A theory for context-dependent effects of mammalian trampling on ecosystem nitrogen cycling.

Large mammalian herbivores substantially impact ecosystem functioning. As their populations are dramatically altered globally, disentangling their consumptive and non-consumptive effects is critical to advance mechanistic understanding and improve prediction of effects over ecosystem and Earth-system spatial extents. Mathematical models have played an important role in clarifying potential mechanisms of herbivore zoogeochemistry, based mostly on their consumptive effects as primary consumers and recyclers of organic and inorganic matter via defecation and urination. Trampling is a ubiquitous effect among walking vertebrates, but the consequences and potential mechanisms of trampling in diverse environments remain poorly understood. We derive a novel mathematical model of large mammalian herbivore effects on ecosystem nitrogen cycling, focusing on how trampling and environmental context impact soil processes. We model herbivore trampling with a linear positive or negative additive effect on soil-mediated nitrogen cycling processes. Combining analytical and numerical analyses, we find trampling by large mammalian herbivores is likely to decrease nitrogen mineralisation rate across diverse environments, such as temperate grassland and boreal forest. These effects are mediated by multiple potential mechanisms, including trampling-induced changes to detritivore biomass and functioning (e.g. rate of organic matter consumption). We also uncover scenarios where trampling can increase nitrogen mineralisation rate, contingent on the environment-specific relative sensitivity of detritivore mineral-nitrogen release and detritivore mortality, to trampling. In contrast to some consumptive mechanisms, our results suggest the pace of soil nitrogen cycling prior to trampling has little influence over the direction of the trampling net effect on nitrogen mineralisation, but that net effects may be greater in slow-cycling systems (e.g. boreal forests) than in fast-cycling systems (e.g. grasslands). Our model clarifies the potential consequences of previously overlooked mechanisms of zoogeochemistry that are common to all terrestrial biomes. Our results provide empirically testable predictions to guide future progress in empirical and theoretical studies of herbivore effects in diverse environmental contexts. Resolving ecological contingencies around animal consumptive and non-consumptive effects will improve whole-ecosystem management efforts such as restoration and rewilding.

Safety and tolerance of combination of monoamine oxidase inhibitors and direct dopamine agonists in adults and older adults with highly resistant depression.

INTRODUCTION: Dopamine (DA) is likely to be involved in some depressive dimensions, such as anhedonia and amotivation, which account for a part of treatment-resistant forms. Monoamine oxidase inhibitors (MAOI) and direct D2 and D3 receptors agonists (D2/3r-dAG) are known to help, but we lack safety data about their combined usage. We report on safety and tolerance of the MAOI+D2r-dAG combination in a clinical series. METHOD: All patients referred to our recourse center for depression between 2013 and 2021 were screened to select those who did receive the combo. Data were extracted from clinical files. RESULTS: Sixteen patients of 60±17 years of age (8 women, 7 with age>65years, all suffered from treatment resistant depression, 7 with bipolar disorder) received the combo. There were no life-threatening adverse effects (AE). However, AE were reported by 14 patients (88%) most of which were mild and consisted of insomnia, nausea, nervousness, confusion, impulse control disorder and/or "sleep attacks". One patient presented a serious AE requiring a short hospitalization for confusion. Intolerance led to failure to introduce treatment in two patients (13%). The retrospective non-interventional design, the variety of molecules, and the modest sample size limited the scope of these results. CONCLUSION: There was no life-threatening safety issue in combining MAOI and D2/3r-dAG, especially regarding cardiovascular side effects. The systematic screening of AE might account for their frequency, but these precluded the treatment in only two patients. Comparative studies are needed to assess the efficacy of this new combination.

Towards a mechanistic understanding of animal-ecosystem interactions.

