bluuebunny/crossref_metadata_2025_split huggingface dataset:
Validation of soluble amyloid‐β precursor protein assays as diagnostic CSF biomarkers for neurodegenerative diseases
Authors: van Waalwijk van Doorn Linda J.C. , Koel‐Simmelink Marleen J. , Haußmann Ute , Klafki Hans , Struyfs Hanne , Linning Philipp , Knölker Hans‐Joachim , Twaalfhoven Harry , Kuiperij H. Bea , Engelborghs Sebastiaan , Scheltens Philip , Verbeek Marcel M. , Vanmechelen Eugeen , Wiltfang Jens , Teunissen Charlotte E. 
Published: January 2016

AbstractAnalytical validation of a biomarker assay is essential before implementation in clinical practice can occur. In this study, we analytically validated the performance of assays detecting soluble amyloid‐β precursor protein (sAPP) α and β in CSF in two laboratories according to previously standard operating procedures serving this goal. sAPPα and sAPPβ ELISA assays from two vendors (IBL‐international, Meso Scale Diagnostics) were validated. The performance parameters included precision, sensitivity, dilutional linearity, recovery, and parallelism. Inter‐laboratory variation, biomarker comparison (sAPPα vs. sAPPβ) and clinical performance was determined in three laboratories using 60 samples of patients with subjective memory complaints, Alzheimer's disease, or frontotemporal dementia. All performance parameters of the assays were similar between labs and within predefined acceptance criteria. The only exceptions were minor out‐of‐range results for recovery at low concentrations and, despite being within predefined acceptance criteria, non‐comparability of the results for evaluation of the dilutional linearity and hook‐effect. Based on the inter‐laboratory correlation between Lab #1 and Lab #2, the IBL‐international assays were more robust (sAPPα: r2 = 0.92, sAPPβ: r2 = 0.94) than the Meso Scale Diagnostics (MSD) assay (sAPPα: r2 = 0.70, sAPPβ: r2 = 0.80). Specificity of assays was confirmed using assay‐specific peptide competitors. Clinical validation showed consistent results across the clinical groups in the different laboratories for all assays. The validated sAPP assays appear to be of sufficient technical quality and perform well. Moreover, the study shows that the newly developed standard operating procedures provide highly useful tools for the validation of new biomarker assays. A recommendation was made for renewed instructions to evaluate the dilutional linearity and hook‐effect.
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We analytically validated the performance of assays detecting soluble amyloid‐β precursor protein (sAPP) α and β in CSF according to SOPs in agreement with ISO15189 guidelines. The validated sAPP assays appear to be of sufficient technical quality and perform well. Moreover, this study proofs that the newly developed SOPs, with a minor modification, provide highly useful tools for the validation of new biomarker assays.
Acute selective serotonin reuptake inhibitors regulate the dorsal raphe nucleus causing amplification of terminal serotonin release
Authors: Dankoski Elyse C. , Carroll Susan , Wightman Robert Mark 
Published: January 2016

