Δευτέρα, 4 Δεκεμβρίου 2017

Analysis of the multi-echo spin-echo pulse sequence

Abstract

The multi-echo spin-echo sequence is a series of operators, referred to as periodic operators. Each periodic operator consists of a free rotation (no RF), a refocusing RF pulse, and another free rotation, identical to the first one. A preparation operator that precedes the periodic operators converts the equilibrium magnetization Mz into an initial magnetization Mi. It is shown that a multi-echo sequence is equivalent to a simple rotation of the magnetization about a tilted axis. The component of Mi along the rotation axis is stationary and provides a stable signal, denoted pseudo steady-state. The perpendicular component rotates and eventually de-phases. Using this model, we derive analytic expressions to the signal for different preparation operators, and show how to align Mi with the rotation axis such that the signal is maximized. A simple and efficient algorithm is presented to calculate the Fourier coefficients of the magnetization during the sequence using the discrete Fourier transform. Finally, formulas of the echo signal when unavoidable phase errors are generated are derived. We show how to eliminate artifacts caused by these errors and restore the original image.



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Scimitar Syndrome CXR : DAMS Unplugged

Presenting a brief teaching video on scimitar syndrome diagnosed on CXR.


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Phase I–III development of the EORTC QLQ-ANL27, a health-related quality of life questionnaire for anal cancer

There is currently no health-related quality of life (HRQoL) measure specific to anal cancer. Our objective was to develop an anal cancer HRQoL module to supplement the EORTC QLQ-C30 questionnaire using EORTC Quality of Life Group Guidelines.

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Clinical pathologic conference: diffuse papillomatous lesions of the gingiva with posterolateral neck skin tags.

Clinical pathologic conference: diffuse papillomatous lesions of the gingiva with posterolateral neck skin tags.

Oral Surg Oral Med Oral Pathol Oral Radiol. 2017 Nov 06;:

Authors: Lin SI, Mort JR, Hinchey PM, Lewis JS, Zwerner J

PMID: 29195813 [PubMed - as supplied by publisher]



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Effects of a single condylar neck fracture without condylar cartilage injury on traumatic heterotopic ossification around the temporomandibular joint in mice.

Effects of a single condylar neck fracture without condylar cartilage injury on traumatic heterotopic ossification around the temporomandibular joint in mice.

Oral Surg Oral Med Oral Pathol Oral Radiol. 2017 Nov 06;:

Authors: Ouyang N, Zhu X, Li H, Lin Y, Shi J, Dai J, Shen G

Abstract
OBJECTIVES: In this study, we tried to explore the effects of a single condylar neck fracture without condylar cartilage injury during the pathogenesis process of traumatic heterotopic ossification around the temporomandibular joint (THO-TMJ).
STUDY DESIGN: One-month-old C57 BL/6 J male mice were divided into 2 groups. In group 1, condylar cartilage was partially removed in the right joint to induce THO. In group 2, a single fracture on the condylar neck was created using small scissors. The condylar head was repositioned to its original place if any displacement occurred. The phenotypes were observed using gross observation, micro-computed tomography, and histologic examination.
RESULTS: The results showed obvious hyperplasia in the right condyle in group 1, with ectopic bones and cartilage in the periarticular region. In group 2, the surface of condyle was smooth, but the size of the right condylar head became smaller.
CONCLUSIONS: Taking these findings together, we concluded that it is condylar cartilage injury, and not a single condylar neck fracture without condylar cartilage injury, that contributes to the development of THO-TMJ.

PMID: 29195812 [PubMed - as supplied by publisher]



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Variations in the origins of the thyroid arteries on CT angiography

Abstract

Objective

To investigate the anatomical variations in the origins of the thyroid arteries on CT angiography images.

Methods

The presence and the origins of the superior thyroid artery, the inferior thyroid artery, and the thyroidea ima artery were retrospectively evaluated based on carotid CT angiography examinations. The bifurcation level of the common carotid artery with respect to the cervical vertebrae and disc spaces was also determined. A total of 640 patients were included in the study.

Results

The right and left superior thyroid arteries arose from the external carotid artery in 413 (64.5%) and 254 (39.7%) patients, from the bifurcation of the common carotid artery in 131 (20.5%) and 148 (23.1%) patients, and from the common carotid artery in 90 (14.1%) and 226 (35.3%) patients, respectively. We could not observe the right and the left superior thyroid arteries in 6 (0.9%) and 12 (1.9%) of the patients, respectively. However, the right and left inferior thyroid arteries were not identified in 14 (2.2%) and 45 (7%) of the patients, respectively. The thyroidea ima artery was detected in 2.3% of the patients.

Conclusion

The visualization of thyroid arteries on CT angiography images enables the anatomy of the arterial supply system of the thyroid gland to be explored in a noninvasive manner prior to surgery.



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Squalene Extraction by Supercritical Fluids from Traditionally Puffed Amaranthus hypochondriacus Seeds

Extraction of squalene, a potent natural antioxidant, from puffed A. hypochondriacus seeds was performed by supercritical fluid extraction (SCFE); besides, to have a blank for comparison, extraction was performed also by Soxhlet method using organic solvents (hexane). Chemical proximal composition and seed morphology were determined in raw, puffed, and SCFE-extracted seeds. Extracts were obtained with a 500 mL capacity commercial supercritical extractor and performed between 10 and 30 MPa at 313, 323, and 333 K under constant CO2 flow of 0.18 kg CO2/h during 8 h. The squalene content was determined and the fatty acids present in the extracts were identified by GC-MS. The extract obtained by SCFE from puffed amaranth seeds reached 460 ± 28.1 g/kg squalene in oily extract at 313 K/20 MPa.

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Local Parametric Approach of Wireless Capsule Endoscope Localization Using Randomly Scattered Path Loss Based WCL

We propose scattered path loss based weighted centroid localization (WCL) algorithm for wireless video capsule endoscope (VCE). The main challenge in this approach is the random deviation in the measured received signal strength indicator (RSSI) caused by multipath propagation and shadowing effects of human body channel which in turn increases the localization error. To address this issue, we propose local parameter dependent path loss representation in the training phase and apply adaptive least square error (LSE) method to extract the parameters. Then, in the test phase, we estimate distance using the extracted parameters and the randomly scattered path loss. The position of capsule is estimated using non-degree based WCL followed by a calibration process. We propose suboptimal method of estimating the calibration coefficient and also compute the optimal value of coefficient analytically to set the benchmark. We develop a simulation platform using MATLAB to present the results and to verify the performance. We gradually increase the number of sensors and place them in different topologies using different dimensions. The obtained accuracy by our proposed suboptimal method of WCL is very close to the optimal benchmark for all cases. Our proposed approach also outperforms existing works in terms of localization accuracy.

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Comparative Analysis and Classification of Cassette Exons and Constitutive Exons

Alternative splicing (AS) is a major engine that drives proteome diversity in mammalian genomes and is a widespread cause of human hereditary diseases. More than 95% of genes in the human genome are alternatively spliced, and the most common type of AS is the cassette exon. Recent discoveries have demonstrated that the cassette exon plays an important role in genetic diseases. To discover the formation mechanism of cassette exon events, we statistically analyze cassette exons and find that cassette exon events are strongly influenced by individual exons that are smaller in size and that have a lower GC content, more codon terminations, and weaker splice sites. We propose an improved random-forest-based hybrid method of distinguishing cassette exons from constitutive exons. Our method achieves a high accuracy in classifying cassette exons and constitutive exons and is verified to outperform previous approaches. It is anticipated that this study will facilitate a better understanding of the underlying mechanisms in cassette exons.

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DOCK2 Deficiency in a Patient with Hyper IgM Phenotype



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Deutsche Übersetzung und Adaptation der «Uncertainty Stress Scale High Risk Pregnancy Version III» (USS-HRPV) für hospitalisierte Frauen mit Risikoschwangerschaft

A number of medical and societal factors currently contribute to an increasing number of women who are hospitalised because they are experiencing high-risk pregnancies. The unpredictability of the further course of pregnancy may lead to a feeling of uncertainty, as well as to stress, depending on coping strategies.; The aims of this study were thus to translate and adapt the USS-HRPV so that uncertainty and stress could be systematically measured on affected women in German speaking areas.; Translation of the scale was undertaken by first translating into German and then back into English. The two-phase adaptation, carried out with affected women (n = 24) and midwives (n = 10), comprised cognitive interviews and testing of content validity using the Content Validity Index (CVI). Following each data collection phase the instrument was modified with the help of midwifery experts (n = 3).; For each item the calculated CVI (I-CVI) in the first phase ranged between 0,10 and 1,0 for the sample of relevant women and midwives while the CVI of the total instrument (S-CVI/Ave) was 0,62 and 0,70 respectively. In the second phase the I-CVI values of the hospitalised women ranged between 0,17 and 1,0 while the S-CVI/Ave value was 0,73. With regard to all of the data, 44 of the original 86 items were removed and 28 altered on language grounds.; As a result of the methodical approach utilised, a firm basis for further validation of the instrument for German speaking areas has been provided.

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Erfahrungen junger Eltern mit der familienzentrierten Betreuung in der Primärversorgung in der Schweiz: Eine qualitative Evaluationsstudie

Routine postnatal care normally addresses only the mother and her child. In Switzerland, counselling for all parents and their children is provided by family nurses in a community-based health care setting. We implemented a new approach to ensure father involvement within the framework of the Calgary Family Assessment (CFAM) and the Calgary Intervention Model CFIM of Wright and Leahey (2013) in the northwest of Switzerland.; This qualitative study explored how mothers and fathers experienced the newly developed family-centred consultation.; Data collection was performed by means of participant observation and semi- structured interviews with a sample of five first-time parents with healthy neonates. Data were analysed by using content analysis according to Mayring.; Mothers and fathers experienced family-centred consultation as effective. They felt more secure and confident "to handle the new situation" and obtained trustful, concrete and professional support to take care of their baby, particularly with regard to breast feeding, crying and sleeping patterns.; Fathers felt included into postnatal care from the beginning. Family nursing offers a useful framework for family-centred postnatal health care.

