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Objective: To define the reporting of Scoring Hip Osteoarthritis with MRI (SHOMRI) feature prevalence and severity, and to develop criteria to monitor feature change in longitudinal investigations. Methods: Twenty-five participants (50 hips) of the femoroacetabular impingement and hip osteoarthritis cohort study underwent baseline and 2-year follow-up 3 T hip MRIs. Eight hip OA features were assessed using the SHOMRI. All MRIs were read paired with knowledge of timepoint by two blinded musculoskeletal radiologists. We provide definitions to report SHOMRI feature prevalence, severity, and longitudinal change. Results: We report clear definitions for SHOMRI feature prevalence, severity, and change. When we applied the definitions to the studied cohort, we could detect the prevalence, severity, and change of hip OA features. For example, 88% of hips had labral tears (34% graded as severe tears) and 76% had cartilage defects (42% graded as full thickness). Over 70% of hips had feature change over 2 years, highlighting the sensitivity of SHOMRI definitions to assess longitudinal change of hip OA features. Intra-reader reliability was almost perfect (weighted (w)-kappa 0.86 to 1.00), with inter-reader reliability substantial to almost perfect (w-kappa 0.80 to 1.00). Conclusion: This study is the first to provide definitions to report SHOMRI feature prevalence, severity, and change. The proposed definitions will enable comparison between hip MRI studies and improve our understanding of hip OA pathogenesis. [ABSTRACT FROM AUTHOR]

Background: The impact of activity-related joint loading on cartilage is not clear. Abnormal loading is considered to be a mechanical driver of osteoarthritis (OA), yet moderate amounts of physical activity and rehabilitation exercise can have positive effects on articular cartilage. Our aim was to investigate the immediate effects of joint loading activities on knee and hip cartilage in healthy adults, as assessed using magnetic resonance imaging. We also investigated delayed effects of activities on healthy cartilage and the effects of activities on cartilage in adults with, or at risk of, OA. We explored the association of sex, age and loading duration with cartilage changes. Methods: A systematic review of six databases identified studies assessing change in adult hip and knee cartilage using MRI within 48 h before and after application of a joint loading intervention/activity. Studies included adults with healthy cartilage or those with, or at risk of, OA. Joint loading activities included walking, hopping, cycling, weightbearing knee bends and simulated standing within the scanner. Risk of bias was assessed using the Newcastle–Ottawa Scale. Random-effects meta-analysis estimated the percentage change in compartment-specific cartilage thickness or volume and composition (T2 relaxation time) outcomes. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system evaluated certainty of evidence. Results: Forty studies of 653 participants were included after screening 5159 retrieved studies. Knee cartilage thickness or volume decreased immediately following all loading activities investigating healthy adults; however, GRADE assessment indicated very low certainty evidence. Patellar cartilage thickness and volume reduced 5.0% (95% CI 3.5, 6.4, I2 = 89.3%) after body weight knee bends, and tibial cartilage composition (T2 relaxation time) decreased 5.1% (95% CI 3.7, 6.5, I2 = 0.0%) after simulated standing within the scanner. Hip cartilage data were insufficient for pooling. Secondary outcomes synthesised narratively suggest knee cartilage recovers within 30 min of walking and 90 min of 100 knee bends. We found contrasting effects of simulated standing and walking in adults with, or at risk of, OA. An increase of 10 knee bend repetitions was associated with 2% greater reduction in patellar thickness or volume. Conclusion: There is very low certainty evidence that minimal knee cartilage thickness and volume and composition (T2 relaxation time) reductions (0–5%) occur after weightbearing knee bends, simulated standing, walking, hopping/jumping and cycling, and the impact of knee bends may be dose dependent. Our findings provide a framework of cartilage responses to loading in healthy adults which may have utility for clinicians when designing and prescribing rehabilitation programs and providing exercise advice. [ABSTRACT FROM AUTHOR]

Rationale: The basolateral amygdala (BLA) and medial geniculate nucleus of the thalamus (MGN) have both been shown to be necessary for the formation of associative learning. While the role that the BLA plays in this process has long been emphasized, the MGN has been less well-studied and surrounded by debate regarding whether the relay of sensory information is active or passive. Objectives: We seek to understand the role the MGN has within the thalamoamgydala circuit in the formation of associative learning. Methods: Here, we use optogenetics and in vivo electrophysiological recordings to dissect the MGN-BLA circuit and explore the specific subpopulations for evidence of learning and synthesis of information that could impact downstream BLA encoding. We employ various machine learning techniques to investigate function within neural subpopulations. We introduce a novel method to investigate tonic changes across trial-by-trial structure, which offers an alternative approach to traditional trial-averaging techniques. Results: We find that the MGN appears to encode arousal but not valence, unlike the BLA which encodes for both. We find that the MGN and the BLA appear to react differently to expected and unexpected outcomes; the BLA biased responses toward reward prediction error and the MGN focused on anticipated punishment. We uncover evidence of tonic changes by visualizing changes across trials during inter-trial intervals (baseline epochs) for a subset of cells. Conclusion: We conclude that the MGN-BLA projector population acts as both filter and transferer of information by relaying information about the salience of cues to the amygdala, but these signals are not valence-specified. [ABSTRACT FROM AUTHOR]

Purpose: To elicit stakeholder perspectives on the findings from our scoping review on youth participation in mental health policymaking, we conducted a global consultation with young people and adults directly involved in mental health policymaking. Method: Forty-four stakeholders from 16 countries, including 15 young people, 9 policymakers and 20 facilitators of youth participation, took part in individual interviews and/or focus groups. They were asked about how the review findings contrasted with their own experiences in mental health policymaking. The transcribed data were thematically analyzed. Results: All participants viewed lived experience as valuable in identifying policy gaps. Youth pointed out that children and youth with disabilities, diverse sexual orientations, and/or gender identities were often excluded, and spoke about feelings of being an "accessory", illustrating a lack of power-sharing in a tokenized policymaking process. Adult participants' accounts highlighted the challenges inherent in policymaking such as the need for political knowledge and institutional time constraints. A range of cultural, socio-economic, and political barriers to youth participation, that were often context-specific, were identified. Conclusions: The diverse perspectives of stakeholders extended the review results. Based on our findings, we recommend that adults and institutions: (1) recognize lived experience as expertise in shaping mental health policies; (2) include diverse groups; (3) reduce tokenistic relationships through the creation of safer spaces, adult feedback, co-production, and social accountability; and (4) adopt an intersectional approach to address cultural, socio-economic, and political barriers to participation. Methodologically, our work demonstrates why stakeholder consultations are an essential component of scoping reviews. [ABSTRACT FROM AUTHOR]

