Analytical Treatment of the Oscillating Yukawa Potential

Using a suitable Laguerre basis set that ensures a tridiagonal matrix representation of the reference Hamiltonian, we were able to evaluate in closed form the matrix elements of the generalized Yukawa potential with complex screening parameter. This enabled us to treat analytically both the cosine and sine-like Yukawa potentials on equal footing and compute their bound states spectrum as the eigenvalues of the associated analytical matrix representing their Hamiltonians. Finally we used a carefully designed complex scaling method to evaluate the resonance energies and compared our results satisfactorily with those obtained in the literature.Comment: 8 pages 2 table

Widespread transfer of resistance genes between bacterial species in an intensive care unit: implications for hospital epidemiology

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Eculizumab is a safe and effective treatment in pediatric patients with atypical hemolytic uremic syndrome

Atypical hemolytic uremic syndrome (aHUS) is caused by alternative complement pathway dysregulation, leading to systemic thrombotic microangiopathy (TMA) and severe end-organ damage. Based on 2 prospective studies in mostly adults and retrospective data in children, eculizumab, a terminal complement inhibitor, is approved for aHUS treatment. Here we prospectively evaluated efficacy and safety of weight-based dosing of eculizumab in eligible pediatric patients with aHUS in an open-label phase II study. The primary end point was complete TMA response by 26 weeks. Twenty-two patients (aged 5 months-17 years) were treated; 16 were newly diagnosed, 12 had no prior plasma exchange/infusion during current TMA symptomatology, 11 received baseline dialysis, and 2 had prior renal transplants. By week 26, 14 achieved a complete TMA response, 18 achieved hematologic normalization, and 16 had 25% or better improvement in serum creatinine. Plasma exchange/infusion was discontinued in all, and 9 of the 11 patients who required dialysis at baseline discontinued, whereas none initiated new dialysis. Eculizumab was well tolerated; no deaths or meningococcal infections occurred. Bone marrow failure, wrist fracture, and acute respiratory failure were reported as unrelated severe adverse events. Thus, our findings establish the efficacy and safety of eculizumab for pediatric patients with aHUS and are consistent with proposed immediate eculizumab initiation following diagnosis in children

Changes in duodenal tissue-associated microbiota following hookworm infection and consecutive gluten challenges in humans with coeliac disease

A reduced diversity of the gastrointestinal commensal microbiota is associated with the development of several inflammatory diseases. Recent reports in humans and animal models have demonstrated the beneficial therapeutic effects of infections by parasitic worms (helminths) in some inflammatory disorders, such as inflammatory bowel disease (IBD) and coeliac disease (CeD). Interestingly, these studies have described how helminths may alter the intestinal microbiota, potentially representing a mechanism by which they regulate inflammation. However, for practical reasons, these reports have primarily analysed the faecal microbiota. In the present investigation, we have assessed, for the first time, the changes in the microbiota at the site of infection by a parasitic helminth (hookworm) and gluten-dependent inflammation in humans with CeD using biopsy tissue from the duodenum. Hookworm infection and gluten exposure were associated with an increased abundance of species within the Bacteroides phylum, as well as increases in the richness and diversity of the tissue-resident microbiota within the intestine, results that are consistent with previous reports using other helminth species in humans and animal models. Hence, this may represent a mechanism by which parasitic helminths may restore intestinal immune homeostasis and exert a therapeutic benefit in CeD, and potentially other inflammatory disorders

Novel mutations expand the clinical spectrum of DYNC1H1-associated spinal muscular atrophy

OBJECTIVE To expand the clinical phenotype of autosomal dominant congenital spinal muscular atrophy with lower extremity predominance (SMA-LED) due to mutations in the dynein, cytoplasmic 1, heavy chain 1 (DYNC1H1) gene. METHODS Patients with a phenotype suggestive of a motor, non-length-dependent neuronopathy predominantly affecting the lower limbs were identified at participating neuromuscular centers and referred for targeted sequencing of DYNC1H1. RESULTS We report a cohort of 30 cases of SMA-LED from 16 families, carrying mutations in the tail and motor domains of DYNC1H1, including 10 novel mutations. These patients are characterized by congenital or childhood-onset lower limb wasting and weakness frequently associated with cognitive impairment. The clinical severity is variable, ranging from generalized arthrogryposis and inability to ambulate to exclusive and mild lower limb weakness. In many individuals with cognitive impairment (9/30 had cognitive impairment) who underwent brain MRI, there was an underlying structural malformation resulting in polymicrogyric appearance. The lower limb muscle MRI shows a distinctive pattern suggestive of denervation characterized by sparing and relative hypertrophy of the adductor longus and semitendinosus muscles at the thigh level, and diffuse involvement with relative sparing of the anterior-medial muscles at the calf level. Proximal muscle histopathology did not always show classic neurogenic features. CONCLUSION Our report expands the clinical spectrum of DYNC1H1-related SMA-LED to include generalized arthrogryposis. In addition, we report that the neurogenic peripheral pathology and the CNS neuronal migration defects are often associated, reinforcing the importance of DYNC1H1 in both central and peripheral neuronal functions

