Developmental Pb exposure increases AD risk via altered intracellular Ca2+ homeostasis in hiPSC-derived cortical neurons.

Exposure to environmental chemicals such as lead (Pb) during vulnerable developmental periods can result in adverse health outcomes later in life. Human cohort studies have demonstrated associations between developmental Pb exposure and Alzheimer's disease (AD) onset in later life which were further corroborated by findings from animal studies. The molecular pathway linking developmental Pb exposure and increased AD risk, however, remains elusive. In this work, we used human iPSC-derived cortical neurons as a model system to study the effects of Pb exposure on AD-like pathogenesis in human cortical neurons. We exposed neural progenitor cells derived from human iPSC to 0, 15, and 50 ppb Pb for 48 h, removed Pb-containing medium, and further differentiated them into cortical neurons. Immunofluorescence, Western blotting, RNA-sequencing, ELISA, and FRET reporter cell lines were used to determine changes in AD-like pathogenesis in differentiated cortical neurons. Exposing neural progenitor cells to low-dose Pb, mimicking a developmental exposure, can result in altered neurite morphology. Differentiated neurons exhibit altered calcium homeostasis, synaptic plasticity, and epigenetic landscape along with elevated AD-like pathogenesis markers, including phosphorylated tau, tau aggregates, and Aß42/40. Collectively, our findings provide an evidence base for Ca dysregulation caused by developmental Pb exposure as a plausible molecular mechanism accounting for increased AD risk in populations with developmental Pb exposure.

Cognitive rehabilitation effects on grey matter volume and Go-NoGo activity in progressive multiple sclerosis: results from the CogEx trial.

BACKGROUND: Research on cognitive rehabilitation (CR) and aerobic exercise (EX) to improve cognition in progressive multiple sclerosis (PMS) remains limited. CogEx trial investigated the effectiveness of CR and EX in PMS: here, we present MRI substudy volumetric and task-related functional MRI (fMRI) findings. METHODS: Participants were randomised to: 'CR plus EX', 'CR plus sham EX (EX-S)', 'EX plus sham CR (CR-S)' and 'CR-S plus EX-S' and attended 12-week intervention. All subjects performed physical/cognitive assessments at baseline, week 12 and 6 months post intervention (month 9). All MRI substudy participants underwent volumetric MRI and fMRI (Go-NoGo task). RESULTS: 104 PMS enrolled at four sites participated in the CogEx MRI substudy; 84 (81%) had valid volumetric MRI and valid fMRI. Week 12/month 9 cognitive performances did not differ among interventions; however, 25-62% of the patients showed Symbol Digit Modalities Test improvements. Normalised cortical grey matter volume (NcGMV) changes at week 12 versus baseline were heterogeneous among interventions (p=0.05); this was mainly driven by increased NcGMV in 'CR plus EX-S' (p=0.02). Groups performing CR (ie, 'CR plus EX' and 'CR plus EX-S') exhibited increased NcGMV over time, especially in the frontal (p=0.01), parietal (p=0.04) and temporal (p=0.04) lobes, while those performing CR-S exhibited NcGMV decrease (p=0.008). In CR groups, increased NcGMV (r=0.36, p=0.01) at week 12 versus baseline correlated with increased California Verbal Learning Test (CVLT)-II scores. 'CR plus EX-S' patients exhibited Go-NoGo activity increase (p<0.05, corrected) at week 12 versus baseline in bilateral insula. CONCLUSIONS: In PMS, CR modulated grey matter (GM) volume and insular activity. The association of GM and CVLT-II changes suggests GM plasticity contributes to cognitive improvements. TRIAL REGISTRATION NUMBER: NCT03679468.

Firearm Ownership: A Key Factor to Consider in Firearm Suicide Deaths in Children, Despite State Gun Laws.

