Persistence of Contact Lens-Induced Corneal Parainflammation Following Lens Removal.

Purpose: Contact lens wear induces corneal parainflammation involving increased immune cell numbers after 24 hours' (CD11c+, Lyz2+, γδ-T cells) and six days' (Ly6G+ cells) wear. We investigated the time course of onset and resolution of these responses.

Methods: LysMcre or C57BL/6J mice were fitted with a contact lens (four to 48 hours).

Rapid surveillance of New York City healthcare center egress behaviors during the 2020 COVID-19 lockdown.

This rapid response surveillance project was funded by the National Science Foundation (NSF) to collect "perishable" data on egress behaviors and neighborhood conditions surrounding healthcare centers (HCCs) in New York City (NYC) during the initial NYC COVID-19 PAUSE ordinance from March 22nd to May 19th, 2020. Anonymized data on NYC HCC egress behaviors were collected by observational field workers using phone-based mapping applications. Each egress trip record includes the day of week, time of day, destination category type, along with an array of behavioral outcome categories, ambient weather conditions and socio-economic factors.

Immunogenicity of Cemiplimab: Low Incidence of Antidrug Antibodies and Cut-Point Suitability Across Tumor Types.

The immunogenicity of cemiplimab, a fully human immunoglobulin G4 monoclonal antibody directed against programmed cell death 1, was assessed in patients across multiple tumor types. The development of antidrug antibodies (ADAs) against cemiplimab was monitored using a validated bridging immunoassay. To identify ADA-positive samples in the assay, statistically determined cut points were established by analyzing baseline clinical study samples from a mixed population of different tumor types, and this validation cut point was used to assess immunogenicity in all subsequent studies.

Contact lens-induced corneal parainflammation involving Ly6G+ cell infiltration requires IL-17A and γδ T cells.

Purpose: Previously, using a murine model, we reported that contact lens (CL) wear induced corneal parainflammation involving CD11c+ cells after 24 h and Ly6G+ cells (neutrophils) after 5-6 days. Here, we investigated the role of IL-17 and γδ T cells in the CL-induced neutrophil response.

Methods: CL-wearing C57BL/6 wild-type (WT) mice were compared to lens-wearing IL-17A/F single or double gene knock-out mice, or mice treated with UC7-13D5 monoclonal antibody to functionally deplete γδ T cells.

Relations Between Adolescent Sensation Seeking and Risky Sexual Behaviors Across Sex, Race, and Age: A Meta-Analysis.

Sensation seeking (SS)-the seeking of novel and intense sensations or experiences and the willingness to take risks for the sake of such experiences-has been shown to be related to various risky sexual behaviors (RSBs) in areas such as multiple sexual partners, condom use, and sexual initiation. The aims of the current meta-analysis were to examine (1) how SS relates to specific RSBs in adolescents and (2) how the overall relationship between SS and RSB differs across sex, race, and age. Overall, a total of 40 studies met the inclusion criteria for our meta-analysis examining the relationship between SS and RSB, contributing 102 effect sizes.

Ultra-deep sequencing validates safety of CRISPR/Cas9 genome editing in human hematopoietic stem and progenitor cells.

As CRISPR-based therapies enter the clinic, evaluation of safety remains a critical and active area of study. Here, we employ a clinical next generation sequencing (NGS) workflow to achieve high sequencing depth and detect ultra-low frequency variants across exons of genes associated with cancer, all exons, and genome wide. In three separate primary human hematopoietic stem and progenitor cell (HSPC) donors assessed in technical triplicates, we electroporated high-fidelity Cas9 protein targeted to three loci (AAVS1, HBB, and ZFPM2) and harvested genomic DNA at days 4 and 10.

Topical antibiotics reduce CD11c+ cell numbers in the healthy murine cornea and modulate their response to contact lens wear.

