Biodistribution and function of coupled polymer-DNA origami nanostructures.

Spatial control over the distribution of therapeutics is a highly desired feature, which could limit the side effects of many drugs. Here we describe a nanoscale agent, fabricated from a coupled polymer-DNA origami hybrid that exhibits stability in serum and slow diffusion through tissues, in a manner correlating with shape and aspect ratio. Coupling to fragments of polyethylene glycol (PEG) through polyamine electrostatic interactions resulted in marked stability of the agents in-vivo, with > 90% of the agents maintaining structural integrity 5 days following subcutaneous injection.

Imaging findings of fibroid torsion in pregnancy: A case report.

When our patient presented emergently to labor and delivery at 18 weeks pregnant with severe right abdominal pain, the common diagnoses (such as appendicitis, cholecystitis, etc.) were on the top of the differential. However, US and MRI revealed a rarer cause of her pain, a pedunculated fibroid.

Helium Hand - High Pressure Injection Injury.

High-pressure injection injuries are clinically significant injuries which may be underappreciated on initial physical exam and which require a high index of suspicion and early clinical intervention to avoid negative outcomes.

The HIV-1 Capsid-Targeted Inhibitor GSK878 Alters Selection of Target Sites for HIV DNA Integration.

Decades of effort have yielded highly effective antiviral agents to treat HIV, but viral strains have evolved resistance to each inhibitor type, focusing attention on the importance of developing new inhibitor classes. A particularly promising new target is the HIV capsid, the function of which can be disrupted by highly potent inhibitors that persist long term in treated subjects. Studies with such inhibitors have contributed to an evolving picture of the role of capsid itself-the inhibitors, like certain capsid protein (CA) amino acid substitutions, can disrupt intracellular trafficking to alter the selection of target sites for HIV DNA integration in cellular chromosomes.

Antiviral Properties of HIV-1 Capsid Inhibitor GSK878.

GSK878 is a newly described HIV-1 inhibitor that binds to the mature capsid (CA) hexamer in a pocket originally identified as the binding site of the well-studied CA inhibitor PF-74. Here, we show that GSK878 is highly potent, inhibiting an HIV-1 reporter virus in MT-2 cells with a mean 50% effective concentration (EC) of 39 pM and inhibiting a panel of 48 chimeric viruses containing diverse CA sequences with a mean EC of 94 pM. CA mutations associated with reduced susceptibility to other inhibitors that bind to PF-74 binding site (L56I, M66I, Q67H, N74D, T107N, and Q67H/N74D) also reduced susceptibility to GSK878, with M66I, Q67H/N74D, and L56I having the greatest impact on antiviral activity.

Potent Long-Acting Inhibitors Targeting the HIV-1 Capsid Based on a Versatile Quinazolin-4-one Scaffold.

Long-acting (LA) human immunodeficiency virus-1 (HIV-1) antiretroviral therapy characterized by a ≥1 month dosing interval offers significant advantages over daily oral therapy. However, the criteria for compounds that enter clinical development are high. Exceptional potency and low plasma clearance are required to meet dose size requirements; excellent chemical stability and/or crystalline form stability is required to meet formulation requirements, and new antivirals in HIV-1 therapy need to be largely free of side effects and drug-drug interactions.

Sex differences in apoptosis do not contribute to sex differences in blood pressure or renal T cells in spontaneously hypertensive rats.

Apoptosis is a physiological and anti-inflammatory form of cell death that is indispensable for normal physiology and homeostasis. Several studies have reported aberrant activation of apoptosis in various tissues at the onset of hypertension. However, the functional significance of apoptosis during essential hypertension remains largely undefined.

Genome Sequences of Microbacterium foliorum Phages Anseraureola, Pondwater, and Yasuo.

Anseraureola, Pondwater, and Yasuo are bacteriophages with siphovirus morphology that infect Microbacterium foliorum NRRL B-24224. They were isolated from soil collected in Amherst, Massachusetts, and have genome lengths between 17,362 bp and 17,453 bp. These phages each contain 25 predicted protein-coding genes and are assigned to phage cluster EE.

Discovery and Preclinical Profiling of GSK3839919, a Potent HIV-1 Allosteric Integrase Inhibitor.