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Transition – Wie Jugendliche mit Cystischer Fibrose und ihre Eltern den Übertritt von der Kinder- in die Erwachsenenmedizin erleben

Cystic Fibrosis is the most common autosomal-recessive hereditary disease among white Europeans. The average survival of CF patients has increased to above 40 years and transition from paediatric to adult care has therefore become a significant issue.; With this study, experiences of adolescents with CF and their parents with the transition from the paediatric to the adult care were explored.; At a Swiss university CF centre, six adolescents and their mothers were recruited. Twelve narrative interviews were conducted on how the phase of transition was experienced. The transcribed interviews were analysed according to the method of hermeneutic phenomenology.; Positive and negative experiences with long term routine care in the paediatric service, general themes of adolescence and the quality of the relationship with paediatric doctors influenced the families' experience during transition significantly. For mothers, insensitive information on the CF diagnosis might have influenced the transition experience. The adolescents welcomed an individualized and age appropriate care. Continuity in care, the announcement of, and involvement in the planning of the transfer were of great importance. The families particularly appreciated the timed adaptations of the transfer to individual needs.; Flexibility and a strong collaboration between paediatric and adult CF teams are most relevant in the care of families.

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Wie Angehörige die pflegerische Betreuung von dialysepflichtigen Patientinnen und Patienten mit Demenz auf der Hämodialysestation erleben – Eine qualitative Studie

Up to 70 % of dialysis patients over 55 years suffer from some degree of dementia. For a patient with dementia eventually agitated, staying at rest during the whole haemodialysis session could be difficult, which represents a real challenge for the haemodialysis team. Although relatives of patients with dementia or haemodialysis patients were described as care experts because of their support in everyday life, the perspective of relatives of haemodialysis patients with dementia has not yet been researched.; The purpose of this qualitative study was to explore the experience of nursing care of relatives of haemodialysis patients with dementia in a haemodialysis unit.; Data were collected through eight interviews with relatives. Content analysis was used to analyse data.; Relatives knew that the patients were in good hands with their nurses. Their own attendance of the dialysis sessions was of variable duration, frequency and regularity, and they were hardly involved in the care. Relatives and nurses rarely communicated regarding the patients' situation. Although relatives described symptoms of dementia, it was important for them to attest that the patients were still "mentally all right".; Relatives of patients with dementia have diverse needs concerning their attendance during the therapy and the exchange of information with clinicians. Nurses should approach relatives and assess their individual needs to achieve a better collaboration.

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Zooming in on spatial scaling: preschool children and adults use mental transformations to scale spaces

Spatial scaling is an important prerequisite for many spatial tasks and involves an understanding of how distances in different-sized spaces correspond. Previous studies have found evidence for such an understanding in preschoolers; however, the mental processes involved remain unclear. In the present study, we investigated whether children and adults use mental transformations to scale distances in space. Adults and 4- and 5-year-old children (N = 60) were asked to use maps to locate target objects in a larger referent space on a touch screen. The size of the referent space was held constant, but the sizes of the maps were varied systematically, resulting in 7 scaling factors. A linear increase in response times and errors with increasing scaling factor suggested that participants of every age group mentally transformed the size of the map to compare it to the referent, providing evidence for an analog imagery strategy in children's and adults' spatial scaling.

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The role of age and motivation for the experience of social acceptance and rejection

A study with n = 55 younger (18-33 years, M = 23.67) and n = 58 older (61-85 years, M = 71.44) adults investigated age-related differences in social approach and avoidance motivation and their consequences for the experience of social interactions. Results confirmed the hypothesis that a predominant habitual approach motivation in younger adults shifts toward a stronger avoidance motivation in older adults. Moreover, age and momentary motivation predicted the experience of an actual social interaction. Younger adults reported stronger negative emotions in a rejection situation when striving to approach acceptance rather than avoid rejection. Conversely, older adults reported fewer positive emotions in a rejection situation when they attempted to avoid rejection rather than approach acceptance. Taken together, the present study demonstrates that the same motivation has different consequences for the experience of potentially threatening social situations in younger and older adults. People seem to react emotionally when the achievement of important developmental goals (approaching others in young adulthood, avoiding negative social interactions in older adulthood) is thwarted. Moreover, results suggest that approach and avoidance motivation play an important role for socioemotional development.

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Differences in health behaviour between recipients of allogeneic haematopoietic SCT and the general population: a matched control study

Little is known of health-relevant behaviour among long-term survivors of haematological disorders treated with haematopoietic SCT. This comparative cross-sectional multicentre study aimed (1) to explore the prevalence of selected behaviours in this group and (2) to compare them with those of the general population. Self-reported data of 376 survivors (mean age: 50.4 (s.d. = 12.8); median 7 years postallogeneic SCT (interquartile range (IQR) = 8.9; range 1-33) were compared with controls derived from the Swiss Health Survey 2007 by propensity score matching. Survivors were more physically inactive (26.8% vs 12.5%; P ⩽ 0.001) and consumed fewer portions of vegetables (⩾ 3 pieces: 10% vs 21.6%; P < 0.001), fruits (⩾ 3 pieces: 6.5% vs 10.6%; P < 0.001) and fish (31.2% vs 60.9% weekly fish dish; P < 0.001). More survivors consumed dairy products daily (92.5% vs 62.9%; P < 0.001), used sun protection regularly (94.5% vs 85.3%, P < 0.001) and had received influenza vaccinations in the past year (58.4% vs 21.5%; P < 0.001); fewer survivors smoked (13.4% vs 35.4%; P < 0.001). Survivors' weekly alcohol consumption was lower (median 1.5 servings (IQR 4) vs median 4.5 (IQR 10.3); P < 0.001). Of those taking immunosuppressants, 65.7% were non-adherent. Similar to the general population, survivors experience problems executing several health-enhancing behaviours, warranting corrective interventions.

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MAOA and mechanisms of panic disorder revisited: from bench to molecular psychotherapy

Panic disorder with agoraphobia (PD/AG) is a prevalent mental disorder featuring a substantial complex genetic component. At present, only a few established risk genes exist. Among these, the gene encoding monoamine oxidase A (MAOA) is noteworthy given that genetic variation has been demonstrated to influence gene expression and monoamine levels. Long alleles of the MAOA-uVNTR promoter polymorphism are associated with PD/AG and correspond with increased enzyme activity. Here, we have thus investigated the impact of MAOA-uVNTR on therapy response, behavioral avoidance and brain activity in fear conditioning in a large controlled and randomized multicenter study on cognitive behavioral therapy (CBT) in PD/AG. The study consisted of 369 PD/AG patients, and genetic information was available for 283 patients. Carriers of the risk allele had significantly worse outcome as measured by the Hamilton Anxiety scale (46% responders vs 67%, P=0.017). This was accompanied by elevated heart rate and increased fear during an anxiety-provoking situation, that is, the behavioral avoidance task. All but one panic attack that happened during this task occurred in risk allele carriers and, furthermore, risk allele carriers did not habituate to the situation during repetitive exposure. Finally, functional neuroimaging during a classical fear conditioning paradigm evidenced that the protective allele is associated with increased activation of the anterior cingulate cortex upon presentation of the CS+ during acquisition of fear. Further differentiation between high- and low-risk subjects after treatment was observed in the inferior parietal lobes, suggesting differential brain activation patterns upon CBT. Taken together, we established that a genetic risk factor for PD/AG is associated with worse response to CBT and identify potential underlying neural mechanisms. These findings might govern how psychotherapy can include genetic information to tailor individualized treatment approaches.

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Substrate-bound outward-open state of the betaine transporter BetP provides insights into Na+ coupling

The Na(+)-coupled betaine symporter BetP shares a highly conserved fold with other sequence unrelated secondary transporters, for example, with neurotransmitter symporters. Recently, we obtained atomic structures of BetP in distinct conformational states, which elucidated parts of its alternating-access mechanism. Here, we report a structure of BetP in a new outward-open state in complex with an anomalous scattering substrate, adding a fundamental piece to an unprecedented set of structural snapshots for a secondary transporter. In combination with molecular dynamics simulations these structural data highlight important features of the sequential formation of the substrate and sodium-binding sites, in which coordinating water molecules play a crucial role. We observe a strictly interdependent binding of betaine and sodium ions during the coupling process. All three sites undergo progressive reshaping and dehydration during the alternating-access cycle, with the most optimal coordination of all substrates found in the closed state.

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The predictability of molecular evolution during functional innovation

Determining the molecular changes that give rise to functional innovations is a major unresolved problem in biology. The paucity of examples has served as a significant hindrance in furthering our understanding of this process. Here we used experimental evolution with the bacterium Escherichia coli to quantify the molecular changes underlying functional innovation in 68 independent instances ranging over 22 different metabolic functions. Using whole-genome sequencing, we show that the relative contribution of regulatory and structural mutations depends on the cellular context of the metabolic function. In addition, we find that regulatory mutations affect genes that act in pathways relevant to the novel function, whereas structural mutations affect genes that act in unrelated pathways. Finally, we use population genetic modeling to show that the relative contributions of regulatory and structural mutations during functional innovation may be affected by population size. These results provide a predictive framework for the molecular basis of evolutionary innovation, which is essential for anticipating future evolutionary trajectories in the face of rapid environmental change.

