Brain development in children with new onset epilepsy: A prospective controlled cohort investigation

Purpose: To characterize prospective neurodevelopmental changes in brain structure in children with new and recent‐onset epilepsy compared to healthy controls. Methods: Thirty‐four healthy controls (mean age 12.9 years) and 38 children with new/recent‐onset idiopathic epilepsy (mean age 12.9 years) underwent 1.5 T magnetic resonance imaging (MRI) at baseline and 2 years later. Prospective changes in total cerebral and lobar gray and white matter volumes were compared within and between groups. Results: Prospective changes in gray matter volume were comparable for the epilepsy and control groups, with significant (p < 0.0001) reduction in total cerebral gray matter, due primarily to significant (p < 0.001) reductions in frontal and parietal gray matter. Prospective white matter volume changes differed between groups. Controls exhibited a significant (p = 0.0012) increase in total cerebral white matter volume due to significant (p < 0.001) volume increases in the frontal, parietal, and temporal lobes. In contrast, the epilepsy group exhibited nonsignificant white matter volume change in the total cerebrum (p = 0.51) as well as across all lobes (all p’s > 0.06). The group by white matter volume change interactions were significant for total cerebrum (p = 0.04) and frontal lobe (p = 0.04). Discussion: Children with new and recent‐onset epilepsy exhibit an altered pattern of brain development characterized by delayed age‐appropriate increase in white matter volume. These findings may affect cognitive development through reduced brain connectivity and may also be related to the impairments in executive function commonly reported in this population.     

Broad Coverage of Genetically Diverse Strains of Clostridium difficile by Actoxumab and Bezlotoxumab Predicted by In Vitro Neutralization and Epitope Modeling

Clostridium difficile infections (CDIs) are the leading cause of hospital-acquired infectious diarrhea and primarily involve two exotoxins, TcdA and TcdB. Actoxumab and bezlotoxumab are human monoclonal antibodies that neutralize the cytotoxic/cytopathic effects of TcdA and TcdB, respectively. In a phase II clinical study, the actoxumab-bezlotoxumab combination reduced the rate of CDI recurrence in patients who were also treated with standard-of-care antibiotics. However, it is not known whether the antibody combination will be effective against a broad range of C. difficile strains. As a first step toward addressing this, we tested the ability of actoxumab and bezlotoxumab to neutralize the activities of toxins from a number of clinically relevant and geographically diverse strains of C. difficile. Neutralization potencies, as measured in a cell growth/survival assay with purified toxins from various C. difficile strains, correlated well with antibody/toxin binding affinities. Actoxumab and bezlotoxumab neutralized toxins from culture supernatants of all clinical isolates tested, including multiple isolates of the BI/NAP1/027 and BK/NAP7/078 strains, at antibody concentrations well below plasma levels observed in humans. We compared the bezlotoxumab epitopes in the TcdB receptor binding domain across known TcdB sequences and found that key substitutions within the bezlotoxumab epitopes correlated with the relative differences in potencies of bezlotoxumab against TcdB of some strains, including ribotypes 027 and 078. Combined with in vitro neutralization data, epitope modeling will enhance our ability to predict the coverage of new and emerging strains by actoxumab-bezlotoxumab in the clinic.     

The Biomedical Research Hub: a federated platform for patient research data

ObjectiveThe objective was to develop and operate a cloud-based federated system for managing, analyzing, and sharing patient data for research purposes, while allowing each resource sharing patient data to operate their component based upon their own governance rules. The federated system is called the Biomedical Research Hub (BRH).Materials and MethodsThe BRH is a cloud-based federated system built over a core set of software services called framework services. BRH framework services include authentication and authorization, services for generating and assessing findable, accessible, interoperable, and reusable (FAIR) data, and services for importing and exporting bulk clinical data. The BRH includes data resources providing data operated by different entities and workspaces that can access and analyze data from one or more of the data resources in the BRH.ResultsThe BRH contains multiple data commons that in aggregate provide access to over 6 PB of research data from over 400 000 research participants.Discussion and conclusionWith the growing acceptance of using public cloud computing platforms for biomedical research, and the growing use of opaque persistent digital identifiers for datasets, data objects, and other entities, there is now a foundation for systems that federate data from multiple independently operated data resources that expose FAIR application programming interfaces, each using a separate data model. Applications can be built that access data from one or more of the data resources.     

