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Background/Aims: The registry ClinicalTrials.gov was created to provide investigators and patients an accessible database of relevant clinical trials. Methods: To understand the state of sickle cell disease clinical trials, a comprehensive review of all 174 “closed,” “interventional” sickle cell trials registered at ClinicalTrials.gov was completed in January 2015. Results: The majority of registered sickle cell disease clinical trials listed an academic center as the primary sponsor and were an early phase trial. The primary outcome for sickle cell disease trials focused on pain (23%), bone marrow transplant (BMT) (13%), hydroxyurea (8%), iron overload (8%), and pulmonary hypertension (8%). A total of 52 trials were listed as terminated or withdrawn, including 25 (14% of all trials) terminated for failure to enroll participants. At the time of this review, only 19 trials uploaded results and 29 trials uploaded a manuscript in the ClinicalTrials.gov database. A systematic review of pubmed.gov revealed that only 35% of sickle cell studies completed prior to 2014 resulted in an identified manuscript. In comparison, of 80 thalassemia trials registered in ClinicalTrials.gov, four acknowledged failure to enroll participants as a reason for trial termination or withdrawal, and 48 trials (60%) completed prior to 2014 resulted in a currently identified manuscript. Conclusion: ClinicalTrials.gov can be an important database for investigators and patients with sickle cell disease to understand the current available research trials. To enhance the validity of the website, investigators must update their trial results and upload trial manuscripts into the database. This study, for the first time, quantifies outcomes of sickle cell disease trials and provides support to the belief that barriers exist to successful completion, publication, and dissemination of sickle cell trial results.

Patients with hemoglobin SC (Hb SC) and hemoglobin SB+ (Hb SB+) thalassemia suffer from frequent hospitalizations yet strong evidence of a clinical benefit of hydroxyurea (HU) in this population is lacking. Patients with recurrent hospitalizations for pain crisis are offered HU at our institution based on small cohort data and anecdotal benefit. This study identifies outcomes from a large cohort of patients with Hb SC and SB+ thalassemia who were treated with HU for 2 years. A retrospective review was conducted of 32 patients with Hb SC and SB+ thalassemia who were treated with HU. We reviewed the number, and reasons for hospitalization in the 2 years prior to, and 2 years post-HU treatment as well as laboratory changes from baseline, over 1 year. Patients with Hb SC and SB+ thalassemia started on HU for frequent pain, had a significant reduction in hospitalizations over 2 years as compared to the 2 years prior to HU initiation (mean total hospitalizations/year: pre-HU: 1.6 vs post-HU 0.4 hospitalizations, P<0.001; mean pain hospitalizations/year: pre-HU 1.5 vs post-HU 0.3 hospitalizations, P<0.001). Patients demonstrated hematologic changes including an increase in percent fetal hemoglobin (%HbF) pre-post HU (4.5% to 7.7%, P=0.002), mean corpuscular volume (74 to 86 fL, P<0,0001), and decrease in absolute neutrophil count (5.0 to 3.2×10(9)/L, P=0.007). Patients with higher doses of HU demonstrated the greatest reduction in hospitalizations but this was unrelated to absolute neutrophil count. This cohort of patients with Hb SC and SB+ thalassemia provides additional support for using HU in patients with recurrent hospitalizations for pain. A large randomized multicenter trial of HU to reduce pain admissions should be conducted to confirm these data and provide much needed evidence based recommendations for this population.

Background Patients who develop sickle cell disease (SCD) nephropathy are at a high risk for mortality. The pathophysiology of vaso-occlusive pain crisis may contribute to acute kidney injury (AKI). Non-steroidal anti-inflammatory drugs, known inducers of AKI, are used to treat pain crises. Multiple gaps exist in the knowledge about the impact of AKI in SCD. Methods We conducted a 2-year retrospective review of AKI events in patients admitted for vaso-occlusive crisis. AKI was defined by an increase of ≥0.3 mg/dL or 50% in serum creatinine from baseline. Laboratory values and ketorolac administration by days and dose (mg/kg) were identified from hospital records. A generalized mixed effects model for binary outcomes evaluated AKI based on laboratory variables and ketorolac administration. A generalized mixed Poisson effects model analyzed the association of AKI with hospital length of stay. Results Thirty-three out of 197 admissions for vaso-occlusive pain crisis (17%) were associated with AKI. Fifty-two percent of the cases presented to the Emergency Room (ER) with AKI. Every one unit decrease in hemoglobin from baseline to admission increased the risk of AKI by 49%. Among patients who received ketorolac for pain, both total days and doses of ketorolac were associated with AKI. Finally, patients with pain and AKI required longer periods of hospitalization than patients without AKI. Conclusion Acute kidney injury during sickle cell pain crisis is common and may be an important modifiable risk factor for developing chronic kidney disease (CKD). Further studies are needed to determine the impact of nephrotoxic medications on progressive SCD nephropathy.

Traveling to and from university-based clinics is a major health care barrier for children with sickle cell disease in Alabama. To reduce this barrier, the University of Alabama at Birmingham (UAB) developed satellite clinics. This study seeks to determine if these satellite clinics provide a similar level of comprehensive care when compared with the university-based clinic using four surrogate markers: 1) attendance rates, 2) percentage of patients on hydroxyurea, 3) percentage of screening MRIs obtained, and 4) percentage of transcranial dopplers (TCD) completed. A retrospective review of sickle cell visits from June 1, 2012 to May 31, 2013 demonstrated that satellite clinics can provide levels of medical care for children with sickle cell disease similar to those provided by university-based clinics.

