Angiotensin 1‐7 modulates electrophysiological characteristics and calcium homoeostasis in pulmonary veins cardiomyocytes via MAS/PI3K/eNOS signalling pathway

Background

Atrial fibrillation (AF) is the most common sustained arrhythmia, and pulmonary veins (PVs) play a critical role in triggering AF. Angiotensin (Ang)‐(1‐7) regulates calcium (Ca²⁺) homoeostasis and also plays a critical role in cardiovascular pathophysiology. However, the role of Ang‐(1‐7) in PV arrhythmogenesis remains unclear.

Materials and methods

Conventional microelectrodes, whole‐cell patch‐clamp and the fluo‐3 fluorimetric ratio technique were used to record ionic currents and intracellular Ca²⁺ in isolated rabbit PV preparations and in single isolated PV cardiomyocytes, before and after administration of Ang‐(1‐7).

Results

Ang (1‐7) concentration dependently (0.1, 1, 10 and 100 nmol/L) decreased PV spontaneous electrical activity. Ang‐(1‐7) (100 nmol/L) decreased the late sodium (Na⁺), L‐type Ca²⁺ and Na⁺‐Ca²⁺ exchanger currents, but did not affect the voltage‐dependent Na⁺ current in PV cardiomyocytes. In addition, Ang‐(1‐7) decreased intracellular Ca²⁺ transient and sarcoplasmic reticulum Ca²⁺ content in PV cardiomyocytes. A779 (a Mas receptor blocker, 3 μmol/L), L‐NAME (a NO synthesis inhibitor, 100 μmol/L) or wortmannin (a specific PI3K inhibitor, 10 nmol/L) attenuated the effects of Ang‐(1‐7) (100 nmol/L) on PV spontaneous electric activity.

Conclusion

Ang‐(1‐7) regulates PV electrophysiological characteristics and Ca²⁺ homoeostasis via Mas/PI3K/eNOS signalling pathway.     

Evaluating the size criterion for PI-RADSv2 category 5 upgrade: is 15 mm the best threshold?

Purpose

The purpose of the study was to determine if the ≥ 15 mm threshold currently used to define PIRADS 5 lesions is the optimal size threshold for predicting high likelihood of clinically significant (CS) cancers.

Materials

Three hundred and fifty-eight lesions that may be changed from category 4 to 5 or vice versa on the basis of the size criterion (category 4: n = 288, category 5: n = 70) from 255 patients were evaluated. Kendall’s tau-b statistic accounting for inter-lesion correlation, generalized estimation equation logistic regression, and receiver operating curve analysis evaluated two lesion size-metrics (lesion diameter and relative lesion diameter—defined as lesion diameter/prostate volume) for ability to identify CS (Gleason grade ≥ 3 + 4) cancer at targeted biopsy. Optimal cut-points were identified using the Youden index. Analyses were performed for the whole prostate (WP) and zone-specific sub-cohorts of lesions in the peripheral and transition zones (PZ and TZ).

Results

Lesion diameter showed a modest correlation with Gleason grade (WP: τB = 0.21, p < 0.0001; PZ: τB = 0.13, p = 0.02; TZ: τB = 0.32, p = 0.001), and association with CS cancer detection (WP: AUC = 0.63, PZ: AUC = 0.59, TZ: AUC = 0.74). Empirically derived thresholds (WP: 14 mm, PZ: 13 mm, TZ: 16 mm) performed similarly to the current ≥ 15 mm standard. Lesion relative lesion diameter improved identification of CS cancers compared to lesion diameter alone (WP: τB = 0.30, PZ: τB = 0.24, TZ: τB = 0.42, all p < 0.0001). AUC also improved for WP and PZ lesions (WP: AUC = 0.70, PZ: AUC = 0.68, and TZ: AUC = 0.74).

Conclusions

The current ≥ 15 mm diameter threshold is a reasonable delineator of PI-RADS category 4 and category 5 lesions in the absence of extraprostatic extension to predict CS cancers. Additionally, relative lesion diameter can improve identification of CS cancers and may serve as another option for distinguishing category 4 and 5 lesions.