INTRODUCTION: Firearm-related suicides among children present a significant public health concern and a tragic loss of young lives. This study explores the relationship between firearm-related suicides, gun ownership, and state-specific gun laws. METHODS: This retrospective cohort study collected data from the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research on children under 18 who died by firearm-related suicides between 2009 and 2016 in all 50 states and D.C. It also utilized data from the RAND State-Level Estimates of Household Firearm Ownership. The study focused on the rate of child firearm suicide deaths per 100,000 individuals. The key variable of interest was the percentage of guns owned per household in each state. Univariable analysis was conducted to examine the association between individual gun laws and child firearm suicide mortalities, while multivariable regression, adjusting for household gun ownership and significant firearm legislation, was employed to assess connection to child firearm suicide mortality. RESULTS: From 2009 to 2016, 3903 children died from firearm-related suicides in the United States. In our analysis, 15 out of 44 firearm laws were found to be associated with reducing the rates of firearm suicides among children (P < 0.05). However, multivariable regression showed that higher state gun ownership rates were the primary predictor of increased child fatalities from firearms, with children in such states being 325% more likely to die when analyzing handgun laws and 337% more likely when analyzing long gun laws, as indicated by coefficients of 4.25 and 4.37, respectively. No state laws alone notably improved death rates. CONCLUSIONS: Gun ownership has a stronger association with child suicide rates than state-specific gun laws. Given the weight of gun ownership, future research should prioritize comprehensive public health initiatives to prevent child firearm-related suicides.

Systematic Literature Review of Health-Related Quality-of-Life Measures for Caregivers of Older Adult Trauma Patients.

INTRODUCTION: As the older adult population increases, hospitals treat more older adults with injuries. After leaving, these patients suffer from decreased mobility and independence, relying on care from others. Family members often assume this responsibility, mostly informally and unpaid. Caregivers of other older adult populations have increased stress and decreased caregiver-related quality of life (CRQoL). Validated CRQoL measures are essential to capture their unique experiences. Our objective was to review existing CRQoL measures and their validity in caregivers of older adult trauma patients. METHODS: A professional librarian searched published literature from the inception of databases through August 12, 2022 in MEDLINE (via PubMed), Embase (via Elsevier), and CINAHL Complete (via EBSCO). We identified 1063 unique studies of CRQoL in caregivers for adults with injury and performed a systematic review following COnsensus-based Standards for the selection of health Measurement Instruments guidelines for CRQoL measures. RESULTS: From the 66 studies included, we identified 54 health-related quality-of-life measures and 60 domains capturing caregiver-centered concerns. The majority (83%) of measures included six or fewer CRQoL content domains. Six measures were used in caregivers of older adults with single-system injuries. There were no validated CRQoL measures among caregivers of older adult trauma patients with multisystem injuries. CONCLUSIONS: While many measures exist to assess healthcare-related quality of life, few, if any, adequately assess concerns among caregivers of older adult trauma patients. We found that CRQoL domains, including mental health, emotional health, social functioning, and relationships, are most commonly assessed among caregivers. Future measures should focus on reliability and validity in this specific population to guide interventions.

Factors Associated With Triage Decisions in Older Adult Trauma Patients: Impact on Mortality and Morbidity.

INTRODUCTION: As medical advances have significantly increased the life expectancy among older adults, the number of older patients requiring trauma care has risen proportionately. Nevertheless, it is unclear among this growing population which sociodemographic and economic factors are associated with decisions to triage and transfer to level I/II centers. This study aims to assess for any association between patient sociodemographic characteristics, triage decisions, and outcomes during acute trauma care presentations. METHODS: The National Trauma Data Bank was queried for patients aged 65 and older with an injury severity score > 15 between the years 2007 to 2017. Factors associated with subsequent levels of triage on presentation were assessed using multivariate logistic regression, and associations of levels of triage with outcomes of mortality, morbidity, and hospital length of stay are examined using logistic and linear regression models. RESULTS: Triage of 210,310 older adult trauma patients showed significant findings. American Indian patients had higher odds of being transferred to level I/II centers, while Asian, Black, and Native Hawaiian patients had lower odds of being transferred to level I/II centers when compared to Caucasian patients (P < 0.001). Regarding insurance, self-pay (uninsured) patients were less likely to be transferred to a higher level of care; however, this was also demonstrated in private insurance holders (P < 0.001). Caucasian patients had significantly higher odds of mortality, with Black patients (odds ratio [OR] 0.80 [0.75, 0.85]) and American Indian patients (OR 0.87 [0.72, 1.04]) having significantly lower odds (P < 0.001). Compared to government insurance, private insurance holders (OR 0.82 [0.80, 0.85]) also had significantly lower odds of mortality, while higher odds among self-pay were observed (OR 1.75 [1.62, 1.90]), (P < 0.001). CONCLUSIONS: Access to insurance is associated with triage decisions involving older adults sustaining trauma, with lower access increasing mortality risk. Factors such as race and gender were less likely to be associated with triage decisions. However, due to this study's retrospective design, further prospective analysis is necessary to fully assess the decisions that influence trauma triage decisions in this patient population.

