FOXO3 longevity interactome on chromosome 6.

FOXO3 has been implicated in longevity in multiple populations. By DNA sequencing in long-lived individuals, we identified all single nucleotide polymorphisms (SNPs) in FOXO3 and showed 41 were associated with longevity. Thirteen of these had predicted alterations in transcription factor binding sites.

Marinesco bodies and substantia nigra neuron density in Parkinson's disease.

Aim: Marinesco bodies (MB) are intranuclear inclusions in pigmented neurons of the substantia nigra (SN). While rare in children, frequency increases with normal ageing and is high in Alzheimer's disease, dementia with Lewy bodies and other neurodegenerative disorders. Coinciding with the age-related rise in MB frequency is initiation of cell death among SN neurons.

HLA-DRB1*04:05 allele is associated with intracortical lesions on three-dimensional double inversion recovery images in Japanese patients with multiple sclerosis.

Background: Cortical lesions (CLs) frequently observed in Caucasian patients with multiple sclerosis (MS) contribute to disability. However, it remains unclear whether CLs are associated with clinical features and genetic risk factors, such as HLA-DRB1*15:01 and -DRB1*04:05 in Asian MS patients.

Objective: To elucidate the frequency of CLs and their association with HLA-DRB1 and DPB1 alleles in Japanese MS patients.

Serum HMGB1 concentrations at 4 weeks is a useful predictor of extreme poor prognosis for advanced hepatocellular carcinoma treated with sorafenib and hepatic arterial infusion chemotherapy.

Background: Biomarkers predicting the response to the anticancer treatment and prognosis in patients with advanced hepatocellular carcinoma (HCC) are required. Recently, high mobility group box 1 (HMGB1) was reported to promote HCC progression and be associated with poor prognosis for patients with HCC. The purpose of this study was to assess serum HMGB1 concentrations before and during sorafenib treatment or hepatic arterial infusion chemotherapy (HAIC) and to explore the ability of serum HMGB1 concentrations to predict prognosis.

Effective enhancement of polylactic acid-degrading enzyme production by Amycolatopsis sp. strain SCM_MK2-4 using statistical and one-factor-at-a-time approaches.

This study aims to find the optimal medium and conditions for polylactic acid (PLA)-degrading enzyme production by Amycolatopsis sp. SCM_MK2-4. Screening of the most effective components in the enzyme production medium by Plackett-Burman design revealed that the silk cocoon and PLA film were the most significant variables enhancing the PLA-degrading enzyme production.

Individual patient data meta-analysis of controlled attenuation parameter (CAP) technology for assessing steatosis.

Background & Aims: The prevalence of fatty liver underscores the need for non-invasive characterization of steatosis, such as the ultrasound based controlled attenuation parameter (CAP). Despite good diagnostic accuracy, clinical use of CAP is limited due to uncertainty regarding optimal cut-offs and the influence of covariates. We therefore conducted an individual patient data meta-analysis.

Th1 cells downregulate connexin 43 gap junctions in astrocytes via microglial activation.

We previously reported early and extensive loss of astrocytic connexin 43 (Cx43) in acute demyelinating lesions of multiple sclerosis (MS) patients. Because it is widely accepted that autoimmune T cells initiate MS lesions, we hypothesized that infiltrating T cells affect Cx43 expression in astrocytes, which contributes to MS lesion formation. Primary mixed glial cell cultures were prepared from newborn mouse brains, and microglia were isolated by anti-CD11b antibody-conjugated magnetic beads.

Progression of coronary artery calcium in Japanese American men and white men in the ERA JUMP study.

Background: Progression of coronary artery calcium (CAC) is associated with increased risk of coronary heart disease (CHD) and is reported to be greater in whites than blacks, Hispanics, and Chinese in the US. Our objective was to compare progression of CAC between Japanese Americans and whites.

Methods: Population-based sample of 303 Japanese American men and 310 white men aged 40-49years, free of clinical cardiovascular disease at baseline, were examined for CAC at baseline (2004-2007) and follow-up (2008-2013).

Allergic Inflammation Leads to Neuropathic Pain via Glial Cell Activation.

Unlabelled: Allergic and atopic disorders have increased over the past few decades and have been associated with neuropsychiatric conditions, such as autism spectrum disorder and asthmatic amyotrophy. Myelitis presenting with neuropathic pain can occur in patients with atopic disorder; however, the relationship between allergic inflammation and neuropathic pain, and the underlying mechanism, remains to be established. We studied whether allergic inflammation affects the spinal nociceptive system.

Increased Aortic Calcification Is Associated With Arterial Stiffness Progression in Multiethnic Middle-Aged Men.

Arterial stiffness is established as an independent predictor of cardiovascular morbidity and mortality. The objective was to prospectively evaluate association of aortic calcification burden with progression of arterial stiffness in population-based samples of healthy middle-aged men from ERA JUMP cohort (Electron-Beam Computed Tomography and Risk Factor Assessment in Japanese and US Men in the Post-World War II Birth Cohort). Men (n=635) aged 40 to 49 years (207 white American, 45 black American, 142 Japanese American, and 241 Japanese in Japan) were examined at baseline and 4 to 7 years later.

A Significant Positive Association of Vitamin D Deficiency with Coronary Artery Calcification among Middle-aged Men: For the ERA JUMP Study.

Objective: Although a significant positive association of vitamin D deficiency with coronary heart disease has been demonstrated in cross-sectional as well as prospective studies, only a few studies have examined the association of vitamin D deficiency with subclinical atherosclerosis. We examined whether vitamin D deficiency is associated with subclinical atherosclerosis, as measured by coronary artery calcification (CAC) in asymptomatic adults.

