Comparison of genome-scale DNA methylation profiles in hepatocellular carcinoma by viral status.

Hepatocellular carcinoma (HCC) incidence has steadily increased in the US over the past 30 years. Our understanding of epigenetic regulation in HCC is still limited, especially the impact of hepatitis B virus (HBV) or hepatitis C virus (HCV) infection on aberrant DNA methylation. We performed genome-wide DNA methylation profiling in 33 fresh frozen tumor samples, including 10 HBV-HCC, 13 HCV-HCC, and 10 non-infected (NIV-HCC) using the Illumina HumanMethylation450 BeadChip.

Longitudinal brain structural alterations and systemic inflammation in obstructive sleep apnea before and after surgical treatment.

Background: Systemic inflammation, neurocognitive impairments, and morphologic brain changes are associated with obstructive sleep apnea (OSA). Understanding their longitudinal evolution and interactions after surgical treatment provides clues to the pathogenesis of cognitive impairment and its reversibility. In the present study, we investigate clinical disease severity, systemic inflammation, cognitive deficits, and corresponding gray matter volume (GMV) changes in OSA, and the modifications following surgery.

The value of serial serum cell adhesion molecules in predicting acute kidney injury after severe sepsis in adults.

Background: Septic acute kidney injury (AKI) is a common complication of severe sepsis. We tested the hypothesis that serum cell adhesion molecule levels are substantially increased in early septic AKI and decreased after antimicrobial therapy and their level can predict prognosis.

Methods: Seventy-two nontraumatic, nonsurgical adult patients with severe sepsis admitted to the emergency department were evaluated.

Cytogenetics Does Not Impact Outcomes in Adult Patients with Acute Lymphoblastic Leukemia Undergoing Allogeneic Hematopoietic Cell Transplantation.

The prognostic relevance of cytogenetics at diagnosis on the outcome of allogeneic hematopoietic stem cell transplantation (alloHCT) for adult acute lymphoblastic leukemia (ALL) remains unclear. We retrospectively analyzed outcomes of 333 adult ALL patients who underwent alloHCT at our institution over a 10-year period. Patients were classified according to disease status at transplantation (complete response [CR] 1 [n = 202] or > CR1) and according to cytogenetic risk, defined as good (2%), intermediate (42%), poor (46%), or unknown (10%) based on available outcome data for each of the cytogenetic abnormalities.

Examining the clinical course of genotype 1 chronic hepatitis C patients treated with the cosmos regimen: including patients with advanced liver disease and East Asian ancestry.

Background/objectives: The COSMOS study was a phase 2a clinical trial that showed high cure rates of genotype 1 chronic hepatitis C (CHC) and a favorable side effect profile using a 12-week regimen of simeprevir + sofosbuvir (SIM + SOF). Given the small number of patients treated with the SIM + SOF regimen in the COSMOS trial, there is uncertainty regarding the efficacy and safety of this combination therapy. We now report our experience with the COSMOS regimen in the multiethnic population of Hawaii, including patients of East Asian ancestry and with decompensated cirrhosis.

Feedback modulation of neural network synchrony and seizure susceptibility by Mdm2-p53-Nedd4-2 signaling.

Background: Neural network synchrony is a critical factor in regulating information transmission through the nervous system. Improperly regulated neural network synchrony is implicated in pathophysiological conditions such as epilepsy. Despite the awareness of its importance, the molecular signaling underlying the regulation of neural network synchrony, especially after stimulation, remains largely unknown.

Association Between Autonomic Impairment and Structural Deficit in Parkinson Disease.

Patients with Parkinson disease (PD) have impaired autonomic function and altered brain structure. This study aimed to evaluate the relationship of gray matter volume (GMV) determined by voxel-based morphometry (VBM) to autonomic impairment in patients with PD. Whole-brain VBM analysis was performed on 3-dimensional T1-weighted images in 23 patients with PD and 15 sex- and age-matched healthy volunteers.

Diabetic Retinopathy Is Strongly Predictive of Cardiovascular Autonomic Neuropathy in Type 2 Diabetes.

