Citrullinated human and murine MOG35-55 display distinct biophysical and biochemical behavior.

The peptide spanning residues 35 to 55 of the protein myelin oligodendrocyte glycoprotein (MOG) has been studied extensively in its role as a key autoantigen in the neuroinflammatory autoimmune disease multiple sclerosis. Rodents and nonhuman primate species immunized with this peptide develop a neuroinflammatory condition called experimental autoimmune encephalomyelitis, often used as a model for multiple sclerosis. Over the last decade, the role of citrullination of this antigen in the disease onset and progression has come under increased scrutiny. We recently reported on the ability of these citrullinated MOG35-55 peptides to aggregate in an amyloid-like fashion, suggesting a new potential pathogenic mechanism underlying this disease. The immunodominant region of MOG is highly conserved between species, with the only difference between the murine and human protein, a polymorphism on position 42, which is serine in mice and proline for humans. Here, we show that the biophysical and biochemical behavior we previously observed for citrullinated murine MOG35-55 is fundamentally different for human and mouse MOG35-55. The citrullinated human peptides do not show amyloid-like behavior under the conditions where the murine peptides do. Moreover, we tested the ability of these peptides to stimulate lymphocytes derived from MOG immunized marmoset monkeys. While the citrullinated murine peptides did not produce a proliferative response, one of the citrullinated human peptides did. We postulate that this unexpected difference is caused by disparate antigen processing. Taken together, our results suggest that further study on the role of citrullination in MOG-induced experimental autoimmune encephalomyelitis is necessary.

Pessary or surgery for a symptomatic pelvic organ prolapse: the PEOPLE study, a multicentre prospective cohort study.

OBJECTIVE: To compare the 24-month efficacy of pessary or surgery as the primary treatment for symptomatic pelvic organ prolapse (POP). DESIGN: Multicentre prospective comparative cohort study. SETTING: Twenty-two Dutch hospitals. POPULATION: Women referred with symptomatic POP of stage ≥2 and moderate-to-severe POP symptoms. METHODS: The primary outcome was subjective improvement at the 24-month follow-up according to the Patient Global Impression of Improvement (PGI-I) scale. Secondary outcomes included improvement in prolapse-related symptoms measured with the Pelvic Floor Distress Inventory (PFDI-20), improvement in subjective severeness of symptoms according to the Patient Global Impression of Severity (PGI-S) scale and crossover between therapies. The primary safety outcome was the occurrence of adverse events. MAIN OUTCOME MEASURE: PGI-I at 24 months. RESULTS: We included 539 women, with 335 women (62.2%) in the pessary arm and 204 women (37.8%) in the surgery arm. After 24 months, subjective improvement was reported by 134 women (83.8%) in the surgery group compared with 180 women (74.4%) in the pessary group (risk difference 9.4%, 95% CI 1.4-17.3%, P < 0.01). Seventy-nine women (23.6%) switched from pessary to surgery and 22 women (10.8%) in the surgery group underwent additional treatment. Both groups showed a significant reduction in bothersome POP symptoms (P ≤ 0.01) and a reduction in the perceived severity of symptoms (P ≤ 0.001) compared with the baseline. CONCLUSIONS: Significantly more women in the surgery group reported a subjective improvement after 24 months. Both therapies, however, showed a clinically significant improvement of prolapse symptoms. TWEETABLE ABSTRACT: Pessary treatment and vaginal surgery are both efficacious in reducing the presence and severity of prolapse symptoms, although the chance of significant improvement is higher following surgery.

Sound localization with bilateral bone conduction devices.

