N-Acetyl-leucine in progressive CACNA1A ataxia: A case series.

Background: CACNA1A-related disorders are rare and progressive; to date, there is no approved treatment. Trials with N-acetyl-leucine (NAL) demonstrated efficacy in disorders featuring ataxia, cognitive impairment, and epilepsy. Accordingly, we hypothesized that NAL may be effective in CACNA1A-associated disorders.

Orthogonal IMiD-Degron Pairs Induce Selective Protein Degradation in Cells.

Immunomodulatory imide drugs (IMiDs) including thalidomide, lenalidomide, and pomalidomide, can be used to induce degradation of a protein of interest that is fused to a short zinc finger (ZF) degron motif. These IMiDs, however, also induce degradation of endogenous neosubstrates, including IKZF1 and IKZF3. To improve degradation selectivity, we took a bump-and-hole approach to design and screen bumped IMiD analogs against 8380 ZF mutants.

The clinical spectrum of SMA-PME and in vitro normalization of its cellular ceramide profile.

Objective: The objectives of this study were to define the clinical and biochemical spectrum of spinal muscular atrophy with progressive myoclonic epilepsy (SMA-PME) and to determine if aberrant cellular ceramide accumulation could be normalized by enzyme replacement.

Methods: Clinical features of 6 patients with SMA-PME were assessed by retrospective chart review, and a literature review of 24 previously published cases was performed. Leukocyte enzyme activity of acid ceramidase was assessed with a fluorescence-based assay.

Development of a High Strength Geopolymer Incorporating Quarry Waste Diabase Mud (DM) and Ground Granulated Blast-Furnace Slag (GGBS).

This study presents the development and experimental assessment of novel, high strength, cementless binders that incorporate alkali-activated local waste. A silica-rich diabase mud (DM), currently considered as waste, was previously investigated for geopolymerization, signifying that the DM lacked the necessary reactivity to provide a stable geopolymer binder alone. Moreover, even after incorporation of small amounts of cement and metakaolin, the DM mixtures still did not yield adequate mechanical properties.

Investigation of the Geopolymerization Potential of a Waste Silica-Rich Diabase Mud.

Diabase mud (DM) is a silica-rich residue yielding from aggregate crushing and washing operations in quarries. This work focuses on identifying the geopolymerization potential of a diabase mud through characterization of its mineralogical composition, investigation of its reactivity, and assessment of the early compressive strengths of alkali activated mixtures formulated based on the mud's dissolution results. The findings suggest that considerably low amounts of Al and Si metals were dissolved following the dissolution tests conducted on DM, however, the incorporation of small quantities of CEM I, gypsum, and metakaolin (MK) moderately at a NaSiO:NaOH ratio of 50:50 and with a molarity of NaOH of 4 M enhanced the geopolymerization compared to low L/S ratio mixtures cured at different conditions.

Children's Involvement in Different Sport Types Differentiates Their Motor Competence but Not Their Executive Functions.

Sports provide a context where important aspects of children's health, such as motor skills and cognitive functions, can be enhanced. However, it is unknown which type of sport may be better for the development of motor competence (MC) and executive functions (EFs). This study investigated potential differences in MC and EFs in boys and girls, being involved in different types of sports (team, individual open skill, individual closed skill).

Effect of Mechanically Treated Recycled Aggregates on the Long Term Mechanical Properties and Durability of Concrete.

The objective of this research was to study the effect of an optimal mechanical treatment method to reduce the mortar adhered on recycled aggregates (RCA) on the long-term mechanical properties and durability of concretes containing RCA at different replacement levels. It was found that concretes incorporating treated RCA exhibited sharper and more significant increase on 90- and 365-day compressive strengths than any other investigated mixture. The same mixtures also benefitted from a 'shrinkage-controlling' effect, where strains and mass losses were reduced by almost 15% and 10%, respectively, compared to the reference concrete.

The Complex Interplay of Cortex, Cerebellum, and Age in a Cohort of Pediatric Patients With Tuberous Sclerosis Complex.

Background: The neurodevelopmental impairment in tuberous sclerosis complex (TSC) has a multifactorial origin. Various factors have been proposed as predictors of neurological outcome such as tuber load, seizure onset, and TSC2 mutation. Cerebellar lesions have been associated with worse neuroradiological phenotype, but their contribution is not well understood.

Longitudinal Data in Patients with Niemann-Pick Type C Disease Under Combined High Intrathecal and Low Intravenous Dose of 2-hydroxylpropyl-β-cyclodextrin.

Niemann-Pick Type C disease (NPC) is a rare, incurable, autosomal-recessive, lysosomal storage disorder with protean and progressive neurovisceral manifestations characterized by accumulation of intracellular unesterified cholesterol. The investigational use of 2-hydroxypropyl-beta-cyclodextrin (HP-β-CD) in the treatment of NPC has shown promising results in improving life expectancy and reducing neurological damage in this patient population. This case report describes two children with the neurological form of NPC: a 5-year-old male patient in advanced stage of the disease and an 11-year-old female patient in moderately advanced stage.

Effects of measles-containing vaccination in children with severe underlying neurologic disease.