Allosteric HIV-1 integrase inhibitors (ALLINIs) have been of interest recently because of their novel mechanism of action. Strategic modifications to the C5 moiety of a class of 4-(4,4-dimethylpiperidinyl)-2,6-dimethylpyridinyl ALLINIs led to the identification of a tetrahydroisoquinoline heterocycle as a suitable spacer element to project the distal hydrophobic aryl ring. Subsequent optimization of the aryl substitutions identified as an ALLINI with single-digit nanomolar inhibitory potency and low clearance across preclinical species.

Scaffold modifications to the 4-(4,4-dimethylpiperidinyl) 2,6-dimethylpyridinyl class of HIV-1 allosteric integrase inhibitors.

Allosteric integrase inhibitors (ALLINIs) of HIV-1 may hold promise as a novel mechanism for HIV therapeutics and cure. Scaffold modifications to the 4-(4,4-dimethylpiperidinyl) 2,6-dimethylpyridinyl class of ALLINIs provided a series of potent compounds with differentiated 5/6 fused ring systems. Notably, inhibitors containing the 1,2,4-triazolopyridine and imidazopyridine core exhibited single digit nM antiviral potency and low to moderate clearance after intravenous (IV) dosing in rat pharmacokinetic (PK) studies.

Racial and ethnic disparities in H1N1 vaccine uptake in Medicaid: Lessons learned for a COVID-19 vaccine rollout.

Background: Racial and ethnic minorities in the US have been disproportionately affected by the COVID-19 pandemic and are at risk for disparities in COVID-19 vaccinations. The H1N1 flu vaccine experience provides lessons learned to address and prevent racial and ethnic disparities in COVID-19 vaccinations. We aim to identify racial/ethnic and geographic disparities in H1N1 vaccinations among Medicaid enrollees to inform equitable COVID-19 vaccination policies and strategies.

Splenectomy increases blood pressure and abolishes sex differences in renal T-regulatory cells in spontaneously hypertensive rats.

Over the past decade there has been increasing support for a role of the immune system in the development of hypertension. Our lab has previously reported that female spontaneously hypertensive rats (SHRs) have a blood pressure (BP)-dependent increase in anti-inflammatory renal regulatory T cells (Tregs), corresponding to lower BP compared with males. However, little is known regarding the mechanism for greater renal Tregs in females.

Stimulation of angiotensin II receptor 2 preserves cognitive function and is associated with an enhanced cerebral vascular density after stroke.

Angiotensin signaling is known to be sexually dimorphic. Although it is a well-studied target for intervention in stroke and cognitive impairment, female studies are rare. With females suffering a disproportionately greater negative impact of stroke and dementia vs.

Leveraging Emergency Department Encounters to Improve Cancer Screening Adherence.

Objective: We aimed to estimate the proportion of patients visiting the emergency department (ED) who were not up to date with cancer screening guidelines to assess the scope of need and potential impact of ED-based cancer screening interventions.

Methods: Adult participants from the 2015 National Health Interview Survey were included. Among patients nonadherent to national breast, colorectal, or lung cancer screening guidelines, the proportion of patients reporting an ED visit within the last year was estimated, accounting for complex survey sampling design features.

Adverse Maternal and Fetal Outcomes in a Novel Experimental Model of Pregnancy after Recovery from Renal Ischemia-Reperfusion Injury.

Background: Recent clinical studies report that women with a history of AKI have an increased incidence of maternal and fetal adverse outcomes during pregnancy, despite fully recovering renal function prior to conception. The mechanisms contributing to such adverse outcomes in pregnancy after AKI are not yet understood.

Methods: To develop a rodent model to investigate fetal and maternal outcomes in female animals with a history of AKI, we used ischemia-reperfusion injury as an experimental model of AKI in female Sprague Dawley rats.

Discovery of BMS-986144, a Third-Generation, Pan-Genotype NS3/4A Protease Inhibitor for the Treatment of Hepatitis C Virus Infection.

The discovery of a pan-genotypic hepatitis C virus (HCV) NS3/4A protease inhibitor based on a P1-P3 macrocyclic tripeptide motif is described. The all-carbon tether linking the P1-P3 subsites of is functionalized with alkyl substituents, which are shown to effectively modulate both potency and absorption, distribution, metabolism, and excretion (ADME) properties. The CFBoc-group that caps the P3 amino moiety was discovered to be an essential contributor to metabolic stability, while positioning a methyl group at the C1 position of the P1' cyclopropyl ring enhanced plasma trough values following oral administration to rats.

