Morbidity and mortality associated with gastrointestinal dysfunction in neuromuscular disease: a single-centre case series.

Gastrointestinal dysfunction in neuromuscular disease is associated with significant morbidity and mortality. It is often underreported despite its prevalence in this cohort. There are a number of issues reported, with gastrointestinal dysmotility and intestinal pseudo-obstruction carrying a poor outcome.

Venous Thromboembolism Requiring Anticoagulation Following Knee Arthroscopy in a Young Woman With an Intravaginal Contraceptive Device.

Venous thromboembolism following elective knee arthroscopy remains relatively rare. NuvaRing (Merck & Co), an intravaginal contraceptive device, has received attention recently due to reports detailing unexpected catastrophic pulmonary embolism and further suggesting an increased risk of venous and arterial thrombotic events in women who use it. A healthy, 30-year-old woman with a NuvaRing contraceptive device presented to the sports medicine clinic with knee pain, swelling, and mechanical symptoms.

Range of motion and ankle injury history association with sex in pediatric and adolescent athletes.

Background: Ankle sprain is one of the most common musculoskeletal injuries among young athletes, and there remains a gap in the literature regarding susceptibility to such injuries among physically active youth.

Objective: The primary purpose of this study was to determine the associations between sex, a history of ankle sprain, and ankle range of motion (ROM) in pediatric and adolescent athletes.

Methods: Athletes under the age of 18 years old who presented to a sports injury prevention center underwent ankle ROM measurements including plantarflexion (PF), inversion (IV), and eversion (EV).

Mechanical characterisation of agarose-based chromatography resins for biopharmaceutical manufacture.

Mechanical characterisation of agarose-based resins is an important factor in ensuring robust chromatographic performance in the manufacture of biopharmaceuticals. Pressure-flow profiles are most commonly used to characterise these properties. There are a number of drawbacks with this method, including the potential need for several re-packs to achieve the desired packing quality, the impact of wall effects on experimental set up and the quantities of chromatography media and buffers required.

Drying techniques for the visualisation of agarose-based chromatography media by scanning electron microscopy.

The drying of chromatography resins prior to scanning electron microscopy is critical to image resolution and hence understanding of the bead structure at sub-micron level. Achieving suitable drying conditions is especially important with agarose-based chromatography resins, as over-drying may cause artefact formation, bead damage and alterations to ultrastructural properties; and under-drying does not provide sufficient resolution for visualization under SEM. This paper compares and contrasts the effects of two drying techniques, critical point drying and freeze drying, on the morphology of two agarose based resins (MabSelect™/d ≈85 µm and Capto™ Adhere/d ≈75 µm) and provides a complete method for both.

Neurocognitive functioning in adults with congenital heart disease.

Objective: Adults with congenital heart disease (CHD) are at increased risk of psychological disorders and cognitive deficiencies due to structural/acquired neurological abnormalities and neurodevelopmental disorders as children. However, limited information is known about the neuropsychological functioning of adults with CHD. This study screened neuropsychological abilities and explored group differences related to cardiac disease severity and neurological risk factors in adults with CHD.

The β subunit of yeast AMP-activated protein kinase directs substrate specificity in response to alkaline stress.

Saccharomyces cerevisiae express three isoforms of Snf1 kinase that differ by which β subunit is present, Gal83, Sip1 or Sip2. Here we investigate the abundance, activation, localization and signaling specificity of the three Snf1 isoforms. The relative abundance of these isoforms was assessed by quantitative immunoblotting using two different protein extraction methods and by fluorescence microscopy.

Activation and inhibition of Snf1 kinase activity by phosphorylation within the activation loop.

The AMP-activated protein kinase is a metabolic regulator that transduces information about energy and nutrient availability. In yeast, the AMP-activated protein kinase, called Snf1, is activated when energy and nutrients are scarce. Earlier studies have demonstrated that activation of Snf1 requires the phosphorylation of the activation loop on threonine 210.

2-Deoxyglucose impairs Saccharomyces cerevisiae growth by stimulating Snf1-regulated and α-arrestin-mediated trafficking of hexose transporters 1 and 3.

The glucose analog 2-deoxyglucose (2DG) inhibits the growth of Saccharomyces cerevisiae and human tumor cells, but its modes of action have not been fully elucidated. Yeast cells lacking Snf1 (AMP-activated protein kinase) are hypersensitive to 2DG. Overexpression of either of two low-affinity, high-capacity glucose transporters, Hxt1 and Hxt3, suppresses the 2DG hypersensitivity of snf1Δ cells.

Intrapleural tissue plasminogen activator and deoxyribonuclease for pleural infection. An effective and safe alternative to surgery.

Rationale: Intrapleural tissue plasminogen activator (tPA)/deoxyribonuclease (DNase) therapy for pleural infection given at the time of diagnosis has been shown to significantly improve radiological outcomes. Published cases are limited to only a single randomized controlled trial and a few case reports.

Objectives: Multinational observation series to evaluate the pragmatic "real-life" application of tPA/DNase treatment for pleural infection in a large cohort of unselected patients.

Genetic analysis of resistance and sensitivity to 2-deoxyglucose in Saccharomyces cerevisiae.

