BACKGROUND: Diffuse midline glioma, H3 K27-altered (DMG) is a fatal tumour that arises in the midline structures of the brain. When located in the pons, it is more commonly referred to as diffuse intrinsic pontine glioma (DIPG). DMG/DIPG is usually diagnosed when children are < 10 years, and it has a median overall survival of < 12 months after diagnosis. Radiological imaging is still the gold standard for DIPG diagnosis while the use of biopsy procedures led to our knowledge on its biology, such as with the identification of the canonical histone H3K27M mutation. However, the need to improve survival encourages the development of non-invasive, fast and inexpensive assays on biofluids for optimizing molecular diagnoses in DMG/DIPG. Here, we propose a rapid, new, imaging and epigenetics-based approach to diagnose DMG/DIPG in the plasma of paediatric patients. METHODS: A total of 20 healthy children (mean age: 10.5 years) and 24 children diagnosed with DMG/DIPG (mean age: 8.5 years) were recruited. Individual histones (H2A, H2B, H3, H4, macroH2A1.1 and macroH2A1.2), histone dimers and nucleosomes were assayed in biofluids by means of a new advanced flow cytometry ImageStream(X)-adapted method. RESULTS: We report a significant increase in circulating histone dimers and tetramers (macroH2A1.1/H2B versus control: p value < 0.0001; macroH2A1.2/H2B versus control: p value < 0.0001; H2A/H2B versus control: p value < 0.0001; H3/H4 versus control: p value = 0.008; H2A/H2B/H3/H4 versus control: p value < 0.0001) and a significant downregulation of individual histones (H2B versus control: p value < 0.0001; H3 versus control: p value < 0.0001; H4 versus control: p value < 0.0001). Moreover, histones were also detectable in the cerebrospinal fluid (CSF) of patients with DMG/DIPG and in the supernatant of SF8628, OPBG-DIPG002 and OPBG-DIPG004 DMG/DIPG cell lines, with patterns mostly similar to each other, but distinct compared to blood plasma. CONCLUSIONS: In summary, we identified circulating histone signatures able to detect the presence of DMG/DIPG in biofluids of children, using a rapid and non-invasive ImageStream(X)-based imaging technology, which may improve diagnosis and benefit the patients.

• MeSH
• difuzní intrinsický pontinní gliom genetika   diagnóza   krev   MeSH
• dítě MeSH
• epigeneze genetická MeSH
• gliom genetika   diagnóza   krev   patologie   diagnostické zobrazování   MeSH
• histony * genetika   metabolismus   krev   MeSH
• lidé MeSH
• mladiství MeSH
• mutace MeSH
• nádorové biomarkery krev   MeSH
• nádory mozkového kmene genetika   diagnóza   krev   diagnostické zobrazování   patologie   metabolismus   MeSH
• předškolní dítě MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND: Despite secondary prevention with aspirin, patients with stable cardiovascular disease (CVD) remain at elevated long-term risk of major adverse cardiovascular events. The Cardiovascular Outcomes in People Using Anticoagulant Strategies (COMPASS) double-blind, randomized clinical trial demonstrated that aspirin plus low-dose rivaroxaban (COMPASS regime) significantly decreased the incidence of major adverse cardiovascular events by 24% compared with aspirin alone. However, the mechanisms underlying these potential synergistic/nonantithrombotic effects remain elusive. Extracellular vesicles (EVs) are crucial messengers regulating a myriad of biological/pathological processes and are highly implicated in CVD. OBJECTIVES: We hypothesized that circulating EV profiles reflect the cardioprotective properties of the COMPASS regime. METHODS: A cohort of stable CVD patients (N = 40) who participated in the COMPASS trial and were previously randomized to receive aspirin were prospectively recruited and assigned a revised regimen of open-label aspirin plus rivaroxaban. Blood samples were obtained at baseline (aspirin only) and 6-month follow-up. Plasma EV concentration, size, and origin were analyzed by nanoparticle tracking analysis and flow cytometry. EVs were enriched by ultracentrifugation for proteomic analysis. RESULTS: The COMPASS regime fundamentally altered small (<200 nm) and large (200-1000 nm) EV concentration and size compared with aspirin alone. Crucially, levels of platelet-derived and myeloperoxidase-positive EVs became significantly decreased at follow-up. Comparative proteomic characterization further revealed a significant decrease in highly proinflammatory protein expression at follow-up. CONCLUSION: The observed changes in EV subpopulations, together with the differential protein expression profiles, suggest amelioration of an underlying proinflammatory and prothrombotic state upon dual therapy, which may be of clinical relevance toward understanding the fundamental mechanism underlying the reported superior cardiovascular outcomes associated with this antithrombotic regimen.