Previously we reported contact lens-induced CD11c+ cell responses in healthy mouse corneas, a phenomenon that also occurs in humans. To test involvement of ocular-associated bacteria, the impact of topical antibiotics on corneal CD11c+ cell populations during 24 h of lens wear was examined. Corneas were treated with gentamicin and ofloxacin (0.

Bioanalytical Challenges due to Prior Checkpoint Inhibitor Exposure: Interference and Mitigation in Drug Concentration and Immunogenicity Assays.

Monoclonal antibodies (mAbs) are a leading class of biotherapeutics. In oncology, patients often fail on early lines of biologic therapy to a specific target. Some patients may then enroll in a new clinical trial with a mAb specific for the same target.

Toward best practice in cancer mutation detection with whole-genome and whole-exome sequencing.

Clinical applications of precision oncology require accurate tests that can distinguish true cancer-specific mutations from errors introduced at each step of next-generation sequencing (NGS). To date, no bulk sequencing study has addressed the effects of cross-site reproducibility, nor the biological, technical and computational factors that influence variant identification. Here we report a systematic interrogation of somatic mutations in paired tumor-normal cell lines to identify factors affecting detection reproducibility and accuracy at six different centers.

SENTI-101, a Preparation of Mesenchymal Stromal Cells Engineered to Express IL12 and IL21, Induces Localized and Durable Antitumor Immunity in Preclinical Models of Peritoneal Solid Tumors.

Advanced peritoneal carcinomatosis including high-grade ovarian cancer has poor prognoses and a poor response rate to current checkpoint inhibitor immunotherapies; thus, there is an unmet need for effective therapeutics that would provide benefit to these patients. Here we present the preclinical development of SENTI-101, a cell preparation of bone marrow-derived mesenchymal stromal (also known as stem) cells (MSC), which are engineered to express two potent immune-modulatory cytokines, IL12 and IL21. Intraperitoneal administration of SENTI-101 results in selective tumor-homing and localized and sustained cytokine production in murine models of peritoneal cancer.

Case of hypoactive delirium precipitated by thiamine deficiency.

Thiamine is an essential cofactor in the process of nucleic acid synthesis. Neuronal tissues are especially sensitive to thiamine deficiency, manifesting as Wernicke's encephalopathy (WE). The typical triad of WE, encephalopathy, oculomotor dysfunction and gait ataxia, is only present in less than one-third of the cases.

Policy and Pandemic: The Changing Practice of Nephrology During the Coronavirus Disease-2019 Outbreak.

The coronavirus (coronavirus disease-2019) pandemic has changed care delivery for patients with end-stage kidney disease. We explore the US healthcare system as it pertains to dialysis care, including existing policies, modifications implemented in response to the coronavirus disease-2019 crisis, and possible next steps for policy makers and nephrologists. This includes policies related to resource management, use of telemedicine, prioritization of dialysis access procedures, expansion of home dialysis modalities, administrative duties, and quality assessment.

Skeletal tissue regulation by catalase overexpression in mitochondria.

Accumulation of oxidative damage from excess reactive oxygen species (ROS) may contribute to skeletal aging and mediate adverse responses to physiological challenges. Wild-type (WT) mice and transgenic mice (male, 16 wk of age) with human catalase targeted to the mitochondria (mCAT) were analyzed for skeletal responses to the remodeling stimuli of combined hind-limb unloading and exposure to ionizing radiation (Cs, 2 Gy). Treatment for 2 wk caused lipid peroxidation in the bones WT but not mCAT mice, showing that transgene expression mitigated oxidative stress.

COVID-19 Extrapulmonary illness - The Impact of COVID-19 on Nephrology care.

Coronavirus disease-2019 (COVID-19) has caused a pandemic that has affected millions of people worldwide. COVID-19 is caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and is spread by close contact and by respiratory droplets. It has also impacted different aspects of caring for people with kidney disease, including those with acute kidney injury (AKI), chronic kidney disease (CKD), those requiring kidney replacement therapy (KRT), and those with a kidney transplant.

A luminescence-based assay for monitoring changes in alpha-synuclein aggregation in living cells.