Differential Developmental Neurotoxicity and Tissue Uptake of the Per- and Polyfluoroalkyl Substance Alternatives, GenX and PFBS.

Per- and polyfluoroalkyl substances (PFAS) are a class of synthetic chemicals with several applications. Multiple adverse health effects are reported for longer carbon chain (≤C8) PFAS. Shorter carbon chain PFAS, [e.g., hexafluoropropylene oxide dimer acid (HFPO-DA; GenX) and perfluorobutanesulfonic acid (PFBS)] were introduced as alternatives. Past studies indicate that longer-chain PFAS are neurotoxic targeting the dopamine pathway, but it is not known if shorter-chain PFAS act similarly. This study aimed to evaluate developmental neurotoxicity and tissue uptake of GenX and PFBS using the zebrafish (Danio rerio). First, acute toxicity was assessed by measuring LC50 at 120 h postfertilization (hpf). Body burden was determined after embryonic exposure (1-72 hpf) to sublethal concentrations of GenX or PFBS by LC-ESI-MS/MS. Locomotor activity using a visual motor response assay at 120 hpf and dopamine levels at 72 hpf was assessed after embryonic exposure. PFBS was more acutely toxic and bioaccumulative than GenX. GenX and PFBS caused hyperactivity at 120 hpf, but stronger behavioral alterations were observed for PFBS. An increase in whole organism dopamine occurred at 40 ppb of GenX, while a decrease was observed at 400 ppb of PFBS. Differences detected in dopamine for these two PFAS indicate differential mechanisms of developmental neurotoxicity.

Management of adult renal trauma: a practice management guideline from the eastern association for the surgery of trauma.

BACKGROUND: The kidney is the most frequently injured component of the genitourinary system, accounting for 5% of all trauma cases. Several guidelines by different societies address the management of urological trauma. However, unanswered questions remain regarding optimal use of angioembolization in hemodynamically stable patients, indications for operative exploration of stable retroperitoneal hematomas and renal salvage techniques in the setting of hemodynamic instability, and imaging practices for patients undergoing non-operative management. We performed a systematic review, meta-analysis, and developed evidence-based recommendations to answer these questions in both blunt and penetrating renal trauma. METHODS: The working group formulated four population, intervention, comparator, outcome (PICO) questions regarding the following topics: (1) angioembolization (AE) usage in hemodynamically stable patients with evidence of ongoing bleeding; (2) surgical approach to stable zone II hematomas (exploration vs. no exploration) in hemodynamically unstable patients and (3) surgical technique (nephrectomy vs. kidney preservation) for expanding zone II hematomas in hemodynamically unstable patients; (4) frequency of repeat imaging (routine or symptom based) in high-grade traumatic renal injuries. A systematic review and meta-analysis of currently available evidence was performed. RevMan 5 (Cochran Collaboration) and GRADEpro (Grade Working Group) software were used. Recommendations were voted on by working group members and concurrence was obtained for each final recommendation. RESULTS: A total of 20 articles were identified and analyzed. Two prospective studies were encountered; the majority were retrospective, single-institution studies. Not all outcomes projected by PICO questions were reported in all studies. Meta-analysis was performed for all PICO questions except PICO 3 secondary to the discrepant patient populations included in those studies. PICO 1 had the greatest number of articles included in the meta-analysis with nine studies; yet, due to differences in study design, no critical outcomes emerged; similar differences among a smaller set of articles prevented observation of critical outcomes for PICO 4. Analyses of PICOs 2 and 3 favored a non-invasive or minimally invasive approach in-line with current international practice trends. CONCLUSION: In hemodynamically stable adult patients with clinical or radiographic evidence of ongoing bleeding, no recommendation could be made regarding the role of AE vs. observation. In hemodynamically unstable adult patients, we conditionally recommend no renal exploration vs. renal exploration in stable zone II hematomas. In hemodynamically unstable adult patients, we conditionally recommend kidney preserving techniques vs. nephrectomy in expanding zone II hematomas. No recommendation could be made for the optimal timing of repeat imaging in high grade renal injury. LEVEL OF EVIDENCE: Guideline; systematic review, level III.

