provides valuable insight on both the metabolic and regulatory functions of the lost gene. The pgi gene, whose product catalyzes the second step in glycolysis, was deleted in a growth-optimized Escherichia coli K-12 MG1655 strain. The initial knockout (KO) strain exhibited an 80% drop in growth rate that was largely recovered in eight replicate, but phenotypically distinct, cultures after undergoing adaptive laboratory evolution (ALE). Multi-omic data sets showed that the loss of pgi substantially shifted pathway usage, leading to a redox and sugar phosphate stress response. These stress responses were overcome by unique combinations of innovative mutations selected for by ALE. Thus, the coordinated mechanisms from genome to metabolome that lead to multiple optimal phenotypes after the loss of a major gene product were revealed.IMPORTANCE A mechanistic understanding of how microbes are able to overcome the loss of a gene through regulatory and metabolic changes is not well understood. Eight independent adaptive laboratory evolution (ALE) experiments with pgi knockout strains resulted in eight phenotypically distinct endpoints that were able to overcome the gene loss. Utilizing multi-omics analysis, the coordinated mechanisms from genome to metabolome that lead to multiple optimal phenotypes after the loss of a major gene product were revealed