Parkinson's disease is characterized by the accumulation of protein aggregates in the brain, termed Lewy bodies. Lewy bodies are predominantly composed of α-synuclein and mutations that increase the aggregation potential of α-synuclein have been associated with early on-set disease. Assays capable of reporting on the solubility of α-synuclein in living cells could provide a means to interrogate the influence of mutations on aggregation as well as identify small molecules capable of modulating the aggregation of α-synuclein.

Correlating computed tomography pulmonary angiography signs of right ventricular strain in pulmonary embolisms to clinical outcomes.

Introduction: Right ventricular strain (RVS) in pulmonary embolism (PE) can be used to stratify risk and direct intervention. The clinical significance of computed tomography pulmonary angiogram (CTPA)-derived radiologic signs of RVS, however, remains incompletely characterized. We retrospectively analyzed a cohort of persons with acute PE to determine which, if any, findings of RVS on CTPA correlate with clinical outcomes.

Classification accuracy of the rare symptoms and symptom combinations scales of the Structured Inventory of Malingered Symptomatology in three archival samples.

Objective: The Structured Inventory of Malingered Symptomatology (SIMS; Widows & Smith, 2005) is a 75-item self-report measure intended to screen for potentially feigned symptoms of mental illness and/or cognitive impairment. We investigated the classification accuracy of 2 new detection scales (Rare Symptoms [RS] and Symptom Combinations [SC]) developed by Rogers, Robinson, and Gillard (2014) that appeared useful in identifying simulated mental disorder in their derivation sample of psychiatric inpatients.

Hypothesis: We hypothesized that the rates of classification accuracy Rogers et al.

HIV and pericardial fat are associated with abnormal cardiac structure and function among Ugandans.

Objectives: To examine the relationship between pericardial fat (PCF) and cardiac structure and function among HIV-infected patients in the sub-Saharan African country of Uganda. People living with HIV (PLHIV) have altered fat distribution and an elevated risk for heart failure. Whether altered quantity and radiodensity of fat surrounding the heart relates to cardiac dysfunction in this population is unknown.

Temporal stability and dynamic convergence of the Personality Assessment Screener in a prison sample.

Although the Personality Assessment Screener (PAS; Morey, 1997) has garnered substantial research interest, the measure's temporal stability and sensitivity to change have remained largely uninvestigated. The present study employs a dynamic approach to investigating the convergent and discriminant validity of the PAS by examining relationships between temporal changes on the PAS and changes on external criterion measures, thereby exploring the extent to which changes on the PAS offer meaningful information regarding changes in psychological functioning. Data were obtained from a public dataset funded by the United States Department of Justice in which male inmates were administered various psychological measures at 5 time points spanning the course of a year.

Incarcerated diaphragmatic hernia following Heimlich maneuver.

The Heimlich maneuver or abdominal thrust is a recognized effective therapy for foreign-body airway obstruction. Serious complications, however, have been described. We present a case of an incarcerated diaphragmatic hernia secondary to Heimlich maneuver.

Chemotherapy can induce weight normalization of morbidly obese mice despite undiminished ingestion of high fat diet.

Morbidly obese patients who accomplish substantial weight loss often display a long-term decline in their resting metabolism, causing even relatively restrained caloric intake to trigger a relapse to the obese state. Paradoxically, we observed that morbidly obese mice receiving chemotherapy for cancer experienced spontaneous weight reduction despite unabated ingestion of their high fat diet (HFD). This response to chemotherapy could also be achieved in morbidly obese mice without cancer.

Temporal Analysis of PP2A Phosphatase Activity During Insulin Stimulation Using a Direct Activity Probe.

Protein serine/threonine phosphatases (PSPs) are ubiquitously expressed in mammalian cells. In particular, PP2A accounts for up to 1% of the total protein within cells. Despite clear evidence for the role of PP2A in cellular signaling, there is a lack of information concerning the magnitude and temporal dynamics of PP2A catalytic activity during insulin stimulation.