How Do Employment Outcomes of Medicaid Buy-In Participants Vary Based on Prior Medicaid Coverage? An Example from Massachusetts

Summary: The Medicaid Buy-In program is a key component of the federal effort to make it easier for people with disabilities to work without losing health benefits. Authorized by the Balanced Budget Act of 1997 (“BBA”) and the Ticket to Work and Work Incentives Improvement Act of 1999 (“Ticket Act”), the Buy-In program allows states to expand Medicaid coverage to workers with disabilities whose income and assets would ordinarily make them ineligible for Medicaid. To be eligible for the program, an individual must have a disability (as defined by the Social Security Administration) and earned income, and must meet other financial eligibility requirements established by states. States have some flexibility to customize their Buy-In programs to their specific needs, resources, and objectives. As of July 1, 2008, 33 states with a Medicaid Infrastructure Grant (MIG) reported covering 82,488 individuals in the Medicaid Buy-In program. The CommonHealth Working (CHW) program in Massachusetts is the oldest Buy-In program in the nation. It began in 1988 as a state-funded program and was folded into the state’s 1115 Medicaid research and demonstration project in 1996. This issue brief, the eighth in a series on workers with disabilities, compares the employment outcomes of newly enrolled CHW participants based on whether or not they were previously enrolled in MassHealth, Massachusetts’s Medicaid program, under another eligibility category. For those who had been enrolled in MassHealth, employment outcomes before and after CHW enrollment are contrasted

Structural brain anomalies in patients with FOXG1 syndrome and in Foxg1+/- mice

Objective FOXG1 syndrome is a rare neurodevelopmental disorder associated with heterozygous FOXG1 variants or chromosomal microaberrations in 14q12. The study aimed at assessing the scope of structural cerebral anomalies revealed by neuroimaging to delineate the genotype and neuroimaging phenotype associations. Methods We compiled 34 patients with a heterozygous (likely) pathogenic FOXG1 variant. Qualitative assessment of cerebral anomalies was performed by standardized re-analysis of all 34 MRI data sets. Statistical analysis of genetic, clinical and neuroimaging data were performed. We quantified clinical and neuroimaging phenotypes using severity scores. Telencephalic phenotypes of adult Foxg1+/- mice were examined using immunohistological stainings followed by quantitative evaluation of structural anomalies. Results Characteristic neuroimaging features included corpus callosum anomalies (82%), thickening of the fornix (74%), simplified gyral pattern (56%), enlargement of inner CSF spaces (44%), hypoplasia of basal ganglia (38%), and hypoplasia of frontal lobes (29%). We observed a marked, filiform thinning of the rostrum as recurrent highly typical pattern of corpus callosum anomaly in combination with distinct thickening of the fornix as a characteristic feature. Thickening of the fornices was not reported previously in FOXG1 syndrome. Simplified gyral pattern occurred significantly more frequently in patients with early truncating variants. Higher clinical severity scores were significantly associated with higher neuroimaging severity scores. Modeling of Foxg1 heterozygosity in mouse brain recapitulated the associated abnormal cerebral morphology phenotypes, including the striking enlargement of the fornix. Interpretation Combination of specific corpus callosum anomalies with simplified gyral pattern and hyperplasia of the fornices is highly characteristic for FOXG1 syndrome.Peer reviewe

Efficacy of emodepside plus praziquantel tablets (Profender tablets for dogs) against mature and immature cestode infections in dogs

The efficacy of a novel flavoured tablet formulation of emodepside plus praziquantel (Profender tablets for dogs) against intestinal cestodes was investigated in four randomised, blinded placebo-controlled dose confirmation studies in dogs experimentally infected with Echinococcus granulosus or E. multilocularis and in dogs naturally infected with Dipylidium caninum or Taenia spp. The tablets were used at the minimum recommended dose of 1 mg emodepside and 5 mg praziquantel per kg body weight. The studies demonstrated 100% efficacy against mature and immature E. granulosus and E. multilocularis and mature Taenia spp. and D. caninum. Additionally, one of the studies demonstrated non-interference of emodepside with the efficacy of praziquantel against D. caninum. No side effects of the treatment were observed. It is concluded that emodepside plus praziquantel tablets are safe and effective against mature and immature stages of E. granulosus and E. multilocularis and mature stages of Taenia spp. and D. caninum

Combined high-throughput library screening and next generation RNA sequencing uncover microRNAs controlling human cardiac fibroblast biology.