PURPOSE: To investigate sound localization in patients bilaterally fitted with bone conduction devices (BCDs). Additionally, clinically applicable methods to improve localization accuracy were explored. METHODS: Fifteen adults with bilaterally fitted percutaneous BCDs were included. At baseline, sound localization, (un)aided pure-tone thresholds, device use, speech, spatial and qualities of hearing scale (SSQ) and York hearing-related quality of life (YHRQL) questionnaire were measured. Settings to optimize sound localizing were added to the BCDs. At 1 month, sound localization was assessed again and localization was practiced with a series of sounds with visual feedback. At 3 months¸ localization performance, device use and questionnaire scores were determined again. RESULTS: At baseline, one patient with congenital hearing loss demonstrated near excellent localization performance and four other patients (three with congenital hearing loss) localized sounds (quite) accurately. Seven patients with acquired hearing loss were able to lateralize sounds, i.e. identify whether sounds were coming from the left or right side, but could not localize sounds accurately. Three patients (one with congenital hearing loss) could not even lateralize sounds correctly. SSQ scores were significantly higher at 3 months. Localization performance, device use and YHRQL scores were not significantly different between visits. CONCLUSION: In this study, the majority of experienced bilateral BCD users could lateralize sounds and one third was able to localize sounds (quite) accurately. The localization performance was robust and stable over time. Although SSQ scores were increased at the last visit, optimizing device settings and a short practice session did not improve sound localization.

Reducing Seroma Formation and Its Sequelae After Mastectomy by Closure of the Dead Space: A Multi-center, Double-Blind Randomized Controlled Trial (SAM-Trial).

BACKGROUND: Seroma is a common complication after mastectomy, with an incidence of 3% to 85%. Seroma is associated with pain, delayed wound healing, and additional outpatient clinic visits, leading potentially to repeated seroma aspiration or even surgical interventions. This study aimed to assess the effect of flap fixation using sutures or tissue glue in preventing seroma formation and its sequelae. METHODS: Between June 2014 and July 2018, 339 patients with an indication for mastectomy or modified radical mastectomy were enrolled in this randomized controlled trial in the Netherlands. Patients were randomly allocated to one of the three following arms: conventional wound closure (CON, n = 115), flap fixation using sutures (FFS, n = 111) or flap fixation using tissue glue (FFG, n = 113). The primary outcome was the need for seroma aspiration. The secondary outcomes were additional outpatient department visits, surgical-site infection, shoulder function and mobility, cosmesis, skin-dimpling, and postoperative pain scores. RESULTS: Flap fixation after mastectomy leads to fewer seroma aspirations than conventional wound closure (CON 17.5% vs FFS 7.3% vs FFG 10.8%; p = 0.057), with a significant difference between flap fixation with sutures and conventional wound closure (odds ratio [OR], 0.37; 95% confidence interval [CI], 0.16-0.89; p = 0.025). Flap fixation has no significant negative effect on surgical-site infections, shoulder function and mobility, cosmesis, skin-dimpling, or postoperative pain. CONCLUSION: Flap fixation using sutures leads to a significant reduction in aspirations of post-mastectomy seromas. The authors strongly advise surgeons to use sutures for flap fixation in patients undergoing mastectomy. (ClinicalTrials.gov no. NCT03305757). PREREGISTRATION: The trial was registered after enrollment of the first participant. However, no specific explanation exists for this except that through the years more importance has been given to central trial registration. Our research team can ensure that after enrollment of the first participant, no changes were made to the trial, analysis plan, and/or study design.

[Treatment of tracheo(broncho)malacia in children]. / Comment je traite la trachéo(broncho)malacie de l'enfant ?

Tracheomalacia (TM) is characterized by tracheal collapse due to an intrinsic anomaly resulting in a lack of rigidity of the cartilaginous rings and/or the posterior membrane during expiration, coughing or crying. It may also be secondary to external compression or acquired during endobronchial diseases. TM is commonly associated with other syndromes or airway abnormalities. Tracheomalacia can be localized or diffused and if the main bronchi are involved, the term of tracheobronchomalacia (TBM) is used. The most common symptoms include expiratory stridor, barking cough and recurrent respiratory tract infections. If tracheal weakness is severe, Acute Life Threating Events (ALTE) or Brief Resolved Unexplained Event (BRUE) can occur. While mild forms usually do not require any treatment, severe TBM may require medical and/or surgical management. Amongst several possible treatments, including tracheostomy, noninvasive ventilation and airway stenting, the pexy surgical approach (posterior, anterior tracheopexy or aortopexy) is currently the favoured option.

