bluuebunny/crossref_metadata_2025 huggingface dataset:
The specific ex vivo released cytokine profile is associated with ischemic stroke outcome and improves its prediction
Authors: Klimiec-Moskal Elzbieta , Piechota Marcin , Pera Joanna , Weglarczyk Kazimierz , Slowik Agnieszka , Siedlar Maciej , Dziedzic Tomasz
Published: January 2020

Background

Inflammation is associated with poor outcome after stroke. A relationship between ex vivo cytokine synthesis and stroke outcome remains unclear. We explored an association between ex vivo cytokine release, circulating interleukin (IL)-6 as a marker of systemic inflammation, and stroke prognosis. We assessed the utility of ex vivo synthesized cytokines for predicting stroke outcome.

Methods

We collected blood from 248 ischemic stroke patients and stimulated it ex vivo with lipopolysaccharide. We measured concentration of synthesized cytokines (TNFα, IP-10, IL-1β, IL-6, IL-8, IL-10, and IL-12) and plasma IL-6. We assessed functional outcome 3 months after stroke using the modified Rankin Scale. To assess the prognostic ability of cytokines, we applied multivariate logistic regression, cluster analysis, and construction of multimarker score.

Results

Decreased release of IP-10, TNFα, IL-1β, and IL-12; increased release of IL-10 and IL-8; and higher plasma IL-6 level were associated with poor outcome. Cluster analysis identified three groups of patients with distinct cytokine profiles. The group with the worst outcome demonstrated high synthesis of IL-10, IL-8, IL-1β, and IL-6 and low synthesis of IL-12, IP-10, and TNFα accompanied by high circulating IL-6 level. The group with the best prognosis showed high synthesis of TNFα, IP-10, IL-12, IL-1β, and IL-6; low synthesis of IL-10 and IL-8; and low plasma IL-6. Patients with intermediate outcome had low synthesis of all cytokines accompanied by low circulating IL-6. We constructed a multimarker score composed of ex vivo released IL-12, IL-10, TNFα, and plasma IL-6. Addition of this score to clinical variables led to significant increase in c-statistic (0.81 vs 0.73,p= 0.02) and net reclassification improvement.

Conclusion

The decreased ex vivo release of pro-inflammatory cytokines and increased release of IL-10 and IL-8 are related to poor outcome after stroke. Cytokine-based multimarker score adds prognostic value to clinical model for predicting stroke outcome.
Does the frontal sensory organ in adults of the hoplonemertean Quasitetrastemma stimpsoni originate from the larval apical organ?
Authors: Magarlamov Timur Yu , Dyachuk Vyacheslav , Chernyshev Alexey V.
Published: January 2020

Background

The apical organ is the most prominent neural structure in spiralian larvae. Although it has been thoroughly investigated in larvae of the class Pilidiophora in phylum Nemertea, studies on its structure in other nemertean larvae are limited. Most adult hoplonemertean worms have a frontal organ located in a position corresponding to that of the larval apical organ. The development and sensory function of the frontal organ has not been thoroughly characterized to date.

Results

The apical organ in the early rudiment stage of Quasitetrastemma stimpsoni larvae consists of an apical plate enclosed by ducts of frontal gland cells and eight apical neurons. The apical plate is abundantly innervated by neurites of apical neurons. During the late rudiment stage, the larval apical organ has external innervation from below by two subapical-plate neurons, along with 11 apical neurons, and its plate contains serotonin-like immunoreactive (5-HT-lir) cells. In the vermicular stage (free-swimming juvenile), the number of apical neurons is reduced, and their processes are resorbed. Serotonin is detected in the apical plate with no visible connection to apical neurons. In adult worms, the frontal organ has a small apical pit with openings for the frontal gland ducts. The organ consists of 8 to 10 densely packed 5-HT-lir cells that form the roundish pit.

Conclusions

Although the ultrastructure of the Q. stimpsoni larval apical organ closely resembles that of the apical organ of Polycladida larvae, the former differs in the presence of flask-shaped neurons typical of Spiralia. Significant differences in the structure of the apical organs of hoplonemertean and pilidia larvae point to two different paths in the evolutionary transformation of the ancestral apical organ. Ultrastructural and immunoreactive analyses of the apical organ of a hoplonemertean larva in the late rudiment and vermicular stages and the frontal organ of the adult worms identified common morphological and functional features. Thus, we hypothesize that the larval apical organ is modified during morphogenesis to form the adult frontal organ, which fulfills a sensory function in the hoplonemertean worm. This unique developmental trait distinguishes the Hoplonemertea from other nemertean groups.
Decay of infectious adenovirus and coliphages in freshwater habitats is differentially affected by ambient sunlight and the presence of indigenous protozoa communities
Authors: McMinn Brian R. , Rhodes Eric R. , Huff Emma M. , Korajkic Asja
Published: January 2020

Background

Sanitary quality of recreational waters worldwide is assessed using fecal indicator bacteria (FIB), such asEscherichia coliand enterococci. However, fate and transport characteristics of FIB in aquatic habitats can differ from those of viral pathogens which have been identified as main etiologic agents of recreational waterborne illness. Coliphages (bacteriophages infectingE. coli) are an attractive alternative to FIB because of their many morphological and structural similarities to viral pathogens.

