Clinical and biochemical improvements in a patient with MNGIE following enzyme replacement.

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a rare autosomal recessive metabolic disorder caused by a deficiency of thymidine phosphorylase (TP, EC2.4.2.4) due to mutations in the nuclear gene TYMP. TP deficiency leads to plasma and tissue accumulations of thymidine and deoxyuridine which generate imbalances within the mitochondrial nucleotide pools, ultimately leading to mitochondrial dysfunction.1 MNGIE is characterized clinically by leukoencephalopathy, external ophthalmoplegia, peripheral polyneuropathy, cachexia, and enteric neuromyopathy manifesting as gastrointestinal dysmotility. The condition is relentlessly progressive, with patients usually dying from a combination of nutritional and neuromuscular failure at an average age of 37 years.2 Allogeneic hematopoietic stem cell transplantation (AHSCT) offers a permanent cure. Clinical and biochemical improvements following AHSCT have been reported but it carries a high mortality risk and is limited by matched donor availability.3 A consensus proposal for standardizing AHSCT recommends treatment of patients without irreversible end-stage disease and with an optimally matched donor; a majority of patients are ineligible and thus there is a critical requirement for an alternative treatment

Reinforced feedback in virtual environment for rehabilitation of upper extremity dysfunction after stroke: preliminary data from a randomized controlled trial.

OBJECTIVES: To study whether the reinforced feedback in virtual environment (RFVE) is more effective than traditional rehabilitation (TR) for the treatment of upper limb motor function after stroke, regardless of stroke etiology (i.e., ischemic, hemorrhagic). DESIGN: Randomized controlled trial. Participants. Forty-four patients affected by stroke. Intervention. The patients were randomized into two groups: RFVE (N = 23) and TR (N = 21), and stratified according to stroke etiology. The RFVE treatment consisted of multidirectional exercises providing augmented feedback provided by virtual reality, while in the TR treatment the same exercises were provided without augmented feedbacks. Outcome Measures. Fugl-Meyer upper extremity scale (F-M UE), Functional Independence Measure scale (FIM), and kinematics parameters (speed, time, and peak). RESULTS: The F-M UE (P = 0.030), FIM (P = 0.021), time (P = 0.008), and peak (P = 0.018), were significantly higher in the RFVE group after treatment, but not speed (P = 0.140). The patients affected by hemorrhagic stroke significantly improved FIM (P = 0.031), time (P = 0.011), and peak (P = 0.020) after treatment, whereas the patients affected by ischemic stroke improved significantly only speed (P = 0.005) when treated by RFVE. CONCLUSION: These results indicated that some poststroke patients may benefit from RFVE program for the recovery of upper limb motor function. This trial is registered with NCT01955291

The Space Filling Dirichlet 3-Brane in N=2, D=4 Superspace

We discuss a four-dimensional Volkov-Akulov supersymmetric theory on a D3-brane with N=2 supersymmetry broken down to N=1.Comment: LaTeX2e file, espcrc2.sty, 8 pages. Based on talks given at the D. V. Volkov Memorial Conference "Supersymmetry and Quantum Field Theory" (25-29 July, 2000, Kharkov, Ukraine). To be published in Nuclear Physics B Conference Supplement

Poor Outcome in a Mitochondrial Neurogastrointestinal Encephalomyopathy Patient with a Novel TYMP Mutation: The Need for Early Diagnosis.

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a devastating autosomal recessive disorder due to mutations in TYMP, which cause loss of function of thymidine phosphorylase (TP), nucleoside accumulation in plasma and tissues and mitochondrial dysfunction. The clinical picture includes progressive gastrointestinal dysmotility, cachexia, ptosis and ophthalmoparesis, peripheral neuropathy and diffuse leukoencephalopathy, which usually lead to death in early adulthood. Therapeutic options are currently available in clinical practice (allogeneic hematopoietic stem cell transplantation and carrier erythrocyte entrapped TP therapy) and newer, promising therapies are expected in the near future. However, successful treatment is strictly related to early diagnosis. We report on an incomplete MNGIE phenotype in a young man harboring the novel heterozygote c.199 C>T (Q67X) mutation in exon 2, and the previously reported c.866 A>C (E289A) mutation in exon 7 in TYMP. The correct diagnosis was achieved many years after the onset of symptoms and unfortunately, the patient died soon after diagnosis because of multiorgan failure due to severe malnutrition and cachexia before any therapeutic option could be tried. To date, early diagnosis is essential to ensure that patients have the opportunity to be treated. MNGIE should be suspected in all patients who present with both gastrointestinal and nervous system involvement, even if the classical complete phenotype is lacking

Twistor--like Formulation of the Supermembrane in D=11 ∗^*

We propose a new formulation of the D=11 supermembrane theory that involves commuting spinors (twistor--like variables) and exhibits a manifest $n$--extended world volume supersymmetry $(1\leq n\leq 8)$. This supersymmetry replaces $n$ components of the usual $\kappa$--symmetry. We show that this formulation is classically equivalent to the standard one.Comment: 18 pages, Te