Associations of Variability in Blood Pressure, Glucose and Cholesterol Concentrations, and Body Mass Index With Mortality and Cardiovascular Outcomes in the General Population.

Background: Variability in metabolic parameters, such as fasting blood glucose and cholesterol concentrations, blood pressure, and body weight can affect health outcomes. We investigated whether variability in these metabolic parameters has additive effects on the risk of mortality and cardiovascular outcomes in the general population.

Methods: Using nationally representative data from the Korean National Health Insurance System, 6 748 773 people who were free of diabetes mellitus, hypertension, and dyslipidemia and who underwent ≥3 health examinations from 2005 to 2012 were followed to the end of 2015.

A novel peripheral cannabinoid 1 receptor antagonist, AJ5012, improves metabolic outcomes and suppresses adipose tissue inflammation in obese mice.

The overactivity of cannabinoid 1 receptor (CB1R) is associated with obesity and type 2 diabetes. First-generation CB1R antagonists, such as rimonabant, offered therapeutic advantages for the control of obesity and related metabolic abnormalities, but their therapeutic potential was limited by undesirable neuropsychiatric side effects. Here, we evaluated AJ5012 as a novel potent peripheral CB1R antagonist and, using this antagonist, investigated the role of peripheral CB1R on adipose tissue inflammation in obese mouse models.

Nondiagnostic Percutaneous Transthoracic Needle Biopsy of Lung Lesions: A Multicenter Study of Malignancy Risk.

Purpose To evaluate the malignancy risk of lung lesions that show nondiagnostic results at transthoracic needle biopsy (PTNB) of the lung and to identify any malignancy-associated risk factors in each nondiagnostic category. Materials and Methods In this retrospective study, 9384 initial PTNBs (9239 patients [mean age, 65 years; age range, 20-99 years] consisting of 5729 men [mean age, 66 years; age range, 20-99 years] and 3510 women [mean age, 63 years; age range, 20-94 years]) were performed in eight institutions between January 2010 and December 2014. PTNB results were categorized as diagnostic (malignant or specifically benign) or nondiagnostic (nonspecific benign pathologic findings, atypical cells, or insufficient specimen), and the proportion of final malignant diagnoses per nondiagnostic category was obtained.

The Role of Culture of Origin on the Effectiveness of a Parents-Involved Intervention to Prevent Substance Use Among Latino Middle School Youth: Results of a Cluster Randomized Controlled Trial.

The purpose of this study was to assess the combined effectiveness of a parenting intervention, Families Preparing the New Generation (FPNG), and a youth curriculum, keepin' it REAL (kiR), on substance use prevention for middle school students in a large urban metro area of the southwest USA. The study aimed to generate usable knowledge on what works in adolescent substance use prevention and how it works best-a combined parent and youth programming or parent-only programming. A total of 532 adolescents in the 7th grade from 19 participating middle schools were randomly assigned into three intervention conditions: parent-youth (PY), parent-only (PO), and comparison (C).

Leveraging the genetic basis of Rett syndrome to ascertain pathophysiology.

Mutations in the methyl-CpG binding protein 2 (MECP2) gene cause Rett syndrome (RTT), a progressive X-linked neurological disorder characterized by loss of developmental milestones, intellectual disability and breathing abnormality. Despite being a monogenic disorder, the pathogenic mechanisms by which mutations in MeCP2 impair neuronal function and underlie the RTT symptoms have been challenging to elucidate. The seemingly simple genetic root and the availability of genetic data from RTT patients have led to the generation and characterization of a series of mouse models recapitulating RTT-associated genetic mutations.

Racial differences in neuromyelitis optica spectrum disorder.

Objective: We aimed to evaluate racial differences in the clinical features of neuromyelitis optica spectrum disorder.

Methods: This retrospective review included 603 patients (304 Asian, 207 Caucasian, and 92 Afro-American/Afro-European), who were seropositive for anti-aquaporin-4 antibody, from 6 centers in Denmark, Germany, South Korea, United Kingdom, United States, and Thailand.

Results: Median disease duration at last follow-up was 8 years (range 0.

Lack of Cardiac Improvement After Cardiosphere-Derived Cell Transplantation in Aging Mouse Hearts.

Rationale: Aging is one of the most significant risk factors for cardiovascular diseases, and the incidence of myocardial ischemia increases dramatically with age. Some studies have reported that cardiosphere-derived cells (CDCs) could benefit the injured heart. Nevertheless, the convincing evidence on CDC-induced improvement of aging heart is still limited.