AbstractSelective serotonin reuptake inhibitors (SSRIs) were designed to treat depression by increasing serotonin levels throughout the brain via inhibition of clearance from the extracellular space. Although increases in serotonin levels are observed after acute SSRI exposure, 3–6 weeks of continuous use is required for relief from the symptoms of depression. Thus, it is now believed that plasticity in multiple brain systems that are downstream of serotonergic inputs contributes to the therapeutic efficacy of SSRIs. The onset of antidepressant effects also coincides with desensitization of somatodendritic serotonin autoreceptors in the dorsal raphe nucleus (DRN), suggesting that disrupting inhibitory feedback within the serotonin system may contribute to the therapeutic effects of SSRIs. Previously, we showed that chronic SSRI treatment caused a frequency‐dependent facilitation of serotonin signaling that persisted in the absence of uptake inhibition. In this work, we use in vivo fast‐scan cyclic voltammetry in mice to investigate a similar facilitation after a single treatment of the SSRI citalopram hydrobromide. Acute citalopram hydrobromide treatment resulted in frequency‐dependent increases of evoked serotonin release in the substantia nigra pars reticulata. These increases were independent of changes in uptake velocity, but required SERT expression. Using microinjections, we show that the frequency‐dependent enhancement in release is because of SERT inhibition in the DRN, demonstrating that SSRIs can enhance serotonin release by inhibiting uptake in a location distal to the terminal release site. The novel finding that SERT inhibition can disrupt modulatory mechanisms at the level of the DRN to facilitate serotonin release will help future studies investigate serotonin's role in depression and motivated behavior.
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In this work, stimulations of the dorsal raphe nucleus (DRN) evoke serotonin release that is recorded in the substantia nigra pars reticulata (SNpr) using in vivo fast‐scan cyclic voltammetry. Systemic administration of a selective serotonin reuptake inhibitor (SSRI) causes both an increase in t1/2 and an increase in [5‐HT]max in the SNpr. Local application of SSRI to the DRN recapitulates the increase in [5‐HT]max observed in the SNpr without affecting uptake. Thus, SSRIs increase serotonin signaling via two distinct SERT‐mediated mechanisms.
Therapeutic approaches in Parkinson's disease and related disorders
Authors: Valera Elvira , Masliah Eliezer 
Published: January 2016

AbstractThe lack of effective therapies for neurodegenerative disorders is one of the most relevant challenges of this century, considering that, as the global population ages, the incidence of these type of diseases is quickly on the rise. Among these disorders, synucleinopathies, which are characterized by the abnormal accumulation and spreading of the synaptic protein alpha‐synuclein in the brain, already constitute the second leading cause of parkinsonism and dementia in the elderly population. Disorders with alpha‐synuclein accumulation include Parkinson's disease, dementia with Lewy bodies and multiple system atrophy. Numerous therapeutic alternatives for synucleinopathies are being tested in pre‐clinical models and in the clinic; however, only palliative treatments addressing the dopaminergic deficits are approved to date, and no disease‐modifying options are available yet. In this article, we provide a brief overview of therapeutic approaches currently being explored for synucleinopathies, and suggest possible explanations to the clinical trials outcomes. Finally, we propose that a deeper understanding of the pathophysiology of synucleinopathies, together with a combination of therapies tailored to each disease stage, may lead to better therapeutic outcomes in synucleinopathy patients.
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Synucleinopathies, neurodegenerative disorders characterized by the abnormal accumulation of the protein alpha‐synuclein, constitute the second leading cause of parkinsonism and dementia in the elderly population, however, no disease‐modifying options are available yet. In this review, we summarize the therapeutic approaches currently being explored for synucleinopathies, suggest possible explanations to the clinical outcomes, and propose areas of further therapeutic improvement.This article is part of a special issue on Parkinson disease.
Salsolinol Up‐Regulates Oxytocin Expression and Release During Lactation in Sheep
Authors: Górski K. , Marciniak E. , Zielińska‐Górska M. , Misztal T. 
Published: January 2016

Salsolinol (1‐methyl‐6,7‐dihydroxy‐1,2,3,4‐tetrahydroisoquinoline) is a dopamine‐derived compound present in the central nervous system and pituitary gland. Several previous studies on lactating sheep and rats have reported that salsolinol plays a crucial role in the regulation of prolactin secretion. The present study investigated the effects of salsolinol, which was infused into the third ventricle of the brain, on oxytocin expression and release in lactating sheep, 48 h after weaning of 8‐week‐old lambs. Serial 30‐min infusions of salsolinol and vehicle were performed at 30‐min intervals from 10.00 to 15.00 h. Blood samples were collected every 10 min. The supraoptic nucleus (SON), paraventricular nucleus (PVN) and posterior pituitary were collected immediately after the experiment. Expression levels ofmRNAs for oxytocin and peptidylglycine α‐amidating monooxygenase (PAM), the terminal enzyme in the oxytocin synthesis pathway, were measured using a real‐time polymerase chain reaction. Oxytocin peptide content in the posterior pituitary was measured by an enzyme‐linked immunosorbent assay, and plasma oxytocin concentration was measured by radioimmunoassay. Salsolinol treatment significantly up‐regulated oxytocin andPAMgene expression in theSON(P < 0.01 and P < 0.05, respectively),PVN(P < 0.01 and P < 0.05, respectively) and posterior pituitary (P < 0.05 and P < 0.05, respectively). Oxytocin peptide content in the posterior pituitary and the area under the response curve of plasma oxytocin were significantly (P < 0.05 and P < 0.01, respectively) higher in salsolinol‐treated sheep than in control animals. The present study shows for the first time that salsolinol stimulates oxytocin secretion during lactation in sheep.
Long‐term efficacy of rituximab in IgM anti‐myelin‐associated glycoprotein neuropathy: RIMAG follow‐up study
Authors: Iancu Ferfoglia Ruxandra , Guimarães‐Costa Raquel , Viala Karine , Musset Lucile , Neil Jean , Marin Benoit , Léger Jean‐Marc 
Published: January 2016