• MeSH
• Aspirin * aplikace a dávkování   terapeutické užití   škodlivé účinky   MeSH
• dvojitá slepá metoda MeSH
• extracelulární vezikuly * metabolismus   účinky léků   MeSH
• inhibitory agregace trombocytů * aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• inhibitory faktoru Xa * aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• kardiovaskulární nemoci * krev   prevence a kontrola   farmakoterapie   MeSH
• kombinovaná farmakoterapie * MeSH
• lidé středního věku MeSH
• lidé MeSH
• mediátory zánětu krev   MeSH
• prospektivní studie MeSH
• proteomika metody   MeSH
• rivaroxaban * aplikace a dávkování   MeSH
• senioři MeSH
• trombóza krev   prevence a kontrola   farmakoterapie   MeSH
• výsledek terapie MeSH
• zánět krev   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• randomizované kontrolované studie MeSH

Úvod: Primární tumory a infiltrativní procesy očnice zahrnují poměrně širokou škálu dia gnóz. Nádory a infiltrace, které vycházejí primárně z tkání prostoru očnice ohraničeného periorbitou, označujeme jako primární, zatímco sekundární tumory zasahují do orbity z okolních tkání vně od periorbity. Speciální skupinu tvoří léze metastatické. Cíl: Retrospektivní observační analýza souboru pacientů diagnostikovaných pro primární tumor a primární infiltraci očnice na Klinice otorinolaryngologie a chirurgie hlavy a krku v Nemocnici u sv. Anny v Brně (KOCHHK) v letech 2000– 2023. Metodika: Zařazeni byli pacienti ve věku ≥ 18 let, kteří absolvovali otorinolaryngologické a oftalmologické vyšetření, zobrazovací vyšetření (CT/ MR) a podstoupili stanovenou léčbu. Hodnoceny byly demografické parametry, symptomatologie, diagnostický a terapeutický přístup, histologická charakteristika procesů a efekt léčby. Výsledky: Ve sledovaném souboru byl nejčastějším benigním procesem pseudotumor očnice (12 pacientů, 33 %), z toho jedenáct pacientů podstoupilo kortikoidní terapii. U sedmi pacientů došlo ke kompletní regresi, u jednoho pacienta k parciální regresi, u čtyř byla pozorována recidiva. Z maligních infiltrací byl nejvíce zastoupen lymfom (10 pacientů, 27 %), přičemž u šesti pacientů se jednalo o MALT-lymfom. U devíti pacientů došlo ke kompletní remisi, u jednoho pacienta k remisi parciální. Závěr: Dia gnostika a terapie primárních lézí očnice nevyhnutelně vyžaduje mezioborovou spolupráci oftalmologa, neurochirurga, otorinolaryngologa, radiologa, histopatologa, event. hematoonkologa a dalších. Pro diagnostiku a adekvátní léčbu je klíčové zobrazovací vyšetření doplněno zpravidla i o histologickou verifikaci. Její provedení a event. chirurgické odstranění léze je značně limitováno lokalizací. Prognóza závisí nejen na maligním potenciálu léze, ale významně také na jejím vztahu k okolí a k důležitým strukturám v očnici.

Introduction: Primary tumors and infiltrative processes of the orbit include a fairly wide range of diagnoses. Tumors and infiltrations that arise primarily from the tissues of the orbital space bounded by the periorbita are termed primary, while secondary tumors encroach into the orbit from surrounding tissues outside the periorbita. A special group consists of metastatic lesions. Aim: Retrospective observational analysis of a cohort of patients diagnosed for a primary tumor or infiltration of the orbit at the Department of Otorhinolaryngology and Head and Neck Surgery at St. Anne‘s Hospital in Brno (KOCHHK) between 2000 and 2023. Methods: Patients aged ≥ 18 years who underwent otorhinolaryngological and ophthalmological examinations, imaging (CT/MRI), and treatment were included. Demographic parameters, symptomatology, diagnostic and therapeutic approaches, histological characteristics of the processes, and treatment effect were evaluated. Results: In the study group, the most common benign process was a pseudotumour of the orbit (12 patients, 33%), of which 11 patients underwent corticosteroid therapy. Complete regression was observed in 7 patients, partial regression was in 1 patient, and recurrence was in 4 patients. Lymphoma was the most common malignant infiltration (10 patients, 27%), with 6 patients having MALT-lymphoma. Nine patients had complete remission and 1 patient had partial remission. Conclusion: Diagnosis and therapy of primary lesions of the orbit inevitably require interdisciplinary cooperation of the ophthalmologist, neurosurgeon, otorhinolaryngologist, radiologist, histopathologist, hematooncologist, and others. For diagnosis and adequate treatment, imaging examination is crucial, usually supplemented by histological verification. Its performance, and if necessary, surgical removal of the lesion is limited by localization. Prognosis depends not only on the malignant potential of the lesion, but also significantly on its relationship to the surrounding area and to important structures in the orbit.

• MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• lymfom chirurgie   diagnostické zobrazování   diagnóza   MeSH
• nádory orbity * chirurgie   diagnostické zobrazování   diagnóza   klasifikace   MeSH
• oftalmologické chirurgické výkony metody   MeSH
• orbita diagnostické zobrazování   patologie   MeSH
• poruchy hybnosti oka diagnóza   etiologie   MeSH
• pseudotumor orbity chirurgie   diagnostické zobrazování   diagnóza   klasifikace   MeSH
• retrospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH

INTRODUCTION: Pathogenesis of large B-cell lymphomas (LBCL) and follicular lymphomas (FL) is a multistep process associated with the development of diverse DNA alterations and consequent deregulation of critical cellular processes. Detection of tumor-associated mutations within non-tumor compartments (mainly plasma) is the basis of the 'liquid biopsy' concept. Apart from tumor mutational profiling, quantitative analysis of circulating tumor DNA (ctDNA) allows longitudinal assessment of tumor burden. ctDNA-based technologies provide a new tool for tumor diagnostics and treatment personalization. AREAS COVERED: Our review provides a comprehensive overview and summary of available ctDNA studies in LBCL and FL. The accuracy of ctDNA-based detection of lymphoma-associated DNA alterations is correlated to known LBCL and FL molecular landscape. Additionally, we summarized available evidence that supports and justifies the clinical use of ctDNA for lymphoma risk stratification, treatment response evaluation, and treatment response-adapted therapy. Lastly, we discuss other clinically important ctDNA applications: monitoring of lymphoma clonal evolution within resistance and/or relapse development and utilization of ctDNA for diagnostics in non-blood fluids and compartments (e.g. cerebrospinal fluid in primary CNS lymphomas). EXPERT OPINION: Despite certain challenges, including methodological standardization, ctDNA holds promise to soon become an integral part of lymphoma diagnostics and treatment management.

• MeSH
• cirkulující nádorová DNA * krev   genetika   MeSH
• difúzní velkobuněčný B-lymfom * diagnóza   genetika   terapie   krev   MeSH
• folikulární lymfom * diagnóza   genetika   terapie   krev   MeSH
• lidé MeSH
• mutace MeSH
• nádorové biomarkery * krev   genetika   MeSH
• prognóza MeSH
• tekutá biopsie metody   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Cell communication systems based on polypeptide ligands use transmembrane receptors to transmit signals across the plasma membrane. In their biogenesis, receptors depend on the endoplasmic reticulum (ER)-Golgi system for folding, maturation, transport and localization to the cell surface. ER stress, caused by protein overproduction and misfolding, is a well-known pathology in neurodegeneration, cancer and numerous other diseases. How ER stress affects cell communication via transmembrane receptors is largely unknown. In disease models of multiple myeloma, chronic lymphocytic leukemia and osteogenesis imperfecta, we show that ER stress leads to loss of the mature transmembrane receptors FGFR3, ROR1, FGFR1, LRP6, FZD5 and PTH1R at the cell surface, resulting in impaired downstream signaling. This is caused by downregulation of receptor production and increased intracellular retention of immature receptor forms. Reduction of ER stress by treatment of cells with the chemical chaperone tauroursodeoxycholic acid or by expression of the chaperone protein BiP resulted in restoration of receptor maturation and signaling. We show a previously unappreciated pathological effect of ER stress; impaired cellular communication due to altered receptor processing. Our findings have implications for disease mechanisms related to ER stress and are particularly important when receptor-based pharmacological approaches are used for treatment.