Trajectory of Change in Parental Accommodation and Its Relation to Symptom Severity and Impairment in Pediatric OCD.

Family accommodation (FA) has been shown to relate to poorer treatment outcomes in pediatric obsessive compulsive disorder (OCD), yet few studies have examined the trajectory of change in FA throughout treatment and its relation to treatment outcomes. This study examined change in FA in relation to change in symptom severity and impairment in 63 youth receiving a family-based intervention for early-onset OCD. FA, symptom severity and functional impairment were assessed at baseline, week 5, week 9, and post-treatment (week 14). Results suggested that changes in FA in the beginning stages of treatment preceded global symptom improvement (but not OCD specific improvement) whereas changes in functional impairment preceded changes in FA. In the latter half of treatment, changes in FA preceded improvement in global and OCD specific symptom severity as well as functional impairment. These findings highlight the importance of reducing FA, especially in the later stages of treatment, in order to optimize treatment outcomes in early-onset OCD.

Measuring the cost-effectiveness of treatments for people with multiple sclerosis: Beyond quality-adjusted life-years.

BACKGROUND: It is a familiar story. A promising multiple sclerosis (MS) treatment clears the three regulatory hurdles of safety, quality and efficacy, only to fall at the fourth: cost-effectiveness. This has led to concerns about the validity of the measures typically used to quantify treatment effects in cost-effectiveness analyses and in 2012, in the United Kingdom, the National Institute for Health and Care Excellence called for an improvement in the cost-effectiveness framework for assessing MS treatments. OBJECTIVE AND METHODS: This review describes what is meant by cost-effectiveness in health/social care funding decision-making, and usual practice for assessing treatment benefits. RESULTS: We detail the use of the quality-adjusted life-year (QALY) in resource allocation decisions, and set out limitations of this approach in the context of MS. CONCLUSION: We conclude by highlighting methodological and policy developments which should aid addressing these limitations.

The relationship between processing speed and verbal and non-verbal new learning and memory in progressive multiple sclerosis.

OBJECTIVE: Processing speed (PS) deficits are the most common cognitive deficits in multiple sclerosis (MS), followed by learning and memory deficits, and are often an early cognitive problem. It has been argued that impaired PS is a primary consequence of MS, which in turn decreases learning. The current analysis examined the association between PS and learning in a large cohort of individuals with progressive MS. METHODS: Baseline data from a randomized clinical trial on rehabilitation taking place at 11 centers across North America and Europe were analyzed. Participants included 275 individuals with clinically definite progressive MS (primary, secondary) consented into the trial. RESULTS: Symbol Digit Modalities Test (SDMT) significantly correlated with California Verbal Learning Test-II (CVLT-II) (r = 0.21, p = 0.0003) and Brief Visuospatial Memory Test-Revised (BVMT-R) (r = 0.516, p < 0.0001). Receiver operating characteristic (ROC) analysis of the SDMT z score to distinguish between impaired and non-impaired CVLT-II performance demonstrated an area under the curve (AUC) of 0.61 (95% confidence interval (CI): 0.55-0.68) and a threshold of -1.62. ROC analysis between SDMT and BVMT-R resulted in an AUC of 0.77 (95% CI: 0.71-0.83) and threshold of -1.75 for the SDMT z score to predict impaired BVMT-R. CONCLUSION: Results indicate little ability beyond chance to predict CVLT-II from SDMT (61%), albeit statistically significant. In contrast, there was a 77% chance that the model could distinguish between impaired and non-impaired BVMT-R. Several potential explanations are discussed.

Cardiorespiratory fitness and free-living physical activity are not associated with cognition in persons with progressive multiple sclerosis: Baseline analyses from the CogEx study.

