Search

Irritability is a transdiagnostic indicator of child and adolescent internalizing and externalizing problems that is measurable from early life. The objective of this systematic review was to determine the strength of the association between irritability measured from 0 to 5 years and later internalizing and externalizing problems, to identify mediators and moderators of these relationships, and to explore whether the strength of the association varied according to irritability operationalization. Relevant studies published in peer-reviewed, English-language journals between the years 2000 and 2021 were sought from EMBASE, PsycINFO, MEDLINE, CINAHL, and ERIC. We synthesized studies that included a measure of irritability within the first 5 years of life and reported associations with later internalizing and/or externalizing problems. Methodological quality was assessed using the JBI-SUMARI Critical Appraisal Checklist. Of 29,818 identified studies, 98 met inclusion criteria, with a total number of 932,229 participants. Meta-analysis was conducted on 70 studies (n = 831,913). Small, pooled associations were observed between infant irritability (0-12 months) and later internalizing (r = 0.14, 95% CI = 0.09, 0.20) and externalizing symptoms (r = 0.16, 95% CI = 0.11, 0.21) symptoms. For toddler/preschool irritability (13-60 months), small-to-moderate pooled associations were observed for internalizing (r = 0.21, 95% CI = 0.14, 0.28) and externalizing (r = 0.24, 95% CI = 0.18, 0.29) symptoms. These associations were not moderated by the lag between irritability and outcome assessment, although the strength of the associations varied according to irritability operationalization. Early irritability is a consistent transdiagnostic predictor of internalizing and externalizing symptoms in childhood and adolescence. More work is required to understand how to accurately characterize irritability across this developmental period, and to understand mechanisms underlying the relationship between early irritability and later mental health problems. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented racial and/or ethnic groups in science. One or more of the authors of this paper self-identifies as living with a disability. We actively worked to promote sex and gender balance in our author group. We actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our author group. Early irritability as a transdiagnostic neurodevelopmental vulnerability to early onset mental health problems: A systematic review; https://www.crd.york.ac.uk/prospero/ ; CRD42020214658. [ABSTRACT FROM AUTHOR]

RasGAP (p120RasGAP), the founding member of the GTPase-activating protein (GAP) family, is one of only nine human proteins to contain two SH2 domains and is essential for proper vascular development. Despite its importance, its interactions with key binding partners remains unclear. In this study we provide a detailed viewpoint of RasGAP recruitment to various binding partners and assess their impact on RasGAP activity. We reveal the RasGAP SH2 domains generate distinct binding interactions with three well-known doubly phosphorylated binding partners: p190RhoGAP, Dok1, and EphB4. Affinity measurements demonstrate a 100-fold weakened affinity for RasGAP-EphB4 binding compared to RasGAP-p190RhoGAP or RasGAP-Dok1 binding, possibly driven by single versus dual SH2 domain engagement with a dominant N-terminal SH2 interaction. Small-angle X-ray scattering reveals conformational differences between RasGAP-EphB4 binding and RasGAPp190RhoGAP binding. Importantly, these interactions do not impact catalytic activity, implying RasGAP utilizes its SH2 domains to achieve diverse spatial-temporal regulation of Ras signaling in a previously unrecognized fashion. [ABSTRACT FROM AUTHOR]

Obsessive-compulsive disorder (OCD) is a condition with poor treatment outcomes. Improved understanding of the aetiology can inform prevention and treatment approaches; hence several studies have assessed early maladaptive schemas (EMSs) in OCD. This systematic review and meta-analysis aimed to synthesise the evidence on relationships between the 18 EMSs and OCD. The study was conducted according to PRISMA guidelines and registered on PROSPERO (CRD42022329337). A systematic search of PubMed, PsycINFO, and CINAHL Complete was conducted on 4 June 2022. Studies in peer-reviewed journal articles were included if they assessed EMSs and OCD (diagnosis or symptom severity) in adults with a mean age of 18 years or older. Studies were excluded if they were not in English, did not include original quantitative data, or reported on case studies. Study details were tabulated and the meta-analysis findings were presented using forest plots. Methodological quality was assessed using the Appraisal tool for Cross-Sectional Studies (AXIS). Based on 22 studies (pooled N = 3699), all 18 EMSs were positively correlated with OCD. The largest associations were with the dependence/incompetence (r = 0.40 95 % CI [0.32, 0.47]), vulnerability to harm or illness (r = 0.40 95 % CI [0.32, 0.48]), and negativity/pessimism schemas (r = 0.42 95 % CI [0.22, 0.58]). Several meta-analyses showed considerable heterogeneity and publication bias. The findings suggest all EMSs, particularly those relating to disproportionate negative expectations and a perceived inability to cope, are implicated in OCD. Psychological prevention and treatment for OCD may benefit from targeting these schemas. • All 18 early maladaptive schemas are associated with obsessive-compulsive disorder. • Dependence, vulnerability to harm, and pessimism had the largest associations. • Schemas representing negative expectations and coping inability are related to OCD. [ABSTRACT FROM AUTHOR]

To validate a culturally tailored 7-day beverage intake questionnaire for Latino children (BIQ-L). Cross-sectional. Federally qualified health center in San Francisco, CA. Latino parents and their children aged 1–5 years (n = 105). Parents completed the BIQ-L for each child and three 24-hour dietary recalls. Participants' height and weight were measured. Correlations between the mean intake of beverages in 4 categories as determined by the BIQ-L and three 24-hour dietary recalls were assessed. Multivariable linear regression examined the association between sugar-sweetened beverages (SSB) servings as determined by the BIQ-L and child body mass index z-score. Mean daily intake of SSB (r = 0.52, P < 0.001), 100% fruit juice (r = 0.45, P < 0.001), flavored milk (r = 0.7, P < 0.001), and unflavored milk (r = 0.7, P < 0.001) from the BIQ-L were correlated with intake assessed via three 24-hour dietary recalls. In the multivariable model, weekly servings of SSBs were associated with child body mass index z-score (β = 0.15, P = 0.02). Culturally specific beverages comprised 38% of the SSB intake reported on the BIQ-L. The BIQ-L is a valid tool for assessing beverage intake among Latino children aged 1–5 years. The inclusion of culturally specific beverages is critical for accurately assessing beverage intake among Latino children. [ABSTRACT FROM AUTHOR]

• Disrupting reconsolidation may allow new treatments for mental health disorders. • There are challenges in translating reconsolidation-based approaches to the clinic. • Understanding boundary conditions should facilitate clinical translation. Reconsolidation results in the restabilisation, and thus persistence, of a memory made labile by retrieval, and interfering with this process is thought to enable modification or weakening of the original trace. As such, reconsolidation-blockade has been a focus of research aiming to target the maladaptive memories underlying mental health disorders, including post-traumatic stress disorder and drug addiction. Current first-line therapies are not effective for all patients, and a substantial proportion of those for whom therapies are effective later relapse. A reconsolidation-based intervention would be invaluable as an alternative treatment for these conditions. However, the translation of reconsolidation-based therapies to the clinic presents a number of challenges, with arguably the greatest being the overcoming of the boundary conditions governing the opening of the reconsolidation window. These include factors such as the age and strength of memory, and can broadly be divided into two categories: intrinsic features of the targeted memory itself, and parameters of the reactivation procedure used. With maladaptive memory characteristics inevitably varying amongst individuals, manipulation of the other limitations imposed by procedural variables have been explored to circumvent the boundary conditions on reconsolidation. Although several apparently discrepant results remain to be reconciled and these limitations yet to be truly defined, many studies have produced successful results which encouragingly demonstrate that boundary conditions may be overcome using various proposed strategies to enable translation of a reconsolidation-based intervention to clinical use. [ABSTRACT FROM AUTHOR]

The preanalytical phase of testing, including sample transportation, is a common source of error in laboratory testing. Previous studies have shown inversion of centrifuged plasma separator tubes (PST) results in elevation in certain analytes. However, it remains unclear if routine transportation practices, without full inversion, can have a similar impact. This study used 12 residual samples submitted in PST and 4 PST tube samples collected from healthy donors. All samples were measured at baseline. Analytes measured were white blood cells (WBCs), red blood cells (RBCs), platelets (PLTs) using the Sysmex XN-1000 and potassium (K), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), sodium (NA), and alanine aminotransferase (ALT) using the Ortho Vitros 4600. The samples were split into two groups: 1 group was placed vertically in racks and the other group were laid horizontally in a messenger bag-style soft-sided cooler used by lab couriers. A cold pack was placed in the bag, equidistant from both groups of samples. To mimic courier transportation, the bag was carried for 30 min, returned to the laboratory and immediately analyzed. Subsequently, the samples were re-centrifuged and analyzed again. Statistics were performed using GraphPad Prism. LDH increased following transportation for vertical and horizontal samples and remained elevated despite re-centrifugation. K was only increased in the horizontal samples following re-centrifugation. Notably, AST as well as WBCs, RBCs, and PLTs all increased following transportation, but dropped to baseline concentrations following re-centrifugation. Centrifuged PSTs should be kept in a vertical position during transportation by courier. Re-centrifugation of plasma gel tubes after transportation may be necessary for certain chemistry tests. [ABSTRACT FROM AUTHOR]