Efficacy and safety of concurrent anti-Cancer and anti-tuberculosis chemotherapy in Cancer patients with active Mycobacterium tuberculosis: a retrospective study.

Background: In our previous study, colorectal cancer (CRC) patients with active Mycobacterium tuberculosis (MTB) tolerated concurrent anti-cancer chemotherapy (anti-CCT) and anti-MTB chemotherapy. In this study, we retrospectively confirmed the efficacy and safety of concurrent chemotherapy in a greater number of patients with different types of malignancies.

Methods: We enrolled 30 patients who were treated concurrently with anti-CCT and anti-MTB regimens between January 2006 and February 2016.

RNA editing derived epitopes function as cancer antigens to elicit immune responses.

In addition to genomic mutations, RNA editing is another major mechanism creating sequence variations in proteins by introducing nucleotide changes in mRNA sequences. Deregulated RNA editing contributes to different types of human diseases, including cancers. Here we report that peptides generated as a consequence of RNA editing are indeed naturally presented by human leukocyte antigen (HLA) molecules.

Self-management Needs of Breast Cancer Survivors After Treatment: Results From a Focus Group Interview.

Background: Recognition of the importance of self-management (SM) for breast cancer survivors (BCSs) is increasing, but evidence from investigations of their needs focusing on SM is limited.

Objectives: The aim of this study was to explore the SM needs of BCSs who had completed treatment.

Methods: Using a qualitative study design, we interviewed a focus group of 20 BCSs who underwent cancer therapy (mean time since diagnosis 3.

C1q/TNF-α-Related Protein 1 (CTRP1) Maintains Blood Pressure Under Dehydration Conditions.

Rationale: Circulating CTRP1 (C1q/TNF-α [tumor necrosis factor-α]-related protein 1) levels are increased in hypertensive patients compared with those in healthy subjects. Nonetheless, little is known about the molecular and physiological function of CTRP1 in blood pressure (BP) regulation.

Objective: To investigate the physiological/pathophysiological role of CTRP1 in BP regulation.

Differential effects of completed and incomplete pregnancies on the risk of Alzheimer disease.

Objective: To investigate the effects of completed pregnancy with childbirth and incomplete pregnancy without childbirth on the late-life cognition and the risk of Alzheimer disease (AD) in women.

Methods: Using the pooled data of 3,549 women provided by 2 population-based cohort studies, we conducted logistic regression analyses to examine retrospectively the associations of completed and incomplete pregnancy with the risks of mild cognitive impairment and AD. For women without dementia, we also conducted analyses of covariance to examine the associations of completed and incomplete pregnancy with Mini-Mental State Examination (MMSE) score.

Proinsulin C-peptide prevents hyperglycemia-induced vascular leakage and metastasis of melanoma cells in the lungs of diabetic mice.

C-peptide has a beneficial effect against diabetic complications, but its role in hyperglycemia-induced metastasis is unknown. We investigated hyperglycemia-mediated pulmonary vascular leakage and metastasis and C-peptide inhibition of these molecular events using human pulmonary microvascular endothelial cells (HPMVECs) and streptozotocin-induced diabetic mice. VEGF, which is elevated in the lungs of diabetic mice, activated transglutaminase 2 (TGase2) in HPMVECs by sequential elevation of intracellular Ca and reactive oxygen species (ROS) levels.

Trajectory Groups of 24-Hour Systolic Blood Pressure After Acute Ischemic Stroke and Recurrent Vascular Events.

Background and Purpose- Blood pressure dynamics in patients with acute ischemic stroke may serve as an important modifiable and prognostic factor. Methods- A total of 8376 patients with acute ischemic stroke were studied from a prospective multicenter registry. Patients were eligible if they had been admitted within 24 hours of symptom onset and had ≥5 systolic blood pressure (SBP) measurements during the first 24 hours of hospitalization.

Intracranial Hemorrhage in Deep Vein Thrombosis/Pulmonary Embolus Patients Without Atrial Fibrillation.

Background and Purpose- Deep vein thrombosis (DVTs) is a common disease with high morbidity if it progresses to pulmonary embolus (PE). Anticoagulation is the treatment of choice; warfarin has long been the standard of care. Early experience with direct oral anticoagulants (DOACs) suggests that these agents may be may be a safer and equally effective alternative in the treatment of DVT/PE.

