Role of physicochemical properties in silica nanoparticle-mediated immunostimulation.

Immunostimulation caused by nanoparticles may be beneficial or adverse depending on their intended application. Activation of immune cells is beneficial for indications targeting the immune system for therapeutic purposes, such as tumor microenvironment reprogramming, immunotherapy, and vaccines. When it is unwanted, however, immunostimulation may lead to excessive inflammation, cytokine storm, and hypersensitivity reactions.

Aged mice exhibit faster acquisition of intravenous opioid self-administration with variable effects on intake.

Although opioid abuse is more prevalent in young individuals, opioid use, overdose, and use disorders continue to climb at a rapid rate among the elderly. Little is known about abuse potential in a healthy aged population, in part due to technical and logistical difficulties testing intravenous self-administration in aged rodents. The goal of this study was to address the critical gap in the literature regarding age-dependent differences in opioid (remifentanil and fentanyl) self-administration between old and young mice.

Gynecologic Cancer InterGroup CA125 response has a high negative predictive value for CHK1 inhibitor RECIST response in recurrent ovarian cancer.

We investigated the association of CA125 response with prognosis and RECIST response/progressive disease (PD) criteria in recurrent high grade serous ovarian cancer (HGSOC) patients treated with a cell cycle checkpoint kinase 1 inhibitor (CHK1i), prexasertib. 81 patients had measurable disease per RECISTv1.1, of which 72 and 70 were measurable by Gynecologic Cancer InterGroup (GCIG) CA125 response and PD criteria, respectively.

The CHK1 inhibitor prexasertib in BRCA wild-type platinum-resistant recurrent high-grade serous ovarian carcinoma: a phase 2 trial.

The multi-cohort phase 2 trial NCT02203513 was designed to evaluate the clinical activity of the CHK1 inhibitor (CHK1i) prexasertib in patients with breast or ovarian cancer. Here we report the activity of CHK1i in platinum-resistant high-grade serous ovarian carcinoma (HGSOC) with measurable and biopsiable disease (cohort 5), or without biopsiable disease (cohort 6). The primary endpoint was objective response rate (ORR).

Do Long-Segment Blocking Screws Increase the Stability of Intramedullary Nail Fixation in Proximal Tibia Fractures, Eliminating the "Bell-Clapper Effect?".

Objectives: To determine change in stiffness and horizontal translation of a geriatric extra-articular proximal tibia fracture model after intramedullary nailing with distal (long)-segment blocking screws versus proximal (short)-segment blocking screws.

Methods: Unstable extra-articular proximal tibia fractures (OTA/AO 41-A3) were created in 12 geriatric cadaveric tibias. Intramedullary nails were locked with a standard construct (4 proximal screws and 2 distal screws).

Multicolor flow cytometry-based immunophenotyping for preclinical characterization of nanotechnology-based formulations: an insight into structure activity relationship and nanoparticle biocompatibility profiles.

Introduction: Immunophenotyping, which is the identification of immune cell subsets based on antigen expression, is an integral technique used to determine changes of cell composition and activation in various disease states or as a response to different stimuli. As nanoparticles are increasingly utilized for diagnostic and therapeutic applications, it is important to develop methodology that allows for the evaluation of their immunological impact. Therefore, the development of techniques such as immunophenotyping are desirable.

Bacterial Genotype, Carrier Risk Factors, and an Antimicrobial Stewardship Approach Relevant To Methicillin-resistant Prevalence in a Population of Macaques Housed in a Research Facility.

Methicillin-resistant (MRSA) remains a significant problem for human and animal health and can negatively affect the health status of macaques and other nonhuman primates (NHP) in research colonies. However, few publications provide guidance on the prevalence, genotype, or risk factors for macaques with MRSA and even fewer on how to effectively respond to MRSA once identified in a population. After having a clinical case of MRSA in a rhesus macaque, we sought to determine the MRSA carrier prevalence, risk factors, and genotypes of MRSA in a population of research NHPs.

High- Versus Low-Energy Intertrochanteric Hip Fractures in Young Patients: Injury Characteristics and Factors Associated With Complications.

Objective: To compare fracture patterns and associated injuries for young patients with high- versus low-energy intertrochanteric hip fractures and to report on factors associated with complications after surgical fixation of high-energy fractures.

Design: Retrospective comparative study.

Setting: Academic Level 1 Trauma Center.