1. Enhance the learner's knowledge of the nursing home palliative care referral process. 2. Enhance the learner's knowledge of palliative care referral barriers and recommended solutions as perceived by nursing home staff and providers. This qualitative descriptive study examines the perspective of clinicians involved in the care of nursing home residents. Participants describe the palliative care referral process and important barriers along the referral pathway with actionable recommendations. Palliative care can improve comfort, quality of life, and patient/family care experiences while decreasing cost. Despite these positive outcomes, nursing home residents do not receive palliative care consultation services relative to the high prevalence of perceived need. To examine the nursing home palliative care referral process and describe the barriers and solutions to consultation as perceived by nursing home staff, providers and palliative care specialists. We applied a rapid qualitative approach to analyze semi-structured interviews using directed content analysis. Participants were eligible if they worked in the nursing home setting or provided palliative care to nursing home residents. Seventeen participants representing various roles (e.g., nurses, physician, nurse practitioners) participated. Overall, each group described the various processes of referring residents for palliative care consultation in nursing homes and common barriers. The referral process was described as a complex multistep process comprising several distinct stages that were common among all participants. The stages [and barriers] encompass: 1) resident identification [lack of referral standards, lack staff knowledge, staff focus on tasks such as medication administration] 2) eligibility assessment [financial disincentive], 3) consensus-building [misperceptions, conflicted goals of care], and 4) consultation [transportation, workforce limitations]. In addition, many participants spontaneously provided recommendations for ways to improve the referral process and mitigate these barriers. Our findings describe the nursing home palliative care referral process including the barriers and solutions as perceived by nursing home staff, providers, and palliative care specialists. For nursing home administrators and policymakers, the identified barriers can inform the development of targeted training programs and resources for staff to address these challenges effectively. The results highlight the complex multistep palliative care referral process and provide targets for future interventions aimed at improving access to palliative care for nursing home residents. [ABSTRACT FROM AUTHOR]

1. Enhance the learner's knowledge of palliative care benefits for nursing home residents. 2. Enhance the learner's knowledge of barriers to palliative care for nursing home residents. This qualitative descriptive study records the perspective of clinicians involved in the care of nursing home residents. Participants describe the benefits and barriers of palliative care at the resident and facility level. The results provide targets for future interventions aimed at improving access to palliative care for nursing home residents. Palliative care can improve comfort, quality of life, and patient/family care experiences while decreasing cost. Despite these positive outcomes, nursing home residents do not receive palliative care services relative to the high prevalence of perceived need. To identify and describe the benefits and barriers of palliative care in nursing homes from the perspective of nursing home staff, primary care practitioners, and specialty palliative care providers. We applied a rapid qualitative approach to analyze semi-structured interviews using directed content analysis. Participants were eligible if they worked in the nursing home setting or provided palliative care to nursing home residents. Participants (N=17) included nursing home key informants representing a variety of roles (e.g., nurses, physician, nurse practitioners). Participant perceptions of benefits and barriers are organized at the resident and facility level. Benefits. Resident-level: 1) improved symptom management; and 2) extra support and services [subthemes: spiritual care, bereavement, transparent discussions and anticipatory guidance]. Facility-level: 3) legal and regulatory compliance [subthemes of opioid prescribing, behavior management, and nursing home regulations]; and 4) extra medical support [subtheme of preventing hospitalization]. Barriers. Resident-level: 1) misperceptions of palliative care [subtheme of stigma]; 2) transportation difficulties; 3) conflicted goals of care [subthemes of rehabilitation, complex family dynamics, and lack of anticipatory guidance]; and 4) financial disincentives. Facility-level: 5) financial disincentives; 6) workforce limitations; and 7) lack of referral standards. Our findings describe perceived benefits and barriers of palliative care in nursing homes from the perspective of key informants. For nursing home administrators and policymakers, the identified barriers can inform the development of targeted training programs and resources for staff to address these challenges effectively. Moreover, recognizing the benefits can emphasize the value of investing in palliative care services and encourage the integration of such programs into the standard care provided. Scientific Research / Models of Palliative Care Delivery [ABSTRACT FROM AUTHOR]

The re-ignition of memory reconsolidation research sparked by Karim Nader in the early 2000s led to great excitement that 'reconsolidation-based' interventions might be developed for mental health disorders such as post-traumatic stress disorder and substance use disorder. Two decades on, it is clear that reconsolidation-based interventions have been more challenging to translate to the clinic than initially thought. We argue that this challenge could be addressed with a better understanding of how prior expectations interact with information presented in a putative memory reactivation / cue reminder session, and through the identification of non-invasive biomarkers for memory destabilisation that would allow reminder sessions to be 'tuned' to enhance memory lability in an ad hoc manner. [ABSTRACT FROM AUTHOR]

Legislation allows adolescents to access comprehensive contraceptive care; however, provider practices remain unclear. We examined predictors of provider knowledge and comfort surrounding the provision of contraceptive care to adolescents. We mailed a survey to Illinois contraceptive providers (n = 251). Study outcomes include 1) knowledge of adolescent consent laws, 2) comfort asking for time alone with adolescents, 3) comfort providing contraception to adolescents without parental consent, and 4) comfort providing long-acting reversible contraception (LARC) to adolescents without parental consent. Using multivariable logistic regression, we estimated adjusted odds ratios (aORs) and 95% confidence intervals (CIs). Most providers are knowledgeable of consent laws (90%) and report being comfortable asking for time alone with adolescents (94%) and comfortable providing contraception to adolescents without parental consent (88%). Having a large proportion of patients who are eligible for family planning services was associated with increased comfort asking for time alone with adolescents (aOR, 7.03; 95% CI, 1.58–31.3) and providing contraception to adolescents (aOR, 4.0; 95% CI, 1.4–11.1). Only one-half (54%) were comfortable providing LARC methods to adolescents, with higher comfort among providers who: received more than 2 days of formal family planning training (aOR, 2.77; 95% CI, 1.2–6.2), specialized in obstetrics-gynecology (aOR, 5.64; 95% CI, 2.1–15.1), and had a patient population with more than 50% patients from minoritized racial/ethnic groups (aOR, 2.9; 95% CI, 1.2–6.6). Although knowledge of consent laws was high, gaps remain. Only one-half of our sample indicated comfort with the provision of LARC methods without parental consent. Additional efforts to increase provider comfort with all contraceptive methods and training on adolescent-centered practices may be required to meet the needs of adolescent patients. [ABSTRACT FROM AUTHOR]

Objective: While health podcasts can be effective in reducing stigma and increasing knowledge, we know little about their mechanisms of action. This qualitative study explored the mechanisms of how women connected with the podcast 'menopause: unmuted', which presented menopause information in a storytelling format.Methods: A diverse sample of 30 women aged 40-60 years were interviewed after listening to the podcast. Interviews covered participant's views and perceptions of the stories presented. Transcripts were analyzed thematically.Findings: Two overarching themes were identified. 'Openness and authenticity' describes the value of personal stories told in an authentic way by real experts-by-experience. 'Relatability and representation' explores participants' emotional reaction to the podcast, influenced by the extent to which they identified with the stories and storytellers on the podcast.Conclusions: Authenticity and relatability were identified as key mechanisms through which participants connected with audio stories, consistent with Fisher's narrative theory. These findings have important implications for the application of storytelling in podcasts designed to influence health behaviors.Practice Implications: Diverse stories representing a range of demographic characteristics and experiences are needed when creating podcasts about health information to increase listener's relatability and connection. [ABSTRACT FROM AUTHOR]

The objective of this study was to determine the association of traumatic brain injury (TBI) with mortality in military veterans and whether this association differs as a function of TBI severity, timing, and cause of death. This national cohort study used U.S. Department of Veterans Affairs' (VA) data of patients 18 years and older with TBI diagnoses (N = 213,290) and 1:1 propensity-matched comparison random sample of patients without TBI (N = 213,290). The main outcome measure was mortality within 6 months of TBI diagnosis and longer-term (after 6 months). Cox proportional hazards models were used to examine risk of all-cause mortality according to TBI severity and Fine-Gray proportional hazards regression to examine time to cause-specific mortality, accounting for competing risk of other deaths. For patients with moderate-to-severe TBI (compared with no TBI), hazard ratios (HRs) for mortality were highest within first 6 months of injury (fully-adjusted HR: 2.42, 95% CI: 2.32–2.53); for mild TBIs, HRs for mortality were lower and relatively constant over time (fully-adjusted HR within first 6 months: 1.33, 95% CI: 1.26–1.39). Veterans with mild and moderate-to-severe TBI had higher risk of future death over short term for 9 out 10 of the U.S. leading causes of death, with only unintentional injury, stroke, and suicide showing differences by TBI severity. Associations attenuated significantly from within to after 6 months TBI diagnosis. These findings indicate that adults with TBI are at increased risk of majority of leading causes of death, with differential risk by TBI severity and timing of death. • Propensity-matched cohort study of over 400,000 adults. • Traumatic brain injury (TBI) and risk of mortality differ by TBI severity. • Risk of death higher within 6 months of TBI diagnosis. • Differential risk by TBI severity for unintentional, stroke, and suicide death. [ABSTRACT FROM AUTHOR]