Background: Measles outbreaks pose significant risk for those unvaccinated.

Patients And Methods: Measles-containing vaccine was offered to unvaccinated children with severe neurologic diseases during a measles outbreak. Vaccination adverse events were reported by parents 30 days following vaccination.

Expanding the clinical and genetic spectrum of CAD deficiency: an epileptic encephalopathy treatable with uridine supplementation.

Purpose: Biallelic CAD variants underlie CAD deficiency (or early infantile epileptic encephalopathy-50, [EIEE-50]), an error of pyrimidine de novo biosynthesis amenable to treatment via the uridine salvage pathway. We further define the genotype and phenotype with a focus on treatment.

Methods: Retrospective case series of 20 patients.

Left ventricular hypertrophy assessed by electrocardiogram is associated with more severe stroke and with higher in-hospital mortality in patients with acute ischemic stroke.

Background And Aims: Left ventricular hypertrophy (LVH), assessed by electrocardiogram (ECG), is associated with increased risk for stroke. However, few studies that evaluated whether ECG-detected LVH predicts ischemic stroke severity and outcome. We aimed to evaluate these associations.

Diagnosis of sporadic neurofibromatosis type 2 in the paediatric population.

Objective: Onset of symptoms in severe sporadic neurofibromatosis type 2 (NF2) is typically within childhood; however, there is poor awareness of presenting features in young children, potentially resulting in delayed diagnosis and poorer outcome. We have reviewed presentation of sporadic paediatric NF2 to raise awareness of early features, highlighting those requiring further investigation.

Design: Patients diagnosed with NF2 at age ≤16 and seen between 2012 and 2015 were notified via the British Paediatric Neurology Surveillance Unit or identified through the English NF2 service.

Effect of antihypertensive treatment on the long-term outcome of patients discharged after acute ischemic stroke.

We aimed to evaluate the effects of the five main classes of antihypertensive agents on the long-term outcome of 313 consecutive patients discharged after acute ischemic stroke (36.4% males, age 78.5 ± 6.

Stress hyperglycemia and acute ischemic stroke in-hospital outcome.

Background And Aims: Stress hyperglycemia is frequent in patients with acute ischemic stroke. However, it is unclear whether stress hyperglycemia only reflects stroke severity or if it is directly associated with adverse outcome. We aimed to evaluate the prognostic significance of stress hyperglycemia in acute ischemic stroke.

Prognostic significance of major lipids in patients with acute ischemic stroke.

Although dyslipidemia increases the risk for ischemic stroke, previous studies reported conflicting data regarding the association between lipid levels and stroke severity and outcome. To evaluate the predictive value of major lipids in patients with acute ischemic stroke. We prospectively studied 790 consecutive patients who were admitted with acute ischemic stroke (41.

Treatment with Clopidogrel Prior to Acute Non-Cardioembolic Ischemic Stroke Attenuates Stroke Severity.

Background: Clopidogrel reduces the risk of non-cardioembolic ischemic stroke, but it is unclear whether it affects the severity and outcome of stroke. We aimed at evaluating the effect of prior treatment with clopidogrel on acute non-cardioembolic ischemic stroke severity and in-hospital outcome.

Methods: We prospectively studied 608 consecutive patients (39.

No Association Observed Between Blood Pressure Variability During the Acute Phase of Ischemic Stroke and In-Hospital Outcomes.

Background: Recent data suggest that blood pressure (BP) variability confers increased cardiovascular risk independently of BP. We aimed to evaluate the association between BP variability during the acute phase of ischemic stroke and the in-hospital outcome.

Methods: We prospectively studied 608 consecutive patients admitted with acute ischemic stroke (39.

Acenocoumarol vs. low-dose dabigatran in real-world patients discharged after ischemic stroke.

The aim of this study was to compare the efficacy of dabigatran 110 mg twice daily and acenocoumarol in patients with atrial fibrillation discharged after ischemic stroke. We prospectively studied 436 consecutive patients who were discharged after acute ischemic stroke (39.2% males, age 78.

Comparative effects of more versus less aggressive treatment with statins on the long-term outcome of patients with acute ischemic stroke.

Background And Aims: There are no studies that compared the effects of different intensities of statin treatment on the long-term outcome of patients with recent ischemic stroke. We aimed to evaluate these effects.

Methods: We prospectively studied 436 consecutive patients who were discharged after acute ischemic stroke (39.

Prior treatment with dipeptidyl peptidase 4 inhibitors is associated with better functional outcome and lower in-hospital mortality in patients with type 2 diabetes mellitus admitted with acute ischaemic stroke.

It is unclear whether prior antidiabetic treatment affects stroke severity and outcome. To evaluate this association, we prospectively studied all patients who were admitted in our Department with acute ischaemic stroke (n = 378, mean age = 78.8 ± 6.

Adequacy of preadmission oral anticoagulation with vitamin K antagonists and ischemic stroke severity and outcome in patients with atrial fibrillation.

It is unclear whether vitamin K antagonists affect stroke severity and outcome in patients with atrial fibrillation (AF). We aimed to evaluate this association. We prospectively studied 539 consecutive patients admitted with acute ischemic stroke (41.