Association between calcifications of mitro-aortic continuity and mitral regurgitation in patients undergoing transcatheter aortic valve replacement

Background: The presence of mitral annular calcification (MAC) affects prognosis in patients undergoing transcatheter aortic valve implantation (TAVI). MAC frequently coexists with calcifications of mitro-aortic continuity (CMAC).Aims: We aimed at qualitative and semi-quantitative analysis of calcifications of the mitral complex — MAC and CMAC in multi-slice computed tomography, in order to assess their impact on the occurrence and dynamics of mitral regurgitation (MR) following TAVI.Methods: The study group consisted of 94 patients (mean [SD] age was 79.9 [8.02] years; 67.1% female). Agatston scale — Calcium Score was used for quantitative analysis. MAC and CMAC were also assessed semi-quantitatively as either non-severe or severe. MR following TAVI was defined as unchanged, improved or worsened by at least one degree.Results: Patients with MAC (59.6%) had higher mean aortic gradients (P = 0.02) and smaller left ventricular diastolic diameter (P = 0.002). Patients with CMAC (48.9%) had higher Calcium Score aortic valve (P = 0.006). After TAVI MR improved in 17 (18.1%) patients and worsened in 7 (7.5%) patients. In multivariable logistic regression analysis MR worsening was associated with higher CMAC (OR, 1.092; 95% CI, 1.006–1.185; P = 0.03), as well as bicuspid aortic valve (OR, 6.348; 95% CI, 1.048–38.436; P = 0.04).Conclusions: CMAC was associated with MR worsening following TAVI. This is of relevance in procedural planning in patients with severe aortic stenosis (AS) and coexisting MR in whom arguments for and against surgical repair of concomitant mitral insufficiency are considered

Mutations in GDAP1 Influence Structure and Function of the Trans-Golgi Network

Charcot-Marie-Tooth disease (CMT) is a heritable neurodegenerative disease that displays great genetic heterogeneity. The genes and mutations that underlie this heterogeneity have been extensively characterized by molecular genetics. However, the molecular pathogenesis of the vast majority of CMT subtypes remains terra incognita. Any attempts to perform experimental therapy for CMT disease are limited by a lack of understanding of the pathogenesis at a molecular level. In this study, we aim to identify the molecular pathways that are disturbed by mutations in the gene encoding GDAP1 using both yeast and human cell, based models of CMT-GDAP1 disease. We found that some mutations in GDAP1 led to a reduced expression of the GDAP1 protein and resulted in a selective disruption of the Golgi apparatus. These structural alterations are accompanied by functional disturbances within the Golgi. We screened over 1500 drugs that are available on the market using our yeast-based CMT-GDAP1 model. Drugs were identified that had both positive and negative effects on cell phenotypes. To the best of our knowledge, this study is the first report of the Golgi apparatus playing a role in the pathology of CMT disorders. The drugs we identified, using our yeast-based CMT-GDAP1 model, may be further used in translational research

Interaction of prion protein with microtubules

Nieprawidłowo sfałdowane białko prionowe (PrPTSE) uważane jest za główny czynnik prowadzący do rozwoju zakaźnych chorób neurodegeneracyjnych, zwanych pasażowalnymi encefalopatiami gąbczastymi (TSE). Mechanizm konwersji fizjologicznej formy białka prionowego PrPC do patologicznej PrPTSE, jak i forma neurotoksyczna tego białka, nie zostały jak dotąd w pełni scharakteryzowane. W warunkach fizjologicznych PrPc występuje głównie zewnątrzkomórkowo, gdzie przyczepione jest za pomocą kotwicy GPI do powierzchni błony komórkowej. Znane są jednak, również zlokalizowane w cytoplazmie formy PrP, zwane cytoPrP. Co ciekawe, stężenie cytoPrP znacząco wzrasta w TSE. Badania ostatnich lat dowodzą, że nieprawidłowo zlokalizowane w cytoplazmie PrP może być czynnikiem neurotoksycznym, a mechanizm neurotoksyczności związany jest prawdopodobnie z bezpośrednim oddziaływaniem tej formy białka prionowego z tubuliną. Oddziaływanie to prowadzi do agregacji tubuliny, zahamowania formowania MT, rozpadu cytoszkieletu mikrotubularnego i w konsekwencji śmierci komórki. Stabilizacja MT, np. przez obniżenie poziomu ufosforylowania związanych z mikrotubulami białek MAP chroni neurony przed toksycznością cytoplazmatycznej formy PrP.Misfolded prion protein (PrP ) is known as a major agent leading to infectious neurodegenerative diseases, known as transmissible spongiform encephalopathies (TSE). The mechanism of conversion of the physiological form of prion protein (PrP C ) into the pathological PrP TSE as well as the identity of neurotoxic form of this protein is not fully characterized. Under physiological conditions, PrP C one, is predominantly extracellular, tethered to the plasma membrane surface through the GPI anchor. However, cytosolic forms of PrP, termed as cytoPrP have also been found. Interestingly, a significant increase in the concentration of cytoPrP is observed in TSE. Recently, it was shown that mislocalized PrP can be a neurotoxic agent. The mechanism of neurotoxicity might be linked to the direct interaction of this form of PrP with tubulin. This interaction leads to tubulin aggregation, inhibition of microtubules (MT) assembly, disruption of microtubular cytoskeleton and eventually cell death. MT stabilization, by decreasing the level of MAP phosphorylation, can protect neurons from toxic effect of cytosolic forms of PrP