Research Highlight: Ferraro, K. M., Welker, L., Ward, E. B., Schmitz, O. J., & Bradford, M. A. (2023). Plant mycorrhizal associations mediate the zoogeochemical effects of calving subsidies by a forest ungulate. Journal of Animal Ecology, https://doi.org/10.1111/1365-2656.14002. Animals play large roles in ecosystem elemental cycling but predicting effects in diverse contexts remains a substantial challenge. Fundamental to progress is (1) identifying mechanisms by which animals impact nutrient distribution and cycling, and (2) disentangling how environmental context mediates the operation of alternative mechanisms. In an elegant field experiment, Ferraro et al. (2023) provide the first detailed exploration of the impact of nutrient inputs from mammalian parturition on soil functioning and the stoichiometry of plant tissues. The authors find that nitrogen from experimental additions of ungulate parturition material (natal fluids) is rapidly incorporated into microsite soil organic pools and plant tissues. They also find that soil processes (soil microbial biomass, rates of carbon mineralization, nitrogen mineralization and nitrification) and the nitrogen content of plant tissues above- and belowground are increased by addition of parturition material. Notably, the authors identify that increases in some soil processes and plant tissue nitrogen are weaker in microsites dominated by ericoid mycorrhizal plants than those dominated by ectomycorrhizal plants. These findings demonstrate that parturition depositions, a ubiquitous but overlooked mechanism of mammalian impacts on ecosystems, impact ecosystem processes and plant tissue stoichiometry. Furthermore, plant-fungal associations are a predictive axis of context dependency mediating zoogeochemical effects at fine scales. Ferraro et al.'s (2023) novel approach simultaneously advances mechanistic understanding of animal-ecosystem interactions at fine scales and facilitates prediction of ungulate effects on nutrient availability at landscape extents.

[Anticholinergic scales: Use in psychiatry and update of the anticholinergic impregnation scale]. / Les échelles anticholinergiques : usage en psychiatrie et mise à jour de l'échelle d'imprégnation anticholinergique.

Anticholinergic properties are well known to prescribers, notably in mental health, as a therapeutic strategy for i.e. extrapyramidal syndrome but also as a source of numerous adverse side effects. Herein, we propose a narrative literature review describing: (i) cholinergic pharmacology and anticholinergic properties; (ii) the importance of anticholinergic therapeutic properties in psychiatry; (iii) the existing anticholinergic drug scales and their usage limitations in Psychiatry and; last (iv) an update to the anticholinergic drug impregnation scale, designed for the French psychiatry practice. The anticholinergic side effects can appear both in the peripheral level (dry mouth, constipation, etc.) and in the central level (especially as cognitive deficits). Many of the so called « anticholinergic ¼ drugs are in fact entirely or mostly antimuscarinic and act essentially as parasympathetic system antagonists. Overall, anticholinergic/antimuscarinic side effects are usually attributed to psychotropic medications: to certain antipsychotics, notably classical neuroleptics such as phenothiazine and also to tricyclic antidepressants. In practice, the impact of anticholinergic toxicity treatments is often highlighted due to their excessively prolonged use in patients on antipsychotics. Interestingly, these antipsychotic treatments are better known for their anticholinergic side effects, especially cognitive ones, with an early onset specially in elder patients and/or in the case of polymedication. In order to evaluate anticholinergic side effects, metrics known as anticholinergic burden scales were created in the last few decades. Nowadays, 13 different scales are documented and accepted by the international academic community, but only three of them are commonly used: the Anticholinergic Drug Scale (ADS), the Anticholinergic Risk Scale (ARS) and the Anticholinergic Burden Scale (ACB). All of them are based on a similar principle, consisting of grading treatments individually, and they are normally scored from 0 - no presence of side effects - to 3 - anticholinergic effects considered to be strong or very strong. Using these scales enables the calculation of the so-called "anticholinergic burden", which corresponds to the cumulative effect of using multiple medications with anticholinergic properties simultaneously. The application of anticholinergic scales to patients with psychiatric disorders has revealed that schizophrenic patients seem to be especially sensitive to anticholinergic cognitive side effects, while elder and depressed patients were more likely to show symptoms of dementia when exposed to higher anticholinergic burden. Unfortunately, these tools appear to have a low parallel reliability, and so they might induce large differences when assessing side effects predictability. In addition, the capacity of these scales to predict central adverse effects is limited due to the fact they poorly or do not differentiate, the ability of treatments to cross the blood-brain barrier. Finally, one last limitation on the validity of these scales is prescription posology is not accounted for side effects considered to be dose dependent. Recently, the MARANTE (Muscarinic Acetylcholine Receptor ANTagonist Exposure) scale has incorporated an anticholinergic burden weighting by posology. Nevertheless, this new model can be criticized, due to the limited number of medications included and due to testing a limited number of potency ranges and dosages for each treatment. Herein, we propose an update to the Anticholinergic Impregnation Scale, developed specifically for the French Psychiatry practice. The scale validation was based on an evaluation of the prescriptions correcting anticholinergic peripheral side effects (constipation, xerostomia and xeropthalmia). This indirect evaluation allowed us to show patients with an anticholinergic impregnation score higher than 5 received significantly more treatments for constipation and xerostomia. This strategy bypasses the bias of a cognitive evaluation in patients with severe mental health disorders. Moreover, the relevance of a tool developed specifically for French psychiatry is justified by the fact that some highly prescribed treatments for mental illness in France (cyamemazine and tropatemine) are strong anticholinergics, and also by the fact they are rarely included in the existing anticholinergic scales. This update of the original scale, published in 2017, includes information whether prescribed drugs cross the blood-brain barrier and thus makes possible a more accurate assessment when evaluating anticholinergic central side effects. Finally, the anticholinergic impregnation scale will soon be integrated into a prescription help software, which is currently being developed to take into consideration dose dependent adverse effects.

