Wide metabolite coverage LC-MS/MS assay for the diagnosis of inherited metabolic disorders in urine.

Objective: The laboratory diagnosis of inherited metabolic disorders (IMD) has undergone significant development in recent decades, mainly due to the use of mass spectrometry, which allows rapid multicomponent analysis of a wide range of metabolites. Combined with advanced software tools, the diagnosis becomes more efficient as a benefit for both physicians and patients.

Methods: A hydrophilic interaction liquid chromatography coupled with tandem mass spectrometry assay for determination of urinary purines, pyrimidines, N-acylglycines, N-acetylated amino acids, sugars, sugar alcohols and other diagnostically important biomarkers was developed and validated.

The dementia-friendly community and its implications for healthcare.

Principal goal of the article is to inform health care professionals about the concept of dementia-friendly community (DFC) reflecting the contemporary thinking of living with dementia, i.e. dementia as a disability, equal human rights, a sense of meaning.

SLIDE-Novel Approach to Apocrine Sweat Sampling for Lipid Profiling in Healthy Individuals.

We designed a concept of 3D-printed attachment with porous glass filter disks-SLIDE (Sweat sampLIng DevicE) for easy sampling of apocrine sweat. By applying advanced mass spectrometry coupled with the liquid chromatography technique, the complex lipid profiles were measured to evaluate the reproducibility and robustness of this novel approach. Moreover, our in-depth statistical evaluation of the data provided an insight into the potential use of apocrine sweat as a novel and diagnostically relevant biofluid for clinical analyses.

Directly Measured Adherence to Treatment in Chronic Heart Failure: LEVEL-CHF Registry.

Background: Currently, most available data on the medication adherence of patients with chronic heart failure are based on indirect methods. We examined the level of adherence to medical therapy using a direct method - serum drug level testing.

Methods: We carried out a prospective single-centre registry of patients with chronic heart failure (LEVEL-CHF registry), in whom we analysed serum levels of the medications prescribed for the treatment of heart failure: angiotensin converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers and mineralocorticoid receptor antagonists.

A newborn screening approach to diagnose 3-hydroxy-3-methylglutaryl-CoA lyase deficiency.

3-Hydroxy-3-methylglutaryl-coenzyme A lyase deficiency (HMGCLD) is a rare autosomal recessively inherited metabolic disorder. Patients suffer from avoidable neurologically devastating metabolic decompensations and thus would benefit from newborn screening (NBS). The diagnosis is currently made by measuring dry blood spot acylcarnitines (C5OH and C6DC) followed by urinary organic acid profiling for the differential diagnosis from several other disorders.

Workplace stress and employees' well-being: Evidence from long-term care in the Czech Republic.

Objectives: The aim of this study was to verify the Effort-Reward Imbalance (ERI) model, which served as the basic concept of mapping workplace stress, on the sample of Czech professional caregivers. ERI model examines the relationship between the long-term subjectively perceived level of workers' effort and rewards and analyses the physical and psychosocial consequences of the (im)balance.

Methods: The verification of ERI model in combination with well-being (and its psychosocial consequences) was conducted on a sample of Czech professionals caring for older people in 2014 (N = 265).

Newborn foal with atypical myopathy.

The case of atypical myopathy (AM) in newborn Haflinger foal with clinical signs of depression and weakness appearing 6 hours after birth resulting in recumbency 12 hours after birth is described. The foal's dam was diagnosed with AM in the 6th month of gestation based on clinical signs of a myopathy, elevated serum activity of creatine kinase, metabolomic analysis and the presence of methylenecyclopropyl acetyl carnitine (MCPA-carnitine) in the blood. At the time of delivery, the mare was grazing on a pasture near sycamore trees but was free of clinical signs of AM.

Radio-sensitizing effects of VE-821 and beyond: Distinct phosphoproteomic and metabolomic changes after ATR inhibition in irradiated MOLT-4 cells.

Current anti-cancer strategy takes advantage of tumour specific abnormalities in DNA damage response to radio- or chemo-therapy. Inhibition of the ATR/Chk1 pathway has been shown to be synthetically lethal in cells with high levels of oncogene-induced replication stress and in p53- or ATM- deficient cells. In the presented study, we aimed to elucidate molecular mechanisms underlying radiosensitization of T-lymphocyte leukemic MOLT-4 cells by VE-821, a higly potent and specific inhibitor of ATR.

Hemodiafiltration and plasma levels of axitinib in a patient with metastatic renal clear cell carcinoma.

