Myofilament lattice structure in presence of a skeletal myopathy-related tropomyosin mutation

Human tropomyosin mutations deregulate skeletal muscle contraction at the cellular level. One key feature is the slowing of the kinetics of force development. The aim of the present study was to characterize the potential underlying molecular mechanisms by recording and analyzing the X-ray diffraction patterns of human membrane-permeabilized muscle cells expressing a particular β-tropomyosin mutation (E41K). During resting conditions, the d_1,0 lattice spacing, Δ_1,0 and I_1,1 to I_1,0 ratio were not different from control values. These results suggest that, in presence of the E41K β-tropomyosin mutation, the myofilament lattice geometry is well maintained and therefore may not have any detrimental influence on the contraction mechanisms and thus, on the rate of force generation.     

Variation in the HTR1A and HTR2A genes and social adjustment in depressed patients

Background

Social adjustment is impaired in depressed patients. The difficulty to adjust to social circumstances has been hypothesized to be one of the causes of depression, as well as a consequence of the disorder. Genetic variation in the serotonin transporter gene has been previously associated with social adjustment levels in patients with mood disorders.

Methods

We investigated whether variations on the HTR1A (rs6295) and HTR2A (rs7997012) genes were associated with levels of social adjustment using the Social Adjustment Scale in two samples of depressed patients (total n=156).

Results

Patients carrying the GG genotype of the HTR2A-rs7997012 showed better social adjustment in areas of work and family unit bonding.

Limitations

These findings did not survive correction for multiple testing and should be interpreted with caution.

Conclusion

Our finding is in line with previous observations that have associated the G allele of the HTR2A-rs7997012 with higher rate of antidepressant response. The HTR2A-rs7997012 is worthy of further investigation in studies examining factors that are related to depression course and outcome.     

Prognostic relevance of clinical and molecular risk factors in children with high-risk medulloblastoma treated in the phase II trial PNET HR+5

BackgroundHigh-risk medulloblastoma is defined by the presence of metastatic disease and/or incomplete resection and/or unfavorable histopathology and/or tumors with MYC amplification. We aimed to assess the 3-year progression-free survival (PFS) and define the molecular characteristics associated with PFS in patients aged 5–19 years with newly diagnosed high-risk medulloblastoma treated according to the phase II trial PNET HR+5.MethodsAll children received postoperative induction chemotherapy (etoposide and carboplatin), followed by 2 high-dose thiotepa courses (600 mg/m²) with hematological stem cell support. At the latest 45 days after the last stem cell rescue, patients received risk-adapted craniospinal radiation therapy. Maintenance treatment with temozolomide was planned to start between 1–3 months after the end of radiotherapy. The primary endpoint was PFS. Outcome and safety analyses were per protocol (all patients who received at least one dose of induction chemotherapy).ResultsFifty-one patients (median age, 8 y; range, 5–19) were enrolled. The median follow-up was 7.1 years (range: 3.4–9.0). The 3 and 5-year PFS with their 95% confidence intervals (95% CI) were 78% (65–88) and 76% (63–86), and the 3 and 5-year OS were 84% (72–92) and 76% (63–86), respectively. Medulloblastoma subtype was a statistically significant prognostic factor (P-value = 0.039) with large-cell/anaplastic being of worse prognosis, as well as a molecular subgroup (P-value = 0.012) with sonic hedgehog (SHH) and group 3 being of worse prognosis than wingless (WNT) and group 4. Therapy was well tolerated.ConclusionsThis treatment based on high-dose chemotherapy and conventional radiotherapy resulted in a high survival rate in children with newly diagnosed high-risk medulloblastoma.     

Unilateral duplication of the acromioclavicular joint: case report and literature review

Clavicle duplication is a rare anatomical variation of the scapular belt: only seven cases have been reported in the literature to date, and only one took note of the existence of a duplication of the acromioclavicular joint. Two hypotheses have been proposed to interpret this variation: genetic factors, or trauma occurred in the growth period. Clavicle duplication should not be mistaken for a quite frequent coracoclavicular joint widely described. The authors report the case of a left acromioclavicular joint duplication in a 51-year-old male patient presenting with left shoulder pain. This case was the first of literature providing 3D CT-scan images.     

A retrospective analysis of autotransplanted teeth including an evaluation of a novel surgical technique

Clinical Oral Investigations - To assess survival rates and frequency of complications for immature and mature autotransplanted teeth after at least 1 year in function. All consecutive patients who...