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Specific inhibition of diverse pathogens in human cells by synthetic microRNA-like oligonucleotides inferred from RNAi screens

Systematic genetic perturbation screening in human cells remains technically challenging. Typically, large libraries of chemically synthesized siRNA oligonucleotides are used, each designed to degrade a specific cellular mRNA via the RNA interference (RNAi) mechanism. Here, we report on data from three genome-wide siRNA screens, conducted to uncover host factors required for infection of human cells by two bacterial and one viral pathogen. We find that the majority of phenotypic effects of siRNAs are unrelated to the intended "on-target" mechanism, defined by full complementarity of the 21-nt siRNA sequence to a target mRNA. Instead, phenotypes are largely dictated by "off-target" effects resulting from partial complementarity of siRNAs to multiple mRNAs via the "seed" region (i.e., nucleotides 2-8), reminiscent of the way specificity is determined for endogenous microRNAs. Quantitative analysis enabled the prediction of seeds that strongly and specifically block infection, independent of the intended on-target effect. This prediction was confirmed experimentally by designing oligos that do not have any on-target sequence match at all, yet can strongly reproduce the predicted phenotypes. Our results suggest that published RNAi screens have primarily, and unintentionally, screened the sequence space of microRNA seeds instead of the intended on-target space of protein-coding genes. This helps to explain why previously published RNAi screens have exhibited relatively little overlap. Our analysis suggests a possible way of identifying "seed reagents" for controlling phenotypes of interest and establishes a general strategy for extracting valuable untapped information from past and future RNAi screens.

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Developmental origin of patchy axonal connectivity in the neocortex: a computational model

Injections of neural tracers into many mammalian neocortical areas reveal a common patchy motif of clustered axonal projections. We studied in simulation a mathematical model for neuronal development in order to investigate how this patchy connectivity could arise in layer II/III of the neocortex. In our model, individual neurons of this layer expressed the activator-inhibitor components of a Gierer-Meinhardt reaction-diffusion system. The resultant steady-state reaction-diffusion pattern across the neuronal population was approximately hexagonal. Growth cones at the tips of extending axons used the various morphogens secreted by intrapatch neurons as guidance cues to direct their growth and invoke axonal arborization, so yielding a patchy distribution of arborization across the entire layer II/III. We found that adjustment of a single parameter yields the intriguing linear relationship between average patch diameter and interpatch spacing that has been observed experimentally over many cortical areas and species. We conclude that a simple Gierer-Meinhardt system expressed by the neurons of the developing neocortex is sufficient to explain the patterns of clustered connectivity observed experimentally.

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Frontmatter



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Acknowledgment



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Evaluation of long-term stability of cannabinoids in standardized preparations of cannabis flowering tops and cannabis oil by ultra-high-performance liquid chromatography tandem mass spectrometry

Authors: Pacifici, Roberta / Marchei, Emilia / Salvatore, Francesco / Guandalini, Luca / Busardò, Francesco Paolo / Pichini, Simona


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Three-year customer satisfaction survey in laboratory medicine in a Chinese university hospital

Authors: Guo, Siqi / Duan, Yifei / Liu, Xiaojuan / Jiang, Yongmei


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Method comparison – a practical approach based on error identification

Authors: Ungerer, Jacobus Petrus Johannes / Pretorius, Carel Jacobus


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Analytical evaluation of the performances of Diazyme and BRAHMS procalcitonin applied to Roche Cobas in comparison with BRAHMS PCT-sensitive Kryptor

Authors: Ceriotti, Ferruccio / Marino, Irene / Motta, Andrea / Carobene, Anna


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PR3-anti-neutrophil cytoplasmic antibodies (ANCA) in ulcerative colitis

Authors: Mahler, Michael / Damoiseaux, Jan / Ballet, Vera / Dillaerts, Doreen / Bentow, Chelsea / Cohen Tervaert, Jan-Willem / Blockmans, Daniel / Boeckxstaens, Guy / Aguilera-Lizarraga, Javier / Csernok, Elena / Vermeire, Severine / Bossuyt, Xavier


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The diagnostic accuracy of biomarkers for diagnosis of primary biliary cholangitis (PBC) in anti-mitochondrial antibody (AMA)-negative PBC patients: a review of literature

Authors: de Liso, Federica / Matinato, Caterina / Ronchi, Mariangela / Maiavacca, Rita


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Determination of serum calcium levels by 42Ca isotope dilution inductively coupled plasma mass spectrometry

Authors: Han, Bingqing / Ge, Menglei / Zhao, Haijian / Yan, Ying / Zeng, Jie / Zhang, Tianjiao / Zhou, Weiyan / Zhang, Jiangtao / Wang, Jing / Zhang, Chuanbao


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Analytical evaluation of the new Beckman Coulter Access high sensitivity cardiac troponin I immunoassay

Authors: Lippi, Giuseppe / Ferrari, Anna / Gandini, Giorgio / Gelati, Matteo / Lo Cascio, Claudia / Salvagno, Gian Luca


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Processing-independent proANP measurement for low concentrations in plasma: reference intervals and effect of body mass index and plasma glucose

Authors: Mark, Peter D. / Hunter, Ingrid / Terzic, Dijana / Goetze, Jens P.


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Excessive hypercortisolemia due to ectopic Cushing’s syndrome requiring extending the reportable range for plasma cortisol for management

Authors: Furman, Arianne / Jialal, Ishwarlal


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Reference intervals and longitudinal changes in copeptin and MR-proADM concentrations during pregnancy

Authors: Joosen, Annemiek M.C.P. / van der Linden, Ivon J.M. / Schrauwen, Lianne / Theeuwes, Alisia / de Groot, Monique J.M. / Ermens, Antonius A.M.


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Performance of automated digital cell imaging analyzer Sysmex DI-60

Authors: Kim, Hyeong Nyeon / Hur, Mina / Kim, Hanah / Kim, Seung Wan / Moon, Hee-Won / Yun, Yeo-Min


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Definition of the upper reference limit of glycated albumin in blood donors from Italy

Authors: Bellia, Chiara / Zaninotto, Martina / Cosma, Chiara / Agnello, Luisa / Lo Sasso, Bruna / Bivona, Giulia / Plebani, Mario / Ciaccio, Marcello


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New drugs for Parkinson's disease: The regulatory and clinical development pathways in the United States



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Cerebrospinal fluid, plasma, and saliva in the BioFIND study: Relationships among biomarkers and Parkinson's disease Features

ABSTRACT

Objective: Examine relationships among neurodegenerative biomarkers and PD motor and nonmotor symptoms.

Background: CSF alpha-synuclein is decreased in PD versus healthy controls, but whether plasma and saliva alpha-synuclein differentiate these groups is controversial. Correlations of alpha-synuclein among biofluids (CSF, plasma, saliva) or biomarkers (eg, beta-amyloid, tau [total, phosphorylated]) are not fully understood. The relationships of these biomarkers with PD clinical features remain unclear.

Methods: BioFIND, a cross-sectional, observational study, examines clinical and biomarker characteristics in moderate-advanced PD and matched healthy controls. We compared alpha-synuclein concentrations across diagnosis, biofluids, and CSF biomarkers. Correlations of CSF biomarkers and MDS-UPDRS, motor phenotype, MoCA, and rapid eye movement sleep behavior disorder questionnaire scores in PD were examined.

Results: CSF alpha-synuclein was lower in PD versus controls (P = .01), controlling for age, gender, and education. Plasma and saliva alpha-synuclein did not differ between PD and controls, and alpha-synuclein did not significantly correlate among biofluids. CSF beta-amyloid1-42 was lower in PD versus controls (P < .01), and correlated weakly with MoCA recall scores (r = 0.23, P = .02). CSF alpha-synuclein was lower in the postural instability/gait difficulty phenotype than other motor phenotypes (P < .01). No CSF biomarkers predicted or correlated with total motor or rapid eye movement sleep behavior disorder scores. CSF alpha-synuclein correlated with beta-amyloid1-42, total-tau, and phosphorylated-tau (r = 0.41, 0.81, 0.43, respectively; Ps < .001).

Conclusion: Lower CSF alpha-synuclein is associated with diagnosis and motor phenotype in moderate-advanced PD. Plasma and saliva alpha-synuclein neither correlate with CSF alpha-synuclein, nor distinguish PD from controls. CSF beta-amyloid1-42 remains a potential biomarker for cognitive impairment in PD. © 2017 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.



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Predictive testing and clinical trials in Huntington's disease: An ethical analysis



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Induction of axon growth in the adult brain: A new approach to restoration in Parkinson's disease



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The premotor syndrome of cervical dystonia: Disordered processing of salient environmental stimuli



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Beyond the lysosome: Cholesterol role on endoplasmic reticulum and lipid droplets in Parkinson's disease



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Comparing Safety and Efficacy of “Third-Generation” Antiepileptic Drugs: Long-Term Extension and Post-marketing Treatment

Abstract

Four “third-generation” antiepileptic drugs (AEDs) were approved for adjunctive treatment of refractory focal onset seizures during the past 10 years. Long-term efficacy and safety of the drugs were demonstrated in large extension studies and in reports of subgroups of patients not studied in pivotal trials. Reviewing extension study and post-marketing outcome series for the four newer AEDs—lacosamide, perampanel, eslicarbazepine acetate and brivaracetam—can guide clinicians in treating and monitoring patients. AED extension studies evaluate treatment retention, drug tolerability, and drug safety during individualized treatment with flexible dosing and thus provide information not available in rigid pivotal trials. Patient retention in the studies ranged from 75 to 80% at 1 year and from 36 to 68% at 2-year treatment intervals. Safety findings were generally similar to those of pivotal trials, with no major safety risks identified and with several specific adverse drug effects, such as hyponatremia, reported. The third-generation AEDs, some through new mechanisms and others with improved tolerability compared to related AEDs, provide new options in efficacy and tolerability.



