bluuebunny/crossref_metadata_2025 huggingface dataset:
Questioning the benefit of restrictive transfusion practice in older adults
Authors: Simon Geoff I. , Craswell Alison , Thom Ogilvie , Fung Yoke Lin
Published: September 2018

Restrictive transfusion practice is widely promoted, with many international guidelines recommending haemoglobin thresholds of 70 to 80 g/l for adult patients who are asymptomatic. Randomized controlled trials comparing outcomes associated with liberal and restrictive transfusion strategies underpin this approach. Meta‐analyses including trials of adult patients >18 years of age have concluded that restrictive practice is noninferior to liberal transfusion approaches. A restrictive approach to transfusion reduces resource consumption and cost, as well as the hazards associated with unnecessary exposure to blood products. Although adults aged ≥65 years consume over half of the blood supply, there are few randomized controlled transfusion trials exclusive to this cohort. Our 2017 meta‐analysis of a small number of trials focussed on older adults found that higher transfusion haemoglobin thresholds were associated with lower mortality and fewer cardiac complications in this age group. Other studies have also shown that higher transfusion haemoglobin thresholds are beneficial in older adults. This paper presents recent evidence regarding transfusion outcomes in older adults and discusses aspects of the pathophysiology of ageing that impact on the reduced resilience of older patients to anaemic states. This evidence challenges the use of Hb thresholds that apply across the adult lifespan, regardless of age. It proposes that older age be considered as a risk factor in assessing transfusion requirements, and that transfusion practice in older adults may require higher haemoglobin thresholds than for younger adults.
Effects of Coolant Feed Direction on Additively Manufactured Film Cooling Holes
Authors: Stimpson Curtis K. , Snyder Jacob C. , Thole Karen A. , Mongillo Dominic
Published: September 2018

Gas turbine components subjected to high temperatures can benefit from improved designs enabled by metal additive manufacturing (AM) with nickel alloys. Previous studies have shown that the impact on fluid flow and heat transfer resulting from surface roughness of additively manufactured parts is significant; these impacts must be understood to design turbine components successfully for AM. This study improves understanding of these impacts by examining the discharge coefficient and the effect of the coolant delivery direction on the performance of additively manufactured shaped film cooling holes. To accomplish this, five test coupons containing a row of baseline shaped film cooling holes were made from a high-temperature nickel alloy using a laser powder bed fusion (L-PBF) process. Flow and pressure drop measurements across the holes were collected to determine the discharge coefficient from the film cooling holes. Temperature measurements were collected to assess the overall effectiveness of the coupon surface as well as the cooling enhancement due to film cooling. The Biot number of the coupon wall was matched to a value one might find in a turbine engine to ensure this data is relevant. It was discovered that the flow experienced greater aerodynamic losses in film cooling holes with greater relative roughness, which resulted in a decreased discharge coefficient. The effectiveness measurements showed that the film cooling performance is better when coolant is fed in a co-flow configuration compared to a counter-flow configuration.
Dynamic Stability Analysis of a Flexible Rotor Filled With Liquid Based on Three-Dimensional Flow
Authors: Wang Guangding , Yuan Huiqun
Published: September 2018

This paper deals with the dynamic stability of a flexible liquid-filled rotor. On the basis of three-dimensional flow, the fluid perturbation motion is analyzed and the fluid–structure interaction equation is established, combining with continuity equation, the expression of fluid force exerted on rotor is derived in terms of Fourier series expansion. Considering the complex nonlinear relationship between fluid dynamic pressure and the rotor deformation function, they are expanded in terms of the eigenfunction of a dry rotor. The whirling frequency equation of a flexible rotor partially filled with liquid is obtained based on the rotor static equilibrium equation. Finally, the numerical technique is used to analyze the dynamic stability of the rotor system, and the influences of system parameters on unstable region are discussed.
Voltage-driven, local, and efficient excitation of nitrogen-vacancy centers in diamond
Authors: Labanowski Dominic , Bhallamudi Vidya Praveen , Guo Qiaochu , Purser Carola M. , McCullian Brendan A. , Hammel P. Chris , Salahuddin Sayeef
Published: September 2018

Leveraging magnetoelastic coupling, we show a power efficient mechanism for exciting nitrogen-vacancy centers in diamond.
Clonal expansion of vaccine-elicited T cells is independent of aerobic glycolysis
Authors: Klarquist Jared , Chitrakar Alisha , Pennock Nathan D. , Kilgore Augustus M. , Blain Trevor , Zheng Connie , Danhorn Thomas , Walton Kendra , Jiang Li , Sun Jie , Hunter Christopher A. , D’Alessandro Angelo , Kedl Ross M.
Published: September 2018

T cell responses to subunit vaccination require both IL-27 and IL-15 to support an aerobic glycolysis–independent metabolic program.
Molecular Epidemiology, Ecology, and Evolution of Group A Streptococci
Authors: Bessen Debra E. , Smeesters Pierre R. , Beall Bernard W.
Published: September 2018

The clinico-epidemiological features of diseases caused by group A streptococci (GAS) is presented through the lens of the ecology, population genetics, and evolution of the organism. The serological targets of three typing schemes (M, T, SOF) are themselves GAS cell surface proteins that have a myriad of virulence functions and a diverse array of structural forms. Horizontal gene transfer expands the GAS antigenic cell surface repertoire by generating numerous combinations of M, T, and SOF antigens. However, horizontal gene transfer of the serotype determinant genes is not unconstrained, and therein lies a genetic organization that may signify adaptations to a narrow ecological niche, such as the primary tissue reservoirs of the human host. Adaptations may be further shaped by selection pressures such as herd immunity. Understanding the molecular evolution of GAS on multiple levels—short, intermediate, and long term—sheds insight on mechanisms of host-pathogen interactions, the emergence and spread of new clones, rational vaccine design, and public health interventions.
Developing tools to enhance the use of systematic reviews for clinical care in health systems
Authors: Morrow Allison S , Whiteside Stephen P , Sim Leslie A , Brito Juan P , Wang Zhen , Murad Mohammad H
Published: September 2018

