Sporadic and familial myoclonic dystonia: Report of three cases and review of literature

Myoclonic dystonia refers to a clinical syndrome characterized by rapid jerky movements along with dystonic posturing of the limbs. Clinically, it is characterized by sudden, brief, electric shock-like movements, mostly involving the upper extremities, shoulders, neck and trunk. Characteristically, the movements wane with consumption of small dose of alcohol in about 50% of cases. Additionally, dystonic contractions are observed in most of the patients in the affected body parts and some patients may exhibit cervical dystonia or graphospasm as well. It may manifest as an autosomal dominant condition or sometimes, as a sporadic entity, though there are doubts whether these represent cases with reduced penetrance. The condition is usually treated with a combination of an anticholinergic agent like, benztropine, pimozide and tetrabenazine. We report one sporadic case and one familial case where the father and the son are affected. The cases were collected from the Movement Disorders Clinic of Bangur Institute of Neurosciences, Kolkata, West Bengal in a period of ten months. Myoclonic dystonia is a rare condition and to the best of our knowledge, this series is the first one reported from our country. Videos of the patients are also provided with the article.     

Human peripheral gammadelta T cells potentiate the early proinflammatory cytokine response to staphylococcal toxic shock syndrome toxin-1

Toxic shock syndrome toxin (TSST)-1 is a superantigen known to profoundly induce proinflammatory cytokines by activation of V beta -specific alpha beta T cells, but its effect on gamma delta T cells, which normally constitute 1%-5% of peripheral blood mononuclear cells (PBMCs), is unclear. Here, we demonstrate that TSST-1 induced significantly higher levels of interferon (IFN)- gamma, tumor necrosis factor (TNF)- alpha, and interleukin (IL)-2, and a lower level of IL-10 in human PBMCs when the gamma delta subpopulation has been primed by isopentylpyrophosphate, compared with that in control PBMCs. Furthermore, depletion of the gamma delta subpopulation completely abrogated this effect. Thus, peripheral gamma delta T cells markedly modulate both the proinflammatory and anti-inflammatory cytokine responses of TSST-1.     

Simbios: an NIH national center for physics-based simulation of biological structures

Physics-based simulation provides a powerful framework for understanding biological form and function. Simulations can be used by biologists to study macromolecular assemblies and by clinicians to design treatments for diseases. Simulations help biomedical researchers understand the physical constraints on biological systems as they engineer novel drugs, synthetic tissues, medical devices, and surgical interventions. Although individual biomedical investigators make outstanding contributions to physics-based simulation, the field has been fragmented. Applications are typically limited to a single physical scale, and individual investigators usually must create their own software. These conditions created a major barrier to advancing simulation capabilities. In 2004, we established a National Center for Physics-Based Simulation of Biological Structures (Simbios) to help integrate the field and accelerate biomedical research. In 6 years, Simbios has become a vibrant national center, with collaborators in 16 states and eight countries. Simbios focuses on problems at both the molecular scale and the organismal level, with a long-term goal of uniting these in accurate multiscale simulations.     

Can fall risk be incorporated into fracture risk assessment algorithms: a pilot study of responsiveness to clodronate

Summary  

Fall risk does not significantly impact on the efficacy of the bisphosphonate clodronate in reducing the incidence of fracture.     

Ten-year fracture probability identifies women who will benefit from clodronate therapy—additional results from a double-blind, placebo-controlled randomised study

Summary

Fracture risk prediction can be enhanced by the concurrent assessment of other clinical risk factors. This study demonstrates that the estimation of an individual’s 10-year probability of fracture by the FRAX® algorithm identifies patients at high risk of fracture who will respond to bisphosphonate therapy.

Introduction

Treatments for osteoporosis are targeted largely to patients with low bone density (BMD) or a prior fragility fracture. Fracture risk prediction can be enhanced by the concurrent assessment of other clinical risk factors, but it is important to determine whether the risk so identified can be reduced by intervention. We determined the effect of a bisphosphonate on fracture rates when risk was calculated using a new risk algorithm (FRAX®).