Although youth participation is oft-acknowledged as underpinning mental health policy and service reform, little robust evidence exists about the participation of children and youth in mental health policymaking. A scoping review based on Arksey and O'Malley's framework was conducted to identify and synthesize available information on children and youth's participation in mental health policymaking. Published studies up to November 30, 2020 were searched in Medline (OVID), PsycINFO (OVID), Scopus, and Applied Social Sciences Index and Abstracts (PROQUEST). Further studies were identified through Google Scholar and a grey literature search was conducted using Google and targeted web searches from October to December, 2020. Three reviewers performed screening and data extraction relevant to the review objective, followed by an online consultation. From 2,981 records, 25 publications were included. A lack of diversity among the youth involved was found. Youth were often involved in situational analysis and policy design, but seldom in policy implementation and evaluation. Both the facilitators of and barriers to participation were multifaceted and interconnected. Despite a range of expected outcomes of participation for youth, adults, organizations, and communities, perceived and actual effects were neither substantially explored nor reported. Our recommendations for mental health policymaking highlight the inclusion of children and youth from diverse groups, and the creation of relational spaces that ensure safety, inclusiveness, and diversity. Identified future research directions are: the outcomes of youth participation in mental health policymaking, the role of adults, and more generally, how the mental health of children and youth shapes and is shaped by the policymaking process. [ABSTRACT FROM AUTHOR]