La trachéomalacie (TM) est caractérisée par un collapsus trachéal plus ou moins important durant l'expiration, lors des efforts de toux ou des pleurs. Elle peut être due à une anomalie intrinsèque, par manque de rigidité des anneaux cartilagineux et/ou de la membrane postérieure. Elle peut aussi avoir une origine extrinsèque, soit secondaire à une compression externe, soit acquise dans le cadre de pathologies endo-bronchiques. Elle peut enfin être associée à certains syndromes ou malformations des voies respiratoires. La TM peut être localisée ou généralisée, et si les bronches principales sont atteintes, on parlera de trachéobronchomalacie (TBM). Les symptômes les plus courants sont : un stridor expiratoire, une toux aboyante, et des infections respiratoires récurrentes. Dans les cas les plus sévères, des événements menaçant la vie de l'enfant (Acute Life-Threatening Event «ALTE¼ ou Brief Resolved Unexplained Event «BRUE¼) peuvent survenir. Alors que les formes légères ne requièrent généralement pas de traitement, la TBM sévère peut nécessiter une prise en charge médicale et/ou chirurgicale. Parmi les divers choix thérapeutiques, incluant notamment la trachéostomie, la ventilation non invasive et les stents trachéaux, l'approche chirurgicale par pexie (aortopexie, trachéopexie postérieure ou antérieure) est actuellement l'option favorite.

Systematic Review on Late Cochlear Implantation in Early-Deafened Adults and Adolescents: Clinical Effectiveness.

OBJECTIVES: Cochlear implantation in early-deafened patients, implanted as adolescents or adults, is not always advised due to poor expected outcomes. In order to judge whether such reluctance is justified, the current systematic review aimed to gather all available evidence on postoperative outcomes obtained by early-deafened patients using a state-of-the art cochlear implant (CI). DESIGN: Five electronic databases (PubMed, Embase, the Cochrane library, CINAHL, and PsycInfo) were systematically searched for studies in English, French, German, or Dutch, published between 2000 and September 2017. Studies that reported pre- and postoperative outcomes on any measure of speech or sound perception, audiovisual or subjective benefit (quality of life) were included. Study quality was assessed with the Institute of Health Economics quality appraisal tool for case series studies. RESULTS: The systematic search and subsequent full-text evaluation identified 38 studies meeting the inclusion criteria. Only a limited number of studies were judged to be of high quality according to the Institute of Health Economics tool, with lack of (clear) presentation of relevant study information being a recurring problem. Twenty-five studies presented viable outcomes on open-set speech understanding in quiet: mean postoperative scores obtained with CI remained below 50% for the vast majority of studies; significant postoperative improvements were found in 16 studies, although this number might have been higher if appropriate statistical testing had been performed in all studies. Eight studies observed increased audiovisual performance after implantation, which was statistically significant in six studies. A validated measure of hearing-related quality of life was used in only 5 of the 16 studies assessing subjective outcomes, showing significant postoperative improvements for most questionnaire domains. The relation between auditory and subjective outcomes was assessed in two studies, with contradictory results. CONCLUSIONS: The current review showed that late cochlear implantation in early-deafened subjects resulted in significantly improved open-set speech perception, audiovisual speech perception, and (hearing-related) quality of life in the majority of the studies involved. Nonetheless, more and especially higher-quality research is needed in order to gain a more detailed understanding of the outcomes of cochlear implantation in this population.

Systematic Review on Late Cochlear Implantation in Early-Deafened Adults and Adolescents: Predictors of Performance.

