The mixed lineage kinase-3 inhibitor URMC-099 improves therapeutic outcomes for long-acting antiretroviral therapy.

During studies to extend the half-life of crystalline nanoformulated antiretroviral therapy (nanoART) the mixed lineage kinase-3 inhibitor URMC-099, developed as an adjunctive neuroprotective agent was shown to facilitate antiviral responses. Long-acting ritonavir-boosted atazanavir (nanoATV/r) nanoformulations co-administered with URMC-099 reduced viral load and the numbers of HIV-1 infected CD4+ T-cells in lymphoid tissues more than either drug alone in infected humanized NOD/SCID/IL2Rγc-/- mice. The drug effects were associated with sustained ART depots.

Management of Hospitalized Febrile Neonates Without CSF Analysis: A Study of US Pediatric Hospitals.

Objective: Management of febrile neonates includes obtaining blood, urine, and cerebrospinal fluid (CSF) cultures with hospitalization for empiric parenteral antibiotic therapy. Outcomes and management for neonates were compared based on whether CSF was obtained.

Methods: This multicenter retrospective review of the 2002 to 2012 Pediatric Health Information System database included hospitalized infants aged ≤28 days (neonates) admitted to an inpatient ward with a diagnosis code for fever or neonatal fever.

Lysyl Hydroxylase 3 Localizes to Epidermal Basement Membrane and Is Reduced in Patients with Recessive Dystrophic Epidermolysis Bullosa.

Recessive dystrophic epidermolysis bullosa (RDEB) is caused by mutations in COL7A1 resulting in reduced or absent type VII collagen, aberrant anchoring fibril formation and subsequent dermal-epidermal fragility. Here, we identify a significant decrease in PLOD3 expression and its encoded protein, the collagen modifying enzyme lysyl hydroxylase 3 (LH3), in RDEB. We show abundant LH3 localising to the basement membrane in normal skin which is severely depleted in RDEB patient skin.

Citalopram and sertraline exposure compromises embryonic bone development.

Selective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed treatments for depression and, as a class of drugs, are among the most used medications in the world. Concern regarding possible effects of SSRI treatment on fetal development has arisen recently as studies have suggested a link between maternal SSRI use and an increase in birth defects such as persistent pulmonary hypertension, seizures and craniosynostosis. Furthermore, SSRI exposure in adults is associated with decreased bone mineral density and increased fracture risk, and serotonin receptors are expressed in human osteoblasts and osteoclasts.

Clinical and Geographic Characterization of 30-Day Readmissions in Pediatric Sickle Cell Crisis Patients.

Background And Objectives: Sickle cell disease (SCD) is a blood disorder affecting many US children that is often associated with hospital readmission. Although previous studies have reported on the clinical factors that influence readmission risk, potential geographic factors have not been fully investigated. The goal of this study was to investigate the importance of geographic risk factors and to confirm previously derived clinical risk factors that influence readmissions for SCD pain crises.

Measuring the attitudes of dental students towards social accountability following dental education - Qualitative findings.

Background: The term social accountability has gained increased interest in medical education, but is relatively unexplored in dentistry.

Aims: The aim of this study is to explore dental students' attitudes towards social accountability.

Methods: A qualitative study utilizing focus groups with University of Otago final year (5th year) Bachelor of Dental Surgery (BDS) students was carried out.

Transesophageal Echocardiography Guidance of Antegrade Cardioplegia Delivery for Cardiac Surgery.

Objectives: The initial volume of antegrade cardioplegia used to induce asystole during aortic cross-clamp still is based on empiric methods and may be excessive, potentially leading to hyperkalemia, myocardial edema, and acute left ventricular distention from aortic regurgitation. The objectives were to determine whether the volume of cardioplegia required to induce asystole is proportional to left ventricular mass, and whether the degree of left ventricular distention is proportional to the severity of aortic regurgitation.

Design: Prospective observational study.