We aimed to develop tools that can facilitate uptake of evidence summarised in systematic reviews by clinical decision makers in health systems. After conducting a systematic review on the management of anxiety in children, we interviewed health system representatives, clinicians and patients to ask about additional information needed for decision-making. Using stakeholders’ feedback and literature searches for contextual and implementation information, we developed two tools (decision aids (DAs)), one for the health system and the second for the clinical encounter. This information mapped to factors of the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) Evidence to Decision Framework. The health system DAs provided information on which patients are candidate for treatment, values and preferences, costs and resources, acceptability, impact on health equity, feasibility, drug dosing, alternative therapies, remission rates and prognosis. Health system stakeholders found the DA useful for clinical decision-making and generalisable to other conditions. The encounter DA was produced as cards containing information on issues that drive treatment decisions (effect on symptoms, effect on function, treatment burden, side effects and cost). Patients and parents prioritised the cards and chose the order in which these issues were discussed with clinician. The encounter DA was found to be helpful by patients, parents and clinicians. We conclude that the uptake of evidence summaries by health systems can be enhanced by developing tools that provide contextual and implementation information about clinical care. A dual approach addressing health system stakeholders as well as clinicians and patients is likely feasible and helpful.
Long-read sequencing identified intronic repeat expansions inSAMD12from Chinese pedigrees affected with familial cortical myoclonic tremor with epilepsy
Authors: Zeng Sheng , Zhang Mei-yun , Wang Xue-jing , Hu Zheng-mao , Li Jin-chen , Li Nan , Wang Jun-ling , Liang Fan , Yang Qi , Liu Qian , Fang Li , Hao Jun-wei , Shi Fu-dong , Ding Xue-bing , Teng Jun-fang , Yin Xiao-meng , Jiang Hong , Liao Wei-ping , Liu Jing-yu , Wang Kai , Xia Kun , Tang Bei-sha
Published: September 2018

Background

The locus for familial cortical myoclonic tremor with epilepsy (FCMTE) has long been mapped to 8q24 in linkage studies, but the causative mutations remain unclear. Recently, expansions of intronic TTTCA and TTTTA repeat motifs withinSAMD12were found to be involved in the pathogenesis of FCMTE in Japanese pedigrees. We aim to identify the causative mutations of FCMTE in Chinese pedigrees.

Methods

We performed genetic linkage analysis by microsatellite markers in a five-generation Chinese pedigree with 55 members. We also used array-comparative genomic hybridisation (CGH) and next-generation sequencing (NGS) technologies (whole-exome sequencing, capture region deep sequencing and whole-genome sequencing) to identify the causative mutations in the disease locus. Recently, we used low-coverage (~10×) long-read genome sequencing (LRS) on the PacBio Sequel and Oxford Nanopore platforms to identify the causative mutations, and used repeat-primed PCR for validation of the repeat expansions.

Results

Linkage analysis mapped the disease locus to 8q23.3–24.23. Array-CGH and NGS failed to identify causative mutations in this locus. LRS identified the intronic TTTCA and TTTTA repeat expansions inSAMD12as the causative mutations, thus corroborating the recently published results in Japanese pedigrees.

Conclusions

We identified the pentanucleotide repeat expansion inSAMD12as the causative mutation in Chinese FCMTE pedigrees. Our study also suggested that LRS is an effective tool for molecular diagnosis of genetic disorders, especially for neurological diseases that cannot be positively diagnosed by conventional clinical microarray and NGS technologies.
Transient in-stent stenosis at mid-term angiographic follow-up in patients treated with SILK flow diverter stents: incidence, clinical significance and long-term follow-up
Authors: Essbaiheen Fahad , AlQahtani Hanan , Almansoori Taleb Mohamed , Cora Elena Adela , Patro Satya , Tsehmaister-Abitbul Vered , Drake Brian , Lesiuk Howard , Finitsis Stephanos Nikolaos , Iancu Daniela
Published: September 2018

Background

Little is known about in-stent stenosis (ISS) in patients with aneurysms treated with flow diverter (FD) stents. The reported incidence in the literature varies significantly.

Objective

The aim of this study was to assess the incidence, severity, distribution, clinical significance, and possible predictors for ISS.

Methods

Between July 2012 and June 2016 we retrospectively reviewed all patients treated with SILK FDs in our center. Only cases with short-term (4±2 months) and long-term (>1 year) follow-ups with digital subtraction angiograms were included. ISS was graded as mild (<25%), moderate (25–50%) or severe (>50%). The following predictors for ISS were assessed: gender, age, the presence of subarachnoid hemorrhage, aneurysm size, location, occlusion status, and post-stenting angioplasty.

Results

Thirty-six patients met the inclusion criteria. At mid-term follow-up, ISS was observed in 16/36 patients (44%). Eleven patients (69%) had mild ISS, three (19%) moderate, and two (12%) severe ISS. ISS was diffuse in 11 patients (69%) and focal in five patients (31%). All patients were asymptomatic. Thirteen patients were maintained on dual antiplatelet therapy and three on aspirin alone. At long-term follow-up, complete ISS resolution was seen in 11 patients, improvement in three and worsening in two patients. No de novo ISS occurrence was observed. On univariate analysis there was no significant predictor for ISS.

