Oxford Vaccine Hesitancy Scale (OVHS): a UK-based and US-based online mixed-methods psychometric development and validation study of an instrument to assess vaccine hesitancy.

Objectives: To describe the development, validation and reliability of the Oxford Vaccine Hesitancy Scale (OVHS), a new instrument to assess vaccine hesitancy in the general population.

Design: Cross-sectional validation study.

Setting: Internet-based study with participants in the UK and USA.

The Oxford Needle Experience (ONE) scale: a UK-based and US-based online mixed-methods psychometric development and validation study of an instrument to assess needle fear, attitudes and expectations in the general public.

Objectives: To develop and validate the Oxford Needle Experience (ONE) scale, an instrument to assess needle fear, attitudes and expectations in the general population.

Design: Cross-sectional validation study.

Setting: Internet-based with participants in the UK and USA.

Sonosensitive Cavitation Nuclei-A Customisable Platform Technology for Enhanced Therapeutic Delivery.

Ultrasound-mediated cavitation shows great promise for improving targeted drug delivery across a range of clinical applications. Cavitation nuclei-sound-sensitive constructs that enhance cavitation activity at lower pressures-have become a powerful adjuvant to ultrasound-based treatments, and more recently emerged as a drug delivery vehicle in their own right. The unique combination of physical, biological, and chemical effects that occur around these structures, as well as their varied compositions and morphologies, make cavitation nuclei an attractive platform for creating delivery systems tuned to particular therapeutics.

Clinical trial protocol for PanDox: a phase I study of targeted chemotherapy delivery to non-resectable primary pancreatic tumours using thermosensitive liposomal doxorubicin (ThermoDox®) and focused ultrasound.

Background: The dense stroma of pancreatic ductal adenocarcinomas is a major barrier to drug delivery. To increase the local drug diffusion gradient, high doses of chemotherapeutic agent doxorubicin can be released from thermally-sensitive liposomes (ThermoDox®) using ultrasound-mediated hyperthermia at the tumour target. PanDox is designed as a Phase 1 single centre study to investigate enhancing drug delivery to adult patients with non-operable pancreatic ductal adenocarcinomas.

Cavitation-Mediated Immunomodulation and Its Use with Checkpoint Inhibitors.

The promotion of anti-tumour immune responses can be an effective route to the complete remission of primary and metastatic tumours in a small proportion of patients. Hence, researchers are currently investigating various methods to further characterise and enhance such responses to achieve a beneficial impact across a wider range of patients. Due to its non-invasive, non-ionising, and targetable nature, the application of ultrasound-mediated cavitation has proven to be a popular method to enhance the delivery and activity of immune checkpoint inhibitors.

Methods Reporting Quality and its Association with Methods Section Length: A Cross-sectional Assessment of STROBE and CONSORT Reporting Adherence in Top-cited Dermatology Journals.

Background: Adequate methods reporting in observational and trial literature is critical to interpretation and implementation.

Objective: Evaluate methodology reporting adherence in the dermatology literature and compare this to internal medicine (IM) literature.

Methods: We performed a cross-sectional review of randomly-selected dermatology and IM manuscripts published between 2014-2018.

Management of anti-M antibody during pregnancy: a case report.

Background: Anti-M antibodies are relatively common and naturally occurring. When anti-M antibodies cross the placenta, they may cause hemolytic disease of the fetus and newborn (HDFN). Anti-M antibodies account for less than 15 cases of HDFN reported in the published English literature.

Optimization of energy and time predicts dynamic speeds for human walking.

Humans make a number of choices when they walk, such as how fast and for how long. The preferred steady walking speed seems chosen to minimize energy expenditure per distance traveled. But the speed of actual walking bouts is not only steady, but rather a time-varying trajectory, which can also be modulated by task urgency or an individual's movement vigor.

Inhibitory Antibodies against PCSK9 Reduce Surface CD36 and Mitigate Diet-Induced Renal Lipotoxicity.

Background: PCSK9 modulates the uptake of circulating lipids through a range of receptors, including the low-density lipoprotein receptor (LDLR) and CD36. In the kidney, CD36 is known to contribute to renal injury through pro-inflammatory and -fibrotic pathways. In this study, we sought to investigate the role of PCSK9 in modulating renal lipid accumulation and injury through CD36 using a high fat diet (HFD)-induced murine model.