AbstractThe Rituximab vs. Placebo in Polyneuropathy Associated With Anti‐MAG IgM Monoclonal Gammopathy (RIMAG) study showed no improvement using the inflammatory neuropathy cause and treatment sensory score (ISS) as primary outcome in patients with IgM anti‐myelin‐associated glycoprotein neuropathy (IgM anti‐MAG neuropathy) treated with rituximab, when compared with placebo. However, some secondary outcomes seemed to improve in the per protocol analysis. Patients from one participating center in the RIMAG study underwent a new evaluation after a median follow‐up of 6 (interquartile range (IQR) 4.9; 6.5) years, using the same outcome measures used in the original study. Data were recorded in seven rituximab patients (group 1) and in eight placebo patients (group 2). In group 2, six of eight patients received immunotherapy during follow‐up, while only two of seven did in group 1. No significant change was observed in either the ISS or the secondary outcomes in both groups, with the exception of worsening in the 10‐m walk time in group 2 (p = 0.016). The RIMAG follow‐up study failed to find any significant change in most outcome measures in patients from the RIMAG study, some of them having received new immunotherapies. This study stresses the lack of useful clinical scales sensitive enough to capture small, even meaningful, improvement in IgM anti‐MAG neuropathy.
Cerebrospinal fluid profile and seroprevalence of antiganglioside reactivity in patients with neuralgic amyotrophy
Authors: Stich Oliver , Glos Daniela , Brendle Marie , Dersch Rick , Rauer Sebastian 
Published: January 2016

AbstractNeuralgic amyotrophy (NA), also known as acute brachial plexitis, is postulated as an autoimmune pathogenesis. In a well‐defined cohort of patients with NA, we analyzed the cerebrospinal fluid (CSF) profile and the prevalence of antiganglioside antibodies. Patients with Varicella zoster‐associated radiculitis and healthy blood donors served as controls. An abnormal routine laboratory CSF profile was found in 29% of those with NA, mostly showing a disruption of the blood–brain barrier. Antibodies predominantly from the immunoglobulin M (IgM) isotype against at least one human ganglioside were detected in 36% of sera from patients with NA but in only 2% of controls. An NA‐specific reactivity pattern was not detected, and there was no significant association with clinical or CSF parameters. This suggests that the seroprevalence of antiganglioside autoantibodies in patients with NA is nonspecific.
Three‐dimensional reconstruction of Haversian systems in human cortical bone using synchrotron radiation‐based micro‐CT: morphology and quantification of branching and transverse connections across age
Authors: Maggiano Isabel S. , Maggiano Corey M. , Clement John G. , Thomas C. David L. , Carter Yasmin , Cooper David M. L. 
Published: January 2016

