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Background: SMA1, a rapidly progressing disease, results in muscle weakness, respiratory failure, hospitalization, and early death. This study highlights the value of onasemnogene abeparvovec (AVXS-101) gene-replacement therapy for SMA1. Methods: Twelve SMA1 patients received a one-time intravenous proposed therapeutic dose of AVXS-101 (CL-101; NCT02122952). Event-free survival (no death/permanent ventilation), pulmonary/nutritional interventions, swallow function, hospitalization rates, CHOP-INTEND, motor milestones, and safety were assessed (2-year follow-up). Results: By study end, all 12 patients survived event-free; 7 did not require non-invasive ventilation; 11 had stable/improved swallowing function (6 exclusively fed by mouth); 11 spoke. On average, patients experienced 1.4 (SD=0.41, range=0–4.8) respiratory hospitalizations/year. The mean proportion of time hospitalized was 4.4% (range=0–18.3%); mean unadjusted rate of hospitalization/year was 2.1 (range=0–7.6), with a mean hospital stay of 6.7 (range=3–12.1) days. CHOP-INTEND increased by 9.8 (SD=3.9) and 15.4 (SD=6.4) points at 1- and 3-months post-treatment. At long-term follow-up, 11 patients sat unassisted, 4 stood with assistance, and 2 walked. Adverse events included elevated serum aminotransferase levels, which were attenuated by prednisolone. Conclusions: AVXS-101 in CL-101 resulted in dramatic survival and motor function improvements. The reduced healthcare utilization in treated infants could decrease cost and alleviate patient, caregiver, and societal burden.
Background: Sotos syndrome is a genetic condition caused by NSD1 alterations, characterized by overgrowth, macrocephaly, dysmorphic features, and learning disability. Approximately half of children with Sotos syndrome develop seizures. We investigated the spectrum of seizure phenotypes in these patients. Methods: Patients were recruited from clinics and referral from support groups. Those withclinical or genetic diagnosis of Sotos syndrome and seizures were included. Phenotyping data was collected via structured clinical interview and medical chart review. Results: 25 patients with typical Sotos syndrome features were included. Of 14 tested patients, 64% (n=9) had NSD1 alterations. Most had developmental impairment (80%, n=20) and neuropsychiatric comorbidities (68%, n=17). Seizure onset was variable (2 months to 12 years). Febrile and absence seizures were the most frequent types (64%, n=16). Afebrile generalized tonicclonic (40%, n=10) and atonic (24%, n=6) seizures followed. Most patients (60%, n=15) had multiple seizure types. The majority (72%, n=18) was controlled on a single antiepileptic, or none; 4% (n=1) remained refractory to antiepileptics. Conclusions: The seizure phenotype in Sotos syndrome most commonly involves febrile convulsions or absence seizures. Afebrile tonic-clonic or atonic seizures may also occur. Seizures are typically well-controlled with antiepileptics. The rate of developmental impairment and neuropsychiatric comorbidities is high.
Production of maize in western Kenya is severely constrained by the parasitic weed striga. Although productivity of maize can be improved through adoption of improved varieties, adoption of such varieties remains low in the region, as the majority of smallholder farmers still grow unimproved open-pollinated varieties (landraces). The performance of two improved hybrid varieties was evaluated against six landraces in striga-infested soils in western Kenya. The varieties were planted in plots under natural striga infestation and were supplemented with pot experiments under artificial infestation. Striga emergence was lower in landraces than in the hybrid varieties in both field and pot experiments. Similarly, height of maize plants at harvest and grain yields were higher in the landraces than in the hybrids. After three continuous cropping seasons, in all treatments, striga seedbank density increased two to seven times. Seedbank increase was higher with hybrids and two of the landraces, ‘Rachar' and ‘Endere'. These results provide an insight into the potential role landraces could play in efforts toward an integrated management approach for striga in smallholder cropping systems. They also highlight the need to develop hybrid maize lines with local adaptation to biotic constraints, specifically striga.
Background: The use of 3D endoscopy for posterior fossa surgery gradually adopted. In this study we compare the 3D to classic 2D endoscopy in evaluating neurovascular complexes in posterior fossa. Methods: Twenty retrosigmoid craniotomies, with a maximal diameter of 2cm were performed under neuronavigation on 10 fresh cadaveric heads. The posterior fossa dura matter was opened with a C-shaped incision and the base of the dural flap was placed over the sigmoid sinus. We used 3D and 2D endoscopes, with 0 and 45 degree angulations, connected to high definition camera lenses for optimal visualization of posterior fossa structures. Results: The superior, middle and inferior neurovascular complexes of the cerebellopontine angle were better visualized with 3D comparing to 2D endoscope. A detailed view of the porus trigeminous and structures associated with the tentorial incisura was also attained with 3D endoscopy. Conclusion: The high quality and resolution obtained by 3D endoscopy makes it a potentially valuable surgical and teaching tool in the armamentarium for endoscopic posterior fossa surgery. The stereoscopic view of the critical neurovascular structures of the posterior fossa, offered by 3D images, allows for a more detailed dissection in the difficult area of the cerebellopontine angle.
