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Antonsen Vinding posted an update 6 months ago
The activity profile of T-CEP on human T cells ex vivo suggests its use in generating human T cell populations that are more suited for adoptive cell therapy.Inosine triphosphate pyrophosphatase (ITPA) hydrolyzes inosine triphosphate (ITP) and other deaminated purine nucleotides to the corresponding nucleoside monophosphates. In humans, ITPA deficiency causes severe encephalopathy with epileptic seizure, microcephaly, and developmental retardation. In this study, we established neural stem cell-specific Itpa-conditional KO mice (Itpa-cKO mice) to clarify the effects of ITPA deficiency on the neural system. The Itpa-cKO mice showed growth retardation and died within 3 weeks of birth. We did not observe any microcephaly in the Itpa-cKO mice, although the female Itpa-cKO mice did show adrenal hypoplasia. The Itpa-cKO mice showed limb-clasping upon tail suspension and spontaneous and/or audiogenic seizure. Whole-cell patch-clamp recordings from entorhinal cortex neurons in brain slices revealed a depolarized resting membrane potential, increased firing, and frequent spontaneous miniature excitatory postsynaptic current and miniature inhibitory postsynaptic current in the Itpa-cKO mice compared with ITPA-proficient controls. Accumulated ITP or its metabolites, such as cyclic inosine monophosphates, or RNA containing inosines may cause membrane depolarization and hyperexcitability in neurons and induce the phenotype of ITPA-deficient mice, including seizure.
To test the hypothesis that myeloneuropathy is a presenting phenotype of paraneoplastic neurologic syndromes we retrospectively reviewed clinical, radiologic, and serologic features of 32 patients with concomitant paraneoplastic spinal cord and peripheral nervous system involvement.
Observational study investigating patients with myeloneuropathy and underlying cancer or onconeural antibody seropositivity.
Among 32 patients with paraneoplastic myeloneuropathy, 20 (63%) were women with median age 61 years (range 27-84 years). RMC-4630 Twenty-six patients (81%) had classified onconeural antibodies (amphiphysin, n = 8; antineuronal nuclear antibody type 1 , n = 5; collapsin response mediator protein 5 , n = 6; Purkinje cell cytoplasmic antibody type 1 , n = 1; Purkinje cell cytoplasmic antibody type 2 , n = 2; kelch-like protein 11 , n = 1; and combinations thereof ANNA1/CRMP5, n = 1; ANNA1/amphiphysin, n = 1; ANNA3/CRMP5, n = 1). Cancer was confirmed itic etiologies should be considered in the evaluation of subacute myeloneuropathies. Recognition of key characteristics of paraneoplastic myeloneuropathy may facilitate early tumor diagnosis and initiation of immunosuppressive treatment.
Paraneoplastic etiologies should be considered in the evaluation of subacute myeloneuropathies. Recognition of key characteristics of paraneoplastic myeloneuropathy may facilitate early tumor diagnosis and initiation of immunosuppressive treatment.
To determine the association between the extent of diffusion restriction and T2/fluid-attenuated inversion recovery (FLAIR) injury on brain MRI and outcomes after pediatric out-of-hospital cardiac arrest (OHCA).
Diffusion restriction and T2/FLAIR injury were described according to the pediatric MRI modification of the Alberta Stroke Program Early Computed Tomography Score (modsASPECTS) for children from 2005 to 2013 who had an MRI within 14 days of OHCA. The primary outcome was unfavorable neurologic outcome defined as ≥1 change in Pediatric Cerebral Performance Category (PCPC) from baseline resulting in a hospital discharge PCPC score 3, 4, 5, or 6. Patients with unfavorable outcomes were further categorized into alive with PCPC 3-5, dead due to withdrawal of life-sustaining therapies for poor neurologic prognosis (WLST-neuro), or dead by neurologic criteria.
We evaluated MRI scans from 77 patients (median age 2.21 years) performed 4 (2, 6) days postarrest. Patients wial discharge.
To assess the burden of rare genetic variants and to estimate the contribution of known amyotrophic lateral sclerosis (ALS) genes in an Italian population-based cohort, we performed whole genome sequencing in 959 patients with ALS and 677 matched healthy controls.
We performed genome sequencing in a population-based cohort (Piemonte and Valle d’Aosta Registry for ALS ). A panel of 40 ALS genes was analyzed to identify potential disease-causing genetic variants and to evaluate the gene-wide burden of rare variants among our population.
A total of 959 patients with ALS were compared with 677 healthy controls from the same geographical area. Gene-wide association tests demonstrated a strong association with
, whose rare variants are the second most common cause of disease after
expansion. A lower signal was observed for
, proving that its effect on our cohort is driven by a few known causal variants. We detected rare variants in other known ALS genes that did not surpass statistical significance in gene-wise tests, thus highlighting that their contribution to disease risk in our cohort is limited.
We identified potential disease-causing variants in 11.9% of our patients. We identified the genes most frequently involved in our cohort and confirmed the contribution of rare variants in disease risk. Our results provide further insight into the pathologic mechanism of the disease and demonstrate the importance of genome-wide sequencing as a diagnostic tool.
We identified potential disease-causing variants in 11.9% of our patients. We identified the genes most frequently involved in our cohort and confirmed the contribution of rare variants in disease risk. Our results provide further insight into the pathologic mechanism of the disease and demonstrate the importance of genome-wide sequencing as a diagnostic tool.
To examine the effect of sex on clinical response to triptans in migraine and to determine whether these differences are related to pharmacokinetics of triptans in men and women, we performed a systematic review and meta-analysis.
We searched clinical trials distinguishing clinical response to or pharmacokinetic parameters of triptans between sexes in PubMed, MEDLINE, Cochrane Library, Embase, and Web of Science up to Dec 12, 2019. Analysis was based on data extracted from published reports. Male-to-female pooled risk ratios (RR) were calculated for clinical outcomes and pooled ratio of means (RoM) for pharmacokinetic outcomes using random-effects models.
Of 1,188 publications on clinical trials with triptans, 244 were identified with sex-related search terms. Only 19 publications presented sex-specific results, comprising n = 2,280 men and n = 13,899 women. No sex differences were revealed for 2-hour headache and pain-free responses, but men had a lower risk for headache recurrence (male-to-female RR 0.
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