Methods

In this in situ field study, we used a submersible aquatic mesocosm to compare decay characteristics of somatic and F+ coliphages to those of infectious human adenovirus 2 in a freshwater lake. In addition, we also evaluated the effect of ambient sunlight (and associated UV irradiation) and indigenous protozoan communities on decay of somatic and F+ coliphage, as well as infectious adenovirus.

Results

Our results show that decay of coliphages and adenovirus was similar (p = 0.0794), indicating that both of these bacteriophage groups are adequate surrogates for decay of human adenoviruses. Overall, after 8 days the greatest log10reductions were observed when viruses were exposed to a combination of biotic and abiotic factors (2.92 ± 0.39, 4.48 ± 0.38, 3.40 ± 0.19 for somatic coliphages, F+ coliphages and adenovirus, respectively). Both, indigenous protozoa and ambient sunlight, were important contributors to decay of all three viruses, although the magnitude of that effect differed over time and across viral targets.

Conclusions

While all viruses studied decayed significantly faster (p < 0.0001) when exposed to ambient sunlight, somatic coliphages were particularly susceptible to sunlight irradiation suggesting a potentially different mechanism of UV damage compared to F+ coliphages and adenoviruses. Presence of indigenous protozoan communities was also a significant contributor (pvalue range: 0.0016 to < 0.0001) to decay of coliphages and adenovirus suggesting that this rarely studied biotic factor is an important driver of viral reductions in freshwater aquatic habitats.
The ABCA1 blocking agent probucol decreases capacitation in ejaculated dog spermatozoa
Authors: Schäfer-Somi Sabine , Budik Sven
Published: January 2020

Background

The ATP binding cassette (ABC) transporters participate in the cholesterol and phospholipid transport within and through cell membranes of many cells including spermatozoa. Cholesterol efflux is important for capacitation of spermatozoa. ABCA1 expression has been assessed in canine spermatozoa previously but its role in capacitation still has to be determined. The aim of the study was to test whether inhibition of ABCA1 (1) decreases capacitation in ejaculated and epididymal canine sperm samples and (2) decreases cholesterol efflux in the same samples. Twenty-one ejaculates and sperm from 22 epididymal tails were collected from healthy dogs. Motility was measured by CASA and viability assessed after staining with SYBR-14/PI. Samples from ejaculated sperm and sperm from epididymal tails were aliquoted. One part was incubated with the ABCA1 inhibitor probucol, the other served as a negative control. In all samples, capacitation was evaluated by chlortetracyclin (CTC) assay and cholesterol was measured by cholesterol efflux assay and colorimetric enzymatic assay.

Results

In ejaculated sperm, blockade of ABCA1 with 100 µM of probucol/mL of sample resulted in a significantly higher percentage of uncapacitated and acrosome reacted spermatozoa (P < 0.001 and P = 0.031), capacitation was significantly decreased (35% in probucol samples vs 54.2% in controls, P < 0.001). In probucol inhibited sperm samples from epididymal tails, the percentage of capacitated spermatozoa did not differ between groups but the percentage of acrosome reacted spermatozoa increased significantly (P = 0.014). The cholesterol measurement revealed significantly lower cholesterol concentration in the probucol group when compared to the controls (P = 0.035), however only in ejaculated sperm samples.

Conclusions

CTC assay and cholesterol measurement revealed significant differences between groups; we conclude that inhibition of ABCA1 significantly decreased capacitation and cholesterol efflux in ejaculated canine spermatozoa. The inhibition was not complete but ABCA1 is supposed to contribute to capacitation in canine ejaculated spermatozoa. ABCA1 is probably not important for capacitation of epididymal spermatozoa but might exert other functions during spermatozoa ripening.
The refugee post-migration stress scale (RPMS) – development and validation among refugees from Syria recently resettled in Sweden
Authors: Malm Andreas , Tinghög Petter , Narusyte Jurgita , Saboonchi Fredrik
Published: January 2020

Background

Despite the growing recognition of the impact of post-resettlement factors on the mental health of refugees, a clear definition of the concept of post-migration stress, as well as an updated, valid instrument for assessing the construct, are still lacking. The aim of the current study was to develop and validate the Refugee Post-Migration Stress Scale (RPMS), a concise, multi-dimensional instrument for assessing post-migration stress among refugees.

Results

Based on a review of previous research and observations from a refugee trauma clinic, a preliminary 24-item instrument was developed, covering seven hypothesized domains of post-migration stress: perceived discrimination, lack of host country specific competences, material and economic strain, loss of home country, family and home country concerns, social strain, and family conflicts.

In the context of a population-based survey of mental health among refugees from Syria recently resettled in Sweden (n = 1215), the factorial structure of the RPMS was investigated. Confirmatory Factor Analysis revealed slightly insufficient fit for the initial theorized multi-domain model. Exploratory Factor Analysis in four iterations resulted in the omission of three items and an adequate fit of a 7-factor model, corresponding to the seven hypothesized domains of post-migration stress. To assess concurrent validity, correlational analyses with measures of anxiety, depression, post-traumatic stress disorder (PTSD), and mental wellbeing were carried out. All domains of post-migration stress showed significant correlations with anxiety, depression, and PTSD scores, and significant negative correlations with mental wellbeing scores.