Behavioural performance improvement in visuomotor learning correlates with functional and microstructural brain changes.

A better understanding of practice-induced functional and structural changes in our brains can help us design more effective learning environments that provide better outcomes. Although there is growing evidence from human neuroimaging that experience-dependent brain plasticity is expressed in measurable brain changes that are correlated with behavioural performance, the relationship between behavioural performance and structural or functional brain changes, and particularly the time course of these changes, is not well characterised. To understand the link between neuroplastic changes and behavioural performance, 15 healthy participants in this study followed a systematic eye movement training programme for 30 min daily at home, 5 days a week and for 6 consecutive weeks. Behavioural performance statistics and eye tracking data were captured throughout the training period to evaluate learning outcomes. Imaging data (DTI and fMRI) were collected at baseline, after two and six weeks of continuous training, and four weeks after training ended. Participants showed significant improvements in behavioural performance (faster task completion time, lower fixation number and fixation duration). Spatially overlapping reductions in microstructural diffusivity measures (MD, AD and RD) and functional activation increases (BOLD signal) were observed in two main areas: extrastriate visual cortex (V3d) and the frontal part of the cerebellum/Fastigial Oculomotor Region (FOR), which are both involved in visual processing. An increase of functional activity was also recorded in the right frontal eye field. Behavioural, structural and functional changes were correlated. Microstructural change is a better predictor for long-term behavioural change than functional activation is, whereas the latter is superior in predicting instantaneous performance. Structural and functional measures at week 2 of the training programme also predict performance at week 6 and 10, which suggests that imaging data at an early stage of training may be useful in optimising practice environments or rehabilitative training programmes.

Murine Model for the Study of Influenza D Virus.

A novel genus within the Orthomyxoviridae family was identified in the United States and named influenza D virus (IDV). Bovines have been proposed to be the primary host, and three main viral lineages (D/OK-like, D/660-like, and D/Japan-like) have been described. Experimental infections had previously been performed in swine, ferrets, calves, and guinea pigs in order to study IDV pathogenesis. We developed a murine experimental model to facilitate the study of IDV pathogenesis and the immune response. DBA/2 mice were inoculated with 105 50% tissue culture infective dose (TCID50) of D/bovine/France/5920/2014 (D/OK-like). No clinical signs or weight loss were observed. Viral replication was observed mainly in the upper respiratory tract (nasal turbinates) but also in the lower respiratory tract of infected mice, with a peak at 4 days postinfection. Moreover, the virus was also detected in the intestines. All infected mice seroconverted by 14 days postinfection. Transcriptomic analyses demonstrated that IDV induced the activation of proinflammatory genes, such as gamma interferon (IFN-γ) and CCL2. Inoculation of NF-κB-luciferase and Ifnar1-/- mice demonstrated that IDV induced mild inflammation and that a type I interferon response was not necessary in IDV clearance. Adaptation of IDV by serial passages in mice was not sufficient to induce disease or increased pathogenesis. Taken together, present data and comparisons with the calf model show that our mouse model allows for the study of IDV replication and fitness (before selected viruses may be inoculated on calves) and also of the immune response.IMPORTANCE Influenza D virus (IDV), a new genus of Orthomyxoviridae family, presents a large host range and a worldwide circulation. The pathogenicity of this virus has been studied in the calf model. The mouse model is frequently used to enable a first assessment of a pathogen's fitness, replication, and pathogenesis for influenza A and B viruses. We showed that DBA/2 mice are a relevant in vivo model for the study of IDV replication. This model will allow for rapid IDV fitness and replication evaluation and will enable phenotypic comparisons between isolated viruses. It will also allow for a better understanding of the immune response induced after IDV infection.

