Histological and Immunohistochemical Evaluation of Biphasic Calcium Phosphate and a Mineral Trioxide Aggregate for Bone Healing in Rat Calvaria

This work focused on the process of bone repair of defects in standardized calvaria of Wistar rats treated with biphasic calcium phosphate (BCP), mineral trioxide aggregate (MTA), or a combination of the two. Eighty Wistar rats were divided into four treatment groups and were examined at 2 and 8 weeks. A surgical defect was created in the calvaria using a 6-mm diameter trephine drill. The cavity was treated with BCP, MTA, or BCP + MTA; untreated rats with clot formation served as controls. Samples were evaluated histologically and by immunohistochemical staining for areas of new osteoid tissue and new bone tissue, as well as the percentage of labelled cells using anti-bone morphogenetic protein receptor type 1B (anti-BMPR1B) antibodies. Statistically significant differences were found for all dependent variables (area of new osteoid tissue, area of new bone, and percentage immunostaining) by group (P \u3c 0.0001) and time (P \u3c 0.0001), and for the interaction of the two (P \u3c 0.0001). The MTA group at 8 weeks showed the highest amount of osteoid tissue. The same group also exhibited the highest amount of bone tissue formation. The 2-week MTA samples and 2-week BCP + MTA samples exhibited the highest percentages of stained cells. The best results in terms of the area of osteoid and bone tissue formation and the percentage of BMPR1B were observed for the MTA group, confirming that the combination of BCP + MTA does not result in a significant improvement

Demonstration of early functional compromise of bone marrow derived hematopoietic progenitor cells during bovine neonatal pancytopenia through in vitro culture of bone marrow biopsies

<p>Abstract</p> <p>Background</p> <p>Bovine neonatal pancytopenia (BNP) is a syndrome characterised by thrombocytopenia associated with marked bone marrow destruction in calves, widely reported since 2007 in several European countries and since 2011 in New Zealand. The disease is epidemiologically associated with the use of an inactivated bovine virus diarrhoea (BVD) vaccine and is currently considered to be caused by absorption of colostral antibody produced by some vaccinated cows (“BNP dams”). Alloantibodies capable of binding to the leukocyte surface have been detected in BNP dams and antibodies recognising bovine MHC class I and β-2-microglobulin have been detected in vaccinated cattle. In this study, calves were challenged with pooled colostrum collected from BNP dams or from non-BNP dams and their bone marrow hematopoietic progenitor cells (HPC) cultured <it>in vitro</it> from sternal biopsies taken at 24 hours and 6 days post-challenge.</p> <p>Results</p> <p>Clonogenic assay demonstrated that CFU-GEMM (colony forming unit-granulocyte/erythroid/macrophage/megakaryocyte; pluripotential progenitor cell) colony development was compromised from HPCs harvested as early as 24 hour post-challenge. By 6 days post challenge, HPCs harvested from challenged calves failed to develop CFU-E (erythroid) colonies and the development of both CFU-GEMM and CFU-GM (granulocyte/macrophage) was markedly reduced.</p> <p>Conclusion</p> <p>This study suggests that the bone marrow pathology and clinical signs associated with BNP are related to an insult which compromises the pluripotential progenitor cell within the first 24 hours of life but that this does not initially include all cell types.</p

Star formation in IC1396:Kinematics and subcluster structure revealed by Gaia

Aims. We investigate the star formation history of the IC1396 region by studying its kinematics and completing the population census. Methods. We used multiwavelength data, combining optical spectroscopy to identify and classify new members and near-infrared photometry to trace shocks, jets, and outflows as well as the interactions between the cluster members and the cloud. We also used Gaia EDR3 data to identify new potential members in the multidimensional proper motion and parallax space. Results. The revised Gaia EDR3 distance is 925±73 pc, slightly closer than previously obtained with DR2. The Gaia data reveal four distinct subclusters in the region. These subclusters are consistent in distance but display differences in proper motion. This result, with their age differences, hints toward a complex and varied star formation history. The Gaia data also unveil intermediate-mass objects that tend to evade spectroscopic and disk surveys. Our analysis has allowed us to identify 334 new members. We estimate an average age of ∼4 Myr, confirming previous age estimates. With the new members added to our study, we estimate a disk fraction of 28%, lower than previous values, due to our method detecting mainly new, diskless, intermediate-mass stars. We find age differences between the subclusters, which offers evidence of a complex star formation history with different episodes of star formation

Understanding the role of intersectoral convergence in the delivery of essential maternal and child nutrition interventions in Odisha, India: a qualitative study.