Background: Meningiomas represent the commonest benign intracranial tumor and surgical resection is the first line treatment. Tumor recurrence after surgical resection is common. The aim of this study is to identify peri-operative predictors of meningioma recurrence following surgical resection Methods: This was a retrospective hospital-based study of all surgical cases between January 1990 and June 2014. Information regarding age, gender, peri-operative imaging parameters such as peri-tumoral edema or post-operative hemorrhage or residual, and grade were collected. Linear and volumetric measurements (of both tumor volume and volume of edema) were collected as well. Results: Overall, 464 patients were reviewed; n=154(34%) percent of patients were male. The grade distribution was: 296 (74.6%) were Grade I, 78 (19.6%) Grade II, and 23 (5.8%) Grade III. Post-operative tumor bed hemorrhage, noted in 119 (29.9%) of cases, and preoperative peri-tumoral edema volume were significant predictors of tumor recurrence following resection (P= 0.002 and 0.037, respectively). These parameters did not correlate with the MIB-1 index, tumour residual, grade of the tumour, or primary versus recurrent presentation. Conclusions: Pre-operative peri-tumoral edema and post-operative tumor bed hemorrhage are independent predictive of tumor recurrence. Identification of other molecular and/or radiological predictive of recurrence factors could add in our understanding of meningioma behavior.
Neonates with severe pulmonary valve stenosis tend to remain oxygen dependent, despite resolution of the transpulmonary gradient. Alpha 2 blockers – phentolamine – and angiotensin-converting enzyme inhibitors – captopril – were reported to improve oxygen saturation.
To describe the role of phentolamine and captopril in the treatment of these patients.
In a retrospective cohort study, 28 neonates with severe pulmonary valve stenosis underwent balloon valvuloplasty. Among them, 20 remained oxygen or prostaglandin dependent after intervention, and were treated with phentolamine or captopril. Oxygen saturation was monitored before and after intervention and following treatment with these medications. Mean duration of hospitalisation was recorded.
Mean age and weight were 25.2 days and 3.1 kg, respectively. Before balloon dilation, 18/20 (90%) neonates were on prostaglandin, whereas after the procedure only 6/18 patients required it. All 20 patients required oxygen after the procedure, and nine patients (45%) were started on phentolamine. Among them, one patient with severe infundibular stenosis did not respond favourably, and 11 patients (55%) were started on captopril. After starting phentolamine or captopril treatment, prostaglandin could be discontinued after a mean time of 15.86 hours. Within <2 days, there was an increase in mean oxygen saturation from 76.6 to 93.0%.
Phentolamine and captopril seem to have therapeutic roles in neonates with severe pulmonary valve stenosis who remain oxygen dependent after balloon dilation. Both drugs led to vasodilation of the pulmonary and systemic vascularisation and facilitated inflow to the right ventricle. Right-to-left shunt across a patent foramen ovale or atrial septal defect decreased and saturation improved, leading to a significant reduction in the length of hospitalisation.
We describe the technique of closure of native right ventricular outflow tract by Amplatzer muscular ventricular septal defect device because of severe regurgitation in a patient who had tetralogy of Fallot repair with conduit at 3 years of age followed by percutaneous Melody valve implant 6 years later.
Diosmin (DM) is a naturally occurring flavone and has been found to possess numerous therapeutic properties. In this study, we used DM as a protective agent against the nephrotoxic effects of the environmental toxicant trichloroethylene (TCE). Male Wistar rats were divided into five groups (I–V, n 6). Groups II, III and IV received an oral administration of TCE at a dose of 1000 mg/kg body weight for twenty consecutive days. The animals in groups II and III received an oral treatment of DM at doses of 20 and 40 mg/kg body weight, respectively, for twenty consecutive days, while groups I and V were given maize oil (5 ml/kg body weight and DM 40 mg/kg body weight, respectively) for 20 d. The protective effects of DM on TCE-induced oxidative stress and caspase-dependent apoptosis were investigated by assaying oxidative stress biomarkers, lipid peroxidation (LPO), serum toxicity markers, alkaline unwinding assay, caspase-3, -7 and -9, Bax and p53 expression. Oral administration of TCE in rats enhanced renal LPO, depleted glutathione content and antioxidant enzymes, induced DNA strand breaks (P< 0·001), modulated the expression of Bax and p53 protein and induced the expression of caspase-3, -7 and -9. Co-treatment with DM prevented oxidative stress by restoring the levels of antioxidant enzymes; furthermore, a significant dose-dependent decrease in DNA disintegration and kidney toxicity markers such as blood urea N, creatinine, lactate dehydrogenase and kidney injury molecule-1 was observed. DM also effectively decreased the TCE-induced up-regulation of Bax and p53. Data from the present study establish the protective role of DM against TCE-induced renal damage.