Psychotropics and COVID-19: An analysis of safety and prophylaxis.

The use of psychotropics during the COVID-19 pandemic has raised two questions, in order of importance: first, what changes should be made to pharmacological treatments prescribed to mental health patients? Secondly, are there any positive side effects of these substances against SARS-CoV-2? Our aim was to analyze usage safety of psychotropics during COVID-19; therefore, herein, we have studied: (i) the risk of symptomatic complications of COVID-19 associated with the use of these drugs, notably central nervous system activity depression, QTc interval enlargement and infectious and thromboembolic complications; (ii) the risk of mistaking the iatrogenic impact of psychotropics with COVID-19 symptoms, causing diagnostic error. Moreover, we provided a summary of the different information available today for these risks, categorized by mental health disorder, for the following: schizophrenia, bipolar disorder, anxiety disorder, ADHD, sleep disorders and suicidal risk. The matter of psychoactive substance use during the pandemic is also analyzed in this paper, and guideline websites and publications for psychotropic treatments in the context of COVID-19 are referenced during the text, so that changes on those guidelines and eventual interaction between psychotropics and COVID-19 treatment medication can be reported and studied. Finally, we also provide a literature review of the latest known antiviral properties of psychotropics against SARS-CoV-2 as complementary information.

A comparison of self and proxy quality of life ratings for people with dementia and their carers: a European prospective cohort study.

Objectives: To identify correlates of self-rated and proxy-rated quality of life (QoL) in people with dementia on (i) a dementia-specific and (ii) a capability-wellbeing QoL measure at baseline and 12-month follow-up, and to consider such factors in the context of QoL intervention development.Method: Prospective clinical and demographic data were collected from 451 community-dwelling dyads (mild-moderate dementia) across eight European countries. QoL was measured using the QOL-AD and the ICECAP-O. Multivariate modelling identified correlates of self- and proxy-rated QoL at baseline and at 12-month follow-up.Results: Carer's proxy-ratings of QoL were significantly lower than self-ratings at all time-points for both measures. Proxy-ratings declined over time, but self-ratings remained stable. Baseline predictors of greater self-rated QoL were education, and greater functional ability and relationship quality. Greater proxy-rated QoL was associated with education and greater functional ability, relationship quality, carer social support and carer QoL, lower carer anxiety/depression and less severe neuropsychiatric symptoms in people with dementia. At follow-up, greater self-rated QoL was predicted by greater functional ability, relationship quality, carer social support and having a spousal carer. Greater proxy-rated QoL at follow-up was associated with the same factors as at baseline; however, the dyad living together was an additional predictive factor.Conclusion: Both proxy-ratings and self-ratings of QoL should be interpreted with caution and in the context of each individual caregiving relationship. Different functional, psychosocial, relational and contextual factors influence self- and proxy-ratings, and both sets of factors should be considered in the context of QoL intervention development for the dyad.

[Challenges for psychotropics in the context of the SARS-Cov-2 pandemic]. / Enjeux de l'utilisation des psychotropes dans le cadre de la pandémie au SARS-Cov-2.

French recommendations have been proposed for psychotropics use and possible adaptations during the SARS-CoV-2 epidemic. Between uncertainties linked to the lack of data and speculations about possible benefits of psychotropics against the coronavirus, we propose here elements allowing to base the pharmacotherapeutic decisions potentially useful in Covid+ patients with psychiatric disorders.

[Informations on psychotropics and their adaptations for patients suffering from mental disorders in France during the SARS-CoV-2 epidemic]. / Informations relatives aux psychotropes et à leurs adaptations éventuelles pour les patients souffrant de troubles psychiques en France pendant l'épidémie à SARS-CoV-2.

