Characterization and identification of dityrosine cross-linked peptides using tandem mass spectrometry

The use of mass spectrometry coupled with chemical cross-linking of proteins has become a powerful tool for proteins structure and interactions studies. Unlike structural analysis of proteins using chemical reagents specific for lysine or cysteine residues, identification of gas-phase fragmentation patterns of endogenous dityrosine cross-linked peptides have not been investigated. Dityrosine cross-linking in proteins and peptides are clinical markers of oxidative stress, aging, and neurodegenerative diseases including Alzheimer’s disease and Parkinson’s disease. In this study, we investigated and characterized the fragmentation pattern of a synthetically prepared dityrosine cross-linked dimer of Aβ(1–16) using ESI tandem mass spectrometry. We then detailed the fragmentation pattern of dityrosine cross-linked Aβ(1–16), using collision induced dissociation (CID), higher-energy collision induced dissociation (HCD), electron transfer dissociation (ETD), and electron capture dissociation (ECD). Application of these generic fragmentation rules of dityrosine cross-linked peptides allowed for the identification of dityrosine cross-links in peptides of Aβ and α-synuclein generated in vitro by enzymatic peroxidation. We report, for the first time, the dityrosine cross-linked residues in human hemoglobin and α-synuclein under oxidative conditions. Together these tools open up the potential for automated analysis of this naturally occurring post-translation modification in neurodegenerative diseases as well as other pathological conditions

Antipsychotics for treatment of delirium in hospitalised non-ICU patients

Background: Guidelines suggest limited and cautious use of antipsychotics for treatment of delirium where nonpharmacological interventions have failed and symptoms remain distressing or dangerous, or both. It is unclear how well these recommendations are supported by current evidence. Objectives: Our primary objective was to assess the efficacy of antipsychotics versus nonantipsychotics or placebo on the duration of delirium in hospitalised adults. Our secondary objectives were to compare the efficacy of: 1) antipsychotics versus nonantipsychotics or placebo on delirium severity and resolution, mortality, hospital length of stay, discharge disposition, health-related quality of life, and adverse effects; and 2) atypical vs. typical antipsychotics for reducing delirium duration, severity, and resolution, hospital mortality and length of stay, discharge disposition, health-related quality of life, and adverse effects. Search methods: We searched MEDLINE, Embase, Cochrane EBM Reviews, CINAHL, Thomson Reuters Web of Science and the Latin American and Caribbean Health Sciences Literature (LILACS) from their respective inception dates until July 2017. We also searched the Database of Abstracts of Reviews of Effects (DARE), Health Technology Assessment Database, Web of Science ISI Proceedings, and other grey literature. Selection criteria: We included randomised and quasi-randomised trials comparing 1) antipsychotics to nonantipsychotics or placebo and 2) typical to atypical antipsychotics for the treatment of delirium in adult hospitalised (but not critically ill) patients. Data collection and analysis: We examined titles and abstracts of identified studies to determine eligibility. We extracted data independently in duplicate. Disagreements were settled by further discussion and consensus. We used risk ratios (RR) with 95% confidence intervals (CI) as a measure of treatment effect for dichotomous outcomes, and between-group standardised mean differences (SMD) with 95% CI for continuous outcomes. Main results: We included nine trials that recruited 727 participants. Four of the nine trials included a comparison of an antipsychotic to a nonantipsychotic drug or placebo and seven included a comparison of a typical to an atypical antipsychotic. The study populations included hospitalised medical, surgical, and palliative patients. No trial reported on duration of delirium. Antipsychotic treatment did not reduce delirium severity compared to nonantipsychotic drugs (standard mean difference (SMD) -1.08, 95% CI -2.55 to 0.39; four studies; 494 participants; very low-quality evidence); nor was there a difference between typical and atypical antipsychotics (SMD -0.17, 95% CI -0.37 to 0.02; seven studies; 542 participants; low-quality evidence). There was no evidence antipsychotics resolved delirium symptoms compared to nonantipsychotic drug regimens (RR 0.95, 95% CI 0.30 to 2.98; three studies; 247 participants; very low-quality evidence); nor was there a difference between typical and atypical antipsychotics (RR 1.10, 95% CI 0.79 to 1.52; five studies; 349 participants; low-quality evidence). The pooled results indicated that antipsychotics did not alter mortality compared to nonantipsychotic regimens (RR 1.29, 95% CI 0.73 to 2.27; three studies; 319 participants; low-quality evidence) nor was there a difference between typical and atypical antipsychotics (RR 1.71, 95% CI 0.82 to 3.35; four studies; 342 participants; low-quality evidence). No trial reported on hospital length of stay, hospital discharge disposition, or health-related quality of life. Adverse event reporting was limited and measured with inconsistent methods; in those reporting events, the number of events were low. No trial reported on physical restraint use, long-term cognitive outcomes, cerebrovascular events, or QTc prolongation (i.e. increased time in the heart's electrical cycle). Only one trial reported on arrhythmias and seizures, with no difference between typical or atypical antipsychotics. We found antipsychotics did not have a higher risk of extrapyramidal symptoms (EPS) compared to nonantipsychotic drugs (RR 1.70, 95% CI 0.04 to 65.57; three studies; 247 participants; very-low quality evidence); pooled results showed no increased risk of EPS with typical antipsychotics compared to atypical antipsychotics (RR 12.16, 95% CI 0.55 to 269.52; two studies; 198 participants; very low-quality evidence). Authors' conclusions: There were no reported data to determine whether antipsychotics altered the duration of delirium, length of hospital stay, discharge disposition, or health-related quality of life as studies did not report on these outcomes. From the poor quality data available, we found antipsychotics did not reduce delirium severity, resolve symptoms, or alter mortality. Adverse effects were poorly or rarely reported in the trials. Extrapyramidal symptoms were not more frequent with antipsychotics compared to nonantipsychotic drug regimens, and no different for typical compared to atypical antipsychotics