• MeSH
• chaperon endoplazmatického retikula BiP MeSH
• kyselina taurochenodeoxycholová farmakologie   MeSH
• lidé MeSH
• nádorové buněčné linie MeSH
• receptory buněčného povrchu * metabolismus   MeSH
• signální transdukce * účinky léků   MeSH
• stres endoplazmatického retikula * účinky léků   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Proteomics is nowadays increasingly becoming part of the routine clinical practice of diagnostic laboratories, especially due to the advent of advanced mass spectrometry techniques. This review focuses on the application of proteomic analysis in the identification of pathological conditions in a hospital setting, with a particular focus on the analysis of protein biomarkers. In particular, the main purpose of the review is to highlight the challenges associated with the identification of specific disease-causing proteins, given their complex nature and the variety of posttranslational modifications (PTMs) they can undergo. PTMs, such as phosphorylation and glycosylation, play critical roles in protein function but can also lead to diseases if dysregulated. Proteomics plays an important role especially in various medical fields ranging from cardiology, internal medicine to hemato-oncology emphasizing the interdisciplinary nature of this field. Traditional methods such as electrophoretic or immunochemical methods have been mainstay in protein detection; however, these techniques are limited in terms of specificity and sensitivity. Examples include the diagnosis of multiple myeloma and the detection of its specific protein or amyloidosis, which relies heavily on these conventional methods, which sometimes lead to false positives or inadequate disease monitoring. Mass spectrometry in this respect emerges as a superior alternative, providing high sensitivity and specificity in the detection and quantification of specific protein sequences. This technique is particularly beneficial for monitoring minimal residual disease (MRD) in the diagnosis of multiple myeloma where traditional methods fall short. Furthermore mass spectrometry can provide precise typing of amyloid proteins, which is crucial for the appropriate treatment of amyloidosis. This review summarizes the opportunities for proteomic determination using mass spectrometry between 2012 and 2024, highlighting the transformative potential of mass spectrometry in clinical proteomics and encouraging its wider use in diagnostic laboratories.

• MeSH
• amyloidóza * diagnóza   MeSH
• biologické markery analýza   MeSH
• hmotnostní spektrometrie * metody   MeSH
• lidé MeSH
• mnohočetný myelom * diagnóza   MeSH
• posttranslační úpravy proteinů MeSH
• proteomika * metody   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Vitamin D je skupina steroidních hormonů. Většina v těle vzniká za pomoci UV záření ze slunce, ale je obsažen v různých potravinách, jako jsou oleje z mořských ryb apod. V těle je postupně hydroxylován na účinný metabolit v játrech a ledvinách. V krvi je transportován bílkovinou VDBP (vitamin D binding protein). Váže se v jádře buňky na receptor VDR (vitamin D Rreceptor). Na koncentraci vitaminu D má vliv mnoho faktorů jako zeměpisná poloha, sezóna (délka slunečního svitu), pigmentace kůže i množství tukové a svalové tkáně. Jeho nejznámější funkcí je regulace kalcio-fosfátového metabolizmu, avšak podílí se rovněž na regulaci buněčného cyklu, indukci apoptózy a také hraje roli v regulaci imunitního systému. Obecně lze říci, že jeho působení vede spíše k imunotoleranci. Nedostatek vitaminu D se v populaci projevuje stále častěji, dnes jím trpí až téměř 50 % evropské populace. Deficience se spojuje s vyšší agresivitou nádorů vč. Nehodgkinových lymfomů a je prokázáno, že pacienti s vyššími hladinami vitaminu D vykazují lepší celkové přežití i dobu do progrese. Nabízí se tedy otázka, zda by suplementace vitaminem D mohla příznivě ovlivnit prognózu pacienta s lymfomy. Výsledky publikovaných studií jsou v tomto ohledu dosud rozporuplné. Navzdory ne zcela jednoznačným výsledkům se uvádí, že suplementace by měla být zvážena u pacientů s insuficientními hladinami vitaminu D.

Vitamin D is a group of steroid hormones, produced with the help of UV radiation of the sun in the skin. It is also contained in various foods such as marine fish oils etc. In the body, it is subsequently transformed into its active form in the liver and kidneys. In the blood, it is transported by the VDBP (vitamin D binding protein). In the cell nucleus, it is bound to the VDR receptor (vitamin D receptor). The concentration of vitamin D in plasma is influenced by many factors: geographical latitude, season (length of sunshine), skin pigmentation, amount of fat, and muscle tissue. The best-known function of vitamin D is the regulation of calcium-phosphate metabolism, but it is involved in many processes such as the regulation of the cell cycle and the induction of apoptosis. It plays a role in the regulation of the immune system as well. Its immunomodulatory action is required for adequate anti-infectious and anti-tumoral immune response. It prevents an exaggerated inflammatory reaction and leads to immunotolerance. Deficiency has become more common in our population, affecting up to 50% of Europeans. Deficiency is also associated with a higher aggressiveness of tumours, including non-Hodgkin lymphomas. It has been shown that higher levels of vitamin D are associated with better overall survival and time to progression. The question is, whether vitamin D supplementation could impact and improve prognosis. Despite the ambiguous results of published studies, vitamin D supplementation should be considered in patients with diagnosed deficiency.