The 2019-20 coronavirus pandemic (SARS-CoV-2; severe acute respiratory syndrome coronavirus 2) has dramatic consequences on populations in terms of morbidity and mortality and in social terms, the general confinement of almost half of the world's population being a situation unprecedented in history, which is difficult today to measure the impact at the individual and collective levels. More specifically, it affects people with various risk factors, which are more frequent in patients suffering from psychiatric disorders. Psychiatrists need to know: (i) how to identify, the risks associated with the prescription of psychotropic drugs and which can prove to be counterproductive in their association with COVID-19 (coronavirus disease 2019), (ii) how to assess in terms of benefit/risk ratio, the implication of any hasty and brutal modification on psychotropic drugs that can induce confusion for a differential diagnosis with the evolution of COVID-19. We carried out a review of the literature aimed at assessing the specific benefit/risk ratio of psychotropic treatments in patients suffering from COVID-19. Clinically, symptoms suggestive of COVID-19 (fever, cough, dyspnea, digestive signs) can be caused by various psychotropic drugs and require vigilance to avoid false negatives and false positives. In infected patients, psychotropic drugs should be used with caution, especially in the elderly, considering the pulmonary risk. Lithium and Clozapine, which are the reference drugs in bipolar disorder and resistant schizophrenia, warrant specific attention. For these two treatments the possibility of a reduction in the dosage - in case of minimal infectious signs and in a situation, which does not allow rapid control - should ideally be considered taking into account the clinical response (even biological; plasma concentrations) observed in the face of previous dose reductions. Tobacco is well identified for its effects as an inducer of CYP1A2 enzyme. In a COVID+ patient, the consequences of an abrupt cessation of smoking, particularly related with the appearance of respiratory symptoms (cough, dyspnea), must therefore be anticipated for patients receiving psychotropics metabolized by CYP1A2. Plasma concentrations of these drugs are expected to decrease and can be related to an increase risk of relapse. The symptomatic treatments used in COVID-19 have frequent interactions with the most used psychotropics. If there is no curative treatment for infection to SARS-CoV-2, the interactions of the various molecules currently tested with several classes of psychotropic drugs (antidepressants, antipsychotics) are important to consider because of the risk of changes in cardiac conduction. Specific knowledge on COVID-19 remains poor today, but we must recommend rigor in this context in the use of psychotropic drugs, to avoid adding, in patients suffering from psychiatric disorders, potentially vulnerable in the epidemic context, an iatrogenic risk or loss of efficiency.

[Psychopharmacotherapeutic guidelines : a challenge during health crisis]. / Recommandations psychopharmacothérapeutiques : un défi en temps de crise sanitaire.

The construction of pharmacological guidelines is a complex endeavor, and this is all the truer amidst a health crisis such as the current SARS-CoV-2 pandemic. In psychiatric settings, guidelines have to consider the handling of other drugs (i.e., psychotropic medications), that have been suggested as potentially prophylactic for COVID-19. These dialectics are discussed here, and the methodological foundations used for the elaboration of guidelines are put forward.

Réaliser des recommandations pharmacothérapeutiques est une démarche complexe, plus encore dans une période de crise sanitaire, comme celle que nous traversons avec la pandémie liée au SARS-CoV-2. En psychiatrie, les préconisations formulées se doivent de rappeler la légitime prudence à adopter dans le maniement des psychotropes, dans un contexte qui, par ailleurs, présente certaines de ces médications comme potentiellement prophylactiques de la COVID-19. Ces enjeux contradictoires sont débattus, les concepts méthodologiques de l'élaboration des recommandations sont rappelés.

Physicians' decision about long-term thromboprophylaxis in cancer outpatients: CAT AXIS, a case vignette study on clinical practice in France.

