Child and adolescent patients may display mental health concerns within some contexts and not others (e.g., home vs. school). Thus, understanding the specific contexts in which patients display ...concerns may assist mental health professionals in tailoring treatments to patients' needs. Consequently, clinical assessments often include reports from multiple informants who vary in the contexts in which they observe patients' behavior (e.g., patients, parents, teachers). Previous meta-analyses indicate that informants' reports correlate at low-to-moderate magnitudes. However, is it valid to interpret low correspondence among reports as indicating that patients display concerns in some contexts and not others? We meta-analyzed 341 studies published between 1989 and 2014 that reported cross-informant correspondence estimates, and observed low-to-moderate correspondence (mean internalizing: r = .25; mean externalizing: r = .30; mean overall: r = .28). Informant pair, mental health domain, and measurement method moderated magnitudes of correspondence. These robust findings have informed the development of concepts for interpreting multi-informant assessments, allowing researchers to draw specific predictions about the incremental and construct validity of these assessments. In turn, we critically evaluated research on the incremental and construct validity of the multi-informant approach to clinical child and adolescent assessment. In so doing, we identify crucial gaps in knowledge for future research, and provide recommendations for "best practices" in using and interpreting multi-informant assessments in clinical work and research. This article has important implications for developing personalized approaches to clinical assessment, with the goal of informing techniques for tailoring treatments to target the specific contexts where patients display concerns.
A pharmacological and genetic blockade of the dopamine D3 receptor (D3R) has shown to be neuroprotective in models of Parkinson's disease (PD). The anxiolytic drug buspirone, a serotonin receptor 1A ...agonist, also functions as a potent D3R antagonist. To test if buspirone elicited neuroprotective activities, C57BL/6 mice were subjected to rotenone treatment (10mg/kg i.p for 21 days) to induce PD-like pathology and were co-treated with increasing dosages of buspirone (1, 3, or 10 mg/kg i.p.) to determine if the drug could prevent rotenone-induced damage to the central nervous system (CNS). We found that high dosages of buspirone prevented the behavioural deficits caused by rotenone in the open field test. Molecular and histological analyses confirmed that 10 mg/kg of buspirone prevented the degeneration of TH-positive neurons. Buspirone attenuated the induction of interleukin-1β and interleukin-6 expression by rotenone, and this was paralleled by the upregulation of arginase-1, brain-derived neurotrophic factor (BDNF), and activity-dependent neuroprotective protein (ADNP) in the midbrain, striatum, prefrontal cortex, amygdala, and hippocampus. Buspirone treatment also improved mitochondrial function and antioxidant activities. Lastly, the drug prevented the disruptions in the expression of two neuroprotective peptides, pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP). These results pinpoint the neuroprotective efficacy of buspirone against rotenone toxicity, suggesting its potential use as a therapeutic agent in neurodegenerative and neuroinflammatory diseases, such as PD.
Cognitive flexibility is an executive functioning skill that develops in childhood, and when impaired, has transdiagnostic implications for psychiatric disorders. To identify how intrinsic neural ...architecture at rest is linked to cognitive flexibility performance, we used the data-driven method of Independent Components Analysis (ICA) to investigate resting state networks (RSNs) and their whole-brain connectivity associated with levels of cognitive flexibility performance in children. We hypothesized differences by cognitive flexibility performance in RSN connectivity strength in cortico-striatal circuitry, which would manifest via the executive control network, right and left frontoparietal networks (FPN), salience network, default mode network (DMN), and basal ganglia network. We selected participants from the Adolescent Brain Cognitive Development (ABCD) Study who scored at the 25th, (“CF-Low”), 50th (“CF-Average”), or 75th percentiles (“CF-High”) on a cognitive flexibility task, were early to middle puberty, and did not exhibit significant psychopathology (n = 967, 47.9% female; ages 9–10). We conducted whole-brain ICA, identifying 14 well-characterized RSNs. Groups differed in connectivity strength in the right FPN, anterior DMN, and posterior DMN. Planned comparisons indicated CF-High had stronger connectivity between right FPN and supplementary motor/anterior cingulate than CF-Low. CF-High had more anti-correlated connectivity between anterior DMN and precuneus than CF-Average. CF-Low had stronger connectivity between posterior DMN and supplementary motor/anterior cingulate than CF-Average. Post-hoc correlations with reaction time by trial type demonstrated significant associations with connectivity. In sum, our results suggest childhood cognitive flexibility performance is associated with DMN and FPN connectivity strength at rest, and that there may be optimal levels of connectivity associated with task performance that vary by network.
•We investigated resting state networks associated with cognitive flexibility.•Using Independent Components Analysis, 14 resting state networks identified.•Cognitive flexibility performance is associated with DMN, FPN connectivity strength.•Connectivity strength with networks differed in regions linked to shifting tasks.•Future studies can determine how these circuits may give rise to psychopathology.