Population policies and education: exploring the contradictions of neo-liberal globalisation

The world is increasingly characterised by profound income, health and social inequalities (Appadurai, 2000). In recent decades development initiatives aimed at reducing these inequalities have been situated in a context of increasing globalisation with a dominant neo-liberal economic orthodoxy. This paper argues that neo-liberal globalisation contains inherent contradictions regarding choice and uniformity. This is illustrated in this paper through an exploration of the impact of neo-liberal globalisation on population policies and programmes. The dominant neo-liberal economic ideology that has influenced development over the last few decades has often led to alternative global visions being overlooked. Many current population and development debates are characterised by polarised arguments with strongly opposing aims and views. This raises the challenge of finding alternatives situated in more middle ground that both identify and promote the socially positive elements of neo-liberalism and state intervention, but also to limit their worst excesses within the population field and more broadly. This paper concludes with a discussion outling the positive nature of middle ground and other possible alternatives

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

A study of emerging style in the development of contructive conversations

SIGLEAvailable from British Library Document Supply Centre- DSC:DX174698 / BLDSC - British Library Document Supply CentreGBUnited Kingdo

The role of religion in decision-making on antenatal screening of congenital anomalies: A qualitative study amongst Muslim Turkish origin immigrants

Objective: to explore what role religious beliefs of pregnant Muslim women play in their decision-making on antenatal screening, particularly regarding congenital abnormalities and termination, and whether their interpretations of the religious doctrines correspond to the main sources of Islam. Design: qualitative pilot study using in-depth interviews with pregnant Muslim women. Setting: one midwifery practice in a medium-sized city near Amsterdam participated in the study. Participants: 10 pregnant Muslim women of Turkish origin who live in a high density immigrant area and who attended primary midwives for antenatal care were included in the study. Data collection and data analysis: to explore the role of religion in decision-making on antenatal screening tests, a topic list was constructed, including four subjects: being a (practising) Muslim, the view on unborn life, the view on disabled life and the view on termination. To analyse the interviews, open and axial coding based on the Grounded Theory was used and descriptive and analytical themes were identified and interpreted. Findings: all 10 interviewees stated that their faith played a role in their decision-making on antenatal screening, specific to the combined test. They did not consider congenital anomalies as a problem and did not consider termination to be an option in case of a disabled fetus. However, the Islamic jurisprudence considers that termination is allowed if the fetus has serious abnormalities, but only before 19 weeks plus one day of gestation. Key conclusions: religious convictions play a role regarding antenatal screening in pregnant Muslim women of Turkish origin. The interviewees did not consider a termination in case of an affected child. Women were unaware that within Islamic tradition there is the possibility of termination if a fetus has serious anomalies. Incomplete knowledge of religious doctrines may be influencing both decisions of antenatal screening and diagnostic tests uptake and of terminating a pregnancy for fetuses with serious anomalies. Implications for practise: counsellors should be aware of the role of religious beliefs in the decision-making process on antenatal screening tests. © 2013 The Authors