PURPOSE: Data on long-term venous thromboembolism prophylaxis in cancer outpatients remain scarce. In the absence of clear and consistent treatment guidelines, our objectives were to describe and better understand clinical practice and to identify factors influencing the use of thromboprophylaxis. METHODS: CAT AXIS was a multicentred cross-sectional study based on the completion of physician-profile questionnaires and the assessment of 10 e-mailed credible clinical scenarios of lung, colon and breast cancers by each of participants using the case vignette-validated method. RESULTS: A total of 224 physicians participated allowing the completion and the analysis of 2085 reviewed case vignettes corresponding to 765, 703 and 617 fictive clinical scenarios on lung, colon and breast cancers, respectively. The overall rate of thromboprophylaxis was 680/2085 (32.6%) among participants with a comparable proportion for the three types of cancer. Low-molecular-weight heparin (LMWH) was the most frequently used, by 92.7, 93.8 and 83.9% of participants for lung, colon and breast cancers, respectively; thromboprophylaxis duration of ≥ 3 months was used by 74.4% of participants. Multivariate analyses revealed that the Eastern Cooperative Oncology Group index, metastatic malignancy, chemotherapy and history of thrombosis were significantly associated with the therapeutic decision unlike Khorana score and anaemia. CONCLUSION: In the absence of clear guidance, the use of thromboprophylaxis remains low and rather empiric even though the selection of LMWH by the majority of participants and treatment duration seems appropriate based on available data to date. Specific guidelines with corresponding awareness are required.

Access to community care for people with dementia and their informal carers : Case vignettes for a European comparison of structures and common pathways to formal care.

BACKGROUND: People with dementia and their informal carers often do not receive appropriate professional support or it is not received at the right time. OBJECTIVES: Description and comparison of common pathways to formal community dementia care in eight European countries as a part of the transnational Actifcare project. MATERIALS AND METHODS: The German team was responsible for creating an individual case scenario as a starting point. The research teams in Ireland, Italy, the Netherlands, Norway, Portugal, Sweden, and the United Kingdom were then asked to describe a common pathway to formal dementia care by writing their own vignette using the provided individual case scenario. RESULTS: A transnational qualitative content analysis was used to identify the following categories as being the most important: involved professionals, dementia-specific and team-based approaches, proactive roles, and financial aspects. General practitioners (GPs) are described as being the most important profession supporting the access to formal care in all the involved countries. In some countries other professionals take over responsibility for the access procedure. Dementia-specific approaches are rarely part of standard care; team-based approaches have differing significances in each of the countries. Informal carers are mainly proactive in seeking formal care. The Nordic countries demonstrate how financial support enhances access to the professional system. CONCLUSION: Enhanced cooperation between GPs and other professions might optimize access to formal dementia care. Team-based approaches focusing on dementia care should be developed further. Informal carers should be supported and relieved in their role. Financial barriers remain which should be further investigated and reduced.

Key role of endothelium in the eNOS-dependent cardioprotection with exercise training.

Modulation of endothelial nitric oxide synthase (eNOS) activation is recognized as a main trigger of the cardioprotective effects of exercise training on heart vulnerability to ischemia-reperfusion (IR). However, this enzyme is expressed both in coronary endothelial cells and cardiomyocytes and the contribution of each one to such cardioprotection has never been challenged. The aim of this study was to investigate the role of eNOS from the cardiomyocytes vs. the endothelium in the exercise cardioprotection. Male Wistar rats were assigned to a chronic aerobic training (Ex) (vs. sedentary group; Sed) and we investigated the role of eNOS in the effects of exercise on sensitivity to IR or anoxia-reoxygenation (A/R) at whole heart, isolated cardiomyocytes and left coronary artery (LCA) levels. We observed that exercise increased eNOS activation (Ser1177 phosphorylation) and protein S-nitrosylation in whole heart but not at cardiomyocyte level, suggesting the specific target of endothelial cells by exercise. Consistently, in isolated cardiomyocytes submitted to the A/R procedure, exercise reduced cell death and improved cells contractility, but independently of the eNOS pathway. Next, to evaluate the contribution of endothelial cells in exercise cardioprotection, LCA were isolated before and after an IR procedure performed on Langendorff hearts. Exercise improved basal relaxation sensitivity to acetylcholine and markedly reduced the alteration of endothelium-dependent coronary relaxation induced by IR. Furthermore, inactivation of coronary endothelial cells activity just before IR, obtained with a bolus of Triton X-100, totally suppressed cardioprotective effects of exercise on both left ventricular functional recovery after IR and infarct size, whereas no effect of Triton X-100 was observed in Sed group. In conclusion, these results show that coronary endothelial cells rather than cardiomyocytes play a key role in the eNOS-dependent cardioprotection of exercise.