Background: Hop testing is widely used by clinicians to monitor rehabilitation and decide when to return to sport following anterior cruciate ligament reconstruction (ACLR); however, the trajectory of long-term hop performance has not been summarised.To investigate hop performance change over time after ACLR.Systematic review with longitudinal meta-analysis.MEDLINE, EMBASE, CINAHL, Scopus, Cochrane CENTRAL and SPORTDiscus to 28 February 2023.Studies with ≥ 50 participants following primary ACLR, with mean participant age of 18–40 years, reporting a quantitative measure of hop performance (e.g. single forward hop distance). Results had to be reported for the ACLR limb and compared with (1) the contralateral limb (within person) and/or (2) an uninjured control limb (between person).We included 136 studies of 23,360 participants. Performance was similar across different hop tests, with steep initial improvements in within-person symmetry, tailing off after 18–24 months. ACLR limb hop performance was 5–10% lower compared with the contralateral limb at 1 year post-surgery, with largest deficits observed for vertical hop [87.0% contralateral limb (95% CI 85.3–88.8) compared with single forward hop 93.8% (95% CI 92.8–94.9)]. By 3–5 years, results were similar between ACLR and contralateral limbs. There were limited data for between-person comparisons (n = 17 studies). Exploratory analyses showed deficits in all forward hopping tests to be very strongly correlated with each other [e.g. single forward and triple hop rho = 0.96 (95% CI 0.90–0.99)], though there was discordance in the relationship between single forward hop and vertical hop performance [rho = 0.27 (95% CI − 0.53 to 0.79)].Hop performance is comparable to the uninjured limb by 3–5 years post-ACLR, with the greatest deficits in within-person symmetry present in vertical and side hop tests. Assessment of hopping in multiple planes and comparison with uninjured controls, may provide the most complete evaluation of functional performance.Objective: Hop testing is widely used by clinicians to monitor rehabilitation and decide when to return to sport following anterior cruciate ligament reconstruction (ACLR); however, the trajectory of long-term hop performance has not been summarised.To investigate hop performance change over time after ACLR.Systematic review with longitudinal meta-analysis.MEDLINE, EMBASE, CINAHL, Scopus, Cochrane CENTRAL and SPORTDiscus to 28 February 2023.Studies with ≥ 50 participants following primary ACLR, with mean participant age of 18–40 years, reporting a quantitative measure of hop performance (e.g. single forward hop distance). Results had to be reported for the ACLR limb and compared with (1) the contralateral limb (within person) and/or (2) an uninjured control limb (between person).We included 136 studies of 23,360 participants. Performance was similar across different hop tests, with steep initial improvements in within-person symmetry, tailing off after 18–24 months. ACLR limb hop performance was 5–10% lower compared with the contralateral limb at 1 year post-surgery, with largest deficits observed for vertical hop [87.0% contralateral limb (95% CI 85.3–88.8) compared with single forward hop 93.8% (95% CI 92.8–94.9)]. By 3–5 years, results were similar between ACLR and contralateral limbs. There were limited data for between-person comparisons (n = 17 studies). Exploratory analyses showed deficits in all forward hopping tests to be very strongly correlated with each other [e.g. single forward and triple hop rho = 0.96 (95% CI 0.90–0.99)], though there was discordance in the relationship between single forward hop and vertical hop performance [rho = 0.27 (95% CI − 0.53 to 0.79)].Hop performance is comparable to the uninjured limb by 3–5 years post-ACLR, with the greatest deficits in within-person symmetry present in vertical and side hop tests. Assessment of hopping in multiple planes and comparison with uninjured controls, may provide the most complete evaluation of functional performance.Design: Hop testing is widely used by clinicians to monitor rehabilitation and decide when to return to sport following anterior cruciate ligament reconstruction (ACLR); however, the trajectory of long-term hop performance has not been summarised.To investigate hop performance change over time after ACLR.Systematic review with longitudinal meta-analysis.MEDLINE, EMBASE, CINAHL, Scopus, Cochrane CENTRAL and SPORTDiscus to 28 February 2023.Studies with ≥ 50 participants following primary ACLR, with mean participant age of 18–40 years, reporting a quantitative measure of hop performance (e.g. single forward hop distance). Results had to be reported for the ACLR limb and compared with (1) the contralateral limb (within person) and/or (2) an uninjured control limb (between person).We included 136 studies of 23,360 participants. Performance was similar across different hop tests, with steep initial improvements in within-person symmetry, tailing off after 18–24 months. ACLR limb hop performance was 5–10% lower compared with the contralateral limb at 1 year post-surgery, with largest deficits observed for vertical hop [87.0% contralateral limb (95% CI 85.3–88.8) compared with single forward hop 93.8% (95% CI 92.8–94.9)]. By 3–5 years, results were similar between ACLR and contralateral limbs. There were limited data for between-person comparisons (n = 17 studies). Exploratory analyses showed deficits in all forward hopping tests to be very strongly correlated with each other [e.g. single forward and triple hop rho = 0.96 (95% CI 0.90–0.99)], though there was discordance in the relationship between single forward hop and vertical hop performance [rho = 0.27 (95% CI − 0.53 to 0.79)].Hop performance is comparable to the uninjured limb by 3–5 years post-ACLR, with the greatest deficits in within-person symmetry present in vertical and side hop tests. Assessment of hopping in multiple planes and comparison with uninjured controls, may provide the most complete evaluation of functional performance.Data Sources: Hop testing is widely used by clinicians to monitor rehabilitation and decide when to return to sport following anterior cruciate ligament reconstruction (ACLR); however, the trajectory of long-term hop performance has not been summarised.To investigate hop performance change over time after ACLR.Systematic review with longitudinal meta-analysis.MEDLINE, EMBASE, CINAHL, Scopus, Cochrane CENTRAL and SPORTDiscus to 28 February 2023.Studies with ≥ 50 participants following primary ACLR, with mean participant age of 18–40 years, reporting a quantitative measure of hop performance (e.g. single forward hop distance). Results had to be reported for the ACLR limb and compared with (1) the contralateral limb (within person) and/or (2) an uninjured control limb (between person).We included 136 studies of 23,360 participants. Performance was similar across different hop tests, with steep initial improvements in within-person symmetry, tailing off after 18–24 months. ACLR limb hop performance was 5–10% lower compared with the contralateral limb at 1 year post-surgery, with largest deficits observed for vertical hop [87.0% contralateral limb (95% CI 85.3–88.8) compared with single forward hop 93.8% (95% CI 92.8–94.9)]. By 3–5 years, results were similar between ACLR and contralateral limbs. There were limited data for between-person comparisons (n = 17 studies). Exploratory analyses showed deficits in all forward hopping tests to be very strongly correlated with each other [e.g. single forward and triple hop rho = 0.96 (95% CI 0.90–0.99)], though there was discordance in the relationship between single forward hop and vertical hop performance [rho = 0.27 (95% CI − 0.53 to 0.79)].Hop performance is comparable to the uninjured limb by 3–5 years post-ACLR, with the greatest deficits in within-person symmetry present in vertical and side hop tests. Assessment of hopping in multiple planes and comparison with uninjured controls, may provide the most complete evaluation of functional performance.Eligibility Criteria: Hop testing is widely used by clinicians to monitor rehabilitation and decide when to return to sport following anterior cruciate ligament reconstruction (ACLR); however, the trajectory of long-term hop performance has not been summarised.To investigate hop performance change over time after ACLR.Systematic review with longitudinal meta-analysis.MEDLINE, EMBASE, CINAHL, Scopus, Cochrane CENTRAL and SPORTDiscus to 28 February 2023.Studies with ≥ 50 participants following primary ACLR, with mean participant age of 18–40 years, reporting a quantitative measure of hop performance (e.g. single forward hop distance). Results had to be reported for the ACLR limb and compared with (1) the contralateral limb (within person) and/or (2) an uninjured control limb (between person).We included 136 studies of 23,360 participants. Performance was similar across different hop tests, with steep initial improvements in within-person symmetry, tailing off after 18–24 months. ACLR limb hop performance was 5–10% lower compared with the contralateral limb at 1 year post-surgery, with largest deficits observed for vertical hop [87.0% contralateral limb (95% CI 85.3–88.8) compared with single forward hop 93.8% (95% CI 92.8–94.9)]. By 3–5 years, results were similar between ACLR and contralateral limbs. There were limited data for between-person comparisons (n = 17 studies). Exploratory analyses showed deficits in all forward hopping tests to be very strongly correlated with each other [e.g. single forward and triple hop rho = 0.96 (95% CI 0.90–0.99)], though there was discordance in the relationship between single forward hop and vertical hop performance [rho = 0.27 (95% CI − 0.53 to 0.79)].Hop performance is comparable to the uninjured limb by 3–5 years post-ACLR, with the greatest deficits in within-person symmetry present in vertical and side hop tests. Assessment of hopping in multiple planes and comparison with uninjured controls, may provide the most complete evaluation of functional performance.Results: Hop testing is widely used by clinicians to monitor rehabilitation and decide when to return to sport following anterior cruciate ligament reconstruction (ACLR); however, the trajectory of long-term hop performance has not been summarised.To investigate hop performance change over time after ACLR.Systematic review with longitudinal meta-analysis.MEDLINE, EMBASE, CINAHL, Scopus, Cochrane CENTRAL and SPORTDiscus to 28 February 2023.Studies with ≥ 50 participants following primary ACLR, with mean participant age of 18–40 years, reporting a quantitative measure of hop performance (e.g. single forward hop distance). Results had to be reported for the ACLR limb and compared with (1) the contralateral limb (within person) and/or (2) an uninjured control limb (between person).We included 136 studies of 23,360 participants. Performance was similar across different hop tests, with steep initial improvements in within-person symmetry, tailing off after 18–24 months. ACLR limb hop performance was 5–10% lower compared with the contralateral limb at 1 year post-surgery, with largest deficits observed for vertical hop [87.0% contralateral limb (95% CI 85.3–88.8) compared with single forward hop 93.8% (95% CI 92.8–94.9)]. By 3–5 years, results were similar between ACLR and contralateral limbs. There were limited data for between-person comparisons (n = 17 studies). Exploratory analyses showed deficits in all forward hopping tests to be very strongly correlated with each other [e.g. single forward and triple hop rho = 0.96 (95% CI 0.90–0.99)], though there was discordance in the relationship between single forward hop and vertical hop performance [rho = 0.27 (95% CI − 0.53 to 0.79)].Hop performance is comparable to the uninjured limb by 3–5 years post-ACLR, with the greatest deficits in within-person symmetry present in vertical and side hop tests. Assessment of hopping in multiple planes and comparison with uninjured controls, may provide the most complete evaluation of functional performance.Conclusions: Hop testing is widely used by clinicians to monitor rehabilitation and decide when to return to sport following anterior cruciate ligament reconstruction (ACLR); however, the trajectory of long-term hop performance has not been summarised.To investigate hop performance change over time after ACLR.Systematic review with longitudinal meta-analysis.MEDLINE, EMBASE, CINAHL, Scopus, Cochrane CENTRAL and SPORTDiscus to 28 February 2023.Studies with ≥ 50 participants following primary ACLR, with mean participant age of 18–40 years, reporting a quantitative measure of hop performance (e.g. single forward hop distance). Results had to be reported for the ACLR limb and compared with (1) the contralateral limb (within person) and/or (2) an uninjured control limb (between person).We included 136 studies of 23,360 participants. Performance was similar across different hop tests, with steep initial improvements in within-person symmetry, tailing off after 18–24 months. ACLR limb hop performance was 5–10% lower compared with the contralateral limb at 1 year post-surgery, with largest deficits observed for vertical hop [87.0% contralateral limb (95% CI 85.3–88.8) compared with single forward hop 93.8% (95% CI 92.8–94.9)]. By 3–5 years, results were similar between ACLR and contralateral limbs. There were limited data for between-person comparisons (n = 17 studies). Exploratory analyses showed deficits in all forward hopping tests to be very strongly correlated with each other [e.g. single forward and triple hop rho = 0.96 (95% CI 0.90–0.99)], though there was discordance in the relationship between single forward hop and vertical hop performance [rho = 0.27 (95% CI − 0.53 to 0.79)].Hop performance is comparable to the uninjured limb by 3–5 years post-ACLR, with the greatest deficits in within-person symmetry present in vertical and side hop tests. Assessment of hopping in multiple planes and comparison with uninjured controls, may provide the most complete evaluation of functional performance. [ABSTRACT FROM AUTHOR]

