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o manipulate Wnt signaling in the clinical setting.C-X-C Motif Chemokine Ligand 12 (CXCL12; aka SDF1α) is a major regulator of a number of cellular systems, including hematopoiesis where it influences hematopoietic cell trafficking, proliferation, and survival during homeostasis and upon stress and disease. A variety of constitutive, temporal, ubiquitous and cell-specific loss-of-function models have documented the functional consequences on hematopoiesis upon deletion of Cxcl12. Here, in contrast to loss-of-function experiments, we implemented a gain-of-function approach by generating a dox-inducible transgenic mouse model that enables spatial and temporal overexpression of Cxcl12. We demonstrated that ubiquitous CXCL12 overexpression led to an increase in multipotent progenitors in the bone marrow and spleen. The CXCL12+ mice displayed reduced reconstitution potential as either donors or recipients in transplantation experiments. Additionally, we discovered that Cxcl12 overexpression improved hematopoietic stem and progenitor cell mobilization into the blood, and conferred radioprotection by promoting quiescence. Thus, this new CXCL12+ mouse model provided new insights on major facets of hematopoiesis and serves as a versatile resource for studying CXCL12 function in a variety of contexts. © AlphaMed Press 2020 SIGNIFICANCE STATEMENT The novel, inducible CXCL12 overexpression mouse model will enable in depth mechanistic interrogation of CXCL12 function in development and disease. Here, using this model, we demonstrated that CXCL12 influences trafficking, proliferation and radioresistance of hematopoietic stem cells and progenitors. These findings are important for understanding hematopoietic development, cancer and transplantation therapies.The hypoparathyroidism, deafness and renal dysplasia (HDR) syndrome is an autosomal dominant disorder caused by heterozygous mutations of the GATA3 gene. In the last 20 years, since the identification of the genetic cause of the HDR syndrome, GATA3 mutations have been reported in 124 families (177 patients). The clinical aspects and molecular genetics of the HDR syndrome are reviewed here together with the reported mutations and phenotypes. Reported mutations consist of 40% frameshift deletions or insertions, 23% missense mutations, 14% nonsense mutations, 6% splice-site mutations, 1% in-frame deletions or insertions, 15% whole gene deletions and 1% whole gene duplication. Missense mutations were found to cluster in the regions encoding the two GATA3 zinc finger domains. Patients showed great clinical variability and the penetrance of each HDR defect increased with age. The most frequently observed abnormality was deafness (93%), followed by hypoparathyroidism (87%) and renal defects (61%). The mean age of diagnosis of hypoparathyroidism, deafness and renal dysplasia was 15.3, 7.5 and 14.0 years, respectively. However, patients with whole gene deletions and protein-truncating mutations were diagnosed earlier than patients with missense mutations. This article is protected by copyright. All rights reserved.Given the pervasive nature of child abuse and neglect, multilevel public health approaches are necessary. Implementation science can help in understanding the most effective ways to build infrastructure and support delivery of such approaches. In this theoretical paper, we describe the implementation of the Positive Parenting Program (Triple P), an evidence-based population-level parenting program in South Carolina. While implementation science has informed how to move population-level efforts to scale, we discuss challenges that persist in practice, such as when there is a need for multiple stakeholders to understand, support, and apply implementation best practices in a systematic and consistent way. To address this challenge, we introduce the role of a Community Capacity Coach, who lives in the local community and works towards the implementation of Triple P. The Coach is responsible for bridging gaps between the local community and statewide support systems. We detail the ways in which the Coach’s role aligns with key intermediary functions, and how the Coach is embedded within the larger Triple P statewide support system. We then discuss the assessment of the Coach’s impact; and conclude with future directions and next steps for this role within Triple P South Carolina.LARS2 variants are associated with Perrault syndrome, characterised by premature ovarian failure and hearing loss, and with an infantile lethal multi-system disorder hydrops, lactic acidosis, sideroblastic anemia (HLASA) in one individual. Recently we reported LARS2 deafness with (ovario) leukodystrophy. Here we describe five patients with a range of phenotypes, in whom we identified biallelic LARS2 variants three patients with a HLASA-like phenotype, an individual with Perrault syndrome whose affected siblings also had leukodystrophy, and an individual with a reversible mitochondrial myopathy, lactic acidosis and developmental delay. Three HLASA cases from two unrelated families were identified. All were males with genital anomalies. Two survived multisystem disease in the neonatal period; both have developmental delay and hearing loss. A 55 year old male with deafness has not displayed neurological symptoms while his female siblings with Perrault syndrome developed leukodystrophy and died in their 30’s. Analysis of muscle from a child with a reversible myopathy showed reduced LARS2 and mitochondrial complex I levels, and an unusual form of degeneration. Analysis of recombinant LARS2 variant proteins showed they had reduced amino-acylation efficiency, with HLASA-associated variants having the most severe effect. A broad phenotypic spectrum should be considered in association with