Generation of Rhesus Macaque Embryos with Expanded CAG Trinucleotide Repeats in the Gene.

Huntington's disease (HD) arises from expanded CAG repeats in exon 1 of the () gene. The resultant misfolded HTT protein accumulates within neuronal cells, negatively impacting their function and survival. Ultimately, HTT accumulation results in cell death, causing the development of HD.

Temporal Alterations in Cerebrovascular Glycocalyx and Cerebral Blood Flow after Exposure to a High-Intensity Blast in Rats.

The glycocalyx is a proteoglycan-glycoprotein structure lining the luminal surface of the vascular endothelium and is susceptible to damage due to blast overpressure (BOP) exposure. The glycocalyx is essential in maintaining the structural and functional integrity of the vasculature and regulation of cerebral blood flow (CBF). Assessment of alterations in the density of the glycocalyx; its components (heparan sulphate proteoglycan (HSPG/syndecan-2), heparan sulphate (HS), and chondroitin sulphate (CS)); CBF; and the effect of hypercapnia on CBF was conducted at 2-3 h, 1, 3, 14, and 28 days after a high-intensity (18.

Exposure to Low-Intensity Blast Increases Clearance of Brain Amyloid Beta.

The long-term effects of exposure to blast overpressure are an important health concern in military personnel. Increase in amyloid beta (Aβ) has been documented after non-blast traumatic brain injury (TBI) and may contribute to neuropathology and an increased risk for Alzheimer's disease. We have shown that Aβ levels decrease following exposure to a low-intensity blast overpressure event.

Metabotropic Glutamate Receptor 2 Expression Is Chronically Elevated in Male Rats With Post-Traumatic Stress Disorder Related Behavioral Traits Following Repetitive Low-Level Blast Exposure.

Many military veterans who experienced blast-related traumatic brain injuries in the conflicts in Iraq and Afghanistan currently suffer from chronic cognitive and mental health problems that include depression and post-traumatic stress disorder (PTSD). Male rats exposed to repetitive low-level blast develop cognitive and PTSD-related behavioral traits that are present for more than 1 year after exposure. We previously reported that a group II metabotropic receptor (mGluR2/3) antagonist reversed blast-induced behavioral traits.

(2R,6R)-Hydroxynorketamine Treatment of Rats Exposed to Repetitive Low-Level Blast Injury.

Many military veterans who experienced blast-related traumatic brain injuries (TBIs) in the conflicts in Iraq and Afghanistan suffer from chronic cognitive and mental health problems, including post-traumatic stress disorder (PTSD). Male rats subjected to repetitive low-level blast exposure develop chronic cognitive and PTSD-related traits that develop in a delayed manner. Ketamine has received attention as a treatment for refractory depression and PTSD.

Progressive Transcriptional Changes in the Amygdala Implicate Neuroinflammation in the Effects of Repetitive Low-Level Blast Exposure in Male Rats.

Chronic mental health problems are common among military veterans who sustained blast-related traumatic brain injuries. The reasons for this association remain unexplained. Male rats exposed to repetitive low-level blast overpressure (BOP) exposures exhibit chronic cognitive and post-traumatic stress disorder (PTSD)-related traits that develop in a delayed fashion.

CRISPR/Cas9 editing of the MYO7A gene in rhesus macaque embryos to generate a primate model of Usher syndrome type 1B.

Mutations in the MYO7A gene lead to Usher syndrome type 1B (USH1B), a disease characterized by congenital deafness, vision loss, and balance impairment. To create a nonhuman primate (NHP) USH1B model, CRISPR/Cas9 was used to disrupt MYO7A in rhesus macaque zygotes. The targeting efficiency of Cas9 mRNA and hybridized crRNA-tracrRNA (hyb-gRNA) was compared to Cas9 nuclease (Nuc) protein and synthetic single guide (sg)RNAs.

Blastocyst development after fertilization with in vitro spermatids derived from nonhuman primate embryonic stem cells.

Objective: To demonstrate that functional spermatids can be derived in vitro from nonhuman primate pluripotent stem cells.

