Single-cell chromatin accessibility identifies pancreatic islet cell type- and state-specific regulatory programs of diabetes risk.

Single-nucleus assay for transposase-accessible chromatin using sequencing (snATAC-seq) creates new opportunities to dissect cell type-specific mechanisms of complex diseases. Since pancreatic islets are central to type 2 diabetes (T2D), we profiled 15,298 islet cells by using combinatorial barcoding snATAC-seq and identified 12 clusters, including multiple alpha, beta and delta cell states. We cataloged 228,873 accessible chromatin sites and identified transcription factors underlying lineage- and state-specific regulation.

Intron 1-Mediated Regulation of Expression in EGFR-Dependent Malignancies Is Mediated by AP-1 and BET Proteins.

The epidermal growth factor receptor (EGFR) is overexpressed in numerous solid tumors and is the subject of extensive therapeutic efforts. Much of the research on EGFR is focused on protein dynamics and downstream signaling; however, few studies have explored its transcriptional regulation. Here, we identified two enhancers (CE1 and CE2) present within the first intron of the gene in models of glioblastoma (GBM) and head and neck squamous cell carcinoma (HNSCC).

A randomized comparison of the efficacy of 2 techniques for piriformis muscle injection: ultrasound-guided versus nerve stimulator with fluoroscopic guidance.

Background: Piriformis muscle injections are most often performed using fluoroscopic guidance; however, ultrasound (US) guidance has recently been described extensively in the literature. No direct comparisons between the 2 techniques have been performed. Our objective was to compare the efficacy and efficiency of fluoroscopic- and US-guided techniques.

Disorders of childhood growth and development: childhood obesity.

The incidence of childhood obesity in the United States is estimated at 17%, or 12 million children ages 2 to 19 years. Obesity is a multifactorial condition with syndromic and nonsyndromic variants. Genetic, social, ethnic, endocrinologic, and behavioral issues are all potential etiologic factors.

Treatment of meralgia paresthetica with ultrasound-guided pulsed radiofrequency ablation of the lateral femoral cutaneous nerve.

A 23-year-old female with an 18-month history of left anterolateral thigh paresthesias and burning pain consistent with meralgia paresthetica was referred to our clinic after failing trials of physical therapy, nonsteroidal anti-inflammatories, gabapentin, and amitriptyline. We performed 3 lateral femoral cutaneous nerve blocks with corticosteroid over a 4-month period; however, each block provided only temporary relief. As this pain was limiting the patient's ability to perform her functions as an active duty service member, we elected to perform a pulsed radiofrequency treatment of the lateral femoral cutaneous nerve with ultrasound guidance and nerve stimulation.

ASSOCIATION BETWEEN DE NOVO DONOR SPECIFIC HLA ANTIBODY, C4D STAINING IN RENAL GRAFT BIOPSY AND GRAFT OUTCOME: A SINGLE CENTER EXPERIENCE.

In 69 renal transplant recipients (RTR), all had a functioning graft (SCr < 2.0) at one year. After one year, transplant dysfunction was observed and these 69 RTR were biopsied, tested for C4d deposition and donor specific antibodies (DSA).

The evolving notion of "senior" kidney transplant recipients.

The maximum age of recipients expected to benefit with a kidney transplant has increased in the past three decades. In 1980, patients older than age 50 were not listed for a transplant. In 2004, almost 90% aged 50-60 yr with end-stage renal disease were listed, and some were even older than age 80.

High seroprevalence of anti-HTLV-I/II antibodies among solid organ donors necessitates confirmatory testing.

Background: Human T-cell lymphotrophic virus (HTLV) type I has been linked to adult T-cell leukemia/lymphoma (ATL) and HTLV-I associated myelopathy (HAM). Transmission of HTLV by blood and organ transplantation has been documented, with some infections leading to clinical disease. Organ donors are tested for anti-HTLV antibodies and donor suitability is determined primarily by results from enzyme immunoassays (EIA).

Evaluation of the L2 spinal nerve root infiltration as a diagnostic tool for discogenic low back pain.

