Autosomal Recessive Spinocerebellar Ataxia 7 (SCAR7) is Caused by Variants in TPP1, The Gene Involved in Classic Late‐Infantile Neuronal Ceroid Lipofuscinosis 2 Disease (CLN2 Disease)

Spinocerebellar ataxias are phenotypically, neuropathologically, and genetically heterogeneous. The locus of autosomal recessive spinocerebellar ataxia type 7 (SCAR7) was previously linked to chromosome band 11p15. We have identified TPP1 as the causative gene for SCAR7 by exome sequencing. A missense and a splice site variant in TPP1, cosegregating with the disease, were found in a previously described SCAR7 family and also in another patient with a SCAR7 phenotype. TPP1, encoding the tripeptidyl‐peptidase 1 enzyme, is known as the causative gene for late infantile neuronal ceroid lipofuscinosis disease 2 (CLN2 disease). CLN2 disease is characterized by epilepsy, loss of vision, ataxia, and a rapidly progressive course, leading to early death. SCAR7 patients showed ataxia and low activity of tripeptidyl‐peptidase 1, but no ophthalmologic abnormalities or epilepsy. Also, the slowly progressive evolution of the disease until old age and absence of ultra structural curvilinear profiles is different from the known CLN2 phenotypes. Our findings now expand the phenotypes related to TPP1‐variants to SCAR7. In spite of the limited sample size and measurements, a putative genotype–phenotype correlation may be drawn: we hypothesize that loss of function variants abolishing TPP1 enzyme activity lead to CLN2 disease, whereas variants that diminish TPP1 enzyme activity lead to SCAR7.     

Maximal strength training improves work economy, rate of force development and maximal strength more than conventional strength training

This study compared maximal strength training (MST) with equal training volume (kg × sets × repetitions) of conventional strength training (CON) primarily with regard to work economy, and second one repetition maximum (1RM) and rate of force development (RFD) of single leg knee extension. In an intra-individual design, one leg was randomized to knee-extension MST (4 or 5RM) and the other leg to CON (3 × 10RM) three times per week for 8 weeks. MST was performed with maximal concentric mobilization of force while CON was performed with moderate velocity. Eight untrained or moderately trained men (26 ± 1 years) completed the study. The improvement in gross work economy was ?0.10 ± 0.08 L min^?1 larger after MST (P = 0.011, between groups). From pre- to post-test the MST and CON improved net work economy with 31 % (P < 0.001) and 18 % (P = 0.01), respectively. Compared with CON, the improvement in 1RM and dynamic RFD was 13.7 ± 8.4 kg (P = 0.002) and 587 ± 679 N s^?1 (P = 0.044) larger after MST, whereas isometric RFD was of borderline significance 3,028 ± 3,674 N s^?1 (P = 0.053). From pre- to post-test, MST improved 1RM and isometric RFD with 50 % (P < 0.001) and 155 % (P < 0.001), respectively whereas CON improved 1RM and isometric RFD with 35 % (P < 0.001) and 83 % (P = 0.028), respectively. Anthropometric measures of quadriceps femoris muscle mass and peak oxygen uptake did not change. In conclusion, 8 weeks of MST was more effective than CON for improving work economy, 1RM and RFD in untrained and moderately trained men. The advantageous effect of MST to improve work economy could be due to larger improvements in 1RM and RFD.     

Can attachment and peer relation constructs predict anxiety in ethnic minority youths? A longitudinal exploratory study

ABSTRACT

Anxiety is the most prevalent psychiatric disturbance in childhood effecting typically 15–20% of all youth. It has been associated with attachment insecurity and reduced competence in peer relations. Prior work has been limited by including mainly White samples, relying on questionnaires, and applying a cross-sectional design. The present study addressed these limitations by considering how at-risk non-White youth (n = 34) responded to the Friends and Family Interview (FFI) in middle childhood and how this linked up with anxiety symptoms and an anxiety diagnosis three years later in early adolescence. Five dimensions of secure attachment, namely, (i) to mother, (ii) to father, (iii) coherence, (iv) developmental understanding, and (v) social competence and quality of contact with best friend in middle childhood, were found to correlate significantly (and negatively) with self-reported anxiety symptoms. Linear regression results showed independent influences of female gender, and (low) quality of best friend contact as the most efficient model predicting anxiety symptoms. Logistic regression results suggested a model that included female gender, low social competence, and immature developmental understanding as efficient predictors of an anxiety diagnosis, evident in only 18% of the sample. These results point to the usefulness of after-school programs for at-risk minority youth in promoting peer competence, developmental awareness, and minimizing anxiety difficulties.     

Cytokine Expression in Human Osteoblasts After Antiseptic Treatment: A Comparative Study Between Polyhexanide and Chlorhexidine

Purpose/Aim of the study: Chlorhexidine and polyhexanide are frequently used antiseptics in clinical practice and have a broad antimicrobial range. Both antiseptics are helpful medical agents for septic wound treatment with a high potential for defeating joint infections. Their effect on human osteoblasts has, so far, not been sufficiently evaluated. The aim of this study was to investigate the activating potential of polyhexanide and chlorhexidine on inflammatory cytokines/chemokines in human osteoblasts in vitro. Materials and Methods: Human osteoblasts were isolated and cultivated in vitro and then treated separately with 0.1% and 2% chlorhexidine and 0.04% polyhexanide as commonly applied concentrations in clinical practice. Detection of cell structure and cell morphology was performed by light microscopic inspection. Cytokine and chemokine secretion was determined by using a multiplex suspension array. Results: Cell shrinking, defective cell membrane, and the loss of cell adhesion indicated cell damage of human osteoblasts after treatment with both antiseptics was evaluated by using light microscopy. Polyhexanide, but not chlorhexidine, caused human osteoblasts to secrete various interleukins (1β, 6, and 7), interferon γ, tumor necrosis factor α, vascular endothelial growth factor, eotaxin, fibroblast growth factor basic, and granulocyte macrophage colony-stimulating factor as quantified by multiplex suspension array. Conclusions: Both antiseptics induced morphological cell damage at an optimum exposure between 1 and 10 min. But only polyhexanide mediated a pronounced secretion of inflammatory cytokines and chemokines in human osteoblasts. Therefore, we recommend a preferred usage of chlorhexidine in septic surgery to avoid the induction of an inflammatory reaction.     

Pilot study of Sandostatin (octreotide) therapy of refractory HIV-associated diarrhea

Seventeen AIDS patients were enrolled in a prospective open-label dose-finding study of octreotide (Sandostatin) therapy for refractory diarrhea. Five were nonevaluable due to progression of AIDS symptomatology, and one was excluded because of lack of confirmation of HIV infection. Five of 11 evaluable patients responded to therapy (45%); two each at 50 g and 100 g, and one at 250 g thrice daily doses. A sixth patient demonstrated a moderate reduction in stool volume at 250 g thrice daily, which, although deemed clinically relevant, did not meet the criteria for response. On discontinuation of therapy, diarrhea recurred in all patients within 1–12 days, and responded to reinitiation of octreotide in those five patients who resumed treatment. Only one of the three patients with concurrent cryptosporidial infection responded to treatment. The drug was well tolerated, with mild symptomatology in three patients. Long-term treatment at a stable dose was effective in three of five treated patients for periods for seven months in one (moderate responder) and one year in two. One patient required dose increases to control symptoms, but after one year of treatment developed severe nausea following injections, which required dose cessation. One patient had partial control of his diarrhea for only three months despite two dose increases. These data suggest that octreotide may be of useful therapeutic value in HIV-associated diarrhea and that further studies are indicated.This study was supported by Sandoz Canada Inc.