Magnetic resonance imaging of folic acid-coated magnetite nanoparticles reflects tissue biodistribution of long-acting antiretroviral therapy.

Regimen adherence, systemic toxicities, and limited drug penetrance to viral reservoirs are obstacles limiting the effectiveness of antiretroviral therapy (ART). Our laboratory's development of the monocyte-macrophage-targeted long-acting nanoformulated ART (nanoART) carriage provides a novel opportunity to simplify drug-dosing regimens. Progress has nonetheless been slowed by cumbersome, but required, pharmacokinetic (PK), pharmacodynamics, and biodistribution testing.

Pharmacodynamics of folic acid receptor targeted antiretroviral nanotherapy in HIV-1-infected humanized mice.

Long-acting nanoformulated antiretroviral therapy (nanoART) can sustain plasma drug levels and improve its biodistribution. Cell targeted-nanoART can achieve this and bring drug efficiently to viral reservoirs. However, whether such improvements affect antiretroviral responses remains unknown.

Potential of N-acetylated-para-aminosalicylic acid to accelerate manganese enhancement decline for long-term MEMRI in rodent brain.

Background: Manganese (Mn(2+))-enhanced MRI (MEMRI) is a valuable imaging tool to study brain structure and function in normal and diseased small animals. The brain retention of Mn(2+) is relatively long with a half-life (t1/2) of 51-74 days causing a slow decline of MRI signal enhancement following Mn(2+) administration. Such slow decline limits using repeated MEMRI to follow the central nervous system longitudinally in weeks or months.

Evidence for West Nile virus spillover into the squirrel population in Atlanta, Georgia.

Background: In the United States, spillover of West Nile virus (WNV) into wild mammal populations has been reported since the introduction of the virus into the New World in 1999. Eastern gray squirrels (Sciurus carolinensis) exhibit a high seroprevalence for WNV in urban settings where high virus circulation and human spillover have been reported. In Atlanta, Georgia, human cases of WNV are uncommon despite high infection rates in birds and mosquitoes.

Offspring size at weaning affects survival to recruitment and reproductive performance of primiparous gray seals.

Offspring size affects survival and subsequent reproduction in many organisms. However, studies of offspring size in large mammals are often limited to effects on juveniles because of the difficulty of following individuals to maturity. We used data from a long-term study of individually marked gray seals (Halichoerus grypus; Fabricius, 1791) to test the hypothesis that larger offspring have higher survival to recruitment and are larger and more successful primiparous mothers than smaller offspring.

Parental reasoning about growth attenuation therapy: report of a single-case study.

In 2006 a case report was published about a 6-year-old girl, Ashley, who has profound developmental disabilities and was treated with oestrogen patches to limit her final height, along with a hysterectomy and the removal of her breast buds. Ashley's parents claimed that attenuating her growth would make it possible for them to lift and move her more easily, facilitating greater involvement in family activities and making routine care more straightforward. The 'Ashley treatment' provoked public comment and academic debate and remains ethically controversial.

Mode-locked ultrashort pulse generation from on-chip normal dispersion microresonators.

We describe generation of stable mode-locked pulse trains from on-chip normal dispersion microresonators. The excitation of hyperparametric oscillation is facilitated by the local dispersion disruptions induced by mode interactions. The system is then driven from hyperparametric oscillation to the mode-locked state with over 200 nm spectral width by controlled pump power and detuning.

Usability testing of a prototype multi-user telehealth kiosk.

The overall purpose of this study was to learn how community-dwelling older adults would interact with our prototype multi-user telehealth kiosk and their views about its usability. Seven subjects participated in laboratory-based usability sessions to evaluate the physical design, appearance, functionality and perceived ease of use of a multi-user telehealth kiosk prototype. During usability testing participants recommended 18 new features (29% of comments), identified 15 software errors (23% of comments) and 29 user interface errors (47% of comments).

Enabling nanomaterial, nanofabrication and cellular technologies for nanoneuromedicines.