OBJECTIVES: Early-deafened, late-implanted adolescents and adults constitute a unique group of cochlear implant (CI) users, showing a large variability in outcomes. The current systematic review aimed to determine which preimplantation factors are relevant in predicting postoperative outcomes in this patient group. DESIGN: A systematic search for studies published between 2000 and September 2017 was performed in five electronic databases (PubMed, Embase, the Cochrane library, CINAHL, and PsycInfo). Prognostic studies that assessed the relation between patient-related factors and CI outcomes in early-deafened but late-implanted adolescent and adult CI users were included. Study quality was assessed with the Quality In Prognosis Studies (QUIPS) tool. RESULTS: The systematic search and subsequent full-text evaluation identified 13 studies that had a clear prognostic study goal. Eight out of these 13 studies had a high risk of bias for at least one of the five QUIPS domains. Analysis of the outcomes identified that communication mode (in childhood), preoperative speech intelligibility, and preoperative speech recognition scores were significantly related to speech perception outcomes for this group of CI users. A number of additional factors considered worth for further investigation were also identified. CONCLUSIONS: The analysis of the studies assessing the effect of a number of patient-related factors on outcome with CI in early-deafened adolescents and adults identified three potential prognostic factors and a number of additional factors to be incorporated in future research. More high-quality prognosis studies in the investigated patient population are still needed.

Elevated viscosities in a simulated moving bed for γ-aminobutyric acid recovery.

Process streams of agro-food industries are often large and viscous. In order to fractionate such a stream the viscosity can be reduced by either a high temperature or dilution, the former is not an option in case of temperature sensitive components. Such streams are diluted prior to chromatographic fractionation, resulting in even larger volumes and high energy costs for sub-sequential water removal. The influence of feed viscosity on the performance of simulated moving bed chromatography has been investigated in a case study of the recovery of a γ-aminobutyric acid rich fraction from tomato serum. This work addresses the chromatographic system design, evaluates results from a pilot scale operation, and uses these to calculate the productivity and water use at elevated feed concentration. At the two higher feed viscosities (2.5 and 4 mPa·s) water use is lower and productivity higher, compared to the lowest feed viscosity (1 mPa·s). The behavior of the sugars for different feed viscosities can be described well by the model using the ratio of feed to eluent as dilution factor. The behavior of γ-aminobutyric acid is highly concentration dependent and the recovery could not be accurately predicted.

SAFE: an eHealth intervention for women experiencing intimate partner violence - study protocol for a randomized controlled trial, process evaluation and open feasibility study.

BACKGROUND: Intimate partner violence (IPV) affects almost one in three women worldwide. However, disclosing violence or seeking help is difficult for affected women. eHealth may represent an effective alternative to the standard support offers, which often require face-to-face interaction, because of easy accessibility and possibility of anonymous usage. In the Netherlands we are developing SAFE, an eHealth intervention for female victims of IPV, which will be evaluated in a randomized controlled trial and a process evaluation, followed by an open feasibility study to assess real-world user data. METHODS/DESIGN: The randomized controlled trial is a two-arm parallel design comparing an intervention arm and a control group. The groups both have access to eHealth but differ in the offer of interactive features compared to static information. Both groups complete questionnaires at three or four time points (baseline, three months, six months, 12 months) with self-efficacy at 6 months as the primary outcome, measured with the General Self-Efficacy (GSE) scale. The process evaluation consists of quantitative data (from the website and from web evaluation questionnaires) and qualitative data (from interviews) on how the website was used and the users' experiences. DISCUSSION: eHealth has the potential to reach a large number of women who experience IPV. The internet-based design can lower access barriers and encourage help-seeking behavior ultimately reducing the lag time between subjective awareness and protective action. TRIAL REGISTRATION: Trial registered on 15 August 2017 at the Netherlands Trial Register NL7108 (NTR7313).

Field distribution patterns of pests are asymmetrically affected by the presence of other herbivores.