Conclusions

Transient ISS after FD deployment is a common asymptomatic finding on mid-term angiographic follow-up. Complete resolution or improvement at long-term follow-up is seen in most patients who are maintained on dual antiplatelet therapy.
A crosslinked and ribosylated actin trimer does not interact productively with myosin
Authors: Sidhu Navneet , Dawson John F.
Published: September 2018

A purified F-actin-derived actin trimer that interacts with end-binding proteins did not activate or bind the side-binding protein myosin under rigor conditions. Remodeling of the actin trimer by the binding of gelsolin did not rescue myosin binding, nor did the use of different means of inhibiting the polymerization of the trimer. Our results demonstrate that ADP-ribosylation on all actin subunits of an F-actin-derived trimer inhibits myosin binding and that the binding of DNase-I to the pointed end subunits of a crosslinked trimer also remodels the myosin binding site. Taken together, this work highlights the need for a careful balance between modification of actin subunits and maintaining protein–protein interactions to produce a physiologically relevant short F-actin complex.
Inter- and intra-varietal variation in aerobic methane emissions from environmentally stressed pea plants
Authors: Abdulmajeed Awatif M. , Abo Gamar Mohammad I. , Qaderi Mirwais M.
Published: September 2018

Environmental stress factors can influence methane (CH4) emissions from plants. There are a few studies on the interactive effects of stress factors on plant aerobic CH4, but none on the comparative evaluation of CH4 emissions between and among plant varieties. We examined the effects of temperature, UVB radiation, and watering regime on CH4 emissions from 10 pea (Pisum sativum L.) varieties first and then selected two varieties with the highest (237J Sundance; var. 1) and lowest (422 Ho Lan Dow; var. 2) emissions for further studies. Plants were grown in controlled-environment growth chambers under two temperature regimes (22 °C / 18 °C and 28 °C / 24 °C, 16 h light / 8 h dark), two UVB levels (0 and 5 kJ·m−2·d−1), and two watering regimes (well-watered and water-stressed) for 14 days, after one week of growth under 22 °C / 18 °C. Higher temperatures and water stress increased CH4 emissions, and increased emission was associated with stress. Pea varieties varied in growth and CH4 emissions; var. 1 was more stressed and had higher emission than var. 2. In the stressed variety, the water-stressed plants grown under higher temperatures at UVB5 had the highest CH4 emission, whereas the well-watered plants grown under lower temperatures at UVB5 had the lowest emission. We conclude that climatic stress conditions increase CH4 emissions, which vary with plant varieties.
Facile direct synthesis of amides from trichloroethyl esters using catalytic DBU
Authors: La Minh Thanh , Kim Hee-Kwon
Published: September 2018

A practical method for the direct synthesis of amide compounds is described. Using small quantities of DBU as a catalyst, the direct conversion of 2,2,2-trichloroethyl esters to their corresponding amides was readily achieved. Based on this protocol, various amide compounds were successfully synthesized in high yield, suggesting a promising approach for the practical one-pot aminolysis from 2,2,2-trichloroethyl protected esters.
Generic immersions and totally real embeddings
Authors: Kasuya Naohiko , Takase Masamichi
Published: September 2018

We show that, for a closed orientable [Formula: see text]-manifold, with [Formula: see text] not congruent to 3 modulo 4, the existence of a CR-regular embedding into complex [Formula: see text]-space ensures the existence of a totally real embedding into complex [Formula: see text]-space. This implies that a closed orientable [Formula: see text]-manifold with non-vanishing Kervaire semi-characteristic possesses no CR-regular embedding into complex [Formula: see text]-space. We also pay special attention to the cases of CR-regular embeddings of spheres and of simply-connected 5-manifolds.
Gauge approach to the symmetric teleparallel gravity
Authors: Adak Muzaffer
Published: September 2018

We discuss a gauge invariant gravity model in a non-Riemannian geometry in which the curvature and the torsion both are zero, the nonmetricity is nonzero. We also argue that only a metric ansatz is enough to start finding solutions to the field equations. As an application, we obtain explicitly a conformally flat solution.
The Statistical Characteristics of Static Friction
Authors: Wang Jian , Wang Gangfeng , Yuan Weike , Bian Jianjun
Published: September 2018

Friction is one of the fundamental issues in physics, mechanics and material science with many practical applications. However, the understanding of macroscopic friction phenomena from microscopic aspect is still on the way. In this paper, molecular dynamics simulations are performed to investigate the static friction between two planar crystal surfaces. The friction force experienced by each atom is tracked and the statistical characteristics of atomic friction force are illuminated. More importantly, the influences of normal load and temperature on the statistical features are generalized. This study provides a new insight on the micro-states of friction.
Combination of Taper and Hierarchy to Improve Crushing Efficiency of Thin-Walled Tubes
Authors: Li Weiwei , Lai Changliang , Fan Hualin
Published: September 2018

To improve the energy absorption capacity of thin-walled tubular structures and simultaneously reduce their initial peak force (IPF), hierarchical hexagonal tapered tube (HHTT) is proposed combining advantages of the hierarchical hexagonal tube (HHT) and the tapered tube (TT), for HHTs can greatly improve the mean crushing force (MCF) while TTs can reduce the IPF. Crushing behaviors of HHTTs under quasi-static compression are investigated through numerical simulations and theoretical analyses. According to the folding modes, a theory to predict the MCF of the HHTT is proposed. According to the research, it is found that the combination of hierarchy and tapering improves the MCF of the tubular structure and the crushing force efficiency (CFE), defined by the ratio of the MCF to the IPF. It is also found that increasing the tapered angle, the wall thickness and the cell number of the lattice wall can effectively improve the CFE of the HHTT.
Short loops in surfaces with a circular boundary component
Authors: Papasoglu Panos
Published: September 2018

