A multicenter, randomised, double-blind, placebo-controlled, prospective crossover trial

Objective To evaluate the efficacy and safety of bupropion in the treatment of apathy in Huntington’s disease (HD). Methods In this phase 2b multicentre, double-blind, placebo-controlled crossover trial, individuals with HD and clinical signs of apathy according to the Structured Clinical Interview for Apathy—Dementia (SCIA-D), but not depression (n = 40) were randomized to receive either bupropion 150/300mg or placebo daily for 10 weeks. The primary outcome parameter was a significant change of the Apathy Evaluation Scale (AES) score after ten weeks of treatment as judged by an informant (AES-I) living in close proximity with the study participant. The secondary outcome parameters included changes of 1. AES scores determined by the patient (AES-S) or the clinical investigator (AES-C), 2. psychiatric symptoms (NPI, HADS-SIS, UHDRS-Behavior), 3. cognitive performance (SDMT, Stroop, VFT, MMSE), 4. motor symptoms (UHDRS-Motor), 5. activities of daily function (TFC, UHDRS-Function), and 6. caregiver distress (NPI-D). In addition, we investigated the effect of bupropion on brain structure as well as brain responses and functional connectivity during reward processing in a gambling task using magnetic resonance imaging (MRI). Results At baseline, there were no significant treatment group differences in the clinical primary and secondary outcome parameters. At endpoint, there was no statistically significant difference between treatment groups for all clinical primary and secondary outcome variables. Study participation, irrespective of the intervention, lessened symptoms of apathy according to the informant and the clinical investigator. Conclusion Bupropion does not alleviate apathy in HD. However, study participation/placebo effects were observed, which document the need for carefully controlled trials when investigating therapeutic interventions for the neuropsychiatric symptoms of HD. Trial registration ClinicalTrials.gov 0191496

Long-term evolution and coupling of the boundary layers in the Stratus Deck Regions of the eastern Pacific (STRATUS)

A surface mooring was deployed in the eastern tropical Pacific west of northern Chile from the R/V Melville as part of the Eastern Pacific Investigation of Climate (EPIC). EPIC is a CLIVAR study with the goal of investigating links between sea surface temperature variability in the eastern tropical Pacific and climate over the American continents. Important to that goal is an understanding of the role of clouds in the eastern Pacific in modulating atmosphere-ocean coupling. The mooring was deployed near 20°S 85°W, at a location near the western edge of the stratocumulus cloud deck found west of Peru and Chile. This deployment started a three-year occupation of that site by a WHOI surface mooring in order to collect accurate time series of surface forcing and upper ocean variability. The surface mooring was deployed by the Upper Ocean Processes Group of the Woods Hole Oceanographic Institution (WHOI). In collaboration with investigators from the University of Concepcion, Concepcion, Chile, an XBT section was made on the way out to the mooring from Arica, Chile, and an XBT and CTD section was made on the way into Arica. The buoy was equipped with meteorological instrumentation, including two Improved METeorological (IMET) systems. The mooring also carried Vector Measuring Current Meters, single-temperature recorders, and conductivity and temperature recorders located in the upper meters of the mooring line. In addition to the instrumentation noted above, a variety of other instruments, including an acoustic current meter, an acoustic doppler current profiler, a bio-optical instrument package, and an acoustic rain guage, were deployed. This report describes, in a general manner, the work that took place and the data collected during the Cook 2 cruise aboard the R/V Melville. The surface mooring deployed during this cruise will be recovered and re-deployed after approximately 12 months and again after 24 months, with a final recovery planned for 36 months after the first setting. Details of the mooring design and preliminary data from the XBT and CTD sections are included.Funding was provided by the National Oceanic and Atmospheric Administration under grant number NA96GP0429

Quality of life and clinical characteristics of self-improving congenital ichthyosis within the disease spectrum of autosomal recessive congenital ichthyosis