Conclusions

The newly developed RPMS appears to be a valid instrument for assessing refugee post-migration stress. Our findings that post-migration stress primarily relating to social and economic factors seems to be associated with mental ill health among refugees is in line with previous research.
The effect of discharge destination and primary insurance provider on hospital discharge delays among patients with traumatic brain injury: a multicenter study of 1,543 patients
Authors: Sorensen Melissa , Sercy Erica , Salottolo Kristin , Waxman Michael , West Thomas A. , Tanner Allen , Bar-Or David
Published: January 2020

Background

Hospital length of stay (HLOS) is a commonly used measure of hospital quality and is influenced by clinical and non-clinical factors. To reduce HLOS, it is key to identify factors placing patients at increased risk of lengthy HLOS and discharge delays.

Methods

This was a retrospective cohort study of patients age ≥ 18 admitted to four level 1 trauma centers between 1/1/2015 and 3/31/2018 with traumatic brain injury (TBI). The primary outcome was discharge delay, defined as discharge ≥24 h after case management notes indicated the patient was ready for discharge. The independent variables of interest were primary insurance provider and discharge destination. Chi-square, Fisher exact, and unadjusted and adjusted logistic regression analyses were used to assess associations between discharge delay and the two primary independent variables, as well as other patient demographic and clinical characteristics. Complications developing during the delay period were also examined.

Results

A total of 1543 patients with TBI were included. The median age was 61 years, and the median HLOS was 5 days. Approximately half of patients were discharged home (54%). The most common insurance providers were Medicare (35%) and commercial/private (35%). Two-hundred ten (14%) patients experienced a discharge delay. The median delay period was 3 days, and the most common reasons for delay were insurance authorization (52%) and lack of accepting bed (41%). Compared to being discharged home, patients discharged to a skilled nursing facility (adjusted odds ratio (AOR) = 10.35) or intermediate care facility (AOR = 10.64) had the highest odds of discharge delay. Compared to Medicare patients, uninsured/self-pay patients (AOR = 2.98) and those with Medicaid (AOR = 2.83) or commercial/private insurance (AOR = 2.22) had higher odds of delay. Thirty-two patients (15% of those delayed) experienced at least one complication during the delay, some of which were clinically severe.

Conclusions

A substantial portion of TBI patients in this study experienced discharge delays, and discharge destination and primary insurance provider were significant drivers of these delays. Evaluation of a facility’s quality of care should consider the specific causes of these delays.
Brainstem dysfunction in critically ill patients
Authors: Benghanem Sarah , Mazeraud Aurélien , Azabou Eric , Chhor Vibol , Shinotsuka Cassia Righy , Claassen Jan , Rohaut Benjamin , Sharshar Tarek
Published: January 2020

The brainstem conveys sensory and motor inputs between the spinal cord and the brain, and contains nuclei of the cranial nerves. It controls the sleep-wake cycle and vital functions via the ascending reticular activating system and the autonomic nuclei, respectively. Brainstem dysfunction may lead to sensory and motor deficits, cranial nerve palsies, impairment of consciousness, dysautonomia, and respiratory failure. The brainstem is prone to various primary and secondary insults, resulting in acute or chronic dysfunction. Of particular importance for characterizing brainstem dysfunction and identifying the underlying etiology are a detailed clinical examination, MRI, neurophysiologic tests such as brainstem auditory evoked potentials, and an analysis of the cerebrospinal fluid. Detection of brainstem dysfunction is challenging but of utmost importance in comatose and deeply sedated patients both to guide therapy and to support outcome prediction. In the present review, we summarize the neuroanatomy, clinical syndromes, and diagnostic techniques of critical illness-associated brainstem dysfunction for the critical care setting.
Therapeutic drug monitoring of infliximab compared to standard clinical treatment with infliximab: study protocol for a randomised, controlled, open, parallel-group, phase IV study (the NOR-DRUM study)
Authors: Syversen Silje W , Goll Guro L , Jørgensen Kristin K , Olsen Inge C , Sandanger Øystein , Gehin Johanna E , Warren David J , Sexton Joseph , Mørk Cato , Jahnsen Jørgen , Kvien Tore K , Bolstad Nils , Haavardsholm Espen A
Published: January 2020

Background

Infliximab (INX) and other tumour necrosis factor inhibitors (TNFi) have revolutionised the treatment of several immune mediated inflammatory diseases. Still, many patients do not respond sufficiently to therapy or lose efficacy over time. The large interindividual variation in serum drug concentrations on standard doses and the development of anti-drug antibodies are thought to be major reasons for treatment failures. Therapeutic drug monitoring (TDM), an individualised treatment strategy based on systematic assessments of serum drug concentrations, has been proposed as a clinical tool to optimise efficacy of INX treatment. TDM seems reasonable both from a clinical and an economical point of view, but the effectiveness of this treatment strategy has not yet been demonstrated in randomised clinical trials. The NORwegian DRUg Monitoring study (NOR-DRUM) aims to assess the effectiveness of TDM, both with regard to the achievement of remission in patients starting INX treatment (part A) as well as to maintain disease control in patients on INX treatment (part B).

Methods

The NOR-DRUM study is a randomised, open, controlled, parallel-group, comparative, multi-centre, national, superiority, phase IV study with two separate parts, NOR-DRUM A and NOR-DRUM B. Patients with rheumatoid arthritis, psoriatic arthritis, spondyloarthritis, ulcerative colitis, Crohn’s disease and psoriasis are included. In both study parts participants are randomised 1:1 to either TDM of infliximab (intervention group) or to standard treatment with infliximab without knowledge of drug levels or ADAb status (control group). NOR-DRUM A will include 400 patients starting INX therapy. The primary outcome is remission at 30 weeks. In NOR-DRUM B, 450 patients on maintenance treatment with INX will be included. The primary endpoint is occurrence of disease worsening during the 52-week study period.