It is a classical theorem of Loewner that the systole of a Riemannian torus can be bounded in terms of its area. We answer a question of a similar flavor of Robert Young showing that if [Formula: see text] is a Riemannian surface with connected boundary in [Formula: see text], such that the boundary curve is a standard unit circle, then the length of the shortest non-contractible loop in [Formula: see text] is bounded in terms of the area of [Formula: see text].
m-Secure vertex cover of a graph
Authors: Pushpam P. Roushini Leely , Suseendran Chitra
Published: September 2018

In this paper, we use multiple guard movements to defend the edges of a graph [Formula: see text] against a single attack. At most, one guard is positioned at each vertex. To defend an attack on an edge, a guard at an incident vertex moves across the attacked edge and the other guards may move (or not) to the neighboring vertices to better configure themselves. This strategy requires the set of vertices containing guards to be a vertex cover before and after an attack. A suitable placement of guards is called an [Formula: see text]-secure vertex cover of [Formula: see text]. We call this the [Formula: see text]-secure vertex cover problem, where [Formula: see text] stands for the multiple guard movements. The minimum number of guards required to defend the edges of [Formula: see text] against a single attack using multiple guard movements is called the [Formula: see text]-secure vertex covering number and it is denoted by [Formula: see text]. In this paper we initiate a study of this parameter.
Self-sealing of claystone under X-ray nanotomography
Authors: Giot Richard , Auvray Christophe , Talandier Jean
Published: September 2018

Self-sealing tests were carried out on cylindrical samples artificially cracked on one-third of the diameter with a perfectly controlled aperture. Water was then injected into the crack. An innovative cell was used that had been developed, the body of which is transparent to X-rays. The sample could fully rotate in the nanotomograph, allowing a 3D reconstruction of images before, during and after tests, a visualization of the evolution of the cracked zone, and a quantification of the variations in crack volume during self-sealing. Permeability measurements were made to quantify the influence of self-sealing on flows. In the present work, two facies of claystone with different CaCO
3
contents were tested. In the clay-rich sample, an important but not total, reduction in volume was observed, as well as a large decrease in permeability, even if a safe claystone value was not recovered and a two-phase kinematic occurred. On the CaCO
3
-rich samples, a small volume reduction of the fracture was observed with a small decrease in water permeability. The influence of the mineralogy on the self-sealing capacity of the claystone was demonstrated and a threshold of carbonate content of around 40% was exhibited to discriminate samples able to self-seal from those that were not.
Status of research on physiology education in Brazil
Authors: Machado Rui Seabra , Mello-Carpes Pâmela Billig
Published: September 2018

Physiology education research aims to investigate teaching-learning aspects and methods specifically applied to physiology teaching and learning. In this paper exploring Brazilian research public data and information from the Brazilian Physiological Society Teaching Committee, we investigated the status of this research topic (physiology education) in Brazil. The data showed that physiology education research needs to be more recognized and supported in Brazil, and more physiologists may become interested in research in this field. Thus this field will become more developed during the physiologists' education.
Sex differences in the vascular function and related mechanisms: role of 17β-estradiol
Authors: Pabbidi Mallikarjuna R. , Kuppusamy Maniselvan , Didion Sean P. , Sanapureddy Padmaja , Reed Joey T. , Sontakke Sumit P.
Published: September 2018

The incidence of cardiovascular disease (CVD) is lower in premenopausal women but increases with age and menopause compared with similarly aged men. Based on the prevalence of CVD in postmenopausal women, sex hormone-dependent mechanisms have been postulated to be the primary factors responsible for the protection from CVD in premenopausal women. Recent Women’s Health Initiative studies, Cochrane Review studies, the Early Versus Late Intervention Trial with Estradiol Study, and the Kronos Early Estrogen Prevention Study have suggested that beneficial effects of hormone replacement therapy (HRT) are seen in women of <60 yr of age and if initiated within <10 yr of menopause. In contrast, the beneficial effects of HRT are not seen in women of >60 yr of age and if commenced after 10 yr of menopause. The higher incidence of CVD and the failure of HRT in postmenopausal aged women could be partly associated with fundamental differences in the vascular structure and function between men and women and in between pre- and postmenopausal women, respectively. In this regard, previous studies from human and animal studies have identified several sex differences in vascular function and associated mechanisms. The female sex hormone 17β-estradiol regulates the majority of these mechanisms. In this review, we summarize the sex differences in vascular structure, myogenic properties, endothelium-dependent and -independent mechanisms, and the role of 17β-estradiol in the regulation of vascular function.
Vascular mitochondrial respiratory function: the impact of advancing age
Authors: Park Soung Hun , Kwon Oh Sung , Park Song-Young , Weavil Joshua C. , Andtbacka Robert H. I. , Hyngstrom John R. , Reese Van , Richardson Russell S.
Published: September 2018