Methods

Women aged 75 years or more were recruited to a randomised, double-blind controlled trial of 800 mg oral clodronate (Bonefos®) daily over 3 years. Baseline clinical risk factors were entered in the FRAX® model to compute the 10-year probability of major osteoporotic fractures with or without input of femoral neck BMD. The interaction between fracture probability and treatment efficacy was examined by Poisson regression.

Results

In 3,974 women, the interaction between fracture probability and treatment efficacy was significant when probability was assessed without BMD (p?=?0.043), but not when BMD was included (p?=?0.10). Efficacy was more evident in those deemed at highest risk. For example women lying at the 75th percentile of fracture probability in the absence of BMD (10-year probability 24%) treatment reduced fracture risk by 27% (HR 0.73, 95%CI 0.58–0.92). In those with a fracture probability of 30% (90th percentile), the fracture risk reduction was 38% (HR 0.62, 0.46–0.84).

Conclusions

The estimation of an individual’s 10-year probability of fracture by the FRAX® algorithm identifies patients at high risk of fracture who will respond to bisphosphonate therapy.     

Women deliver for development

There is a large amount of research into maternal health as a health issue, but maternal health as a development issue has been less explored. This Review analyses the evidence from the past 20 years on the links between maternal health and development to examine maternal health within a development framework. We note that although existing evidence suggests that these links are strong, further research is needed to definitively substantiate how and to what extent maternal health and development affect each other. Further, we find that progress and investment in maternal health have lagged far behind estimates of what is needed to achieve the Millennium Development Goals.     

Altered phase diagram due to a single point mutation in human gammaD-crystallin

The P23T mutant of human gammaD-crystallin (HGD) is associated with cataract. We have previously investigated the solution properties of this mutant, as well as those of the closely related P23V and P23S mutants, and shown that although mutations at site 23 of HGD do not produce a significant structural change in the protein, they nevertheless profoundly alter the solubility of the protein. Remarkably, the solubility of the mutants decreases with increasing temperature, in sharp contrast to the behavior of the native protein. This inverted solubility corresponds to a strong increase in the binding energy with temperature. Here we have investigated the liquid-liquid coexistence curve and the diffusivity of the P23V mutant and find that these solution properties are unaffected by the mutation. This means that the chemical potentials in the solution phase are essentially unaltered. The apparent discrepancy between the interaction energies in the solution phase, as compared with the solid phase, is explicable in terms of highly anisotropic interprotein interactions, which are averaged out in the solution phase but are fully engaged in the solid phase.     

Development of hydroxyapatite-ciprofloxacin bone-implants using "Quality by design"

The present study deals with the development of hydroxyapatite (HAp)-ciprofloxacin bone-implants using the ?Quality by design? approach. The effect of various synthesis parameters like drug amount added in the process, stirring speed and addition rate of orthophosphoric acid in the synthesis on drug concentration in the HAp-ciprofloxacin system synthesized by the precipitation technique using 23 factorial design was analyzed. Optimization methodology utillizing the first-order polynomial equation was used to search for optimal drug concentration in the HAp-ciprofloxacin implant system. The observed responses coincided well with the predicted values from the optimization technique. New implants were manufactured using various HAp-ciprofloxacin composites and 1.5 % (m/V) guar gum as a binder. Characterization of the delivery system was done by XRPD, FTIR spectroscopy and SEM. Even at highest drug concentration (76.6 ± 0.5 %, m/m), ciprofloxacin was present in noncrystalline state. The in vitro ciprofloxacin release from various bone-implants was sustained for several weeks and the drug release pattern correlated well with the Korsmeyer- Peppas model.     

Left atrial extension of lung malignancy with ECG changes resembling STEMI

Lung malignancy extending into left atrium is seen very infrequently. We had a patient with a fast growing symptomatic lung mass and electrocardiogram showing persistent coving ST elevation without any biomarker change. Transthoracic echocardiography showed a large left atrial mass which was fixed to the free walls and extended into the appendage. There was also a large lung mass that was compressing the heart from its lateral aspect. CT-scan of chest corroborated the lung mass & CT-guided FNAC showed small cell carcinoma.