Aerobic glycolysis is a metabolic pathway utilized by human cancer cells and also by yeast cells when they ferment glucose to ethanol. Both cancer cells and yeast cells are inhibited by the presence of low concentrations of 2-deoxyglucose (2DG). Genetic screens in yeast used resistance to 2-deoxyglucose to identify a small set of genes that function in regulating glucose metabolism.

Assessment of barriers to improve diabetes management in older adults: a randomized controlled study.

Objective: To evaluate whether assessment of barriers to self-care and strategies to cope with these barriers in older adults with diabetes is superior to usual care with attention control. The American Diabetes Association guidelines recommend the assessment of age-specific barriers. However, the effect of such strategy on outcomes is unknown.

Ligand binding to the AMP-activated protein kinase active site mediates protection of the activation loop from dephosphorylation.

The AMP-activated protein kinase (AMPK) is a conserved signaling molecule in a pathway that maintains adenosine triphosphate homeostasis. Recent studies have suggested that low energy adenylate ligands bound to one or more sites in the γ subunit of AMPK promote the formation of an active, phosphatase-resistant conformation. We propose an alternative model in which the kinase domain association with the heterotrimer core results in activation of the kinase catalytic activity, whereas low energy adenylate ligands bound in the kinase active site promote phosphatase resistance.

Resting-state brain functional connectivity is altered in type 2 diabetes.

Type 2 diabetes mellitus (T2DM) is a risk factor for Alzheimer disease (AD). Populations at risk for AD show altered brain activity in the default mode network (DMN) before cognitive dysfunction. We evaluated this brain pattern in T2DM patients.

Subunit and domain requirements for adenylate-mediated protection of Snf1 kinase activation loop from dephosphorylation.

Members of the AMP-activated protein kinase (AMPK) family are activated by phosphorylation at a conserved threonine residue in the activation loop of the kinase domain. Mammalian AMPK adopts a phosphatase-resistant conformation that is stabilized by binding low energy adenylate molecules. Similarly, binding of ADP to the Snf1 complex, yeast AMPK, protects the kinase from dephosphorylation.

ADP regulates SNF1, the Saccharomyces cerevisiae homolog of AMP-activated protein kinase.

The SNF1 protein kinase complex plays an essential role in regulating gene expression in response to the level of extracellular glucose in budding yeast. SNF1 shares structural and functional similarities with mammalian AMP-activated protein kinase. Both kinases are activated by phosphorylation on a threonine residue within the activation loop segment of the catalytic subunit.

Reg1 protein regulates phosphorylation of all three Snf1 isoforms but preferentially associates with the Gal83 isoform.

The phosphorylation status of the Snf1 activation loop threonine is determined by changes in the rate of its dephosphorylation, catalyzed by the yeast PP1 phosphatase Glc7 in complex with the Reg1 protein. Previous studies have shown that Reg1 can associate with both Snf1 and Glc7, suggesting substrate binding as a mechanism for Reg1-mediated targeting of Glc7. In this study, the association of Reg1 with the three Snf1 isoforms was measured by two-hybrid analysis and coimmunoprecipitation.

Brain activation during working memory is altered in patients with type 1 diabetes during hypoglycemia.

Objective: To investigate the effects of acute hypoglycemia on working memory and brain function in patients with type 1 diabetes.

Research Design And Methods: Using blood oxygen level-dependent (BOLD) functional magnetic resonance imaging during euglycemic (5.0 mmol/L) and hypoglycemic (2.

RefilinB (FAM101B) targets filamin A to organize perinuclear actin networks and regulates nuclear shape.

The intracellular localization and shape of the nucleus plays a central role in cellular and developmental processes. In fibroblasts, nuclear movement and shape are controlled by a specific perinuclear actin network made of contractile actin filament bundles called transmembrane actin-associated nuclear (TAN) lines that form a structure called the actin cap. The identification of regulatory proteins associated with this specific actin cytoskeletal dynamic is a priority for understanding actin-based changes in nuclear shape and position in normal and pathological situations.

Frequent hypoglycemia among elderly patients with poor glycemic control.

Background: Episodes of hypoglycemia are particularly dangerous in the older population. To reduce the risk of hypoglycemia, relaxation of the standard hemoglobin A(1c) (HbA(1c)) goals has been proposed for frail elderly patients. However, the risk of hypoglycemia in this population with higher HbA(1c) levels is unknown.

PP1 phosphatase-binding motif in Reg1 protein of Saccharomyces cerevisiae is required for interaction with both the PP1 phosphatase Glc7 and the Snf1 protein kinase.

In Saccharomyces cerevisiae, Snf1 kinase, the ortholog of the mammalian AMP-activated protein kinase, is activated by an increase in the phosphorylation of the conserved threonine residue in its activation loop. The phosphorylation status of this key site is determined by changes in the rate of dephosphorylation catalyzed by the yeast PP1 phosphatase Glc7 in a complex with the Reg1 protein. Reg1 and many PP1 phosphatase regulatory subunits utilize some variation of the conserved RVxF motif for interaction with PP1.

Differential roles of the glycogen-binding domains of beta subunits in regulation of the Snf1 kinase complex.

Members of the AMP-activated protein kinase family, including the Snf1 kinase of Saccharomyces cerevisiae, are activated under conditions of nutrient stress. AMP-activated protein kinases are heterotrimeric complexes composed of a catalytic alpha subunit and regulatory beta and gamma subunits. In this study, the role of the beta subunits in the regulation of Snf1 activity was examined.