Association of Atrial Fibrillation with Insomnia in the Elderly Population.

Introduction/objectives: Insomnia is a common sleep disorders that affects most individuals in the United States, and worldwide. Insomnia is linked with an increased risk of atrial fibrillation (AF) in adults, although the strengths of association were weak, especially in the elderly population. AF is estimated to affect approximately 3 to 6 million people in the United States.

Postmortem pathologic findings in dogs that underwent total body irradiation and hematopoietic cell transplant: A case series of five dogs with B-cell multicentric lymphoma.

Alternative therapies that can help achieve complete remission in dogs with lymphoma include total body irradiation and hematopoietic cell transplant, though there are few reports describing successes and pathologic sequelae of these procedures. During a 10-year period, 94 dogs with multicentric lymphoma received a hematopoietic cell transplant following total body irradiation at North Carolina State University College of Veterinary Medicine. Seven of these 94 dogs (7%) died prior to discharge, five (5%) of which presented for postmortem examination.

Association of Risk Factors and Comorbidities With Chronic Pain in the Elderly Population.

Introduction/objective: Chronic pain disorders affect about 20% of adults in the United States, and it disproportionately affects individuals living in the neighborhoods of extreme socioeconomic disadvantage. In many instances, chronic pain has been noted to arise from an aggregation of multiple risk factors and events. Therefore, it is of importance to recognize the modifiable risk factors.

Comorbidities and Risk Factors Associated With Insomnia in the Elderly Population.

Introduction/objectives: Sleep disorders affect around 50 to 70 million Americans, with chronic insomnia being the most common, especially in the elderly population. With an 11-fold increase in the US office visits due to insomnia, from 0.8 to 9.

MTAP deficiency creates an exploitable target for antifolate therapy in 9p21-loss cancers.

Methylthioadenosine phosphorylase, an essential enzyme for the adenine salvage pathway, is often deficient (MTAP) in tumors with 9p21 loss and hypothetically renders tumors susceptible to synthetic lethality by antifolates targeting de novo purine synthesis. Here we report our single arm phase II trial (NCT02693717) that assesses pemetrexed in MTAP urothelial carcinoma (UC) with the primary endpoint of overall response rate (ORR). Three of 7 enrolled MTAP patients show response to pemetrexed (ORR 43%).

Feasibility of a Risk-Based Approach to Cataract Surgery Preoperative Medical Evaluation.

Importance: In 2019, the US Centers for Medicare & Medicaid Services implemented the Patients Over Paperwork initiative, allowing hospitals and ambulatory surgery centers to establish their own policies on preoperative history and physical requirements. A risk-based approach to preoperative medical evaluation may allow surgeons to provide high-value patient care.

Objective: To assess the feasibility of a risk-based approach to cataract surgery preoperative medical evaluation through a lens of safety and throughput.

Current practices in nutrition management and disease incidence of common marmosets (Callithrix jacchus).

Background: A survey was developed to characterize disease incidence, common pathology lesions, environmental characteristics, and nutrition programs within captive research marmoset colonies.

Methods: Seventeen research facilities completed the electronic survey.

Results: Nutritional management programs varied amongst research institutions housing marmosets; eight primary base diets were reported.

Exploring Differences in the Lives and Well-Being of Sexual and Gender Minority Adults Experiencing Homelessness Relative to Their Cisgender Heterosexual Counterparts.

To better understand the lives and experiences of sexual and gender minority (SGM) adults experiencing homelessness relative to their cisgender heterosexual (non-SGM) counterparts. A modified time-location sampling strategy was used to reach a diverse sample of individuals with experiences of homelessness. Interviewer or self-administered paper-based surveys were administered to participants on location.

Time Trends and Predictors of Abnormal Postoperative Body Temperature in Infants Transported to the Intensive Care Unit.

. Despite increasing adoption of active warming methods over the recent years, little is known about the effectiveness of these interventions on the occurrence of abnormal postoperative temperatures in sick infants. .

A Phase l Study of a Tumor-targeted Systemic Nanodelivery System, SGT-94, in Genitourinary Cancers.

Gene therapy development has been limited by our inability to target multifocal cancer with systemic delivery. We developed a systemically administered, tumor-targeted liposomal nanodelivery complex (SGT-94) carrying a plasmid encoding RB94, a truncated form of the RB gene. In preclinical studies, RB94 showed marked cytotoxicity against tumor but not normal cells.