Discussion

As the first trial to assess the effectiveness, safety and cost-effectiveness of TDM in patients receiving TNFi for a range of immune mediated inflammatory diseases, we hope that the NOR-DRUM study will contribute to the advancement of evidence based personalised treatment with biological medicines.

Trial registration

Clinicaltrials.gov, NCT03074656. Registered on 090317.
Vitamin D supplementation compared to placebo in people with First Episode psychosis - Neuroprotection Design (DFEND): a protocol for a randomised, double-blind, placebo-controlled, parallel-group trial
Authors: Gaughran Fiona , Stringer Dominic , Berk Michael , Smith Shubulade , Taylor David , Whiskey Eromona , Landau Sabine , Murray Robin , McGuire Philip , Gardner-Sood Poonam , Wojewodka Gabriella , Ciufolini Simone , Jordan Harriet , Clarke Jessie , Allen Lauren , Krivoy Amir , Stubbs Brendon , Lowe Philippa , Arbuthnott Maurice , Rathod Shanaya , Boardman Andrew , Firdosi Mudasir , McGrath John J.
Published: January 2020

Background

People experiencing their first episode of psychosis are often deficient in vitamin D. Observational studies have reported an association between low vitamin D concentrations and poorer subsequent health outcomes in psychosis. A vitamin D deficiency in neonates and children has been linked to a later increased risk of schizophrenia and psychotic-like experiences. This trial aims to examine the effect of high-dose vitamin D supplementation on outcomes in early psychosis. We hypothesise that vitamin D supplementation will be associated with better mental health outcomes.

Methods/design

The DFEND study is a multicentre double-blind placebo-controlled parallel-group trial of vitamin D supplementation in people with early psychosis. Patients with an ICD-10 diagnosis of functional psychosis will be randomised in a 1:1 ratio to receive either 120,000 IU/month of vitamin D (cholecalciferol) or a matched placebo for 6 months. The primary outcome is the total Positive and Negative Syndrome Scale (PANSS) score at the 6-month follow-up for all patients. Secondary outcomes include assessment of mood (Calgary Depression Scale), general function (Global Assessment of Functioning), cardiovascular risk (body mass index, waist circumference, C-reactive protein, cholesterol and HbA1c) and vitamin D levels at the 6-month follow-up. Additionally, 3- and 6-month total PANSS scores will be analysed for those with inadequate vitamin D levels at the baseline.

Discussion

The DFEND study is the first trial to examine whether vitamin D supplementation in early psychosis is associated with better mental health outcomes. The findings of this study may help to resolve the clinical equipoise regarding the benefits and cost-effectiveness of routine vitamin D supplementation in people with psychosis.

Trial registration

ISRCTN, ISRCTN12424842. Registered on 25 February 2015.
Health Pregnancy, Healthy Baby: testing the added benefits of pregnancy ultrasound scan for child development in a randomised control trial
Authors: Richter Linda , Slemming Wiedaad , Norris Shane A. , Stein Alan , Poston Lucilla , Pasupathy Dharmintra
Published: January 2020

Background

The 2016 World Health Organization Antenatal Guidelines and the 2015 South African Maternal and Child Health Guidelines recommend one early antenatal ultrasound scan to establish gestational age and to detect multiple pregnancies and fetal abnormalities. Prior research indicates that ultrasound scan can also increase parental–fetal attachment. We aim to establish whether, compared to routine care, messages to promote parental attachment and healthy child development, conducted during one or two pregnancy ultrasound scans, improve early child development and growth, exclusive breastfeeding, parental–child interactions and prenatal and postnatal clinic attendance.

Methods

The effect of messages to sensitise mothers and fathers to fetal development will be tested in a three-armed randomised trial with 100 mothers and their partners from Soweto, Johannesburg in each arm. The primary outcome is child development at 6 months postnatally. Secondary outcomes include infant feeding, parental attachment and interaction, parental mental health and infant growth, assessed at 6 weeks and 6 months. Parents in Arm 1 receive a fetal ultrasound scan < 25 weeks during routine antenatal care at tertiary hospitals, and a second standard ultrasound scan at the research site within 2 weeks. Arm 2 participants receive the routine antenatal ultrasound scan and an additional ultrasound scan < 25 weeks at the research site, together with messages to promote parental attachment and healthy child development. Arm 3 participants receive the routine ultrasound scan and two additional ultrasound scans at the research site, < 25 weeks and < 36 weeks, together with messages to promote parental attachment and healthy child development.

Discussion

Evidence from high-income countries suggests that first-time prospective mothers and fathers enjoy seeing their fetus during ultrasound scan and that it is an emotional experience. A number of studies have found that ultrasound scan increases maternal attachment during pregnancy, a predictor of positive parent–infant interactions which, in turn, promotes healthy infant development. It is generally agreed that studies are needed which follow up parental–child behaviour and healthy child development postnatally, include fathers and examine the construct in a wider diversity of settings, especially in low and middle-income countries. Testing the added benefits of pregnancy ultrasound scan for child development is a gap that the proposed trial in South Africa seeks to address.