Background: The standard treatment for metastatic renal cancer is based on vascular endothelial growth factor (VEGF) and mammalian target of rapamycin (mTor) inhibitors. Compared to other advanced tumors, the treatment of renal cancer is highly affected by impaired renal function; therefore, patients with severe renal insufficiency, including patients on hemodialysis, are generally excluded from clinical trials.

Case Report: In the present manuscript we present the case of a renal cancer patient who underwent bilateral nephrectomy and received two lines of treatment.

Family Carers' Perspectives on Integrated Community Care in the Czech Republic.

Aim: The problem of family care for people dependent on another person has only recently become a focus of research. As demand for health and social services has not been adequately met by public service providers, growing attention has been given to informal care and the integration of families within systems of health and social care at the community level. This paper presents the results of a survey on informal carers' views and opinions under the current conditions of social support in the Czech Republic.

Metabolite Profiling of the Plasma and Leukocytes of Chronic Myeloid Leukemia Patients.

The discovery of tyrosine kinase inhibitors (TKIs) brought a major breakthrough in the treatment of patients with chronic myeloid leukemia (CML). Pathogenetic CML events are closely linked with the Bcr-Abl protein with tyrosine kinase activity. TKIs block the ATP-binding site; therefore, the signal pathways leading to malignant transformation are no longer active.

Ultrafast Online SPE-MS/MS Method for Quantification of 3 Tyrosine Kinase Inhibitors in Human Plasma.

Background: With an increasing number of cancer patients receiving tyrosine kinase inhibitors (TKIs), therapeutic drug monitoring of these molecules is becoming more widespread today. It is mainly based on liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) methods with typical run times of several minutes. In an online solid phase extraction-MS/MS (SPE-MS/MS) system, the chromatography column is replaced with a reusable solid phase extraction (SPE) cartridge and the analysis time is shortened to less than half a minute.

Oxidized phosphatidylcholines suggest oxidative stress in patients with medium-chain acyl-CoA dehydrogenase deficiency.

Inborn errors of metabolism encompass a large group of diseases caused by enzyme deficiencies and are therefore amenable to metabolomics investigations. Medium chain acyl-CoA dehydrogenase deficiency (MCADD) is a defect in β-oxidation of fatty acids, and is one of the most well understood disorders. We report here the use of liquid chromatography-mass spectrometry (LC-MS) based untargeted metabolomics and targeted flow injection analysis-tandem mass spectrometry (FIA-TMS) that lead to discovery of novel compounds of oxidative stress.

Untargeted metabolomic analysis of urine samples in the diagnosis of some inherited metabolic disorders.

Background: Metabolomics is becoming an important tool in clinical research and the diagnosis of human diseases. It has been used in the diagnosis of inherited metabolic disorders with pronounced biochemical abnormalities. The aim of this study was to determine if it could be applied in the diagnosis of inherited metabolic disorders (IMDs) with less clear biochemical profiles from urine samples using an untargeted metabolomic approach.

The attitudes of older adults living in institutions and their caregivers to ageing.

Objectives: The aim of this study was to explore the attitudes of older people living in institutions and their caregivers to ageing. Recent outcomes showed prevailing negative social stereotype to ageing in CR.

Methods: The Attitudes to Ageing Questionnaire (AAQ-24) was used in two waves of data collection to measure attitudes of 400 randomly selected residents of 19 Senior Residential Homes.

Targeted metabolomic analysis of plasma samples for the diagnosis of inherited metabolic disorders.

Metabolomics has become an important tool in clinical research and diagnosis of human diseases. In this work we focused on the diagnosis of inherited metabolic disorders (IMDs) in plasma samples using a targeted metabolomic approach. The plasma samples were analyzed with the flow injection analysis method.

Proving tumour cells by acute nutritional/energy deprivation as a survival threat: a task for microscopy.

Malignant cells appear to possess a special aptitude for survival. We attempted to prove this in vitro by acute nutritional and energy deprivation as a survival threat. A phosphate-buffered saline (PBS) survival test in cell culture allowed static observations.

Functional status and depressive symptoms among older adults from residential care facilities in the Czech Republic.

Background: Depressive symptoms are common among older adults, particularly those living in long-term care facilities. However, little is known about factors associated with depressive symptoms among long-term care residents in the Czech Republic and in other Eastern European countries. Moreover, the role of mobility and pain in depressive symptoms among long-term care residents is relatively understudied.