Because plant phenotypes can change in response to attacks by herbivores in highly variable ways, the distribution of herbivores depends on the occurrence of other herbivore species on the same plant. We carried out a field study to evaluate the co-occurrence of three coconut pests, the mites Aceria guerreronis (Acari: Eriophyidae), Steneotarsonemus concavuscutum (Acari: Tarsonemidae) and the moth Atheloca bondari (Lepidoptera: Pyralidae). The eriophyid mite Ac. guerreronis is the most important coconut pest around the world, whereas S. concavuscutum and At. bondari are economically important only in some areas along the Brazilian coast. A previous study suggested that the necrosis caused by Ac. guerreronis facilitates the infestation of At. bondari larvae. Because all three species infest the area under the perianths on coconuts and S. concavuscutum also causes necrosis that could facilitate At. bondari, we evaluated the co-occurrence of all three species. We found that the occurrence of At. bondari was positively associated with Ac. guerreronis, but negatively associated with S. concavuscutum. In addition, the two mite species showed negative co-occurrence. Atheloca bondari was found on nuts of all ages, but more on nuts that had fallen than on those on the trees, suggesting that nuts infested by At. bondari tend to fall more frequently. We discuss the status of At. bondari as a pest and discuss experiments to test the causes of these co-occurrence patterns.

Currently available and experimental dyes for intraoperative near-infrared fluorescence imaging of the ureters: a systematic review.

BACKGROUND: Iatrogenic ureteral injury (IUI) following abdominal surgery has a relatively low incidence, but is associated with high risks of morbidity and mortality. Conventional assessment of IUI includes visual inspection and palpation. This is especially challenging during laparoscopic procedures and has translated into an increased risk of IUI. The use of near-infrared fluorescent (NIRF) imaging is currently being considered as a novel method to identify the ureters intraoperatively. The aim of this review is to describe the currently available and experimental dyes for ureter visualization and to evaluate their feasibility of using them and their effectiveness. METHODS: This article adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standard for systematic reviews. A systematic literature search was performed in the PubMed database. All included articles were screened for eligibility by two authors. Three clinical trial databases were consulted to identify ongoing or completed unpublished trials. Risk of bias was assessed for all articles. RESULTS: The search yielded 20 articles on ureter visualization. Two clinically available dyes, indocyanine green (ICG) and methylene blue (MB), and eight experimental dyes were described and assessed for their feasibility to identify the ureter. Two ongoing clinical trials on CW800-BK and one trial on ZW800-1 for ureter visualization were identified. CONCLUSIONS: Currently available dyes, ICG and MB, are safe, but suboptimal for ureter visualization based on the route of administration and optical properties, respectively. Currently, MB has potential to be routinely used for ureter visualization in most patients, but (cRGD-)ZW800-1 holds potential for this role in the future, owing to its exclusive renal clearance and the near absence of background. To assess the benefit of NIRF imaging for reducing the incidence of IUI, larger patient cohorts need to be examined.

Inhibition of Experimental Tinnitus With High Frequency Stimulation of the Rat Medial Geniculate Body.

BACKGROUND: Neuromodulation is a promising treatment modality for tinnitus, especially in chronic and severe cases. The auditory thalamus plays a key role in the pathophysiology of tinnitus, as it integrates and processes auditory and limbic information. OBJECTIVE: The effect of high frequency stimulation and low frequency stimulation of the medial geniculate bodies on tinnitus in a noise-induced tinnitus rat model is assessed. MATERIALS AND METHODS: Presence of tinnitus was verified using the gap-induced prepulse inhibition of the acoustic startle response paradigm. Hearing thresholds were determined before and after noise trauma with auditory brainstem responses. Anxiety-related side-effects were evaluated in the elevated zero maze and open field. RESULTS: Results show tinnitus development after noise exposure and preserved hearing thresholds of the ear that was protected from noise trauma. We found that high frequency stimulation of the medial geniculate bodies suppressed tinnitus. This effect maintained directly after stimulation when the stimulator was turned off. Low frequency stimulation did not have any effects on the gap:no-gap ratio of the acoustic startle response. CONCLUSION: High frequency stimulation of the MGB has a direct and residual suppressing effect on tinnitus in this animal model. Low frequency stimulation of the MGB did not inhibit tinnitus.