Czy zabiegi medycyny przeciwstarzeniowej mogą poprawić samopoczucie i samoocenę kobiet dojrzałych

Maintaining beauty and youthfulness has always been and still is among the natural desires of women. A modern woman is a woman of success: independent, professionally successful, staying active for many years of her life. This activity as well as the influence of the media induce women to adapt to the existing patterns at all costs. Minimally invasive aesthetic medicine procedures help to repair beauty defects and reduce the ageing processes. They can have a positive influence on life and thinking by increasing well-being and atractiveness as well as helping to get rid of complexes. The aim of this paper is to assess the way in which the minimally invasive aesthetic medicine procedures affect the self-esteem of women and womens' perception of their own body. The study was conducted prospectively using a standardized questionnaire and diagnostic tools examining the perception of one's own body, self-esteem and emotional condition. The procedures performed most often were corrections with the use of hyaluronic acid and the most frequently declared motivation for the surgery was the need to increase sexual attractiveness that follows the first symptoms of aging processes. The undertaken analysis reveals that undergoing various forms of appearance correction has several psychical, physical and social effects. A significant majority of women that decided to undergo the treatments had high or average self-esteem initially, and its levels increased even further after the aesthetic surgery

The effects of the interaction of myosin essential light chain isoforms with actin in skeletal muscles.

In order to compare the ability of different isoforms of myosin essential light chain to interact with actin, the effect of the latter protein on the proteolytic susceptibility of myosin light chains (MLC-1S and MLC-1V - slow specific and same as ventricular isoform) from slow skeletal muscle was examined. Actin protects both slow muscle essential light chain isoforms from papain digestion, similarly as observed for fast skeletal muscle myosin (Nieznańska et al., 1998, Biochim. Biophys. Acta 1383: 71). The effect of actin decreases as ionic strength rises above physiological values for both fast and slow skeletal myosin, confirming the ionic character of the actin-essential light chain interaction. To better understand the role of this interaction, we examined the effect of synthetic peptides spanning the 10-amino-acid N-terminal sequences of myosin light chain 1 from fast skeletal muscle (MLC-1F) (MLCFpep: KKDVKKPAAA), MLC-1S (MLCSpep: KKDVPVKKPA) and MLC-1V (MLCVpep: KPEPKKDDAK) on the myofibrillar ATPase of fast and slow skeletal muscle. In the presence of MLCFpep, we observed an about 19% increase, and in the presence of MLCSpep about 36% increase, in the myofibrillar ATPase activity of fast muscle. On the other hand, in myofibrillar preparations from slow skeletal muscle, MLCSpep as well as MLCVpep caused a lowering of the ATPase activity by about 36%. The above results suggest that MLCSpep induces opposite effects on ATPase activity, depending on the type of myofibrils, but not through its specific N-terminal sequence - which differs from other MLC N-terminal peptides. Our observations lead to the conclusion that the action of different isoforms of long essential light chain is similar in slow and fast skeletal muscle. However the interaction of essential light chains with actin leads to different physiological effects probably depending on the isoforms of other myofibrillar proteins

Stan i rozwój turystyki uzdrowiskowej w województwie podkarpackim

Współczesne społeczeństwo staje się coraz bardziej świadome konieczności dbania o zdrowie oraz pragnie rozwijać zainteresowania i wzbogacać swoje wyjazdy uzdrowiskowe o aspekt poznawczy, krajoznawczy. Uzdrowiska stwarzają możliwość rozwoju i promocji województwa, dzięki wzrastającej liczbie nie tylko kuracjuszy pragnących poprawić stan zdrowia, ale również turystów stawiających na aspekty wypoczynkowe i krajoznawcze. Celem pracy była ocena obecnego stanu bazy i turystyki uzdrowiskowej w podkarpackich ośrodkach lecznictwa uzdrowiskowego oraz wyciągnięcie wniosków dotyczących możliwości rozwoju turystyki na tych terenach. W pracy zastosowano metodę sondażu diagnostycznego, a narzędziem badawczym był kwestionariusz ankiety. W badaniach wzięło udział 12 ośrodków z czterech podkarpackich miejscowości uzdrowiskowych. Ponadto dokonano analizy dostępnej literatury przedmiotowej. Wyniki badań wskazują, że niski poziom rozwoju ośrodków uzdrowiskowych spowodowany jest głównie problemami finansowymi. Z odpowiedzi respondentów wynika, że personel jest przygotowany na przyjęcie turystów zagranicznych. Turystyka uzdrowiskowa jest szansą dla rozwoju i promocji województwa podkarpackiego. Wymaga ciągłych, gruntownych badań, nie tylko w kontekście stanu obecnego (stanu bazy uzdrowiskowej i dokonującego się na jej terenie ruchu turystycznego), ale także w kontekście możliwości jej rozwoju i poszerzania oferty oraz zasięgu działania

Covalent defects restrict supramolecular self-assembly of homopolypeptides: case study of β2-fibrils of poly-L-glutamic acid.