Magnetic resonance elastography (MRE) of the liver has emerged as the non-invasive standard for the evaluation of liver fibrosis in chronic liver diseases (CLDs). The utility of MRE in the evaluation of different CLD in both adults and children has been demonstrated in several studies, and MRE has been recommended by several clinical societies. Consequently, the clinical indications for evaluation of CLD with MRE have increased, and MRE is currently used as an add-on test during routine liver MRI studies or as a standalone test. To meet the increasing clinical demand, MRE is being installed in many academic and private practice imaging centers. There is a need for a comprehensive practical guide to help these practices to deliver high-quality liver MRE studies as well as troubleshoot the common issues with MRE to ensure smooth running of the service. This comprehensive clinical practice review summarizes the indications and provides an overview on why to use MRE, technical requirements, system set-up, patient preparation, acquiring the data, and interpretation. [ABSTRACT FROM AUTHOR]

Many studies have identified associations between maternal depression and decreased quality of parenting. In addition to maternal depression, we examined associations of maternal generalized anxiety and empathy with quality of parenting. Mothers (N = 133) participating in a statewide home visiting implementation study completed baseline and follow-up interviews during which information on demographic and psychosocial characteristics were collected. As part of follow-up data collection, mothers were videotaped for fifteen minutes while playing with their infants, aged 4–13 months, using standardized toys. The videos were coded using qualitative rating scales. Multivariate linear regression was used to assess associations of maternal psychosocial well-being: depression, generalized anxiety, and empathy with two parenting outcomes: sensitive and harsh parenting. Depression and anxiety were negatively associated with sensitive parenting. Empathy was negatively associated with harsh parenting. At follow-up, mothers who screened positive for depression or anxiety exhibited less sensitive parenting than those who screened negative for both conditions. Mothers who screened positive for depression or anxiety at baseline but screened negative at follow-up, had similar sensitive parenting scores to mothers who screened negative at both time points. These findings demonstrate the potential benefits of responding effectively to maternal depression and anxiety and the need for programs to identify and respond to maternal depression and anxiety on a continuing basis, not just at enrollment. Highlights: Maternal anxiety and depression were associated with less sensitive parenting of infants. Maternal empathy was associated with less harsh parenting of infants. Mothers with resolved anxiety or depression parented with similar sensitivity as those never screening positive. Providers should screen perinatal women for depression and anxiety regularly and respond to these conditions. [ABSTRACT FROM AUTHOR]

Preadolescents' involvement in religious congregations may serve as a distal protective factor against aggression. Interviews were conducted to explore Puerto Rico (PR) Christian church and faith-based organization (FBO) leaders' knowledge and perceptions about preadolescent violence, and the role of congregations in its prevention. Bullying was perceived as the most common type of aggression among PR preadolescents. Education, positive role modeling, and relationships with pro-social adults are considered important in its prevention. While willing to engage in violence prevention efforts, congregations may possess limited knowledge on the topic and its relevance. Findings can help inform the development of collaborative research and prevention efforts at the family and community levels. [ABSTRACT FROM AUTHOR]

Background: Home telemonitoring has been used with discharged patients in an attempt to reduce 30-day readmissions with mixed results. Objective: To assess whether home 30-day telemonitoring after discharge for patients at high risk of readmission would reduce readmissions or mortality. Design: Prospective, randomized controlled trial. Patients: We compared 30-day readmission rates and mortality for patients at high risk for readmission who received home telemonitoring versus standard care between November 1, 2014, and November 30, 2018, in 2 tertiary care hospitals. Interventions: The intervention group received home-installed equipment to measure blood pressure, heart rate, pulse oximetry, weight if heart failure was present, and glucose if diabetes was present. Results were transmitted daily and reviewed by a nurse. Both groups received standard care. Main Measures: The primary outcome was a composite end point of hospital readmission or death within 30 days after discharge. The secondary outcome was an emergency department visit within 30 days after discharge. Key Results: A total of 1380 participants (mean [SD] age, 66 [14] years; 722 [52.3%] men and 658 [47.7%] women) participated in this study. Using a modified intention-to-treat analysis, the risk of readmission or death within 30 days among patients at high readmission risk was 23.7% (137/578) in the control group and 18.2% (87/477) in the telemonitoring group (absolute risk difference, − 5.5% [95% CI, − 10.4 to − 0.6%]; relative risk, 0.77 [95% CI, 0.61 to 0.98]; P =.03). Emergency department visits occurred within 30 days after discharge in 14.2% (81/570) of patients in the control group and 8.6% (40/464) of patients in the telemonitoring group (absolute risk difference, − 5.6% [95% CI, − 9.4 to − 1.8%]; relative risk, 0.61 [95% CI, 0.42 to 0.87]; P =.005). Conclusions: Thirty days of postdischarge telemonitoring may reduce readmissions of high-risk patients. Trial Registration: ClinicalTrials.gov identifier: NCT02136186. [ABSTRACT FROM AUTHOR]

Purpose: Collecting patients' pain features for congruent pain relief treatment is time-consuming. We sought to identify implementation issues and evaluate the efficacy of an electronic patient self-reporting pain device in community-based cancer clinics. Methods: In a 2-phase descriptive pilot and randomized controlled trial (RCT) with pretest/posttest design, 178 cancer patients participated (n = 33 pilot phase; n = 145 in the RCT phase). Patients completed PAINReportIt®, an electronic version of the valid and reliable McGill Pain Questionnaire that comprehensively measures the multiple dimensions of pain. All pilot phase and RCT patients were asked to complete PAINReportIt® twice and received usual care. For RCT patients assigned to the experimental group, a copy of the PAINReportIt® Summary was placed in their clinic medical record before they visited their clinicians. Posttest measures were completed 3–7 days later. Results: We identified three implementation barriers: system resistance to deposit of research data into the medical record, staff resistance to change, and patients' physical manipulation of the tablet. The time required to complete the tool did not differ significantly between groups but reduced significantly pre- to posttest in both RCT groups. Current pain intensity and pain quality but not worst pain scores decreased significantly pre- to posttest in the experimental group. None of the pain variables differed significantly between groups. Conclusion: Implementation of PAINReportIt® was feasible in community oncology clinic settings. Barriers identified were expected and were surmountable. The studied tool showed satisfactory time sparing for comprehensive pain assessment with data automatically recorded and easily accessed by the clinician in the form of a summary report. Findings support the need for additional research to demonstrate the clinical efficacy of tablet-based pain assessment on patient outcomes as well as clinical care processes such as pain documentation and analgesic prescriptions. [ABSTRACT FROM AUTHOR]

