A human papillomavirus 16 E2-TopBP1 dependent SIRT1-p300 acetylation switch regulates mitotic viral and human protein levels and activates the DNA damage response.

Unlabelled: An interaction between human papillomavirus 16 (HPV16) E2 and the cellular proteins TopBP1 and BRD4 is required for E2 plasmid segregation function. The E2-TopBP1 interaction promotes increased mitotic E2 protein levels in U2OS and N/Tert-1 cells, as well as in human foreskin keratinocytes immortalized by HPV16 (HFK + HPV16). SIRT1 deacetylation reduces E2 protein stability and here we demonstrate that increased E2 acetylation occurs during mitosis in a TopBP1 interacting-dependent manner, promoting E2 mitotic stabilization.

Hypertension Severity and Declines in Left Ventricular Ejection Fraction Among Women Receiving Adjuvant Chemotherapy for Breast Cancer (WF-97415 UPBEAT).

Background: Hypertension is a risk factor for experiencing left ventricular ejection fraction (LVEF) declines during receipt of potentially cardiotoxic breast cancer (BC) treatment. We sought to determine whether the hypertension stage is associated with LVEF decline during BC treatment.

Methods: Across 24 centers, cardiac magnetic resonance measures of LVEF and brachial arterial blood pressure (BP) measurements were performed in women with stages I to III BC before and 3 months after initiating potentially cardiotoxic chemotherapy.

Perirectal Mucinous Adenocarcinoma After Subtotal-Colectomy for Crohn's Disease: A Case Report.

Colorectal carcinoma (CRC) represents the third most common cancer and the second highest cause of cancer-related death in the United States. CRC is particularly prevalent in patients with underlying inflammatory bowel disease. Adenocarcinoma represents more than 90% of new CRC diagnoses.

Development of Clinical Algorithm Utilizing Vibration-Controlled Transient Elastography to Detect Advanced Hepatic Fibrosis in Liver Transplant Recipients.

Introduction: Vibration-controlled transient elastography (VCTE) based liver stiffness measurement (LSM) is an excellent 'rule-out' test for advanced hepatic fibrosis in liver transplant (LT) recipients, however, its ability to 'rule-in' the disease is suboptimal. The study aimed to improve diagnostic performance of LSM in LT recipients.

Methods: Adult LT recipients with a liver biopsy and VCTE were included (N = 150).

Comparing attention, impulsivity, and executive functions between patients with opiate use disorder: Buprenorphine maintenance treatment versus active users, in comparison with healthy controls.

Background: Opioid use disorders (OUDs) affect over 16 million people worldwide, with a particularly high prevalence rate in Asia. OUDs are associated with significant health consequences, including neurocognitive impairment, which affects individuals' ability to make decisions, respond to stressful situations, and regulate behavior. Understanding the specific ways in which OUDs affect cognitive functioning is important in treatment considerations.

Obesity management for cardiovascular disease prevention.

Background: Obesity is a complex disease that leads to higher morbidity and mortality and its rate in the United States is rapidly rising. Targeting obesity management is one of the cornerstones of preventive medicine. Early intervention can significantly reduce the risk of developing cardiovascular disease.

Global survey of stigma among physicians and patients with nonalcoholic fatty liver disease.

Background & Aims: Patients with fatty liver disease may experience stigma from the disease or comorbidities. In this cross-sectional study, we aimed to understand stigma among patients with nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH) and healthcare providers.

Methods: Members of the Global NASH Council created two surveys about experiences/attitudes toward NAFLD and related diagnostic terms: a 68-item patient and a 41-item provider survey.

Direct interaction with the BRD4 carboxyl-terminal motif (CTM) and TopBP1 is required for human papillomavirus 16 E2 association with mitotic chromatin and plasmid segregation function.

