The Pythagorean theorem reveals the inherent companion of cardiac ejection fraction.

Background: Quantification of ventricular performance requires a comprehensive metric which is manageable for patient care and clinical trials. Ejection fraction (EF) has been embraced as an attractive candidate. However, being a dimensionless ratio, EF has serious limitations.

Liver fibrosis: Pathophysiology, pathogenetic targets and clinical issues.

The progression of chronic liver diseases (CLD), irrespective of etiology, involves chronic parenchymal injury, persistent activation of inflammatory response as well as sustained activation of liver fibrogenesis and wound healing response. Liver fibrogenesis, is a dynamic, highly integrated molecular, cellular and tissue process responsible for driving the excess accumulation of extracellular matrix (ECM) components (i.e.

Apathy in Alzheimer's disease.

Apathy is the most common neuropsychiatric symptom in patients with Alzheimer's disease (AD). The presence of apathy has been related to greater caregiver distress, decreased quality of life, and increased morbidity. Here we review the most recent studies on this neuropsychiatric syndrome, focusing on prevalence, impact on quality of life, behavioural and neuroimaging studies, and treatment options.

Human papillomavirus genotypes in Pacific Islander cervical cancer patients.

Objective: The role of human papillomavirus (HPV) in the development of invasive cervical cancers is widely known. Few HPV studies have targeted geographically isolated regions. The objective of this study was to determine the HPV genotypes in cervical cancer patients from the Pacific Islands referred to Tripler Army Medical Center (TAMC).

Glucose lowering strategies and cardiovascular disease in type 2 diabetes - teachings from the TOSCA.IT study.

TOSCA.IT is an institutional, non-industry-supported, head-to-head study comparing long term cardiovascular effects, efficacy and safety of two antidiabetes drugs (pioglitazone vs sulphonylureas) used in combination with metformin in patients with type 2 diabetes mellitus. The study results show that in the absence of clinically evident cardiovascular disease both treatment strategies represent suitable alternatives; however, in consideration of the greater durability of the metabolic effects, the lower risk of hypoglycemia and the potential benefit on atherosclerotic cardiovascular disease, the combination of metformin and pioglitazone may be considered as the preferential therapeutic option.

Sputum proteomics and airway cell transcripts of current and ex-smokers with severe asthma in U-BIOPRED: an exploratory analysis.

Severe asthma patients with a significant smoking history have airflow obstruction with reported neutrophilia. We hypothesise that multi-omic analysis will enable the definition of smoking and ex-smoking severe asthma molecular phenotypes.The U-BIOPRED cohort of severe asthma patients, containing current-smokers (CSA), ex-smokers (ESA), nonsmokers and healthy nonsmokers was examined.

Burden of illness of chemotherapy in castration-resistant prostate cancer patients in Japan: a retrospective database analysis.

Objective: The objective was to assess the burden of chemotherapy for castration-resistant prostate cancer (CRPC) in Japan.

Methods: Utilizing a large administrative hospital database we compared a set of outcome measures 12 months before and after initiation of chemotherapy, namely total medical costs, number of outpatient visits, number of hospital admissions and number of days spent in hospital.

Results: A total of 598 CRPC patients were identified in the database.

Progression of corticospinal tract dysfunction in pre-ataxic spinocerebellar ataxia type 2: A two-years follow-up TMS study.

Objective: Corticospinal tract (CST) dysfunction is common in the pre-ataxic stage of spinocerebellar ataxia type 2 (SCA2) but quantitative assessment of its progression over time has not been explored. The aim of this study was to quantify the progression of CST dysfunction in pre-ataxic SCA2 using transcranial magnetic stimulation (TMS).

Methods: Thirty-three pre-ataxic SCA2 mutation carriers and a 33 age- and gender-matched healthy controls were tested at baseline and 2-years follow-up by standardized clinical exams, validated clinical scales, and TMS.

Molecular surveillance of novel tick-borne organisms in Madagascar's lemurs.

The discovery and characterization of emerging tick-borne organisms are critical for global health initiatives to improve animal and human welfare (One Health). It is possible that unknown tick-borne organisms underlie a subset of undiagnosed illness in wildlife, domesticated species, and humans. Our study lends support to the One Health concept by highlighting the prevalence of three blood-borne organisms in wild lemurs living in close proximity to domesticated species and humans.

A pilot trial of l-carnitine in patients with traumatic brain injury: Effects on biomarkers of injury.

Objective: To investigate the effects of l-Carnitine on neuron specific enolase (NSE) as a marker of inflammation in patients with traumatic brain injury (TBI).

Methods: Forty patients with severe TBI were randomized into 2 groups. The (LCA-) group received standard treatment with placebo while the (LCA+) group received l-Carnitine 2g/day for one week.

Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2D6 and Tamoxifen Therapy.

Tamoxifen is biotransformed by CYP2D6 to 4-hydroxytamoxifen and 4-hydroxy N-desmethyl tamoxifen (endoxifen), both with greater antiestrogenic potency than the parent drug. Patients with certain CYP2D6 genetic polymorphisms and patients who receive strong CYP2D6 inhibitors exhibit lower endoxifen concentrations and a higher risk of disease recurrence in some studies of tamoxifen adjuvant therapy of early breast cancer. We summarize evidence from the literature and provide therapeutic recommendations for tamoxifen based on CYP2D6 genotype.

Effects of a program of cognitive-behavioural group therapy, vestibular rehabilitation, and psychoeducational explanations on patients with dizziness and no quantified balance deficit, compared to patients with dizziness and a quantified balance deficit.