Phase 1b Trial to Evaluate Tissue Response to a Second Dose of Intravesical Recombinant Adenoviral Interferon α2b Formulated in Syn3 for Failures of Bacillus Calmette-Guerin (BCG) Therapy in Nonmuscle Invasive Bladder Cancer.

Background: A phase 1b trial was conducted to evaluate the duration of interferon-alpha (IFNα) production after intravesical administration of recombinant adenovirus-mediated interferon α2b (Ad-IFN) formulated with the excipient Syn3. The primary aim was to determine whether a second instillation 3 days after initial treatment produced prolonged urinary IFN production.

Methods: The study enrolled seven patients who experienced recurrent non-muscle invasive bladder cancer after bacillus Calmette-Guerin therapy.

Use of monitoring levels of soluble forms of cytokeratin 18 in the urine of patients with superficial bladder cancer following intravesical Ad-IFNα/Syn3 treatment in a phase l study.

A phase l study using intravesical Ad-IFNαSyn3 for patients with bacillus Calmette-Guérin-resistant superficial bladder cancer showed a complete remission (CR) of 43% at 90 days after treatment with high levels of interferon-α (IFNα) being produced. Ad-IFNα kills bladder cancer cells by two apoptotic and one necrotic mechanism that can be measured by soluble forms of cytokeratin 18 (CK18) using M30 and M65 ELISAs, assays for caspase-cleaved (apoptotic) and uncleaved (necrotic) cell death, respectively. Therefore, we determined whether M30 and M65 levels in the urine after treatment could document all three mechanisms of cancer cell kill and also predict having a CR.

Airway exchange failure and complications with the use of the Cook Airway Exchange Catheter®: a single center cohort study of 1177 patients.

There are limited data on rates of failure and airway injury with the use of airway exchange catheters. We performed a single-center retrospective analysis of airway exchange catheters to determine the incidence and associated factors for tube exchange failure and airway injury. Among 1177 cases, failed intubation during attempted tube exchange was noted in 73/527 (13.

Phase I trial of intravesical recombinant adenovirus mediated interferon-α2b formulated in Syn3 for Bacillus Calmette-Guérin failures in nonmuscle invasive bladder cancer.

Purpose: A phase I trial of intravesical recombinant adenovirus mediated interferon-α2b gene therapy (rAd-IFNα) formulated with the excipient SCH Syn3 was conducted in patients with nonmuscle invasive bladder cancer who had disease recurrence after treatment with bacillus Calmette-Guérin. The primary objective was to determine the safety of rAd-IFNα/Syn3. Secondary end points were demonstrated effective rAd-IFNα gene expression and preliminary evidence of clinical activity at 3 months.

Detection of bladder cancer using proteomic profiling of urine sediments.

We used protein expression profiles to develop a classification rule for the detection and prognostic assessment of bladder cancer in voided urine samples. Using the Ciphergen PBS II ProteinChip Reader, we analyzed the protein profiles of 18 pairs of samples of bladder tumor and adjacent urothelium tissue, a training set of 85 voided urine samples (32 controls and 53 bladder cancer), and a blinded testing set of 68 voided urine samples (33 controls and 35 bladder cancer). Using t-tests, we identified 473 peaks showing significant differential expression across different categories of paired bladder tumor and adjacent urothelial samples compared to normal urothelium.

Low molecular weight cyclin E is associated with p27-resistant, high-grade, high-stage and invasive bladder cancer.

Expression of low molecular weight (LMW) isoforms of cyclin E is a strong predictor of poor outcome in patients with breast cancer. The purpose of this study was to examine the expression of full-length and LMW cyclin E in bladder cancer cell lines and patient tumors. We used western blotting, immunoprecipitation and kinase assays to examine the expression and activity of key cell cycle-regulatory proteins in various human bladder cell lines, both tumorigenic and non-tumorigenic.

Direct cytotoxicity produced by adenoviral-mediated interferon α gene transfer in interferon-resistant cancer cells involves ER stress and caspase 4 activation.

Over the past several years we have obtained considerable evidence indicating that adenoviruses-expressing interferon α (Ad-IFNα) can overcome resistance to the IFNα protein itself. Since cancer cells infected with Ad-IFNα also show high perinuclear cytoplasmic IFNα expression, we were interested in whether endoplasmic reticulum (ER) stress and cleavage of caspase 4 could have a major role in Ad-IFNα-produced cancer cell death. Indeed, procaspase 4 was upregulated and cleaved as early as 12 h after Ad-IFNα infection of the cancer cells, which co-localized with IFNα staining and ER tracker.

