Non-functional immunoglobulin G transcripts in a case of hyper-immunoglobulin M syndrome similar to type 4

86% of immunoglobulin G (IgG) heavy-chain gene transcripts were found to be non-functional in the peripheral blood B cells of a patient initially diagnosed with common variable immunodeficiency, who later developed raised IgM, whereas no non-functionally rearranged transcripts were found in the cells of seven healthy control subjects. All the patient's IgM heavy-chain and κ light-chain transcripts were functional, suggesting that either non-functional rearrangements were being selectively class-switched to IgG, or that receptor editing was rendering genes non-functional after class-switching. The functional γ-chain sequences showed a normal rate of somatic hypermutation while non-functional sequences contained few somatic mutations, suggesting that most came from cells that had no functional gene and therefore were not receiving signals for hypermutation. However, apoptosis of peripheral blood lymphocytes was not impaired. No defects have been found in any of the genes currently known to be responsible for hyper-IgM syndrome but the phenotype fits best to type 4

Crown-of-thorns sea star Acanthaster cf. solaris has tissue-characteristic microbiomes with potential roles in health and reproduction

© 2018 American Society for Microbiology. Outbreaks of coral-eating crown-of-thorns sea stars (CoTS; Acanthaster species complex) cause substantial coral loss; hence, there is considerable interest in developing prevention and control strategies. We characterized the microbiome of captive CoTS and assessed whether dysbiosis was evident in sea stars during a disease event. Most tissue types had a distinct microbiome. The exception was female gonads, in which the microbiomes were highly variable among individuals. Male gonads were dominated (> 97% of reads) by a single Mollicutes-related operational taxonomic unit (OTU). Detailed phylogenetic and microscopy analysis demonstrated the presence of a novel Spiroplasma-related bacterium in the spermatogenic layer. Body wall samples had high relative abundance (43 to 64% of reads) of spirochetes, likely corresponding to subcuticular symbionts reported from many echinoderms. Tube feet were characterized by Hyphomonadaceae (24 to 55% of reads). Pyloric cecal microbiomes had high alpha diversity, comprising many taxa commonly found in gastrointestinal systems. The order Oceanospirillales (genera Endozoicomonas and Kistimonas) was detected in all tissues. A microbiome shift occurred in diseased individuals although differences between tissue types were retained. The relative abundance of spirochetes was significantly reduced in diseased individuals. Kistimonas was present in all diseased individuals and significantly associated with diseased tube feet, but its role in disease causation is unknown. While Arcobacter was significantly associated with diseased tissues and Vibrionaceae increased in diversity, no single OTU was detected in all diseased individuals, suggesting opportunistic proliferation of these taxa in this case. This study shows that CoTS have tissuecharacteristic bacterial communities and identifies taxa that could play a role in reproduction and host health

Identification of potential serum peptide biomarkers of biliary tract cancer using MALDI MS profiling.

The aim of this discovery study was the identification of peptide serum biomarkers for detecting biliary tract cancer (BTC) using samples from healthy volunteers and benign cases of biliary disease as control groups. This work was based on the hypothesis that cancer-specific exopeptidase activities in serum can generate cancer-predictive peptide fragments from circulating proteins during coagulation

Yield of comparative genomic hybridization microarray in pediatric neurology practice

OBJECTIVE: The present study investigated the diagnostic yield of array comparative genomic hybridization (aCGH) in a large cohort of children with diverse neurologic disorders as seen in child neurology practice to test whether pathogenic copy number variants (CNVs) were more likely to be detected in specific neurologic phenotypes. METHODS: A retrospective cross-sectional analysis was performed on 555 children in whom a genetic etiology was suspected and who underwent whole-genome aCGH testing between 2006 and 2012. Neurologic phenotyping was performed using hospital medical records. An assessment of pathogenicity was made for each CNV, based on recent developments in the literature. RESULTS: Forty-seven patients were found to carry a pathogenic CNV, giving an overall diagnostic yield of 8.59%. Certain phenotypes predicted for the presence of a pathogenic CNV, including developmental delay (odds ratio [OR] 3.69 [1.30–10.51]), cortical visual impairment (OR 2.73 [1.18–6.28]), dysmorphism (OR 2.75 [1.38–5.50]), and microcephaly (OR 2.16 [1.01–4.61]). The combination of developmental delay/intellectual disability with dysmorphism and abnormal head circumference was also predictive for a pathogenic CNV (OR 2.86 [1.02–8.00]). For every additional clinical feature, there was an increased likelihood of detecting a pathogenic CNV (OR 1.18 [1.01–1.38]). CONCLUSIONS: the use of aCGH led to a pathogenic finding in 8.59% of patients. The results support the use of aCGH as a first tier investigation in children with diverse neurologic disorders, although whole-genome sequencing may replace aCGH as the detection method in the future. In particular, the yield was increased in children with developmental delay, dysmorphism, cortical visual impairment, and microcephaly

