Transient Elastography for Detection of Liver Fibrosis in Children With Autosomal Recessive Polycystic Kidney Disease

Introduction: Congenital hepatic fibrosis (CHF) is invariably present in all patients with autosomal recessive polycystic kidney disease (ARPKD) but is usually clinically asymptomatic. The portal hypertension in the course of CHF develops and progresses over time, so an early detection of liver fibrosis remains crucial.Aim: The aim of the study was to evaluate a predictive value of transient elastography for evaluating liver disease progress in pediatric ARPKD patients.Material and Methods: The study group encompassed 21 pediatric patients with ARPKD and 20 healthy children (control group) from The Children's Memorial Health Institute in Warsaw, Poland. Liver fibrosis was determined by assessing the liver stiffness (LS) with transient elastography (FibroScan®, FS) using size-appropriate probes. In ARPKD group the laboratory findings, results of an abdominal ultrasound examination, and an endoscopic gastroduodenoscopy were also analyzed.Results: Compared with healthy controls, patients with ARPKD had significantly increased median LS values (22 vs. 4.25 kPa, p < 0.0001). Based on FS results, ARPKD group was divided into two subgroups: patients (n = 5) with LS results suggestive of no fibrosis or minimal fibrosis (LS < 6.9 kPa, METAVIR fibrosis stage 0–1) and patients (n = 16) with LS results suggestive of at least significant liver fibrosis (LS ≥ 6.9 kPa, METAVIR fibrosis stage 2–4). In the first subgroup (no fibrosis or minimal fibrosis), all patients had no signs of portal hypertension. In the subgroup with at least significant liver fibrosis, splenomegaly was observed in 87.5% of patients and thrombocytopenia in 69% of patients. An endoscopic gastroduodenoscopy was performed in 15 out of 21 ARPKD patients, nine patients (60%) had esophageal varices. All of these patients had LS results suggestive of at least significant liver fibrosis.Conclusions: TE by FibroScan can be used as an additional method for evaluating liver disease progress in pediatric ARPKD patients

The novel P330L pathogenic variant of aromatic amino acid decarboxylase maps on the catalytic flexible loop underlying its crucial role

Aromatic amino acid decarboxylase (AADC) deficiency is a rare monogenic disease, often fatal in the first decade, causing severe intellectual disability, movement disorders and autonomic dysfunction. It is due to mutations in the gene coding for the AADC enzyme responsible for the synthesis of dopamine and serotonin. Using whole exome sequencing, we have identified a novel homozygous c.989C > T (p.Pro330Leu) variant of AADC causing AADC deficiency. Pro330 is part of an essential structural and functional element: the flexible catalytic loop suggested to cover the active site as a lid and properly position the catalytic residues. Our investigations provide evidence that Pro330 concurs in the achievement of an optimal catalytic competence. Through a combination of bioinformatic approaches, dynamic light scattering measurements, limited proteolysis experiments, spectroscopic and in solution analyses, we demonstrate that the substitution of Pro330 with Leu, although not determining gross conformational changes, results in an enzymatic species that is highly affected in catalysis with a decarboxylase catalytic efficiency decreased by 674- and 194-fold for the two aromatic substrates. This defect does not lead to active site structural disassembling, nor to the inability to bind the pyridoxal 5'-phosphate (PLP) cofactor. The molecular basis for the pathogenic effect of this variant is rather due to a mispositioning of the catalytically competent external aldimine intermediate, as corroborated by spectroscopic analyses and pH dependence of the kinetic parameters. Altogether, we determined the structural basis for the severity of the manifestation of AADC deficiency in this patient and discussed the rationale for a precision therapy

The analysis of mugwort pollen count in selected Polish cities in 2014

Celem pracy było porównanie sezonu pyłkowego bylicy w 2014 r. w Bydgoszczy, Krakowie, Lublinie, Piotrkowie Trybunalskim, Poznaniu, Sosnowcu, Szczecinie i Warszawie. Pomiary stężenia pyłku prowadzono metodą objętościową z zastosowaniem aparatów Burkard oraz Lanzoni. Sezon pyłkowy wyznaczono jako okres, w którym w powietrzu występuje 98% rocznej sumy ziaren pyłku. Indeks SPI obliczono jako sumę średnich dobowych stężeń pyłku w danym sezonie. Sezon pyłkowy bylicy najwcześniej (13 czerwca) rozpoczął się w Szczecinie, a najpóźniej (15 lipca) – w Lublinie i Warszawie. Zanotowano znaczne różnice w czasie trwania sezonu. Najwyższe wartości stężeń zaobserwowano w Poznaniu, maksymalne stężenie wynoszące 172 z/m3 zarejestrowano 19 sierpnia. Maksymalne wartości sezonowe koncentracji pyłku we wszystkich miastach wystąpiły między 27 lipca a 19 sierpnia.The aim of the study was to compare the pollen season of mugwort in the cities of Bydgoszcz, Cracow, Lublin, Piotrków Trybunalski, Poznań, Sosnowiec, Szczecin and Warsaw in 2014. Measurements were performed by the volumetric method (Burkard and Lanzoni pollen sampler). Pollen season was defined as the period in which 98% of the annual total catch occurred. Seasonal Pollen Index (SPI) was estimated as the annual sum of daily average pollen concentrations. The pollen season of mugwort started first in Szczecin, on the 13th of June, and at the latest – on the 15th of July – in Lublin and Warsaw. The differences of pollen seasons duration were considerables. The highest record airborne concentration of 172 pollen grains/m3 was noted in Poznań on the 19th of August. The maximum values of seasonal pollen count occurred between 27th of July and 19th of August in all cities