Background: To assess whether unilateral L2 infiltration with local anesthetic can be used to identify patients who will have negative discograms and thus eliminate the need for the discogram. Discogenic low-back pain is considered to have afferent pathways in the sinuvertebral nerves, mainly originating from the ventral rami of the spinal nerves. There is evidence that pain arising from the lower lumbar intervertebral discs may be transmitted through the sympathetic afferent fibers contained in the L2 spinal nerve root.

Cerebellar herniation after cervical transforaminal epidural injection.

Objective: The purpose of this study is to inform readers of potential catastrophic complications associated with performing cervical transforaminal epidural steroid injections.

Case Report: A 31-year-old man presented to the pain clinic with a history of cervical radicular pain and right upper-extremity radicular symptoms. He was referred from the orthopedic spine clinic for evaluation for epidural steroid injection, having failed conservative treatment consisting of nonsteroidal anti-inflammatory drugs, muscle relaxants, oral steroids, and physical therapy.

Prevalence of antibodies to Trypanosoma cruzi among solid organ donors in Southern California: a population at risk.

Trypanosoma cruzi, a parasite that causes Chagas' disease, is endemic in parts of Mexico, South America, and Central America. Transmission of T. cruzi infection by solid organ transplantation has been reported in Latin America and recently in the United States.

A multicenter, prospective study of C2-monitored cyclosporine microemulsion in a U.S. population of de novo renal transplant recipients.

Background: Monitoring cyclosporine microemulsion (CsA-ME; Neoral) exposure 2 hours postdose (C2) has been reported to optimize the efficacy and safety of CsA-ME therapy. The addition of induction therapy to a maintenance regimen including CsA-ME C2 monitoring has not been evaluated.

Methods: In all, 123 adult renal transplant recipients were recruited at 14 U.

A prospective, randomized trial of tacrolimus in combination with sirolimus or mycophenolate mofetil in kidney transplantation: results at 1 year.

Background: This is the 1-year report of a randomized, multicenter, clinical trial comparing the combination of sirolimus or mycophenolate mofetil (MMF) with tacrolimus-based immunosuppression in kidney transplantation.

Methods: Prior to transplantation, recipients were randomized to receive tacrolimus plus corticosteroids with either sirolimus (n=185) or MMF (n=176). The incidence of biopsy-confirmed acute rejection at 6 months was the primary endpoint of the study.

Everolimus versus mycophenolate mofetil in the prevention of rejection in de novo renal transplant recipients: a 3-year randomized, multicenter, phase III study.

Background: This 36-month, randomized, parallel-group study compared safety and efficacy of two doses of everolimus with mycophenolate mofetil (MMF) in de novo renal-transplant recipients.

Methods: Renal-allograft recipients received 1.5 mg/day or 3 mg/day of everolimus or 2 g/day of MMF, plus full-dose cyclosporine (CsA) and corticosteroids after randomization.

Improved detection of HCV Infection in hemodialysis patients using a new HCV RNA qualitative assay: experience of a transplant center.

Background: Hepatitis C virus (HCV) is frequently a silent infection in hemodialysis (HD) patients with a prevalence of 8-10%. Improving HCV detection in this population prior to transplantation is critical both for infection control and optimal patient care.

Objectives: To assess the current HCV testing practice of the National Institute for Transplantation (PCR testing of enzyme immunoassay (EIA) positive HD patients) by evaluating a subset of EIA positive and EIA negative samples with the VERSANT HCV RNA Qualitative Assay based on transcription mediated amplification (HCV Qual (TMA)) (sensitivity < or = 9.

Randomized trial of tacrolimus in combination with sirolimus or mycophenolate mofetil in kidney transplantation: results at 6 months.

Background: This is the first report of a randomized, multicenter, clinical trial comparing the combination of sirolimus or mycophenolate mofetil (MMF) with tacrolimus-based immunosuppression in kidney transplantation. Results at 6 months of follow-up are presented.

Methods: Before transplantation, patients were randomized to receive tacrolimus plus corticosteroids with sirolimus (n=185) or MMF (n=176).