Little is known about vascular mitochondrial respiratory function and the impact of age. Therefore, skeletal muscle feed arteries were harvested from young (33 ± 7 yr, n = 10), middle-aged (54 ± 5 yr, n = 10), and old (70 ± 7 yr, n = 10) subjects, and mitochondrial respiration as well as citrate synthase (CS) activity were assessed. Complex I (CI) and complex I + II (CI+II) state 3 respiration were greater in young (CI: 10.4 ± 0.8 pmol·s−1·mg−1 and CI+II: 12.4 ± 0.8 pmol·s−1·mg−1, P < 0.05) than middle-aged (CI: 7 ± 0.6 pmol·s−1·mg−1 and CI+II: 8.3 ± 0.5 pmol·s−1·mg−1) and old (CI: 7.2 ± 0.4 pmol·s−1·mg−1 and CI+II: 7.6 ± 0.5 pmol·s−1·mg−1) subjects and, as in the case of complex II (CII) state 3 respiration, were inversely correlated with age [ r = −0.56 (CI), r = −0.7 (CI+II), and r = 0.4 (CII), P < 0.05]. In contrast, state 4 respiration and mitochondria-specific superoxide levels were not different across groups. The respiratory control ratio was greater in young (2.2 ± 0.2, P < 0.05) than middle-aged and old (1.4 ± 0.1 and 1.1 ± 0.1, respectively) subjects and inversely correlated with age ( r = −0.71, P < 0.05). As CS activity was inversely correlated with age ( r = −0.54, P < 0.05), when normalized for mitochondrial content, the age-related differences and relationships with state 3 respiration were ablated. In contrast, mitochondrion-specific state 4 respiration was now lower in young (15 ± 1.4 pmol·s−1·mg−1·U CS−1, P < 0.05) than middle-aged and old (23.4 ± 3.6 and 27.9 ± 3.4 pmol·s−1·mg−1·U CS−1, respectively) subjects and correlated with age ( r = 0.46, P < 0.05). Similarly, superoxide/CS levels were lower in young (0.07 ± 0.01) than old (0.19 ± 0.41) subjects and correlated with age ( r = 0.44, P < 0.05). Therefore, with aging, vascular mitochondrial respiratory function declines, predominantly as a consequence of falling mitochondrial content. However, per mitochondrion, aging likely results in greater mitochondrion-derived oxidative stress, which may contribute to age-related vascular dysfunction.

NEW & NOTEWORTHY This study determined, for the first time, that vascular mitochondrial oxidative respiratory capacity, oxidative coupling efficiency, and mitochondrial content fell progressively with advancing age. In terms of single mitochondrion-specific respiration, the age-related differences were completely ablated and the likelihood of free radical production increased progressively with advancing age. This study reveals that vascular mitochondrial respiratory capacity declines with advancing age, as a consequence of falling mitochondrial content, as does oxidative coupling efficiency.
Updated Survival Analysis after a Median Follow-up of 12 Years of an Anthracycline-Containing Adjuvant Prospective Multicentre, Randomised Phase III Trial on Dose-Dense Chemotherapy in Primary Node-Positive, High-Risk Breast Cancer Patients
Authors: Reinisch Mattea , Gluz Oleg , Ataseven Beyhan , Blohmer Jens-Uwe , Budner Marek , Dittmer-Grabowski Christine , Kohls Andreas , Krocker Jutta , Kümmel Aylin , Hagemann Friederike , Rüland Anna , Traut Alexander , Kümmel Sherko
Published: September 2018

Purpose: Although dose-dense (dd) chemotherapy plays a fundamental role in the treatment of breast cancer (BC), a variety of trials have presented divergent survival results. Here, we present data of patients with more than 3 positive axillary lymph nodes (+aLN) receiving dd chemotherapy after a median follow-up period of 12.3 years. Methods: In the years 1996-2000, 231 patients with invasive BC, ≥pN2a and no evidence of distant metastases were recruited to receive treatment A, i.e. dd 3 × epirubicin (E, 90 mg/m2) + paclitaxel (P, 175 mg/m2) every 2 weeks (q2w) followed by 3 × cyclophosphamide (C)/methotrexate/5-fluorouracil (CMF, 600/40/600 mg/m2, q2w), or treatment B, i.e. 4 × E + C (C, 600 mg/m2) q3w followed by 3 × CMF q3w. Results: 113 patients in arm A and 113 patients in arm B were analysed after an updated median follow-up of 12.3 years. The median age was 55 years, with a median number of 6 +aLN, 50.4% had a T2 and 79.2% hormone receptor-positive BC. The disease-free survival (DFS) rate was 53.1% in arm A and 42.5% in arm B (adjusted p = 0.027). The overall survival (OS) rate was 54.9% in arm A and 48.7% in arm B (adjusted p = 0.058). In the multivariable analysis, the tumour burden was a significant predictor for DFS and OS. Conclusion: The adjuvant use of dd chemotherapy led to a statistically significant improvement of DFS after a follow-up of 12.3 years.
Intensive Expositionsbehandlung bei Angststörungen in einem spezialisierten tagesklinischen Versorgungssetting
Authors: Noack René , Schmidt Ruth , Lorenz Thomas , Rottstaedt Fabian , Beiling Peter , Schurig Susan , Ritschel Gerhard , Weidner Kerstin
Published: September 2018