There is growing interest in the antidepressant potential of statins. We tested whether statin use is associated with cognitive markers previously found to indicate psychological vulnerability to depression within the context of the COVID-19 pandemic. Between April 2020 and February 2021, we conducted an observational online study of 2043 adults in the United Kingdom. Participants completed cognitive tasks assessing processes related to depression vulnerability, including affective bias and reward processing. We also measured working memory, medication use, and current psychiatric symptoms. Using mixed analysis of covariance and regression models, we compared participants on statins alone (n = 81), antihypertensive medication alone (n = 126), both medications (n = 111), and on neither medication (n = 1725). Statin use was associated with reduced recognition of angry and fearful faces (F 1 = 9.19, p =.002; F 1 = 6.9, p =.009) and with increased misclassification of these expressions as positive. Increased recognition of angry faces at baseline predicted increased levels of depression and anxiety 10 months later (β = 3.61, p =.027; β = 2.37, p =.002). Statin use was also associated with reduced learning about stimuli associated with loss (F 1,1418 = 9.90, p =.002). These indicators of reduced negative bias were not seen in participants taking antihypertensive medication alone, suggesting that they were related to statin use in particular rather than nonspecific demographic factors. In addition, we found no evidence of an association between statin use and impairment in working memory. Statin use was associated with cognitive markers indicative of reduced psychological vulnerability to depression, supporting their potential use as a prophylactic treatment for depression. [ABSTRACT FROM AUTHOR]

Evaluating the postoperative neutrophil-to-lymphocyte (NLR) ratio following nephrectomy for localized renal cell carcinoma and oncological outcomes. A prospectively managed database of 996 patients operated between 2005 and 2020. There was no association between NLR dynamics and disease recurrence. Therefore, there is no clinical role for monitoring the NLR in patients after renal surgery. Introduction & Objectives: In systemic therapy trials, a decreasing neutrophil-to-lymphocyte ratio (NLR) after treatment for metastatic renal cell carcinoma (RCC) has been associated with improved oncologic outcomes. Paradoxically, for patients with localized RCC treated with upfront surgery the opposite effect has been reported. We thus aimed to evaluate NLR dynamics on localized RCC recurrence. Materials and Methods: Treatment naïve patients with localized RCC managed surgically between 2005 and 2020 were included. Preoperative NLR was calculated within 6-weeks prior to surgery and postoperative NLR was calculated bet ween 4 and t welve-weeks after surgery. Patients were followed for disease recurrence, noting metastatic sites and postoperative infections. Cox regression were used to determine whether the relative change in postoperative NLR was associated with metastasis-free survival (MFS) and cancerspecific survival (CSS), adjusted for preoperative NLR. Results: In the cohort of 3310 patients, 996 (30%) had postoperative NLR available. These patients generally had more advanced disease, with 100 developing metastases and 38 dying from kidney cancer. Median MFS follow-up was 4.4 years. Decreasing 2-month postoperative NLR was associated with non-statistically significant worse MFS and CSS (HR 0.79, 95% 0.50, 1.24, P = .3; HR 0.83, 95% C.I. 0.40, 1.73; P = .6). On sensitivity analysis, across all NLR measurements, with NLR as a time-dependent covariate, results were similar, with a declining NLR associated with adverse MFS (HR 0.85, 95% CI 0.69, 1.30, P -value = .10), though not meeting conventional levels of significance. Conclusion: In higher-risk localized RCC patients, postoperative NLR is not suitable as a biomarker for predicting recurrences. [ABSTRACT FROM AUTHOR]

Reward-based reinforcement learning impairments are common in major depressive disorder, but it is unclear which aspects of reward-based reinforcement learning are disrupted in remitted major depression (rMDD). Given that the neurobiological substrates that implement reward-based RL are also strongly implicated in psychomotor retardation (PmR), the present study sought to test whether reward-based reinforcement learning is altered in rMDD individuals with a history of PmR. Three groups of individuals (1) rMDD with past PmR (PmR+, N = 34), (2) rMDD without past PmR (PmR-, N = 44), and (3) healthy controls (N = 90) completed a reward-based reinforcement learning task. Computational modeling was applied to test for group differences in model-derived parameters – specifically, learning rates and reward sensitivity. Compared to controls, rMDD PmR + exhibited lower learning rates, but not reduced reward sensitivity. By contrast, rMDD PmR- did not significantly differ from controls on either of the model-derived parameters. Follow-up analyses indicated that the results were not due to current psychopathology symptoms. Results indicate that a history of PmR predicts altered reward-based reinforcement learning in rMDD. Abnormal reward-related reinforcement learning may reflect a scar of past depressive episodes that contained psychomotor symptoms, or a trait-like deficit that preceded these episodes. [ABSTRACT FROM AUTHOR]

This study investigates the intersection of race, gender, and criminality in the language surrounding mental health and illness. Applying computational methods of word embeddings to full text data from major American newspapers between 2000 and 2023, I show that the landscape of mental health is broadly racialized as black, challenging the notion of mental illness as a predominantly white phenomenon. Cultural ideas about mental illness are gendered such that women are medicalized and men are criminalized, yet certain terms blur the boundary between illness and criminality. I highlight how stereotypes embedded in mental health language perpetuate stigma around men's mental health and justify social control with notable implications for black men. I conclude with recommendations for the mental health movement by advocating for more inclusive discussions around men's mental health and revised person-centric language. • Race and gender stereotypes are embedded in mental health language. • Word embeddings uncover these stereotypes via linguistic associations. • Mental health is broadly racialized as black. • Women's mental health experiences are medicalized, and men's are criminalized. [ABSTRACT FROM AUTHOR]

• Identification of early distress may be useful in prevention of suicide transmission in families. • Children of mothers who have a suicide risk history are considered at-risk. • Maternal history of suicidal thoughts and behaviors predicts preschooler aggression. Maternal history of suicidal thoughts and behaviors (STBs) has been identified as a robust risk factor for offspring emotional and behavioral problems, including risk for offspring STBs. The impact of maternal history of STBs has been well-documented in adolescent and young adult samples, with emerging research highlighting the need to examine early clinical correlates of risk in young children, prior to the emergence of STBs. In an extension of prior work, the current study examined associations between maternal history of STBs and previously identified emotional and behavioral correlates of STBs (negative affect, internalizing problems, attention problems, aggressive behavior) in young children. These associations were examined in a mother-preschooler sample (n = 158, mean preschooler age =41.52 months) with approximately half of mothers endorsing a history of STBs and 20 % of the sample scoring at the threshold that indicates suicide risk. In multivariate models, maternal history of STBs was significantly associated with preschooler aggressive behavior, assessed via mother- (β=0.19) and teacher-report (β=0.21), as well as mother-reported negative affect (β=0.22). Results document a link between maternal history of STBs and increased risk for heightened negative affect and aggressive behavior at home and school during the sensitive preschool period. Findings are discussed within the context of enhancing models of intergenerational transmission suicide risk. [ABSTRACT FROM AUTHOR]

The goal of this work was to develop a reliable method to produce the well-validated microglial activation PET tracer, [18F]DPA-714, routinely for clinical and preclinical research using an IBA Synthera®. Optimization of literature methods included reduced precursor mass and use of TBA HCO 3 as the phase transfer agent in place of Kryptofix® 222 in a 65-min synthesis with an average activity yield of 24.6 ± 3.8% (n = 5). Successful quality control testing and process validation results are reported. • An IND-approved method for production of [18F]DPA-714 on an IBA Synthera® is reported. • Reduction of precursor mass and replacement of Kryptofix® 222 as phase transfer agent support production of tracer in reliable quantities for clinical research. • Justification of 5% injected ethanol in pediatric PET tracer preparations was outlined. [ABSTRACT FROM AUTHOR]

Objectives: Learning modern pain biology concepts can improve important clinical outcomes for people with chronic pain. The primary purpose of this scoping review is to examine and report characteristics of chronic musculoskeletal pain education programs from an instructional design perspective.Methods: Following PRISMA-ScR guidelines, PubMed, Medline, and CINAHL databases were systematically searched. Articles included expert recommendations and those reporting pain education programs used in clinical trials enrolling adults with chronic neuromusculoskeletal pain and published in English between 1990 and 2021. Three authors independently evaluated articles for eligibility through title, abstract, and full text review. Instructional design characteristics such as learning outcomes, support materials, learning assessment methods, and key concepts communicated were summarized.Results: The search revealed 5260 articles of which 40 were included: 27 clinical studies, 7 expert recommendations, and 6 articles reporting on pain education from participant perspectives. Detailed reporting of instructional design characteristics informing replication in subsequent studies is sparse. Most included trials used only lecture and did not assess participant learning.Conclusions: More comprehensive reporting of pain education programs is needed to facilitate replicability.Practical Implications: This article proposes detailed and standardized reporting of trials using pain education programs employing a modified version of the TIDieR checklist. [ABSTRACT FROM AUTHOR]