Background: We examined whether a program combining cognitive-behavioural therapy (CBT), vestibular rehabilitation (VR) and psychoeducation is equally effective in improving psychometric measures in patients with dizziness independent of a balance deficit. Measures of patients with dizziness only (DO) were compared to those of patients also having a quantified balance deficit (QBD).

Methods: 32 patients (23 female, 9 male) with persistent dizziness were analysed as 2 groups based on stance and gait balance control: those with QBD (pathological balance) or DO (normal balance).

Early corticospinal tract damage in prodromal SCA2 revealed by EEG-EMG and EMG-EMG coherence.

Objective: Clinical data suggest early involvement of the corticospinal tract (CST) in spinocerebellar ataxia type 2 (SCA2). Here we tested if early CST degeneration can be detected in prodromal SCA2 mutation carriers by electrophysiological markers of CST integrity.

Methods: CST integrity was tested in 15 prodromal SCA2 mutation carriers, 19 SCA2 patients and 25 age-matched healthy controls, using corticomuscular (EEG-EMG) and intermuscular (EMG-EMG) coherence measures in upper and lower limb muscles.

Generation and characterization of human iPSC lines SANi001-A and SANi002-A from mobilized peripheral blood derived megakaryoblasts.

Mobilized peripheral blood (MPB) CD34+ cells were differentiated to CD34/CD41 megakaryoblasts. Cells were sorted to obtain a pure megakaryoblast population which was reprogrammed with a hOKSM self-silencing polycistronic lentiviral vector. Resulting iPSC showed normal karyotype and expression of pluripotency associated markers and in vitro spontaneous differentiation towards the 3 germ layers confirmed pluripotency of iPSC lines.

Generation and characterization of a human iPSC line SANi005-A containing the gray platelet associated heterozygous mutation p.Q287* in GFI1B.

Peripheral blood mononuclear cells were isolated from an individual harboring a heterozygous c.859C→T p.Q287* mutation in GFI1B, causing an autosomal dominant bleeding disorder, platelet type, 17 (BDPLT17).

Effects of feeding time on daily rhythms of neuropeptide and clock gene expression in the rat hypothalamus.

Shiftworkers are exposed to several adverse health conditions, one being eating at night. Food consumption at an unnatural time-of-day is thought to be one of the main factors responsible for the increased risk of developing metabolic diseases, such as obesity and diabetes mellitus. The underlying mechanism is considered to include disruption of the circadian organization of physiology, leading to disruption of metabolism.

Impact of generic substitution on levetiracetam serum concentration-A prospective study in an outpatient setting.

Background: Switching patients from a branded antiepileptic drug (AED) to a generic is often challenging. Several studies have shown that considerable proportions of patients report deteriorated seizure control or increased adverse effects, enforcing a switchback to the original drug. Since tolerability and seizure control usually correlate with AED serum concentrations, we examined the fluctuation of levetiracetam (LEV) serum concentrations in patients with epilepsy before and after generic substitution.

Sodium-dependent glucose transporters (SGLT) in human ischemic heart: A new potential pharmacological target.

Background: Empagliflozin is reported to reduce cardiovascular mortality and the rate of hospitalization for heart failure in type 2 diabetic patients with prior cardiovascular events. The mechanisms underlying the cardiac effects of this sodium/glucose transporter 2 (SGT2) inhibitor have not yet been clarified, though a direct action of the drug on the cardiomyocytes could be hypothesized. The aim of the present study is to assess the relative expression of SGLT2 and SGLT1, the two most relevant members of the SGLT family being potentially responsive to empagliflozin, in normal, ischemic and hypertrophic human hearts.

Defining Skin Ulcers in Systemic Sclerosis: Systematic Literature Review and Proposed World Scleroderma Foundation (WSF) definition.

Purpose: There is a lack of a valid, definition for skin ulcers in SSc to be used in clinical trials. Our aim was to develop a consensus definition for SSc-skin ulcers based on the results of a systematic literature review (SLR) for skin ulcer definitions and expert opinion; and to evaluate its face validity, reliability and feasibility.

Methods: SLR for skin ulcer definitions was conducted using PubMed, Web of Science, and Cochrane library for articles published from inception to January 1, 2016.

Generation and characterization of human iPSC line MML-6838-Cl2 from mobilized peripheral blood derived megakaryoblasts.

Mobilized peripheral blood (MPB) CD34+ cells were cultured to CD41+/CD34+ megakaryoblasts. Cells were sorted to obtain a pure megakaryoblast population that was reprogramed by a hOKSM self-silencing polycistronic vector using lentiviral delivery. The generated induced pluripotent stem cell (iPSC) lines were tested for silencing of the reprogramming construct by flow cytometry.

High expression of PDGFR-β in prostate cancer stroma is independently associated with clinical and biochemical prostate cancer recurrence.

Due to a lack of sufficient diagnostic tools to predict aggressive disease, there is a significant overtreatment of patients with prostate cancer. Platelet derived growth factors (PDGFs) and their receptors (PDGFRs) are key regulators of mesenchymal cells in the tumor microenvironment, and has been associated with unfavorable outcome in several other cancers. Herein, we aimed to investigate the prognostic impact of PDGFR-β and its ligands (PDGF-B and PDGF-D) in a multicenter prostatectomy cohort of 535 Norwegian patients.

Transmission of hepatitis E virus infection to human-liver chimeric FRG mice using patient plasma.

Hepatitis E virus (HEV) is considered as an important pathogen in developing countries but there is growing evidence of its increasing significance and prevalence in the Western world. Although most acute HEV infections resolve spontaneously, chronicity has been observed in immunocompromised patients. The study of HEV has been hampered by the absence of practical animal models.