Effect of pre-treatment on in vitro gastric digestion of quinoa protein (Chenopodium quinoa Willd.) obtained by wet and dry fractionation.

Quinoa protein was isolated from quinoa seeds using wet fractionation that resulted in a protein isolate (QPI) with a high protein purity of 87.1% (w/dw) and a protein yield of around 54%, and a dry fractionation method delivered a quinoa protein concentrate (QPC) with a purity of 27.8% (w/dw) and yield of around 47%. The dry fractionation process only involves milling and sieving and keeps the protein in its natural, native state. The aim was to study the in vitro gastric digestibility of both protein. Attention was paid to thermal pre-treatment of QPI and QPC. QPC showed significantly higher (p < .05) digestibility than QPI samples. The results were interpreted with a simple double exponential model. The fraction of easily digested protein in QPC is higher than for QPI. The better digestibility of the QPC was explained by the prevention of the formation of large aggregates during pre-heating of the protein.

Gender-specific differences in cannibalism between a laboratory strain and a field strain of a predatory mite.

Many phytoseiid species, including Phytoseiulus persimilis, are known to engage in cannibalism when food is scarce and when there is no possibility to disperse. In nature adult females of P. persimilis are known to disperse when prey is locally depleted. Males, in contrast, are expected to stay and wait for potential mates to mature. During this phase, males can obtain food by cannibalizing. Therefore, we hypothesize that male P. persimilis exhibit a higher tendency to cannibalize than females. Because rearing conditions in the laboratory usually prevent dispersal, prolonged culturing may also affect cannibalistic behavior. We hypothesize that this should especially affect cannibalism by females, because they consume far more food. We tested these hypotheses by comparing males and females from two strains, one of which had been in culture for over 20 years, whereas the other was recently collected from the field. It is known that this predator can discriminate between kin and non-kin and prefers cannibalizing the latter, hence to construct lines with high relatedness we created isofemale lines of these two original strains. We subsequently tested to what extent the adult females and males of the original strains and the isofemale lines cannibalized conspecific larvae from the same strain/line in a closed system. Relatedness with the victims did not affect cannibalistic behavior, but males engaged more often in cannibalism than females, and females of the laboratory strain engaged more in cannibalism than those of the field strain, both in agreement with our ideas. We hypothesize that the difference in cannibalism between the two genders will increase when they have the alternative to disperse.

Towards better dose individualisation: metabolic phenotyping to predict cabazitaxel pharmacokinetics in men with prostate cancer.

BACKGROUND: Cabazitaxel is approved for treatment of castration-resistant metastatic prostate cancer. The current dosing strategy of cabazitaxel is based on body surface area (BSA). Body surface area is known as a poor predictor for total systemic exposure to drugs, since it does not take into account variability in activity of metabolising enzymes, necessary for clearance of drugs. As exposure to cabazitaxel is related to treatment response, it is essential to develop a better individualised dosing strategy. METHODS: Ten patients with metastatic castration-resistant prostate cancer, who received cabazitaxel dosed on BSA as a part of routine palliative care, were enrolled in this study. Midazolam was administered as phenotyping probe for cytochrome P450 isoenzyme 3A (CYP3A). The relationship between midazolam and cabazitaxel clearance was investigated using non-linear mixed effects modelling. RESULTS: The clearance of Midazolam highly correlated with cabazitaxel clearance (R=0.74). Midazolam clearance significantly (P<0.004) explained the majority (∼60%) of the inter-individual variability in cabazitaxel clearance in the studied population. CONCLUSIONS: Metabolic phenotyping of CYP3A using midazolam is a promising strategy to individualise cabazitaxel dosing. Before clinical application, a randomised study is warranted.