Maternal uniparental disomy of chromosome 16 [upd(16)mat]: clinical features are rather caused by (hidden) trisomy 16 mosaicism than by upd(16)mat itself.

Maternal uniparental disomy of chromosome 16 [upd(16)mat] as the result of trisomy 16 is one of the most frequently reported uniparental disomies in humans, but a consistent phenotype is not obvious. Particularly, it is difficult to discriminate between features resulting from upd(16)mat and mosaic trisomy 16. By evaluating literature data (n = 74) and three own cases we aimed to determine whether the clinical features are due to upd(16)mat or to trisomy 16 mosaicism. While in single cases the clinical symptoms were caused by homozygosity of autosomal recessive mutations on chromosome 16, it turned out that clinical features in upd(16)mat are caused by (hidden) trisomy 16 mosaicism and a specific chromosome 16-associated imprinting disorder does not exist. In trisomy 16/upd(16)mat pregnancies, the management should be based on the ultrasound results and on the clinical course of the pregnancy. In fact, mosaic trisomy 16 pregnancies require a close monitoring because of the higher risk for hypertensive disorders. Postnatal testing for upd(16)mat should be considered in case of homozygosity for an autosomal-recessive mutation, in individuals carrying chromosome 16 aberrations and in phenotypes comprising features of the trisomy 16/upd(16)mat spectrum. Finally, upd(16)mat probably represents a bioindicator for a hidden trisomy 16 mosaicism.

Closed-loop gastric electrical stimulation versus laparoscopic adjustable gastric band for the treatment of obesity: a randomized 12-month multicenter study.

OBJECTIVE: To compare the weight loss, change in quality of life (QOL) and safety of closed-loop gastric electrical stimulation (CLGES) versus adjustable gastric band (LAGB) in the treatment of obesity. METHODS: This multicenter, randomized, non-inferiority trial randomly assigned the patients in a 2:1 ratio to laparoscopic CLGES versus LAGB and followed them for 1 year. We enrolled 210 patients, of whom 50 were withdrawn preoperatively. Among 160 remaining patients (mean age=39±11 years; 75% women; mean body mass index=43±6 kg m-2) 106 received CLGES and 54 received LAGB. The first primary end point was non-inferiority of CLGES versus LAGB, ascertained by the proportion of patients who, at 1 year, fulfilled: (a) a ⩾20% excess weight loss (EWL); (b) no major device- or procedure-related adverse event (AE); and (c) no major, adverse change in QOL. Furthermore, ⩾50% of patients had to reach ⩾25% EWL. The incidence and seriousness of all AE were analyzed and compared using Mann-Whitney's U-test. RESULTS: At 1 year, the proportions of patients who reached all components of the primary study end point were 66.7 and 73.0% for the LAGB and CLGES group, respectively, with a difference of -6.3% and an upper 95% CI of 7.2%, less than the predetermined 10% margin for confirming the non-inferiority of CLGES. The second primary end point was also met, as 61.3% of patients in the CLGES group reached ⩾25% EWL (lower 95% CI=52.0%; P<0.01). QOL improved significantly and similarly in both groups. AE were significantly fewer and less severe in the CLGES than in the LAGB group (P<0.001). CONCLUSIONS AND RELEVANCE: This randomized study confirmed the non-inferiority of CLGES compared with LAGB based on the predetermined composite end point. CLGES was associated with significantly fewer major AE.

Cerebral microglia activation in hepatitis C virus infection correlates to cognitive dysfunction.