Background: Research on perinatal mental health during the COVID-19 pandemic has largely focused on data from community samples. This study sought to understand the experiences of pregnant and postpartum women with histories of clinically elevated symptoms of depression.Methods: Participants included 60 perinatal women who participated in wellness intervention trials for women with antenatal depression. We used a mixed methods approach, assessing depression, anxiety, stressors and coping behaviors, along with narrative responses to questions regarding COVID-specific effects on mental health.Results: Over three-fourths of the sample indicated a worsening of mental health during the pandemic, with 31.7% of women endorsing clinically elevated depression symptoms and 36.7% screening positive for anxiety. Women reported negative impacts on their emotional wellbeing, especially a resurgence of mental health symptoms. Participants also articulated positive experiences during the pandemic, including an appreciation for increased time with family, especially infants. Women detailed numerous, mostly adaptive, coping strategies they had used to mitigate stress; self-isolation and spending time outdoors were associated with having depression above or below the clinical cut off, respectively.Limitations: The study had a small sample, and the generalizability of findings may be limited, given that participants were clinical trial completers.Conclusions: Although the pandemic upended many aspects of life for perinatal women and raised mental health concerns, many also reported adaptive means of coping and positive experiences or 'silver linings' related to pandemic restrictions. Some coping strategies that were utilized, including wellness-based behaviors, may have helped to mitigate the impact of COVID-19 related stress. [ABSTRACT FROM AUTHOR]

• Weight change patterns were not associated with long-term diabetes status. • Participants who maintained their weight loss had lower glycaemia levels. • Regainers had similar glycaemia levels to participants who did not lose weight. • The different associations suggest the necessity of maintaining weight loss. To investigate the associations between weight change patterns and 5-year incident non-diabetic hyperglycaemia (NDH), and glycated haemoglobin (HbA 1c) levels among individuals who had overweight or obesity. This longitudinal cohort study (N = 435) pooled data from a weight management trial. Participants were adults with a body mass index of ≥28 kg/m2. They were categorised as "no weight loss", "maintainers", and "regainers" based on their weight at 3 months and 12 months after baseline. Multivariable logistic regression models and linear regressions were conducted to examine the associations. Between 1-year and 5-year follow-ups, 77 participants developed NDH. We found no statistically significant association between weight change patterns and incident NDH at 5 years. Among weight loss maintainers, mean HbA 1c was −0.15% (95% confidence intervals (CI): −0.22, −0.10) lower after 1 year and −0.15% (95% CI: −0.23, −0.06) lower after 5 years compared to the no weight loss group. There was no difference between weight loss regainers and no weight loss group in HbA 1c levels. Compared to those who did not lose weight, participants who maintained their weight loss had lower HbA 1c levels after 1 year and 5 years, which highlights the importance of providing long-term support to prevent weight regain. [ABSTRACT FROM AUTHOR]

[Display omitted] Two new tetradentate, dianionic N^N−^N−^N ligands combining amido and π-extended phenanthridine (benzo[ c ]quinoline) donors are presented. The coordination chemistry of the ligands was explored via construction of complexes of divalent transition metal Ni(II), Cu(II), and Pd(II) ions. Single-crystal X-ray diffraction confirmed the expected distorted square-planar geometry for examples of each metal, consistent with both ligand-field expectations and the geometric restrictions of the ligand framework. The complexes absorb strongly in the visible region of the electromagnetic spectrum, with steady-state electronic absorption spectra containing a prominent low energy band attributed by time-dependent density functional theory (TD-DFT) to transitions of mixed ILCT/MLCT character, with contributions from d → d transitions. Cyclic voltammetry and spectroelectrochemical experiments were used to probe the ability of the new ligand frameworks to support electron-transfer. [ABSTRACT FROM AUTHOR]

• Aligning methods will allow for comparison across future studies. • Bite acceptance and typical feeding behaviors differ by texture. • The presence of feeding behaviors alone is not indicative of problematic feeding. • Feeding concerns decline as infants get older. • Clinicians can use these new methods to measure progress during therapy. The lack of age-appropriate expectations for feeding acceptance patterns in early childhood is a barrier to early and accurate identification of pediatric feeding disorder (PFD). The objective of the study was to describe the process by which typically developing children 8–12 months of age accept or refuse bite presentations and their corresponding feeding behaviors, aiming to establish age-appropriate normative data for feeding acceptance. Using cross-sectional methodology, we studied the proportion of bite presentations accepted, the type of feeding behaviors-passive, disruptive, expulsion, feeding concerns- observed at presentation and acceptance or refusal, and the duration between presentation to acceptance or refusal in 63 healthy infants between 8 and 12 months of age. Descriptive statistics and a one-way ANOVA were conducted to compare the effect of age and texture. Findings reveal high levels of bite acceptance of 80 % or > for children across ages, but with lower texture-specific differences. Both passive and disruptive behaviors were present even during acceptance of bites without any expulsion. Feeding concerns showed developmental trends with rapid reduction by 12 months suggesting improvement in oral feeding skills. The duration of acceptance and refusals revealed clear patterns by age and texture with an average of 3 s for acceptance but <1 s for refusal. This study describes bite acceptance patterns in a cohort of typically developing infants between 8 and 12 months of age by examining the acceptance of bites, frequency and type of feeding behaviors, and duration differences when children accept versus refuse a bite. Findings may be applied in the future to provide more sensitive detection of problematic feeding patterns to aid in the detection of pediatric feeding disorder. [ABSTRACT FROM AUTHOR]

The prevalence of substance use disorders (SUDs) is growing among older adults, and older adults in rural areas face disparities in access to SUD care. Rural older adults with SUDs commonly have comorbid chronic conditions that puts them at risk for frequent acute healthcare utilization. In rural areas, primary care for patients with SUDs are increasingly provided by nurse practitioners (NPs), and quality primary care services may decrease ED visits in this population. Yet, NP-delivered primary care for rural older adults with SUDs may be limited by work environment barriers, which include lack of support, autonomy, and visibility. This study assessed the relationship between the NP work environment and ED utilization among rural older adults with SUDs. This was a secondary analysis of cross-sectional data from a large survey of NPs in six U.S. states merged with Medicare claims. The study measured the NP work environment by the four subscales of the Nurse Practitioner Primary Care Organizational Climate Questionnaire (NP-PCOCQ), which measure 1) independent practice and support, 2) NP-physician relations, 3) NP-administration, and 4) professional visibility. Multilevel logistic regression models, adjusted for practice and patient covariates, assess the relationship between the NP work environment and all-cause ED use. The sample included 1152 older adults with SUDs who received care at 126 rural NP primary care practices. NP independent practice and support at the practice was associated with 49 % lower odds of all-cause ED visits among older adults with SUDs. There were no relationships between the other NP-PCOCQ subscales and all-cause ED visits. Organizational support for NP independent practice is associated with lower odds of all-cause ED utilization among rural older adults with SUDs. Practice administrators should ensure that NPs have access to support and resources to enhance their ability to care for rural older adults with SUDs. Ultimately, these practice changes could reduce ED utilization and health disparities in this population. • Rural older adults with substance use disorders frequently use the emergency room. • Relations, teamwork, autonomy, and support may impact nurse practitioner (NP) care. • Support for NP independent practice associated with less emergency room use. • Organizational administrators should ensure NP autonomy and access to support. [ABSTRACT FROM AUTHOR]

Non-target analysis (NTA) using high-resolution mass spectrometry is becoming a useful approach to screen for suspect and unknown chemicals. For comprehensive analyses, data-independent acquisition (DIA), like Sequential Windowed Acquisition of all THeoretical Mass Spectra (SWATH-MS) on Sciex instruments, is necessary, usually followed by library matching for feature annotation. The choice of parameters, such as acquisition window number and size, may influence the comprehensiveness of the suspect features detected. The goal of this study was to assess how mass spectrometric DIA settings may influence the ability to obtain confident annotations and identifications of features in environmental (river water, passive sample extract (PSE)), wastewater (unpreserved and acidified) and biological (urine) sample matrices. Each matrix was analysed using 11 different MS methods, with 5–15 variable size acquisition windows. True positive (TP) annotation (i.e., matching experimental and library spectra) rates were constant for PSE (40%) and highest for urine (18%), wastewater (34% and 36%, unpreserved and acidified, respectively) and river water (8%) when using higher numbers of windows (15). The number of annotated features was highest for PSE (12%) and urine (8.5%) when using more acquisition windows (9 and 14, respectively). Less complex matrices (based on average total ion chromatogram intensities) like river water, unpreserved and acidified wastewater have higher annotation rates (7.5%, 8% and 13.2%, respectively) when using less acquisition windows (5–6), indicating matrix dependency of optimum settings. Library scores varied widely for correct (scores between 6 and 100) as well as incorrect annotations (scores between 2 and 100), making it hard to define specific ideal cut-off values. Results highlight the need for properly curated libraries and careful optimization of SWATH-MS and other DIA methods for each individual matrix, finding the best ratio of total annotations to true positive, (i.e., correct) annotations to achieve best NTA results. [Display omitted] • Library scores highly variable for both, correct as well as incorrect annotations. • Rate of true positive library matches changes with number of acquisition windows. • Complexity of matrix influences optimal settings for MS/MS data acquisition. • Careful optimization of methods is needed for high quality MS/MS data. [ABSTRACT FROM AUTHOR]

