Changes in cross-bridge cycling underlie muscle weakness in patients with tropomyosin 3-based myopathy.

Nemaline myopathy, the most common non-dystrophic congenital myopathy, is caused by mutations in six genes, all of which encode thin-filament proteins, including NEB (nebulin) and TPM3 (α tropomyosin). In contrast to the mechanisms underlying weakness in NEB-based myopathy, which are related to loss of thin-filament functions normally exerted by nebulin, the pathogenesis of muscle weakness in patients with TPM3 mutations remains largely unknown. Here, we tested the hypothesis that the contractile phenotype of TPM3-based myopathy is different from that of NEB-based myopathy and that this phenotype is a direct consequence of the loss of the specific functions normally exerted by tropomyosin.

Inhibition of activin receptor type IIB increases strength and lifespan in myotubularin-deficient mice.

X-linked myotubular myopathy (XLMTM) is a congenital disorder caused by deficiency of the lipid phosphatase, myotubularin. Patients with XLMTM often have severe perinatal weakness that requires mechanical ventilation to prevent death from respiratory failure. Muscle biopsy specimens from patients with XLMTM exhibit small myofibers with central nuclei and central aggregations of organelles in many cells.

I/We narratives among African American families raising children with special needs.

This paper examines a statistics debate among African American caregivers raising children with disabilities for insights into the work of "African American mothering." Using ethnographic, narrative and discourse analyses, we delineate the work that African American mothers do--in and beyond this conversation--to cross ideological and epistemological boundaries around race and disability. Their work entails choosing to be an "I" and, in some cases, actively resisting being seen as a "they" and/or part of a collective "we" in order to chart alternative futures for themselves and their children.

Activation of paternally expressed genes and perinatal death caused by deletion of the Gtl2 gene.

The Dlk1-Gtl2 imprinting locus is located on mouse distal chromosome 12 and consists of multiple maternally expressed non-coding RNAs and several paternally expressed protein-coding genes. The imprinting of this locus plays a crucial role in embryonic development and postnatal growth. At least one cis-element, the intergenic differentially methylated region (IG-DMR) is required for expression of maternally expressed genes and repression of silenced paternally expressed genes.

Effect of the look AHEAD study intervention on medication use and related cost to treat cardiovascular disease risk factors in individuals with type 2 diabetes.

Objective: To examine the effect of a lifestyle intervention to produce weight loss and increased physical fitness on use and cost of medications to treat cardiovascular disease (CVD) risk factors in people with type 2 diabetes.

Research Design And Methods: Look AHEAD is a multicenter randomized controlled trial of 5,145 overweight or obese individuals with type 2 diabetes, aged 45-76 years. An intensive lifestyle intervention (ILI) involving group and individual meetings to achieve and maintain weight loss through decreased caloric intake and increased physical activity was compared with a diabetes support and education (DSE) condition.

Functional muscle analysis of the Tcap knockout mouse.

Autosomal recessive limb-girdle muscular dystrophy type 2G (LGMD2G) is an adult-onset myopathy characterized by distal lower limb weakness, calf hypertrophy and progressive decline in ambulation. The disease is caused by mutations in Tcap, a z-disc protein of skeletal muscle, although the precise mechanisms resulting in clinical symptoms are unknown. To provide a model for preclinical trials and for mechanistic studies, we generated knockout (KO) mice carrying a null mutation in the Tcap gene.

Registering wishes about organ and tissue donation: personal discussion during licence renewal may be superior to online registration.

Consent to organ and tissue donation is higher when the deceased has indicated a wish to donate. The Australian Organ Donor Register (AODR) is the national register of preferences regarding donation. The AODR has a number of limitations; it has no mechanism for requiring individuals to register their wishes, while the online format both raises concerns about the validity of the consent obtained and precludes personal discussion of fears and concerns about donation.

Neuropathology of a fatal case of posterior reversible encephalopathy syndrome.

The pathology of posterior reversible encephalopathy syndrome (PRES) is undefined, since it is rarely fatal and is biopsied in only exceptional circumstances. We describe rapidly progressive PRES following stem cell transplant for acute lymphoblastic leukemia. After development of altered mental status, this 8-year-old girl had T2 prolongation of the white matter in a posterior-dominant distribution, eventually developing cerebellar edema, hemorrhage, hydrocephalus, and herniation.

Specific unwillingness to donate eyes: the impact of disfigurement, knowledge and procurement on corneal donation.

Although willingness, attitudes and beliefs surrounding solid-organ donation have been extensively investigated, much less is known about corneal donation. Despite evidence that a substantial number of families who agree to multiorgan donation also specifically refuse corneal donation, it is unclear why this occurs and what can be done to increase rates of corneal donation. We conducted a survey of 371 Australian adults regarding their views on corneal donation.

Mutations of tropomyosin 3 (TPM3) are common and associated with type 1 myofiber hypotrophy in congenital fiber type disproportion.

Congenital fiber type disproportion (CFTD) is a rare congenital myopathy characterized by hypotonia and generalized muscle weakness. Pathologic diagnosis of CFTD is based on the presence of type 1 fiber hypotrophy of at least 12% in the absence of other notable pathological findings. Mutations of the ACTA1 and SEPN1 genes have been identified in a small percentage of CFTD cases.

An interesting case of adenoviral hepatitis in a cardiac transplant recipient.

Adenoviral infections are commonly described in pediatric transplant populations. However, much less information is available regarding the incidence of infection and clinical spectrum of disease in adult transplant recipients. Moreover, this infection usually manifests as involvement of the transplanted organ in one pathologic form or the other, in addition to other systemic manifestations.

S-adenosyl homocysteine hydrolase is required for Myc-induced mRNA cap methylation, protein synthesis, and cell proliferation.