Outcomes After Acute Versus Staged Fixation of Complete Articular Tibial Plafond Fractures.

Objective: To determine the outcomes after acute versus staged fixation of complete articular tibial plafond fractures.

Design: Retrospective cohort study.

Setting: Single Level 1 Trauma center.

Does a Reduced Secondary Operation Rate Offset Higher Implant Charges when Utilizing Suture Button Fixation for Syndesmotic Injuries?

Objective: To determine whether a reduced secondary operation rate offsets higher implant charges when using suture button fixation for syndesmotic injuries.

Design: Retrospective cohort study.

Setting: Single, urban, Level 1 trauma center.

An In Vitro Assessment of Immunostimulatory Responses to Ten Model Innate Immune Response Modulating Impurities (IIRMIs) and Peptide Drug Product, Teriparatide.

Understanding, predicting, and minimizing the immunogenicity of peptide-based therapeutics are of paramount importance for ensuring the safety and efficacy of these products. The so-called anti-drug antibodies (ADA) may have various clinical consequences, including but not limited to the alteration in the product's distribution, biological activity, and clearance profiles. The immunogenicity of biotherapeutics can be influenced by immunostimulation triggered by the presence of innate immune response modulating impurities (IIRMIs) inadvertently introduced during the manufacturing process.

Academic Well-Being in Higher Education: A Cross-Country Analysis of the Relationship Between Perceptions of Instruction and Academic Well-Being.

The purpose of this research was to explore the relationship between university students' perceptions of the overall quality of instruction (PQI) they experienced since COVID-19 and their academic well-being. This relationship was examined in the context of a moderated moderation with students' household income and the cultural value of power distance (PD), which measures the extent to which less powerful members of an organization expect and accept that power is unequally distributed. Two countries with societally moderate levels of PD (South Africa and the United States) were assessed.

Sequential Analysis of Binding and Neutralizing Antibody in COVID-19 Convalescent Patients at 14 Months After SARS-CoV-2 Infection.

Durability of SARS-CoV-2 Spike antibody responses after infection provides information relevant to understanding protection against COVID-19 in humans. We report the results of a sequential evaluation of anti-SARS-CoV-2 antibodies in convalescent patients with a median follow-up of 14 months (range 12.4-15.

Control of SARS-CoV-2 infection after Spike DNA or Spike DNA+Protein co-immunization in rhesus macaques.

The speed of development, versatility and efficacy of mRNA-based vaccines have been amply demonstrated in the case of SARS-CoV-2. DNA vaccines represent an important alternative since they induce both humoral and cellular immune responses in animal models and in human trials. We tested the immunogenicity and protective efficacy of DNA-based vaccine regimens expressing different prefusion-stabilized Wuhan-Hu-1 SARS-CoV-2 Spike antigens upon intramuscular injection followed by electroporation in rhesus macaques.

SARS-CoV-2 antibody kinetics eight months from COVID-19 onset: Persistence of spike antibodies but loss of neutralizing antibodies in 24% of convalescent plasma donors.

Elucidating the characteristics of human immune response against SARS-CoV-2 is of high priority and relevant for determining vaccine strategies. We report the results of a follow-up evaluation of anti-SARS-CoV-2 antibodies in 148 convalescent plasma donors who participated in a phase 2 study at a median of 8.3 months (range 6.

Antibody-mediated depletion of viral reservoirs is limited in SIV-infected macaques treated early with antiretroviral therapy.

The effectiveness of virus-specific strategies, including administered HIV-specific mAbs, to target cells that persistently harbor latent, rebound-competent HIV genomes during combination antiretroviral therapy (cART) has been limited by inefficient induction of viral protein expression. To examine antibody-mediated viral reservoir targeting without a need for viral induction, we used an anti-CD4 mAb to deplete both infected and uninfected CD4+ T cells. Ten rhesus macaques infected with barcoded SIVmac239M received cART for 93 weeks starting 4 days after infection.

A Primary Care Answer to a Pandemic: Keeping a Population of Patients Safe at Home through Chronic Care Management and Remote Patient Monitoring.

The pandemic caused by the coronavirus disease of 2019 (COVID-19) challenged primary care providers (PCPs) to continue to deliver care for their patients, while also remaining financially stable. Most practices have experienced declining revenue due to fewer in-person patient visits. To help offset this and to continue to provide safe patient care, practices have shifted toward using remote options.