Human papillomavirus 16 (HPV16) is a causative agent in around 3%-4% of all human cancers, and currently, there are no anti-viral therapeutics available for combating this disease burden. In order to identify new therapeutic targets, we must increase our understanding of the HPV16 life cycle. Previously, we demonstrated that an interaction between E2 and the cellular protein TopBP1 mediates the plasmid segregation function of E2, allowing distribution of viral genomes into daughter nuclei following cell division.

Ocular toxicities associated with antibody drug conjugates and immunotherapy in oncology: clinical presentation, pathogenesis, and management strategies.

Introduction: The development of molecularly targeted anticancer therapies and immunotherapy continues to revolutionize the treatment of cancer. FDA accelerated approvals of novel targeted therapies allowed for introduction of these agents into the clinic at a rapid rate. On-and off-target ocular toxicities are prevalent treatment-related adverse events of newer therapies including antibody drug conjugates (ADCs) and immunotherapy.

Skeletal Fluorosis in a Patient With Computer Cleaner Inhalant Abuse.

Skeletal fluorosis is a metabolic bone disease caused by excessive consumption of fluoride from fluoride-contaminated water or foods. Such a condition often takes place in developing countries without proper handling of drinking water or food. However, in recent years, multiple cases of skeletal fluorosis have been observed in the United States due to the increasing frequency of recreational substance abuse.

Reduced metabolic flexibility is a predictor of weight gain among liver transplant recipients.

Metabolic flexibility is the ability to match biofuel availability to utilization and is inversely associated with increased metabolic burden among liver transplant (LT) recipients. The present study evaluated the impact of metabolic flexibility on weight gain following LT. LT recipients were enrolled prospectively (n = 47) and followed for 6 months.

Bioactive lipid mediators in plasma are predictors of preeclampsia irrespective of aspirin therapy.

There are few early biomarkers to identify pregnancies at risk of preeclampsia (PE) and abnormal placental function. In this cross-sectional study, we utilized targeted ultra-performance liquid chromatography-ESI MS/MS and a linear regression model to identify specific bioactive lipids that serve as early predictors of PE. Plasma samples were collected from 57 pregnant women prior to 24-weeks of gestation with outcomes of either PE (n = 26) or uncomplicated term pregnancies (n = 31), and the profiles of eicosanoids and sphingolipids were evaluated.

Proposal for a Two-Tier Re-classification of Stage IV/M1 domain of Renal Cell Carcinoma into M1 ("Oligometastatic") and M2 ("Polymetastatic") subdomains: Analysis of the Registry for Metastatic Renal Cell Carcinoma (REMARCC).

Purpose: We hypothesized that two-tier re-classification of the "M" (metastasis) domain of the Tumor-Node-Metastasis (TNM) staging of Renal Cell Carcinoma (RCC) may improve staging accuracy than the current monolithic classification, as advancements in the understanding of tumor biology have led to increased recognition of the heterogeneous potential of metastatic RCC (mRCC).

Methods: Multicenter retrospective analysis of patients from the REMARCC (REgistry of MetAstatic RCC) database. Patients were stratified by number of metastases into two groups, M1 (≤3, "Oligometastatic") and M2 (>3, "Polymetastatic").

Impacts of the COVID-19 Pandemic on United States Emergency Medicine Education: A Council of Residency Directors in Emergency Medicine (CORD) Task Force Survey-Based Analysis.

Introduction The COVID-19 pandemic presented unpredicted challenges to Emergency Medicine (EM) education. The rapid onset of the pandemic created clinical, operational, administrative, and home-life challenges for virtually every member of the medical education community, demanding an educational and professional response at all levels including undergraduate medical education (UME), graduate medical education (GME), and faculty. The Council of Residency Directors in Emergency Medicine (CORD) COVID-19 Educational Impact Task Force was established in 2021 to examine these effects and the response of the EM educational community.

Human Papillomavirus 16 E2 Interaction with TopBP1 Is Required for E2 and Viral Genome Stability during the Viral Life Cycle.