Case report: Complete esophageal obliteration secondary to cytomegalovirus in AIDS patient

HIV‐related benign esophageal strictures have been reported secondary to idiopathic esophageal ulceration, cytomegalovirus (CMV) esophagitis, herpetic esophagitis, and increased sensitivity to radiation therapy. Despite extensive and deep nature of CMV ulceration, stricture formation is uncommon. There have been anecdotal reports of esophageal strictures secondary to CMV infection in HIV patients. Esophageal stricture has been reported during active CMV ulceration as well as subsequent to successful treatment. Esophageal strictures secondary to CMV have also been reported without prior ulceration. We report a patient with CMV esophagitis presenting with ulceration and stricture who developed total obliteration of esophageal lumen following treatment with gancyclovir.     

Flow cytometric analysis of human spermatozoa treated with antiserum to human seminal inhibin

Inhibin from human seminal plasma is structurally identical to sperm coating antigen. Using the flow cytometric technique it has been demonstrated that there is a positive correlation between initial motility of sperm and the amount of inhibin coated on the spermatozoal surface.     

Role of inhibin in polycystic ovarian syndrome

The possible role of inhibin in the etiology of polycystic ovarian syndrome (PCO) was studied. In rats PCO was induced by thiouracil and human chorionic gonadotropin (hCG). These animals were grouped under different treatment schedules: inhibin; antibodies to inhibin; ovine follicle stimulating hormone (FSH). In rats treated with antibodies to inhibin, there was a decrease in ovarian weight concomitant with specific increase in serum FSH levels. No changes in serum luteinizing hormone (LH) and prolactin levels were observed. However, testosterone levels were significantly decreased. Histological examination of the ovaries showed a marked arrest in the cyst formation with new growing follicles. In animals treated with inhibin, testosterone levels increased without any accompanying changes in ovarian weight. The circulating levels of prolactin and LH were unaffected. A decrease in serum FSH levels was accompanied by an increase in the number of cysts. The study corroborates the hypothesis that inhibin is involved in the development of PCO syndrome. Hence, an antagonist to inhibin may prove useful for the treatment of women with this condition.     

Neonatal screening for congenital hypothyroidism in a developing country: problems and strategies

Neonatal screening in India poses more organisational and socio-economic rather than medical challenges. Based on the pilot study of 450 cord sera, the plan for screening considered cord TSH<30 μU/ml as normal, 30 to 80 as borderline with recall by letters and >80 as indicative of hypothyroid state, with recall by home visits. Of the 17,240 live births only 12,407 cord sera were collected. Envisaging follow-up difficulties, T₄ was assayed in cord sera when TSH was>30 μ U/ml. 2·81% (350) babies needed recall. Only 30% of 302 (2·43%) babies with cord TSG 30 to 80 responded, to recall letters and were normal; availability of both cord TSH and T₄ helped in excluding hypothyroidism in majority of non-respondents. Forty-eight (0·38%) newborns had TSH>90 μU/ml; 80% of this group and 100% with TSH> 100 μU/ml were traced by home visits. Hypothyroidism was confirmed in 5/48, biochemically and by thyroid scan. All five hypothyroids had cord TSH>300 μU/ml. The incidence in this nonendemic region of India was 1∶2481. Thus false elevation of cord TSH 30 to 300 μU/ml was noted in 0·34% with a chance of detecting a hypothyroid 1 in 10 when TSH>80 μU/ml. Screening strategies in a developing country must ensure meticulous clerical assistance, co-operation and education of nurses and parents, precise and cost effective technics and facilities for continued surveilance of detected hypothyroids.