Identification of the factors associated with outcomes in a condition management programme

<p>Background: A requirement of the Government’s Pathways to Work (PtW) agenda was to introduce a Condition Management Programme (CMP). The aim of the present study was to identify the differences between those who engaged and made progress in this telephone-based biopsychosocial intervention, in terms of their health, and those who did not and to determine the client and practitioner characteristics and programme elements associated with success in a programme aimed at improving health.</p> <p>Methods: Data were obtained from the CMP electronic spreadsheets and clients paper-based case records. CMP standard practice was that questionnaires were administered during the pre- and post-assessment phases over the telephone. Each client’s record contains their socio-demographic data, their primary health condition, as well as the pre- and post-intervention scores of the health assessment tool administered. Univariate and multivariate statistical analysis was used to investigate the relationships between the database variables. Clients were included in the study if their records were available for analysis from July 2006 to December 2007.</p> <p> Results: On average there were 112 referrals per month, totalling 2016 referrals during the evaluation period. The majority (62.8%) of clients had a mental-health condition. Successful completion of the programme was 28.5% (575 “completers”; 144 “discharges”). Several factors, such as age, health condition, mode of contact, and practitioner characteristics, were significant determinants of participation and completion of the programme. The results showed that completion of the CMP was associated with a better mental-health status, by reducing the number of clients that were either anxious, depressed or both, before undertaking the programme, from 74% to 32.5%.</p> <p>Conclusions: Our findings showed that an individual's characteristics are associated with success in the programme, defined as completing the intervention and demonstrating an improved health status. This study provides some evidence that the systematic evaluation of such programmes and interventions could identify ways in which they could be improved.</p&gt

Managing change in the nursing handover from traditional to bedside handover – a case study from Mauritius

BACKGROUND: The shift handover forms an important part of the communication process that takes place twice within the nurses' working day in the gynaecological ward. This paper addresses the topic of implementing a new system of bedside handover, which puts patients central to the whole process of managing care and also addresses some of the shortcomings of the traditional handover system. METHODS: A force field analysis in terms of the driving forces had shown that there was dissatisfaction with the traditional method of handover which had led to an increase in the number of critical incidents and complaints from patients, relatives and doctors. The restraining forces identified were a fear of accountability, lack of confidence and that this change would lead to more work. A 3 – step planned change model consisting of unfreezing, moving and refreezing was used to guide us through the change process. Resistance to change was managed by creating a climate of open communication where stakeholders were allowed to voice opinions, share concerns, insights, and ideas thereby actively participating in decision making. RESULTS: An evaluation had shown that this process was successfully implemented to the satisfaction of patients, and staff in general. CONCLUSION: This successful change should encourage other nurses to become more proactive in identifying areas for change management in order to improve our health care system

Observed Reductions in Schistosoma mansoni Transmission from Large-Scale Administration of Praziquantel in Uganda: A Mathematical Modelling Study

To date schistosomiasis control programmes based on chemotherapy have largely aimed at controlling morbidity in treated individuals rather than at suppressing transmission. In this study, a mathematical modelling approach was used to estimate reductions in the rate of Schistosoma mansoni reinfection following annual mass drug administration (MDA) with praziquantel in Uganda over four years (2003-2006). In doing this we aim to elucidate the benefits of MDA in reducing community transmission.Age-structured models were fitted to a longitudinal cohort followed up across successive rounds of annual treatment for four years (Baseline: 2003, TREATMENT: 2004-2006; n = 1,764). Instead of modelling contamination, infection and immunity processes separately, these functions were combined in order to estimate a composite force of infection (FOI), i.e., the rate of parasite acquisition by hosts.MDA achieved substantial and statistically significant reductions in the FOI following one round of treatment in areas of low baseline infection intensity, and following two rounds in areas with high and medium intensities. In all areas, the FOI remained suppressed following a third round of treatment.This study represents one of the first attempts to monitor reductions in the FOI within a large-scale MDA schistosomiasis morbidity control programme in sub-Saharan Africa. The results indicate that the Schistosomiasis Control Initiative, as a model for other MDA programmes, is likely exerting a significant ancillary impact on reducing transmission within the community, and may provide health benefits to those who do not receive treatment. The results obtained will have implications for evaluating the cost-effectiveness of schistosomiasis control programmes and the design of monitoring and evaluation approaches in general

Interactions between Schistosoma haematobium group species and their Bulinus spp. intermediate hosts along the Niger River Valley