AbstractThis study uses synchrotron radiation‐based micro‐computed tomography (CT) scans to reconstruct three‐dimensional networks of Haversian systems in human cortical bone in order to observe and analyse interconnectivity of Haversian systems and the development of total Haversian networks across different ages. A better knowledge of how Haversian systems interact with each other is essential to improve understanding of remodeling mechanisms and bone maintenance; however, previous methodological approaches (e.g. serial sections) did not reveal enough detail to follow the specific morphology of Haversian branching, for example. Accordingly, the aim of the present study was to identify the morphological diversity of branching patterns and transverse connections, and to understand how they change with age. Two types of branching morphologies were identified: lateral branching, resulting in small osteon branches bifurcating off of larger Haversian canals; and dichotomous branching, the formation of two new osteonal branches from one. The reconstructions in this study also suggest that Haversian systems frequently target previously existing systems as a path for their course, resulting in a cross‐sectional morphology frequently referred to as ‘type II osteons’. Transverse connections were diverse in their course from linear to oblique to curvy. Quantitative assessment of age‐related trends indicates that while in younger human individuals transverse connections were most common, in older individuals more evidence of connections resulting from Haversian systems growing inside previously existing systems was found. Despite these changes in morphological characteristics, a relatively constant degree of overall interconnectivity is maintained throughout life. Altogether, the present study reveals important details about Haversian systems and their relation to each other that can be used towards a better understanding of cortical bone remodeling as well as a more accurate interpretation of morphological variants of osteons in cross‐sectional microscopy. Permitting visibility of reversal lines, synchrotron radiation‐based micro‐CT is a valuable tool for the reconstruction of Haversian systems, and future analyses have the potential to further improve understanding of various important aspects of bone growth, maintenance and health.
Combined autologous platelet‐rich plasma with microneedling verses microneedling with distilled water in the treatment of atrophic acne scars: a concurrent split‐face study
Authors: Asif Mohd , Kanodia Sanjay , Singh Kishor 
Published: January 2016

SummaryBackgroundAcne scarring causes cosmetic discomfort, depression, low self‐esteem and reduced quality of life. Microneedling is an established treatment for scars, although the efficacy of platelet‐rich plasma (PRP) has not been explored much.ObjectiveThe objective of this study was to evaluate the efficacy and safety of platelet‐rich plasma (PRP) combined with microneedling for the treatment of atrophic acne scars.MethodsFifty patients of 17–32 years of age with atrophic acne scars were enrolled. Microneedling was performed on both halves of the face. Intradermal injections as well as topical application of PRP was given on right half of the face, while the left half of the face was treated with intradermal administration of distilled water. Three treatment sessions were given at an interval of 1 month consecutively. Goodman's Quantitative scale and Quantitative scale were used for the final evaluation of results.ResultsRight and left halves showed 62.20% and 45.84% improvement, respectively, on Goodman's Quantitative scale. Goodman's Qualitative scale showed excellent response in 20 (40%) patients and good response in 30 (60%) patients over right half of the face, while the left half of the face showed excellent response in 5 (10%) patients, good response in 42 (6%) patients and poor response in three patients.ConclusionWe conclude that PRP has efficacy in the management of atrophic acne scars. It can be combined with microneedling to enhance the final clinical outcomes in comparison with microneedling alone.
Medication administration errors from a nursing viewpoint: a formal consensus of definition and scenarios using a Delphi technique
Authors: Shawahna Ramzi , Masri Dina , Al‐Gharabeh Rawan , Deek Rawan , Al‐Thayba Lama , Halaweh Masa 
Published: January 2016

Aims and objectivesTo develop and achieve formal consensus on a definition of medication administration errors and scenarios that should or should not be considered as medication administration errors in hospitalised patient settings.BackgroundMedication administration errors occur frequently in hospitalised patient settings. Currently, there is no formal consensus on a definition of medication administration errors or scenarios that should or should not be considered as medication administration errors.DesignThis was a descriptive study using Delphi technique.MethodsA panel of experts (n = 50) recruited from major hospitals, nursing schools and universities in Palestine took part in the study. Three Delphi rounds were followed to achieve consensus on a proposed definition of medication administration errors and a series of 61 scenarios representing potential medication administration error situations formulated into a questionnaire.ResultsIn the first Delphi round, key contact nurses’ views on medication administration errors were explored. In the second Delphi round, consensus was achieved to accept the proposed definition of medication administration errors and to include 36 (59%) scenarios and exclude 1 (1·6%) as medication administration errors. In the third Delphi round, consensus was achieved to consider further 14 (23%) and exclude 2 (3·3%) as medication administration errors while the remaining eight (13·1%) were considered equivocal. Of the 61 scenarios included in the Delphi process, experts decided to include 50 scenarios as medication administration errors, exclude three scenarios and include or exclude eight scenarios depending on the individual clinical situation.ConclusionConsensus on a definition and scenarios representing medication administration errors can be achieved using formal consensus techniques.Relevance to clinical practiceResearchers should be aware that using different definitions of medication administration errors, inclusion or exclusion of medication administration error situations could significantly affect the rate of medication administration errors reported in their studies. Consensual definitions and medication administration error situations can be used in future epidemiology studies investigating medication administration errors in hospitalised patient settings which may permit and promote direct comparisons of different studies.
Making time and space: the impact of mindfulness training on nursing and midwifery practice. A critical interpretative synthesis
Authors: Hunter Louise 
Published: January 2016