Thermosensitive liposomes: a promising step toward localised chemotherapy.

Introduction: Many small molecules and biologic therapeutics have been developed for solid tumor therapy. However, the unique physiology of tumors makes the actual delivery of these drugs into the tumor mass inefficient. Such delivery requires transport from blood vessels, across the vasculature and into and through interstitial space within a tumor.

Risk Factors and Predictors of Survival Among Patients with Amelanotic Melanoma Compared to Melanotic Melanoma in the National Cancer Database.

Background: Amelanotic melanoma (AM) is a rare form of melanoma lacking pigment. Data on AM risk factors and factors predicting survival are limited.

Objectives: We sought to identify predictors of AM, survival differences in AM and melanotic melanoma, and AM-specific survival rates.

The successful migration of total joint arthroplasty from the hospital inpatient to outpatient ASC setting.

Background: This study was undertaken to analyze the clinical results and complication rate of patients undergoing outpatient total joint arthroplasty by a single orthopedic group. All surgeries were performed in the practice-owned ambulatory surgery center (ASC).

Methods: All patients indicated for outpatient total joint arthroplasty from 2016-2019 with complete pre and post-operative patient reported outcomes were enrolled in the study including hip, knee and partial knee replacements.

Inhibition of histone deacetylation with vorinostat does not prevent tunicamycin-mediated acute kidney injury.

Endoplasmic reticulum (ER) stress is associated with acute kidney injury (AKI) caused by various mechanisms, including antibiotics, non-steroidal anti-inflammatory drugs, cisplatin, and radiocontrast. Tunicamycin (TM) is a nucleoside antibiotic that induces ER stress and is a commonly used model of AKI. 4-phenylbutyrate (4-PBA) is a chemical chaperone and histone deacetylase (HDAC) inhibitor and has been shown to protect the kidney from ER stress, apoptosis, and structural damage in a tunicamycin model of AKI.

The continued inappropriate use and overuse of combination topical clotrimazole-betamethasone.

Objective: Combination topical clotrimazole/ betamethasone dipropionate (C-BM) contains a high-potency topical corticosteroid and is not infrequently prescribed for inappropriate patient groups and body sites. Use of C-BM can lead to inadequate clearance or exacerbation of fungal infections as well as cutaneous atrophy, striae, and other skin maladies.

Methods: We performed a retrospective chart review of 1,978 clinical visits where C-BM was prescribed within the University of Utah Health system between 2014 and 2018 to better understand current prescribing patterns.

3-Bromopyruvate-mediated MCT1-dependent metabolic perturbation sensitizes triple negative breast cancer cells to ionizing radiation.

Background: Triple negative breast cancer (TNBC) poses a serious clinical challenge as it is an aggressive form of the disease that lacks estrogen receptor, progesterone receptor, and ERBB2 (formerly HER2) gene amplification, which limits the treatment options. The Warburg phenotype of upregulated glycolysis in the presence of oxygen has been shown to be prevalent in TNBC. Elevated glycolysis satisfies the energy requirements of cancer cells, contributes to resistance to treatment by maintaining redox homeostasis and generating nucleotide precursors required for cell proliferation and DNA repair.

TDAG51 induces renal interstitial fibrosis through modulation of TGF-β receptor 1 in chronic kidney disease.

Chronic kidney disease (CKD) is characterized by the gradual loss of renal function and is a major public health concern. Risk factors for CKD include hypertension and proteinuria, both of which are associated with endoplasmic reticulum (ER) stress. ER stress-induced TDAG51 protein expression is increased at an early time point in mice with CKD.

Oligonucleotide-Functionalized Gold Nanoparticles for Synchronous Telomerase Inhibition, Radiosensitization, and Delivery of Theranostic Radionuclides.

Telomerase represents an attractive target in oncology as it is expressed in cancer but not in normal tissues. The oligonucleotide inhibitors of telomerase represent a promising anticancer strategy, although poor cellular uptake can restrict their efficacy. In this study, gold nanoparticles (AuNPs) were used to enhance oligonucleotide uptake.