Background: Myocardial fibrosis is a hallmark of the failing heart, contributing to the most common causes of deaths worldwide. Several microRNAs (miRNAs, miRs) controlling cardiac fibrosis were identified in recent years; however, a more global approach to identify miRNAs involved in fibrosis is missing. Methods and results: Functional miRNA mimic library screens were applied in human cardiac fibroblasts (HCFs) to identify annotated miRNAs inducing proliferation. In parallel, miRNA deep sequencing was performed after subjecting HCFs to proliferating and resting stimuli, additionally enabling discovery of novel miRNAs. In-depth in vitro analysis confirmed the pro-fibrotic nature of selected, highly conserved miRNAs miR-20a-5p and miR-132-3p. To determine downstream cellular pathways and their role in the fibrotic response, targets of the annotated miRNA candidates were modulated by synthetic siRNA. We here provide evidence that repression of autophagy and detoxification of reactive oxygen species by miR-20a-5p and miR-132-3p explain some of their pro-fibrotic nature on a mechanistic level. Conclusion: We here identified both miR-20a-5p and miR-132-3p as crucial regulators of fibrotic pathways in an in vitro model of human cardiac fibroblast biology

Long noncoding RNA-enriched vesicles secreted by hypoxic cardiomyocytes drive cardiac fibrosis

Long non-coding RNAs (lncRNAs) have potential as novel therapeutic targets in cardiovascular diseases, but detailed information about the intercellular lncRNA shuttling mechanisms in the heart is lacking. Here, we report an important novel crosstalk between cardiomyocytes and fibroblasts mediated by the transfer of lncRNA-enriched extracellular vesicles (EVs) in the context of cardiac ischemia. lncRNA profiling identified two hypoxia-sensitive lncRNAs: ENSMUST00000122745 was predominantly found in small EVs, whereas lncRNA Neat1 was enriched in large EVs in vitro and in vivo. Vesicles were taken up by fibroblasts, triggering expression of profibrotic genes. In addition, lncRNA Neat1 was transcriptionally regulated by P53 under basal conditions and by HIF2A during hypoxia. The function of Neat1 was further elucidated in vitro and in vivo. Silencing of Neat1 in vitro revealed that Neat1 was indispensable for fibroblast and cardiomyocyte survival and affected fibroblast functions (reduced migration capacity, stalled cell cycle, and decreased expression of fibrotic genes). Of translational importance, genetic loss of Neat1 in vivo resulted in an impaired heart function after myocardial infarction highlighting its translational relevance

Cerebrospinal fluid findings in patients with myelin oligodendrocyte glycoprotein (MOG) antibodies, part 2: results from 108 lumbar punctures in 80 pediatric patients