Methods: In a population-based cross-sectional study, 195 men aged 40 to 49 years without cardiovascular disease were randomly selected (98 Caucasian and 97 Japanese American men).

Antiviral effects of anti-HBs immunoglobulin and vaccine on HBs antigen seroclearance for chronic hepatitis B infection.

Background And Aims: Interferon and nucleotide/nucleoside analogues are the main treatments for chronic hepatitis B. These drugs effectively reduce serum hepatitis B virus (HBV) DNA titers but fail to sufficiently reduce hepatitis B surface antigen (HBsAg) levels. Following the recent identification of sodium taurocholate cotransporting polypeptide as a receptor for HBV entry, inhibition of HBV entry has become an attractive therapeutic target for chronic hepatitis B treatment.

The role of initial and longitudinal change in blood pressure on progression of arterial stiffness among multiethnic middle-aged men.

Objective: A few studies have examined the longitudinal association of blood pressure (BP) with arterial stiffness progression, and the results were inconsistent. The objective of this study was to investigate the roles of initial BP and its longitudinal change on the progression of arterial stiffness measured using brachial-ankle pulse wave velocity (baPWV).

Method: Study participants (n = 656) were from population-based samples of healthy men aged 40-49 years at baseline (213 White Americans, 47 African-Americans, 152 Japanese Americans and 244 Japanese in Japan).

The Effect of Vascular Neuropathology on Late-life Cognition: Results from the SMART Project.

Background: Cerebral vascular pathology may contribute to cognitive decline experienced by some elderly near death. Given evidence for mixed neuropathologies in advanced age, preventing or reducing cerebrovascular burden in late life may be beneficial.

Objective: To correlate measures of cerebral vascular pathology with cognitive trajectories.

Longevity-Associated FOXO3 Genotype and its Impact on Coronary Artery Disease Mortality in Japanese, Whites, and Blacks: A Prospective Study of Three American Populations.

Background: We recently reported that protection against coronary artery disease (CAD) mortality is the major contributor to longer life associated with FOXO3 genotype. The present study examined this relation in more detail.

Methods: We performed a 15-year observational study of 3,584 older American men of Japanese ancestry from the Kuakini Honolulu Heart Program cohort and 1,595 White and 1,067 Black elderly individuals from the Health Aging and Body Composition study.

Subclinical Thyroid Dysfunction and the Risk of Cognitive Decline: a Meta-Analysis of Prospective Cohort Studies.

Context: Although both overt hyper- and hypothyroidism are known to lead to cognitive impairment, data on the association between subclinical thyroid dysfunction and cognitive function are conflicting.

Objective: This study sought to determine the risk of dementia and cognitive decline associated with subclinical thyroid dysfunction among prospective cohorts.

Data Sources: We searched in MEDLINE and EMBASE from inception until November 2014.

Highly multiplexed CRISPR-Cas9-nuclease and Cas9-nickase vectors for inactivation of hepatitis B virus.

CRISPR-Cas9-mediated genome-editing technology contributes not only to basic genomic studies but also to clinical studies such as genetic correction and virus inactivation. Hepatitis B virus (HBV) is a major target for potential application of CRISPR-Cas9 in eliminating viral DNA from human cells. However, the high stability of covalently closed circular DNA (cccDNA) makes it difficult to completely clear HBV infection.

What's the Plan? Needing Assistance with Plan of Care Is Associated with In-Hospital Death for ICU Patients Referred for Palliative Care Consultation.

To inform earlier identification of intensive care unit (ICU) patients needing palliative care, we examined factors associated with in-hospital death among ICU patients (N=260) receiving palliative care consultations at a 542-bed tertiary care hospital (2005-2009). High pre-consultation length of stay (LOS, ≥7 days) (adjusted odds ratio (aOR)=5.0, 95% confidence interval (95% CI)=2.

The relationship between HBcrAg and HBV reinfection in HBV related post-liver transplantation patients.

Background: Post-transplant hepatitis B virus (HBV) reinfection is one of the major problems facing patients who undergo HBV-related liver transplantation (LT). We analyzed the clinical impact of serum hepatitis B core-related antigen (HBcrAg) on HBV reinfection in post-LT patients with HBV-related liver diseases.

Methods: Serum hepatitis B surface antigen (HBsAg), HBV DNA, and HBcrAg were measured over time in 32 post-LT patients.

Association of Polymorphisms in Connective Tissue Growth Factor and Epidermal Growth Factor Receptor Genes With Human Longevity.

Growth pathways play key roles in longevity. The present study tested single-nucleotide polymorphisms (SNPs) in the connective tissue growth factor gene (CTGF) and the epidermal growth factor receptor gene (EGFR) for association with longevity. Comparison of allele and genotype frequencies of 12 CTGF SNPs and 41 EGFR SNPs between 440 American men of Japanese ancestry aged ≥95 years and 374 men of average life span revealed association with longevity at the p < .

Person-centered Feeding Care: A Protocol to Re-introduce Oral Feeding for Nursing Home Patients with Tube Feeding.

Background: Although the literature on nursing home (NH) patients with tube feeding (TF) has focused primarily on the continuation vs. discontinuation of TF, the reassessment of these patients for oral feeding has been understudied. Re-assessing patients for oral feeding may be better received by families and NH staff than approaches focused on stopping TF, and may provide an opportunity to address TF in less cognitively impaired patients as well as those with end-stage conditions.