Primary gastrointestinal (GI) mantle cell lymphoma (MCL) is rare and the optimal management is unknown. We reviewed 800 newly diagnosed MCL cases and found 22 primary (2.8%) and 79 (9.9%) secondary GI MCL cases. Age, sex, and performance status were similar between primary and secondary cases. Secondary cases had more elevations in lactate dehydrogenase (28% vs 0%, P = 0.03) and a trend for a higher MCL international prognostic index (P = 0.07). Observation or local therapy was more common for primary GI MCL (29% vs 8%, P < 0.01), and autologous stem-cell transplant was more common for secondary GI MCL (35% vs 14%, P < 0.05). The median follow-up was 85 months. Primary and secondary GI MCL had similar 5-year progression-free survival (PFS) (30% vs 28%, P = 0.59) and overall survival (OS) (65% vs 66%, P = 0.83). The extent of GI involvement in primary GI MCL affected treatment selection but not outcome, with a 5-year PFS of 43% vs 14% vs 31% (P = 0.48) and OS of 57% vs 71% vs 69% (P = 0.54) in cases with single lesion vs multiple lesions in 1 organ vs multiple lesions in ≥2 organs. Less aggressive frontline treatment for primary GI MCL is reasonable. It is unknown whether more aggressive treatment can result in improved outcomes. Highlights: Primary GI MCL is rare. These patients tend to be treated less aggressively in the frontline setting yet have similar outcomes as those with secondary GI MCL. Less aggressive frontline treatment for primary GI MCL is reasonable given decent outcome, although it is unknown whether more aggressive treatment can result in improved outcomes. [ABSTRACT FROM AUTHOR]

Objectives: Fostering, a professional or semi-professional role that is in increasing demand, involves potential exposure to material related to children's trauma in a domestic setting. Yet, professional vulnerability to secondary traumatic stress (STS) is under-researched in foster carers, as is the suitability of associated intervention techniques. We therefore investigated incidence of STS and psychological predictors relevant to secondary and primary stress appraisal in UK foster carers. Methods: British foster carers (n = 187; 81% female; aged 23–72 years; mean length of experience 9 years) were approached through a range of organizations managing paid foster caring in the UK for a survey study. Self-report measures were obtained on STS, burnout and compassion satisfaction from the Professional Quality of Life (ProQOL) scale, as well as on primary trauma and variables previously recommended for inclusion in training targeting secondary trauma: empathy, resilience and self-care. Results: High levels of STS and burnout were found among foster carers. In multivariate model testing, STS was directly and positively predicted by burnout, compassion satisfaction and primary trauma (R2 = 0.54, p < 0.001). Resilience, empathy and self-care did not show direct associations with STS, but self-care had a significant indirect effect on STS. Conclusions: Findings support the view that STS is a substantial risk factor in foster caring. While self-care is confirmed as a promising factor in intervention, the roles of empathy and resilience are more ambiguous. [ABSTRACT FROM AUTHOR]

To determine the longitudinal association of baseline body mass index and change in body mass index over 8 years to incident of patellofemoral osteoarthritis at the 8-year follow-up. A sample of 528 women and men, aged 45–65 years, with knee complaints and without radiographic evidence of patellofemoral and tibiofemoral osteoarthritis at baseline, were selected from the Cohort Hip and Cohort Knee cohort. Incidence of patellofemoral osteoarthritis was defined as presence of radiographic patellofemoral osteoarthritis (with or without tibiofemoral osteoarthritis) at the 8-year follow-up. Baseline body mass index data were categorized into normal, overweight, and obese weight-categories. Logistic regression analyses, adjusted for age and sex, were conducted to determine the association of baseline body mass index and change in body mass index to patellofemoral osteoarthritis incidence 8 years later. Obesity was associated with greater odds of radiographic patellofemoral osteoarthritis incident (odds ratio: 1.8 [95% CI 1.1, 3.1]) 8 years later. There were no significant associations observed between body mass index change over 8 years and incidence of radiographic patellofemoral osteoarthritis in overweight and obese individuals. Obesity is associated with increased odds of developing radiographic patellofemoral osteoarthritis 8 years later. [ABSTRACT FROM AUTHOR]

Background: Hip arthroscopy is a common surgical intervention for young and middle-aged adults with hip-related pain and dysfunction, who have high expectations for returning to physical activity following surgery. The purpose of this review was to evaluate the impact of hip arthroscopy on physical activity post-arthroscopy. Methods: A systematic search of electronic databases was undertaken in identifying studies from January 1st 1990 to December 5th 2019. The search included English language articles reporting physical activity as an outcome following hip arthroscopy in adults aged 18-50 years. Quality assessment, data extraction and synthesis of included studies were undertaken. Results: Full text articles (n = 234) were assessed for eligibility following screening of titles and abstracts (n = 2086), yielding 120 studies for inclusion. The majority (86%) of the studies were level 4 evidence. No studies reported objective activity data. The most frequently occurring patient-reported outcome measure was the Hip Outcome Score-sport-specific subscale (HOS-SS, 84% of studies). Post--arthroscopy improvement was indicated by large effect sizes for patient-reported outcome measures (standard paired difference [95% confidence interval] −1.35[−1.61 to −1.09] at more than 2 years post-arthroscopy); however, the majority of outcome scores for the HOS-SS did not meet the defined level for a patient-acceptable symptom state. Conclusion: The current level of available information regarding physical activity for post arthroscopy patients is limited in scope. Outcomes have focused on patients' perceived difficulties with sport-related activities with a paucity of information on the type, quality and quantity of activity undertaken. Level of Evidence: Level IV, systematic review of Level 2 through to Level 4 studies [ABSTRACT FROM AUTHOR]

First Steps (FS) is a brief obstetrics-based primary prevention strategy that aims to strengthen protective factors to prevent child maltreatment. This randomized controlled trial assessed how well FS services aligned with family interests and needs, how FS providers used communication strategies to build partnership with mothers, and the impact of FS on mothers' parenting knowledge in core content areas and access to services. Mothers completed a baseline survey and were randomly assigned to FS and control conditions (n = 374 and 375, respectively). The parenting education services provided to mothers were assessed by independent participant report immediately postintervention for the full FS group and by analysis of audio-recordings of the FS encounter for a subsample (n = 150). Outcomes were measured at 4 months via maternal survey. Compared to controls at follow-up, FS mothers had significantly higher knowledge scores in some areas but similar access to needed services. Few mothers lacked access to most services at baseline, and FS content was similar to that provided by other hospital personnel. FS providers' communication style promoted rapport, but providers did not tailor content to mothers' educational and service access needs. Implications of the findings for similar services are discussed. [ABSTRACT FROM AUTHOR]

Background: In athletes, hip and groin pain is considered to be associated with hip intra-articular pathologies and hip osteoarthritis (OA). A greater understanding of the relationship between hip and groin pain and imaging findings is required. Objective: Our objective was to undertake a systematic review and meta-analysis to determine the prevalence of hip intra-articular pathologies and hip OA in athletes with and without hip and groin pain. Methods: Seven electronic databases were searched on 29 January 2018 for studies investigating the prevalence of hip intra-articular pathologies and hip OA using X-ray, magnetic resonance imaging, magnetic resonance arthrography or computed tomography. The search, study selection, quality appraisal and data extraction were performed by two independent reviewers. When studies were considered homogenous, meta-analysis was undertaken. A strength of evidence was given to pooled results. Results: Twenty studies reporting on the prevalence of hip intra-articular pathologies and hip OA in athletes were identified. Included studies were considered moderate to high risk of bias, with only three studies adjudged as low risk of bias. In asymptomatic athletes, limited evidence identified a labral tear prevalence of 54% per person and moderate evidence of 33% per hip. In symptomatic athletes, moderate evidence of a labral tear prevalence of 20% per hip was found. Moderate evidence of a cartilage defect prevalence of 10% per person was reported in asymptomatic athletes. In symptomatic athletes, cartilage defect prevalence was 7–40%. In asymptomatic athletes, the prevalence of hip OA was 0–17%, compared with 2% in symptomatic athletes. Conclusion: The prevalence of hip intra-articular pathologies and hip OA in symptomatic and asymptomatic athletes is variable. Labral tears and cartilage defects appear to be seen often in athletes with and without pain. Hip OA is rarely seen in athletes either with or without hip and groin pain. Study Registration: PROSPERO registration CRD42017082457. [ABSTRACT FROM AUTHOR]