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Viruses, Vol. 9, Pages 371: Characterization of a Novel Bat Adenovirus Isolated from Straw-Colored Fruit Bat (Eidolon helvum)

Viruses, Vol. 9, Pages 371: Characterization of a Novel Bat Adenovirus Isolated from Straw-Colored Fruit Bat (Eidolon helvum)

Viruses doi: 10.3390/v9120371

Authors: Hirohito Ogawa Masahiro Kajihara Naganori Nao Asako Shigeno Daisuke Fujikura Bernard Hang’ombe Aaron Mweene Alisheke Mutemwa David Squarre Masao Yamada Hideaki Higashi Hirofumi Sawa Ayato Takada

Bats are important reservoirs for emerging zoonotic viruses. For extensive surveys of potential pathogens in straw-colored fruit bats (Eidolon helvum) in Zambia, a total of 107 spleen samples of E. helvum in 2006 were inoculated onto Vero E6 cells. The cell culture inoculated with one of the samples (ZFB06-106) exhibited remarkable cytopathic changes. Based on the ultrastructural property in negative staining and cross-reactivity in immunofluorescence assays, the virus was suspected to be an adenovirus, and tentatively named E. helvum adenovirus 06-106 (EhAdV 06-106). Analysis of the full-length genome of 30,134 bp, determined by next-generation sequencing, showed the presence of 28 open reading frames. Phylogenetic analyses confirmed that EhAdV 06-106 represented a novel bat adenovirus species in the genus Mastadenovirus. The virus shared similar characteristics of low G + C contents with recently isolated members of species Bat mastadenoviruses E, F and G, from which EhAdV 06-106 diverged by more than 15% based on the distance matrix analysis of DNA polymerase amino acid sequences. According to the taxonomic criteria, we propose the tentative new species name “Bat mastadenovirus H”. Because EhAdV 06-106 exhibited a wide in vitro cell tropism, the virus might have a potential risk as an emerging virus through cross-species transmission.



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A systematic review of symptomatic diagnosis of lung cancer

Lung cancer (LC) is often diagnosed late when curative intervention is no longer viable. However, current referral guidelines (e.g. UK National Institute for Health and Care Excellence guidelines) for suspected LC are based on a weak evidence base. Aim. The purpose of this systematic review is to identify symptoms that are independently associated with LC and to identify the key methodological issues relating to symptomatic diagnosis research in LC.; Medline, Ovid and Cumulative Index to Nursing and Allied Health Literature were searched for the period between 1946 and 2012 using the MeSH terms 'lung cancer' and 'symptom*'. Quality of each paper was assessed using Scottish Intercollegiate Guidelines Network and Consolidated Criteria for Reporting Qualitative Research Checklists and checked by a second and third reviewer.; Evidence regarding the diagnostic values of most symptoms was inconclusive; haemoptysis was the only symptom consistently indicated as a predictor of LC. Generally, evidence was weakened by methodological issues such as the lack of standardized data collection (recording bias) and the lack of comparability of findings across the different studies that extend beyond the spectrum of disease. Qualitative studies indicated that patients with LC experienced symptoms months before diagnosis but did not interpret them as serious enough to seek health care. Therefore, early LC symptoms might be under-represented in primary care clinical notes.; Current evidence is insufficient to suggest a symptom profile for LC across the disease stages, nor can it be concluded that classical LC symptoms are predictors of LC apart from, perhaps, haemoptysis. Prospective studies are now needed that systematically record symptoms and explore their predictive values for LC diagnosis.

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Functional characterization of C. elegans Y-box-binding proteins reveals tissue-specific functions and a critical role in the formation of polysomes

The cold shock domain is one of the most highly conserved motifs between bacteria and higher eukaryotes. Y-box-binding proteins represent a subfamily of cold shock domain proteins with pleiotropic functions, ranging from transcription in the nucleus to translation in the cytoplasm. These proteins have been investigated in all major model organisms except Caenorhabditis elegans. In this study, we set out to fill this gap and present a functional characterization of CEYs, the C. elegans Y-box-binding proteins. We find that, similar to other organisms, CEYs are essential for proper gametogenesis. However, we also report a novel function of these proteins in the formation of large polysomes in the soma. In the absence of the somatic CEYs, polysomes are dramatically reduced with a simultaneous increase in monosomes and disomes, which, unexpectedly, has no obvious impact on animal biology. Because transcripts that are enriched in polysomes in wild-type animals tend to be less abundant in the absence of CEYs, our findings suggest that large polysomes might depend on transcript stabilization mediated by CEY proteins.

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Characterization of vemurafenib phototoxicity in a mouse model

Vemurafenib is a first-in-class, small molecule B-Raf kinase inhibitor for the treatment of patients with unresectable or metastatic melanoma carrying the BRAFV600E mutation, commercially available since 2011. A general phototoxic potential was identified early during development; however, based on results of an animal study in hairless rats, it was concluded that there would exist no relevant risk for humans. Surprisingly, signs of clinical photosensitivity were reported in many patients during clinical development. Therefore, it became a fundamental question to understand this discrepancy. An established mouse model (oral UV-Local Lymph Node Assay, UV-LLNA) for the assessment of in vivo photosafety was used to investigate the impact of formulations, dose levels, duration of treatment, and timing of irradiation. Moreover, a basic pharmacokinetic profile was established within the same mouse strain. We were able to demonstrate dose- and time-dependent phototoxicity of vemurafenib using commercially available tablets (stabilized amorphous material). The lowest phototoxic dose was 350 mg/kg administrated for 3 consecutive days followed by exposure to UV-visible irradiation at a UVA-normalized dose of 10 J/cm². In comparison, pure vemurafenib, which easily forms crystalline variants and is known to have poor bioavailability, was tested at 350 mg/kg, and no signs of phototoxicity could be seen. The most apparent difference between the early study in hairless rats and this study in mice was the spectral range of the irradiation light source (350-400 nm vs 320-700 nm). Because vemurafenib does not absorb sufficiently light above 350 nm, this difference can easily explain the negative earlier study result in hairless rats.

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Chemical tuning enhances both potency toward nrf2 and in vitro therapeutic index of triterpenoids

The transcription factor Nrf2 protects against a number of experimental pathologies, and is a promising therapeutic target. The clinical investigation of a potent Nrf2-inducing agent, the triterpenoid (TP) bardoxolone methyl (BARD), was recently halted due to adverse cardiovascular events in chronic kidney disease patients, although the underlying mechanisms are yet to be resolved. The majority of small molecule Nrf2 inducers are electrophilic and trigger Nrf2 accumulation via the chemical modification of its redox-sensitive repressor Keap1. Therefore, it is pertinent to question whether the therapeutic targeting of Nrf2 could be hindered in many cases by the inherent reactivity of a small molecule inducer toward unintended cellular targets, a key mechanism of drug toxicity. Using H4IIE-ARE8L hepatoma cells, we have examined the relationship between (a) Nrf2 induction potency, (b) toxicity and (c) in vitro therapeutic index (ratio of b:a) for BARD and a number of other small molecule activators of Nrf2. We show that BARD exhibits the highest potency toward Nrf2 and the largest in vitro therapeutic index among compounds that have been investigated clinically (namely BARD, sulforaphane and dimethylfumarate). Through further examination of structurally related TPs, we demonstrate that an increase in potency toward Nrf2 is associated with a relatively smaller increase in toxicity, indicating that medicinal chemistry can be used to enhance the specificity of a compound as an inducer of Nrf2 signaling whilst simultaneously increasing its therapeutic index. These findings will inform the continuing design and development of drugs targeting Nrf2.

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Nurses' shift length and overtime working in 12 European countries: the association with perceived quality of care and patient safety

Despite concerns as to whether nurses can perform reliably and effectively when working longer shifts, a pattern of two 12- to 13-hour shifts per day is becoming common in many hospitals to reduce shift to shift handovers, staffing overlap, and hence costs.; To describe shift patterns of European nurses and investigate whether shift length and working beyond contracted hours (overtime) is associated with nurse-reported care quality, safety, and care left undone.; Cross-sectional survey of 31,627 registered nurses in general medical/surgical units within 488 hospitals across 12 European countries.; A total of 50% of nurses worked shifts of ≤ 8 hours, but 15% worked ≥ 12 hours. Typical shift length varied between countries and within some countries. Nurses working for ≥ 12 hours were more likely to report poor or failing patient safety [odds ratio (OR)=1.41; 95% confidence interval (CI), 1.13-1.76], poor/fair quality of care (OR=1.30; 95% CI, 1.10-1.53), and more care activities left undone (RR=1.13; 95% CI, 1.09-1.16). Working overtime was also associated with reports of poor or failing patient safety (OR=1.67; 95% CI, 1.51-1.86), poor/fair quality of care (OR=1.32; 95% CI, 1.23-1.42), and more care left undone (RR=1.29; 95% CI, 1.27-1.31).; European registered nurses working shifts of ≥ 12 hours and those working overtime report lower quality and safety and more care left undone. Policies to adopt a 12-hour nursing shift pattern should proceed with caution. Use of overtime working to mitigate staffing shortages or increase flexibility may also incur additional risk to quality.

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A tailored web-based psycho-educational intervention for cancer patients and family caregivers

BACKGROUND: Most programs addressing psychosocial concerns of cancer survivors are in-person programs that are expensive to deliver, have limited availability, and seldom deal with caregivers' concerns. OBJECTIVE: This study examined the feasibility of translating an efficacious nurse-delivered program (FOCUS Program) for patients and their caregivers to a tailored, dyadic Web-based format. Specific aims were to (1) test the preliminary effects of the Web-based intervention on patient and caregiver outcomes, (2) examine participants' program satisfaction, and (3) determine the feasibility of using a Web-based delivery format. METHODS: A phase 2 feasibility study was conducted with cancer patients (lung, breast, colorectal, prostate) and their family caregivers (N = 38 dyads). The Web-based intervention provided information and support tailored to the unique characteristics of each patient, caregiver, and their dyadic relationship. Primary outcomes were emotional distress and quality of life. Secondary outcomes were benefits of illness/caregiving, communication, support, and self-efficacy. Analyses included descriptive statistics and repeated-measures analysis of variance. RESULTS: Dyads had a significant decrease in emotional distress, increase in quality of life, and perceived more benefits of illness/caregiving. Caregivers also had significant improvement in self-efficacy. There were no changes in communication. Participants were satisfied with program usability, but recommended additional content. CONCLUSIONS: It was possible to translate a clinician-delivered program to a Web-based format that was easy to use and had positive effects on dyadic outcomes. IMPLICATIONS FOR PRACTICE: The Web-based program is a promising way to provide psychosocial care to more patients and caregivers using fewer personnel. It needs further testing in a larger randomized clinical trial.