     

Trends in Medicare Part D Medication Therapy Management Eligibility Criteria

Background

To increase the enrollment rate of medication therapy management (MTM) programs in Medicare Part D plans, the US Centers for Medicare & Medicaid Services (CMS) lowered the allowable eligibility thresholds based on the number of chronic diseases and Part D drugs for Medicare Part D plans for 2010 and after. However, an increase in MTM enrollment rates has not been realized.

Objectives

To describe trends in MTM eligibility thresholds used by Medicare Part D plans and to identify patterns that may hinder enrollment in MTM programs.

Methods

This study analyzed data extracted from the Medicare Part D MTM Programs Fact Sheets (2008–2014). The annual percentages of utilizing each threshold value of the number of chronic diseases and Part D drugs, as well as other aspects of MTM enrollment practices, were analyzed among Medicare MTM programs that were established by Medicare Part D plans.

Results

For 2010 and after, increased proportions of Medicare Part D plans set their eligibility thresholds at the maximum numbers allowable. For example, in 2008, 48.7% of Medicare Part D plans (N = 347:712) opened MTM enrollment to Medicare beneficiaries with only 2 chronic disease states (specific diseases varied between plans), whereas the other half restricted enrollment to patients with a minimum of 3 to 5 chronic disease states. After 2010, only approximately 20% of plans opened their MTM enrollment to patients with 2 chronic disease states, with the remaining 80% restricting enrollment to patients with 3 or more chronic diseases.

Conclusion

The policy change by CMS for 2010 and after is associated with increased proportions of plans setting their MTM eligibility thresholds at the maximum numbers allowable. Changes to the eligibility thresholds by Medicare Part D plans might have acted as a barrier for increased MTM enrollment. Thus, CMS may need to identify alternative strategies to increase MTM enrollment in Medicare plans.     

Patients at lower risk of arrhythmia recurrence: a subgroup in whom implantable defibrillators may not offer benefit. Antiarrhythmics Versus Implantable Defibrillator (AVID) Trial Investigators

OBJECTIVES: The goal of this study was to identify subgroups of arrhythmia patients who do not benefit from use of the implantable cardiac defibrillator (ICD). BACKGROUND: Treatment of serious ventricular arrhythmias has evolved toward more common use of the ICD. Since estimates of the cost per year of life saved by ICD therapy vary from $25,000 to perhaps $125,000, it is important to identify patient subgroups that do not benefit from the ICD. METHODS: Data for 491 ICD patients enrolled in the Antiarrhythmics Versus Implantable Defibrillators Study were used to create a hazards model relating baseline factors to time to first recurrent arrhythmia. The model was used to predict the hazard for recurrent arrhythmia among all trial patients. A priori cut points provided lower and higher recurrent arrhythmia risk strata. For each stratum the incremental years of life due to ICD versus antiarrhythmic drug therapy were calculated. RESULTS: Factors that predicted recurrent arrhythmia were: ventricular tachycardia as the index arrhythmia, history of cerebrovascular disease, lower left ventricular ejection fraction, a history of any tachyarrhythmia before the index event and the absence of revascularization after the index event. Survival times (over a follow-up of three years) were identical in each arm of the lowest risk sextile (survival advantage 0.03 +/- 0.12 [se] years), while the survival advantage for patients above the first sextile was 0.27 +/- 0.07 (se) years (two-sided p = 0.05). CONCLUSIONS: Patients presenting with an isolated episode of ventricular fibrillation in the absence of cerebrovascular disease or history of prior arrhythmia who have undergone revascularization or who have moderately preserved left ventricular function (left ventricular ejection fraction > 0.27) are not likely to benefit from ICD therapy compared with amiodarone therapy.     

The high prevalence of Legionella pneumophila contamination in hospital potable water systems in Taiwan: implications for hospital infection control in Asia.