The c-Myc proto-oncogene promotes mRNA cap methylation, which is essential for almost all mRNA translation. The mRNA cap methylation reaction produces an inhibitory byproduct, S-adenosyl homocysteine. Here we report that Myc promotes upregulation of S-adenosyl homocysteine hydrolase (SAHH), an enzyme which hydrolyzes S-adenosyl homocysteine, thus neutralizing its inhibitory effects, and this is required for c-Myc-induced mRNA cap methylation.

Healthy Living Partnerships to Prevent Diabetes (HELP PD): design and methods.

Although the Diabetes Prevention Program (DPP) developed a lifestyle weight loss intervention that has been demonstrated to prevent type 2 diabetes in high-risk individuals, it has yet to be widely adopted at the community level. The Healthy Living Partnership to Prevent Diabetes study (HELP PD) was designed to translate the DPP approach for use in community settings as a cost-effective intervention led by Community Health Workers (CHW's) and administered through a Diabetes Care Center (DCC). Approximately 300 overweight and obese (BMI 25-40 kg/m(2)) individuals with prediabetes (fasting blood glucose 95-124 mg/dl) were randomly assigned to either a lifestyle weight loss intervention (LW) or an enhanced usual care comparison condition (UC).

Boundaries, shading, and border ownership: A cusp at their interaction.

The association of borders with "figure" rather than "background" provides a topological organizing principle for early vision. Such global influences have recently been shown to have local effects, with neuronal activity modulated by stimulus properties from well outside the classical receptive field. We extend the theoretical analysis of such phenomena by developing the geometry of interaction between shading, boundaries, and boundary ownership for smooth surfaces.

Early discharge care with ongoing follow-up support may reduce hospital readmissions in COPD.

Background: Early discharge care and self-management education, although effective in the management of chronic obstructive pulmonary disease (COPD), do not typically reduce hospital re-admission rates for exacerbations of the disease. We hypothesized that a respiratory outreach programme that comprises early discharge care followed by continued rapid-access out-patient support would reduce the need for hospital readmission in these patients.

Methods: Two hundred and forty-six patients, acutely admitted with exacerbations of COPD, were recruited to the respiratory outreach programme that included early discharge care, follow-up education, telephone support and rapid future access to respiratory out-patient clinics.

Prolonged duration local anesthesia with minimal toxicity.

Injectable local anesthetics that would last for many days could have a marked impact on periprocedural care and pain management. Formulations have often been limited in duration of action, or by systemic toxicity, local tissue toxicity from local anesthetics, and inflammation. To address those issues, we developed liposomal formulations of saxitoxin (STX), a compound with ultrapotent local anesthetic properties but little or no cytotoxicity.

Curcumin-induced degradation of PKC delta is associated with enhanced dentate NCAM PSA expression and spatial learning in adult and aged Wistar rats.

Polysialylation of the neural cell adhesion molecule (NCAM PSA) is necessary for the consolidation processes of hippocampus-based learning. Previously, we have found inhibition of protein kinase C delta (PKCdelta) to be associated with increased polysialyltransferase (PST) activity, suggesting inhibitors of this kinase might ameliorate cognitive deficits. Using a rottlerin template, a drug previously considered an inhibitor of PKCdelta, we searched the Compounds Available for Purchase (CAP) database with the Accelrys((R)) Catalyst programme for structurally similar molecules and, using the available crystal structure of the phorbol-binding domain of PKCdelta, found that diferuloylmethane (curcumin) docked effectively into the phorbol site.

Effect of chemical permeation enhancers on nerve blockade.

Chemical permeation enhancers (CPEs) have the potential to improve access of local anesthetics to the nerve, thereby improving nerve block performance. We assessed the effects of six CPEs on nerve blockade from tetrodotoxin (TTX) and from bupivacaine. Each of the six surfactants, representing three CPE subgroups (anionic, cationic, and nonionic surfactants) was coinjected with TTX or bupivacaine at the sciatic nerve of Sprague-Dawley rats.

Three-dimensional conductive constructs for nerve regeneration.

The unique electrochemical properties of conductive polymers can be utilized to form stand-alone polymeric tubes and arrays of tubes that are suitable for guides to promote peripheral nerve regeneration. Noncomposite, polypyrrole (PPy) tubes ranging in inner diameter from 25 microm to 1.6 mm as well as multichannel tubes were fabricated by electrodeposition.

Comparison of surface-enhanced resonance Raman scattering and fluorescence for detection of a labeled antibody.

A comparison is made of the quantitative detection of a labeled antibody by surface-enhanced resonance Raman scattering (SERRS) and by fluorescence using the same instrument with the same laser excitation source. The area under the curve for the fluorescence band is greater than for any single peak in the SERRS spectrum, but the broad fluorescence band is more difficult to discriminate from the background at low concentrations. Using the peak height of one SERRS band and the peak height at the fluorescence maximum, the detection limit for SERRS was lower (1.

Comparison of immediate postoperative walking ability in patients receiving minimally invasive and standard-incision hip arthroplasty: a prospective blinded study.

Minimally invasive hip arthroplasty is thought to result in less soft tissue damage, earlier ambulation, and improved rehabilitation. This prospective blinded cohort study objectively analyzed early functional walking ability by stride analysis 2 days postoperatively. Ninety-five patients were analyzed, 43 of who received the minimal incision and 52 the traditional incision.

Public education and organ donation: untested assumptions and unexpected consequences.

While the number of individuals able to benefit from transplantation increases with technological developments, donation rates remain insufficient to cater for demand. A universal response to the insufficient number of donor organs has been public education to increase knowledge about donation and transplantation, and to encourage individuals to register their wishes about donation. Although education appears to have increased knowledge and encouraged individuals to register their wishes, it has not increased the number of organs available for transplantation.