Hintergrund: Angststörungen sind häufig, oft chronifizierend, jedoch auch gut behandelbar. Leitlinienbehandlung ist die auf Exposition fokussierende Verhaltenstherapie. In der ambulanten Versorgungspraxis finden Expositionen jedoch selten statt. Die Angst-Tagesklinik am Universitätsklinikum Dresden realisiert die evidenzbasierte Behandlung von Angststörungen. In einer 5-wöchigen Kurzzeitbehandlung werden wöchentlich 4 begleitete und zeitoffene Expositionssitzungen durchgeführt. Untersucht wurden die Symptomverläufe und die Responder-Raten. Methoden: Zu Therapieaufnahme und -ende sowie zur Katamnese nach 3 Monaten und 1 Jahr wurde die Entwicklung der Symptombelastung bei n = 332 PatientInnen untersucht, die von 2009 bis 2015 behandelt wurden. Etwa zwei Drittel waren psychotherapeutisch vorbehandelt. Eingesetzt wurden spezifische etablierte Fragebögen. Berechnet wurden Mixed Models, Effektstärken und Responder-Raten. Ergebnisse: 90% der PatientInnen schlossen die Behandlung regulär ab. Es zeigten sich signifikante Linderungen bei Belastungen durch Angst- und depressive Symptome. Die höchsten Effektstärken um 0,9 ergaben sich bei verhaltensbezogenen Skalen und besonders bei den Agoraphobien und Panikstörungen, die die größte Störungsgruppe ausmachen. Die Responseraten lagen bei 60%. Zu den Katamnesezeitpunkten waren die Symptomverbesserungen stabil und bei den kognitiven Symptomen weiter steigend. Schlussfolgerungen: Die Behandlung in spezialisierten (teil)stationären Versorgungssettings mit Fokus auf hochfrequente Exposition, wie hier beispielhaft vorgestellt, zeigt eine gute Akzeptanz und gute bis sehr gute und längerfristig stabile Veränderungen der Symptombelastung. Diese Settings erfordern eine besondere strukturelle Ausstattung und Ressourcen.
Corneal Blood Staining after Complicated Cataract Surgery
Authors: Krauthammer Mark , Mandelblum Jorje , Spierer Oriel
Published: September 2018

Purpose: To report the case of a patient with corneal blood staining after a complicated cataract surgery. Observations: We report on a 68-year-old woman who developed corneal blood staining secondary to hyphema after cataract surgery, despite the fact that intraocular pressure was not increased for a prolonged time. The corneal staining spontaneously cleared from the periphery towards the center. It was fully resolved after 2.5 years of follow-up. Conclusions and Importance: In case of hyphema induced by cataract surgery, performance of early anterior chamber washout should be considered to prevent corneal blood staining and poor visual outcome.
Nivolumab-Induced Impressive Response of Refractory Pulmonary Sarcomatoid Carcinoma with Brain Metastasis
Authors: Salati Massimiliano , Baldessari Cinzia , Calabrese Fiorella , Rossi Giulio , Pettorelli Elisa , Grizzi Giulia , Dominici Massimo , Barbieri Fausto
Published: September 2018

Background: Pulmonary sarcomatoid carcinoma is a rare, poorly differentiated, and highly aggressive type of non-small cell lung cancer. High tumor mutational burden and PD-L1 overexpression make it an excellent candidate for immunotherapy. Objectives and Method: We presented the case of a patient who underwent left inferior lobectomy with concurrent right paravertebral muscular metastasectomy for an infiltrative neoplastic mass, whose final diagnosis was consistent with stage IV pulmonary sarcomatoid carcinoma. He received first- and second-line chemotherapy without any benefit. Since March 2016, he has been treated with the anti-PD1 agent nivolumab with a dramatic improvement of symptoms, disappearance of a brain lesion, and partial response on other metastatic sites. He tolerated the treatment well and is still responding after 22 months from the beginning. Results and Conclusions: In very lethal non-small cell lung cancer subtypes such as the sarcomatoid variants, high tumor burden and deteriorated general conditions should not preclude, at least in some cases, the use of immunotherapy. Anti-PD1 may also have a reliable role in disease control in the brain. Lastly, the strong rationale behind sarcomatoid histology should further prompt trials exploring immunotherapeutic approaches in this subset of non-small cell lung cancer.
Integrin β3 Mediates the Endothelial-to-Mesenchymal Transition via the Notch Pathway
Authors: Wang Weisen , Wang Zhi , Tian Dingyuan , Zeng Xi , Liu Yangdong , Fu Qining , Liang Anlin , Zhang Yi , Gao Qiangguo , Cheng Jizhong , Wang Yun
Published: September 2018

Background/Aims: Neointimal hyperplasia is responsible for stenosis, which requires corrective vascular surgery, and is also a major morphological feature of many cardiovascular diseases. This hyperplasia involves the endothelial-to-mesenchymal transition (EndMT). We investigated whether integrin β3 can modulate the EndMT, as well as its underlying mechanism. Methods: Integrin β3 was overexpressed or knocked down in human umbilical vein endothelial cells (HUVECs). The expression of endothelial markers and mesenchymal markers was determined by real-time reverse transcription PCR (RT-PCR), immunofluorescence staining, and western blot analysis. Notch signaling pathway components were detected by real-time RT-PCR and western blot analysis. Cell mobility was evaluated by wound-healing, Transwell, and spreading assays. Fibroblast-specific protein 1 (FSP-1) promoter activity was determined by luciferase assay. Results: Transforming growth factor (TGF)-β1 treatment or integrin β3 overexpression significantly promoted the EndMT by downregulating VE-cadherin and CD31 and upregulating smooth muscle actin α and FSP-1 in HUVECs, and by enhancing cell migration. Knockdown of integrin β3 reversed these effects. Notch signaling was activated after TGF-β1 treatment of HUVECs. Knockdown of integrin β3 suppressed TGF-β1-induced Notch activation and expression of the Notch downstream target FSP-1. Conclusion: Integrin β3 may promote the EndMT in HUVECs through activation of the Notch signaling pathway.
Connexin 43: a New Therapeutic Target Against Chronic Kidney Disease
Authors: Prakoura Niki , Kavvadas Panagiotis , Chadjichristos Christos E. 
Published: September 2018