The global burden of chronic pain is projected to be large and growing, in concert with the burden of noncommunicable diseases. This is the first systematic review and meta-analysis of the prevalence ...of chronic pain without clear etiology in general, elderly, and working populations of low- and middle-income countries (LMICs).
We collected and reported data using Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines, excluding acute pain or pain associated with a concurrent medical condition. One hundred nineteen publications in 28 LMICs were identified for systematic review; the 68 reports that focused on general adult populations (GP), elderly general populations (EGP), or workers (W) were evaluated using mixed-effects regression meta-analysis.
Average chronic pain prevalence is reported as a percentage of the population, with 95% confidence interval for each pain type and population (GP, EGP, and W; NA is equal to not available): unspecified chronic pain (3426-42, 6241-81, and NA); low back pain (2115-27, 2816-42, and 5226-77); headache (4227-58, 3019-43, and 5113-88); chronic daily headache (53-7, 51-12, and 100-33); chronic migraine (GP 126-19); chronic tension type headache (GP 83-15); musculoskeletal pain (2519-33, 4428-62, and 7960-94); joint pain (1411-18, 3416-54, and NA); chronic pelvic/prostatitis pain (GP 40-14); temporomandibular disorder (354-78, 80-24, and NA); abdominal pain (EGP 176-32); fibromyalgia (Combined GP, EGP, W 65-7); and widespread pain (71-18, 198-32, and NA). Chronic low back pain and musculoskeletal pain were 2.50 (1.21-4.10) and 3.11 (2.13-4.37) times more prevalent among W, relative to a GP. Musculoskeletal, joint, and unspecified pain were 1.74 (1.03-2.69), 2.36 (1.09-4.02), and 1.83 (1.13-2.65) times more prevalent among the EGP, relative to a GP. There was significant heterogeneity among studies for all pain types (I > 90%).
Chronic pain is prevalent in LMICs, and where there was sufficient evidence, generally more prevalent in EGP and W. This meta-analysis reveals the spectrum of chronic pain without clear etiology in LMICs. Steps should be taken to reduce heterogeneity in the assessment of global chronic pain. Possible actions may include standardization of chronic pain definition, widespread adoption of validated questionnaires across cultures, attention to inequitably burdened populations, and inclusion of queries regarding known associations of chronic pain with social and psychological factors that, in combination, increase the global burden of noncommunicable disease and disability.
The advent of highly active antiretroviral therapy (HAART), which constitutes HIV protease inhibitors, nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors and ...nucleotide reverse transcriptase inhibitors, has dramatically reduced the morbidity and mortality associated with human immunodeficiency virus (HIV) infection in resource-rich countries. However, this disease still kills several million people each year. Though the reason for therapeutic failure is multi-factorial, an important concern is the treatment and control of HIV within the central nervous system (CNS). Due to the restricted entry of anti-HIV drugs, the brain is thought to form a viral sanctuary site. This not only results in virological resistance, but also is often associated with the development of complications such as HIV-associated dementia. The CNS delivery of anti-HIV drugs is limited by the blood–brain and blood–CSF interfaces due to a combination of restricted paracellular movement, powerful metabolic enzymes and numerous transporters including members of the ATP binding cassette (ABC) and solute carrier (SLC) superfamilies. A better appreciation of the transporters present at the brain barriers will prove a valuable milestone in understanding the limited brain penetration of anti-HIV drugs in HIV and also aid the development of new anti-HIV drugs and drug combinations, with enhanced efficacy in the CNS. This review aims to summarise current knowledge on the transport of anti-HIV drugs across the blood–brain barrier and the choroid plexus, as well as provide recommendations for future research.
Traumatic event exposure is a risk factor for the development and maintenance of psychopathology. Social-affective responses to trauma exposure (e.g. shame, guilt, revenge, social alienation) could ...moderate this relationship, but little is known about their relevance for different types of psychopathology. Moreover, the interplay of different social-affective responses to trauma exposure in predicting psychopathology is poorly understood.
In a sample of N = 1321 trauma-exposed German soldiers, we examined cross-sectional associations of trauma-related social alienation, revenge, guilt and shame with depressive disorder, alcohol use disorder, posttraumatic stress disorder and dimensional measures of depression and anxiety. Latent class analysis was conducted to identify possible patterns of social-affective responses to trauma exposure, and their relation to psychopathology.
All social-affective responses to trauma exposure predicted current posttraumatic stress disorder, depressive disorder, alcohol use disorder and higher depressive and anxiety symptoms. Three latent classes fitted the data best, reflecting groups with (1) low, (2) moderate and (3) high risk for social-affective responses to trauma exposure. The low-risk group demonstrated the lowest expressions on all psychopathology measures.