Objective: To compare the clinical pregnancy rate (CPR) and live birth rate (LBR) of embryo transfer episodes (ETEs) performed by Reproductive Endocrinology and Infertility fellows vs. those of ETEs performed by faculty physicians.Design: Retrospective cohort analysis.Setting: Academic reproductive endocrinology and infertility practice.Patient(s): In total, 3,073 ETEs for 1,488 unique patients were performed by fellows or faculty physicians between January 2009 and January 2020.Intervention(s): None.Main Outcome Measure(s): Clinical pregnancy rate and LBR.Result(s): Fifteen fellows performed 1,225 (39.9%) of 3,073 ETEs after completing 30 mock transfers. On comparing outcomes among fellowship years (FY1, FY2, and FY3), CPR (44.1% vs. 43.2% vs. 45.7%, respectively, P = .83) and LBR (39.1% vs. 38.1% vs. 38.4%, respectively, P = .97) were not significantly different. Fellowship year 1 fellows' initial 30 ETEs vs. all the remaining FY1 ETEs had a significantly higher CPR (48.1% vs. 40.5%, respectively, P = .030) and LBR (45.4% vs. 34.3%, respectively, P = .001). There were no significant differences between faculty versus fellow ETEs in terms of CPR (43.0% vs. 45.0%, respectively, P = .30) or LBR (37.3% vs. 39.8%, respectively, P = .16), even after adjusting for patient age, body mass index, primary infertility diagnosis, autologous vs. donor oocyte, fresh vs. frozen embryo, number of embryos transferred, type of transfer catheter, and year of transfer (P = .32 for CPR, P = .22 for LBR).Conclusion(s): Appropriately trained FY1 fellows had success rates maintained throughout all FYs. There were no significant differences in clinical outcomes between fellow- and faculty-performed transfers. These data demonstrated that allowing fellows to perform live embryo transfers is not detrimental to clinical outcomes. [ABSTRACT FROM AUTHOR]

Respiratory silicosis is a preventable occupational disease that develops secondary to the aspiration of crystalline silicon dioxide (silica) into the lungs, activation of the NLRP3 inflammasome, and IL-1β production. Cathepsin Z has been associated with the development of inflammation and IL-1β production; however, the mechanism of how cathepsin Z leads to IL-1β production is unknown. Here, the requirement for cathepsin Z in silicosis was determined using WT mice and mice deficient in cathepsin Z. The activation of the NLRP3 inflammasome in macrophages was studied using WT and cathepsin Z-deficient bone marrow-derived murine dendritic cells and the human monocytic cell line THP-1. The cells were activated with silica, and IL-1β release was determined using enzyme-linked immunosorbent assay or IL-1β bioassays. The relative contribution of the active domain or integrin-binding domain of cathepsin Z was studied using recombinant cathepsin Z constructs and the α5 integrin neutralizing antibody. We report that the lysosomal cysteine protease cathepsin Z potentiates the development of inflammation associated with respiratory silicosis by augmenting NLRP3 inflammasome-derived IL-1β expression in response to silica. The secreted cathepsin Z functions nonproteolytically via the internal integrin-binding domain to impact caspase-1 activation and the production of active IL-1β through integrin α5 without affecting the transcription levels of NLRP3 inflammasome components. This work reveals a regulatory pathway for the NLRP3 inflammasome that occurs in an outside-in fashion and provides a link between extracellular cathepsin Z and inflammation. Furthermore, it reveals a level of NLRP3 inflammasome regulation that has previously only been found downstream of extracellular pathogens. [ABSTRACT FROM AUTHOR]

Trauma and trauma-related disorders are characterized by impaired learning processes, including reinforcement learning (RL). Identifying which aspects of learning are altered by trauma is critical endeavor, as this may reveal key mechanisms of impairment and potential intervention targets. There are at least two types of RL that have been delineated using computational modeling: model-free and model-based RL. Although these RL processes differentially predict decision-making behavior, most research has examined the impact of trauma on model-free RL. Currently unclear whether model-based RL, which involves building abstract and nuanced representations of stimulus-outcome relationships, is impaired among individuals with a history of trauma. The present study sought to test the hypothesis of impaired model-based RL among adolescent females exposed to assaultive trauma. Participants (n = 60; 29 without a history of assault and 31 with a history of assault with and without PTSD) completed a three-arm bandit task during fMRI acquisition. Two computational models compared the degree to which participants' task behavior fit the use of a model-free versus model-based RL strategy. Although a history of assaultive trauma did not predict poorer model-based RL, greater sexual abuse severity predicted less use of model-based compared to model-free RL. Additionally, severe sexual abuse predicted less left frontoparietal network encoding of model-based RL updates. Altered model-based RL, which supports goal-directed behavior, may be an important route through which clinical impairment emerges among individuals with a history of severe sexual abuse and should be examined further in future studies. [ABSTRACT FROM AUTHOR]

Objective: To determine the durability of ureteroneocystostomy as well as pre- or post-operative factors that may be associated with failure to provide appropriate renal drainage.Methods: A total of 290 patients who underwent ureteral reimplantation to native bladder between 2003 and 2015 were identified. After excluding pediatric patients and those without any follow-up, 255 patients, 3 of whom had a subsequent contralateral reimplantation were included, for 258 observations. Kaplan-Meier method and univariate Cox models were used to assess whether factors such as radiation, prior abdominal surgery, age at re-implantation, gender and BMI are associated with re-implantation failure.Results: Among 258 observations, there were 27 failures. Median follow-up time was 1.1 years from re-implantation surgery among patients without a failure.1 and 5-year ureteral re-implantation failure is 7% (95% CI 4%, 12%) and 22% (95% CI 15%, 33%), respectively. On univariate analysis, post-operative radiation was found to be strongly associated with poorer ureteral re-implantation survival (HR: 6.62; CI 2.40, 18.29; P = .0003) No significant association between re-implantation failure-free survival and age at reimplantation, gender, BMI, previous abdominal surgery, preoperative radiation and adjuvant radiation was noted (all P > .4).Conclusions: Ureteroneocystotomy in the malignant setting has reasonable success rates through five years. No preoperative factors were associated with re-implantation failure. While all patients need to be followed due to increasing rates of failure with time, patients receiving palliative or salvage radiation therapy appear to be more prone to failure requiring further intervention. [ABSTRACT FROM AUTHOR]

Objective: To describe the safety and efficacy of partial nephrectomy (PN) in comparison to radical nephrectomy (RN) for surgically managed renal hilar tumors.Materials and Methods: We retrospectively reviewed institutional records of patients with a small (<5 cm) solitary renal (hilar or non-hilar) mass who underwent PN or RN between 2008 and 2018. Hilar tumors were defined as those at medial position, abutting the renal vessels. Recurrence-free, cancer-specific, and overall survival were estimated using the Kaplan-Meier method.Results: Of 1,951 eligible patients, 399 had hilar tumors (292 scheduled for PN, 107 RN) and 1,552 had non-hilar tumors (scheduled for PN). We found no significant differences in survival measures between hilar and non-hilar tumors in patients selected for PN. Patients scheduled for PN for hilar tumors had higher rates of ≥grade II postoperative surgical complications compared to patients scheduled to receive PN for non-hilar tumors (13% vs 8.6%; log-rank P = .018) and non-statistically significantly elevated rates of ≥grade II complications compared to patients scheduled for RN for hilar tumors (13% vs 6.5%; difference 6%, 95% CI 0.4%, 13%; log-rank P = .07).Conclusion: PN for hilar and non-hilar renal masses (<5cm) experience comparable oncologic outcomes though increased risk of complications for hilar masses. PN for hilar tumors was associated with better renal function and overall survival with non-statistically elevated risk of grade II or higher complications than RN. A renal tumor located at the hilum should not be a contra-indication for performing PN. [ABSTRACT FROM AUTHOR]

Paraspeckles are RNA–protein structures within the nucleus of mammalian cells, capable of orchestrating various biochemical processes. An overexpression of the architectural component of paraspeckles, a long non-coding RNA called NEAT1 (Nuclear Enriched Abundant Transcript 1), has been linked to a variety of cancers and is often associated with poor patient prognosis. Thus, there is an accumulating interest in the role of paraspeckles in carcinogenesis, however there is a limited understanding of how NEAT1 expression is regulated. Here, we demonstrate that both nuclear G-quadruplex (G4) and paraspeckle formation are significantly increased in a human breast cancer cell line compared to non-tumorigenic breast cells. Moreover, we identified and characterized G4-forming sequences within the NEAT1 promoter and demonstrate stabilization of G4 DNA with a G4-stabilizing small molecule results in a significant alteration in both paraspeckle formation and NEAT1 expression. This G4-mediated alteration of NEAT1 at both the transcriptional and post-transcriptional levels was evident in U2OS osteosarcoma cells, MCF-7 breast adenocarcinoma and MDA-MB-231 triple negative breast cancer cells. • NEAT1_2 lncRNA and DNA G-quadruplexes are altered in multiple cancers. • We identify and characterise potential G-quadruplexes in the NEAT1 gene promoter. • Stabilization of G-quadruplexes alters NEAT1_2 expression and paraspeckle formation. [ABSTRACT FROM AUTHOR]