Chronic kidney disease is an incurable to date pathology with a continuously growing incidence that contributes to the increase of the number of deaths worldwide. With currently no efficient prognostic or therapeutic options being available, the only possibility for treatment of end-stage renal disease is renal replacement therapy through dialysis or transplantation. Understanding the molecular mechanisms participating in the progression of renal diseases and uncovering the pathways implicated will permit the identification of novel and more efficient targets of therapy. Connexin43 was recently identified as a novel player in the development of chronic kidney disease. It was found de novo expressed and/or differentially localized in various renal cell populations during progression of renal disease, indicating an abnormal connexin signaling, both in patients and animal models. Subsequent in vivo studies demonstrated that connexin43 is involved in mediating inflammatory and fibrotic processes contributing to renal damage. Genetic, pharmaco-genetic or peptide-based inhibition of connexin43 in animal models and cell culture systems was successful in preventing the progression of the pathology and preserving the cell phenotypes. This review will summarize the recent advances on connexin43 in the field of kidney diseases and discuss the potential of future connexin43-based therapies against chronic kidney disease.
Ganoderma Lucidum Polysaccharide Peptide Alleviates Hepatoteatosis via Modulating Bile Acid Metabolism Dependent on FXR-SHP/FGF
Authors: Zhong Dandan , Xie Zhengwei , Huang Boyue , Zhu Shuai , Wang Guoqian , Zhou Hong , Lin Shuqian , Lin Zhibin , Yang Baoxue
Published: September 2018

Background/Aims: Non-alcoholic fatty liver disease (NAFLD) encompasses a series of pathologic changes ranging from steatosis to steatohepatitis, which may progress to cirrhosis and hepatocellular carcinoma. The purpose of this study was to determine whether ganoderma lucidum polysaccharide peptide (GLPP) has therapeutic effect on NAFLD. Methods: Ob/ ob mouse model and ApoC3 transgenic mouse model were used for exploring the effect of GLPP on NAFLD. Key metabolic pathways and enzymes were identified by metabolomics combining with KEGG and PIUmet analyses and key enzymes were detected by Western blot. Hepatosteatosis models of HepG2 cells and primary hepatocytes were used to further confirm the therapeutic effect of GLPP on NAFLD. Results: GLPP administrated for a month alleviated hepatosteatosis, dyslipidemia, liver dysfunction and liver insulin resistance. Pathways of glycerophospholipid metabolism, fatty acid metabolism and primary bile acid biosynthesis were involved in the therapeutic effect of GLPP on NAFLD. Detection of key enzymes revealed that GLPP reversed low expression of CYP7A1, CYP8B1, FXR, SHP and high expression of FGFR4 in ob/ob mice and ApoC3 mice. Besides, GLPP inhibited fatty acid synthesis by reducing the expression of SREBP1c, FAS and ACC via a FXR-SHP dependent mechanism. Additionally, GLPP reduced the accumulation of lipid droplets and the content of TG in HepG2 cells and primary hepatocytes induced by oleic acid and palmitic acid. Conclusion: GLPP significantly improves NAFLD via regulating bile acid synthesis dependent on FXR-SHP/FGF pathway, which finally inhibits fatty acid synthesis, indicating that GLPP might be developed as a therapeutic drug for NAFLD.
In Vitro Analyses of Novel HCN4 Gene Mutations
Authors: Möller Melina , Silbernagel Nicole , Wrobel Eva , Stallmayer Birgit , Amedonu Elsie , Rinné Susanne , Peischard Stefan , Meuth Sven G. , Wünsch Bernhard , Strutz-Seebohm Nathalie , Decher Niels , Schulze-Bahr Eric , Seebohm Guiscard
Published: September 2018

Background/Aims: The hyperpolarization-activated cyclic nucleotide-gated cation channel HCN4 contributes significantly to the generation of basic cardiac electrical activity in the sinus node and is a mediator of modulation by β–adrenergic stimulation. Heterologous expression of sick sinus syndrome (SSS) and bradycardia associated mutations within the human HCN4 gene results in altered channel function. The main aim was to describe the functional characterization of three (two novel and one known) missense mutations of HCN4 identified in families with SSS. Methods: Here, the two-electrode voltage clamp technique on Xenopus laevis oocytes and confocal imaging on transfected COS7 cells respectively, were used to analyze the functional effects of three HCN4 mutations; R378C, R550H, and E1193Q. Membrane surface expressions of wild type and the mutant channels were assessed by confocal microscopy, chemiluminescence assay, and Western blot in COS7 and HeLa cells. Results: The homomeric mutant channels R550H and E1193Q showed loss of function through increased rates of deactivation and distinctly reduced surface expression in all three homomeric mutant channels. HCN4 channels containing R550H and E1193Q mutant subunits only showed minor effects on the voltage dependence and rates of activation/deactivation. In contrast, homomeric R378C exerted a left-shifted activation curve and slowed activation kinetics. These effects were reduced in heteromeric co-expression of R378C with wild-type (WT) channels. Conclusion: Dysfunction of homomeric/heteromeric mutant HCN4-R378C, R550H, and E1193Q channels in the present study was primarily caused by loss of function due to decreased channel surface expression.
ЕНДОТЕЛІАЛЬНІ Й ІМУНОЛОГІЧНІ ЗМІНИ ПРИ КОМПРЕСІЙНО-ІШЕМІЧНІЙ РАДИКУЛОМІЄЛОПАТІЇ ТА ЇХ ЕНЕРГЕТИЧНА КОРЕКЦІЯ
Authors: Pogorelov V. V. , Bagmut I. Y. , Zhukov V. I.
Published: September 2018

