Open-source electrophilic fragment screening platform to identify chemical starting points for UCHL1 covalent inhibitors.

Target-based screening of covalent fragment libraries with mass spectrometry has emerged as a powerful strategy to identify chemical starting points for small molecule inhibitors or find new binding pockets on proteins of interest. These libraries span diverse chemical space with a modest number of compounds. Screening covalent fragments against purified protein targets reduces the demands on the mass spectrometer with respect to absolute throughput, detection limit, and dynamic range.

Staged Hip Arthroscopy and Periacetabular Osteotomy in Active Patients Aged 45 Years and Older Produce Comparable Improvements in Outcome Scores to Younger Patients.

Purpose: To determine staged hip arthroscopy and periacetabular osteotomy (PAO) mid-term outcomes in active patients aged 45 years and older compared with a younger group.

Methods: All patients aged 45 years and older who underwent staged arthroscopy and PAO between 2015 and 2021 were retrospectively analyzed and compared with a case-matched control group of younger patients. All patients underwent at least 6 months of nonoperative management prior to surgery.

Association Between Low-Dose Ketamine After Periacetabular and/or Femoral Osteotomy and Postoperative Opioid Requirements.

Background: Previous studies have sought to determine the effect of inpatient ketamine therapy on postoperative pain in a variety of surgical specialties.

Purpose: To determine the effects of postoperative ketamine analgesia after periacetabular osteotomy (PAO) and/or derotational femoral osteotomy (DFO) on opioid requirements, pain, and discharge time.

Study Design: Cohort study; Level of evidence, 3.

The Everted Acetabular Labrum: Outcomes of Surgical Management.

Background: An everted acetabular labrum (EL) is a pathologic variant in which the labrum is flipped to the capsular side of the acetabular rim. An iatrogenic EL is a known complication of a poorly executed labral repair, and a recent study described the native acetabular EL.

Purpose: To analyze surgical outcomes after advancement or reconstruction of an EL in a native hip.

Superior mesenteric artery mycotic aneurysm repaired with bifurcated saphenous vein graft.

A mycotic aneurysm of the superior mesenteric artery caused by was successfully treated with aneurysmectomy and reconstruction with a bifurcated saphenous vein graft. A 49-year-old man with a history of type 2 diabetes mellitus and a recent left transmetatarsal amputation for osteomyelitis presented to the emergency department with severe abdominal pain, an unexplained 30-lb weight loss, and wound dehiscence. Computed tomography angiography showed an aneurysm of the superior mesenteric artery and a splenic abscess.

During Postless Hip Arthroscopy, Male Patients, High Body Mass Index, Low Beighton Scores, and Limited Range of Motion Require High Traction Force.

Purpose: To determine the effects of demographic and anatomic factors on traction force required during postless hip arthroscopy.

Methods: A prospectively collected database was retrospectively analyzed on patients undergoing hip arthroscopy by the senior author, including patient sex, age, body mass index (BMI), Beighton Hypermobility Score, hip range of motion in clinic and under anesthesia, hip dysplasia, acetabular version, and femoral version. All patients underwent postless hip arthroscopy under general anesthesia.

Six Month Interim Outcomes from SECURE: A Single arm, Multicenter, Prospective, Clinical Study on a Novel Minimally Invasive Posterior Sacroiliac Fusion Device.

Introduction: Sacroiliac joint disease is a prominent diagnosis across the world. A novel fixation technique employing a posterior approach, single point, bone allograft transfixation has proven to be helpful anecdotally. The purpose of this is study is to investigate prospectively the safety and efficacy of this approach.

A mechanism linking perinatal 2,3,7,8 tetrachlorodibenzo-p-dioxin exposure to lower urinary tract dysfunction in adulthood.

Benign prostatic hyperplasia/lower urinary tract dysfunction (LUTD) affects nearly all men. Symptoms typically present in the fifth or sixth decade and progressively worsen over the remainder of life. Here, we identify a surprising origin of this disease that traces back to the intrauterine environment of the developing male, challenging paradigms about when this disease process begins.

Biosynthesis of d--l--Heptose in the Capsular Polysaccharides of .

is the leading cause of food poisoning in the United States and Europe. The exterior cell surface of is coated with a capsular polysaccharide (CPS) that is essential for the maintenance and integrity of the bacterial cell wall and evasion of the host immune response. The identity and sequences of the monosaccharide components of the CPS are quite variable and dependent on the specific strain of .