Poly-L-glutamic acid (PLGA) often serves as a model in studies on amyloid fibrils and conformational transitions in proteins, and as a precursor for synthetic biomaterials. Aggregation of PLGA chains and formation of amyloid-like fibrils was shown to continue on higher levels of superstructural self-assembly coinciding with the appearance of so-called β2-sheet conformation manifesting in dramatic redshift of infrared amide I' band below 1600 cm(-1). This spectral hallmark has been attributed to network of bifurcated hydrogen bonds coupling C = O and N-D (N-H) groups of the main chains to glutamate side chains. However, other authors reported that, under essentially identical conditions, PLGA forms the conventional in terms of infrared characteristics β1-sheet structure (exciton-split amide I' band with peaks at ca. 1616 and 1683 cm(-1)). Here we attempt to shed light on this discrepancy by studying the effect of increasing concentration of intentionally induced defects in PLGA on the tendency to form β1/β2-type aggregates using infrared spectroscopy. We have employed carbodiimide-mediated covalent modification of Glu side chains with n-butylamine (NBA), as well as electrostatics-driven inclusion of polylysine chains, as two different ways to trigger structural defects in PLGA. Our study depicts a clear correlation between concentration of defects in PLGA and increasing tendency to depart from the β2-structure toward the one less demanding in terms of chemical uniformity of side chains: β1-structure. The varying predisposition to form β1- or β2-type aggregates assessed by infrared absorption was compared with the degree of morphological order observed in electron microscopy images. Our results are discussed in the context of latent covalent defects in homopolypeptides (especially with side chains capable of hydrogen-bonding) that could obscure their actual propensities to adopt different conformations, and limit applications in the field of synthetic biomaterials

Czynniki medyczne i psychologiczne wpływające na stan psychiczny pielęgniarek z długoletnim stażem pracy

The purpose of this study is to define medical and psychological factors characterizing the nurses with many years of the professional experience who are took part of bridging studies. Fifty nine nurses were participating in this survey. Main goal of this survey was to investigate association between clinical depression symptoms, level of neurotransmitters and the number of years in the nursing profession. Data analysis showed no symptoms of clinical depression. The level of neurotransmitters, serotonin, dopamine and noradrenaline was maintained in medium level in the whole group. Respondents were characterized by higher disposition to feel gratitude and average life satisfaction. There was no sig- nificant correlation between experience in the nursing profession, depression factors and the level of neurotransmitters

Covalent Defects Restrict Supramolecular Self-Assembly of Homopolypeptides: Case Study of β₂-Fibrils of Poly-L-Glutamic Acid

<div><p>Poly-L-glutamic acid (PLGA) often serves as a model in studies on amyloid fibrils and conformational transitions in proteins, and as a precursor for synthetic biomaterials. Aggregation of PLGA chains and formation of amyloid-like fibrils was shown to continue on higher levels of superstructural self-assembly coinciding with the appearance of so-called β₂-sheet conformation manifesting in dramatic redshift of infrared amide I′ band below 1600 cm⁻¹. This spectral hallmark has been attributed to network of bifurcated hydrogen bonds coupling C = O and N-D (N-H) groups of the main chains to glutamate side chains. However, other authors reported that, under essentially identical conditions, PLGA forms the conventional in terms of infrared characteristics β₁-sheet structure (exciton-split amide I′ band with peaks at ca. 1616 and 1683 cm⁻¹). Here we attempt to shed light on this discrepancy by studying the effect of increasing concentration of intentionally induced defects in PLGA on the tendency to form β₁/β₂-type aggregates using infrared spectroscopy. We have employed carbodiimide-mediated covalent modification of Glu side chains with n-butylamine (NBA), as well as electrostatics-driven inclusion of polylysine chains, as two different ways to trigger structural defects in PLGA. Our study depicts a clear correlation between concentration of defects in PLGA and increasing tendency to depart from the β₂-structure toward the one less demanding in terms of chemical uniformity of side chains: β₁-structure. The varying predisposition to form β₁- or β₂-type aggregates assessed by infrared absorption was compared with the degree of morphological order observed in electron microscopy images. Our results are discussed in the context of latent covalent defects in homopolypeptides (especially with side chains capable of hydrogen-bonding) that could obscure their actual propensities to adopt different conformations, and limit applications in the field of synthetic biomaterials.</p></div

Cross-section view at a model of different inter-sheet distances and packing modes of Glu side chains in the β₁/β₂-type structural variants of PLGA aggregates with the antiparallel arrangement of strands (A).

<p>Red circles mark sites of three-center hydrogen bonds with bifurcated carbonyl acceptors. Random covalent modification of Glu side chains (within frames) cause local structural defects and result in less-densely-packed β₁ fibrils (B).</p