BACKGROUND: Aerobic exercise training (physical activity for improving cardiorespiratory fitness) represents a promising approach for managing cognitive impairment in multiple sclerosis (MS). However, there is limited evidence that levels of physical activity and fitness are associated with cognition in progressive MS. OBJECTIVE: We examined associations among cardiorespiratory fitness, moderate-to-vigorous physical activity (MVPA), and cognitive performance in a large, international progressive MS sample. METHODS: Two hundred forty European and North American persons with progressive MS underwent cardiorespiratory fitness measurement on a recumbent stepper, wore an ActiGraph GT3X + accelerometer for 7 days for measuring MVPA, and underwent the Brief International Cognitive Assessment in MS. RESULTS: Cardiorespiratory fitness was not significantly correlated with Symbol Digit Modalities Test (SDMT; r = -0.01; r = -0.04), California Verbal Learning Test-II (CVLT-II; r = 0.05; r = 0.05), or Brief Visuospatial Memory Test-Revised (BVMT-R; r = -0.14; r = -0.14) z-scores controlling for age, sex, and education. MVPA and SDMT (r = 0.05), CVLT-II (r = -0.07), and BVMT-R (r = 0.01) z-scores were not significantly correlated. CONCLUSION: Cardiorespiratory fitness and MVPA were not associated with cognition in this large progressive MS sample, yet these outcomes represent critical manipulation checks for documenting the success of the CogEx trial. This highlights the importance of examining other exercise-related mechanisms-of-action for improving cognition in progressive MS.

Impact of the hepatoselective glucokinase activator TTP399 on ketoacidosis during insulin withdrawal in people with type 1 diabetes.

AIMS: To determine the effect of TTP399, a hepatoselective glucokinase activator, on the risk of ketoacidosis during insulin withdrawal in individuals with type 1 diabetes (T1D). MATERIALS AND METHODS: Twenty-three participants with T1D using insulin pump therapy were randomized to 800 mg TTP399 (n = 12) or placebo (n = 11) for 7 to 10 days. After the treatment period, an insulin withdrawal test (IWT) was performed, during which insulin pumps were removed to induce ketogenesis. The IWT was stopped after 10 hours or if blood glucose reached >399 mg/dL [22.1 mmol/L], if beta-hydroxybutyrate (BHB) was >3.0 mmol/L, or for patient discomfort. The primary endpoint was the proportion of participants who reached BHB concentrations of 1 mmol/L or greater. RESULTS: During the 7- to 10-day treatment period, mean fasting plasma glucose was significantly reduced ( -27.6 vs. -4.4 mg/dL [-1.5 vs. -0.2 mmol/L]; P = 0.03) and there were fewer adverse events, including hypoglycaemia, in the TTP399-treated arm. During the IWT, no differences were observed between TTP399 and placebo in mean serum BHB concentration, mean duration of IWT, or BHB at termination of IWT. However, serum bicarbonate was numerically higher and urine acetoacetate was quantitatively lower in the TTP399-treated participants. As a result of higher bicarbonate values, none of the TTP399-treated participants met the prespecified criteria for diabetic ketoacidosis (DKA), defined as BHB >3 mmol/L and serum bicarbonate <18 mEq/L, compared to 42% of placebo-treated participants. CONCLUSIONS: When used as an adjunctive therapy to insulin, TTP399 improves glycaemia without increasing hypoglycaemia in individuals with T1D. During acute insulin withdrawal, TTP399 did not increase BHB concentrations and decreased the incidence of DKA.

Precision Implementation: An Approach to Mechanism Testing in Implementation Research.

Advancing mechanism-focused research in implementation science is a priority given its potential to improve tailoring and efficiency of implementation strategies. Experimental therapeutics, or experimental medicine, offers an approach for mechanism testing that has been promoted by the NIH Science of Behavior Change and endorsed by the National Institute for Mental Health. This approach has been applied across the translational spectrum - with initial applications to biological research and more recent applications to psychosocial treatment development research. We describe further advancement of experimental therapeutics along the translational spectrum and describe how it is ideally suited to inform precision experimental tests of implementation strategy mechanisms, which we term precision implementation. Such an approach to mechanism testing will allow for identification of causal dose-response relationships between implementation strategies, presumed mechanisms, and implementation outcomes. We discuss the tension between the scientific rigor required to conduct mechanism-focused research using experimental therapeutics and the "real world" conditions in which implementation research takes place. We provide a series of example studies that show "beginning to end" application of this framework in research focused on provider implementation of an evidence-based intervention in routine clinical care settings.

Creation of a Clinical Demonstration Unit: Embedding Academic Research into Point of Care in a Geriatric Unit.