Predator performance is impaired by the presence of a second prey species.

The simultaneous infestation of a plant by several species of herbivores may affect the attractiveness of plants to the natural enemies of one of the herbivores. We studied the effect of coconut fruits infested by the pests Aceria guerreronis and Steneotarsonemus concavuscutum, which are generally found together under the coconut perianth. The predatory mite Neoseiulus baraki produced lower numbers of offspring on fruits infested with S. concavuscutum and on fruits infested with both prey than on fruits with A. guerreronis only. The predators were attracted by odours emanating from coconuts with A. guerreronis, but not by odours from coconuts with S. concavuscutum, even when A. guerreronis were present on the same fruit. Fewer N. baraki were recaptured on fruits with both prey or with S. concavuscutum than on fruits with only A. guerreronis. Furthermore, the quality of A. guerreronis from singly and multiply infested coconuts as food for N. baraki did not differ. Concluding, our results suggest that N. baraki does not perform well when S. concavuscutum is present on the coconuts, and the control of A. guerreronis by N. baraki may be negatively affected by the presence of S. concavuscutum.

Fitting prelingually deafened adult cochlear implant users based on electrode discrimination performance.

OBJECTIVE: This study investigated the hypotheses that (1) prelingually deafened CI users do not have perfect electrode discrimination ability and (2) the deactivation of non-discriminable electrodes can improve auditory performance. DESIGN: Electrode discrimination difference limens were determined for all electrodes of the array. The subjects' basic map was subsequently compared to an experimental map, which contained only discriminable electrodes, with respect to speech understanding in quiet and in noise, listening effort, spectral ripple discrimination and subjective appreciation. STUDY SAMPLE: Subjects were six prelingually deafened, late implanted adults using the Nucleus cochlear implant. RESULTS: Electrode discrimination difference limens across all subjects and electrodes ranged from 0.5 to 7.125, with significantly larger limens for basal electrodes. No significant differences were found between the basic map and the experimental map on auditory tests. Subjective appreciation was found to be significantly poorer for the experimental map. CONCLUSIONS: Prelingually deafened CI users were unable to discriminate between all adjacent electrodes. There was no difference in auditory performance between the basic and experimental map. Potential factors contributing to the absence of improvement with the experimental map include the reduced number of maxima, incomplete adaptation to the new frequency allocation, and the mainly basal location of deactivated electrodes.

Maternal prenatal depression is associated with decreased placental expression of the imprinted gene PEG3.

BACKGROUND: Maternal prenatal stress during pregnancy is associated with fetal growth restriction and adverse neurodevelopmental outcomes, which may be mediated by impaired placental function. Imprinted genes control fetal growth, placental development, adult behaviour (including maternal behaviour) and placental lactogen production. This study examined whether maternal prenatal depression was associated with aberrant placental expression of the imprinted genes paternally expressed gene 3 (PEG3), paternally expressed gene 10 (PEG10), pleckstrin homology-like domain family a member 2 (PHLDA2) and cyclin-dependent kinase inhibitor 1C (CDKN1C), and resulting impaired placental human placental lactogen (hPL) expression. METHOD: A diagnosis of depression during pregnancy was recorded from Manchester cohort participants' medical notes (n = 75). Queen Charlotte's (n = 40) and My Baby and Me study (MBAM) (n = 81) cohort participants completed the Edinburgh Postnatal Depression Scale self-rating psychometric questionnaire. Villous trophoblast tissue samples were analysed for gene expression. RESULTS: In a pilot study, diagnosed depression during pregnancy was associated with a significant reduction in placental PEG3 expression (41%, p = 0.02). In two further independent cohorts, the Queen Charlotte's and MBAM cohorts, placental PEG3 expression was also inversely associated with maternal depression scores, an association that was significant in male but not female placentas. Finally, hPL expression was significantly decreased in women with clinically diagnosed depression (44%, p < 0.05) and in those with high depression scores (31% and 21%, respectively). CONCLUSIONS: This study provides the first evidence that maternal prenatal depression is associated with changes in the placental expression of PEG3, co-incident with decreased expression of hPL. This aberrant placental gene expression could provide a possible mechanistic explanation for the co-occurrence of maternal depression, fetal growth restriction, impaired maternal behaviour and poorer offspring outcomes.

