A model of lymphocryptovirus-associated post-transplant lymphoproliferative disorder in immunosuppressed Mauritian cynomolgus macaques.

Immunocompromised individuals are at risk for developing lymphocryptovirus-associated lymphoproliferative diseases, such as Epstein Barr virus (EBV)-associated B cell lymphomas and post-transplant lymphoproliferative disorder (PTLD). We previously reported development of cynomolgus lymphocryptovirus (CyLCV)-associated PTLD in Mauritian cynomolgus macaques (MCMs) undergoing hematopoietic stem cell transplantation (HSCT), which mirrored EBV-PTLD in transplant patients. Here, we sought to develop a MCM model of lymphocryptovirus-associated lymphoproliferative disease in immunosuppressed MCMs without HSCT.

Evaluation of Nutrition and Performance Parameters in Division 1 Collegiate Athletes.

Background: Testing and evaluating athletes is necessary and should include performance, body composition, and nutrition. The purpose of this study was to report assessments of dietary intake, V˙O, and body composition in D1 collegiate athletes and examine relationships between these assessments.

Methods: Dietary intake was assessed with 3-day recalls and compared to recommendations, and body composition was assessed via bioelectrical impedance analysis (BIA) ( = 48).

Allogeneic immunity clears latent virus following allogeneic stem cell transplantation in SIV-infected ART-suppressed macaques.

Allogeneic hematopoietic stem cell transplantation (alloHSCT) from donors lacking C-C chemokine receptor 5 (CCR5) can cure HIV, yet mechanisms remain speculative. To define how alloHSCT mediates HIV cure, we performed MHC-matched alloHSCT in SIV, anti-retroviral therapy (ART)-suppressed Mauritian cynomolgus macaques (MCMs) and demonstrated that allogeneic immunity was the major driver of reservoir clearance, occurring first in peripheral blood, then peripheral lymph nodes, and finally in mesenteric lymph nodes draining the gastrointestinal tract. While allogeneic immunity could extirpate the latent viral reservoir and did so in two alloHSCT-recipient MCMs that remained aviremic >2.

Terumo spectra optia leukapheresis of cynomolgus macaques for hematopoietic stem cell and T cell collection.

Macaques are physiologically relevant animal models of human immunology and infectious disease that have provided key insights and advanced clinical treatment in transplantation, vaccinology, and HIV/AIDS. However, the small size of macaques is a stumbling block for studies requiring large numbers of cells, such as hematopoietic stem cells (HSCs) for transplantation, antigen-specific lymphocytes for in-depth immunological analysis, and latently-infected CD4+ T-cells for HIV cure studies. Here, we provide a detailed protocol for collection of large numbers of HSCs and T-cells from cynomolgus macaques as small as 3 kg using the Terumo Spectra Optia apheresis system, yielding an average of 5.

Viral opportunistic infections in Mauritian cynomolgus macaques undergoing allogeneic stem cell transplantation mirror human transplant infectious disease complications.

Allogeneic hematopoietic stem cell transplantation (HSCT) and xenotransplantation are accompanied by viral reactivations and virus-associated complications resulting from immune deficiency. Here, in a Mauritian cynomolgus macaque model of fully MHC-matched allogeneic HSCT, we report reactivations of cynomolgus polyomavirus, lymphocryptovirus, and cytomegalovirus, macaque viruses analogous to HSCT-associated human counterparts BK virus, Epstein-Barr virus, and human cytomegalovirus. Viral replication in recipient macaques resulted in characteristic disease manifestations observed in HSCT patients, such as polyomavirus-associated hemorrhagic cystitis and tubulointerstitial nephritis or lymphocryptovirus-associated post-transplant lymphoproliferative disorder.

To What Degree Are the 13 Entrustable Professional Activities Already Incorporated Into Physicians' Performance Schemas for Medical Students?

There is an abundance of literature on Entrustable Professional Activities (EPAs) in theory, but there are few studies on the EPAs in practice for undergraduate clinical education. In addition, little is known about the degree to which the EPAs are or are not aligned with physician assessors' performance schemas of the clerkship student. Investigating the degree to which physician assessors' performance schemas are already aligned with the activities described by the EPAs is critical for effective workplace assessment design.

Hepatocytic expression of human sodium-taurocholate cotransporting polypeptide enables hepatitis B virus infection of macaques.

Hepatitis B virus (HBV) is a major global health concern, and the development of curative therapeutics is urgently needed. Such efforts are impeded by the lack of a physiologically relevant, pre-clinical animal model of HBV infection. Here, we report that expression of the HBV entry receptor, human sodium-taurocholate cotransporting polypeptide (hNTCP), on macaque primary hepatocytes facilitates HBV infection in vitro, where all replicative intermediates including covalently closed circular DNA (cccDNA) are present.

Allogeneic stem cell transplantation in fully MHC-matched Mauritian cynomolgus macaques recapitulates diverse human clinical outcomes.