IL-10 treatment decreases blood pressure in male, but not female, spontaneously hypertensive rats.

Interleukin-10 (IL-10) is an anti-inflammatory cytokine that induces nitric oxide (NO) production. IL-10 supplementation has been previously shown to lower blood pressure (BP) in male hypertensive mice, but the effect of exogenous IL-10 in hypertensive female rodents has not been studied. For the present study, we hypothesized that chronic infusion of IL-10 in hypertensive rats would lower BP concomitant with an increase in renal NO synthase (NOS) activity.

Hypertensive female Sprague-Dawley rats require an intact nitric oxide synthase system for compensatory increases in renal regulatory T cells.

We have previously shown that hypertensive female rats have more regulatory T cells (Tregs), which contribute more to blood pressure (BP) control in female versus male rats. Based on known protective properties of Tregs, the goal of the present study was to investigate the mechanisms by which female rats maintain Tregs. The present study was designed to ) compare the impact of three hypertension models on the percentage of renal Tregs and ) test the hypothesis that nitric oxide synthase (NOS) inhibition prevents increases in renal Tregs and exacerbates renal damage in female Sprague-Dawley rats.

Size of Initial Bone Bruise Predicts Future Lateral Chondral Degeneration in ACL Injuries: A Radiographic Analysis.

Background: Bone marrow contusions are common after an acute anterior cruciate ligament (ACL) injury. It is unknown whether the severity of this initial bruise can predict the potential of developing chondral changes even after ACL reconstructive surgery (ACLR).

Purpose: To investigate whether the initial bone bruise area could be predictive of progressive chondral defects.

Greater T Regulatory Cells in Females Attenuate DOCA-Salt-Induced Increases in Blood Pressure Versus Males.

Hypertension is the most common risk factor for cardiovascular disease, causing over 18 million deaths a year. Although the mechanisms controlling blood pressure (BP) in either sex remain largely unknown, T cells play a critical role in the development of hypertension. Further evidence supports a role for the immune system in contributing to sex differences in hypertension.

Necrosis Contributes to the Development of Hypertension in Male, but Not Female, Spontaneously Hypertensive Rats.

Necrosis is a pathological form of cell death that induces an inflammatory response, and immune cell activation contributes to the development and maintenance of hypertension. Necrosis was measured in kidney, spleen, and aorta of 12- to 13-week-old male and female SHRs (spontaneously hypertensive rats); male SHRs had greater renal necrotic cell death than female SHRs. Because male SHRs have a higher blood pressure (BP) and a more proinflammatory T-cell profile than female SHRs, the current studies tested the hypothesis that greater necrotic cell death in male SHRs exacerbates increases in BP and contributes to the proinflammatory T-cell profile.

Patient-Centered and Specialty-Specific Case Work-Up: An Effective Method for Teaching Appropriateness of Imaging to Medical Students.

Rationale And Objectives: Our institution has developed a mini-course program within the diagnostic radiology elective curriculum that promotes active learning, using patient cases specifically tailored to students' future specialties. The purpose of this study is to evaluate the effectiveness of this mini-course on medical student knowledge of imaging appropriateness and attitude toward radiologist consultation.

Materials And Methods: During each month-long radiology elective course, students were divided into teams of up to four students based on their specialty interest and assigned recent patient cases with imaging findings relevant to their specialties.

Publisher Correction: m6A modification controls the innate immune response to infection by targeting type I interferons.

In the version of this article initially published, the penultimate sentence of the abstract included a typographical error ('cxgenes'). The correct word is 'genes'. The error has been corrected in the HTML and PDF version of the article.

Unusual Focal Muscle FDG Activity Related to Altered Biomechanics.

A 20 year old man suffered severe right knee pain, especially when his right foot touched ground. The MRI findings suggested periosteal osteosarcoma, which led to a staging FDG PET/CT. The images showed not only a hypermetabolic right knee lesion but also focally elevated activity in select muscles, which was attributed to altered biomechanics.