Trial registration

Pan African Clinical Trials Registry,PACTR201808107241133. Registered on 15 August 2018.
Effect and associated factors of a clinical pharmacy model in the incidence of medication errors (EACPharModel) in the Hospital Pablo Tobón Uribe: study protocol for a stepped wedge randomized controlled trial (NCT03338725)
Authors: Granados J. , Salazar-Ospina A. , Botero-Aguirre J. P. , Valencia-Quintero A. F. , Ortiz N. , Amariles P.
Published: January 2020

Background

According to WHO, medication error (ME) is a subject that requires attention at all levels of care to reduce severe and preventable damage related to medication use. Clinical pharmacy practice standards have been proposed around the world so that the pharmacist, as part of a multidisciplinary health team, can help improve patient safety; however, further evidence derived from adequate studies is needed to demonstrate this. This study aims to assess the effect of a clinical pharmacy practice model (CPPM) in preventing MEs associated with the medication use process.

Methods

A prospective, stepped-wedge, cluster-randomized, controlled trial with a duration of 14 months will be performed to compare the effect of a CPPM along with the usual care process of patients in the Pablo Tobón Uribe Hospital (Medellin, Colombia). The study is designed as a cluster-randomized controlled trial, involving five hospital wards (clusters) and 720 patients. Medical wards are allocated to interventions using a stepped-wedge design. Clusters are initially assigned to the control group. After a 2-month observation period, hospital clusters were randomly allocated to the intervention group. Study outcomes will be assessed at baseline and at 2, 4, 6, 8, 10, and 12 months after randomization. The primary outcome will be to assess the effect of a CPPM on the incidence of medication errors associated with the medication use process. Drug-related problems and factors that contribute to the occurrence of MEs will be assessed as secondary outcomes. Statistical analyses will be performed using a mixed model, with the treatment group and time as fixed effects and the clustering structure as a random effect. Statistical analysis will be performed using Pearson chi-square tests and Student’s t-tests, and a P value < 0.05 will be considered statistically significant.

Discussion

As far as we know, this is the first stepped-wedge, cluster-randomized, controlled trial designed to assess the change of a CPPM on the incidence of medication errors in a hospital in Colombia, and it could generate valuable information about a standardized and patient-centered clinical pharmacy model to improve the safety of inpatient care.

Trial registration

ClinicalTrials.gov, NCT03338725. Registered on 9 November 2017. The first patient was randomized on 2 February 2018.

Protocol version

0010112018JG
Effects of the Informed Health Choices primary school intervention on the ability of children in Uganda to assess the reliability of claims about treatment effects, 1-year follow-up: a cluster-randomised trial
Authors: Nsangi Allen , Semakula Daniel , Oxman Andrew D. , Austvoll-Dahlgren Astrid , Oxman Matt , Rosenbaum Sarah , Morelli Angela , Glenton Claire , Lewin Simon , Kaseje Margaret , Chalmers Iain , Fretheim Atle , Ding Yunpeng , Sewankambo Nelson K.
Published: January 2020

Introduction

We evaluated an intervention designed to teach 10- to 12-year-old primary school children to assess claims about the effects of treatments (any action intended to maintain or improve health). We report outcomes measured 1 year after the intervention.

Methods

In this cluster-randomised trial, we included primary schools in the central region of Uganda that taught year 5 children (aged 10 to 12 years). We randomly allocated a representative sample of eligible schools to either an intervention or control group. Intervention schools received the Informed Health Choices primary school resources (textbooks, exercise books and a teachers’ guide). The primary outcomes, measured at the end of the school term and again after 1 year, were the mean score on a test with two multiple-choice questions for each of the 12 concepts and the proportion of children with passing scores.

Results

We assessed 2960 schools for eligibility; 2029 were eligible, and a random sample of 170 were invited to recruitment meetings. After recruitment meetings, 120 eligible schools consented and were randomly assigned to either the intervention group (n = 60 schools; 76 teachers and 6383 children) or the control group (n = 60 schools; 67 teachers and 4430 children). After 1 year, the mean score in the multiple-choice test for the intervention schools was 68.7% compared with 53.0% for the control schools (adjusted mean difference 16.7%; 95% CI, 13.9 to 19.5;P < 0.00001). In the intervention schools, 3160 (80.1%) of 3943 children who completed the test after 1 year achieved a predetermined passing score (≥ 13 of 24 correct answers) compared with 1464 (51.5%) of 2844 children in the control schools (adjusted difference, 39.5%; 95% CI, 29.9 to 47.5).

Conclusion

Use of the learning resources led to a large improvement in the ability of children to assess claims, which was sustained for at least 1 year.

Trial registration

Pan African Clinical Trial Registry (www.pactr.org), PACTR201606001679337. Registered on 13 June 2016.
Molecular identification of four Sarcocystis species in the herring gull, Larus argentatus, from Lithuania
Authors: Prakas Petras , Butkauskas Dalius , Juozaitytė-Ngugu Evelina
Published: January 2020

Background

Birds of the family Laridae have not been intensively examined for infections with Sarcocystis spp. To date, sarcocysts of two species, S. lari and S. wobeseri, have been identified in the muscles of gulls. The aim of the present study was to evaluate the species richness of Sarcocystis in the herring gull, Larus argentatus, from Lithuania.

Methods

In the period between 2013 and 2019, leg muscles of 35 herring gulls were examined for sarcocysts of Sarcocystis spp. Sarcocystis spp. were characterised morphologically based on a light microscopy study. Four sarcocysts isolated from the muscles of each infected bird were subjected to further molecular examination. Sarcocystis species were identified by means of ITS1 sequence analysis.