Factors affecting the uptake of prenatal screening tests for congenital anomalies; a multicentre prospective cohort study

BACKGROUND: Two prenatal screening tests for congenital anomalies are offered to all pregnant women in the Netherlands on an opt-in basis: the Combined Test (CT) for Down syndrome at twelve weeks, and the Fetal Anomaly Scan (FAS) at around twenty weeks. The CT is free for women who are 36 or older; the FAS is free for all women. We investigated factors associated with the CT and FAS uptake

A qualitative study on how Muslim women of Moroccan descent approach antenatal anomaly screening

Objective: to extend the knowledge on Muslim women's approach of antenatal anomaly screening. Design: qualitative interview study with pregnant Muslim women from Moroccan origin. Setting: one midwifery practice in a medium-sized city near Amsterdam participated in the study. Participants: twelve pregnant Muslim women who live in a high density immigrant area and who attended primary midwives for antenatal care were included in the study. Data collection and data analyses: we conducted open interviews with pregnant Moroccan Muslim women for the purpose of studying how they made decisions about antenatal anomaly screening. We used a thematic analysis approach. Findings: women experienced the combined test as 'a test' that could identify potentially anomalous infants, and could result in being offered termination of the pregnancy; a fact that resulted in their extensive deliberations and hesitation about the test uptake. Only two women had the combined test. Conversely, women opted for the Fetal Anomaly Scan and saw it as 'only an ultrasound to see the baby'. Above all, women emphasised that whether or not to participate in antenatal anomaly tests was their own, individual decision as ultimately they were accountable for their choices. All women, including nulliparous women, viewed becoming pregnant as the point of becoming a mother - and considered antenatal screening through the lens of motherhood. Key conclusions: motherhood was the lens through which the decision to participate in antenatal anomaly screening was approached. Religious beliefs influenced values on termination and disability and were influential in the deliberations for antenatal testing. Combined test but not Fetal Anomaly Scan was considered to be a antenatal screening test. Implications for practice: counsellors should have knowledge of the different Islamic beliefs about - the latest possible day for - termination and an awareness that Muslim women make their own conscious choices, also beyond Islamic rulings

Antenatal counselling for congenital anomaly tests: Pregnant Muslim Moroccan women's preferences

Objective: to gain insight into pregnant Muslim Moroccan women's preferences regarding the content of and approach to antenatal counselling for anomaly screening. Design: qualitative study using in-depth interviews. Setting: participants were recruited from one midwifery practice in a medium-sized city near Amsterdam. Participants: 12 pregnant Muslim Moroccan women who live in an area with a high density of immigrants. Data collection and data analyses: we conducted open interviews after the cut-off date for the 20 week fetal anomaly scan and used techniques from the thematic analysis approach described by Braun and Clarke (2006). Findings: pregnant Muslim Moroccan women's preferences towards counselling could be summarised in three main findings. Firstly, pregnant Muslim Moroccan women underlined the importance of accurate and detailed information about the tests procedures and the anomalies that could be detected. Secondly, pregnant Muslim Moroccan women preferred counsellors to initiate discussions about moral topics and its relationship with the women's religious beliefs and values to facilitate an informed choice about whether or not to participate in the screening tests. Thirdly, pregnant Muslim Moroccan women preferred a counsellor who respects and treats them as an individual who has an Islamic background. The counsellor should have practical knowledge of Islamic rulings that are relevant to the anomaly tests. Key conclusions: pregnant Muslim Moroccan women preferred to be accurately informed about antenatal anomaly tests and to be asked about their individual views on life by a counsellor who has genuine interest in the individual client and applied knowledge of Islamic beliefs regarding the value of life. Implications for practice: counsellors should explore clients moral values about quality of life and termination and its relationship with religious beliefs. Counsellors should know about Islamic rulings related to antenatal anomaly screening