Anemia in Patients With Resistance to Thyroid Hormone α: A Role for Thyroid Hormone Receptor α in Human Erythropoiesis

Context: Patients with resistance to thyroid hormone (TH) α (RTHα) are characterized by growth retardation, macrocephaly, constipation, and abnormal thyroid function tests. In addition, almost all RTHα patients have mild anemia, the pathogenesis of which is unknown. Animal studies suggest an important role for TH and TH receptor (TR)α in erythropoiesis. Objective: To investigate whether a defect in TRα affects the maturation of red blood cells in RTHα patients. Design, Setting, and Patients: Cultures of primary human erythroid progenitor cells (HEPs), from peripheral blood of RTHα patients (n = 11) harboring different inactivating mutations in TRα (P398R, F397fs406X, C392X, R384H, A382fs388X, A263V, A263S), were compared with healthy controls (n = 11). During differentiation, erythroid cells become smaller, accumulate hemoglobin, and express different cell surface markers. We assessed cell number and cell size, and used cell staining and fluorescence-activated cell sorter analysis to monitor maturation at different time points. Results: After ∼14 days of ex vivo expansion, both control and patient-derived progenitors differentiated spontaneously. However, RTHα-derived cells differentiated more slowly. During spontaneous differentiation, RTHα-derived HEPs were larger, more positive for c-Kit (a proliferation marker), and less positive for glycophorin A (a differentiation marker). The degree of abnormal spontaneous maturation of RTHα-derived progenitors did not correlate with severity of underlying TRα defect. Both control and RTHα-derived progenitors responded similarly when differentiation was induced. T3 exposure accelerated differentiation of both control- and RTHα patient-derived HEPs. Conclusions: Inactivating mutations in human TRα affect the balance between proliferation and differentiation of progenitor cells during erythropoiesis, which may contribute to the mild anemia seen in most RTHα patients.A.L.M.v.G., M.E.M., and R.P.P. are supported by ZonMWTOP Grant 91212044 and an Erasmus MC Medical Research Advisory Committee (MRACE) grant. A.L.M.v.G. and R.P.P. are also supported by a European Thyroid Association (ETA) research grant. K. Chatterjee is supported by Wellcome Trust Investigator Award 095564/Z/11/Z. K. Chatterjee and C.M. are supported by the National Institute for Health Research Cambridge Biomedical Research Centre

Społeczno-ekonomiczne aspekty finansowania spożycia społecznego w dziedzinie oświaty i ochrony zdrowia m.Łodzi

Niniejsza praca porusza problematykę sfery zjawisk finansowych, związaną ze stosunkami społecznymi, realizowanymi na gruncie społecznego funduszu spożycia. Podstawowym założeniem jest teza o bezposrednim związku między zjawiskami społecznymi a finansowymi

Changes in the area of value management on the niche culture market – on the example of arts cinemas

Celem artykułu jest zaprezentowanie zmian, jakie zachodzą w obszarze zarządzania wartością dla klienta na rynku niszowych usług kulturalnych świadczonych przez kina studyjne. Umacnianie ich pozycji konkurencyjnej oraz utrzymanie się na rynku implikuje konieczność bieżącego monitorowania oczekiwań klientów, aby podejmować działania dostosowawcze w zakresie oferowanych im korzyści. W proces zarządzania powinien być włączany klient oraz inne podmioty partnerskie. Podstawę empiryczną opracowania stanowią badania przeprowadzone w 2011 r. i 2014 r. wśród pracowników polskich kin studyjnych, odnoszące się do weryfikacji procesu zarządzania wartością dla klienta ujmującego jego podstawowe elementy: definiowanie, kreowanie, komunikowanie i dostarczanie wartości, a także współpracę z klientem i podmiotami zewnętrznymi.The goal of the article is a presentation of changes that occur in the area of value management for customers on the niche market of cultural services as provided by arts cinemas. Strengthening their competitive position and the need to stay on the market imply the necessity to constantly monitor customer expectations in order to possibly adjust benefits offered to them. The customer and partners should be included into the management process. The empirical basis for the article was research conducted in 2011 and 2014 among employees of Polish arts cinemas, which aimed at the validation of value management and its principle elements: definition, creation, communication and delivery of value as well as cooperation with customers and internal subjects

The Influence of Bisphenol A (BPA) on the Occurrence of Selected Active Substances in Neuregulin 1 (NRG1)-Positive Enteric Neurons in the Porcine Large Intestine

Bisphenol A (BPA) is a substance used in the manufacture of plastics which shows multidirectional adverse effects on living organisms. Since the main path of intoxication with BPA is via the gastrointestinal (GI) tract, the stomach and intestine are especially vulnerable to the impact of this substance. One of the main factors participating in the regulation of intestinal functions is the enteric nervous system (ENS), which is characterized by high neurochemical diversity. Neuregulin 1 (NRG1) is one of the lesser-known active substances in the ENS. During the present study (performed using the double immunofluorescence method), the co-localization of NRG1 with other neuronal substances in the ENS of the caecum and the ascending and descending colon has been investigated under physiological conditions and after the administration of BPA. The obtained results indicate that NRG1-positive neurons also contain substance P, vasoactive intestinal polypeptide, a neuronal isoform of nitric oxide synthase and galanin and the degree of each co-localization depend on the type of enteric plexus and the particular fragment of the intestine. Moreover, it has been shown that BPA generally increases the degree of co-localization of NRG1 with other substances