MyD88 signaling by neurons induces chemokines that recruit protective leukocytes to the virus-infected CNS.

Viral encephalitis initiates a series of immunological events in the brain that can lead to brain damage and death. Astrocytes express IFN-β in response to neurotropic infection, whereas activated microglia produce proinflammatory cytokines and accumulate at sites of infection. Here, we observed that neurotropic vesicular stomatitis virus (VSV) infection causes recruitment of leukocytes into the central nervous system (CNS), which requires MyD88, an adaptor of Toll-like receptor and interleukin-1 receptor signaling.

The liver X receptor agonist LXR 623 restricts flavivirus replication.

The vector-borne flaviviruses (VBFVs) are well known for causing great misery and death in humans worldwide. The VBFVs include those transmitted by mosquitos, such as Zika virus (ZIKV), dengue virus; and those transmitted by ticks including the tick-borne flavivirus serocomplex and Powassan virus (POWV). Two of our recent reports showed that intracranial POWV infection in the reservoir host, , was restricted and caused no overt clinical disease.

The Geographic Distribution of Videolaryngostroboscopy in the United States.

Purpose: To study the geographic utilization of videolaryngostroboscopy (VLS) with the hypothesis that office-based voice care is unevenly distributed across the United States.

Materials And Methods: This is a cross-sectional database analysis of Medicare beneficiaries. The Centers for Medicare and Medicaid Services Provider Utilization and Payment Data Physician and Other Supplier Public Use File from 2012 to 2017 was analyzed to evaluate VLS utilization.

An Integrated Molecular Grafting Approach for the Design of Keap1-Targeted Peptide Inhibitors.

Inhibiting the Nrf2:Keap1 interaction to trigger cytoprotective gene expression is a promising treatment strategy for oxidative stress-related diseases. A short linear motif from Nrf2 has the potential to directly inhibit this protein-protein interaction, but poor stability and limited cellular uptake impede its therapeutic development. To address these limitations, we utilized an integrated molecular grafting strategy to re-engineer the Nrf2 motif.

Rational design, synthesis and testing of novel tricyclic topoisomerase inhibitors for the treatment of bacterial infections part 2.

Building on our previously-reported novel tricyclic topoisomerase inhibitors (NTTIs), we disclose the discovery of REDX07965, which has an MIC of 0.5 μg mL against , favourable pharmacokinetic properties, selectivity human topoisomerase II and an acceptable toxicity profile. The results herein validate a rational design approach to address the urgent unmet medical need for novel antibiotics.

Rational design, synthesis and testing of novel tricyclic topoisomerase inhibitors for the treatment of bacterial infections part 1.

The alarming reduction in drug effectiveness against bacterial infections has created an urgent need for the development of new antibacterial agents that circumvent bacterial resistance mechanisms. We report here a series of DNA gyrase and topoisomerase IV inhibitors that demonstrate potent activity against a range of Gram-positive and selected Gram-negative organisms, including clinically-relevant and drug-resistant strains. In part 1, we present a detailed structure activity relationship (SAR) analysis that led to the discovery of our previously disclosed compound, REDX05931, which has a minimum inhibitory concentration (MIC) of 0.

Combining Stereotactic Body Radiotherapy and Microwave Ablation Appears Safe and Feasible for Renal Cell Carcinoma in an Early Series.

Microwave (MW) ablation and stereotactic body radiation therapy (SBRT) are both used in treating inoperable renal cell carcinoma (RCC). MW ablation and SBRT have potentially complementary advantages and limitations. Combining SBRT and MW ablation may optimize tumor control and toxicity for patients with larger (> 5 cm) RCCs or those with vascular involvement.

Teamwork in clinical genomics: A dynamic sociotechnical healthcare setting.

Rationale, Aims And Objectives: Teamworking across sociotechnical boundaries in healthcare is growing as technological advances in medicine abound. With this progress, teams need to find new ways of working together in non-traditional settings. The novel field of clinical genomics provides the opportunity to rethink the existing approach to teamworking and how it needs to evolve.

What a city eats: Examining the dietary preferences of families living in communities at high risk for food insecurity.

Introduction: Food insecurity (FI) is the lack of consistent access to enough food for an active and healthy life. Community-based hunger relief programs often serve as emergency food sources for families with FI. However, these programs may not provide foods that diverse populations of people prefer.

Rapalogs downmodulate intrinsic immunity and promote cell entry of SARS-CoV-2.

SARS-CoV-2 infection in immunocompromised individuals is associated with prolonged virus shedding and evolution of viral variants. Rapamycin and its analogs (rapalogs, including everolimus, temsirolimus, and ridaforolimus) are FDA-approved as mTOR inhibitors for the treatment of human diseases, including cancer and autoimmunity. Rapalog use is commonly associated with increased susceptibility to infection, which has been traditionally explained by impaired adaptive immunity.

Broadly neutralizing monoclonal antibodies protect against multiple tick-borne flaviviruses.

Although Powassan virus (POWV) is an emerging tick-transmitted flavivirus that causes severe or fatal neuroinvasive disease in humans, medical countermeasures have not yet been developed. Here, we developed a panel of neutralizing anti-POWV mAbs recognizing six distinct antigenic sites. The most potent of these mAbs bind sites within domain II or III of the envelope (E) protein and inhibit postattachment viral entry steps.