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How hospital leaders contribute to patient safety through the development of trust

The aim of this study was to explore the associations between hospital management support for patient safety, registered nurses' trust in hospital management, and their overall perception of patient safety, considering aspects of safety communication as possible mediating variables.; Limited research exists regarding how key elements of a patient safety culture, that is, leadership, safety communication, and trust, are interrelated.; This study used cross-sectional nurse survey data from 1,633 registered nurses working in 35 acute care hospitals participating in the Swiss arm of the RN4CAST (Nurse Forecasting in Europe) study.; A path analysis revealed that the indirect associations between "management support for patient safety" and "overall perception of patient safety" were more prominent than the direct association.; Our findings confirm that safety communication plays a partially mediating role between "management support for patient safety" and nursing professionals' assessments of patient safety. This suggests that hospital leader-unit exchanges might improve patient safety.

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Daytime sleepiness in renal transplant recipients is associated with immunosuppressive non-adherence: a cross-sectional, multi-center study

The aims of this study were to determine the prevalence of immunosuppressive non-adherence (NA) in renal transplant patients and describe whether the degree of daytime sleepiness (DS) and depressive symptomatology are associated with immunosuppressive NA.; Using a cross-sectional design, 926 home-dwelling renal transplant recipients who were transplanted at one of three Swiss transplant centers provided data by self-report. The Basel Assessment of Adherence Scale for immunosuppressive was used to measure the following: taking, timing, and overall NA to immunosuppressive medication. DS was assessed with the Epworth Sleepiness Scale (ESS) (cut-off ≥6 for DS) and the Swiss Transplant Cohort Study DS item (cut-off ≥4 for DS), and depressive symptomatology was assessed with the Depression, Anxiety, and Stress Scale (cut-off>10). An ordinal logistical regression model was applied for statistical analysis.; The prevalence of the ESS-DS was 51%. NA for taking, timing, and the median overall NA level assessed by 0-100% visual analog scale (VAS) was 16%, 42%, and 0%, respectively. Based on the multivariate analysis, DS was significantly associated (p < 0.001) with taking (1.08 [1.04-1.13]), timing (1.07 [1.03-1.10]), and overall NA (1.09 [1.05-1.13]). Very similar results were found for the Swiss Transplant Cohort Study DS item.; DS is associated with immunosuppressive medication NA in renal transplant recipients. Admittedly, the association's strength is limited.

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Nurses' practice patterns in relation to adherence-enhancing interventions in stem cell transplant care: a survey from the Nurses Group of the European Group for Blood and Marrow Transplantation

Recipients of stem cell transplants (SCT) must accurately manage multiple medications as non-adherence jeopardises treatment benefits. There is an evidence base for the efficacy of adherence-enhancing interventions; however, level of clinical implementation is unknown. This study aimed to identify patterns of practice in assessing medication adherence, screening for risk factors of non-adherence, interventions used in SCT to improve adherence and how nurses perceive the effectiveness of such interventions. A convenience sample of 143 European nurses completed a 29-item questionnaire measuring the frequency and perceived effectiveness of assessment/screening methods for adherence and three types of intervention (educational/cognitive, counselling/behavioural and psychological/affective). Questioning patients about adherence was the most regularly used assessment method (51.5%). Nurses used a median of seven interventions (interquartile range: six) 'frequently', the most popular being provision of reading materials (79%). The interventions perceived as most effective were; providing individual patient/family with teaching and reading materials. This is the first study exploring patterns of practice relating to adherence in SCT. Educational interventions were the most frequently employed style of intervention, which is at odds with recent data suggesting limited efficacy with this style of intervention. Combining educational, behavioural and psychological interventions would more accurately embrace current understanding.

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Swiss Nursing Homes Human Resources Project (SHURP): protocol of an observational study

To explore the relationships among various nursing homes characteristics including work environment, careworker outcomes and resident outcomes in Swiss nursing homes.; In Switzerland, a growing number of older people live in nursing homes. Although research has addressed the issue of quality of nursing care in such facilities, few have integrated a range of interrelated factors that may influence the quality and safety of residential care. The Swiss Nursing Homes Human Resources Project will comprehensively assess key organizational factors, their interrelationships and the associations between these factors and careworker and resident outcomes.; Cross-sectional design.; Three-year multi-centre study (2011-2013) including a representative sample of approximately 160 nursing homes across the three language regions in Switzerland. Survey data will come from approximately 6000 careworkers and 160 administrators. Survey questionnaires will include variables on organizational facility characteristics and resident outcomes, careworker socio-demographic and professional characteristics, the quality of their work environments, resident safety climates and careworker outcomes. Appropriate descriptive and comparative analysis will be used and multivariate and multilevel analyses will be applied to examine the relationships among the various factors including quality of the work environment, safety climate, work stressors, rationing of care, workload, careworker and resident characteristics, as well as resident and careworker outcomes.; The study results will contribute to a comprehensive understanding of the interrelationships between key organizational factors and resident/careworker outcomes and will also support planning and conducting interventions to improve quality of care concerning organizational factors affecting careworkers in daily practice.

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Scientific misconduct: also an issue in nursing science?

Scientific misconduct (SMC) is an increasing concern in nursing science. This article discusses the prevalence of SMC, risk factors and correlates of scientific misconduct in nursing science, and highlights interventional approaches to foster good scientific conduct.; Using the "Fostering Research Integrity in Europe" report of the European Science Foundation as a framework, we reviewed the literature in research integrity promotion.; Although little empirical data exist regarding prevalence of scientific misconduct in the field of nursing science, available evidence suggests a similar prevalence as elsewhere. In studies of prospective graduate nurses, 4% to 17% admit data falsification or fabrication, while 8.8% to 26.4% report plagiarizing material. Risk factors for SMC exist at the macro, meso, and micro levels of the research system. Intervention research on preventing scientific misconduct in nursing is limited, yet findings from the wider field of medicine and allied health professions suggest that honor codes, training programs, and clearly communicated misconduct control mechanisms and misconduct consequences improve ethical behavior.; Scientific misconduct is a multilevel phenomenon. Interventions to decrease scientific misconduct must therefore target every level of the nursing research systems.; Scientific misconduct not only compromises scientific integrity by distorting empirical evidence, but it might endanger patients. Because nurses are involved in clinical research, raising their awareness of scientifically inappropriate behavior is essential.

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Stress-induced cortisol secretion impairs detection performance in x-ray baggage screening for hidden weapons by screening novices

Aviation security strongly depends on screeners' performance in the detection of threat objects in x-ray images of passenger bags. We examined for the first time the effects of stress and stress-induced cortisol increases on detection performance of hidden weapons in an x-ray baggage screening task. We randomly assigned 48 participants either to a stress or a nonstress group. The stress group was exposed to a standardized psychosocial stress test (TSST). Before and after stress/nonstress, participants had to detect threat objects in a computer-based object recognition test (X-ray ORT). We repeatedly measured salivary cortisol and X-ray ORT performance before and after stress/nonstress. Cortisol increases in reaction to psychosocial stress induction but not to nonstress independently impaired x-ray detection performance. Our results suggest that stress-induced cortisol increases at peak reactivity impair x-ray screening performance.

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The diguanylate cyclase SadC is a central player of the Gac/Rsm-mediated biofilm formation in Pseudomonas aeruginosa

Pseudomonas aeruginosa is a Gram-negative opportunistic human pathogen and a threat for immune-compromised and Cystic Fibrosis patients. It is responsible for acute and chronic infections and can switch between these lifestyles upon taking an informed decision involving complex regulatory networks. The RetS/LadS/Gac/Rsm network and the c-di-GMP signaling pathways are both central to this phenomenon redirecting the P. aeruginosa population towards a biofilm mode of growth, which is associated with chronic infections. While these two pathways were traditionally studied independently from each other, we recently showed that cellular levels of c-di-GMP are increased in the hyperbiofilm retS mutant. Here, we have formally established the link between the two networks by showing that the SadC diguanylate cyclase is central to the Gac/Rsm-associated phenotypes, notably biofilm formation. Importantly, SadC is involved in the signaling that converges onto the RsmA translational repressor either via RetS/LadS or via HptB/HsbR. Although the level of expression of the sadC gene does not seem impacted by the regulatory cascade, the production of the SadC protein is tightly repressed by RsmA. This adds to the growing complexity of the signaling network associated with c-di-GMP in P. aeruginosa. While this organism possesses more than forty c-di-GMP-related enzymes it remains unclear how signaling specificity is maintained within the c-di-GMP network. The finding that SadC but no other diguanylate cyclase is related to the formation of biofilm governed by the Gac/Rsm pathway further contributes to understand this insulation mechanism.

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Pneumococcal colonisation density: a new marker for disease severity in HIV-infected adults with pneumonia

OBJECTIVE: A high genomic load of Pneumococcus from blood or cerebrospinal fluid has been associated with increased mortality. We aimed to analyse whether nasopharyngeal colonisation density in HIV-infected patients with community-acquired pneumonia (CAP) is associated with markers of disease severity or poor outcome. METHODS: Quantitative lytA real-time PCR was performed on nasopharyngeal swabs in HIV-infected South African adults hospitalised for acute CAP at Chris Hani Baragwanath Hospital, Soweto, South Africa. Pneumonia aetiology was considered pneumococcal if any sputum culture or Gram stain, urinary pneumococcal C-polysaccharide-based antigen, blood culture or whole blood lytA real-time PCR revealed pneumococci. RESULTS: There was a moderate correlation between the mean nasopharyngeal colonisation densities and increasing CURB65 scores among all-cause patients with pneumonia (Spearman correlation coefficient r=0.15, p=0.06) or with the Pitt bacteraemia score among patients with pneumococcal bacteraemia (p=0.63). In patients with pneumococcal pneumonia, nasopharyngeal pneumococcal colonisation density was higher among non-survivors than survivors (7.7 vs 6.1 log10 copies/mL, respectively, p=0.02) and among those who had pneumococci identified from blood cultures and/or by whole blood lytA real-time PCR than those with non-bacteraemic pneumococcal pneumonia (6.6 vs 5.6 log10 copies/mL, p=0.03). Nasopharyngeal colonisation density correlated positively with the biomarkers procalcitonin (Spearman correlation coefficient r=0.37, p>0.0001), proadrenomedullin (r=0.39, p=0.008) and copeptin (r=0.30, p=0.01). CONCLUSIONS: In addition to its previously reported role as a diagnostic tool for pneumococcal pneumonia, quantitative nasopharyngeal colonisation density also correlates with mortality and prognostic biomarkers. It may also be useful as a severity marker for pneumococcal pneumonia in HIV-infected adults.