A well-established, comprehensive, and simple test battery was used here to re-evaluate risk factors for cardiovascular autonomic neuropathy (CAN) in type 2 diabetes. One hundred and seventy-four patients with type 2 diabetes were evaluated through the methods of deep breathing and Valsalva maneuver for correlation with factors that might influence the presence and severity of CAN. The Composite Autonomic Scoring Scale (CASS) was used to grade the severity of autonomic impairment, and CAN was defined as a CASS score ≥2.

Engraftment and outcomes following autologous stem cell transplantation in Hodgkin lymphoma patients mobilized with plerixafor.

Plerixafor has been used to improve peripheral blood stem cell (PBSC) mobilization in multiple myeloma, non-Hodgkin lymphoma, and very recently in Hodgkin lymphoma (HL) patients. Because prior studies have suggested that mobilization with plerixafor affects the composition of mobilized cells, there are concerns that this may in turn adversely impact the immune reconstitution and longer term outcomes of transplanted patients. However, data on the engraftment characteristics and long-term post-transplant outcomes in patients transplanted with plerixafor-mobilized PBSCs are lacking.

Inhibition of breast cancer with transdermal tamoxifen-encapsulated lipoplex.

Background: Tamoxifen is currently used for the treatment of both early and advanced estrogen receptor (ER) positive breast cancer in pre- and post-menopausal women. However, using tamoxifen routinely to inhibit endogenous or exogenous estrogen effects is occasionally difficult because of its potential side effects.

Objectives: The aim of this study is to design a local drug delivery system to encapsulate tamoxifen for observing their efficacy of skin penetration, drug accumulation and cancer therapy.

Dopaminergic Therapy Modulates Cortical Perfusion in Parkinson Disease With and Without Dementia According to Arterial Spin Labeled Perfusion Magnetic Resonance Imaging.

Arterial spin labeling (ASL) magnetic resonance imaging analyses allow for the quantification of altered cerebral blood flow, and provide a novel means of examining the impact of dopaminergic treatments. The authors examined the cerebral perfusion differences among 17 Parkinson disease (PD) patients, 17 PD with dementia (PDD) patients, and 17 healthy controls and used ASL-MRI to assess the effects of dopaminergic therapies on perfusion in the patients. The authors demonstrated progressive widespread cortical hypoperfusion in PD and PDD and robust effects for the dopaminergic therapies.

Disparate access to treatment regimens in chronic hepatitis C patients: data from the TRIO network.

Despite the clinical success in the real-world of all oral hepatitis C virus (HCV) therapy with response rates approaching that seen in the clinical trials, access has been limited by many payers with discussion of prioritization of treatment based upon AASLD guidelines. We evaluated patients in the TRIO network who were prescribed sofosbuvir (SOF)-based regimens to determine reasons for not starting treatment. Trio Health is a disease management company that works in partnership with academic medical centres, community physicians and specialty pharmacies in the United States to optimize care for HCV.

Circulating endothelial progenitor cells may predict outcomes in adult patients with severe sepsis in the emergency department.

Background: Dysfunctional and decreased numbers of endothelial progenitor cells (EPCs) may play an essential role in the initiation of organ dysfunction caused by severe sepsis. We evaluated the role of serial circulating EPCs in outcomes of patients with severe sepsis.

Methods: In total, 101 adult patients with severe sepsis and septic shock were evaluated.

Real-world Experience with Sofosbuvir-based Regimens for Chronic Hepatitis C, Including Patients with Factors Previously Associated with Inferior Treatment Response.

The introduction of sofosbuvir, a direct acting antiviral, has revolutionized the treatment of chronic hepatitis C virus (HCV). Phase 3 clinical trials have demonstrated the efficacy, simplicity, and tolerability of sofosbuvir-based regimens and report high rates of sustained virological response (SVR) rates. The purpose of this study was to assess whether clinical trial findings translate into a real-world setting, particularly with treatment of chronic HCV in our diverse, multiethnic population of Hawai'i.

Brain mediators of systemic oxidative stress on perceptual impairments in Parkinson's disease.

Background: Parkinson's disease (PD) is well documented to be associated with elevated systemic oxidative stress and perceptual impairments. Furthermore, the striatum and extrastriatal cortical areas, which are involved in the coordination of perceptual functions, are impaired at an early stage of the disease. However, the possible pathophysiology involved in perceptual impairments remains unclear.