Genetic background but not prostatic epithelial beta-catenin influences susceptibility of male mice to testosterone and estradiol-induced urinary dysfunction.

Urinary voiding dysfunction in aging men can cause bothersome symptoms and irreparable tissue damage. Underlying mechanisms are not fully known. We previously demonstrated that subcutaneous, slow-release testosterone and estradiol implants (T+E2) drive a pattern of urinary voiding dysfunction in male mice that resembles that of aging men.

An immunohistochemical prostate cell identification key indicates that aging shifts procollagen 1A1 production from myofibroblasts to fibroblasts in dogs prone to prostate-related urinary dysfunction.

Background: The identity and spatial distribution of prostatic cell types has been determined in humans but not in dogs, even though aging- and prostate-related voiding disorders are common in both species and mechanistic factors, such as prostatic collagen accumulation, appear to be shared between species. In this publication we characterize the regional distribution of prostatic cell types in the young intact dog to enable comparisons with human and mice and we examine how the cellular source of procollagen 1A1 changes with age in intact male dogs.

Methods: A multichotomous decision tree involving sequential immunohistochemical stains was validated for use in dog and used to identify specific prostatic cell types and determine their distribution in the capsule, peripheral, periurethral and urethral regions of the young intact canine prostate.

Misannotations of the genes encoding sugar N-formyltransferases.

Tens of thousands of bacterial genome sequences are now known due to the development of rapid and inexpensive sequencing technologies. An important key in utilizing these vast amounts of data in a biologically meaningful way is to infer the function of the proteins encoded in the genomes via bioinformatics techniques. Whereas these approaches are absolutely critical to the annotation of gene function, there are still issues of misidentifications, which must be experimentally corrected.

Prostate epithelial-specific expression of activated PI3K drives stromal collagen production and accumulation.

We genetically engineered expression of an activated form of P110 alpha, the catalytic subunit of PI3K, in mouse prostate epithelium to create a mouse model of direct PI3K activation (Pbsn-cre4Prb;PI3K ). We hypothesized that direct activation would cause rapid neoplasia and cancer progression. Pbsn-cre4Prb;PI3K mice developed widespread prostate intraepithelial hyperplasia, but stromal invasion was limited and overall progression was slower than anticipated.

Treatment of human polyomavirus-7-associated rash and pruritus with topical cidofovir in a lung transplant patient: Case report and literature review.

Human polyomavirus-7-associated rash and pruritus (PVARP) is a chronic superficial viral skin infection, which primarily impacts immunocompromised individuals. We report on a case of PVARP in a lung transplant recipient. Our patient developed symptoms 13 years after being on his immunosuppressive regimen, with an insidious course of progressive gray lichenification with marked islands of sparing and quality of life-altering pruritus.

Eruptive sebaceous hyperplasia as a side effect of oral tacrolimus in a renal transplant recipient.

Sebaceous hyperplasia, a benign proliferation ofsebaceous glands, has been well documented in organ transplant recipients treated with cyclosporine. Sebaceous hyperplasia has not been strongly associated with any other immunosuppressive medications. We report a case of eruptive sebaceous hyperplasia in a renal transplant recipient with no previous exposure to cyclosporine that was recently started on tacrolimus, mycophenolate mofetil, and prednisone.

Two cases of alopecia areata treated with ruxolitinib: a discussion of ideal dosing and laboratory monitoring.

Background: Alopecia areata is a relatively common condition affecting patients seen in community dermatology clinics. A 2014 study implicated the JAK1/JAK2 inhibitor, ruxolitinib in short-term treatment of alopecia, however little information exists about the long-term use in otherwise healthy individuals in the community setting.

Methods: A patient with chronic alopecia areata and a patient with acute onset alopecia universalis were treated with oral ruxolitinib for over a year.

IL-9 regulates allergen-specific Th1 responses in allergic contact dermatitis.

The cytokine IL-9, derived primarily from T-helper 9 (Th9) lymphocytes, promotes expansion of the Th2 subset and is implicated in the mechanisms of allergic asthma. We hypothesize that IL-9 also has a role in human allergic contact dermatitis (ACD). To investigate this hypothesis, skin biopsy specimens of positive patch-test sites from non-atopic patients were assayed using quantitative PCR and immunohistochemistry.