Allogeneic hematopoietic stem cell transplantation (HSCT) is a critically important therapy for hematological malignancies, inborn errors of metabolism, and immunodeficiency disorders, yet complications such as graft-vs.-host disease (GvHD) limit survival. Development of anti-GvHD therapies that do not adversely affect susceptibility to infection or graft-vs.

Spontaneous baroreflex measures are unable to detect age-related impairments in cardiac baroreflex function during dynamic exercise in humans.

The dynamic relationship between 'spontaneous' fluctuations in arterial blood pressure (BP) and heart rate (HR) is increasingly being used to provide an estimate of resting cardiac baroreflex sensitivity. Given the ease of use and clinical utility, spontaneous methods are now also being used to examine cardiac baroreflex sensitivity in distinct subject groups during various laboratory stressors and tasks encountered during daily life, such as physical activity. However, the utility of such spontaneous measures to estimate cardiac baroreflex function during exercise remains unclear, particularly when comparing groups.

Quantitative contrast enhanced magnetic resonance imaging for the evaluation of peripheral arterial disease: a comparative study versus standard digital angiography.

Objective: The purpose of this study is to evaluate the accuracy of semiautomated analysis of contrast enhanced magnetic resonance angiography (MRA) in patients who have undergone standard angiographic evaluation for peripheral vascular disease (PVD).

Background: Magnetic resonance angiography is an important tool for evaluating PVD. Although this technique is both safe and noninvasive, the accuracy and reproducibility of quantitative measurements of disease severity using MRA in the clinical setting have not been fully investigated.

Testicular microlithiasis and its relation to testicular cancer on ultrasound findings of symptomatic men.

Purpose: We reviewed testicular microlithiasis (TM) on scrotal ultrasound in relation to the incidence of testicular neoplasm in males 17 to 45 years old with scrotal symptoms.

Materials And Methods: We reviewed the radiographic and medical records of males age 4 weeks to 84 years with symptomatic complaint of scrotal pain or swelling between September 1998 and April 2002. Subgroup analysis was performed on 160 male patients between 17 and 45 years old since they were at higher risk for testicular carcinoma.

Microchip isoelectric focusing using a miniature scanning detection system.

A miniature scanning fluorescent detector has been developed for plastic microchannel isoelectric focusing (mIEF) analysis. The detector, comprised of a lamp and photomultiplier tube (PMT) on a moving stage, measured the real-time distribution of fluorescently labeled peptides subjected to gel-free mIEF. During the run, the effective length of the 6-cm channel was scanned every 9 s.

Lysing bacterial spores by sonication through a flexible interface in a microfluidic system.

Cell disruptions using ultrasonic energy transmitted through a flexible interface into a liquid region has limitations because the motion of the vibrating tip is not completely transferred into the liquid. To ensure that some degree of contact will be maintained between the ultrasonic horn tip and the flexible interface, the liquid must be pressurized. The pressure conditions that yield consistent coupling between the ultrasonic horn tip and the liquid region were explored in this study by using an analytical model of the system and test fixture experiments.

A battery-powered notebook thermal cycler for rapid multiplex real-time PCR analysis.

A compact, real-time PCR instrument was developed for rapid, multiplex analysis of nucleic acids in an inexpensive, portable format. The instrument consists of a notebook computer, two reaction modules with integrated optics for four-color fluorescence detection, batteries, and a battery-charging system. The instrument weighs 3.

A microfluidic cartridge to prepare spores for PCR analysis.

A prototype cartridge system is described that rapidly disrupts Bacillus spores by sonication, adds PCR reagent to the disrupted spores, and dispenses the mixture into a PCR tube. The total time to automatically process the spores in the cartridge and then detect the spore DNA by real-time PCR was 20 min.

A minisonicator to rapidly disrupt bacterial spores for DNA analysis.

Concerns about the use of anthrax spores as a weapon of mass destruction have motivated the development of portable instruments capable of detecting and monitoring a suspected release of the agent. Optimal detection of bacterial spores by PCR requires that the spores be disrupted to make the endogenous DNA available for amplification. The entire process of spore lysis, PCR, and detection can take several hours using conventional methods and instruments.

Rapid, automated nucleic acid probe assays using silicon microstructures for nucleic acid concentration.

A system for rapid point-of-use nucleic acid (NA) analysis based on PCR techniques is described. The extraction and concentration of DNA from test samples has been accomplished utilizing silicon fluidic microchips with high surface-area-to-volume ratios. Short (500 bp) and medium size (48,000 bp) DNA have been captured, washed, and eluted using the silicon dioxide surfaces of these chips.

Real-time microchip PCR for detecting single-base differences in viral and human DNA.

This report describes real-time 5' nuclease PCR assays to rapidly distinguish single-base polymorphism using a battery-powered miniature analytical thermal cycling instrument (MATCI). Orthopoxviruses and the human complement component C6 gene served as targets to demonstrate the feasibility of using the MATCI for diagnosis of infectious diseases and genetic disorders. In the Orthopoxvirus assay, consensus Orthopoxvirus PCR primers were designed to amplify 266-281 base-pair (bp) segments of the hemagglutinin (HA) gene in camelpox, cowpox, monkeypox, and vaccinia viruses.