Background Autosomal-recessive congenital ichthyosis (ARCI) is a heterogeneous group of ichthyoses presenting at birth. Self-improving congenital ichthyosis (SICI) is a subtype of ARCI and is diagnosed when skin condition improves remarkably (within years) after birth. So far, there are sparse data on SICI and quality of life (QoL) in this ARCI subtype. This study aims to further delineate the clinical spectrum of SICI as a rather unique subtype of ARCI. Objectives This prospective study included 78 patients (median age: 15 years) with ARCI who were subdivided in SICI (n = 18) and non-SICI patients (nSICI, n = 60) by their ARCI phenotype. Methods Quality of life (QoL) was assessed using the (Children's) Dermatology Life Quality Index. Statistical analysis was performed with chi-squared and t-Tests. Results The genetically confirmed SICI patients presented causative mutations in the following genes: ALOXE3 (8/16; 50.0%), ALOX12B (6/16; 37.5%), PNPLA1 (1/16; 6.3%) and CYP4F22 (1/16; 6.3%). Hypo-/anhidrosis and insufficient vitamin D levels (<30 ng/mL) were often seen in SICI patients. Brachydactyly (a shortening of the 4th and 5th fingers) was statistically more frequent in SICI (P = 0.023) than in nSICI patients. A kink of the ear's helix was seen in half of the SICI patients and tends to occur more frequently in patients with ALOX12B mutations (P = 0.005). QoL was less impaired in patients under the age of 16, regardless of ARCI type. Conclusions SICI is an underestimated, milder clinical variant of ARCI including distinct features such as brachydactyly and kinking of the ears. Clinical experts should be aware of these features when seeing neonates with a collodion membrane. SICI patients should be regularly checked for clinical parameters such as hypo-/anhidrosis or vitamin D levels and monitored for changes in quality of life

Monitoring retinal changes with optical coherence tomography predicts neuronal loss in experimental autoimmune encephalomyelitis.

BACKGROUND:Retinal optical coherence tomography (OCT) is a clinical and research tool in multiple sclerosis, where it has shown significant retinal nerve fiber (RNFL) and ganglion cell (RGC) layer thinning, while postmortem studies have reported RGC loss. Although retinal pathology in experimental autoimmune encephalomyelitis (EAE) has been described, comparative OCT studies among EAE models are scarce. Furthermore, the best practices for the implementation of OCT in the EAE lab, especially with afoveate animals like rodents, remain undefined. We aimed to describe the dynamics of retinal injury in different mouse EAE models and outline the optimal experimental conditions, scan protocols, and analysis methods, comparing these to histology to confirm the pathological underpinnings. METHODS:Using spectral-domain OCT, we analyzed the test-retest and the inter-rater reliability of volume, peripapillary, and combined horizontal and vertical line scans. We then monitored the thickness of the retinal layers in different EAE models: in wild-type (WT) C57Bl/6J mice immunized with myelin oligodendrocyte glycoprotein peptide (MOG35-55) or with bovine myelin basic protein (MBP), in TCR2D2 mice immunized with MOG35-55, and in SJL/J mice immunized with myelin proteolipid lipoprotein (PLP139-151). Strain-matched control mice were sham-immunized. RGC density was counted on retinal flatmounts at the end of each experiment. RESULTS:Volume scans centered on the optic disc showed the best reliability. Retinal changes during EAE were localized in the inner retinal layers (IRLs, the combination of the RNFL and the ganglion cell plus the inner plexiform layers). In WT, MOG35-55 EAE, progressive thinning of IRL started rapidly after EAE onset, with 1/3 of total loss occurring during the initial 2 months. IRL thinning was associated with the degree of RGC loss and the severity of EAE. Sham-immunized SJL/J mice showed progressive IRL atrophy, which was accentuated in PLP-immunized mice. MOG35-55-immunized TCR2D2 mice showed severe EAE and retinal thinning. MBP immunization led to very mild disease without significant retinopathy. CONCLUSIONS:Retinal neuroaxonal damage develops quickly during EAE. Changes in retinal thickness mirror neuronal loss and clinical severity. Monitoring of the IRL thickness after immunization against MOG35-55 in C57Bl/6J mice seems the most convenient model to study retinal neurodegeneration in EAE

Bupropion for the treatment of apathy in Huntington's disease:A multicenter, randomised, double-blind, placebo-controlled, prospective crossover trial