Hepatitis C virus (HCV) infection may induce chronic fatigue and cognitive dysfunction. Virus replication was proven within the brain and HCV-positive cells were identified as microglia and astrocytes. We hypothesized that cerebral dysfunction in HCV-afflicted patients is associated with microglia activation. Microglia activation was assessed in vivo in 22 patients with chronic HCV infection compared to six healthy controls using [(11) C]-PK11195 Positron Emission Tomography (PET) combined with magnetic resonance tomography for anatomical localization. Patients were subdivided with regard to their PCR status, Fatigue Impact Scale score (FIS) and attention test sum score (ATS). A total of 12 patients (54.5%) were HCV PCR positive [of which 7 (58.3%) had an abnormal FIS and 7 (58.3%) an abnormal ATS], 10 patients (45.5%) were HCV PCR negative (5 (50%) each with an abnormal FIS or ATS). Patients without attention deficits showed a significantly higher accumulation of [(11) C]-PK11195 in the putamen (P = 0.05), caudate nucleus (P = 0.03) and thalamus (P = 0.04) compared to controls. Patients with and without fatigue did not differ significantly with regard to their specific tracer binding in positron emission tomography. Preserved cognitive function was associated with significantly increased microglia activation with predominance in the basal ganglia. This indicates a probably neuroprotective effect of microglia activation in HCV-infected patients.

Improving the mix of institutional and community care for older people with dementia: an application of the balance of care approach in eight European countries.

OBJECTIVES: To examine whether the mix of community and institutional long-term care (ILTC) for people with dementia (PwD) in Europe could be improved; assess the economic consequences of providing alternative services for particular groups of ILTC entrants and explore the transnational application of the 'Balance of Care' (BoC) approach. METHOD: A BoC study was undertaken in Estonia, Finland, France, Germany, the Netherlands, Spain, Sweden, and the UK as part of the RightTimePlaceCare project. Drawing on information about 2014 PwD on the margins of ILTC admission, this strategic planning framework identified people whose needs could be met in more than one setting, and compared the relative costs of the possible alternatives. RESULTS: The findings suggest a noteworthy minority of ILTC entrants could be more appropriately supported in the community if enhanced services were available. This would not necessarily require innovative services, but more standard care (including personal and day care), assuming quality was ensured. Potential cost savings were identified in all countries, but community care was not always cheaper than ILTC and the ability to release resources varied between nations. CONCLUSIONS: This is believed to be the first transnational application of the BoC approach, and demonstrates its potential to provide a consistent approach to planning across different health and social care systems. Better comparative information is needed on the number of ILTC entrants with dementia, unit costs and outcomes. Nevertheless, the findings offer important evidence on the appropriateness of current provision, and the opportunity to learn from different countries' experience.

Clinically used adhesive ceramic bonding methods: a survey in 2007, 2011, and in 2015.

OBJECTIVES: The objective of the study is to evaluate practices of dentists regarding adhesive cementation of all-ceramic restorations over a period of 8 years. MATERIALS AND METHODS: The authors developed a questionnaire regarding adhesive cementation procedures for all-ceramic restorations. Restorations were distinguished between made out of silicate ceramic or oxide ceramic. The questionnaire was handed out to all dentists participating in a local annual dental meeting in Northern Germany. The returned questionnaires were analyzed to identify incorrect cementation procedures based upon current evidence-based technique from the scientific dental literature. The survey was conducted three times in 2007, 2011, and 2015 and their results were compared. RESULTS: For silicate ceramic restorations, 38-69 % of the participants used evidence-based bonding procedures; most of the incorrect bonding methods did not use a silane containing primer. In case of oxide ceramic restorations, most participants did not use air-abrasion prior to bonding. Only a relatively low rate (7-14 %) of dentists used evidence-based dental techniques for bonding oxide ceramics. CONCLUSION: In adhesive cementation of all-ceramic restorations, the practices of surveyed dentists in Northern Germany revealed high rates of incorrect bonding. During the observation period, the values of evidence-based bonding procedures for oxide ceramics improved while the values for silicate ceramics declined. Based on these results, some survey participants need additional education for adhesive techniques. CLINICAL RELEVANCE: Neglecting scientifically accepted methods for adhesive cementation of all-ceramic restorations may result in reduced longevity of all-ceramic restorations.

Toggling the Local Electric Field with an Embedded Adatom Switch.

By means of scanning probe microscopy we demonstrate that Au(+) on NaCl films adsorbs in an embedded, slightly off-centered Cl-Cl bridge position and can be switched between two equivalent mirror-symmetric configurations using the attractive force exerted by a scanning probe tip. Density functional theory calculations demonstrate that the displacement of the Au atom from the centered position of the bridge configuration is accompanied by a large lifting of the closest Cl atom leading to significant changes in the local electrostatic field. Our findings suggest that Au(+) can be used to toggle the local electrostatic field.