Given that there are limited evidence-informed non-pharmacological interventions to treat behavioural and psychological symptoms of dementia, a specialized psychiatric hospital partnered with an academic university to create a clinical demonstration unit (CDU) - a learning health systems (LHS) model to advance dementia care. In this paper, we identify five key enablers that led to the successful creation of the CDU, its achievements and challenges encountered. The paper provides learnings for other healthcare providers who are considering initiating an LHS model within their setting to advance patient care.

Prioritizing progressive MS rehabilitation research: A call from the International Progressive MS Alliance.

BACKGROUND: People with multiple sclerosis (MS) experience myriad symptoms that negatively affect their quality of life. Despite significant progress in rehabilitation strategies for people living with relapsing-remitting MS (RRMS), the development of similar strategies for people with progressive MS has received little attention. OBJECTIVE: To highlight key symptoms of importance to people with progressive MS and stimulate the design and implementation of high-quality studies focused on symptom management and rehabilitation. METHODS: A group of international research experts, representatives from industry, and people affected by progressive MS was convened by the International Progressive MS Alliance to devise research priorities for addressing symptoms in progressive MS. RESULTS: Based on information from the MS community, we outline a rationale for highlighting four symptoms of particular interest: fatigue, mobility and upper extremity impairment, pain, and cognitive impairment. Factors such as depression, resilience, comorbidities, and psychosocial support are described, as they affect treatment efficacy. CONCLUSIONS: This coordinated call to action-to the research community to prioritize investigation of effective symptom management strategies, and to funders to support them-is an important step in addressing gaps in rehabilitation research for people affected by progressive MS.

Embryonic atrazine exposure and later in life behavioral and brain transcriptomic, epigenetic, and pathological alterations in adult male zebrafish.

Atrazine (ATZ), a commonly used pesticide linked to endocrine disruption, cancer, and altered neurochemistry, frequently contaminates water sources at levels above the US Environmental Protection Agency's 3 parts per billion (ppb; µg/L) maximum contaminant level. Adult male zebrafish behavior, brain transcriptome, brain methylation status, and neuropathology were examined to test the hypothesis that embryonic ATZ exposure causes delayed neurotoxicity, according to the developmental origins of health and disease paradigm. Zebrafish (Danio rerio) embryos were exposed to 0 ppb, 0.3 ppb, 3 ppb, or 30 ppb ATZ during embryogenesis (1-72 h post fertilization (hpf)), then rinsed and raised to maturity. At 9 months post fertilization (mpf), males had decreased locomotor parameters during a battery of behavioral tests. Transcriptomic analysis identified altered gene expression in organismal development, cancer, and nervous and reproductive system development and function pathways and networks. The brain was evaluated histopathologically for morphometric differences, and decreased numbers of cells were identified in raphe populations. Global methylation levels were evaluated at 12 mpf, and the body length, body weight, and brain weight were measured at 14 mpf to evaluate effects of ATZ on mature brain size. No significant difference in genome methylation or brain size was observed. The results demonstrate that developmental exposure to ATZ does affect neurodevelopment and neural function in adult male zebrafish and raises concern for possible health effects in humans due to ATZ's environmental presence and persistence. Graphical abstract.

Comparison of zebrafish in vitro and in vivo developmental toxicity assessments of perfluoroalkyl acids (PFAAs).

Perfluoroalkyl acids (PFAAs) are persistent environmental contaminants that are associated with various adverse health outcomes. Perfluorooctanoic acid (PFOA) is one of the most prominently detected PFAAs in the environment, which is now replaced with shorter chain carbon compounds including perfluorohexanoic acid (PFHxA) and perfluorobutyric acid (PFBA). The aim of this study was to compare the toxicity of four PFAAs as a function of chain length and head group (carboxylate versus sulfonate) with in vitro and in vivo zebrafish assessments, which were subsequently compared to other cell and aquatic models. Mortality rate increased with chain length (PFOA > PFHxA ≫ PFBA) in both whole embryo/larvae and embryonic cell models. The sulfonate group enhanced toxicity with perfluorobutane sulfonate (PFBS) showing higher toxicity than PFBA and PFHxA in both larvae and cells. Toxicity trends were similar among different aquatic models, but sensitivities varied. Discrepancies with other zebrafish studies were confirmed to be associated with a lack of neutralization of acidic pH of dosing solutions in these other investigations, demonstrating the need for rigor in reporting pH of exposure solutions in all experiments. The zebrafish embryonic cell line was also found to be similar to most other cell lines regardless of exposure length. Overall, results agree with findings in other cell lines and organisms where longer chain length and sulfonate group increase toxicity, except in investigations not neutralizing the exposure solutions for these acidic compounds.