Expanding the chemical functionality of DNA nanomaterials generated by rolling circle amplification.

Rolling circle amplification (RCA) is a powerful tool for the construction of DNA nanomaterials such as hydrogels, high-performance scaffolds and DNA nanoflowers (DNFs), hybrid materials formed of DNA and magnesium pyrophosphate. Such DNA nanomaterials have great potential in therapeutics, imaging, protein immobilisation, and drug delivery, yet limited chemistry is available to expand their functionality. Here, we present orthogonal strategies to produce densely modified RCA products and DNFs.

Polymer stealthing and mucin-1 retargeting for enhanced pharmacokinetics of an oncolytic vaccinia virus.

Vaccinia virus (VV) is a powerful tool for cancer treatment with the potential for tumor tropism, efficient cell-to-cell spread, rapid replication in cancer cells, and stimulation of anti-tumor immunity. It has a well-defined safety profile and is being assessed in late-stage clinical trials. However, VV clinical utility is limited by rapid bloodstream neutralization and poor penetration into tumors.

Quantifying cell death induced by doxorubicin, hyperthermia or HIFU ablation with flow cytometry.

Triggered release and targeted drug delivery of potent anti-cancer agents using hyperthermia-mediated focused-ultrasound (FUS) is gaining momentum in the clinical setting. In early phase studies, tissue biopsy samples may be harvested to assess drug delivery efficacy and demonstrate lack of instantaneous cell death due to FUS exposure. We present an optimised tissue cell recovery method and a cell viability assay, compatible with intra-cellular doxorubicin.

In situ evaluation of spatiotemporal distribution of doxorubicin from Drug-eluting Beads in a tissue mimicking phantom.

Understanding the intra-tumoral distribution of chemotherapeutic drugs is extremely important in predicting therapeutic outcome. Tissue mimicking gel phantoms are useful for studying drug distribution in vitro but quantifying distribution is laborious due to the need to section phantoms over the relevant time course and individually quantify drug elution. In this study we compare a bespoke version of the traditional phantom sectioning approach, with a novel confocal microscopy technique that enables dynamic in situ measurements of drug concentration.

Large-Volume Hyperthermia for Safe and Cost-Effective Targeted Drug Delivery Using a Clinical Ultrasound-Guided Focused Ultrasound Device.

Lyso-thermosensitive liposomes (LTSLs) are specifically designed to release chemotherapy agents under conditions of mild hyperthermia. Preclinical studies have indicated that magnetic resonance (MR)-guided focused ultrasound (FUS) systems can generate well-controlled volumetric hyperthermia using real-time thermometry. However, high-throughput clinical translation of these approaches for drug delivery is challenging, not least because of the significant cost overhead of MR guidance and the much larger volumes that need to be heated clinically.

Improved therapeutic antibody delivery to xenograft tumors using cavitation nucleated by gas-entrapping nanoparticles.

Testing ultrasound-mediated cavitation for enhanced delivery of the therapeutic antibody cetuximab to tumors in a mouse model. Tumors with strong EGF receptor expression were grown bilaterally. Cetuximab was coadministered intravenously with cavitation nuclei, consisting of either the ultrasound contrast agent Sonovue or gas-stabilizing nanoscale SonoTran Particles.

Vaccination into the Dermal Compartment: Techniques, Challenges, and Prospects.

In 2019, an 'influenza pandemic' and 'vaccine hesitancy' were listed as two of the top 10 challenges to global health by the WHO. The skin is a unique vaccination site, due to its immune-rich milieu, which is evolutionarily primed to respond to challenge, and its ability to induce both humoral and cellular immunity. Vaccination into this dermal compartment offers a way of addressing both of the challenges presented by the WHO, as well as opening up avenues for novel vaccine formulation and dose-sparing strategies to enter the clinic.

Administrative Burden and Costs of Prior Authorizations in a Dermatology Department.

Importance: Insurance companies use prior authorizations (PAs) to address inappropriate prescribing or unnecessary variations in care, most often for expensive medications. Prior authorizations negatively affect patient care and add costs and administrative burden to dermatology offices.

Objective: To quantify the administrative burden and costs of dermatology PAs.