Ensuring best practice in genomics education and evaluation: reporting item standards for education and its evaluation in genomics (RISE2 Genomics).

Purpose: Widespread, quality genomics education for health professionals is required to create a competent genomic workforce. A lack of standards for reporting genomics education and evaluation limits the evidence base for replication and comparison. We therefore undertook a consensus process to develop a recommended minimum set of information to support consistent reporting of design, development, delivery, and evaluation of genomics education interventions.

Transrectal ultrasound guided prostate biopsy performed by supervised junior and senior residents is safe and does not result in inferior outcomes.

Purpose: To compare transrectal ultrasound guided prostate biopsy (TRUSBx) cancer detection and complication rates between residents at different levels of training and attending physicians at a single academic center.

Methods: We performed a retrospective review of consecutive series of 623 men undergoing TRUSBx from June 2014 to February 2017. The procedure was performed either by resident physicians under direct supervision by an attending physician or by an attending physician.

Preferences and values for rapid genomic testing in critically ill infants and children: a discrete choice experiment.

Healthcare systems are increasingly considering widespread implementation of rapid genomic testing of critically ill children, but evidence on the value of the benefits generated is lacking. This information is key for an optimal implementation into healthcare systems. A discrete choice experiment survey was designed to elicit preferences and values for rapid genomic testing in critically ill children.

From Capsids to Complexes: Expanding the Role of TRIM5α in the Restriction of Divergent RNA Viruses and Elements.

An evolutionary arms race has been ongoing between retroviruses and their primate hosts for millions of years. Within the last century, a zoonotic transmission introduced the Human Immunodeficiency Virus (HIV-1), a retrovirus, to the human population that has claimed the lives of millions of individuals and is still infecting over a million people every year. To counteract retroviruses such as this, primates including humans have evolved an innate immune sensor for the retroviral capsid lattice known as TRIM5α.

Interprofessional teamwork: the role of professional identity and signature pedagogy - a mixed methods study.

Purpose: One overlooked determinant of interprofessional teamwork is the mobilisation of professional identity. Taking a health or social care practitioner out of their professional silo and placing them in an interprofessional team setting will challenge their professional identity. The theory of signature pedagogy was used to investigate the challenges and what is needed to support practitioners to mobilise their professional identity to maximise teamwork.

Flexible Ureteroscopy as the New Standard for the Management of Renal Transplant Urolithiasis <15 mm: A Single-Center Experience.

To determine the safety and efficacy of flexible ureteroscopy in the treatment of transplant urolithiasis. We reviewed a single-center series of 2652 patients who underwent surgical treatment for nephrolithiasis at our institution from 2009 to the present day to identify all patients undergoing ureteroscopy for treatment of transplant lithiasis. We identified 18 patients who underwent ureteroscopy for treatment of urolithiasis within the transplanted kidney or ureter.

Investigating the Adoption of Clinical Genomics in Australia. An Implementation Science Case Study.

Despite the overwhelming interest in clinical genomics, uptake has been slow. Implementation science offers a systematic approach to reveal pathways to adoption and a theory informed approach to addressing barriers presented. Using case study methodology, we undertook 16 in-depth interviews with nongenetic medical specialists to identify barriers and enablers to the uptake of clinical genomics.

Redox state and photoreduction control using X-ray spectroelectrochemical techniques - advances in design and fabrication through additive engineering.

The design and performance of an electrochemical cell and solution flow system optimized for the collection of X-ray absorption spectra from solutions of species sensitive to photodamage is described. A combination of 3D CAD and 3D printing techniques facilitates highly optimized design with low unit cost and short production time. Precise control of the solution flow is critical to both minimizing the volume of solution needed and minimizing the photodamage that occurs during data acquisition.

A dynamic systems view of clinical genomics: a rich picture of the landscape in Australia using a complexity science lens.

Background: Clinical genomics represents a paradigm shifting change to health service delivery and practice across many conditions and life-stages. Introducing this complex technology into an already complex health system is a significant challenge that cannot be managed in a reductionist way. To build robust and sustainable, high quality delivery systems we need to step back and view the interconnected landscape of policymakers, funders, managers, multidisciplinary teams of clinicians, patients and their families, and health care, research, education, and philanthropic institutions as a dynamic whole.

Attitudes and Practices of Australian Nephrologists Toward Implementation of Clinical Genomics.

Introduction: Genomic testing is becoming widely available as a diagnostic tool, although widespread implementation is not yet established in nephrology.

Methods: An anonymous electronic survey was administered to investigate experience and confidence with genomic tests, perceived clinical utility of genomic services, preferences for service delivery models, and readiness for implementation among nephrologists. Questions were guided by a comprehensive literature review and published tools, including a validated theoretical framework for implementation of genomic medicine: Consolidated Framework for Implementation Research (CFIR).

Gender-related differences in the risk factors for repeat stone surgery.

Our objective was to analyze and compare the associations between potential risk factors for nephrolithiasis and repeat stone surgery in male and female patients. We retrospectively analyzed 1970 patients who had stone surgery at our institution in the period from January 2009 to May 2017, were older than 18 years and had at least 12 months of postoperative follow-up. Our definition of surgical recurrence included repeat surgery on the same renal unit or on the opposite renal unit if the original imaging did not demonstrate significant stones on that side.