OBJECTIVE:To evaluate the efficacy and safety of bupropion in the treatment of apathy in Huntington's disease (HD). METHODS:In this phase 2b multicentre, double-blind, placebo-controlled crossover trial, individuals with HD and clinical signs of apathy according to the Structured Clinical Interview for Apathy-Dementia (SCIA-D), but not depression (n = 40) were randomized to receive either bupropion 150/300mg or placebo daily for 10 weeks. The primary outcome parameter was a significant change of the Apathy Evaluation Scale (AES) score after ten weeks of treatment as judged by an informant (AES-I) living in close proximity with the study participant. The secondary outcome parameters included changes of 1. AES scores determined by the patient (AES-S) or the clinical investigator (AES-C), 2. psychiatric symptoms (NPI, HADS-SIS, UHDRS-Behavior), 3. cognitive performance (SDMT, Stroop, VFT, MMSE), 4. motor symptoms (UHDRS-Motor), 5. activities of daily function (TFC, UHDRS-Function), and 6. caregiver distress (NPI-D). In addition, we investigated the effect of bupropion on brain structure as well as brain responses and functional connectivity during reward processing in a gambling task using magnetic resonance imaging (MRI). RESULTS:At baseline, there were no significant treatment group differences in the clinical primary and secondary outcome parameters. At endpoint, there was no statistically significant difference between treatment groups for all clinical primary and secondary outcome variables. Study participation, irrespective of the intervention, lessened symptoms of apathy according to the informant and the clinical investigator. CONCLUSION:Bupropion does not alleviate apathy in HD. However, study participation/placebo effects were observed, which document the need for carefully controlled trials when investigating therapeutic interventions for the neuropsychiatric symptoms of HD. TRIAL REGISTRATION:ClinicalTrials.gov 01914965

Rouw bij mensen met het chronisch vermoeidheidssyndroom (CVS)