LARS2 variants. This article is protected by copyright. All rights reserved.Aims The objective of this study is to ascertain whether an early three-month treatment with electrotherapy and biofeedback restores continence in urinary incontinence patients after radical prostatectomy (RP). Methods Design The study performed a randomized, controlled trial of parallel and open groups. Configuration Secondary care, urology department of a university hospital complex. Participants Patients sent for RP due to prostate cancer (n = 60), 47 patients finally completed the study. Interventions The treatment group (TG) received physiotherapy consisting of electrotherapy and biofeedback, 3 days a week for 3 months, while the control group (CG) received no specific treatment. Both groups received a guide to perform pelvic floor exercises at home. The measurement instruments used were the 1- and 24-hour pad tests and the International Consultation on Incontinence Questionnaire Short-Form. The recording method used was a micturition (urinary) diary. Results The results of the 1-hour pad test (PT) show statistically significant differences between groups at 3 months (P = .001) and 6 months (P = .001), in favor of those in the TG. Sixty-four percent of patients in the TG recovered continence as against 9.1% in the CG after 3 months in the 1-hour PT, in line with the objective of this study. Conclusions An early physiotherapy program helps RP patients with urinary incontinence recover continence after 3 months. Moreover, they lead a better quality life.Background The aim of this study was to estimate the number of blood donors during the COVID-19 incubation period across China. Study design and methods In this study, we developed a predictive model to estimate the number of blood donors during the COVID-19 incubation period among 34 provincial regions in China. Our main assumption was that blood donors of all ages in different regions have a stable blood donation intention and the same infection risk. Results First, we estimated the number of blood donors during the COVID-19 incubation period in Wuhan city, Hubei Province, and China, from December 31, 2019 to March 17, 2020. Second, we compared the number of blood donors during the COVID-19 incubation period in all provinces across China. In addition, we found that if all RBCs, plasma, and cryoprecipitation were stored in isolation until the 14th day, the potential risk of SARS-CoV-2 transmission through blood transfusion was reduced by at least 65.77% after the blood donor safely passed the COVID-19 incubation period. Moreover, if the detection of SARS-CoV-2 RNA was carried out on all platelets, the potential risk would be reduced by 77.48%. Conclusions Although the risk is low, with the rapid spread of the COVID-19 and the appearance of alarmingly high infectivity and a high fatality rate, appropriate measures should be taken by health departments to ensure the safety of clinical blood.Objectives The purpose of this study was to explore the feasibility and safety of robotic PCI performed using an off-siteremote-control system in an animal model. INCB054329 Background Access to primary percutaneous coronary intervention (PCI) remains a challenge in acute myocardial infarction management. The combination of telemedicine and robotic PCI allow the potential delivery of primary PCI to remote locations without the delay of transfer. Methods This single-center prospective pilot preclinical feasibility study compared robotic PCI with remote PCI on swine across three stages (adjacent room, different floor of the same building, two different buildings). Latency up to 1,000 ms was introduced into the operating environment to simulate decreased network quality (blinded to operator). The primary outcome measures were technical success and acute safety. The secondary outcome measures included lesion wiring time, procedural time and qualitative scoring of the PCI experience by the operator. Results Across 52 experiments in 15 animals, technical success was 100%. No procedural complications occurred during the study. No significant difference in lesion treatment time was detected between stages (p = .11) and between time per target vessel when latency up to 1,000 ms was introduced (p = .58). Injected delay >250 ms had the greatest impact on procedure perceived lag. Longer procedure time was associated with lower procedure impact score, regardless of injected latency. Conclusions Remote robotic PCI was feasible and safe in an animal model. Procedural duration was acceptable and unaffected by network latency. Future studies are needed to determine the safety and feasibility of remote PCI in humans.Legume nodules have two types of hemoglobins symbiotic or leghemoglobins (Lbs) and nonsymbiotic or phytoglobins (Glbs). The latter are categorized into three phylogenetic classes differing in heme coordination and O2 affinity. This review is focused on the roles of Lbs and Glbs in the symbiosis of rhizobia with crop legumes and the model legumes for indeterminate (Medicago truncatula) and determinate (Lotus japonicus) nodulation. Only two hemoglobin functions are well established in nodules Lbs deliver O2 to the bacteroids and act as O2 buffers, preventing nitrogenase inactivation; and Glb1-1 modulates nitric oxide concentration during symbiosis, from the early stage, avoiding the plant’s defense response, to nodule senescence. Here, we critically examine early and recent results, update and correct the information on Lbs and Glbs with the latest genome versions, provide novel expression data, and identify targets for future research. Crucial unresolved questions include the expression of multiple Lbs in nodules, their presence in the nuclei and in uninfected nodule cells, and, intriguingly, their expression in nonsymbiotic tissues.