Design: Green fluorescent protein-labeled, rhesus macaque nonhuman primate embryonic stem cells (nhpESCs) were differentiated into advanced male germ cell lineages using a modified serum-free spermatogonial stem cell culture medium. In vitro-derived round spermatid-like cells (rSLCs) from differentiated nhpESCs were assessed for their ability to fertilize rhesus oocytes by intracytoplasmic sperm(atid) injection.

Repetitive Low-Level Blast Exposure Improves Behavioral Deficits and Chronically Lowers Aβ42 in an Alzheimer Disease Transgenic Mouse Model.

Public awareness of traumatic brain injury (TBI) in the military increased recently because of the conflicts in Iraq and Afghanistan where blast injury was the most common mechanism of injury. Besides overt injuries, concerns also exist over the potential adverse consequences of subclinical blast exposures, which are common for many service members. A TBI is a risk factor for the later development of neurodegenerative diseases, including Alzheimer disease (AD)-like disorders.

Failure to Medically Optimize Before Total Hip Arthroplasty: Which Modifiable Risk Factor Is the Most Dangerous?

Background: There is mounting evidence that smoking, abnormal body mass index (BMI), uncontrolled diabetes, and poor nutritional status are associated with complications after total hip arthroplasty (THA). The goal of the present study was to evaluate the consequences of failure to medically optimize Medicare-eligible patients with respect to these key modifiable health targets by assessing complications in the early postoperative period after THA.

Methods: The National Surgical Quality Improvement Program database was queried for all primary THAs performed in 2018.

Failure to Optimize Before Total Knee Arthroplasty: Which Modifiable Risk Factor is the Most Dangerous?

Background: Complications after total knee arthroplasty (TKA) are devastating for patients, and surgeons are held accountable in alternative payment models. Optimization of modifiable risk factors has become a mainstay in the preoperative period. We sought to evaluate the consequence of failure to optimize key risk factors in a modern cohort of patients who underwent TKA.

Blast-induced temporal alterations in blood-brain barrier properties in a rodent model.

The consequences of blast-induced traumatic brain injury (bTBI) on the blood-brain barrier (BBB) and components of the neurovascular unit are an area of active research. In this study we assessed the time course of BBB integrity in anesthetized rats exposed to a single blast overpressure of 130 kPa (18.9 PSI).

Development of a Blast Exposure Estimator from a Department of Defense-Wide Survey Study on Military Service Members.

Long-term, repeated exposure to low-intensity blast overpressure is a potential causal factor of lasting outcomes reminiscent of post-concussion syndrome. Wearable blast sensor engineers are exploring elements of blast that are associated with outcomes. Currently, however, there are no devices that can truly record all blasts experienced by an individual.

Pulmonary injury risk curves and behavioral changes from blast overpressure exposures of varying frequency and intensity in rats.

At present, there are no set guidelines establishing cumulative limits for blast exposure numbers and intensities in military personnel, in combat or training operations. The objective of the current study was to define lung injury, pathology, and associated behavioral changes from primary repeated blast lung injury under appropriate exposure conditions and combinations (i.e.

Blast exposure results in tau and neurofilament light chain changes in peripheral blood.

Objectives: To evaluate how blast exposure impacts peripheral biomarkers.

Unlabelled: in military personnel enrolled in 10-day blast training.

Methods: On day 7, 21 military personnel experienced peak overpressure <2 pounds per square inch (psi); while 29 military personnel experienced peak overpressure ≥5 psi.

Reasons for Failure of Primary Total Hip Arthroplasty Performed Through a Direct Anterior Approach.

The direct anterior approach (DAA) for total hip arthroplasty (THA) is a technique popular among some arthroplasty surgeons. There is currently a paucity of data regarding reasons for failure of THA using the DAA. The authors conducted a retrospective review of prospectively collected data on 56 patients who underwent revision THA at their institution after failing primary THA that was performed through a DAA either at their institution (n=8) or elsewhere (n=48) from January 1, 2010, to June 1, 2017.

Neuroendocrine function and associated mental health outcomes following mild traumatic brain injury in OEF-deployed service members.

Mild traumatic brain injury (mTBI) has been linked to mental health disorders (MHDs) and pituitary function alterations. Due to the complex relationship of mTBI, the neuroendocrine system, and MHDs, we propose that neuroendocrine dysfunction (NED) may play a role in negative long-term health outcomes. The goal of this study was to determine if blast-concussed service members (SMs) have a stronger likelihood of developing NED.