BACKGROUND: Convergence of sectoral programs is important for scaling up essential maternal and child health and nutrition interventions. In India, these interventions are implemented by two government programs - Integrated Child Development Services (ICDS) and National Rural Health Mission (NRHM). These programs are designed to work together, but there is limited understanding of the nature and extent of coordination in place and needed at the various administrative levels. Our study examined how intersectoral convergence in nutrition programming is operationalized between ICDS and NRHM from the state to village levels in Odisha, and the factors influencing convergence in policy implementation and service delivery. METHODS: Semi-structured interviews were conducted with state-level stakeholders (n = 12), district (n = 19) and block officials (n = 66), and frontline workers (FLWs, n = 48). Systematic coding and content analysis of transcripts were undertaken to elucidate themes and patterns related to the degree and mechanisms of convergence, types of actions/services, and facilitators and barriers. RESULTS: Close collaboration at state level was observed in developing guidelines, planning, and reviewing programs, facilitated by a shared motivation and recognized leadership for coordination. However, the health department was perceived to drive the agenda, and different priorities and little data sharing presented challenges. At the district level, there were joint planning and review meetings, trainings, and data sharing, but poor participation in the intersectoral meetings and limited supervision. While the block level is the hub for planning and supervision, cooperation is limited by the lack of guidelines for coordination, heavy workload, inadequate resources, and poor communication. Strong collaboration among FLWs was facilitated by close interpersonal communication and mutual understanding of roles and responsibilities. CONCLUSIONS: Congruent or shared priorities and regularity of actions between sectors across all levels will likely improve the quality of coordination, and clear roles and leadership and accountability are imperative. As convergence is a means to achieving effective coverage and delivery of services for improved maternal and child health and nutrition, focus should be on delivering all the essential services to the mother-child dyads through mechanisms that facilitate a continuum of care approach, rather than sectorally-driven, service-specific delivery processes

Enabling precision medicine in neonatology, an integrated repository for preterm birth research.

Preterm birth, or the delivery of an infant prior to 37 weeks of gestation, is a significant cause of infant morbidity and mortality. In the last decade, the advent and continued development of molecular profiling technologies has enabled researchers to generate vast amount of 'omics' data, which together with integrative computational approaches, can help refine the current knowledge about disease mechanisms, diagnostics, and therapeutics. Here we describe the March of Dimes' Database for Preterm Birth Research (http://www.immport.org/resources/mod), a unique resource that contains a variety of 'omics' datasets related to preterm birth. The database is open publicly, and as of January 2018, links 13 molecular studies with data across tens of thousands of patients from 6 measurement modalities. The data in the repository are highly diverse and include genomic, transcriptomic, immunological, and microbiome data. Relevant datasets are augmented with additional molecular characterizations of almost 25,000 biological samples from public databases. We believe our data-sharing efforts will lead to enhanced research collaborations and coordination accelerating the overall pace of discovery in preterm birth research

Fecal microbiota transplant rescues mice from human pathogen mediated sepsis by restoring systemic immunity.