Direct gene transfer of adenoviral-mediated interferon α into human bladder cancer cells but not the bystander factors produced induces endoplasmic reticulum stress-related cytotoxicity.

We have previously shown that adenoviral-mediated interferon α (Ad-IFNα) is cytotoxic both to cells that are sensitive to recombinant interferon α (IFNα) and to cells which are resistant to IFNα. The cancer cell-specific cytotoxic effects of Ad-IFNα involve three different mechanisms: 1. The direct effect of IFNα production causing cancer cell death in IFNα sensitive cells (1); 2.

Autophagy is induced by adenoviral-mediated interferon alpha treatment in interferon resistant bladder cancer and normal urothelial cells as a cell death protective mechanism but not by the bystander factors produced.

We have previously shown that adenoviral-mediated interferon alpha (Ad-IFNalpha) treatment is highly cytotoxic to tumor cells which are resistant to the IFNalpha protein. We now report that autophagy is produced after Ad-IFNalpha treatment of either IFN resistant bladder cancer cells (UC9 and KU7) or the normal urothelial cell line (TERT-NHUC). After Ad-IFNalpha infection autophagosomes, an early stage of autophagy, were seen in cancer cells whereas autophagolysosomes, a later stage of autophagy, were observed mostly in normal cells by electron microscopy.

Measuring soluble forms of extracellular cytokeratin 18 identifies both apoptotic and necrotic mechanisms of cell death produced by adenoviral-mediated interferon alpha: possible use as a surrogate marker.

Adenoviral transduction of human bladder cancer cells with human interferon alpha-2b (Ad-IFN) produces cancer-specific cell death through direct and indirect mechanisms. The indirect mechanisms involve the secreted IFN produced, which kill, IFN protein-sensitive cancer cells, as well as yet unidentified bystander factors, which are cytotoxic to neighboring cancer cells. The direct cell kill results from transfection and expression of Ad-IFN in the cancer cells.

Early RB94-produced cytotoxicity in cancer cells is independent of caspase activation or 50 kb DNA fragmentation.

RB94, which lacks the N-terminal 112 amino-acid residues of the full-length retinoblastoma protein (RB110) is a more potent inhibitor of cancer cell growth than RB110, being cytotoxic to all cancer cell lines studied, independent of their genetic abnormalities. Although we initially thought RB94-induced cell death was caspase-dependent, such caspase activation now appears to be a late event. Cells that remained attached 48 h after transduction with Ad-RB94 showed, among other changes, nuclear enlargement, peripheral nuclear chromatin condensation and often micronucleation.

Conditioned medium from Ad-IFN-alpha-infected bladder cancer and normal urothelial cells is cytotoxic to cancer cells but not normal cells: further evidence for a strong bystander effect.

We have reported earlier that a bystander effect is seen in cancer cells that are resistant to high concentrations of the interferon-alpha protein (Intron A) when treated with adenoviral-mediated interferon-alpha (Ad-IFN-alpha). We now provide further evidence for this bystander effect using conditioned medium (CM) collected from Ad-IFN-alpha-infected cancer and normal urothelial cells. The CMs collected from UC-9 and KU7 bladder cancer cells as well as normal urothelial cells following transfection with Ad-IFN produce cell death when added to various cancer cell types in culture but not to normal urothelial cells.

Perioperative and long-term operative outcomes after surgery for trigeminal neuralgia: microvascular decompression vs percutaneous balloon ablation.

Objectives: Numerous medical and surgical therapies have been utilized to treat the symptoms of trigeminal neuralgia (TN). This retrospective study compares patients undergoing either microvascular decompression or balloon ablation of the trigeminal ganglion and determines which produces the best long-term outcomes.

Methods: A 10-year retrospective chart review was performed on patients who underwent microvascular decompression (MVD) or percutaneous balloon ablation (BA) surgery for TN.

Understanding the development of human bladder cancer by using a whole-organ genomic mapping strategy.

The search for the genomic sequences involved in human cancers can be greatly facilitated by maps of genomic imbalances identifying the involved chromosomal regions, particularly those that participate in the development of occult preneoplastic conditions that progress to clinically aggressive invasive cancer. The integration of such regions with human genome sequence variation may provide valuable clues about their overall structure and gene content. By extension, such knowledge may help us understand the underlying genetic components involved in the initiation and progression of these cancers.