Purpose: Individuals with impaired knee function after anterior cruciate ligament reconstruction (ACLR) may be at greater risk of developing knee osteoarthritis related to abnormal knee joint movement and loading. The aim of this study was to assess the association between knee biomechanics and knee laxity during hopping and clinically assessed knee function (i.e., patient-reported knee function and hop tests) following ACLR.Methods: Sixty-six participants (23 women, mean age 28 ± 6 years, mean 18 ± 3 months following ACLR) completed a standardized single-leg hopping task. Three-dimensional movement analysis was used to assess knee flexion excursion and body weight/height normalized knee flexion moments during landing for the involved limb. Anterior-posterior knee laxity was assessed with a KT-1000 knee arthrometer. Participants then completed a patient-reported knee function questionnaire and three separate hop tests (% of uninvolved limb) and were divided into poor and satisfactory knee function groups (satisfactory: ≥85% patient-reported knee function and ≥ 85% hop test symmetry). Associations between knee function and hop biomechanics/knee laxity were assessed using logistic regression and interquartile range scaled odds ratios (ORIQR).Results: Greater knee flexion excursion (ORIQR 2.9, 95%CI 1.1-7.8), greater knee flexion moment (ORIQR 4.9, 95%CI 1.6-14.3) and lesser knee laxity (ORIQR 4.7, 95%CI 1.5-14.9) were significantly associated with greater odds of having satisfactory knee function (≥ 85% patient-reported knee function and ≥ 85% hop test symmetry).Conclusion: Greater knee flexion excursion/moment during hop-landing and lesser knee laxity is associated with better patient-reported knee function and single-leg hop test performance following ACLR. Patients with lower levels of knee function following ACLR demonstrated hop-landing biomechanics previously associated with early patellofemoral osteoarthritis. Therefore, interventions aimed at improving hop landing biomechanics in people with poor knee function are likely required.Level Of Evidence: III, Cross-sectional study. [ABSTRACT FROM AUTHOR]

Purpose: To compare the efficacy of use of digital breast tomosynthesis (DBT) with standard digital mammography (DM) workup views in the breast cancer assessment clinic.Materials and Methods: The Tomosynthesis Assessment Clinic trial (TACT), conducted between 16 October 2014 and 19 April 2016, is an ethics-approved, monocenter, multireader, multicase split-plot reading study. After written informed consent was obtained, 144 females (age > 40 years) who were recalled to the assessment clinic were recruited into TACT. These cases (48 cancers) were randomly allocated for blinded review of (1) DM workup and (2) DBT, both in conjunction with previous DM from the screening examination. Fifteen radiologists of varying experience levels in the Australia BreastScreen Program were included in this study, wherein each radiologist read 48 cases (16 cancers) in 3 non-overlapping blocks. Diagnostic accuracy was measured by means of sensitivity, specificity, and positive (PPV) and negative predictive values (NPV). The receiver-operating characteristic area under the curve (AUC) was calculated to determine radiologists' performances.Results: Use of DBT (AUC = 0.927) led to improved performance of the radiologists (z = 2.62, p = 0.008) compared with mammography workup (AUC = 0.872). Similarly, the sensitivity, specificity, PPV, and NPV of DBT (0.93, 0.75, 0.64, 0.96) were higher than those of the workup (0.90, 0.56, 0.49, 0.92). Most radiologists (80%) performed better with DBT than standard workup. Cancerous lesions on DBT appeared more severe (U = 33,172, p = 0.02) and conspicuous (U = 24,207, p = 0.02). There was a significant reduction in the need for additional views (χ2 = 17.63, p < 0.001) and recommendations for ultrasound (χ2 = 8.56, p = 0.003) with DBT.Conclusions: DBT has the potential to increase diagnostic accuracy and simplify the assessment process in the breast cancer assessment clinic.Key Points: • Use of DBT in the assessment clinic results in increased diagnostic accuracy. • Use of DBT in the assessment clinic improves performance of radiologists and also increases the confidence in their decisions. • DBT may reduce the need for additional views, ultrasound imaging, and biopsy. [ABSTRACT FROM AUTHOR]

Dopamine modulates medial prefrontal cortex (mPFC) activity to mediate diverse behavioural functions1,2; however, the precise circuit computations remain unknown. One potentially unifying model by which dopamine may underlie a diversity of functions is by modulating the signal-to-noise ratio in subpopulations of mPFC neurons3-6, where neural activity conveying sensory information (signal) is amplified relative to spontaneous firing (noise). Here we demonstrate that dopamine increases the signal-to-noise ratio of responses to aversive stimuli in mPFC neurons projecting to the dorsal periaqueductal grey (dPAG). Using an electrochemical approach, we reveal the precise time course of pinch-evoked dopamine release in the mPFC, and show that mPFC dopamine biases behavioural responses to aversive stimuli. Activation of mPFC-dPAG neurons is sufficient to drive place avoidance and defensive behaviours. mPFC-dPAG neurons display robust shock-induced excitations, as visualized by single-cell, projection-defined microendoscopic calcium imaging. Finally, photostimulation of dopamine terminals in the mPFC reveals an increase in the signal-to-noise ratio in mPFC-dPAG responses to aversive stimuli. Together, these data highlight how dopamine in the mPFC can selectively route sensory information to specific downstream circuits, representing a potential circuit mechanism for valence processing. Dopamine in the medial prefrontal cortex modulates behavioural responses to aversive stimuli by increasing the signal-to-noise ratio of neurons projecting to the dorsal periaqueductal grey. [ABSTRACT FROM AUTHOR]