Objective: Pelvic floor pain, abdominal wall pain, and central nervous system pain amplification can be contributing factors in chronic pelvic pain (CPP), however; limited research has investigated the association of pelvic floor, abdominal, and uterine tenderness with central nervous system pain amplification. We assessed whether pressure pain thresholds on the non-dominant thumbnail, a marker of central nervous system pain amplification, were associated with pelvic floor, abdominal, and uterine tenderness among women with endometriosis or CPP.Study Design: We conducted a cross-sectional study among 88 females with endometriosis and/or CPP. Abdominal (6 locations), pelvic floor (6 locations) and uterine (1 location) tenderness were assessed via a standardized physical exam. Participants reported their pain levels (0-10 scale) with application of 2 kg of pressure at each area, with a pain rating of ≥4 on the 0-10 scale considered moderate to severe pain. Pain sensitivity was measured on the non-dominant thumbnail by applying discrete pressure stimuli using a previously validated protocol.Results: Overall, 50% (44/88), 42% (37/88), and 58% (51/88) of participants reported high pelvic floor, abdominal, and uterine tenderness, respectively. Pressure intensities needed to elicit 'faint' and 'mild' pain were lower for participants with high vs. low pelvic floor tenderness (median intensity for 'faint' pain = 0.50 kgf/cm2(min-max:0.25-3.25) vs. 1.06(0.25-3.00), p-value = 0.006; median intensity for 'mild' pain = 2.00(0.63-4.88) vs. 2.63(0.75-6.00), p-value = 0.03). No association was observed between pressure pain sensitivity and abdominal or uterine tenderness (p > 0.11). Participants with endometriosis without pain were less likely to have high pelvic floor (22.2%), abdominal (11.1%), and uterine (25.9%) tenderness compared to participants with endometriosis with pain (63.0%, 50%, 65.2%, respectively) and participants with chronic pelvic pain (60%, 73.3%, 93.3%, respectively).Conclusions: These results suggest that high pelvic floor tenderness among women with endometriosis/CPP may be a marker of heightened pain sensitivity suggestive of central nervous system pain amplification and may impact treatment response. Future research should examine whether this clinical phenotype predicts response to medical and behavioral treatments (e.g, anti-convulsants, behavioral therapy, Physical Therapy). [ABSTRACT FROM AUTHOR]

• The nucleus reuniens reciprocally connects the hippocampus and prefrontal cortex. • The nucleus reuniens is critical for spatial working memory in rodents. • Inactivation of reuniens disrupts hippocampal-prefrontal synchronization. • Questions remain about communication in the prefrontal-thalamo-hippocampal circuit. Spatial working memory, the ability to temporarily maintain an internal representation of spatial information for use in guiding upcoming decisions, has been shown to be dependent upon a network of brain structures that includes the hippocampus, a region known to be critical for spatial navigation and episodic memory, and the prefrontal cortex (PFC), a region known to be critical for executive function and goal directed behavior. Oscillatory synchronization between the hippocampus and the prefrontal cortex (PFC) is known to increase in situations of high working memory demand. Most of our knowledge about the anatomical connectivity between the PFC and hippocampus comes from the rodent literature. Thus, most of the findings that will be discussed here model human working memory using spatial working memory-dependent maze navigation tasks in rodents. It has been demonstrated that the ventral midline thalamic nucleus reuniens (Re) is reciprocally connected to both the infralimbic and prelimbic subregions of the PFC, collectively referred to as the medial PFC (mPFC), and the hippocampus. Given that the Re serves as a major anatomical route between the mPFC and hippocampus, it is perhaps not surprising that Re has been shown to be critical for spatial working memory. This review will describe the latest findings and ideas on how the Re contributes to prefrontal-hippocampal synchronization and spatial working memory in rodents. The review will conclude with possible future directions that will advance the understanding of the mechanisms that enable the Re to orchestrate long range synchrony in the prefrontal-hippocampal network. [ABSTRACT FROM AUTHOR]

Insulin infusion sets worn for more than 4–5 days have been associated with a greater risk of unexplained hyperglycemia, a phenomenon that has been hypothesized to be caused by an inflammatory response to preservatives such as m -cresol and phenol. In this cross-over study in diabetic swine, we examined the role of the preservative m -cresol in inflammation and changes in infusion site patency. Insulin pharmacokinetics (PK) and glucose pharmacodynamics (PD) were measured on delivery of a bolus of regular human insulin U-100 (U-100R), formulated with or without 2.5 mg/mL m-cresol, to fasted swine following 0, 3, 5, 7, and 10 days of continuous subcutaneous insulin infusion (CSII). In a subsequent study with the same animals, biopsies were evaluated from swine wearing infusion sets infusing nothing, saline, or U-100R either with or without 2.5 mg/mL m-cresol, following 3, 7, and 10 days of CSII. Exposure to m -cresol did not impact any PK or PD endpoints. PK and PD responses dropped markedly from Days 7–10, regardless of the presence of m -cresol. Histopathology results suggest an additive inflammatory response to both the infusion set and the insulin protein itself , peaking at Day 7 and remaining stable beyond. [ABSTRACT FROM AUTHOR]

Freshwater is an essential resource for human life; however, its future availability is of ongoing concern due to the impacts of climate change, industry, and population pressures. Freshwater mollusc sclerochronology regularly contributes to questions of direct relevance to the future sustainability of this resource, as well as the conservation of endangered freshwater mollusc species, and its relationship with humans through time. Despite this, research within mollusc sclerochronology overwhelmingly focuses on the analysis of marine species. To encourage more interest in this vital subdiscipline, this paper reviews publications on freshwater mollusc sclerochronology published between 2000 and 2021 and highlights key themes and essential findings, challenges, and opportunities specific to freshwater mollusc sclerochronology. The present study reviewed 111 publications where researchers studied the incremental growth patterns and/or completed temporally constrained geochemical analysis of the growth patterns of freshwater molluscs, as well as 22 review papers that addressed freshwater mollusc sclerochronology research. The review identified a focus on the analysis of bivalve taxa from river or lake habitats in the Northern Hemisphere and found that research generally could be divided into four key areas of interest: development of methodology, conservation of habitat or species, paleoenvironmental reconstruction, and archaeology. The paper also considers the effectiveness of different methodologies and geochemical proxies within freshwater contexts and aims to identify unique challenges faced by researchers in the hope to aid and direct future investigations. One key challenge facing this field is the variability of freshwater environments and the need for more high-resolution monitoring of habitats in modern calibration studies. Opportunities for future research include the development of low-cost methodologies to aid in the accessibility of this technique to researchers across the world. • Authors reviewed 133 publications, published between 2000 and 2021. • Discipline focus on the analysis of bivalves from river or lake habitats. • The variability of freshwater environments is a key challenge. • Future focus on more high-resolution modern calibration studies required. [ABSTRACT FROM AUTHOR]

Key evolutionary events in hominin evolution occurred between 3.5 and 2.4 Ma, including the origins of flaked tool technology and the first appearance of the genera Homo and Paranthropus. This period remains poorly understood, however, because deposits of this age are rarely exposed across Africa. The Luangwa River Valley of eastern Zambia is part of the southernmost extension of the East African Rift System; a fossil femur from South Luangwa, identified as Theropithecus cf. darti , hints at the presence of fossiliferous beds of this age in the Luangwa Valley. Additionally, Middle Pleistocene fossils and Early and Middle Stone Age artifacts have also been recovered in sediments adjacent to the Luangwa River. Fossils from these deposits could contribute data on the diversification of hominins and mammals that occurred during the Plio-Pleistocene. The Luangwa River also supports a rich modern mammalian community that represents a critical analogue for reconstructing hominin paleoenvironments. However, no systematic ecological characterizations of living or past mammalian communities of the Luangwa River Valley have been completed. The newly initiated Zambia Rift Valley Research Project (ZRVRP) will analyze the ecology of modern and fossil Luangwa River mammalian and human communities using dental microwear, enamel and collagen isotopic composition, the distribution of bones, fossils, and vegetation on the landscape, and archaeological materials. Patterns of paleoenvironmental change, climatic seasonality, and hominin landscape use over time will provide important comparative context for other Plio-Pleistocene sites. Here, we describe the goals, methods, and community engagement of the ZRVRP, and some challenges involved in launching new paleoanthropological field research. [ABSTRACT FROM AUTHOR]