Death due to sepsis remains a persistent threat to critically ill patients confined to the intensive care unit and is characterized by colonization with multi-drug-resistant healthcare-associated pathogens. Here we report that sepsis in mice caused by a defined four-member pathogen community isolated from a patient with lethal sepsis is associated with the systemic suppression of key elements of the host transcriptome required for pathogen clearance and decreased butyrate expression. More specifically, these pathogens directly suppress interferon regulatory factor 3. Fecal microbiota transplant (FMT) reverses the course of otherwise lethal sepsis by enhancing pathogen clearance via the restoration of host immunity in an interferon regulatory factor 3-dependent manner. This protective effect is linked to the expansion of butyrate-producing Bacteroidetes. Taken together these results suggest that fecal microbiota transplantation may be a treatment option in sepsis associated with immunosuppression

The Tension on dsDNA Bound to ssDNA/RecA Filaments May Play an Important Role in Driving Efficient and Accurate Homology Recognition and Strand Exchange

It is well known that during homology recognition and strand exchange the double stranded DNA (dsDNA) in DNA/RecA filaments is highly extended, but the functional role of the extension has been unclear. We present an analytical model that calculates the distribution of tension in the extended dsDNA during strand exchange. The model suggests that the binding of additional dsDNA base pairs to the DNA/RecA filament alters the tension in dsDNA that was already bound to the filament, resulting in a non-linear increase in the mechanical energy as a function of the number of bound base pairs. This collective mechanical response may promote homology stringency and underlie unexplained experimental results

A Novel PET Imaging Probe for the Detection and Monitoring of Translocator Protein 18 kDa Expression in Pathological Disorders

A new fluorine-substituted ligand, compound 1 (CB251), with a very high affinity (Ki = 0.27 ± 0.09 nM) and selectivity for the 18-kDa translocator protein (TSPO), is presented as an attractive biomarker for the diagnosis of neuroinflammation, neurodegeneration and tumour progression. To test compound 1 as a TSPO PET imaging agent in vivo, 2-(2-(4-(2-[18F]fluoroethoxy)phenyl)-6,8-dichloroimidazo[1,2-a]pyridin-3-yl)-N,N-dipropylacetamide ([18F]1; [18F]CB251) was synthesized by nucleophilic aliphatic substitution in a single-step radiolabelling procedure with a 11.1 ± 3.5% (n = 14, decay corrected) radiochemical yield and over 99% radiochemical purity. In animal PET imaging studies, [18F]CB251 provided a clearly visible image of the inflammatory lesion with the binding potential of the specifically bound radioligand relative to the non-displaceable radioligand in tissue (BPND 1.83 ± 0.18), in a neuroinflammation rat model based on the unilateral stereotaxic injection of lipopolysaccharide (LPS), comparable to that of [11C]PBR28 (BPND 1.55 ± 0.41). [18F]CB251 showed moderate tumour uptake (1.96 ± 0.11%ID/g at 1 h post injection) in human glioblastoma U87-MG xenografts. These results suggest that [18F]CB251 is a promising TSPO PET imaging agent for neuroinflammation and TSPO-rich cancers

GEneSTATION 1.0: A Synthetic Resource of Diverse Evolutionary and Functional Genomic Data for Studying The Evolution of Pregnancy-Associated Tissues and Phenotypes

Mammalian gestation and pregnancy are fast evolving processes that involve the interaction of the fetal, maternal and paternal genomes. Version 1.0 of the GEneSTATION database (http://genestation.org) integrates diverse types of omics data across mammals to advance understanding of the genetic basis of gestation and pregnancy-associated phenotypes and to accelerate the translation of discoveries from model organisms to humans. GEneSTATION is built using tools from the Generic Model Organism Database project, including the biology-aware database CHADO, new tools for rapid data integration, and algorithms that streamline synthesis and user access. GEneSTATION contains curated life history information on pregnancy and reproduction from 23 high-quality mammalian genomes. For every human gene, GEneSTATION contains diverse evolutionary (e.g. gene age, population genetic and molecular evolutionary statistics), organismal (e.g. tissue-specific gene and protein expression, differential gene expression, disease phenotype), and molecular data types (e.g. Gene Ontology Annotation, protein interactions), as well as links to many general (e.g. Entrez, PubMed) and pregnancy disease-specific (e.g. PTBgene, dbPTB) databases. By facilitating the synthesis of diverse functional and evolutionary data in pregnancy-associated tissues and phenotypes and enabling their quick, intuitive, accurate and customized meta-analysis, GEneSTATION provides a novel platform for comprehensive investigation of the function and evolution of mammalian pregnancy