Serious Hypoglycemia and Use of Warfarin in Combination With Sulfonylureas or Metformin.

Prior research suggests that warfarin, when given concomitantly with some sulfonylureas, may increase the risk of serious hypoglycemia. However, the clinical significance remains unclear. We examined rate ratios (RRs) for the association between serious hypoglycemia and concomitant use of warfarin with either sulfonylureas or metformin using a self-controlled case series design and US Medicaid claims (supplemented with Medicare claims) from 1999 to 2011.

The benzodiazepine anesthetic midazolam prevents hyperglycemia-induced microvascular leakage in the retinas of diabetic mice.

We investigated the beneficial effects of midazolam against vascular endothelial growth factor (VEGF)-induced vascular leakage and its molecular mechanism of action in human retinal endothelial cells (HRECs) and the retinas of diabetic mice. Midazolam inhibited VEGF-induced elevation of intracellular Ca, generation of reactive oxygen species (ROS), and transglutaminase activation in HRECs; these effects were reversed by the GABA, type A (GABA) receptor antagonist flumazenil but not by the translocator protein antagonist PK11195. Midazolam also prevented VEGF-induced disassembly of adherens junctions and in vitro permeability.

Tofacitinib induction and maintenance therapy in East Asian patients with active ulcerative colitis: subgroup analyses from three phase 3 multinational studies.

Background/aims: Tofacitinib is an oral, small-molecule Janus kinase inhibitor being investigated for ulcerative colitis (UC). In OCTAVE Induction 1 and 2, patients with moderately to severely active UC received placebo or tofacitinib 10 mg twice daily (BID) for 8 weeks. Clinical responders in OCTAVE Induction were re-randomized to 52 weeks' therapy with placebo, tofacitinib 5 mg BID, or tofacitinib 10 mg BID.

Monitoring Cerebral Perfusion Changes after Revascularization in Patients with Moyamoya Disease by Using Arterial Spin-labeling MR Imaging.

Purpose To determine whether arterial spin-labeling (ASL) magnetic resonance (MR) imaging could be used to identify changes in cerebral blood flow (CBF), collateral blood flow, and anastomosis site patency after revascularization in patients with moyamoya disease. Materials and Methods This retrospective study was conducted in 145 patients with moyamoya disease who underwent middle cerebral artery (MCA)-superficial temporal artery anastomosis. Preoperative, early postoperative, and late postoperative ASL and digital subtraction angiography images were analyzed.

Hydrophobic Patterning-Based 3D Microfluidic Cell Culture Assay.

Engineering physiologically relevant in vitro models of human organs remains a fundamental challenge. Despite significant strides made within the field, many promising organ-on-a-chip models fall short in recapitulating cellular interactions with neighboring cell types, surrounding extracellular matrix (ECM), and exposure to soluble cues due, in part, to the formation of artificial structures that obstruct >50% of the surface area of the ECM. Here, a 3D cell culture platform based upon hydrophobic patterning of hydrogels that is capable of precisely generating a 3D ECM within a microfluidic channel with an interaction area >95% is reported.

Posttreatment National Institutes of Health Stroke Scale Is Superior to the Initial Score or Thrombolysis in Cerebral Ischemia for 3-Month Outcome.

Background And Purpose: The majority of ischemic stroke patients receiving endovascular recanalization therapy (EVT) experience variable changes of neurological severities during the hyperacute period. We hypothesized that the National Institutes of Health Stroke Scale (NIHSS) score after EVT is a better prognostic factor compared with the initial NIHSS score or revascularization status.

Methods: We identified 566 stroke patients who received EVT at Seoul National University Bundang Hospital between April 2008 and December 2015.

Whole-Tumor Histogram and Texture Analyses of DTI for Evaluation of -Mutation and 1p/19q-Codeletion Status in World Health Organization Grade II Gliomas.

Background And Purpose: Prediction of the (IDH1)-mutation and 1p/19q-codeletion status of World Health Organization grade ll gliomas preoperatively may assist in predicting prognosis and planning treatment strategies. Our aim was to characterize the histogram and texture analyses of apparent diffusion coefficient and fractional anisotropy maps to determine -mutation and 1p/19q-codeletion status in World Health Organization grade II gliomas.

Materials And Methods: Ninety-three patients with World Health Organization grade II gliomas with known mutation and 1p/19q-codeletion status (18 wild-type, 45 mutant and no 1p/19q codeletion, 30 mutant and 1p/19q codeleted tumors) underwent DTI.