Controlled release from zein matrices: Interplay of drug hydrophobicity and pH

Purpose: In earlier studies, the corn protein zein is found to be suitable as a sustained release agent, yet the range of drugs for which zein has been studied remains small. Here, zein is used as a sole excipient for drugs differing in hydrophobicity and isoelectric point: indomethacin, paracetamol and ranitidine. Methods: Caplets were prepared by hot-melt extrusion (HME) and injection moulding (IM). Each of the three model drugs were tested on two drug loadings in various dissolution media. The physical state of the drug, microstructure and hydration behaviour were investigated to build up understanding for the release behaviour from zein based matrix for drug delivery. Results: Drug crystallinity of the caplets increases with drug hydrophobicity. For ranitidine and indomethacin, swelling rates, swelling capacity and release rates were pH dependent as a consequence of the presence of charged groups on the drug molecules. Both hydration rates and release rates could be approached by existing models. Conclusion: Both the drug state as pH dependant electrostatic interactions are hypothesised to influence release kinetics. Both factors can potentially be used factors influencing release kinetics release, thereby broadening the horizon for zein as a tuneable release agent

Adaptive Motor Imagery: A Multimodal Study of Immobilization-Induced Brain Plasticity.

The consequences of losing the ability to move a limb are traumatic. One approach that examines the impact of pathological limb nonuse on the brain involves temporary immobilization of a healthy limb. Here, we investigated immobilization-induced plasticity in the motor imagery (MI) circuitry during hand immobilization. We assessed these changes with a multimodal paradigm, using functional magnetic resonance imaging (fMRI) to measure neural activation, magnetoencephalography (MEG) to track neuronal oscillatory dynamics, and transcranial magnetic stimulation (TMS) to assess corticospinal excitability. fMRI results show a significant decrease in neural activation for MI of the constrained hand, localized to sensorimotor areas contralateral to the immobilized hand. MEG results show a significant decrease in beta desynchronization and faster resynchronization in sensorimotor areas contralateral to the immobilized hand. TMS results show a significant increase in resting motor threshold in motor cortex contralateral to the constrained hand, suggesting a decrease in corticospinal excitability in the projections to the constrained hand. These results demonstrate a direct and rapid effect of immobilization on MI processes of the constrained hand, suggesting that limb nonuse may not only affect motor execution, as evidenced by previous studies, but also MI. These findings have important implications for the effectiveness of therapeutic approaches that use MI as a rehabilitation tool to ameliorate the negative effects of limb nonuse

The effect of a sertoli cell-selective knockout of the androgen receptor on testicular gene expression in prepubertal mice

To unravel the molecular mechanisms mediating the effects of androgens on spermatogenesis, testicular gene expression was compared in mice with Sertoli cell-selective androgen receptor knockout (SCARKO) and littermate controls on postnatal d 10. Microarray analysis identified 692 genes with significant differences in expression. Of these, 28 appeared to be down-regulated and 12 up-regulated at least 2-fold in SCARKOs compared with controls. For nine of the more than 2-fold down-regulated genes, androgen regulation was confirmed by treatment of wild-type mice with an antiandrogen ( flutamide). Some of them were previously described to be androgen regulated or essential for spermatogenesis. Serine-type protease inhibitors were markedly overrepresented in this down-regulated subgroup. A time study (d 8-20), followed by cluster analysis, allowed identification of distinct expression patterns of differentially expressed genes. Three genes with a pattern closely resembling that of Pem, a prototypical an-drogen-regulated gene expressed in Sertoli cells, were selected for confirmation by quantitative RTPCR and additional analysis. The data confirm that the SCARKO model allows identification of novel androgen-regulated genes in the testis. Moreover, they suggest that protease inhibitors and other proteins related to tubular restructuring and cell junction dynamics may be controlled in part by androgens