Primary reverse shoulder arthroplasty: how did medialized and glenoid-based lateralized style prostheses compare at 10 years?

Background: The purpose of this study was to compare long-term outcomes, complications, and reoperation rates of primary reverse total shoulder arthroplasty (RTSA) performed at a single institution using 2 implant designs: a Grammont medialized prosthesis (medialized [M] group) and a Frankle glenoid-based lateralized prosthesis (glenoid-lateralized [GL] group).

Methods: Between 2004 and 2008, 100 consecutive single-institution primary RTSAs were performed by reconstructive shoulder surgeons who were not design consultants, with the aim of obtaining 10-year follow-up: 56 in the M group and 44 in the GL group. Patients were followed up until death, until revision surgery, or for a minimum of 10 years.

Primary Total Hip Arthroplasty in Patients 20 Years Old and Younger.

Background: Historically, total hip arthroplasty (THA) performed in patients ≤20 years old has been associated with poor survivorship because of bearing-surface wear with conventional polyethylene, acetabular loosening with cemented sockets, and liner fracture in ceramic-on-ceramic (CoC) THA. For this population, there is a paucity of data regarding outcomes of THAs performed with use of modern implants and bearing surfaces. The purpose of the present study was to examine the mid- to long-term outcomes of modern THA in patients ≤20 years old.

Incidence and risk factors for hardware removal following periacetabular osteotomy and its association with clinical outcomes.

Background: Periacetabular osteotomy (PAO) can be used for joint preservation in symptomatic developmental dysplasia of the hip (DDH) and femoroacetabular impingement (FAI). 1 of the most common procedures following PAO is hardware removal. The aims of this study were to determine the rate of hardware removal and patient characteristics associated with this outcome following PAO.

Assessing a Blast-Related Biomarker in an Operational Community: Glial Fibrillary Acidic Protein in Experienced Breachers.

Mild traumatic brain injury (mTBI) is a risk for military personnel due to blast overpressures, which may result from a variety of sources, including artillery and improvised explosive devices. Much research has gone into the search for a biomarker to identify patients with a TBI. The FDA recently identified two proteins, glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase-L1 (UCH-L1), as biomarkers to evaluate suspected brain injury.

Shoulder arthroplasty in patients with cerebral palsy: a matched cohort study to patients with osteoarthritis.

Background: Patients with cerebral palsy (CP) often experience shoulder impairment via spasticity, muscle contractures, and joint instability. Currently, few studies investigate shoulder arthroplasty (SA) in patients with CP. This study reviewed the outcomes of both anatomic total shoulder arthroplasty (TSA) and reverse total shoulder arthroplasty (RSA) in patients with CP.

Repeated Low-Level Blast Overpressure Leads to Endovascular Disruption and Alterations in TDP-43 and Piezo2 in a Rat Model of Blast TBI.

Recent evidence linking repeated low-level blast overpressure exposure in operational and training environments with neurocognitive decline, neuroinflammation, and neurodegenerative processes has prompted concern over the cumulative deleterious effects of repeated blast exposure on the brains of service members. Repetitive exposure to low-level primary blast may cause symptoms (subclinical) similar to those seen in mild traumatic brain injury (TBI), with progressive vascular and cellular changes, which could contribute to neurodegeneration. At the cellular level, the mechanical force associated with blast exposure can cause cellular perturbations in the brain, leading to secondary injury.

Shoulder arthroplasty in patients with immunosuppression following solid organ transplantation.

Background: The purpose was to determine the risk and outcomes of primary shoulder arthroplasties in patients with immunosuppression who had undergone solid organ transplantation.

Methods: Using a single institution's total joint registry, we reviewed 30 primary shoulder arthroplasties in 25 post-transplantation patients, including 12 total shoulder arthroplasties, 10 hemiarthroplasties, and 8 reverse shoulder arthroplasties, between 1985 and 2012. Therapy and patient variables were recorded, including immunosuppressive therapy protocols, the date of preceding solid organ transplantation, and specific medications taken in the perioperative period.