Tuberculous meningitis (TBM) is the most severe form of TB. Despite treatment, mortality and long-term disability remain unacceptably high. Prevention, early recognition, diagnosis and treatment are fundamental to improving outcomes. However, an effective vaccine remains elusive, initial symptoms are nonspecific, and sensitive diagnostic tests are not available. There has been progress in our understanding of the immunopathology of TBM, and several factors have been found to be associated with susceptibility to infection, disease progression and clinical outcome. However, these have not yet impacted on treatment. Early treatment initiation and uninterrupted continuation, severity on presentation, seizures, stroke, cranial nerve involvement, cerebrospinal fluid cell count and lactate levels, hyponatreamia and coinfection with HIV are all found to be important prognostic factors for outcome. Pathogen lineage (Beijing genotype) and host genetics (polymorphisms in TLR2, TIRAP and LTA4H genes) can influence susceptibility to TBM. However, these findings have not yet impacted on treatment. Progress in vaccine development, opportunities for better diagnostic tests, novel insights into pathogenesis and an increasing evidence base for improving treatment should impact the current high mortality and morbidity, if translated to global and local guidelines.

Preterm birth is a major risk factor for adverse neurological outcomes in ex-preterm children, including motor, cognitive, and behavioral disabilities. N-acetyl-L-cysteine therapy has been used in clinical studies; however, it requires doses that cause significant side effects. In this study, we explore the effect of low dose N-acetyl-L-cysteine therapy, delivered using a targeted, systemic, maternal, dendrimer nanoparticle (DNAC), in a mouse model of intrauterine inflammation. Our results demonstrated that intraperitoneal maternal DNAC administration significantly reduced the preterm birth rate and altered placental immune profile with decreased CD8+ T-cell infiltration. Furthermore, we demonstrated that DNAC improved neurobehavioral outcomes and reduced fetal neuroinflammation and long-term microglial activation in offspring. Our study is the first to provide evidence for the role of CD8+ T-cell in the maternal-fetal interface during inflammation and further support the efficacy of DNAC in preventing preterm birth and prematurity-related outcomes.

Abnormal cord insertion, as well as intrauterine growth restriction, was determined to be correlated with the presence of CHD. On the basis of our results, we conclude that cord insertion should be evaluated at routine obstetric sonography, and further fetal heart evaluation is warranted if abnormal cord insertion is detected.

Purpose To develop a sensitive scale of iris transillumination suitable for clinical and research use, with the capability of using image analysis of photographs or visual matching to a standard image set. Design Evaluation of Diagnostic Technology Participants Seventy study subjects with ocular or oculocutaneous albinism and a broad range of ocular hypopigmentation. Methods Iris transillumination photographic images were taken from existing albinism-related studies. A subset of high-quality images was subjected to computational image analysis and to ranking by both expert and non-expert reviewers. Ordering by a specific image analysis metric was compared with ordering by visual ranking. To establish an eight-point review scale, images were binned based on a specific image analysis metric. Main Outcome Measures Pairwise ranking consistency was evaluated by Spearman’s rank correlation coefficient. Within-technique visual ranking results were compared with Kendall’s coefficient of concordance analysis. Results There was a high degree of correlation among the image analysis, expert-based and non-expert-based image rankings. Pairwise comparisons of the quantitative ranking with each reviewer generated an average correlation coefficient (Kendall tau) of 0.83 +/− 0.04 (s.d.). Inter-rater correlation was also high with Kendall’s W values of 0.96, 0.95 and 0.95 for non-expert, expert, and all reviewers respectively. Conclusions The current standard for assessing iris transillumination is expert review of photographic or clinical exam findings. We adapted a straightforward image-analysis technique to generate quantitative transillumination values. Ranking by the quantitative values was shown to be highly similar to a ranking produced by both expert and non-expert reviewers. This finding suggests that the image characteristics used to quantify iris transillumination are not so subtle as to require expert interpretation. Inter-rater rankings were also highly similar, suggesting that varied methods of transillumination ranking are robust in terms of producing reproducible results.

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