AIM The relationship between family behaviour and depression in adolescents at clinical high risk (CHR) for psychosis remains understudied despite high rates of depression in this population. This study examines the relationship between family problem-solving behaviours and depression in CHR adolescents and the impact of family interventions targeting subthreshold symptoms of psychosis on reducing symptoms of depression over 2-years. METHODS Participants were a subset of the North American Prodrome Longitudinal Study who were randomized to 6-months of family focused therapy for individuals at CHR or family psychoeducational treatment. We evaluated the relationship between communication during family conflict discussion and adolescents’ symptoms of depression before treatment. At follow-up assessments the family treatment groups were compared on depression. Finally, we compared those in family treatment with matched controls. RESULTS Adolescents’ constructive communication was associated with less severe symptoms of depression before treatment. Symptoms of depression improved for adolescents in both family treatment groups. However, there were no significant group by treatment interactions. When adolescents who participated in either type of family intervention were compared to CHR adolescent controls, symptoms of depression improved for adolescents in treatment and control groups, but there were no significant time by treatment interactions. CONCLUSIONS The communication skills of CHR adolescents are related to both depression and their parents’ communication skills pre-treatment. However, reductions in depression over the course of the treatment trial cannot be attributed to family treatment. It is imperative to incorporate interventions that directly target depression into future family treatment studies. © 2020 John Wiley & Sons Australia, Ltd.Our objective was to examine the trends and variation in opioid prescribing in Estonia from 2011 to 2017. This retrospective cross-sectional study is based on a nationwide prescription medicines database. We stratified the analysis by treatment indication (cancer vs noncancer pain). Between 2011 and 2017, annual opioid prescribing rates increased by 67% (from 82.9 to 138.6 prescriptions per 1000 population). The annual number of prescriptions per patient did not change substantially (from 2.94 in 2011 to 2.87 in 2017), and was higher among cancer patients (5.07 vs 2.67 annual prescriptions per cancer and noncancer patients, respectively, in 2017). The use of the most potent opioids (morphine, fentanyl) was higher in noncancer than in cancer patients. The use of prescription opioids is low, and raises concern about the potential undertreatment of cancer pain, in parallel with misuse of opioids for either noncancer pain or diversion. © 2020 The Authors. Pharmacology Research & Perspectives published by John Wiley & Sons Ltd, British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics.In this manuscript, we report the chemical synthesis and derivatization of an ortho-functionalized tetrachlorinated azobenzene diol.  A 4’4-dimethoxytrityl (DMT) phosphoramidite was synthesized for its site-specific incorporation within the sense strand of an siRNA duplex to form ortho-functionalized tetrachlorinated azobenzene-containing siRNAs (Cl-siRNAzos). Compared to a non-halogenated azobenzene, ortho-functionalized tetrachlorinated azobenzenes are capable of red-shifting the  π -> π*  transition from the ultraviolet  (UV) portion of the electromagnetic spectrum into the visible range.  Within this visible range, the azobenzene molecule can be reliably converted from trans to cis with red light (660 nm), and converted back to trans from cis with violet wavelength light (410 nm) and/or thermal relaxation. We also report the gene-silencing ability of these Cl-siRNAzos in cell culture as well as their reversible control with visible light for up to 24 hours. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.Cytomegalovirus (CMV) is a DNA virus of the Herpesviridae family and is estimated to affect 15%-30% of high-risk solid organ transplant recipients. Typical manifestations of CMV end-organ disease in this population include colitis, esophagitis, and pneumonitis, and myocarditis is a rarely reported manifestation. We describe two cases of CMV myocarditis in solid organ transplant recipients and review the literature regarding previously published cases of CMV myocarditis. © 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.BACKGROUND Depression research historically uses both self- and clinician ratings of symptoms with significant and substantial correlations. It is often assumed that manic patients lack insight and cannot accurately report their symptoms. This delayed the development of self-rating scales for mania, but several scales now exist and are used in research. Our objective is to systematically review the literature to identify existing self-ratings of symptoms of (hypo)mania and to evaluate their psychometric properties. METHODS PubMed, Web of Knowledge, and Ovid were searched up until June 2018 using the keywords „(hypo)mania,” „self-report,” and „mood disorder” to identify papers which included data on the validity and reliability of self-rating scales for (hypo)mania in samples including patients with bipolar disorder. RESULTS We identified 55 papers reporting on 16 different self-rating scales claiming to assess (hypo)manic symptoms or states. This included single item scales, but also some with over 40 items. Three of the scales, the Internal State Scale (ISS), Altman Self-Rating Mania Scale (ASRM), and Self-Report Manic Inventory (SRMI), provided data about reliability and/or validity in more than three independent studies. Validity was mostly assessed by comparing group means from individuals in different mood states and sometimes by correlation to clinician ratings of mania. CONCLUSIONS ASRM, ISS, and SRMI are promising self-rating tools for (hypo)mania to be used in clinical contexts. Future