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Exposure to Leadership WalkRounds in neonatal intensive care units is associated with a better patient safety culture and less caregiver burnout

Leadership WalkRounds (WR) are widely used in healthcare organisations to improve patient safety. The relationship between WR and caregiver assessments of patient safety culture, and healthcare worker burnout is unknown.; This cross-sectional survey study evaluated the association between receiving feedback about actions taken as a result of WR and healthcare worker assessments of patient safety culture and burnout across 44 neonatal intensive care units (NICUs) actively participating in a structured delivery room management quality improvement initiative.; Of 3294 administered surveys, 2073 were returned for an overall response rate of 62.9%. More WR feedback was associated with better safety culture results and lower burnout rates in the NICUs. Participation in WR and receiving feedback about WR were less common in NICUs than in a benchmarking comparison of adult clinical areas.; WR are linked to patient safety and burnout. In NICUs, where they occurred more often, the workplace appears to be a better place to deliver and to receive care.

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Case of papuloerythroderma of Ofuji-like eruption during the course of bullous pemphigoid



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Repeated shock stress facilitates basolateral amygdala synaptic plasticity through decreased cAMP-specific phosphodiesterase type IV (PDE4) expression

Abstract

Previous studies have shown that exposure to stressful events can enhance fear memory and anxiety-like behavior as well as increase synaptic plasticity in the rat basolateral amygdala (BLA). We have evidence that repeated unpredictable shock stress (USS) elicits a long-lasting increase in anxiety-like behavior in rats, but the cellular mechanisms mediating this response remain unclear. Evidence from recent morphological studies suggests that alterations in the dendritic arbor or spine density of BLA principal neurons may underlie stress-induced anxiety behavior. Recently, we have shown that the induction of long-term potentiation (LTP) in BLA principal neurons is dependent on activation of postsynaptic D1 dopamine receptors and the subsequent activation of the cyclic adenosine 5′-monophosphate (cAMP)—protein kinase A (PKA) signaling cascade. Here, we have used in vitro whole-cell patch-clamp recording from BLA principal neurons to investigate the long-term consequences of USS on their morphological properties and synaptic plasticity. We provided evidence that the enhanced anxiety-like behavior in response to USS was not associated with any significant change in the morphological properties of BLA principal neurons, but was associated with a changed frequency dependence of synaptic plasticity, lowered LTP induction threshold, and reduced expression of phosphodiesterase type 4 enzymes (PDE4s). Furthermore, pharmacological inhibition of PDE4 activity with rolipram mimics the effects of chronic stress on LTP induction threshold and baseline startle. Our results provide the first evidence that stress both enhances anxiety-like behavior and facilitates synaptic plasticity in the amygdala through a common mechanism of PDE4-mediated disinhibition of cAMP-PKA signaling.



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In vivo evaluation of a novel nanocomposite porous 3D scaffold in a rabbit model: histological analysis

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Polyethyleneimine-capped silver nanoclusters for microRNA oligonucleotide delivery and bacterial inhibition

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Neuroprotective potential of crocin against malathion-induced motor deficit and neurochemical alterations in rats

Abstract

In several epidemiological studies, an association between pesticide exposure and the incidence of Parkinson’s disease (PD) has been reported. Increasing evidence showed that oxidative stress plays an important role in the pathogenesis of PD. The present study investigated the preventive effect of crocin, saffron active components, on malathion (an organophosphate pesticide (OP))-induced Parkinson-like behaviors in rat. Rats were divided into eight groups: control (normal saline), malathion (100 mg/kg/day, i.p), crocin (10, 20, or 40 mg/kg/day, i.p) plus malathion, levodopa (10 mg/kg/day, i.p) plus malathion, crocin (40 mg/kg/day, i.p), and PEG (vehicle of levodopa) groups. Treatments were continued for 28 days. The neurobehavioral tests which include open field, rotarod and catalepsy were performed on day 28. The activity of acetylcholinesterase (AChE) in serum, the levels of malondialdehyde (MDA), reduced glutathione (GSH), TNF-α, and IL-6 in striatum at the end of treatments were evaluated. Results showed that malathion induced neurobehavioral impairments together with elevation of MDA, TNF-α and IL-6 levels, reduction of GSH, and AChE activity. Crocin (10, 20, and 40 mg/kg) improved neurobehavioral impairments induced by malathion but not AChE activity. Crocin (10, 20, and 40 mg/kg) or levodopa plus malathion decreased MDA and increased GSH. Also crocin (10 mg/kg) decreased TNF-α and IL-6 levels in striatum. In summary, subchronic malathion exposure induced Parkinson-like behavior in rat. Crocin exhibited protective effects against malathion-induced Parkinson-like behavior through reducing lipid peroxidation, improvement of motor deficit and anti-inflammatory effects.



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A Uniform Method of Mechanical Disturbance Torque Measurement and Reduction for the Seeker Gimbal in the Assembly Process

In the manufacturing process of seekers, the reduction of disturbance torques (DTs) is a critical but time-consuming work. The innovation of the paper is to present a uniform method to measure and reduce mechanical DTs during gimbal’s assembly process. Firstly, the relationships between assembly parameters and DTs are established and analyzed by theoretical model. And then, a measuring system is established to measure the driven torque of the gimbal’s torque motor. With the goal of stabilizing and minimizing the driven torque, all assembly parameters relating to DTs could be adjusted. Through the proof of a lot of experiments, this proposed method could reduce the bias and fluctuation of these mechanical DTs. This method could also be used for the mechanical DTs reduction of most similar productions and improve the quality and efficiency during their system assembly process.

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Key Parameters on the Microwave Assisted Synthesis of Magnetic Nanoparticles for MRI Contrast Agents

Uniform iron oxide magnetic nanoparticles have been synthesized using a microwave assisted synthesis method in organic media and their colloidal, magnetic, and relaxometric properties have been analyzed after its transference to water and compared with those nanoparticles prepared by thermal decomposition in organic media. The novelty of this synthesis relies on the use of a solid iron oleate as precursor, which assures the reproducibility and scalability of the synthesis, and the microwave heating that resulted in being faster and more efficient than traditional heating methods, and therefore it has a great potential for nanoparticle industrial production. The effect of different experimental conditions such as the solvent, precursor, and surfactant concentration and reaction time as well as the transference to water is analyzed and optimized to obtain magnetic iron oxide nanoparticles with sizes between 8 and 15 nm and finally colloids suitable for their use as contrast agents on Magnetic Resonance Imaging (MRI). The relaxivity values normalized to the square of the saturation magnetization were shown to be constant and independent of the particle size, which means that the saturation magnetization is the main parameter controlling the efficiency of these magnetic nanoparticles as MRI -contrast agents.

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Discriminant Model of Coal Mining Microseismic and Blasting Signals Based on Waveform Characteristics

Generally, there are two important types of microseismic (MS) signals caused by mining and blasting activities at coal mines. The waveform characteristics of MS signals using FFT, STA/LTA method, and envelope analysis were studied to distinguish these two types of MS signals. The main results are as follows: the dominant frequency and duration of two types of signals are significantly different. The following peak envelope curves of two types of MS signals fit a power function. The power exponent was obtained to describe the attenuated speed of the MS signals. The attenuation of the coal mining MS signals is slower and more fluctuant than that of the blasting signal. Waveform characteristics consisting of the dominant frequency, duration, and attenuation coefficient were extracted as the discriminating parameters. The discriminating performance of these parameters was compared and discussed. Based on the waveform characteristics, a discriminant model for coal mining MS and blasting signals was established by using Fisher linear discriminant method and its performance was checked. The results show that the accuracy of the discriminant model is more than 85%, which can meet the requirements of MS monitoring at coal mines.

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Long-Term Follow-Up in Children with Anisocoria: Cocaine Test Results and Patient Outcome

Background. Evaluation of anisocoria including pharmacological testing for Horner’s syndrome in the pediatric population is challenging in view of potential serious underlying disease. We describe cocaine test results, outcome of systemic investigation, and long-term follow-up in children with anisocoria. Methods. Retrospective review of medical records and phone interview of consecutive pediatric patients (

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Exact Solutions for the Wick-Type Stochastic Schamel-Korteweg-de Vries Equation

We consider the Wick-type stochastic Schamel-Korteweg-de Vries equation with variable coefficients in this paper. With the aid of symbolic computation and Hermite transformation, by employing the -expansion method, we derive the new exact travelling wave solutions, which include hyperbolic and trigonometric solutions for the considered equations.

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Prevalence, patterns and predictors of nursing care left undone in European hospitals: results from the multicountry cross-sectional RN4CAST study

Little is known of the extent to which nursing-care tasks are left undone as an international phenomenon.; The aim of this study is to describe the prevalence and patterns of nursing care left undone across European hospitals and explore its associations with nurse-related organisational factors.; Data were collected from 33 659 nurses in 488 hospitals across 12 European countries for a large multicountry cross-sectional study.; Across European hospitals, the most frequent nursing care activities left undone included 'Comfort/talk with patients' (53%), 'Developing or updating nursing care plans/care pathways' (42%) and 'Educating patients and families' (41%). In hospitals with more favourable work environments (B=-2.19; p<0.0001), lower patient to nurse ratios (B=0.09; p<0.0001), and lower proportions of nurses carrying out non-nursing tasks frequently (B=2.18; p<0.0001), fewer nurses reported leaving nursing care undone.; Nursing care left undone was prevalent across all European countries and was associated with nurse-related organisational factors. We discovered similar patterns of nursing care left undone across a cross-section of European hospitals, suggesting that nurses develop informal task hierarchies to facilitate important patient-care decisions. Further research on the impact of nursing care left undone for patient outcomes and nurse well-being is required.

