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Media coverage of non-suicidal self-injury (NSSI) ranges from providing helpful education to displaying graphic images. We offer the first research-informed, consensus-based guidelines for the responsible reporting and depicting of NSSI in the media, while also advising on ideas for dissemination and collaboration between media professionals and healthcare experts.
To evaluate the psychometric characteristics of the Cognitive Difficulties Scale (CDS), a 39-item Likert-type self-report instrument that requires a fifth grade reading level. The CDS is a popular instrument that has been shown to predict cognitive decline in older persons.
Participants were 512 consecutive outpatient referrals (71% women, mean age 60.6, and education 14.6 years) for a neuropsychological examination in a memory disorders clinic as part of a broader neurodiagnostic workup for cognitive decline. A principal components analysis was followed by a varimax rotation (Kaiser). Factor scores were investigated in relation to multiple internal and external criteria including demographics, Cronbach’s alpha, Digit Span, and Wechsler Memory Scale-IV Logical Memory (LM) and Visual Reproduction (VR), and Minnesota Multiphasic Personality Inventory (MMPI)-2 measures of depression, anxiety, somatic preoccupations, and thought disturbance.
Six dimensions of cognitive complaint emerged accounting for 64% of the variance: attention/concentration, praxis, prospective memory, speech problems, memory for people’s names, and temporal orientation. The factors showed good internal consistency (alphas > .850). Correlations with Digit Span, LM, and VR were all nonsignificant. CDS scores were associated with MMPI-2 measures of anxiety, depression, somatic preoccupation, and thought disturbance. Percentiles and T-scores were derived for raw scores on the CDS and its six component subscales.
The CDS is a multidimensional measure of subjective cognitive complaints that provides clinicians with a psychometrically sound basis for deriving a profile with six subscale scores. The test has clinical utility and is a potentially useful tool in research involving age-related cognitive changes and meta-cognition.
Psychosocial stress in childhood and adolescence is linked to stress system dysregulation, although few studies have examined the relative impacts of parental harshness and parental disengagement. This study prospectively tested whether parental harshness and disengagement show differential associations with overall cortisol output in adolescence. Associations between overall cortisol output and adolescent mental health problems were tested concurrently. Adolescents from the Fragile Families and Child Wellbeing Study (FFCWS) provided hair samples for cortisol assay at 15 years (N = 171). Caregivers reported on parental harshness and disengagement experiences at 1, 3, 5, 9, and 15 years, and adolescents reported at 15 years. Both parent and adolescent reported depressive and anxiety symptoms and antisocial behaviors at 15. Greater parental harshness from 1–15 years, and harshness reported at 15 years in particular, was associated with higher overall cortisol output at 15. Greater parental disengagement from 1–15 years, and disengagement at 1 year specifically, was associated with lower cortisol output. There were no significant associations between cortisol output and depressive symptoms, anxiety symptoms, or antisocial behaviors. These results suggest that the unique variances of parental harshness and disengagement may have opposing associations with cortisol output at 15 years, with unclear implications for adolescent mental health.
Air pollution is linked to mortality and morbidity. Since humans spend nearly all their time indoors, improving indoor air quality (IAQ) is a compelling approach to mitigate air pollutant exposure. To assess interventions, relying on clinical outcomes may require prolonged follow-up, which hinders feasibility. Thus, identifying biomarkers that respond to changes in IAQ may be useful to assess the effectiveness of interventions.
We conducted a narrative review by searching several databases to identify studies published over the last decade that measured the response of blood, urine, and/or salivary biomarkers to variations (natural and intervention-induced) of changes in indoor air pollutant exposure.
Numerous studies reported on associations between IAQ exposures and biomarkers with heterogeneity across study designs and methods. This review summarizes the responses of 113 biomarkers described in 30 articles. The biomarkers which most frequently responded to variations in indoor air pollutant exposures were high sensitivity C-reactive protein (hsCRP), von Willebrand Factor (vWF), 8-hydroxy-2′-deoxyguanosine (8-OHdG), and 1-hydroxypyrene (1-OHP).
This review will guide the selection of biomarkers for translational studies evaluating the impact of indoor air pollutants on human health.
Outbreaks of cyclosporiasis, a food-borne illness caused by the coccidian parasite Cyclospora cayetanensis have increased in the USA in recent years, with approximately 2300 laboratory-confirmed cases reported in 2018. Genotyping tools are needed to inform epidemiological investigations, yet genotyping Cyclospora has proven challenging due to its sexual reproductive cycle which produces complex infections characterized by high genetic heterogeneity. We used targeted amplicon deep sequencing and a recently described ensemble-based distance statistic that accommodates heterogeneous (mixed) genotypes and specimens with partial genotyping data, to genotype and cluster 648 C. cayetanensis samples submitted to CDC in 2018. The performance of the ensemble was assessed by comparing ensemble-identified genetic clusters to analogous clusters identified independently based on common food exposures. Using these epidemiologic clusters as a gold standard, the ensemble facilitated genetic clustering with 93.8% sensitivity and 99.7% specificity. Hence, we anticipate that this procedure will greatly complement epidemiologic investigations of cyclosporiasis.
