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Objective To describe the successful use of an autotransfusion technique utilizing 2 syringes in 4 dogs. Case Series Summary All 4 dogs in this series had a hemoabdomen and subsequent hypovolemic shock. During surgery blood was collected from the abdominal cavity by the surgeon and passed to an assistant. The blood was then transferred to a second syringe for direct IV administration. The blood was passed through an inline blood filter prior to reaching the patient. Given the transfusion volume and administration time frame, 3 cases were classified as a massive transfusion. All 4 dogs survived the transfusion, were discharged within 3 days of surgery/transfusion and no complications were noted. New or Unique Information Provided This case series describes a relatively simple method of performing an autotransfuion in patients with hemoabdomen and hypovolemic shock. [ABSTRACT FROM AUTHOR]

Premise of research. Root traits are influenced by a large number of genes, many of which are environmentally sensitive. Despite a growing body of knowledge on root architecture, we have limited understanding of how mutations in genes affecting root traits at the seedling stage influence root traits and performance of ruderal species across nutrient soil environments at mature plant stages. We tested whether insertion mutants (knockouts) in distinct gene types or the position of the mutation within the gene (exon, promoter) differentially influenced root and shoot architecture and size phenotypes. Methodology. Following synthesis of the literature and publicly available expression data sets for Arabidopsis thaliana , we examined knockouts in three categories of genes: genes with previous evidence of influence on root phenotype, genes with previous evidence of influence on root-shoot interactions, and genes with previously no evidence of root function (PNERFs). Using 97 confirmed-homozygous single-insert Salk T-DNA lines with insertion mutations in either the exon or the promoter, we examined how mutation affected root phenotypes. We grew mutant lines, wild-type Col-0 (also known as Columbia), and 10 natural accessions across three nutrient treatments. We phenotyped plants for above- and belowground traits at maturity. Pivotal results. We detected significant phenotypic plasticity for root phenotypes at the adult stage across mutant gene types. Gene types differed in mean performance and trait relationships. Consistent with our prediction, we found that root gene exon mutants respond substantially across environments. A higher proportion of mutant lines outperformed wild-type Col-0 than underperformed, yet this proportion varied by trait and treatment. Conclusions. These data support the ideas that mutational effects are dependent on environmental conditions and that mutations increase or decrease function in stressful low-nutrient environments. Screens at adult life stages uncover new mutant effects for root phenotypes and fruit production. [ABSTRACT FROM AUTHOR]

Abstract Although pediatric leukemia is generally treatable, certain leukemic subtypes face poor prognosis in the clinic suggesting new selective therapeutic agents are needed. Thus, to identify selective apoptosis inducers, a small-molecule library screening approach was conducted using an isogenic leukemic murine p185+ B-ALL cell line pair (BCR-ABL-WT and the BAX/BAK deficient BCR-ABL-DKO). Gratifyingly, the investigation revealed several compounds featuring substituted aromatic five-membered-ring heterocycles with significant activity against murine and human leukemic cellular models. The identified compounds represent potentially novel antileukemic molecular scaffolds exemplified by compounds 1 , 2 and 7 , which demonstrated EC 50 values in the nanomolar and low micromolar range against various leukemia subtypes (SUP-B15, KOPN-8, NALM-06, UoC-B1 cellular models) and pro-apoptotic properties in solid tumor cell models (MDA-MB-231, SUM149) with ample therapeutic index in normal cells. Herein, we highlight compounds 1 , 2 and 7 which promote cell death mediated by caspase 3/7 induction. Our study establishes a strategic platform for the development of potent and selective anti-leukemic agents. Graphical abstract Image 1 Highlights • In silico -library enrichments produce hit compounds with favorable chemical properties. • Use of an isogenic leukemic cell line pair model provides insightful cell death modalities to identify pro-apoptotic agents. • Several unique anti-leukemic compounds with favorable pharmacological properties and therapeutic index in normal cells. [ABSTRACT FROM AUTHOR]

Objective: Moderate alcohol use has been broadly associated with health benefits among older adults, including improved mood. Aims of this study were to evaluate the relationship of moderate alcohol use and depressive symptomatology over a period of eight years, and to examine inflammation, indicated by C-reactive protein (CRP), as one mechanism by which this relationship functions.Methods: The study included 3177 community-dwelling participants over the age of 65 in 2008 drawn from the Health and Retirement Study. Data from the 2006, 2008, 2012, and 2014 waves were used. Alcohol use was measured via self-report and was dichotomized as abstinent (0 drinks per week) and moderate (1-14 drinks per week). Inflammation was measured using CRP, which was collected using an enzyme-linked immunosorbent assay and provided in units of μg/mL. Control variables included gender, age, body mass index (BMI), and medical burden.Results: A latent growth curve model with full information maximum likelihood was used, with results revealing that moderate drinkers endorsed fewer depressive symptoms at baseline and a steeper rate of change over time. Abstinent respondents' depressive symptomatology was characterized by a more linear change rate. Further, moderate drinkers had lower CRP levels suggesting that inflammation partially mediates the relationship between moderate alcohol use and depressive symptomatology.Conclusions: Moderate alcohol use predicts fewer depressive symptoms among older adults. This relationship is partially moderated by CRP and is eroded by the passage of time. Future research should identify additional mechanisms relating alcohol to positive health outcomes and less depressive symptomatology. Copyright © 2017 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The transcription factor ETV6 is required for bone marrow (BM) hematopoiesis and survival of adult hematopoietic stem cells (HSCs), but the mechanisms by which ETV6 regulates these processes remain unclear. We and others reported that germline variants in ETV6 are associated with autosomal dominant thrombocytopenia and occurrence of B-ALL. We identified likely pathogenic variants in 0.8% of 4,405 childhood ALL cases, and functional evaluation of these variants revealed impairment of transcriptional repression activity of ETV6. To investigate the impact of ETV6 variants on hematopoiesis, we generated a CRISPR-Cas9-derived mouse model (Etv6R355X/+) that mirrors an ETV6 R359X variant observed in multiple ALL cases. Flow cytometry of the BM revealed progressive changes in stem and progenitor cells, with 12-month-old ETV6R355X/+ mice showing ∼40% reductions in HSPCs and ∼40% increases in pro-B cells. Lineage-negative, cKit+, Sca1+ (LSK) cells from 3-month-old ETV6R355X/+ mice showed impaired engraftment in a competitive transplant model, as demonstrated by significantly reduced chimerism in primary, secondary, and tertiary recipients. To determine how the ETV6 R355X variant influences the hematopoietic transcriptional landscape, we performed RNA-seq and ATAC-seq from LSK and pro-B cells of 3-month-old WT or Etv6R355X/+ mice. We found 90 and 125 differentially expressed genes in LSK and pro-B cells, respectively. GSEA revealed enrichment of genes associated with hypoxia response and stem cell maintenance. ATAC-seq revealed a preferential shift toward an increase in open chromatin in Etv6R355X/+ cells within regions highly enriched for ETS DNA consensus motifs, indicating a potential loss of ETV6-mediated repression. These findings demonstrate that a pathogenic ETV6 variant can disrupt normal hematopoiesis and alter the transcriptional profile of stem and progenitor cells. [ABSTRACT FROM AUTHOR]