Purpose: Patellofemoral osteoarthritis (PFOA) occurs in approximately half of anterior cruciate ligament (ACL)-injured knees within 10-15 years of trauma. Risk factors for post-traumatic PFOA are poorly understood. Patellofemoral alignment and trochlear morphology may be associated with PFOA following ACL reconstruction (ACLR), and understanding these relationships, particularly early in the post-surgical time period, may guide effective early intervention strategies. In this study, patellofemoral alignment and trochlear morphology were investigated in relation to radiographic features of early PFOA 1-year post-ACLR.Methods: Participants (aged 18-50 years) had undergone ACLR approximately 1 year prior to being assessed. Early PFOA was defined as presence of a definite patellofemoral osteophyte on lateral or skyline radiograph. Sagittal and axial plane alignment and trochlear morphology were estimated using MRI. Using logistic regression, the relationship between alignment or morphology and presence of osteophytes was evaluated.Results: Of 111 participants [age 30 ± 8.5; 41 (37%) women], 19 (17%) had definite osteophytes, only two of whom had had patellofemoral chondral lesions noted intra-operatively. One measure of patellar alignment (bisect offset OR 1.1 [95% confidence interval 1.0, 1.2]) and two measures of trochlear morphology (sulcus angle OR 1.1 [1.0, 1.2], trochlear angle OR 1.2 [1.0, 1.5]) were associated with patellofemoral osteophytes.Conclusions: Patellofemoral malalignment and/or altered trochlear morphology were associated with PFOA 1 year following ACLR compared to individuals post-ACLR without these features. Clarifying the role of alignment and morphology in post-traumatic PFOA may contribute to improving early intervention strategies aimed at secondary prevention.Level Of Evidence: IV. [ABSTRACT FROM AUTHOR]

Purpose: Poor knee function after anterior cruciate ligament reconstruction (ACLR) may increase the risk of future knee symptoms and knee osteoarthritis via abnormal knee joint loading patterns, particularly during high-impact activity. This study aimed to assess the relationship between poor self-reported or clinically measured knee function and knee moments/vertical ground reaction force (vGRF) in individuals following ACLR.Methods: 61 participants (mean 16.5 ± 3 months following ACLR, 23 women) completed a patient-reported knee function questionnaire and three hop tests (% of uninvolved limb). Participants were divided into satisfactory and poor knee function groups (poor < 85% patient-reported knee function and/or < 85% hop test symmetry). The knee biomechanics of both groups were assessed with three-dimensional motion analysis during the stance phase of overland running at self-selected speeds, and the association between knee function and knee moments was assessed using analysis of covariance with running speed as a covariate.Results: Participants with poor knee function (n = 30) ran with significantly smaller peak knee flexion moments (moderate effect size 0.7, p = 0.03) and significantly smaller peak vGRFs (large effect size 1.0, p = 0.002) compared to those with satisfactory knee function (n = 31). No significant differences were observed for knee adduction and knee external rotation moments or knee kinematics.Conclusion: Individuals following ACLR with poor self-reported knee function and/or hop test performance demonstrate knee moments during running that may be associated with lower knee joint contact forces. These findings provide greater understanding of the relationship between knee biomechanics during running and clinical assessments of knee function.Level Of Evidence: III. Cross-sectional study. [ABSTRACT FROM AUTHOR]

Activity remodels neurons, altering their molecular, structural, and electrical characteristics. To enable the selective characterization and manipulation of these neurons, we present FLARE, an engineered transcription factor that drives expression of fluorescent proteins, opsins, and other genetically encoded tools only in the subset of neurons that experienced activity during a user-defined time window. FLARE senses the coincidence of elevated cytosolic calcium and externally applied blue light, which together produce translocation of a membrane-anchored transcription factor to the nucleus to drive expression of any transgene. In cultured rat neurons, FLARE gives a light-to-dark signal ratio of 120 and a high- to low-calcium signal ratio of 10 after 10 min of stimulation. Opsin expression permitted functional manipulation of FLARE-marked neurons. In adult mice, FLARE also gave light- and motor-activity-dependent transcription in the cortex. Due to its modular design, minute-scale temporal resolution, and minimal dark-state leak, FLARE should be useful for the study of activity-dependent processes in neurons and other cells that signal with calcium. [ABSTRACT FROM AUTHOR]

The original article can be found online. [ABSTRACT FROM AUTHOR]

Introduction: If physical impairments that are associated with poorer outcomes can be identified in people with chondrolabral hip pathology, then rehabilitation programmes that target such modifiable impairments could potentially be established to improve quality of life. The aim of this study was to examine the relationship between quality-of-life PROs and physical impairment measurements in people with chondrolabral pathology post-hip arthroscopic surgery.Methods: This was a cross-sectional study where multiple stepwise linear regression analyses were conducted to determine which physical impairment measurements were most associated with poorer quality-of-life patient-reported outcomes (PROs). Eighty-four patients (42 women; all aged 36 ± 10 years) with hip chondrolabral pathology 12- to 24-month post-hip arthroscopy were included. The Hip disability and Osteoarthritis Outcome Score Quality-of-life (HOOS-Q) subscale and International Hip Outcome Tool (IHOT-33) PROs were collected. Measurements of active hip ROM and strength were assessed.Results: Modifiable post-surgical physical impairments were associated with PRO in patients with chondrolabral pathology. Greater hip flexion ROM was independently associated with better scores in both HOOS-Q and IHOT-33 (adjusted r 2 values ranged from 0.249 to 0.341). Greater hip adduction strength was independently associated with better HOOS-Q and IHOT-33 (adjusted r 2 0.227-0.317). Receiver Operator Curve analyses determined that the limit value for hip flexion ROM was 100° (sensitivity 92 %, specificity 75 %), and hip adduction strength was 0.86 Nm/kg (sensitivity 96 %, specificity 70 %).Conclusions: Hip flexion ROM and adduction strength were associated with better quality-of-life PRO scores in patients with chondrolabral pathology 12- to 24-month post-hip arthroscopy. These impairments could be targeted by clinicians designing rehabilitation programmes to this patient group.Level Of Evidence: Cross-sectional study, Level IV. [ABSTRACT FROM AUTHOR]

Human papillomavirus (HPV) infection is the causative agent in cervical cancer, and is associated with numerous other genital cancers, including vulvar, vaginal, and anal cancer. Primary prevention with HPV vaccination is safe and efficacious, and a recently approved HPV vaccine will provide even more extensive protection against several oncogenic HPV strains. Screening strategies for HPV are rapidly evolving, reflecting the essential role that HPV infection plays in cervical cancer. This article highlights new evidence regarding the efficacy of the recently approved 9-valent HPV (9vHPV) vaccine and the use of primary high-risk HPV testing in cervical cancer screening. We consider the utility of urinary HPV testing in routine clinical practice and review current guidelines regarding anal HPV screening. [ABSTRACT FROM AUTHOR]

Purpose: Individuals following anterior cruciate ligament reconstruction (ACLR) with concomitant meniscal pathology have a higher risk of developing knee osteoarthritis (OA) compared to those with isolated ACLR. Knee extensor weakness and altered dynamic knee joint biomechanics have been suggested to play a role in the development of knee OA following ACLR. This study investigated whether these factors differ in people following ACLR who have concomitant meniscal pathology compared to patients with isolated ACLR.Methods: Thirty-three patients with isolated ACLR and 34 patients with ACLR and meniscal pathology underwent strength and gait assessment 12-24 months post-operatively. Primary measures were peak isometric knee extensor torque and knee adduction moment (peak and impulse). Secondary measures included peak knee flexion moment and knee kinematics (sagittal and transverse).Results: There were no between-group differences in knee extensor strength [mean difference (95 % CI) 0.09 (-0.23 to 0.42) Nm/kg, n.s.], peak knee adduction moment [-0.02 (-0.54 to 0.49) Nm/(BW × HT) %, n.s.] or knee adduction moment impulse [0.01 (-0.15 to 0.17) Nm/(BW × HT) %, p = n.s.]. No between-group differences were found for any secondary measures.Conclusions: No evidence was found to suggest that the higher prevalence of OA in patients with ACLR and meniscal pathology compared to patients with isolated ACLR is attributed to reduced knee muscle strength or altered knee joint biomechanics assessed 1-2 years post-surgery. Given that there is a higher incidence of knee OA in patients with concomitant meniscal pathology and ACLR, further investigation is needed so that population-specific rehabilitation protocols can be developed.Level Of Evidence: III. [ABSTRACT FROM AUTHOR]