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Study suggests measurable impact of colorectal cancer screening program

A new study suggests that an American Cancer Society (ACS) program has been effective in promoting improvements in colorectal cancer screening rates in federally qualified health centers (FQHCs). The study appears early online in the American Journal of...

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Fungal diversity notes 603–708: taxonomic and phylogenetic notes on genera and species

Abstract

This is the sixth in a series of papers where we bring collaborating mycologists together to produce a set of notes of several taxa of fungi. In this study we introduce a new family Fuscostagonosporaceae in Dothideomycetes. We also introduce the new ascomycete genera Acericola, Castellaniomyces, Dictyosporina and Longitudinalis and new species Acericola italica, Alternariaster trigonosporus, Amarenomyces dactylidis, Angustimassarina coryli, Astrocystis bambusicola, Castellaniomyces rosae, Chaetothyrina artocarpi, Chlamydotubeufia krabiensis, Colletotrichum lauri, Collodiscula chiangraiensis, Curvularia palmicola, Cytospora mali-sylvestris, Dictyocheirospora cheirospora, Dictyosporina ferruginea, Dothiora coronillae, Dothiora spartii, Dyfrolomyces phetchaburiensis, Epicoccum cedri, Epicoccum pruni, Fasciatispora calami, Fuscostagonospora cytisi, Grandibotrys hyalinus, Hermatomyces nabanheensis, Hongkongmyces thailandica, Hysterium rhizophorae, Jahnula guttulaspora, Kirschsteiniothelia rostrata, Koorchalomella salmonispora, Longitudinalis nabanheensis, Lophium zalerioides, Magnibotryascoma mali, Meliola clerodendri-infortunati, Microthyrium chinense, Neodidymelliopsis moricola, Neophaeocryptopus spartii, Nigrograna thymi, Ophiocordyceps cossidarum, Ophiocordyceps issidarum, Ophiosimulans plantaginis, Otidea pruinosa, Otidea stipitata, Paucispora kunmingense, Phaeoisaria microspora, Pleurothecium floriforme, Poaceascoma halophila, Periconia aquatica, Periconia submersa, Phaeosphaeria acaciae, Phaeopoacea muriformis, Pseudopithomyces kunmingnensis, Ramgea ozimecii, Sardiniella celtidis, Seimatosporium italicum, Setoseptoria scirpi, Torula gaodangensis and Vamsapriya breviconidiophora. We also provide an amended account of Rhytidhysteron to include apothecial ascomata and a J+ hymenium. The type species of Ascotrichella hawksworthii (Xylariales genera incertae sedis), Biciliopsis leptogiicola (Sordariomycetes genera incertae sedis), Brooksia tropicalis (Micropeltidaceae), Bryochiton monascus (Teratosphaeriaceae), Bryomyces scapaniae (Pseudoperisporiaceae), Buelliella minimula (Dothideomycetes genera incertae sedis), Carinispora nypae (Pseudoastrosphaeriellaceae), Cocciscia hammeri (Verrucariaceae), Endoxylina astroidea (Diatrypaceae), Exserohilum turcicum (Pleosporaceae), Immotthia hypoxylon (Roussoellaceae), Licopolia franciscana (Vizellaceae), Murispora rubicunda (Amniculicolaceae) and Doratospora guianensis (synonymized under Rizalia guianensis, Trichosphaeriaceae) were re-examined and descriptions, illustrations and discussion on their familial placement are given based on phylogeny and morphological data. New host records or new country reports are provided for Chlamydotubeufia huaikangplaensis, Colletotrichum fioriniae, Diaporthe subclavata, Diatrypella vulgaris, Immersidiscosia eucalypti, Leptoxyphium glochidion, Stemphylium vesicarium, Tetraploa yakushimensis and Xepicula leucotricha. Diaporthe baccae is synonymized under Diaporthe rhusicola. A reference specimen is provided for Periconia minutissima. Updated phylogenetic trees are provided for most families and genera. We introduce the new basidiomycete species Agaricus purpurlesquameus, Agaricus rufusfibrillosus, Lactifluus holophyllus, Lactifluus luteolamellatus, Lactifluus pseudohygrophoroides, Russula benwooii, Russula hypofragilis, Russula obscurozelleri, Russula parapallens, Russula phoenicea, Russula pseudopelargonia, Russula pseudotsugarum, Russula rhodocephala, Russula salishensis, Steccherinum amapaense, Tephrocybella constrictospora, Tyromyces amazonicus and Tyromyces angulatus and provide updated trees to the genera. We also introduce Mortierella formicae in Mortierellales, Mucoromycota and provide an updated phylogenetic tree.



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3D printing assists implantation of hearing device

2017_10_16_18_44_6737_Italian_flag_400.jThe surgical insertion of bone conduction implants is a complex procedure demanding...


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ECR commits to stay in Vienna through 2025

The European Congress of Radiology (ECR) will be staying put in Vienna through...


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Effect of chronic renal failure on the hepatic, intestinal, and renal expression of bile acid transporters

Although the kidney is believed to play a minor role in bile acid (BA) excretion, chronic renal failure (CRF) has been reported to be associated with increased serum bile acid levels and alterations in BA homeostasis. The mechanisms for elevated BA levels are poorly understood in both clinical and experimental studies. This study was designed to examine the effects of naturally progressing CRF of longer duration on the hepatic and renal mRNA and protein levels of the BA-synthesizing enzyme Cyp7a1 and the BA transporters Ntcp, Bsep, Mrp3, Ost-α, and Ost-β. Sprague-Dawley rats were randomized to the CRF group (&frac56; nephrectomy) or to the sham-operated control group and were analyzed 8 wk after surgery. Results obtained in the CRF rats were compared with those obtained in rats that had undergone uninephrectomy (UNX). The CRF group exhibited significantly increased plasma cholesterol and BA concentrations. Hepatic Cyp7a1 mRNA and protein levels were almost identical in the two groups. Hepatic Mrp3, Ost-α, and Ost-β expression was increased, suggesting increased basolateral efflux of bile acids into the blood. However, no such changes in BA transporter expression were observed in the remnant kidney. In UNX rats, similar changes in plasma BA levels and in the expression of BA transporters were found. We hypothesize that the increase in plasma BA is an early event in the progression of CRF and is caused by increased efflux across the basolateral hepatocyte membrane.

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The prognostic value of midregional proatrial natriuretic peptide in patients with hemorrhagic stroke

BACKGROUND: Atrial natriuretic peptide (ANP) is a well-known prognostic marker of outcome and mortality in patients with cardiovascular disease. Midregional proatrial natriuretic peptide (MR-proANP) is a stable fragment of the ANP precursor hormone. As a prognostic marker after ischemic stroke, it reliably predicts poststroke mortality and functional outcome. This study aimed to analyze the prognostic value of MR-proANP in patients with hemorrhagic stroke, i.e. subarachnoid (SAH) and intracerebral hemorrhage (ICH). METHODS: MR-proANP was analyzed in patients with spontaneous SAH or spontaneous ICH. All patients were prospectively randomized into two treatment arms: (1) a prophylactic normothermia group with a target core temperature 36.5 degrees C using endovascular cooling, and (2) a control group with conventional stepwise predefined fever management using antipyretic medication and surface cooling. Blood samples were obtained on admission and on days 4 and 7. Measurement of MR-proANP was performed in serum using sandwich immunoassay. The primary endpoint was functional outcome [assessed by the Glasgow Outcome Score (GOS)] and the secondary endpoints were mortality within 180 days after hemorrhagic stroke and influence of temperature on MR-proANP. A favorable outcome was defined as GOS 4-5, and the patients were considered to have a poor outcome with a 180-day GOS score between 1 and 3. RESULTS: Analysis of MR-proANP was performed in 24 patients with spontaneous SAH and 22 patients with spontaneous ICH. MR-proANP was elevated on days 4 and 7 as compared to baseline levels (p 120 pmol/l) were associated with increased mortality and poor outcome (after 180 days; p > 0.05, respectively). There was no significant difference regarding MR-proANP serum concentrations between the endovascular and the control groups. CONCLUSIONS: Increased levels of MR-proANP are independently associated with poor functional outcome and increased mortality after 180 days in patients with hemorrhagic stroke. Endovascular temperature control had no significant influence on MR-proANP levels.

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Neural correlates of procedural variants in cognitive-behavioral therapy: a randomized, controlled multicenter FMRI study

Cognitive behavioral therapy (CBT) is an effective treatment for panic disorder with agoraphobia (PD/AG). It is unknown, how variants of CBT differentially modulate brain networks involved in PD/AG. This study was aimed to evaluate the effects of therapist-guided (T+) versus self-guided (T-) exposure on the neural correlates of fear conditioning in PD/AG.; In a randomized, controlled multicenter clinical trial in medication-free patients with PD/AG who were treated with 12 sessions of manualized CBT, functional magnetic resonance imaging (fMRI) was used during fear conditioning before (t1) and after CBT (t2). Quality-controlled fMRI data from 42 patients and 42 healthy subjects (HS) were obtained. Patients were randomized to two variants of CBT (T+, n = 22, and T-, n = 20).; The interaction of diagnosis (PD/AG, HS), treatment group (T+, T-), time point (t1, t2) and stimulus type (conditioned stimulus: yes, no) revealed activation in the left hippocampus and the occipitotemporal cortex. The T+ group demonstrated increased activation of the hippocampus at t2 (t2 > t1), which was positively correlated with treatment outcome, and a decreased connectivity between the left inferior frontal gyrus and the left hippocampus across time (t1 > t2).; After T+ exposure, contingency-encoding processes related to the posterior hippocampus are augmented and more decoupled from processes of the left inferior frontal gyrus, previously shown to be dysfunctionally activated in PD/AG. Linking single procedural variants to neural substrates offers the potential to inform about the optimization of targeted psychotherapeutic interventions.