Results

Sarcocysts were detected in 9/35 herring gulls (25.7%). Using light microscopy, one morphological type of sarcocysts was observed. Sarcocysts were microscopic, thread-like, had a smooth and thin (about 1 µm) cyst wall and were filled with banana-shaped bradyzoites. On the basis of ITS1 sequences, four Sarcocystis species, S. columbae, S. halieti, S. lari and S. wobeseri, were identified. Furthermore, it was demonstrated that a single infected herring gull could host two Sarcocystis species indistinguishable under light microscopy.

Conclusions

Larus argentatus is the first bird species found to act as intermediate host of four Sarcocystis spp. According to current knowledge, five species, S. falcatula, S. calchasi, S. wobeseri, S. columbae and S. halieti can use birds belonging to different orders as intermediate hosts.
Changes in gray matter volume and functional connectivity in dementia with Lewy bodies compared to Alzheimer’s disease and normal aging: implications for fluctuations
Authors: Chabran Eléna , Noblet Vincent , Loureiro de Sousa Paulo , Demuynck Catherine , Philippi Nathalie , Mutter Catherine , Anthony Pierre , Martin-Hunyadi Catherine , Cretin Benjamin , Blanc Frédéric
Published: January 2020

Background

Fluctuations are one of the core clinical features characterizing dementia with Lewy bodies (DLB). They represent a determining factor for its diagnosis and strongly impact the quality of life of patients and their caregivers. However, the neural correlates of this complex symptom remain poorly understood. This study aimed to investigate the structural and functional changes in DLB patients, compared to Alzheimer’s disease (AD) patients and healthy elderly subjects, and their potential links with fluctuations.

Methods

Structural and resting-state functional MRI data were collected from 92 DLB patients, 70 AD patients, and 22 control subjects, who also underwent a detailed clinical examination including the Mayo Clinic Fluctuation Scale. Gray matter volume changes were analyzed using whole-brain voxel-based morphometry, and resting-state functional connectivity was investigated using a seed-based analysis, with regions of interest corresponding to the main nodes of the salience network (SN), frontoparietal network (FPN), dorsal attention network (DAN), and default mode network (DMN).

Results

At the structural level, fluctuation scores in DLB patients did not relate to the atrophy of insular, temporal, and frontal regions typically found in this pathology, but instead showed a weak correlation with more subtle volume reductions in different regions of the cholinergic system. At the functional level, the DLB group was characterized by a decreased connectivity within the SN and attentional networks, while the AD group showed decreases within the SN and DMN. In addition, higher fluctuation scores in DLB patients were correlated to a greater connectivity of the SN with the DAN and left thalamus, along with a decreased connectivity between the SN and DMN, and between the right thalamus and both the FPN and DMN.

Conclusions

Functional connectivity changes, rather than significant gray matter loss, could play an important role in the emergence of fluctuations in DLB. Notably, fluctuations in DLB patients appeared to be related to a disturbed external functional connectivity of the SN, which may lead to less relevant transitions between different cognitive states in response to internal and environmental stimuli. Our results also suggest that the thalamus could be a key region for the occurrence of this symptom.
Prescreening for European Prevention of Alzheimer Dementia (EPAD) trial-ready cohort: impact of AD risk factors and recruitment settings
Authors:   for the IMI-EPAD collaborators, Vermunt Lisa , Muniz-Terrera Graciela , ter Meulen Lea , Veal Colin , Blennow Kaj , Campbell Archie , Carrié Isabelle , Delrieu Julien , Fauria Karine , Huesa Rodríguez Gema , Ingala Silvia , Jenkins Natalie , Molinuevo José Luis , Ousset Pierre-Jean , Porteous David , Prins Niels D. , Solomon Alina , Tom Brian D. , Zetterberg Henrik , Zwan Marissa , Ritchie Craig W. , Scheltens Philip , Luscan Gerald , Brookes Anthony J. , Visser Pieter Jelle
Published: January 2020

Background

Recruitment is often a bottleneck in secondary prevention trials in Alzheimer disease (AD). Furthermore, screen-failure rates in these trials are typically high due to relatively low prevalence of AD pathology in individuals without dementia, especially among cognitively unimpaired. Prescreening on AD risk factors may facilitate recruitment, but the efficiency will depend on how these factors link to participation rates and AD pathology. We investigated whether common AD-related factors predict trial-ready cohort participation and amyloid status across different prescreen settings.

Methods

We monitored the prescreening in four cohorts linked to the European Prevention of Alzheimer Dementia (EPAD) Registry (n = 16,877; mean ± SD age = 64 ± 8 years). These included a clinical cohort, a research in-person cohort, a research online cohort, and a population-based cohort. Individuals were asked to participate in the EPAD longitudinal cohort study (EPAD-LCS), which serves as a trial-ready cohort for secondary prevention trials. Amyloid positivity was measured in cerebrospinal fluid as part of the EPAD-LCS assessment. We calculated participation rates and numbers needed to prescreen (NNPS) per participant that was amyloid-positive. We tested if age, sex, education level,APOEstatus, family history for dementia, memory complaints or memory scores, previously collected in these cohorts, could predict participation and amyloid status.