Background Urogenital schistosomiasis, caused by infection with Schistosoma haematobium, is endemic in Niger but complicated by the presence of Schistosoma bovis, Schistosoma curassoni and S. haematobium group hybrids along with various Bulinus snail intermediate host species. Establishing the schistosomes and snails involved in transmission aids disease surveillance whilst providing insights into snail-schistosome interactions/compatibilities and biology. Methods Infected Bulinus spp. were collected from 16 villages north and south of the Niamey region, Niger, between 2011 and 2015. From each Bulinus spp., 20–52 cercariae shed were analysed using microsatellite markers and a subset identified using the mitochondrial (mt) cox1 and nuclear ITS1 + 2 and 18S DNA regions. Infected Bulinus spp. were identified using both morphological and molecular analysis (partial mt cox1 region). Results A total of 87 infected Bulinus from 24 sites were found, 29 were molecularly confirmed as B. truncatus, three as B. forskalii and four as B. globosus. The remaining samples were morphologically identified as B. truncatus (n = 49) and B. forskalii (n = 2). The microsatellite analysis of 1124 cercariae revealed 186 cercarial multilocus genotypes (MLGs). Identical cercarial genotypes were frequently (60%) identified from the same snail (clonal populations from a single miracidia); however, several (40%) of the snails had cercariae of different genotypes (2–10 MLG’s) indicating multiple miracidial infections. Fifty-seven of the B. truncatus and all of the B. forskalii and B. globosus were shedding the Bovid schistosome S. bovis. The other B. truncatus were shedding the human schistosomes, S. haematobium (n = 6) and the S. haematobium group hybrids (n = 13). Two B. truncatus had co-infections with S. haematobium and S. haematobium group hybrids whilst no co-infections with S. bovis were observed. Conclusions This study has advanced our understanding of human and bovid schistosomiasis transmission in the Niger River Valley region. Human Schistosoma species/forms (S. haematobium and S. haematobium hybrids) were found transmitted only in five villages whereas those causing veterinary schistosomiasis (S. bovis), were found in most villages. Bulinus truncatus was most abundant, transmitting all Schistosoma species, while the less abundant B. forskalii and B. globosus, only transmitted S. bovis. Our data suggest that species-specific biological traits may exist in relation to co-infections, snail-schistosome compatibility and intramolluscan schistosome development

Clinical course, therapeutic responses and outcomes in relapsing MOG antibody-associated demyelination.

Abstract OBJECTIVE: We characterised the clinical course, treatment and outcomes in 59 patients with relapsing myelin oligodendrocyte glycoprotein (MOG) antibody-associated demyelination. METHODS: We evaluated clinical phenotypes, annualised relapse rates (ARR) prior and on immunotherapy and Expanded Disability Status Scale (EDSS), in 218 demyelinating episodes from 33 paediatric and 26 adult patients. RESULTS: The most common initial presentation in the cohort was optic neuritis (ON) in 54% (bilateral (BON) 32%, unilateral (UON) 22%), followed by acute disseminated encephalomyelitis (ADEM) (20%), which occurred exclusively in children. ON was the dominant phenotype (UON 35%, BON 19%) of all clinical episodes. 109/226 (48%) MRIs had no brain lesions. Patients were steroid responsive, but 70% of episodes treated with oral prednisone relapsed, particularly at doses <10\u2009mg daily or within 2 months of cessation. Immunotherapy, including maintenance prednisone (P=0.0004), intravenous immunoglobulin, rituximab and mycophenolate, all reduced median ARRs on-treatment. Treatment failure rates were lower in patients on maintenance steroids (5%) compared with non-steroidal maintenance immunotherapy (38%) (P=0.016). 58% of patients experienced residual disability (average follow-up 61 months, visual loss in 24%). Patients with ON were less likely to have sustained disability defined by a final EDSS of 652 (OR 0.15, P=0.032), while those who had any myelitis were more likely to have sustained residual deficits (OR 3.56, P=0.077). CONCLUSION: Relapsing MOG antibody-associated demyelination is strongly associated with ON across all age groups and ADEM in children. Patients are highly responsive to steroids, but vulnerable to relapse on steroid reduction and cessation

Patterns of Pacific decadal variability recorded by Indian Ocean corals

We investigate Pacific Decadal Oscillation (PDO) signals recorded by two bimonthly resolved coral δ18O series from La Réunion and Ifaty (West Madagascar), Indian Ocean from 1882 to 1993. To isolate the main PDO frequencies, we apply a band pass filter to the time series passing only periodicities from 16 to 28 years. We investigate the covariance patterns of the coral time series with sea surface temperature (SST) and sea level pressure (SLP) of the Indian and Pacific Oceans. In addition, the empirical orthogonal functions of the filtered SST and SLP fields (single and coupled) are related to the filtered coral times series. The covariance maps show the typical PDO pattern for SST and SLP, confirming the coupling between the Indian and Pacific Oceans. Both corals show the strongest signal in boreal summer. The La Réunion (Ifaty) coral better records SST (SLP) than SLP (SST) pattern variability. We suggest that the filtered La Réunion coral δ18O represents δ18O of seawater that varies with the South Equatorial Current, which, in turn, is linked with the SST PDO. The filtered Ifaty coral δ18O represents SST and is remotely linked with the SLP PDO variability. A combined coral record of the Ifaty and La Réunion boreal summer δ18O series explains about 64% of the variance of the coupled SST/SLP PDO time series