Children with idiopathic short stature have significantly different gut microbiota than their normal height siblings: a case-control study

ObjectivesTo investigate the role of gut microbiota (GM) in pathogenesis of idiopathic short stature (ISS) by comparing GM of ISS children to their normal-height siblings.MethodsThis case-control study, conducted at the Schneider Children’s Medical Center’s Institute for Endocrinology and Diabetes between 4/2018-11/2020, involved 30 pairs of healthy pre-pubertal siblings aged 3-10 years, each comprising one sibling with ISS and one with normal height. Outcome measures from fecal analysis of both siblings included GM composition analyzed by 16S rRNA sequencing, fecal metabolomics, and monitoring the growth of germ-free (GF) mice after fecal transplantation.ResultsFecal analysis of ISS children identified higher predicted levels of genes encoding enzymes for pyrimidine, purine, flavin, coenzyme B, and thiamine biosynthesis, lower levels of several amino acids, and a significantly higher prevalence of the phylum Euryarchaeota compared to their normal-height siblings (p<0.001). ISS children with higher levels of Methanobrevibacter, the dominant species in the archaeal gut community, were significantly shorter in stature than those with lower levels (p=0.022). Mice receiving fecal transplants from ISS children did not experience stunted growth, probably due to the eradication of Methanobrevibacter caused by exposure to oxygen during fecal collection.DiscussionOur findings suggest that different characteristics in the GM may explain variations in linear growth. The varying levels of Methanobrevibacter demonstrated within the ISS group reflect the multifactorial nature of ISS and the potential ability of the GM to partially explain growth variations. The targeting of specific microbiota could provide personalized therapies to improve growth in children with ISS

Tumor Tissue Explant Culture of Patient-Derived Xenograft as Potential Prioritization Tool for Targeted Therapy

Despite of remarkable progress made in the head and neck cancer (HNC) therapy, the survival rate of this metastatic disease remain low. Tailoring the appropriate therapy to patients is a major challenge and highlights the unmet need to have a good preclinical model that will predict clinical response. Hence, we developed an accurate and time efficient drug screening method of tumor ex vivo analysis (TEVA) system, which can predict patient-specific drug responses. In this study, we generated six patient derived xenografts (PDXs) which were utilized for TEVA. Briefly, PDXs were cut into 2 × 2 × 2 mm3 explants and treated with clinically relevant drugs for 24 h. Tumor cell proliferation and death were evaluated by immunohistochemistry and TEVA score was calculated. Ex vivo and in vivo drug efficacy studies were performed on four PDXs and three drugs side-by-side to explore correlation between TEVA and PDX treatment in vivo. Efficacy of drug combinations was also ventured. Optimization of the culture timings dictated 24 h to be the time frame to detect drug responses and drug penetrates 2 × 2 × 2 mm3 explants as signaling pathways were significantly altered. Tumor responses to drugs in TEVA, significantly corresponds with the drug efficacy in mice. Overall, this low cost, robust, relatively simple and efficient 3D tissue-based method, employing material from one PDX, can bypass the necessity of drug validation in immune-incompetent PDX-bearing mice. Our data provides a potential rationale for utilizing TEVA to predict tumor response to targeted and chemo therapies when multiple targets are proposed

A MSFD complementary approach for the assessment of pressures, knowledge and data gaps in Southern European Seas : the PERSEUS experience

PERSEUS project aims to identify the most relevant pressures exerted on the ecosystems of the Southern European Seas (SES), highlighting knowledge and data gaps that endanger the achievement of SES Good Environmental Status (GES) as mandated by the Marine Strategy Framework Directive (MSFD). A complementary approach has been adopted, by a meta-analysis of existing literature on pressure/impact/knowledge gaps summarized in tables related to the MSFD descriptors, discriminating open waters from coastal areas. A comparative assessment of the Initial Assessments (IAs) for five SES countries has been also independently performed. The comparison between meta-analysis results and IAs shows similarities for coastal areas only. Major knowledge gaps have been detected for the biodiversity, marine food web, marine litter and underwater noise descriptors. The meta-analysis also allowed the identification of additional research themes targeting research topics that are requested to the achievement of GES. 2015 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license.peer-reviewe

Sepharadim/conversos and premodern Global Hispanism

Sepharadim participated in the Hispanic vernacular culture of the Iberian Peninsula. Even in the time of al-Andalus many spoke Hispano-Romance, and even their Hebrew literature belies a deep familiarity with and love of their native Hispano-Romance languages. However, since the early sixteenth century the vast majority of Sepharadim have never lived in the Hispanic world. Sepharadim lived not in Spanish colonies defined by Spanish conquest, but in a network of Mediterranean Jewish communities defined by diasporic values and institutions. By contrast, the conversos, those Sepharadim who converted to Catholicism, whether in Spain or later in Portugal, Italy, or the New World, lived mostly in Spanish Imperial lands, were officially Catholic, and spoke normative Castilian. Their connections, both real and imagined, with Sephardic cultural practice put them at risk of social marginalization, incarceration, even death. Some were devout Catholics whose heritage and family history doomed them to these outcomes. Not surprisingly, many Spanish and Portugese conversos sought refuge in lands outside of Spanish control where they might live openly as Jews. This exodus (1600s) from the lands formerly known as Sefarad led to a parallel Sephardic community of what conversos who re-embraced Judaism in Amsterdam and Italy by a generation of conversos trained in Spanish universities. The Sephardic/Converso cultural complex exceeds the boundaries of Spanish imperial geography, confuses Spanish, Portuguese, Catholic, and Jewish subjectivities, and defies traditional categories practiced in Hispanic studies, and are a unique example of the Global Hispanophone

Intense Exercise Causing Central Retinal Vein Occlusion in a Young Patient: Case Report and Review of the Literature

We report a 19-year-old patient who developed a central retinal vein occlusion (CRVO) with significant macular edema and visual impairment following intense exercise and dehydration. The patient was treated with 3 intravitreal bevacizumab injections with complete resolution. A review of the literature on the cause and treatment for CRVO in young patients was performed, focusing on the role of intense exercise and dehydration as a rare pathogenesis mechanism of CRVO