Results

A total of 2595 participants were contacted for participation in the EPAD-LCS. Participation rates varied by setting between 3 and 59%. The NNPS were 6.9 (clinical cohort), 7.5 (research in-person cohort), 8.4 (research online cohort), and 88.5 (population-based cohort). Participation in the EPAD-LCS (n = 413 (16%)) was associated with lower age (odds ratio (OR) age = 0.97 [0.95–0.99]), high education (OR = 1.64 [1.23–2.17]), male sex (OR = 1.56 [1.19–2.04]), and positive family history of dementia (OR = 1.66 [1.19–2.31]). Among participants in the EPAD-LCS, amyloid positivity (33%) was associated with higher age (OR = 1.06 [1.02–1.10]) andAPOEɛ4 allele carriership (OR = 2.99 [1.81–4.94]). These results were similar across prescreen settings.

Conclusions

Numbers needed to prescreen varied greatly between settings. Understanding how common AD risk factors link to study participation and amyloid positivity is informative for recruitment strategy of studies on secondary prevention of AD.
Epidemiology and associated factors of atopic dermatitis in Malagasy children
Authors: Sendrasoa F. A. , Ranaivo I. M. , Razanakoto N. H. , Andrianarison M. , Raharolahy O. , Ratovonjanahary V. T. , Sata M. , Rakotoarisaona M. F. , Ramarozatovo L. S. , Rapelanoro Rabenja F.
Published: January 2020

Background

Little is known about the epidemiology and associated factors of childhood AD in the markedly different, low-income, tropical environment like Madagascar.

Methods

We aim to assess the epidemiology and associated factors of AD in individuals fewer than 15 years of age in Antananarivo Madagascar. It was a retrospective and descriptive study over a period of 7 years (2010 to 2016) in children 6 months to 14 years in the Department of Dermatology, Joseph Raseta Befelatanana Antananarivo Madagascar. The diagnosis of AD was based on clinical data.

Results

The prevalence of AD was 5.6% in children aged 6 months to 14 years. The details of 151 cases of atopic dermatitis were analyzed. The mean age of patients was 4 years. There was a female preponderance (sex ratio: 0.7). A family history of AD was noted in 56 cases (37%). No association between breast-feeding and AD was found. The age of onset of AD was before the age of 3 months in 7.5% and between 6 months to 5 years in 70%. Children born in March (dry season) had the highest risk of AD. Consultations for AD increased during the winter (from July to October; p = 0.005). However, the prevalence of AD was similar in urban and rural areas.

Conclusion

Weather may have an impact on the prevalence of atopic dermatitis in Madagascar. No significant correlation was found between the duration of breastfeeding and AD, as well as urbanization.
Dust mite ingestion-associated, exercise-induced anaphylaxis: a case report and literature review
Authors: Sompornrattanaphan Mongkhon , Jitvanitchakul Yanisa , Malainual Nat , Wongsa Chamard , Jameekornrak Aree , Theankeaw Orathai , Thongngarm Torpong
Published: January 2020

Background

Oral mite anaphylaxis (OMA) is a condition characterized by severe allergic reactions after ingesting food containing dust mite-contaminated flour. Physical exertion is recognized as a common trigger factor inducing anaphylaxis. The association of OMA with exercise-induced anaphylaxis has rarely been reported.

Case presentation

We report a 29-year-old Thai woman who had dust mite ingestion-associated, exercise-induced anaphylaxis who tolerated the same bag of contaminated flour without exercise. A sample of contaminated cooking flour was examined under a light microscope. Living mites, Dermatophagoides farinae, were detected by a medical entomologist based on the morphology. We performed skin test to both mite-contaminated and newly opened Gogi® cooking flour, common aeroallergens, food allergens, and all other ingredients in the fried coconut rice cake 5 weeks after the anaphylactic episode. Specific IgE tests, using ImmunoCAP were also performed.

Conclusions

Dust mite ingestion-associated, exercise-induced anaphylaxis may be misdiagnosed as wheat-dependent exercise-induced anaphylaxis and should be suspected in patients with anaphylaxis linked to food intake and exercise, but who have no apparent evidence to the index food ingredients on allergy workup.
Existence of ground state solutions for an asymptotically 2-linear fractional Schrödinger–Poisson system
Authors: Yang Dandan , Bai Chuanzhi
Published: January 2020

In this paper, we investigate the following fractional Schrödinger–Poisson system:
$$\left \{ \textstyle\begin{array}{l@{\quad}l} (-\Delta)^{s} u + u + \phi u = f(u), & \text{in } \mathbb{R}^{3}, \\ (-\Delta)^{t} \phi= u^{2}, & \text{in } \mathbb{R}^{3}, \end{array}\displaystyle \right . $${(−Δ)su+u+ϕu=f(u),in R3,(−Δ)tϕ=u2,in R3, where $\frac{3}{4} < s < 1$34<s<1, $\frac{1}{2} < t < 1$12<t<1, and f is a continuous function, which is superlinear at zero, with $f(\tau) \tau \ge3 F(\tau) \ge0$f(τ)τ≥3F(τ)≥0, $F(\tau) = \int_{0}^{\tau} f(s) \,ds$F(τ)=∫0τf(s)ds, $\tau \in\mathbb{R}$τ∈R. We prove that the system admits a ground state solution under the asymptotically 2-linear condition. The result here extends the existing study.
Moment estimates for invariant measures of stochastic Burgers equations
Authors: Shi Yu , Liu Bin
Published: January 2020

In this paper, we study moment estimates for the invariant measure of the stochastic Burgers equation with multiplicative noise. Based upon an a priori estimate for the stochastic convolution, we derive regularity properties on invariant measure. As an application, we prove smoothing properties for the transition semigroup by introducing an auxiliary semigroup. Finally, the m-dissipativity of the associated Kolmogorov operator is given.
The complex phenomenon of dysrational antibiotics prescribing decisions in German primary healthcare: a qualitative interview study using dual process theory
Authors: Poss-Doering Regina , Kamradt Martina , Stuermlinger Anna , Glassen Katharina , Kaufmann-Kolle Petra , Andres Edith , Wensing Michel
Published: January 2020

Background

Antibiotic prescription rates in primary care in Germany are moderate, but still considered too high. The ARena study (Sustainable reduction of antibiotic-induced antimicrobial resistance) was initiated to foster awareness and understanding of the growing challenge and promotes rational antibiotics use for acute, non-complicated and self-limiting infections.