Moderators of Psychosocial Treatment for Pediatric Obsessive-Compulsive Disorder: Summary and Recommendations for Future Directions.

This brief report examines the evidence for moderators of psychosocial treatment for youth with obsessive-compulsive disorder (OCD). Understanding treatment moderators can help clinicians select the most appropriate intervention for a particular patient and consequently increase the likelihood of initial response. A systematic search of the literature was conducted to identify randomized trials and meta-analyses reporting on moderators of psychosocial treatment for pediatric OCD. All studies included a comparison of cognitive-behavioral therapy (CBT) to active or control conditions. Few studies have evaluated moderators of psychosocial treatment for youth with OCD, and among those studies, few variables have demonstrated a differential effect on treatment response. Moderator analyses require large samples to garner the statistical power necessary to adequately evaluate differential responding in subgroups, and unfortunately, most reports of moderators in this review are post-hoc investigations of datasets from trials with relatively small sample sizes. Given the overwhelming number of CBT treatment variants and potential moderators, it would be impossible to conduct all the necessary head-to-head trials with sufficient sample sizes to develop helpful clinical guidelines. The best option for advancing the moderator literature is to utilize advanced statistical approaches for pooling existing data sets. Recommendations for leveraging emerging techniques in individual participant data meta-analysis (IPD-MA) are briefly discussed.

Core Motivations of Childhood Obsessive-Compulsive Disorder: The Role of Harm Avoidance and Incompleteness.

In an effort to improve patient conceptualization and targeted treatment, researchers have sought to accurately classify OCD subtypes. To date, the most common form of OCD classification has used the content of symptom topography as opposed to functional links between symptoms to categorize OCD. The aim of the current study was to explore the associations between these two forms of OCD classification. Participant topographical symptoms were self-reported using the Obsessive-Compulsive Inventory-Child Version (OCI-CV). Clinicians assessed whether participant symptoms were motivated by harm avoidance and/or incompleteness. Structural equation modeling was employed to explore the associations between harm avoidance and incompleteness and symptom dimensions in youth with OCD. Results showed that harm avoidance was significantly associated with doubting/checking, obsessing, and neutralizing symptoms, whereas incompleteness was associated with doubting/checking, ordering, and neutralizing symptoms. Findings are consistent with child and adult literature and highlight the importance of assessing the underlying function of OC behaviors.

Task specific dystonia - a patients' perspective.

BACKGROUND: Task specific dystonia (TSD) is a subtype of dystonia with no cure and significant limitations on treatments. Few studies have investigated the outcomes of rehabilitative therapy from the patient's perspective. PURPOSE OF THE STUDY: This study explored the interventions that patients have utilized and their perceived effectiveness in treating and managing their TSD, specifically musicians' dystonia (MD) and writer's dystonia (WD). Symptoms and the effect of TSD on the perceived performance of every day and specific tasks, and possible reasons why the condition developed, were also investigated. STUDY DESIGN: Descriptive survey. METHODS: Patients diagnosed with TSD, treated at a private hand therapy unit, who had consented to being contacted for research purposes, were emailed a link to an online survey (or posted if email was not available), administered via KwikSurveys. The survey consisted of 4 subsections: personal information, general medical history, dystonia medical history and dystonia treatment history. RESULTS: Invitations were sent to 105 patients of whom 90% (n = 95/105) responded. Results for both the MD and WD groups were similar. There was a significant association between the 2 groups as to what they viewed may have led to the development of TSD (a change in technique; P < .001) and the most effective treatments (massage P< .043, modifications to the instrument P< .002; ultrasound therapy P< .013.) All reported that daily activities were affected by their condition. DISCUSSION: Although full levels of task specific function (playing their instrument or writing) were not usually regained, participants with both MD and WD perceived improvement in symptoms with rehabilitation intervention. Three treatments were perceived to be most effective in achieving this, suggesting that these should be considered for inclusion within treatment plans. CONCLUSIONS: From the perspective of people with TSD, a range of rehabilitation interventions are effective in enhancing symptom management, providing further evidence to support their use.