studies are, however, needed to further validate these measures; for example, their associations between each other and sensitivity to change, especially if they are meant to be outcome measures in studies. © 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.Human P-glycoprotein (P-gp) is a multispecific drug-efflux transporter, which plays an important role in drug resistance and drug disposition. Recent cryo-electron microscopy structures confirmed its rotationally symmetric architecture, which allows dual interaction with ATP and substrates. We here report the existence of two distinct, symmetry-related outer gates. Experiments were aided by availability of the X-ray structure of a homodimeric eukaryotic homolog of P-gp from red alga (CmABCB1), which defined the role of an apical tyrosine residue (Y358) in outer gate formation. We mutated analogous tyrosine residues in each half of the human full-length transporter (Y310, Y953) to alanine. These mutants were introduced in engineered transporters which bind rhodamine 123 in one of two symmetry-related binding modes only. Outer gate dysfunction was detected by a loss of active transport characteristics, while these mutants retained the ability for outward downhill transport. Our data demonstrate that symmetric tyrosine residues Y310 and Y953 are involved in formation of two distinct symmetry-related outer gates, which operate contingent on the rhodamine 123 binding mode. Hence, the rotationally symmetric architecture of P-gp, which determines duality in ATP binding and rhodamine 123 interaction, also forms the basis for the existence of two independently operating outer gates. © 2020 The Authors. Pharmacology Research & Perspectives published by John Wiley & Sons Ltd, British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics.AIM In patients with Alzheimer’s disease (AD), cognitive impairments cause a progressive reduction in Activities of Daily Living (ADL). Neuropsychiatric symptoms (NPS) also appear in most patients; however, the association between NPS and reductions in ADL remains unclear. The present study evaluated whether NPS influence such reductions using two different ADL measures in patients with AD. METHODS Among 546 consecutive outpatients who visited the memory clinic at the Jikei University Kashiwa Hospital, we recruited 208 patients with AD and investigated the correlations between either the Physical Self-Maintenance Scale (PSMS) score or the Instrumental ADL (IADL) level, and each of the Behavioral Pathology in AD (Behave-AD) subscales. To clarify the causal relationships of these correlations, we then verified the associations between statistically significant demographic variables and the Behave-AD subscales as well as the two ADL scales (PSMS score and IADL percentage) using a general linear model. RESULTS Neither the PSMS nor the IADL results were significantly influenced by the aberrant motor behaviors score. However, the IADL was significantly influenced by the Mini-Mental State Exam (MMSE) score. Furthermore, diurnal rhythm disturbances and the interaction between diurnal rhythm disturbances score and the MMSE score significantly influenced the PSMS results. CONCLUSION Basic ADL reductions may be influenced by diurnal rhythm disturbances, in addition to cognitive impairments in patients with AD. Furthermore, the interaction between the diurnal rhythm disturbances score and cognitive function may also influence basic ADL. Geriatr Gerontol Int 2020; •• ••-••. © 2020 Japan Geriatrics Society.OBJECTIVES Mismatch negativity (MMN), an auditory event-related potential sensitive to deviance detection, is smaller in schizophrenia and psychosis risk. In a multisite study, a regression approach to account for effects of site and age (12-35 years) was evaluated alongside the one-year stability of MMN. METHODS Stability of frequency, duration, and frequency + duration (double) deviant MMN was assessed in 167 healthy subjects, tested on two occasions, separated by 52 weeks, at one of eight sites. Linear regression models predicting MMN with age and site were validated and used to derive standardized MMN z-scores. Variance components estimated for MMN amplitude and latency measures were used to calculate Generalizability (G) coefficients within each site to assess MMN stability. Trait-like aspects of MMN were captured by averaging across occasions and correlated with subject traits. RESULTS Age and site accounted for less than 7% of MMN variance. G-coefficients calculated at electrode Fz were stable (G = 0.63) across deviants and sites for amplitude measured in a fixed window, but not for latency (G = 0.37). Frequency deviant MMN z-scores averaged across tests negatively correlated with averaged global assessment of functioning. CONCLUSION MMN amplitude is stable and can be standardized to facilitate longitudinal multisite studies of patients and clinical features. © 2020 The Authors. International Journal of Methods in Psychiatric Research Published by John Wiley & Sons Ltd.OBJECTIVES A new wireless spinal cord stimulation (SCS) technology, which was introduced in recent years, promises minimal invasive SCS as well as additional advantages such as a wide range of stimulation paradigms and 3-T magnetic resonance imaging (MRI) conditionality. MATERIALS AND METHODS We prospectively evaluated 12 patients suffering from therapy-resistant neuropathic pain, who were implanted with a wireless SCS system from 2017 to 2019. Potential issues pertaining to handling and usability of the SCS device were evaluated from a patients’ as well as from a surgeon’s perspective. RESULTS Mean follow-up was 228.0 days (95% CI, 20.0-518.0 days). We did not record any handling issues nor did we record any relevant local discomfort associated with the implanted SCS device. N = 3/12 patients reported discomfort from wearing the SCS antenna and one patient complained about a short battery life of the controller device. There were no reported incidents during 3-T MRI studies. After an average test period of 51.