Members of genus Capitella (Annelida: Capitellidae) are often found in high abundance in areas of anthropogenic disturbance, such as fish farms and waste-water outflow sites and are frequently cited as ecological indicators of organic pollution. Understanding evolutionary relations and habitat preferences between Capitella species that can tolerate these, and other, harsh environments and those that cannot is important for their continued and improved use as indicators of pollution.Five previously undocumented species of Capitella and Capitella nonatoi, a species described from Brazil, were detected in the Gulf of Mexico (GoM) by DNA barcoding. Most of the new species were found in a single location, with one being distributed throughout the GoM. Two of the proposed species are supported by distinctive life history characteristics. These findings underscore the potential to uncover large amounts of biodiversity in the GoM, a region subject to many anthropogenic and natural disturbances. Additionally, support was found for a single evolutionary origin of acicular spines in Capitella, which seems to be a morphology unique to Western Atlantic estuarine waters.Comparing six species abundance modeling techniques using internal validation metrics with six capitellids in Tampa Bay, Florida indicated that none of the assessed models works best for all species. However, Hurdle and GAM-Tweedie models had good performance overall. This was attributed to how these models handle zero-inflation, which every species had. Species rarity was influential and required consideration. For example, Capitella aciculata was found to be a very rare species and this restricted model specification, resulting in the removal of one of the covariates. Assessment of environmental term importance indicated that depth and bay segment/region are important across all species, with higher abundance in shallow, near-shore regions of the bay.Investigation of the evolution of hypoxia inducible factor (HIF), a key transcription factor in the cellular oxygen-sensing pathway consisting of an alpha and beta subunit, revealed high diversity across Annelida. Some recognized groups of annelids were supported by both gene phylogenies. However, neither of the two genes mirrored current hypotheses of annelid phylogenetics but HIFβ reflected current annelid phylogeny hypotheses more closely, indicating stronger conservation of this gene. Additionally, the protein domains of the two genes were recovered with varying degrees of success. This was attributed to loss of low-quality data during transcriptome assembly and high divergence of the domains.These findings contribute to our understanding of Capitella species diversity, patterns of occurrence, and potential for low-oxygen tolerance. A key component to understanding how Capitella have come to occupy so many different marine habitats (e.g. sulfide vents, deep-sea wood falls, squid egg masses) lies in understanding their functional response to the low oxygen levels they encounter in some of these habitats. This will provide insights into the evolution of the HIF transcription factor across Annelida and its potential role in speciation across the phylum.

The purpose of this study was to determine the relationship between sense of coherence and school connectedness among online public high school students. The connection students make with their school can affect their well-being based on the stress they perceive from the school and its environment. The variables of interest were the sense of coherence score and the school connectedness score. A bivariate correlational research study was performed to determine if there was a significant relationship between the two variables. The sample was 83 high school students enrolled in an online public school. Each completed the Sense of Coherence – Orientation to Life Questionnaire (SOC-13) and the School Connectedness Survey. Data was analyzed using the Pearson’s Product Moment r to examine the relationship between the two variables. Results of the study found a negative correlation between the sense of coherence score, sense of coherence comprehensibility score, sense of coherence manageability score and school connectedness score. No correlation was found between the sense of coherence meaningfulness score and school connectedness score. Recommendations for future research include examining different populations and socioeconomics of the participants. A qualitative study is also recommended to examine motivation and academic support. This study will help online public high school administrators and faculty understand students like those enrolled in their schools and develop programs to help promote school connectedness and reduce stress.

The hepatic acute phase response (APR), stimulated by injury or inflammation, is characterized by significant changes in circulating acute phase protein (APP) concentrations. While individual functions of liver-derived APPs are known, the net consequence of APP changes is unclear. Pneumonia and sepsis elicit systemic inflammation and induce a robust APR. Although APR activation is regarded as a hallmark of infection, direct contributions of liver activation to pulmonary defense during pneumonia and sepsis-induced pneumonia remain unclear. Pneumonia causes a pulmonary inflammatory response coordinated largely by alveolar macrophages, and is typified by cytokine production, leukocyte recruitment and plasma extravasation, the latter of can enable delivery of hepatocyte-derived APPs to the infection site. To determine the functional significance of the hepatic APR during pneumonia, we challenged APR-null mice lacking hepatocyte signal transducer and activator of transcription-3 (STAT3) and RelA with 106 colony-forming units (CFU) Escherichia coli intratracheally. HepSTAT3/RelA-/- mice displayed ablated APP induction, significantly increased mortality, tumor necrosis factor-dependent hepatotoxicity, and pulmonary bacterial burdens. Following a lower (4x10 5 CFU) E. coli inoculum, hepSTAT3/RelA-/- mice had decreased APP concentrations with reduced pulmonary inflammation and diminished airspace macrophage activation. Similar results were obtained in the context of endotoxemia and pneumonia. We employed an endotoxemia/pneumonia model, whereby 18 hours of intraperitoneal E. coli lipopolysaccharide (5 mg/kg) was followed by intratracheal E. coli (10 6 CFU) in mice lacking hepatocyte STAT3 (hepSTAT3-/-) or control hepSTAT3+/+ mice. Following endotoxemia and pneumonia, hepSTAT3-/- mice, with significantly reduced levels of circulating and airspace APPs, exhibited significantly elevated lung and blood bacterial burdens and mortality. While neither recruited airspace neutrophils nor lung injury were altered in endotoxemic hepSTAT3-/- mice, in vivo production of reactive oxygen species in alveolar macrophage was significantly decreased. Additionally, bronchoalveolar lavage fluid from this group of hepSTAT3-/- mice allowed greater bacterial growth ex vivo. These results identify a lung-liver axis, whereby the liver response enhances macrophage activation and pulmonary host defense during pneumonia and sepsis-induced pneumonia. Taken together, induction of liver acute phase gene expression programs contributes to countering the deleterious consequences of pneumonia, whether it is alone or in the context of sepsis-induced infection.