A study on light absorption enhancement of an InAs quantum dots embedded into InxGa1-xAs quantum well with GaAs as a barrier solar cells was carried out. Solar cell devices were fabricated from different structures, which were grown by using molecular beam epitaxy, with the In mole fraction (x) varied between 0 – 25 %. Poly-L-Lysine ligands and ZnO sol-gel was used to modify the surface of the solar cells and act as anti-reflection coatings. The anti-reflection characteristic of the ligands and the sol-gel were investigated by measuring the solar cell characteristics before and after the solar cells surface modifications. The current-voltage characteristics were measured of the fabricated solar cells before and after Poly-L-Lysine and ZnO coatings. A significant enhancement on the order of 40 % of the solar cells performance was observed. This type of enhancement was observed in the power conversion efficiency, spectral response measurements, and external quantum efficiency.
Highly pure iron pyrites (FeS2) cubic phased nanocrystals of diameter ∼ 20 nm were synthesized by colloidal method using only amines acting both as a coordinating and surfactant ligands. The details of synthetic condition at temperature 175 °C, 215 °C, 230 °C, 245 °C were compared and elucidated. The best synthetic conditions using an octylamine as a ligand at 230 °C for 2h have been optimized in an inert atmosphere. The XRD measurement shows diffraction peaks of pure cubic iron pyrite crystal structure without any detectable presence of marcasite, pyrrotite, greigyte and other impurity structures. The UV-Vis spectra depict clear absorption onset at 1200 nm in best sample with estimated band gap of ∼1.03 eV. These high pure and nanostructures based iron pyrite processed from solution route may offer excellent manufacturing scalability at very low cost since it can be used as inks for large scale fabrication. The morphological and optical characterizations are carried out by using XRD, UV-Vis, and SEM techniques.
Fusarium wilt caused by Fusarium oxysporum, Schlecht. emend. Snyd. & Hans. f. sp. ciceri is prevalent in most chickpea-growing countries and is a major devastating disease. Host plant resistance is the most practical method of disease management. Indigenous chickpea germplasm reveals a heterogeneous genetic make-up and the response of resistance to wilt is an unexplored potential source for disease resistance. There are 70 indigenous germplasm lines selected on the basis of their agronomic performance and diverse areas of collections in the country. Of these, four accessions had a highly resistant score of 1 and six had a score of 3 using a 1–9 rating scale, indicating their level of resistance to Fusarium wilt (race 4). Other germplasm accessions of chickpea were found to be moderately resistant to highly susceptible disease reaction. Likewise, the same set of germplasm was also screened for Meloidogyne incognita (race 1) using pot culture under controlled condition. Only one accession was found to be resistant to this pest. These resistant gene sources can be utilised effectively for race-specific chickpea wilt and root-knot resistance breeding programmes.
Magneto-optical properties of Ni- and Co-doped amorphous AlN thin films were investigated as a function of post grown annealing temperature using magneto-optical Kerr effect (MOKE) spectroscopy. The x-ray diffraction spectra confirmed that the as-grown material is amorphous and retained its morphology after thermal treatment; however the sample morphology strongly depends on the concentration of incorporated transition metals. We observed with help of transmission electron microscopy and atomic force microscopy that the films surface containing TMs with concentrations larger than ∼10 at.% undergo morphological changes suggesting possible Ni and Co atom clustering. Significant enhancement of the polar Kerr rotation signal was observed for Ni- and Co-doped a-AlN materials annealed above 300 °C in nitrogen. The studied materials have shown strong magnetic isotropy in polar geometry whereas the MOKE measurements in longitudinal geometry did not show an explicit signal for the transition metals doped a-AlN studied.
The atmospheres of magnetic chemically peculiar (mCP) stars display the presence of magnetic fields of different geometry and strength, ranging from a few hundred G up to tens of kG. Except several very approximate attempts there were no detailed studies of magnetic field effects on model atmospheres structure, possibly leading to errors in the stellar parameter determination and abundance analysis routines. We present the magnetic model atmospheres based on LLmodels code which accounts for the detailed treatment of anomalous Zeeman splitting and polarized radiative transfer.
We report a large congenital fistula connecting the descending thoracic aorta to the right upper pulmonary vein in a newborn baby presenting on the seventh day of life with cardiac failure and a continuous murmur heard posteriorly. The fistula was detected echocardiographically, and shown at cardiac catheterisation not to be suitable for percutaneous occlusion. The anatomy of the fistula was confirmed at surgery, when it was ligated successfully.