Trauma-related social alienation, shame, guilt, and revenge are characteristic of individuals with posttraumatic stress disorder, depressive disorder, alcohol use disorder, and with higher anxiety and depressive symptoms. There was little evidence for distinctive patterns of social-affective responses to trauma exposure despite variation in the overall proneness to show social-affective responses. Social-affective responses to trauma exposure could represent promising treatment targets for both cognitive and emotion-focused interventions.
Tumor necrosis factor (TNF) inhibitors are a mainstay in the treatment of rheumatoid arthritis (RA), as well as in the management of spondyloarthritis (SpA) and inflammatory bowel diseases (IBD). ...Unfortunately, a portion of patients taking these drugs require escalating doses within the approved label to achieve response, while others lose response altogether. This may be due to the development of antibodies against TNFi agents.
Our objective was to examine the immunogenicity of TNF inhibitors (adalimumab, infliximab, etanercept, golimumab, and certolizumab) in RA, SpA, and IBD, and to examine the potential effect of anti-drug antibodies (ADABs) on the loss of clinical response through a systematic literature review and meta-analysis.
We conducted a comprehensive literature search using three databases (PubMed, Web of Science, and the Cochrane library) to identify studies examining the immunogenicity of TNF inhibitors in autoimmune diseases between 1966 and 31 December 2013. Inclusion criteria required that studies be in English, be randomized controlled trials, observational studies, or case reports involving more than five patients, and that the patients be aged 18 years or older. Studies were excluded if they were strictly genetic with no clinical correlate, if the patients had concomitant cancer within 5 years of the study, or if the patients had a renal disease requiring dialysis. Double extraction was followed by a third extraction if needed. Consensus was reached by discussion when disagreements occurred. Random-effect models were generated for the meta-analysis of 68 studies to estimate the odds ratio (OR) of the ADAB effects on TNF inhibitor response. Regression analysis was used to compare among the drugs and diseases.
A total of 68 studies (14,651 patients) matched the inclusion/exclusion criteria. Overall, the cumulative incidence of ADABs was 12.7 % 95 % confidence interval (CI) 9.5-16.7. Of the patients using infliximab, 25.3 % (95 % CI 19.5-32.3) developed ADABs compared with 14.1 % (95 % CI 8.6-22.3) using adalimumab, 6.9 % (95 % CI 3.4-13.5) for certolizumab, 3.8 % (95 % CI 2.1-6.6) for golimumab, and 1.2 % (95 % CI 0.4-3.8) for etanercept. ADABs reduced the odds of clinical response by 67 % overall, although most of the data were derived from articles involving infliximab (nine) and adalimumab (eight). The summary effect for infliximab yielded an estimated OR (with ADABs vs. without) of 0.42 (95 % CI 0.30-0.58); the summary effect for adalimumab yielded an estimated OR (as above) of 0.13 (95 % CI 0.08-0.22); and the OR (as above) for golimumab was 0.42 (95 % CI 0.22-0.81). All figures were statistically significant. ADABS decreased response by 27 % in RA and 18 % in SpA, both of which were statistically significant. However, the effect of ADABS on response was not statistically significant for IBD when we only included the studies that reported the duration of exposure in the regression analysis. The use of concomitant immunosuppressives (methotrexate, 6-mercaptopurine, azathioprine, and others) reduced the odds of ADAB formation in all patients by 74 %. The OR for risk with immunosuppressives versus without was 0.26 (95 % CI 0.21-0.32).
ADABs developed in 13 % of patients. All five TNF inhibitors were associated with ADABs, but to varying degrees depending on the specific TNF inhibitor and the disease. ADABs are associated with reduced clinical response and an increased incidence of infusion reactions and injection site reactions. Concomitant use of immunosuppressives can reduce ADAB formation.
Public demand for outdoor recreation has proved a major impetus for land protection in the United States since the mid-twentieth century, particularly in the US West. Many federal, state, and ...municipal conservation tools-policies, management programs, and funding initiatives-aim to ensure recreation access to public lands in conjunction with natural resources protection. However, as recreation use increases, driven by amenity migration and economic development, land managers face a growing challenge in balancing the trade-offs between recreation access and other conservation objectives. Drawing on original archival research, we describe the strong policy ties between outdoor recreation and conservation that emerged in the post-World War II era in response to widespread urbanization. Through semi-structured interviews with land managers, we assess the implications of those policy decisions for today's public land managers. Current management challenges include: poor visitor awareness of the cumulative impacts of recreation activity, resistance by local communities and user groups to restrictions on recreation access, insufficient scientific data to guide management decisions, and limited resources to manage recreationists and enforce regulations. We conclude by proposing strategies to promote sustainable management of multiple-use landscapes through targeted research, application of conservation planning principles, and enhanced cooperation among jurisdictions.
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