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Copeptin for the prediction of recurrent cerebrovascular events after transient ischemic attack: results from the CoRisk study

BACKGROUND AND PURPOSE: Copeptin has been associated with recurrent cerebrovascular events after transient ischemic attack (TIA). In an independent cohort, we evaluated copeptin for the prediction of recurrent cerebrovascular events within 3 months after TIA and assessed the incremental value of copeptin compared with the ABCD2 (age, blood, clinical features of TIA, duration of symptoms, presence of diabetes mellitus) and ABCD3-I (ABCD2, dual TIA [the presence of </=2 TIA symptoms within 7 days], imaging [the presence of abnormal findings on neuroimaging]) scores. METHODS: This prospective, multicenter cohort study was conducted at 3 tertiary Stroke Centers in Switzerland and Germany. RESULTS: From March 2009 through April 2011, we included 302 patients with TIA admitted within 24 hours from symptom onset. Of 28 patients with a recurrent cerebrovascular event within 3 months (stroke or TIA), 11 patients had a stroke. Although the association of copeptin with recurrent cerebrovascular events was not significant, the association with stroke alone as end point was significant. After adjusting for the ABCD2 score, a 10-fold increase in copeptin levels was associated with an odds ratio for stroke of 3.39 (95% confidence interval, 1.28-8.96; P=0.01). After addition of copeptin to the ABCD2 score, the area under the curve of the ABCD2 score improved from 0.60 (95% confidence interval, 0.46-0.74) to 0.74 (95% confidence interval, 0.60-0.88, P=0.02). In patients with MRI (n=223), the area under the curve of the ABCD3-I score increased in similar magnitude, although not significantly. Based on copeptin, 31.2% of patients were correctly reclassified across the risk categories of the ABCD2 score (net reclassification improvement; P=0.17). CONCLUSIONS: Copeptin improved the prognostic value of the ABCD2 score for the prediction of stroke but not TIA, and it may help clinicians in refining risk stratification for patients with TIA. CLINICAL TRIAL REGISTRATION URL: http://ift.tt/PmpYKN. Unique identifier: NCT00878813.

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Education for nurses working in cardiovascular care: a European survey.

Nurses represent the largest sector of the workforce caring for people with cardiovascular disease in Europe. Little is known about the post-registration education provided to nurses working within this specialty. The aim of this descriptive cross sectional survey was to describe the structure, content, teaching, learning, assessment and evaluation methods used in post-registration cardiovascular nurse education programmes in Europe.; A 24-item researcher generated electronic questionnaire was sent to nurse representatives from 23 European countries. Items included questions about cardiovascular registered nurse education programmes.; Forty-nine respondents from 17 European countries completed questionnaires. Respondents were typically female (74%) and educated at Masters (50%) or doctoral (39%) level. Fifty-one percent of the cardiovascular nursing education programmes were offered by universities either at bachelor or masters level. The most frequently reported programme content included cardiac arrhythmias (93%), heart failure (85%) and ischaemic heart disease (83%). The most common teaching mode was face-to-face lectures (85%) and/or seminars (77%). A variety of assessment methods were used with an exam or knowledge test being the most frequent. Programme evaluation was typically conducted through student feedback (95%).; There is variability in the content, teaching, learning and evaluation methods in post-registration cardiovascular nurse education programmes in Europe. Cardiovascular nurse education would be strengthened with a stronger focus upon content that reflects current health challenges faced in Europe. A broader view of cardiovascular disease to include stroke and peripheral vascular disease is recommended with greater emphasis on prevention, rehabilitation and the impact of health inequalities.

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"Fighting an uphill battle": experience with the HCV triple therapy: a qualitative thematic analysis

Hepatitis C virus (HCV) infections are a severe burden on public health worldwide, causing mortality rates triple that of the general population. Since 2011, for both therapy-naive and therapy-experienced genotype 1 patients, the first generation of direct acting antivirals (DAAs), i.e., the protease-inhibitors (PI) telaprevir and boceprevir have been added to existing dual therapies. The therapeutic effect of the resulting triple therapy is striking; however, treatment regimens are complex and commonly cause side effects. Little is known of how patients implement therapy in their daily lives, or of how they deal with these effects.This study aims to describe HCV patients' experiences with protease-inhibitor-based triple therapy and their support needs.; A qualitative design was used. Patients from three outpatient clinics, with ongoing, completed or discontinued PI treatment experience were recruited using a maximum variation sampling approach. Open-ended interviews were conducted and analyzed using thematic analysis according to Braun & Clarke (Qual Res Psychol 3:77-101, 2006).; Thirteen patients participated in the interviews. All described themselves as highly motivated to undergo treatment, since they saw the new therapy as a "real chance" for a cure. However, all later described the therapy period as a struggle. The constitutive theme-"Fighting an uphill battle"- describes the common existential experience of and negative consequences of coping with side effects. The processes that fostered this common experience followed three sub-themes: "encountering surprises", "dealing with disruption" and "reaching the limits of systems".; HCV patients undergoing outpatient protease-inhibitor-based triple therapy need systematic support in symptom management. This will require specially trained professionals to advise and support them and their families, and to provide rapid responses to their needs throughout this complex course of therapy. As the generation of DAAs for all genotypes, are expected to have less severe side effects, and many HCV patients require treatment, this knowledge can improve treatment support tremendously, especially for patients who are quite difficult to treat. Furthermore, these findings are helpful to illustrate development in HCV treatment.

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Acute cocaine-related health problems in patients presenting to an urban emergency department in Switzerland: a case series

Emergency departments may be a useful information source to describe the demographics and clinical characteristics of patients with acute cocaine-related medical problems. We therefore conducted a retrospective analysis of 165 acute, laboratory-confirmed cocaine intoxications admitted to an urban emergency department in Switzerland between January 2007 and March 2011.; A total of 165 patients with a mean age of 32 years were included. Most patients were male (73%) and unemployed (65%). Only a minority (16%) had abused cocaine alone while 84% of the patients had used at least one additional substance, most commonly ethanol (41%), opioids (38%), or cannabis (36%) as confirmed by their detection in blood samples. The most frequently reported symptoms were chest pain (21%), palpitations (19%), anxiety (36%) and restlessness (36%). Psychiatric symptoms were present in 64%. Hypertension and tachycardia were observed in 53% and 44% of the patients, respectively. Severe poisonings only occurred in patients with multiple substance intoxication (15%). Severe intoxications were non-significantly more frequent with injected drug use compared to nasal, oral, or inhalational drug use. Severe complications included acute myocardial infarction (2 cases), stroke (one case), and seizures (3 cases). Most patients (75%) were discharged home within 24 h after admission. A psychiatric evaluation in the ED was performed in 24% of the patients and 19% were referred to a psychiatric clinic.; Patients with acute cocaine intoxication often used cocaine together with ethanol and opioids and presented with sympathomimetic toxicity and/or psychiatric disorders. Severe acute toxicity was more frequent with multiple substance use. Toxicity was typically short-lasting but psychiatric evaluation and referral was often needed.

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Screening, detection and management of delirium in the emergency department - a pilot study on the feasibility of a new algorithm for use in older emergency department patients: the modified Confusion Assessment Method for the Emergency Department (mCAM-ED)

Delirium in emergency department (ED) patients occurs frequently and often remains unrecognized. Most instruments for delirium detection are complex and therefore unfeasible for the ED. The aims of this pilot study were first, to confirm our hypothesis that there is an unmet need for formal delirium assessment by comparing informal delirium ratings of ED staff with formal delirium assessments performed by trained research assistants. Second, to test the feasibility of an algorithm for delirium screening, detection and management, which includes the newly developed modified Confusion Assessment Method for the Emergency Department (mCAM-ED) at the ED bedside. Third, to test interrater reliability of the mCAM-ED.; This was a pilot study with a pre-post-test design with two data collection periods before and after the implementation of the algorithm. Consecutive ED patients aged 65 years and older were screened and assessed in the ED of a tertiary care center by trained research assistants. The delirium detection rate of informal ratings by nurses and physicians was compared with the standardized mCAM-ED assessment performed by the research assistants. To show the feasibility at the ED bedside, defined as adherence of ED staff to the algorithm, only post-test data were used. Additionally, the ED nurses' assessments were analyzed qualitatively. To investigate the agreement between research assistants and the reference standard, the two data sets were combined.; In total, 207 patients were included in this study. We found that informal delirium assessment was inappropriate, even after a teaching intervention: Sensitivity of nurses to detect delirium without formal assessment was 0.27 pretest and 0.40 post-test, whilst sensitivity of physicians' informal rating was 0.45 pre-test and 0.6 post-test. ED staff demonstrated high adherence to the algorithm (76.5%). Research assistants assessing delirium with the mCAM-ED demonstrated a high agreement compared to the reference standard (kappa = 0.729).; Informal assessment of delirium is inadequate. The mCAM-ED proved to be useful at the ED bedside. Performance criteria need to be tested in further studies. The mCAM-ED may contribute to early identification of delirious ED patients.

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The DSM-5 criteria, level of arousal and delirium diagnosis: inclusiveness is safer

Delirium is a common and serious problem among acutely unwell persons. Although linked to higher rates of mortality, institutionalisation and dementia, it remains underdiagnosed. Careful consideration of its phenomenology is warranted to improve detection and therefore mitigate some of its clinical impact. The publication of the fifth edition of the Diagnostic and Statistical Manual of the American Psychiatric Association (DSM-5) provides an opportunity to examine the constructs underlying delirium as a clinical entity.; Altered consciousness has been regarded as a core feature of delirium; the fact that consciousness itself should be physiologically disrupted due to acute illness attests to its clinical urgency. DSM-5 now operationalises 'consciousness' as 'changes in attention'. It should be recognised that attention relates to content of consciousness, but arousal corresponds to level of consciousness. Reduced arousal is also associated with adverse outcomes. Attention and arousal are hierarchically related; level of arousal must be sufficient before attention can be reasonably tested.; Our conceptualisation of delirium must extend beyond what can be assessed through cognitive testing (attention) and accept that altered arousal is fundamental. Understanding the DSM-5 criteria explicitly in this way offers the most inclusive and clinically safe interpretation.

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