CK2 phosphorylation of HPV16 E2 at serine 23 promotes interaction with TopBP1, and this interaction is important for E2 plasmid segregation function. Here, we demonstrate that the E2-TopBP1 interaction is critical for E2 and viral genome stability during the viral life cycle. Introduction of the S23A mutation into the HPV16 genome results in a loss of E2 expression and viral genome integration during organotypic rafting.

A Novel Low-Cost Uroflowmetry for Patient Telemonitoring.

Uroflowmetry (UF) is a crucial guideline-recommended tool for men with benign prostatic obstruction (BPO). Moreover, UF is a helpful decision-making tool for the management of patients with lower urinary tract symptoms (LUTS) and benign prostatic hyperplasia (BPH). In the last few years, telemedicine and telehealth have increased exponentially as cost-effective treatment options for both patients and physicians.

Astrocytosis, Inflammation, Axonal Damage and Myelin Impairment in the Internal Capsule following Striatal Ischemic Injury.

Secondary degeneration is defined as a set of destructive events that damage cells and structures that were initially spared or only peripherally affected by the primary insult, constituting a key factor for functional impairment after traumatic brain injury or stroke. In the present study, we evaluated the patterns of astrocytosis, inflammatory response, axonal damage and oligodendrocytes/myelin impairment in the internal capsule following a focal injection of endothelin-1 (ET-1) into the dorsal striatum. Animals were perfused at 1, 3 and 7 post-lesion days (PLD), and tissue was processed to immunohistochemistry for neutrophils (MBS1), macrophages/microglia (ED1), astrocytes (GFAP), axonal lesion (βAPP), oligodendrocytes (Tau) and myelin (MBP).

Prognostic Factors for Non-anastomotic Biliary Strictures Following Adult Liver Transplantation: A Systematic Review and Meta-Analysis.

Introduction: The development of non-anastomotic biliary strictures (NAS) following orthotopic adult liver transplantation (OLT) is associated with significant morbidity. We performed a systematic review and meta-analysis to identify all prognostic factors for the development of NAS.

Methods: A systematic review was conducted following preferred reporting items for systematic reviews and meta-analyses (PRISMA) and the meta-analysis of observational studies in epidemiology (MOOSE) guidelines.

Outnumbered: Control Prothrombin Time in Maddrey's Discriminant Function Impacts Steroid Use but Not Mortality in Alcoholic Hepatitis.

Background And Aims: In alcoholic hepatitis (AH), increases in the total bilirubin (TB) and the prothrombin time (PT), which are included in the Maddrey's discriminant function (MDF) and the model for end-stage liver disease (MELD), are associated with poor outcomes. However, the impact of which control PT in the MDF to use compared to the MELD on the outcomes in AH is unknown. Our aim is to determine whether the choice of the control PT used in the MDF calculations has any impact on steroid use and survival when compared to the MELD in those with AH.

Salvage of Hindfoot Charcot with Osteomyelitis and Ulceration: A Case Report.

Diabetic Charcot arthropathy of the ankle, due to the presence of multiplanar deformities, and associated medical comorbidities, poses a challenge for treating physicians. The situation becomes more complicated when accompanied by ulceration and osteomyelitis, leaving limited salvage options. We present a case of advanced Charcot ankle arthropathy with osteomyelitis and ulcerated hindfoot.

Associations of Military Service History and Health Outcomes in the First Five Years After Traumatic Brain Injury.

For many years, experts have recognized the importance of studying traumatic brain injury (TBI) among active-duty service members and veterans. A majority of this research has been conducted in Veterans Administration (VA) or Department of Defense settings. However, far less is known about military personnel who seek their medical care outside these settings.

Osmotic Demyelination Syndrome in a Patient With Tremors.

Osmotic demyelination syndrome is a neurological disorder caused by damage to the myelin sheath of brain cells secondary to rapid correction of hyponatremia. Clinical features are variable depending on the location of demyelination, with diagnosis confirmed by MRI. Once diagnosed, treatment is supportive.