The pathological process of compression-ischemic radiculomyelopathy (CIRMP ) is accompanied by high energy costs. Therefore, topical is the use of drugs that improve energy metabolism in hypoxic conditions.The aim of the study – to investigate the features of the immuno-inflammatory process in CIRMP under the influence of meldonium.Materials and Methods. The parameters of 45 patients with CIRMP were investigated. All patients received conventional therapy. Patients of the group 1 (26 patients) received meldonium additionally, and in the group 2 (the main one – 19 patients) included "capicor". The levels of endothelin-1, cGMP , NO , interleukin-1β and -4, tumor necrosis factor-α were studied, aggregation properties of platelets were studied.Results and Discussion. Against the background of the treatment of patients with the use of meldonium and meldonium+γ-butyrobetan dihydrate, positive changes in the biochemical parameters: endothelin-1, cGMP , NO , interleukins 1β and 4, tumor necrosis factor α, aggregation properties of platelets, improvement of the function of the endothelium and blood circulation in the microvessels of the rootlets, which, in turn, led to the restoration of the functional state of roots and spinal cord.Conclusions. The use of meldonium and meldonium+γ-butyrobetaine in the therapy of patients with CIRMP was accompanied by a regression of clinical manifestations, which is associated with an improvement in blood circulation in the vessels of the spinal roots and back muscles. A more pronounced effect was influenced by meldonium in combination with γ-butyrobetaine.
ФАКТОРИ РИЗИКУ ПРОФЕСІЙНИХ ЗАХВОРЮВАНЬ МЕДИЧНИХ ПРАЦІВНИКІВ (ОГЛЯД ЛІТЕРАТУРИ)
Authors: Bodnar L. P. , Bob A. O. , Bodnar R. Ya. , Reha N. I. , Bodnar T. V.
Published: September 2018

The study of the risk factors of occupational diseases is a medical and social issue from a view point of practice and sociology, it is a theoretical basis for the development of methods for their prevention. The official statistical reports prove that in Ukraine, more than 60 % of 1.1 million health workers undergo harmful exposure and danger, and occupational disease occurrence among them is recorded at the level of 0.71 per 100 thousand working population. In the structure of occupational diseases, tuberculosis is first (80–100 %, on average – 87.7 %), diseases of musculoskeletal system are second (1.3–6.7 %, on average – 3.1 %), allergic diseases are third – 1.0–5.1 % (on average – 2.3 %).The aim of the study – to learn and summarize the causes of professional diseases of medical workers in Ukraine.Materials and Methods. Occupational morbidity of medical staff is caused by the influence of risk factors: mechanical, physical, chemical, biological, nervous-emotional. Medical workers under static work conditions are exposed to negative mechanical influences. The harmful effects of physical factor are considerably increased at present due to a widespread implementation of equipment with light, electromagnetic and radioactive radiation into medical and diagnostic processes. Due to the rapid development of chemical and pharmaceutical industries, the number of chemicals that cause not only the therapeutic effect on a patient but also have a negative impact on healthcare workers in cases of their systematic use has increased significantly.Results and Discussion. A group of occupational diseases caused by pathogens of tuberculosis, toxoplasmosis, viral hepatitis, skin mycoses, syphilis, and HIV infection is an urgent matter of health care in Ukraine. The risk of HIV infection is about 0.3 % and reaches 10 % in cases of hepatitis C virus, and 30 % in hepatitis B virus. In Ukraine, according to the Ministry of Health, every year 30.0–50.0 thousand patients are diagnosed with this illness (84.1 per 100 thousand population). Manifestations of the emotional affection as a symptom complex of “professional burnout” have been revealed in almost 80 % of psychiatrists, psychotherapists, narcologists, in 61.8 % of dentists, and 60.6 % of medical nurses of oncology departments.Conclusion. The analyses of occupational diseases cases among healthcare workers of various medical facilities of Ukraine in 2011–2017 has proved that the highest number of occupational diseases is registered in TB facilities – 70.1–95.5 %. 3.0–6.4 % of all occupational diseases in the healthcare have been registered in community hospitals, 1.5–10.2 – in psychoneurological hospitals, 1.9–3.0 % – in the Bureau of Forensic Medicine and 2.6–3.0 % – in research institutions.
ДИНАМІКА КЛІТИННОГО СКЛАДУ ПЕЧІНКИ ЩУРІВ ПІСЛЯ ВНУТРІШНЬОУТРОБНОГО ВВЕДЕННЯ ДЕКСАМЕТАЗОНУ В РАННЬОМУ ПІСЛЯНАТАЛЬНОМУ ПЕРІОДІ
Authors: Hryhorieva O. A. , Bohdanov P. V.
Published: September 2018

The controversial issue in obstetrics today is the use of glucocorticoids during pregnancy, because they can have both a positive and negative impact on the processes of formation of organs and can lead to pathological conditions in the postnatal period.The aim of the study – to determine the dynamics of the cellular composition of the liver of rats after intrauterine administration of dexamethasone in the early postnatal period.Materials and Methods. The 72 laboratory rats’ liver was studied in this work. All animals were divided into 3 groups: 1 – intact, 2 – control, 3 – experimental (animals which had have injection of dexamethasone in antenatal period). Using histological, morphometric and statistical methods of research, the absolute number of cells per unit area have been calculates in two zones of hepatic lobules – central and peripheral.Results and Discussion. It was established that on the first day of life in experimental animals, the number of hepatocytes increases in comparison with control and significantly reduces the number of endothelial cells of sinusoidal capillaries and stellate macrophages. On the 14th day of life, on the contrary, the number of hepatocytes decreases with the simultaneous increase in the number of sinusoidal endothelial cells, stellate macrophages and lymphocytes.Conclusions. Thus, antenatal dexamethasone influence results in liver bring to changes in the ratio between rat’s liver cells with peaks on the first and fourteenth day of life.