• MeSH
• lidé MeSH
• lymfom * etiologie   terapie   MeSH
• nedostatek vitaminu D komplikace   MeSH
• prognóza MeSH
• retrospektivní studie MeSH
• vitamin D * imunologie   metabolismus   terapeutické užití   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

Východiska: Hledání účinných biomarkerů pro včasnou diagnostiku ovariálního karcinomu (ovarian cancer – OC) patří k naléhavým úkolům moderní onkogynekologie. Metabolické profilování pomocí ultra vysokoúčinné kapalinové chromatografie a hmotnostní spektrometrie (ultraigh performance liquid chromatography and mass spectrometry – UHPLC-MS) poskytuje informace o souhrnu všech nízkomolekulárních metabolitů vzorku biologických tekutin pacienta, které odrážejí procesy probíhající v těle. Cílem studie bylo prozkoumat metabolomický profil krevní plazmy a moči pacientek se serózním ovariálním adenokarcinomem pomocí UHPLC-MS. Materiál a metody: K provedení metabolomické analýzy bylo odebráno 60 vzorků krevní plazmy a 60 vzorků moči pacientek s diagnózou serózního karcinomu vaječníků a 20 vzorků zdravých dobrovolníků. Chromatografická separace byla provedena na chromatografu Vanquish Flex UHPLC System (Thermo Scientific, Německo). Analýza hmotnostní spektrometrií byla provedena na Orbitrap Exploris 480 (Thermo Scientific, Německo) vybaveném elektrosprejovým ionizačním zdrojem. Bioinformatická analýza byla provedena pomocí Compound Discoverer Software (Thermo Fisher Scientific, USA), statistická analýza dat byla provedena v programovacím jazyce Python pomocí knihovny SciPy. Výsledky: Pomocí UHPLC-MS bylo v krevní plazmě identifikováno 1 049 metabolitů různých tříd. U pacientek s OC mělo 8 metabolitů významně nižší koncentraci (p < 0,01) ve srovnání se zdravými dárci, zatímco u 19 látek byly zjištěny vyšší hladiny (p < 0,01). Během metabolomického profilování vzorků moči bylo identifikováno 417 metabolitů: 12 látek mělo významně nižší koncentraci ve srovnání se zjevně zdravými jedinci a u 14 látek byly hladiny vyšší (p < 0,01). U pacientek se serózním adenokarcinomem vaječníků byla zjištěna významná změna v metabolomu krevní plazmy a moči, vyjádřená abnormálními koncentracemi lipidů a jejich derivátů, mastných kyselin a jejich derivátů, acylkarnitinů, fosfolipidů, aminokyselin a jejich derivátů, derivátů dusíkatých bází a steroidů. Mezi nejslibnější markery tohoto onemocnění přitom patří kynurenin, kyselina myristová, lysofosfatidylcholin a L-oktanoylkarnitin. Závěr: Odhalené změny v metabolomu se mohou stát základem pro zlepšení přístupů k diagnostice serózního ovariálního adenokarcinomu.