• Access to evidence-based treatments for bulimia nervosa (BN) remains inadequate. • Online self-help interventions increase access to evidence-based treatments in a scalable and cost-effective manner. • Both clinician-supported and self-help delivery of online CBT were more effective than WLC in reducing BN symptoms. • Clinician-supported was superior to self-help in regards to two secondary variables (laxative use and dietary restraint). High dropout rates and poor adherence associated with digital interventions have prompted research into modifications of these treatments to improve engagement and completion rates. This trial aimed to investigate the added benefit of clinician support when paired alongside a ten-session, online cognitive behaviour therapy (CBT) self-help intervention for bulimia nervosa (BN). As part of a three-arm, phase II randomised controlled trial, 114 participants (16 years or over) with full or subthreshold BN were randomly assigned to complete the intervention in a self-help mode (with administrative researcher contact; n = 38), with adjunct clinician support (weekly 30-minute videoconferencing sessions; n = 37), or a no-treatment waitlist control (WLC; n = 39). Baseline to post-treatment (12-weeks) decreases in objective binge episode frequency were significantly greater for clinician-supported participants as compared to WLC, but not for self-help when compared to WLC. However, due to continued improvements for self-help across follow-up (24-weeks), both arms outperformed WLC when analysed as an overall rate of change across three timepoints. Clinician-supported participants outperformed self-help in regards to laxative use and dietary restraint. Our results demonstrate that good clinical outcomes can be achieved with a relatively brief online CBT-based program even in the absence of structured clinical support, indicating a possible overreliance upon clinician support as a primary adherence-facilitating mechanism. [ABSTRACT FROM AUTHOR]

TRAF3 has diverse signaling functions, which vary by cell type. Uniquely in B lymphocytes, TRAF3 inhibits homeostatic survival. Highlighting the role of TRAF3 as a tumor suppressor, loss-of-function TRAF3 mutations are associated with human B-cell malignancies, while B-cell-specific deletion of TRAF3 in mice leads to autoimmunity and lymphoma development. The role of TRAF3 in inhibiting noncanonical NF-κB activation, CD40 and BAFF-R signaling to B cells is well documented. In contrast, TRAF3 enhances many T-cell effector functions, through associating with and enhancing signaling by the T-cell receptor (TCR)-CD28 complex. The present study was designed to determine the role of TRAF3 in signaling via the B-cell antigen receptor (BCR). The BCR is crucial for antigen recognition, survival, proliferation, and antibody production, and defects in BCR signaling can promote abnormal survival of malignant B cells. Here, we show that TRAF3 is associated with both CD79B and the BCR-activated kinases Syk and Btk following BCR stimulation. BCR-induced phosphorylation of Syk and additional downstream kinases was increased in TRAF3-/- B cells, with regulation observed in both follicular and marginal zone B-cell subsets. BCR stimulation of TRAF3-/- B cells resulted in increased surface expression of MHC-II, CD80, and CD86 molecules. Interestingly, increased survival of TRAF3-/- primary B cells was resistant to inhibition of Btk, while TRAF3-deficient malignant B-cell lines showed enhanced sensitivity. TRAF3 serves to restrain normal and malignant BCR signaling, with important implications for its role in normal Bcell biology and abnormal survival of malignant B cells. [ABSTRACT FROM AUTHOR]

• 42% of customers surveyed store leftover drugs in their homes. • Customer reported dropbox usage was higher at pharmacies with dropboxes. • Pharmacists at dropbox locations gave safe and consistent disposal recommendations. • Increased pharmacy dropbox locations are necessary to improve proper drug disposal. Production and use of pharmaceuticals in the United States is high and continues to grow. This, combined with poor wastewater removal rates for drugs in excreted waste, and improper pharmaceutical disposal leads to the presence of pharmaceuticals in fresh- and marine waters and wildlife. In the United States, safe drug take-back boxes, or dropboxes, were established in pharmacies after federal legislation passed in 2014, allowing for year-round safe collection of leftover pharmaceuticals. The overarching objective of this work was to identify opportunities for improving access to proper pharmaceutical disposal. We assessed consumer behavior regarding drug disposal choices and knowledge of dropboxes at pharmacies, investigated pharmacist attitudes toward and recommendations about leftover drug disposal, and compared responses at locations with and without dropboxes. We also explored obstacles to dropbox adoption and usage. We found that customer awareness of dropboxes as well as knowledge about risks of improper disposal are low, however awareness was greater at pharmacies with dropboxes. Additionally, pharmacists at dropbox locations were more consistent in their messaging to customers, more likely to recommend proper disposal methods, and more supportive of drug take-back programs. Through a focus group, we learned that further consumer education would overwhelm the capacity of the existing dropboxes. Based on our findings, we recommend solutions to improper disposal focus on legislation mandating dropboxes at pharmacies and pressure on the pharmaceutical industry to fund proper disposal of unused pharmaceuticals. [ABSTRACT FROM AUTHOR]

Convolutional Neural Network (CNN) has been increasingly used for land cover mapping of remotely sensed imagery. However, large-area classification using traditional CNN is computationally expensive and produces coarse maps using a sliding window approach. To address this problem, object-based CNN (OCNN) becomes an alternative solution to improve classification performance. However, previous studies were mainly focused on urban areas or small scenes, and implementation of OCNN method is still needed for large-area classification over heterogeneous landscape. Additionally, the massive labeling of segmented objects requires a practical approach for less computation, including object analysis and multiple CNNs. This study presents a new multiscale OCNN (multi-OCNN) framework for large-scale land cover classification at 1-m resolution over 145,740 km2. Our approach consists of three main steps: (i) image segmentation, (ii) object analysis with skeleton-based algorithm, and (iii) application of multiple CNNs for final classification. Also, we developed a large benchmark dataset, called IowaNet, with 1 million labeled images and 10 classes. In our approach, multiscale CNNs were trained to capture the best contextual information during the semantic labeling of objects. Meanwhile, skeletonization algorithm provided morphological representation ("medial axis") of objects to support the selection of convolutional locations for CNN predictions. In general, proposed multi-OCNN presented better classification accuracy (overall accuracy ~87.2%) compared to traditional patch-based CNN (81.6%) and fixed-input OCNN (82%). In addition, the results showed that this framework is 8.1 and 111.5 times faster than traditional pixel-wise CNN 16 or CNN 256 , respectively. Multiple CNNs and object analysis have proved to be essential for accurate and fast classification. While multi-OCNN produced a high-level of spatial details in the land cover product, misclassification was observed for some classes, such as road versus buildings or shadow versus lake. Despite these minor drawbacks, our results also demonstrated the benefits of IowaNet training dataset in the model performance; overfitting process reduces as the number of samples increases. The limitations of multi-OCNN are partially explained by segmentation quality and limited number of spectral bands in the aerial data. With the advance of deep learning methods, this study supports the claim of multi-OCNN benefits for operational large-scale land cover product at 1-m resolution. [ABSTRACT FROM AUTHOR]

Evolutionary genomic studies find that reproductive protein genes, those directly involved in reproductive processes, diversify more rapidly than most other gene categories. Strong postcopulatory sexual selection acting within species is the predominant hypothesis proposed to account for the observed pattern. Recently, relaxed selection due to sex-specific gene expression has also been put forward to explain the relatively rapid diversification. We contend that relaxed selection due to sex-limited gene expression is the correct null model for tests of molecular evolution of reproductive genes and argue that it may play a more significant role in the evolutionary diversification of reproductive genes than previously recognized. We advocate for a re-evaluation of adaptive explanations for the rapid diversification of reproductive genes. Reproductive protein genes evolve more rapidly than almost any other gene category. Strong postcopulatory sexual selection is the predominant hypothesis proposed to account for the observed pattern of rapid evolutionary divergence. However, inferences about the adaptive nature of molecular evolution depend on the comparison of polymorphism within species to divergence between species and most studies of reproductive genes have not considered polymorphism when documenting divergence. Recently, relaxed selection due to sex-specific gene expression has been put forward to explain the relatively rapid diversification. We argue that relaxed selection may play a more significant role in the evolutionary diversification of reproductive genes than previously recognized and that a re-evaluation of the role of adaptive forces in the rapid evolution of reproductive genes is warranted. [ABSTRACT FROM AUTHOR]

Background: Multiple methods of correcting nutrient intake for misreported energy intake have been proposed but have not been extensively compared. The availability of the Women's Health Initiative (WHI) data set, which includes several objective recovery biomarkers, offers an opportunity to compare these corrections with respect to protein intake.Objective: We compared 5 energy-correction methods for self-reported dietary protein against urinary nitrogen-derived protein intake.Methods: As part of the WHI Nutritional Biomarkers Study (NBS) 544 participants (50- to 80-y-old women) completed a FFQ and biomarker assessments using doubly labeled water (DLW) for total energy expenditure (TEE) and 24-h urinary nitrogen. Correction methods evaluated were as follows: 1) DLW-TEE; 2) the Institute of Medicine's (IOM's) estimated energy requirement (EER) TEE prediction equation based on sex, height, weight, and age; 3) published NBS total energy TEE prediction (WHI-NBS-TEE) using age, BMI, race, and income; 4) reported protein versus reported energy linear regression-based residual method; and 5) a Goldberg cutoff to exclude subjects reporting energy intakes <1.35 times their basal metabolic rate. Efficacy was evaluated using correlations obtained by regressing corrected protein against biomarker protein (6.25 × urinary nitrogen/0.81).Results: Unadjusted self-reported protein intake from the FFQ (mean = 66.7 g) correlated weakly (r = 0.31) with biomarker protein (mean = 74.9 g). DLW-TEE-corrected self-reported protein intake (mean = 90.7 g) had the strongest correlation with biomarker protein (r = 0.47). Other energy corrections yielded lower, but still significant correlations: EER, r = 0.44 (mean = 92.1 g); WHI-NBS-TEE, r = 0.37 (mean = 90.4 g); Goldberg cutoff, r = 0.36 (mean = 88.4 g); and residual method, r = 0.35 (mean = 66.7 g).Conclusions: Our data indicate that proportional correction of reported protein intake using a measure of energy requirement from DLW-TEE or IOM-EER performed modestly better than other methods in this cohort. These energy adjustments, however, yielded corrected protein exceeding the biomarker protein, indicating that energy adjustment alone does not eliminate all self-reported protein reporting bias. [ABSTRACT FROM AUTHOR]