BACKGROUND: The major sources of Legionnaires' disease (LD) are the potable water systems of large buildings including hospitals, nursing homes, and hotels. Culturing the hospital water system for Legionella allows a preventive approach for hospital-acquired LD. However, hospital-acquired LD is rarely reported in Taiwan, and environmental cultures of Legionella in hospital water systems in Taiwan have never been systematically performed. OBJECTIVE: The objective of this study was to determine if Legionella is present in hospital water systems in Taiwan. Water quality analysis was also performed to determine if geographic differences in water quality result in different Legionella positivity rates. METHOD: The water systems of 16 hospitals throughout Taiwan were tested for Legionella by culture. Standardized culture procedures were followed. RESULTS: Legionella pneumophila was isolated from 63% (10/16) of the hospital water systems; 19% (3/16) of the hospitals had an L. pneumophila positive rate greater than 30%. L. pneumophila serogroups 1 and 6 (strains that are most responsible for Legionella infections) were isolated from 80% (8/10) and 60% (6/10), respectively, of the hospitals that yielded L. pneumophila in their water distribution systems. CONCLUSION: As was shown in epidemiological studies in the USA and Spain, hospital-acquired legionellosis may be prevalent but underdiagnosed in Taiwan.     

Human seminal relaxin is a product of the same gene as human luteal relaxin.

Unlike that of other species, which have only one gene encoding relaxin, the human genome contains two nonallelic genes for relaxin, designated H1 and H2, which encode markedly different relaxin peptides. Whereas human relaxin gene H2 is selectively expressed in the ovary, no ovarian expression of gene H1 has been detected. Since relaxin is actively produced in the human male, it is possible to postulate divergent gene expression of relaxin in the male and female. We examined this question directly through the structural determination of human seminal relaxin and its comparison with the structure of human luteal relaxin. Partially purified relaxin, prepared from pooled human seminal plasma which had been delipidated by extraction with acid acetone and hexane, subjected to two cycles of HPLC and an additional purification step by ion-exchange chromatography, was further purified by immunoaffinity chromatography, using a monoclonal antibody to the H2 relaxin A chain which cross-reacts with synthetic H1 relaxin, followed by an additional HPLC step performed on a C4 reverse-phase column. The recovered, purified relaxin was then analyzed by N-terminal gas-phase sequencing and fast atom bombardment mass spectroscopy for determination of the amino acid sequence and molecular ions of the A and B chains, respectively. The results demonstrate that the structure of the predominant relaxin in human semen plasma is derived from the product of the H2 gene, consisting of a N-terminal pyroglutamic acid A-24 A chain and a mixture of B-26 and B-27 B chains. With the exception of degradation of the seminal relaxin B chain C-terminus, this structure is identical to the structure of human luteal relaxin. Therefore, both human seminal and luteal relaxin are products of the H2 gene.     

Adenocarcinoma and infection in a solitary hepatic cyst： A case report

Solitary non-parasitic liver cysts are being increasingly diagnosed due to the increased use of abdominal sonography. The majority of solitary liver cysts are asymptomatic; however, there are some complications which include infection, perforation, spontaneous hemorrhage, obstructive jaundice and neoplastic degeneration. In some cases a cystic liver lesion may mimic a tumor and is difficult to differentiate with standard imaging studies or fine needle aspiration cytology. Here in, we report a case of adenocarcinoma arising in a solitary hepatic cyst complicated with Klebsiella pneumoniae infection. High levels of CEA in the cyst fluid levels suggested malignancy, which was confirmed by pathology of the resected specimen.     

Primary structure and biological activity of human brain-derived neurotrophic factor

Brain-derived neurotrophic factor (BDNF) is a 27-kDa basic protein of noncovalently linked 13.5-kD subunits related to nerve growth factor and is produced by the central nervous system (CNS). BDNF has been shown to promote the survival of neurons located in or directly connected with the CNS and is likely to function in adjusting the cell number within neuronal populations to the need of this projection field. Here we describe the primary structure of a human BDNF cDNA, the biological activities of pure recombinant human BDNF, and the tissue distribution of rat BDNF. BDNF mRNA can be found in some peripheral tissues as well as in the CNS, and recombinant human BDNF is a potent neurotrophic factor for primary peripheral sensory neurons.