Methods

The present study was performed as part of the process evaluation of the ARena study. Interviews were conducted with a purposive sample of physicians participating in the ARena study to identify factors relevant to primary care physicians’ decision-making when prescribing antibiotics for acute non-complicated infections. Generated data were audio-recorded. Pseudonymized verbatim transcripts were coded using a pre-defined framework. The Dual Process Theory was applied to provide understanding of individual health professional factors that induce dysrational prescribing decisions.

Results

Based on medical as well as non-medical considerations, physicians developed habits in decision making on antibiotics prescribing. They acknowledged inadequate antibiotics prescribing for acute, non-complicated infections in situations involving uncertainty regarding diagnosis, prognosis, continuity of care, patient expectations and when not knowing the patient. Educative efforts empowered physicians to override habitual prescribing. A theory-driven model provides transparency as to how dysrational prescribing decisions occur and suggests remedy by providing new experiences and new recognizable patterns through educative efforts.

Conclusions

Educational interventions may only change prescribing behaviours if they result in active rational rather than routine-based decision-making on antibiotics prescribing.

Trial registration

ISRCTN, ISRCTN58150046.
Infection prevention practices in the Netherlands: results from a National Survey
Authors: Huis Anita , Schouten Jeroen , Lescure Dominique , Krein Sarah , Ratz David , Saint Sanjay , Hulscher Marlies , Greene M. Todd
Published: January 2020

Objective

To examine the extent to which acute care hospitals in the Netherlands have adopted recommended practices to prevent catheter-associated urinary tract infection (CAUTI), central line-associated bloodstream infection (CLABSI), ventilator-associated pneumonia (VAP), and Clostridioides difficile infection (CDI).

Methods

Between 18 July 2017 and 31 October 2017, we surveyed the infection prevention teams of all acute care hospitals in the Netherlands. The survey instrument was based on the ‘Translating Healthcare-Associated Infection Prevention Research into Practice’ (TRIP) questionnaire and adapted to the Dutch context. Descriptive statistics were used to examine the reported regular use of CAUTI, CLABSI, VAP, and CDI prevention practices as well as the hospital characteristics.

Results

Out of 72 eligible hospitals, 47 (65.3%) responded. Surveillance systems for monitoring CAUTI, CLABSI, VAP, and CDI were present in 17.8, 95.4, 26.2, and 77.3% of hospitals, respectively. Antimicrobial stewardship programs have been established in 91.5% of participating hospitals. For CAUTI, the majority of hospitals regularly used aseptic technique during catheter insertion (95%) and portable bladder ultrasound scanners (86.1%). Intermittent catheterization and catheter stop-orders were regularly used by 65.8 and 62.2% of hospitals. For CLABSI, all hospitals regularly used maximum sterile barrier precautions and chlorhexidine gluconate for insertion site antisepsis. Avoidance of the femoral site for central line insertions was regularly used by 65.9% of hospitals. Urinary catheters and central-lines impregnated with antibiotics or antiseptics were rarely used (≤ 5%). Selective decontamination strategies for preventing VAP were used in 84% of hospitals. With the exception of disposable thermometers (31.8%), all prevention practices to prevent CDI were regularly used by more than 80% of hospitals.

Conclusions

Most Dutch hospitals report regular use of recommended practices for preventing CLABSI and CDI. Several specific practices to prevent CAUTI and VAP were less frequently used, however, providing an opportunity for improvement.
δ-secretase in neurodegenerative diseases: mechanisms, regulators and therapeutic opportunities
Authors: Zhang Zhentao , Tian Ye , Ye Keqiang
Published: January 2020

Mammalian asparagine endopeptidase (AEP) is a cysteine protease that cleaves its protein substrates on the C-terminal side of asparagine residues. Converging lines of evidence indicate that AEP may be involved in the pathogenesis of several neurological diseases, including Alzheimer’s disease, Parkinson’s disease, and frontotemporal dementia. AEP is activated in the aging brain, cleaves amyloid precursor protein (APP) and promotes the production of amyloid-β (Aβ). We renamed AEP to δ-secretase to emphasize its role in APP fragmentation and Aβ production. AEP also cleaves other substrates, such as tau, α-synuclein, SET, and TAR DNA-binding protein 43, generating neurotoxic fragments and disturbing their physiological functions. The activity of δ-secretase is tightly regulated at both the transcriptional and posttranslational levels. Here, we review the recent advances in the role of δ-secretase in neurodegenerative diseases, with a focus on its biochemical properties and the transcriptional and posttranslational regulation of its activity, and discuss the clinical implications of δ-secretase as a diagnostic biomarker and therapeutic target for neurodegenerative diseases.