Although anxiety disorders represent a major societal problem demanding new therapeutic targets, these efforts have languished in the absence of a mechanistic understanding of this subjective emotional state. While it is impossible to know with certainty the subjective experience of a rodent, rodent models hold promise in dissecting well-conserved limbic circuits. The application of modern approaches in neuroscience has already begun to unmask the neural circuit intricacies underlying anxiety by allowing direct examination of hypotheses drawn from existing psychological concepts. This information points toward an updated conceptual model for what neural circuit perturbations could give rise to pathological anxiety and thereby provides a roadmap for future therapeutic development. [ABSTRACT FROM AUTHOR]

The ability to differentiate stimuli predicting positive or negative outcomes is critical for survival, and perturbations of emotional processing underlie many psychiatric disease states. Synaptic plasticity in the basolateral amygdala complex (BLA) mediates the acquisition of associative memories, both positive and negative. Different populations of BLA neurons may encode fearful or rewarding associations, but the identifying features of these populations and the synaptic mechanisms of differentiating positive and negative emotional valence have remained unknown. Here we show that BLA neurons projecting to the nucleus accumbens (NAc projectors) or the centromedial amygdala (CeM projectors) undergo opposing synaptic changes following fear or reward conditioning. We find that photostimulation of NAc projectors supports positive reinforcement while photostimulation of CeM projectors mediates negative reinforcement. Photoinhibition of CeM projectors impairs fear conditioning and enhances reward conditioning. We characterize these functionally distinct neuronal populations by comparing their electrophysiological, morphological and genetic features. Overall, we provide a mechanistic explanation for the representation of positive and negative associations within the amygdala. [ABSTRACT FROM AUTHOR]

The amygdala has long been associated with emotion and motivation, playing an essential part in processing both fearful and rewarding environmental stimuli. How can a single structure be crucial for such different functions? With recent technological advances that allow for causal investigations of specific neural circuit elements, we can now begin to map the complex anatomical connections of the amygdala onto behavioural function. Understanding how the amygdala contributes to a wide array of behaviours requires the study of distinct amygdala circuits. [ABSTRACT FROM AUTHOR]

Site-specific gene addition can allow stable transgene expression for gene therapy. When possible, this is preferred over the use of promiscuously integrating vectors, which are sometimes associated with clonal expansion and oncogenesis. Site-specific endonucleases that can induce high rates of targeted genome editing are finding increasing applications in biological discovery and gene therapy. However, two safety concerns persist: endonuclease-associated adverse effects, both on-target and off-target; and oncogene activation caused by promoter integration, even without nucleases. Here we perform recombinant adeno-associated virus (rAAV)-mediated promoterless gene targeting without nucleases and demonstrate amelioration of the bleeding diathesis in haemophilia B mice. In particular, we target a promoterless human coagulation factor IX (F9) gene to the liver-expressed mouse albumin (Alb) locus. F9 is targeted, along with a preceding 2A-peptide coding sequence, to be integrated just upstream to the Alb stop codon. While F9 is fused to Alb at the DNA and RNA levels, two separate proteins are synthesized by way of ribosomal skipping. Thus, F9 expression is linked to robust hepatic albumin expression without disrupting it. We injected an AAV8-F9 vector into neonatal and adult mice and achieved on-target integration into ∼0.5% of the albumin alleles in hepatocytes. We established that F9 was produced only from on-target integration, and ribosomal skipping was highly efficient. Stable F9 plasma levels at 7-20% of normal were obtained, and treated F9-deficient mice had normal coagulation times. In conclusion, transgene integration as a 2A-fusion to a highly expressed endogenous gene may obviate the requirement for nucleases and/or vector-borne promoters. This method may allow for safe and efficacious gene targeting in both infants and adults by greatly diminishing off-target effects while still providing therapeutic levels of expression from integration. [ABSTRACT FROM AUTHOR]

Mice in which lung epithelial cells can be induced to express an oncogenic KrasG12D develop lung adenocarcinomas in a manner analogous to humans. A myriad of genetic changes accompany lung adenocarcinomas, many of which are poorly understood. To get a comprehensive understanding of both the transcriptional and post-transcriptional changes that accompany lung adenocarcinomas, we took an omics approach in profiling both the coding genes and the non-coding small RNAs in an induced mouse model of lung adenocarcinoma. RNAseq transcriptome analysis of KrasG12D tumors from F1 hybrid mice revealed features specific to tumor samples. This includes the repression of a network of GTPase-related genes (Prkg1, Gnao1 and Rgs9) in tumor samples and an enrichment of Apobec1-mediated cytosine to uridine RNA editing. Furthermore, analysis of known single-nucleotide polymorphisms revealed not only a change in expression of Cd22 but also that its expression became allele specific in tumors. The most salient finding, however, came from small RNA sequencing of the tumor samples, which revealed that a cluster of ∼53 microRNAs and mRNAs at the Dlk1-Dio3 locus on mouse chromosome 12qF1 was markedly and consistently increased in tumors. Activation of this locus occurred specifically in sorted tumor-originating cancer cells. Interestingly, the 12qF1 RNAs were repressed in cultured KrasG12D tumor cells but reactivated when transplanted in vivo. These microRNAs have been implicated in stem cell pleuripotency and proteins targeted by these microRNAs are involved in key pathways in cancer as well as embryogenesis. Taken together, our results strongly imply that these microRNAs represent key targets in unraveling the mechanism of lung oncogenesis. [ABSTRACT FROM AUTHOR]

Optogenetic inhibition of the electrical activity of neurons enables the causal assessment of their contributions to brain functions. Red light penetrates deeper into tissue than other visible wavelengths. We present a red-shifted cruxhalorhodopsin, Jaws, derived from Haloarcula (Halobacterium) salinarum (strain Shark) and engineered to result in red light-induced photocurrents three times those of earlier silencers. Jaws exhibits robust inhibition of sensory-evoked neural activity in the cortex and results in strong light responses when used in retinas of retinitis pigmentosa model mice. We also demonstrate that Jaws can noninvasively mediate transcranial optical inhibition of neurons deep in the brains of awake mice. The noninvasive optogenetic inhibition opened up by Jaws enables a variety of important neuroscience experiments and offers a powerful general-use chloride pump for basic and applied neuroscience. [ABSTRACT FROM AUTHOR]