Background: The search for effective biomarkers for ovarian cancer (OC) early diagnosis is an urgent task of modern oncogynecology. Metabolic profiling by ultra-high performance liquid chromatography and mass spectrometry (UHPLC-MS) provides information on the totality of all low molecular weight metabolites of patient’s biological fluids sample, reflecting the processes occurring in the body. The aim of the study was to research blood plasma and urine metabolomic profile of patients with serous ovarian adenocarcinoma by UHPLC-MS. Material and methods: To perform metabolomic analysis, 60 blood plasma samples and 60 urine samples of patients diagnosed with serous ovarian carcinoma and 20 samples of apparently healthy volunteers were taken. Chromatographic separation was performed on a Vanquish Flex UHPLC System chromatograph (Thermo Scientific, Germany). Mass spectrometric analysis was performed on an Orbitrap Exploris 480 (Thermo Scientific, Germany) equipped with an electrospray ionization source. Bioinformatic analysis was performed using Compound Discoverer Software (Thermo Fisher Scientific, USA), statistical data analysis was performed in the Python programming language using the SciPy library. Results: Using UHPLC-MS, 1,049 metabolites of various classes were identified in blood plasma. In patients with OC, 8 metabolites had a significantly lower concentration (P < 0.01) compared with conditionally healthy donors, while the content of 19 compounds, on the contrary, increased (P < 0.01). During the metabolomic profiling of urine samples, 417 metabolites were identified: 12 compounds had a significantly lower concentration compared to apparently healthy individuals, the content of 14 compounds increased (P < 0.01). In patients with ovary serous adenocarcinoma, a significant change in the metabolome of blood plasma and urine was found, expressed in abnormal concentrations of lipids and their derivatives, fatty acids and their derivatives, acylcarnitines, phospholipids, amino acids and their derivatives, derivatives of nitrogenous bases and steroids. At the same time, kynurenine, myristic acid, lysophosphatidylcholine and L-octanoylcarnitine are the most promising markers of this disease. Conclusion: The revealed changes in the metabolome can become the basis for improving approaches to the diagnosis of serous ovarian adenocarcinoma.

• MeSH
• adenokarcinom diagnóza   MeSH
• biologické markery * analýza   krev   moč   MeSH
• kapalinová chromatografie-hmotnostní spektrometrie metody   MeSH
• lidé MeSH
• metabolom * MeSH
• metabolomika metody   MeSH
• nádory vaječníků * diagnóza   MeSH
• ženy MeSH
• Check Tag
• lidé MeSH

Newborn screening for Phenylketonuria enables early detection and timely treatment with a phenylalanine-restricted diet to prevent severe neurological impairment. Although effective and in use for 60 years, screening, diagnostic, and treatment practices still vary widely across countries and centers. To evaluate the Phenylketonuria newborn screening practices internationally, we designed a survey with questions focusing on the laboratory aspect of the screening system. We analyzed 24 completed surveys from 23 countries. Most participants used the same sampling age range of 48-72 h; they used tandem mass spectrometry and commercial non-derivatized kits to measure phenylalanine (Phe), and had non-negative cut-off values (COV) set mostly at 120 μmol/L of Phe. Participants mostly used genetic analysis of blood and detailed amino acid analysis from blood plasma as their confirmatory methods and set the COV for the initiation of dietary therapy at 360 μmol/L of Phe. There were striking differences in practice as well. While most participants reported a 48-72 h range for age at sampling, that range was overall quite diverse Screening COV varied as well. Additional screening parameters, e.g., the phenylalanine/tyrosine ratio were used by some participants to determine the screening result. Some participants included testing for tetrahydrobiopterin deficiency, or galactosemia in their diagnostic process. Results together showed that there is room to select a best practice from the many practices applied. Such a best practice of PKU-NBS parameters and post-screening parameters could then serve as a generally applicable guideline.

• Publikační typ
• časopisecké články MeSH

Perflorochemicals (PFCs), among which are the most commonly detected perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA), are persistent emergent contaminants of concern in recent times. These compounds have been reported for their cytotoxicity, genotoxicity, carcinogenicity, immunotoxicity, and developmental toxicities. Meanwhile, they have been detected in diverse matrices such as soil, sediment, and, surprisingly, in serum and even breastmilk. Worrisomely, these compounds are detected in drinking water across the globe, aquaculture water, and other surface waters. Thus, it was important to appraise the studies conducted on PFOS and PFOA to provide an overview of the environmental status of contamination regarding them. The present review article sought to provide insights into the occurrence patterns and ecotoxic effects of both pollutants in the water ecosystems within five continents of the world. Based on the information gathered in this article, the ∑PFOS concentration (ng/L) within the five continents is in the order Europe > Asia > Africa > North America > South America, while the ∑PFOA level (ng/L) is in the order Europe > Asia > South America > Africa > North America. The study also investigated the previous works that have been conducted regarding the diverse elimination technologies employed for the removal of these pollutants from the aqueous environments, with plasma combined with surfactant process being the most efficient. Generally, studies on PFOS/PFOA are still scanty when compared to those on pharmaceuticals and personal care products (PPCPs), especially in North America. The information gathered in this study could be useful in establishing thresholds of PFOA and PFOS environmental levels and be adopted by appropriate authorities as safety guidelines.

• Publikační typ
• časopisecké články MeSH
• přehledy MeSH