The Role of Serial Oxidative Stress Levels in Acute Traumatic Brain Injury and as Predictors of Outcome.

Background: Oxidative stress is thought to participate in the pathobiology of secondary brain injury after acute traumatic brain injury (TBI). This study posits that oxidative stress levels in acute TBI are predictive of outcome.

Methods: Two hundred and twenty-nine blood samples from 88 patients admitted within 24 hours after TBI were obtained on admission and on days 4 and 7.

Liposomal n-butylidenephthalide protects the drug from oxidation and enhances its antitumor effects in glioblastoma multiforme.

Background: The natural compound n-butylidenephthalide (BP) can pass through the blood-brain barrier to inhibit the growth of glioblastoma multiforme tumors. However, BP has an unstable structure that reduces its antitumor activity and half-life in vivo.

Objective: The aim of this study is to design a drug delivery system to encapsulate BP to enhance its efficacy by improving its protection and delivery.

Influence of Absorption, Distribution, Metabolism, and Excretion Genomic Variants on Tacrolimus/Sirolimus Blood Levels and Graft-versus-Host Disease after Allogeneic Hematopoietic Cell Transplantation.

Allelic variants of genes implicated in drug absorption, distribution, metabolism, and excretion (ADME) determine the pharmacokinetic variability of many medications and are increasingly recognized as important factors determining the success or failure of medical treatments. Both tacrolimus and sirolimus have narrow therapeutic ranges maintained by therapeutic drug monitoring (TDM). Using an ADME panel that covers >99% of the PharmaADME working group core list (188 single nucleotide polymorphism [SNP] and 12 copy number variant [CNV] assays in 36 pharmacogenetically relevant genes), we studied 177 patients who underwent allogeneic hematopoietic cell transplantation (HCT) using tacrolimus/sirolimus-based graft-versus-host disease (GVHD) prophylaxis.

Cross-cultural comparisons between the earthquake preparedness models of Taiwan and New Zealand.

Taiwan and New Zealand are both located in the Pacific Rim where 81 per cent of the world's largest earthquakes occur. Effective programmes for increasing people's preparedness for these hazards are essential. This paper tests the applicability of the community engagement theory of hazard preparedness in two distinct cultural contexts.

Autoimmune Hepatitis in Hawai'i.

Autoimmune Hepatitis (AIH) is a poorly understood disease. There has been a paucity of reports on the epidemiology and clinical course of AIH in multiethnic populations. The aim of this study is to examine the clinical and serologic features of AIH in the multiethnic population of Hawai'i.

The tumor suppressor p53 guides GluA1 homeostasis through Nedd4-2 during chronic elevation of neuronal activity.

Chronic activity perturbation in neurons can trigger homeostatic mechanisms to restore the baseline function. Although the importance and dysregulation of neuronal activity homeostasis has been implicated in neurological disorders such as epilepsy, the complete signaling by which chronic changes in neuronal activity initiate the homeostatic mechanisms is unclear. We report here that the tumor suppressor p53 and its signaling are involved in neuronal activity homeostasis.

Results of a Multicenter Phase II Trial of Brentuximab Vedotin as Second-Line Therapy before Autologous Transplantation in Relapsed/Refractory Hodgkin Lymphoma.

This multicenter prospective phase II study examines the activity and tolerability of brentuximab vedotin as second-line therapy in patients with Hodgkin lymphoma that was relapsed or refractory after induction therapy. Brentuximab vedotin (1.8 mg/kg) was administered i.

Clinical Features Associated with Frozen Shoulder Syndrome in Parkinson's Disease.

Background. Frozen shoulder syndrome is a common musculoskeletal disease of idiopathic Parkinson's disease (PD) that causes long-term pain and physical disability. A better understanding of the associated factors can help identify PD patients who will require prevention to improve their quality of life.

Increased circulating endothelial progenitor cells and anti-oxidant capacity in obstructive sleep apnea after surgical treatment.

Background: Obstructive sleep apnea (OSA) has increased risk of cardiovascular diseases. Profiles of endothelial progenitor cells (EPCs) reflect the degree of endothelial impairment. This study tested the hypothesis that surgical treatment not only improves clinical outcomes but also increases the number of circulating EPCs and antioxidant capacity.