Nanoparticulate delivery systems represent an area of particular promise for nanoneuromedicines. They possess significant potential for desperately needed therapies designed to combat a range of disorders associated with aging. As such, the field was selected as the focus for the 2014 meeting of the American Society for Nanomedicine.

Positive reinforcement methods to train chimpanzees to cooperate with urine collection.

Positive reinforcement training can be used in many ways to enhance the welfare of captive primates. Training for biologic sample collection is one application of positive reinforcement training. In this study, 35 adult female chimpanzees were trained to cooperate with the collection of urine samples needed to facilitate a research study.

Nanoneuromedicines for degenerative, inflammatory, and infectious nervous system diseases.

Interest in nanoneuromedicine has grown rapidly due to the immediate need for improved biomarkers and therapies for psychiatric, developmental, traumatic, inflammatory, infectious and degenerative nervous system disorders. These, in whole or in part, are a significant societal burden due to growth in numbers of affected people and in disease severity. Lost productivity of the patient and his or her caregiver, and the emotional and financial burden cannot be overstated.

Clinical and serological analysis of patients with positive anticyclic citrullinated Peptide antibodies referred through a Rheumatology Central Triage System.

Objective: Anticitrullinated protein antibodies (ACPA) are a highly specific and sensitive biomarker for the diagnosis of rheumatoid arthritis (RA). Some patients who were found to have a positive ACPA test were referred to our Rheumatology Central Triage (CT; Calgary, Alberta, Canada) for assessment by a rheumatologist. The objectives of our study were to determine the clinical accuracy of ACPA in establishing a diagnosis of RA in a real-time clinical setting.

Opposing regulation of endolysosomal pathways by long-acting nanoformulated antiretroviral therapy and HIV-1 in human macrophages.

Background: Long-acting nanoformulated antiretroviral therapy (nanoART) is designed to improve patient regimen adherence, reduce systemic drug toxicities, and facilitate clearance of human immunodeficiency virus type one (HIV-1) infection. While nanoART establishes drug depots within recycling and late monocyte-macrophage endosomes, whether or not this provides a strategic advantage towards viral elimination has not been elucidated.

Results: We applied quantitative SWATH-MS proteomics and cell profiling to nanoparticle atazanavir (nanoATV)-treated and HIV-1 infected human monocyte-derived macrophages (MDM).

Esophageal visualization as an adjunct to the videofluoroscopic study of swallowing.

Objective: Complaints of dysphagia for solids lead to speech-language pathology (SLP) referral. Yet many of these patients are later diagnosed with esophageal rather than oropharyngeal dysphagia. Fluoroscopic screening involving the oropharynx alone fails to identify these patients.

Child interests in assisted reproductive technology: how is the welfare principle applied in practice?

Study Question: How is the welfare principle interpreted and practised and what meaning does it hold for health professionals who must apply it in assisted reproductive technology (ART)?

Summary Answer: The welfare of a child is a meaningful concept to ART counsellors but it is also impractical when applied preconception.

What Is Known Already: Policy which promotes the interests of a child to be born is inconsistent between and within countries, and has been widely criticized as meaningless, as an unfair imposition and for its lack of clarity and inconsistent translation to ART practice.

Study Design, Size, Duration: We conducted a qualitative study of ART counsellors in Australia and New Zealand in 2012.

Pharmacodynamics of long-acting folic acid-receptor targeted ritonavir-boosted atazanavir nanoformulations.

Long-acting nanoformulated antiretroviral therapy (nanoART) that targets monocyte-macrophages could improve the drug's half-life and protein-binding capacities while facilitating cell and tissue depots. To this end, ART nanoparticles that target the folic acid (FA) receptor and permit cell-based drug depots were examined using pharmacokinetic and pharmacodynamic (PD) tests. FA receptor-targeted poloxamer 407 nanocrystals, containing ritonavir-boosted atazanavir (ATV/r), significantly increased drug bioavailability and PD by five and 100 times, respectively.