Summary Introduction: Mourning is often first associated with the grief that arises from the loss of a loved one. People not immediately think of similar processes and grief reactions after the loss of health. A chronic condition can dramatically change people's lives. This applies to the chronically ill in general and also to patients with chronic fatigue syndrome (CFS). The objective of the current research is to gain more insight into the grieving and loss processing in people with CFS. It will also look at the role of the severity of the condition in the grieving process. The research comprises a literature study and an empirical study. Method: The literature study gives a review of the relevant literature found in PsychINFO. A distinction is made in literature about grief in general, grief in chronic illness, grief in CFS and measuring instruments for mourning. We made a selection of 14 articles and 4 books. The respondents in the empirical study concerning people with CFS who were contracted by the Dutch ME-CFS foundation. 90 patients filled out a digital or written version of a questionnaire. The questionnaire measured mourning, psychological health, quality of life and patients health in general. Conclusion: The study shows that in the process of mourning in people with CFS two domains of mourning play an important role, namely (1) wrestling (2) processing. The domain wrestling is associated with negative feelings and the domain processing with positive feelings. In addition, the analysis shows that there is a correlation between the two domains of mourning and the severity of the disorder. Thus it turns out that the degree of anxiety and depression, is positively related to the domain wrestling and negatively to the domain processing. This means that when the symptoms of anxiety and depression are more severe people mostly seem to be struggling with the loss and much less to process. For the quality of life it seems to be that the more one is satisfied with the current quality of life the more processing it takes. While dissatisfaction with the quality of life just goes together with more wrestling. Also, people who experienced a greater difference between the quality of life before and after the disease especially struggling with the loss and have more difficulty in processing the loss. For the degree of fatigue there’s a positive correlation with the domain struggling and a negative correlation with the domain processing. This means that people with more fatigue symptoms often seem to struggle with the loss and appear to be less concerned with the processing. For both the general health status and the degree of pain we found no correlation with the two domains of mourning. Samenvatting Inleiding: Rouw wordt vaak als eerst geassocieerd met het verdriet dat ontstaat na het verlies van een dierbare. Er wordt bij het woord rouw niet meteen gedacht aan vergelijkbare verwerkingsprocessen en rouwreacties na het verlies van gezondheid. Een chronische aandoening kan het leven van mensen drastisch veranderen. Dit geldt voor chronisch zieken in het algemeen en ook voor patiënten met het chronisch vermoeidheidssyndroom (CVS). De doelstelling van het huidige onderzoek is om meer inzicht te krijgen in het rouw- en verwerkingsproces bij mensen met CVS. Daarbij zal er ook gekeken worden naar de rol van de ernst van de aandoening in het rouw- en verwerkingsproces. Het onderzoek bestaat uit zowel een literatuurstudie als een empirische studie. Methode: Voor de literatuurstudie is in PsychINFO gezocht naar relevante literatuur. Hierbij is een onderscheid gemaakt in literatuur over rouw in het algemeen, rouw bij chronische ziekte, rouw bij CVS en meetinstrumenten voor rouw. Er is een selectie gemaakt van 14 artikelen en 4 boeken. De respondenten in de empirische studie betreffen mensen met de aandoening CVS. De meerderheid van de respondenten is aangesloten bij de ME-CVS Stichting Nederland. Zij zijn geworven door een oproep in het ledenblad MEdium, via een oproep op de website van de ME-CVS Stichting of via een oproep op een andere CVS website. De vragenlijst kon digitaal of schriftelijk worden ingevuld. Het betreft een samengestelde vragenlijst bestaande uit de Vragenlijst Verliesverwerking na Ernstige Ziekte (VeVEZ), de Hospital Anxiety and Depression Scale (HADS) en enkele vragen die de kwaliteit van leven en de algemene gezondheidstoestand meten. Uiteindelijk vormen de gegevens van 90 respondenten de data van dit onderzoek. Conclusie: Uit het onderzoek komt naar voren dat er in het rouw- en verwerkingsproces van mensen met CVS twee domeinen van rouw een rol spelen, namelijk (1) worstelen en (2) verwerking. Het domein worstelen gaat gepaard met negatieve gevoelens en het domein verwerking met positieve gevoelens. Daarnaast komt uit het onderzoek naar voren dat er een samenhang bestaat tussen de twee domeinen van rouw en de ernst van de aandoening. Zo is gebleken dat de mate van angst en depressie positief samenhangt met het domein worstelen en negatief met het domein verwerking. Dit betekent dat naarmate de symptomen van angst en depressie groter zijn mensen voornamelijk lijken te worstelen met het verlies en veel minder te verwerken. Voor de kwaliteit van leven geldt dat naarmate men meer tevreden is over de huidige kwaliteit van leven dit gepaard gaat met meer verwerking. Terwijl ontevredenheid over de kwaliteit van leven juist samengaat met meer worstelen. Daarbij komt dat mensen die een groter verschil ervaren tussen de kwaliteit van leven voor en na de aandoening vooral worstelen met het verlies en meer moeite ondervinden bij het verwerken ervan. Voor de mate van vermoeidheid geldt dat er een positieve samenhang bestaat met het domein worstelen en een negatieve met het domein verwerking. Dit betekent dat mensen met meer vermoeidheidsklachten veelal lijken te worstelen met het verlies en minder bezig lijken te zijn met het verwerken ervan. Voor zowel de algemene gezondheidstoestand als de mate van pijn is geen verband aangetoond met de twee domeinen van rouw.

The Dynamics of Interpersonal Emotion Regulation: How Sharers Elicit Desired (But Not Necessarily Helpful) Support

People frequently tell others about experiences that distress them, a phenomenon termed social sharing. Paradoxically, although people perceive social sharing as beneficial, it often fails to promote emotional recovery. This may be partially explained by sharers seeking - and thereby eliciting - support that is not helpful in the long term. Here, we examined the role that sharers themselves play in eliciting different forms of support. Participants were randomly assigned to the role of sharer (who was asked to discuss an upsetting situation) or listener (who was instructed to respond naturally). Afterwards, both sharer and listener independently watched the interaction on video in 20-second fragments. For each fragment, sharers rated their experienced emotional intensity and socio-affective and cognitive support needs, while listeners rated their perception of the sharer’s emotional intensity and their own support provision. Emotional intensity was associated with an increase in sharers’ socio-affective support needs and listeners' socio-affective support provision, but a decrease in cognitive support provision. Moreover, the more accurately listeners judged sharers’ emotional intensity, the more they fulfilled sharers’ socio-affective (but not cognitive) support needs. These findings illuminate the role of sharers in shaping interpersonal emotion regulation by clarifying how the way they communicate their needs and feelings influences listeners’ support provision. Together with existing evidence that sharers usually desire socio-affective support (which alleviates momentary distress, but does not facilitate long-term recovery), these findings suggest that sharers elicit the support they desire, explaining why they perceive sharing as beneficial although it does not engender emotional recovery