The state of the art of twinning, a concept analysis of twinning in healthcare.

BACKGROUND: Inequities in health have garnered international attention and are now addressed in Sustainable Development Goal 3 (SDG3), which seeks to 'promote well-being for all'. To attain this goal globally requires innovative approaches, one of which is twinning. According to the International Confederation of Midwives, twinning focusses on empowering professionals, who can subsequently be change-agents for their communities. However, twinning in healthcare is relatively new and because the definition and understanding of twinning lacks clarity, rigorous monitoring and evaluation are rare. A clear definition of twinning is essential for the development of a scientific base for this promising form of collaboration. METHOD: We conducted a Concept Analysis (CA) of twinning in healthcare using Morse's method. A qualitative study of the broad literature was performed, including scientific papers, manuals, project reports, and websites. We identified relevant papers through a systematic search using scientific databases, backtracking of references, and experts in the field. RESULTS: We found nineteen papers on twinning in healthcare. This included twelve peer reviewed research papers, four manuals on twinning, two project reports, and one website. Seven of these papers offered no definition of twinning. In the other twelve papers definitions varied. Our CA of the literature resulted in four main attributes of twinning in healthcare. First, and most frequently mentioned, was reciprocity. The other three attributes were that twinning: 2) entails the building of personal relationships, 3) is dynamic process, 4) is between two named organisations across different cultures. The literature also indicated that these four attributes, and especially reciprocity, can have an empowering effect on healthcare professionals. CONCLUSIONS: Based on these four attributes we developed the following operational definition: Twinning is a cross-cultural, reciprocal process where two groups of people work together to achieve joint goals. A greater understanding and a mature definition of twinning results in clear expectations for participants and thus more effective twinning. This can be the starting point for new collaborations and for further international studies on the effect of twinning in healthcare.

Negative pressure wound therapy versus standard wound care on quality of life: a systematic review.

OBJECTIVE: Negative pressure wound therapy (NPWT) is a widely accepted treatment modality for open or infected wounds. Premature ending of NPWT occasionally occurs due to negative effects on the quality of life (QoL), however, the actual impact on QoL is unknown. The aim of this review is to analyse the effect of NPWT versus standard wound care (SWC) on QoL when used for the treatment of open or infected wounds. METHOD: A systematic literature search in a range of databases (PubMed, CINAHL, Medline, Web of Science, Science Direct Freedom Collection, SwetsWise, PSYCArticles and Infrotrac Custom Journals) using the following search terms; 'standard wound care', 'wound dressing', 'dressing', 'treatment', OR 'negative pressure wound therapy [MESH]', OR 'vacuum assisted closure' AND 'quality of life [MESH]', 'patient-satisfaction', OR 'experiences' was performed. Methodological quality was assessed using the methodological index for non-randomised studies (MINORS) checklist. RESULTS: There were 42 studies identified, five matched the inclusion criteria: two randomised clinical trials (RCTs), one clinical comparative study, one exploratory prospective cohort study and one quasi experimental pilot study. Median MINORS-score was 75% (58%-96%). There were seven different questionnaires used to measure QoL or a subsidiary outcome. QoL in the NPWT group was lower in the first week, though no difference in QoL was observed thereafter. CONCLUSION: This systematic review observed that QoL improved at the end of therapy independent of which therapy was used. NPWT led to a lower QoL during the first week of treatment, possible due to aniexty, after which a similar or better QoL was reported when compared with SWC. It could be suggested that NPWT might be associated with increased anxiety. DECLARATION OF INTEREST: All authors of this publication have received no financial support or have personal interests conflicting with the objectivity of this manuscript.