Aims and objectivesTo explore qualitative literature to ascertain whether and how nurses and midwives perceive that mindfulness impacts on their practice, particularly their interactions with patients.BackgroundStress and burnout, which negatively impact patient care, are widely reported among nurses and midwives, who face unique stressors as professionals who often hold little organisational power, but are expected to shoulder the burden of resource cuts and an increasingly complex workload. Mindfulness is recommended as a tool to decrease stress and burnout in health professionals, and may also increase practitioner compassion and improve patient interactions.DesignA critical interpretative synthesis.MethodsA systematic search was undertaken to identify qualitative studies where the majority of participants were qualified nurses and/or midwives who had attended mindfulness training. Retrieved literature was read and reread to identify relevant material, which was then coded into themes. Related themes were grouped into synthetic constructs, and a synthetic argument was produced to illustrate the relationships between these.ResultsFive relevant papers were identified. Findings indicate that mindfulness training enables nurses and midwives to gain some control over their thoughts and stress levels. This then creates a quiet mental space giving them agency and perspective and leading to improved caring, including a more patient‐centred focus and increased presence and listening. Mindfulness appears to alter the way nurses and midwives operate within a stressful work environment, thereby changing the way the environment is experienced by themselves and, potentially, the people in their care.ConclusionsFurther research is needed, but current qualitative research suggests mindfulness may enable nurses and midwives to work with compassion in stressful and demanding work environments.Relevance to clinical practiceMindfulness may offer an enabling way of coping with stress, in contrast to long‐standing strategies such as task‐orientation and depersonalisation.
Circulating calcium concentrations, vascular disease and mortality: a systematic review
Authors: Reid I. R. , Gamble G. D. , Bolland M. J. 
Published: January 2016

AbstractAssociations between serum calcium and vascular disease have been reported, but the consistency of these findings is unknown. We conducted a systematic review to determine whether circulating calcium concentrations are associated with risks of cardiovascular disease and death in normocalcaemic populations. We conducted PubMed searches up to 18 December 2014 and scrutinized reference lists of papers. Eligible studies related serum calcium to mortality or cardiovascular events in humans. A follow‐up of at least one year was required for longitudinal studies. Studies in populations selected on the basis of renal disease or abnormal serum calcium were excluded. Two investigators performed independent data extraction. The results were tabulated and, where possible, meta‐analysed. Five of 11 studies reported a statistically significant positive association between serum calcium and mortality. Meta‐analysis of eight of these studies showed a hazard ratio of death of 1.13 (1.09, 1.18) per standard deviation of serum calcium. Eight of 13 studies reported a statistically significant positive association between serum calcium and cardiovascular disease. Meta‐analysis of eight studies showed a hazard ratio of cardiovascular disease of 1.08 (1.04, 1.13) per standard deviation of serum calcium. For two studies reporting odds ratios, the pooled odds ratio per standard deviation was 1.22 (1.11, 1.32). When hazard ratios adjusted for cardiovascular risk factors were meta‐analysed, the pooled hazard ratio was 1.04 (1.01, 1.08). Other studies demonstrated associations between serum calcium and stroke and between serum calcium and direct measurements of arterial disease and calcification. These observational data indicate that serum calcium is associated with vascular disease and death, but they cannot determine causality.