BACKGROUND: New-generation, cell-based assays have demonstrated a robust association of serum autoantibodies to full-length human myelin oligodendrocyte glycoprotein (MOG-IgG) with (mostly recurrent) optic neuritis, myelitis, and brainstem encephalitis, as well as with neuromyelitis optica (NMO)-like or acute-disseminated encephalomyelitis (ADEM)-like presentations. However, only limited data are yet available on cerebrospinal fluid (CSF) findings in MOG-IgG-associated encephalomyelitis (MOG-EM; also termed MOG antibody-associated disease, MOGAD). OBJECTIVE: To describe systematically the CSF profile in children with MOG-EM. MATERIAL AND METHODS: Cytological and biochemical findings (including white cell counts [WCC] and differentiation; frequency and patterns of oligoclonal bands; IgG/IgM/IgA and albumin concentrations and CSF/serum ratios; intrathecal IgG/IgM/IgA fractions; locally produced IgG/IgM/IgA concentrations; immunoglobulin class patterns; IgG/IgA/IgM reibergrams; Link index; measles/rubella/zoster [MRZ] reaction; other anti-viral and anti-bacterial antibody indices; CSF total protein; CSF L-lactate) from 108 lumbar punctures in 80 pediatric patients of mainly Caucasian descent with MOG-EM were analyzed retrospectively. RESULTS: Most strikingly, CSF-restricted oligoclonal IgG bands, a hallmark of multiple sclerosis (MS), were absent in 89% of samples (N = 96), and the MRZ reaction, the most specific laboratory marker of MS known so far, in 100% (N = 29). If present at all, intrathecal IgG synthesis was low, often transient and mostly restricted to acute attacks. Intrathecal IgM synthesis was present in 21% and exclusively detectable during acute attacks. CSF WCC were elevated in 54% of samples (median 40 cells/μl; range 6-256; mostly lymphocytes and monocytes; > 100/μl in 11%). Neutrophils were present in 71% of samples; eosinophils, activated lymphocytes, and plasma cells were seen only rarely (all < 7%). Blood-CSF barrier dysfunction (as indicated by an elevated albumin CSF/serum ratio) was present in 46% of all samples (N = 79) and at least once in 48% of all patients (N = 67) tested. CSF alterations were significantly more frequent and/or more pronounced in patients with acute spinal cord or brain disease than in patients with acute ON and varied strongly depending on attack severity. CSF L-lactate levels correlated significantly with the spinal cord lesions load (measured in vertebral segments) in patients with acute myelitis (p = 0.0099). An analysis of pooled data from the pediatric and the adult cohort showed a significant relationship of QAlb (p < 0.0005), CST TP (p < 0.0001), and CSF L-lactate (p < 0.0003) during acute attacks with age. CONCLUSION: MOG-IgG-associated EM in children is characterized by CSF features that are distinct from those in MS. With regard to most parameters, no marked differences between the pediatric cohort and the adult cohort analyzed in Part 1 were noted. Our findings are important for the differential diagnosis of pediatric MS and MOG-EM and add to the understanding of the immunopathogenesis of this newly described autoimmune disease

MR imaging in children with transverse myelitis and acquired demyelinating syndromes.

Background: Transverse myelitis (TM) occurs isolated or within other acquired demyelinating syndromes (ADS) such as neuromyelitis optica spectrum disorders (NMOSD), multiple sclerosis (MS) or myelin oligodendrocyte glycoprotein antibody associated disorders (MOGAD). Objective: To describe and compare clinical and MRI features of children with ADS presenting with TM grouped according to antibody status and diagnosis of MS and NMOSD. Patients and methods: Children with TM, radiological involvement of the myelon, MOG and aquaporin-4 antibody status were elegible. Results: 100 children were identified and divided into MOGAD (n=33), NMOSD (n=7), double seronegative TM (n=34), and MS (n=26). MOGAD children had mainly acute disseminated encephalomyelitis + TM/ longitudinally extensive TM (LETM) (42%) or isolated LETM (30%). In MOGAD, LETM was present in more than half of all children (55%) with predominant involvement of only the grey matter (73%). Leptomeningeal enhancement was highly predictive of MOGAD (16/30; p=0.003). In MS patients spinal MRI showed single (50%) or multiple short lesions (46%) with involvement of grey and white matter (68%). Double seronegative children presented with LETM (74%) and brain lesions were less frequent compared to the other groups (30%). Conclusion: Children with ADS presenting with TM reveal important radiological differences such as LETM with predominant involvement of spinal grey matter and leptomeningeal enhancement in MOGAD

Natural Compound Library Screening Identifies New Molecules for the Treatment of Cardiac Fibrosis and Diastolic Dysfunction.

High-throughput natural compound library screening identified 15 substances with antiproliferative effects in human cardiac fibroblasts. Using multiple in vitro fibrosis assays and stringent selection algorithms, we identified the steroid bufalin (from Chinese toad venom) and the alkaloid lycorine (from Amaryllidaceae species) to be effective antifibrotic molecules both in vitro and in vivo, leading to improvement in diastolic function in 2 hypertension-dependent rodent models of cardiac fibrosis. Administration at effective doses did not change plasma damage markers or the morphology of kidney and liver, providing the first toxicological safety data. Using next-generation sequencing, we identified the conserved microRNA 671-5p and downstream the antifibrotic selenoprotein P1 as common effectors of the antifibrotic compounds