The purpose of the present paper is to (a) discuss how intelligent systems can augment cognitive capacity, and through self-regulation, assist learners to engage in critical thinking and (b) provide an example that highlights the information-rich context of the work environment and the role of self-regulation in working in partnership with technology to achieve peak performance. Self-regulation from a social cognitive perspective is conceptualized as a fluid, cyclical process whereby learners use externally provided or self-generated feedback to evaluate and adjust their learning strategies. With advances in technology, this paper attempts to illustrate how workers in jobs of the future will be supported in new ways to analyze data, make interpretation s and draw inferences, evaluate situations, and make decisions within a work context before, during, and post-work. Educational implications will be discussed. [ABSTRACT FROM AUTHOR]

Adverse childhood experiences (ACEs) have been shown to increase risk for negative health outcomes. Recent work has shown that lesbian, gay, and bisexual (LGB) individuals, on average, have higher ACEs scores compared to heterosexual individuals. However, past ACEs research involving LGB people did not assess the influence of experiencing childhood neglect and risk for poor health among this population. Further, this previous work has been limited to LGB people, excluding transgender and gender nonconforming experiences. The purpose of this project was to assess the relationship between ACEs, gender-identity, and physical and mental health status. As part of a larger community-based participatory research study, we surveyed 477 sexual and gender minority individuals about mental and physical health, ACEs, and sociodemographic characteristics. Transgender participants reported emotional abuse, physical neglect, and emotional neglect more frequently compared to cisgender LGB people. Two logistic regression models were run to assess the influence of ACE on quality of physical and mental health. The model adjusted for ACE scores showed that ACEs explained 17.6% of the variance in mental health. Our findings show that neglect is a common experience among LGB/TGN and needs to be assessed along with other ACE domains. Further, there may exist unique adverse experiences among this population during childhood resulting from social stigma. Future research should identify and quantify these experiences as well as assess the role of adversity during adulthood on mental health. [ABSTRACT FROM AUTHOR]

• An instrumented prosthetic socket evaluated shear and normal forces during walking. • The influence of a three ply sock worn within the prosthetic socket was evaluated. • Shear and normal forces were highest with the addition of a three ply sock. • Increased forces cause a decrease in blood perfusion which may lead to ulcers. Patients with transtibial amputation experience ulcers on their residual limb. The loading between the device and underlying material plays a role in loads transmitted to the skin. The objective was to evaluate normal and shear forces at the socket/liner interface during walking. A 53 year old male (85.45 kg and 177.8 cm) with a transtibial amputation participated in this case study. A transtibial prosthesis was instrumented with a load cell to measure normal and shear forces at the socket interface. Three conditions were evaluated during walking: gel liner, additional three ply sock and a hole in the gel liner. Shear and normal forces were highest with the addition of a three ply. Longitudinal shear stresses ranged from 0.4–7.66 kPa, transverse shear stresses ranged from 0.01–7.79 kPa and normal stresses ranged from 2.7–61.9 kPa. Increased shear and normal forces can cause a significant decrease in blood perfusion, linked to an increased risk of ulcer formation. Experimental force results are also important for future work involving finite element modeling of the skin/liner/device interface. [ABSTRACT FROM AUTHOR]

Objective: To describe contemporary management and outcomes of patients experiencing postoperative hemorrhage after minimally invasive radical prostatectomy.Materials and Methods: We retrospectively analyzed data from patients who underwent minimally invasive radical prostatectomy at our institution between January 2010 and January 2017. Clinically significant hemorrhage was defined as a decrease in hemoglobin of ≥30% or 4 g/dL from preoperative to 4 or 14 hours postoperative measurement, receiving a blood transfusion within 30 days, or undergoing a secondary procedure to control bleeding. Patients were analyzed in 3 groups: (1) serially monitored only, (2) received a blood transfusion, and (3) underwent a secondary procedure. Outcomes included imaging studies performed, length of stay, emergency room visits, hospital readmissions, complication rates, and functional outcomes.Results: Of 3749 men, 4% (151/3749) had clinically significant hemorrhage, 1.6% (60/3749) received a transfusion; 0.32% (12/3749) underwent a secondary procedure to control bleeding. In a 30-day composite outcome, increased healthcare utilization (emergency room visit, readmission, or Grade ≥3 complications), was seen in 25% of the serial monitoring group, 65% of the transfusion group, and 100% in the secondary procedure group. This rate in 3598 men without hemorrhage was 12.5%. One-year erectile function was poorest in men who underwent a secondary procedure. Urinary functional outcomes were similar in the 3 groups.Conclusion: Most patients experiencing clinically significant hemorrhage will stabilize without transfusion, and a very small fraction require secondary intervention. Patients experiencing milder bleeding events utilized additional healthcare resources at approximately twice the rate of those who did not, warranting appropriate counseling and postoperative monitoring. [ABSTRACT FROM AUTHOR]

Catalyzed H 2 O 2 propagations (CHP) is characterized by the most robust reactivity of any of the in situ chemical oxidation (ISCO) technologies because it generates the strong oxidant hydroxyl radical along with nucleophiles + reductants, such as superoxide radical. The most common groundwater contaminants, trichloroethylene (TCE) and perchloroethylene (PCE), were used as model contaminants in evaluating the effect of hydrogen peroxide (H 2 O 2) dosage on contaminant destruction kinetics. Both TCE and PCE degradation rates increased with H 2 O 2 dosages up to 0.1 M, and then decreased with higher H 2 O 2 dosages. Parallel reactions conducted with the addition of the hydroxyl radical scavenger 2-propanol and the hydroxyl radical-specific probe nitrobenzene confirmed that hydroxyl radical is primarily responsible for TCE and PCE degradation; however, 5–20% of their degradation was attributed to a non-hydroxyl radical mechanism. Reactions conducted with the superoxide probe tetranitromethane showed that superoxide generation rates increased with increasing H 2 O 2 doses. These results were confirmed by electron spin resonance spectroscopy. Therefore, the non-hydroxyl radical pathway for TCE and PCE degradation at H 2 O 2 ≥0.5 M was likely via nucleophilic attack by superoxide. The results of this research demonstrate that contaminants present in the aqueous phase that are reactive with hydroxyl radical require only low doses of H 2 O 2 (≤0.1 M), but subsurface systems contaminated with species not reactive with hydroxyl radical (e.g., carbon tetrachloride) require H 2 O 2 concentrations ≥0.5 M. Image 1 • Catalyzed H 2 O 2 Propagations is a robust in situ chemical oxidation technology. • TCE and PCE degradation was studied using a range of H 2 O 2 dosages. • Hydroxyl radical was the predominant transforming species. • Superoxide was an additional transforming species at H 2 O 2 dosages ≥0.5 M. • High doses of H 2 O 2 are necessary only when superoxide driven treatment is needed. [ABSTRACT FROM AUTHOR]

• There are conceptual and methodological problems for animal pain assessment. • Facial expression scales are valid, reliable pain recognition and evaluation tools. • Consistent and careful development of facial expression scales is required. • Facial expression scales need feasibility testing to aid use in clinical practice. • Guidelines are provided for development and use of facial expression scales. Effective management of pain is critical to the improvement of animal welfare. For this to happen, pain must be recognised and assessed in a variety of contexts. Pain is a complex phenomenon, making reliable, valid, and feasible measurement challenging. The use of facial expressions as a technique to assess pain in non-verbal human patients has been widely utilised for many years. More recently this technique has been developed for use in a number of non-human species: rodents, rabbits, ferrets, cats, sheep, pigs and horses. Facial expression scoring has been demonstrated to provide an effective means of identifying animal pain and in assessing its severity, overcoming some of the limitations of other measures for pain assessment in animals. However, there remain limitations and challenges to the use of facial expression as a welfare assessment tool which must be investigated. This paper reviews current facial expression pain scales ("Grimace Scales"), discussing the general conceptual and methodological issues faced when assessing pain, and highlighting the advantages of using facial expression scales over other pain assessment methods. We provide guidance on how facial expression scales should be developed so as to be valid and reliable, but we also provide guidance on how they should be used in clinical practice. [ABSTRACT FROM AUTHOR]