Older adults’ mental health problems are a growing public health concern, especially because their rate of mental health service use is particularly low. Decades of mental health service utilisation models have been developed, yet key assumptions from these models focus primarily on factors that facilitate or inhibit access into the treatment system without taking into considering the dynamics of how individuals respond to their mental health problems and engage in service utilisation. More recently, dynamic models like the Network Episode Model (NEM-II) have been developed to challenge the underlying, rational choice assumption of traditional utilisation models. Given the multifaceted and complex nature of older adults’ mental health problems, the objective of this study was to examine whether the NEM-II is a helpful and appropriate model for understanding the dynamic process of how older adults navigate the mental health system, including factors that advanced and delayed help-seeking. Our qualitative analyses from 15 interviews with older adults revealed that their backgrounds, social supports and treatment systems influence, and are influenced by, their illness careers. Factors that delayed help-seeking included: a lack of support, ‘inappropriate’ referrals/advice from treatment professionals and poor mental health literacy. This research suggests the NEM-II is a helpful and appropriate theory for understanding older adults’ pathways to treatment, and has implications to enhance older adults’ access to psychological services.
OBJECTIVES/GOALS: Mammals require iron for hemoglobin, respiration, immunity and as cofactor in enzymes. But free iron is toxic from the production of reactive oxygen species. Ferroportin is the sole exporter of cellular iron and it crucially determines cellular and systemic iron levels. Labile iron must be tightly regulated. This requires structural understanding. METHODS/STUDY POPULATION: We built structure of human ferroportin (FPN1) using the ab ignition prediction approaches of Rosetta/Robetta and by comparative modeling with distance restraints in MODELLER. Templates selected were from solute carrier protein families of distantly related orthologs and homologs including a proton coupled peptide transporter (PDB ID: 4IKV) and the bacterial iron transporter in outward-open and inward-open states, (PDB ID: 5AYM, 5AYO). Each model was validated by experimental mass spectrometry data. The energy minimized structural model was inserted into a lipid bilayer, placed in a rectangular simulation box, covered with TIP3P water solvent balanced with counterions and conditioned. Finally, we carried out 350 nanoseconds molecular dynamics simulations. RESULTS/ANTICIPATED RESULTS: Our first model of FPN1 (571aa), using Rosetta/Robetta ab initio approach, resembles the structure of the proton-dependent transporter, POT and consists of 12 transmembrane helices. The membrane spanning helices veer away from the orientation in the structure of 4IKV. The alternate model using MODELLER and the method of satisfaction of constraints, returned one template, the structure of Bdellovibrio bacteriovorus iron (Fe2+) transporter homolog (5AYN, 440aa) with sequence identity of 19%. Aligning FPN1 on the template sequence incorporating structural information revealed better conservation (29%). This model also comprises 12 transmembrane helices in two bundles separated by a large intracellular loop. The iron binding site predicted in both models match the structures of distant bacterial homologs. DISCUSSION/SIGNIFICANCE OF IMPACT: We are using these experimentally verified structures and functional data to answer questions about the mechanism of ferroportin iron transport, structural dynamics and the significance of mutations in ferroportin seen in different populations, especially the Q248H mutation found in Africans and black Americans with moderate to high prevalence.
OBJECTIVES/GOALS: Breast cancer metastases are stochastic and difficult to detect. Therapy is often ineffective due to phenotypic changes of tumor cells at these sites. We engineered a synthetic metastatic niche to study the role of phenotypic transitions in the microenvironment on tumor cell phenotype. METHODS/STUDY POPULATION: The engineered metastatic niche is composed of a porous polycaprolactone scaffold implanted subcutaneously in Balb/c mice. The mice received an orthotopic inoculation of 4T1 cells (murine triple negative breast cancer) in the fourth right mammary fat pad and the disease was allowed to progress for 7-21 days (pre-metastatic to overt metastatic disease). The scaffolds and lungs (native metastatic site) were explanted and analyzed by single cell RNA-seq via Drop-seq. Cell phenotypes were identified and tracked over time with the Seurat and Monocle3 pipelines. Assessment of the impact of these cell populations on tumor cell phenotype was conducted through Transwell co-cultures. RESULTS/ANTICIPATED RESULTS: Healthy scaffolds are primarily composed of macrophages, dendritic cells, and fibroblasts – consistent with a foreign body response. Despite differences in the lung and scaffold prior to tumor inoculation, both tissues were marked by >5-fold increase in neutrophils/MDSCs. Additionally, 79% of genes at the scaffold that significantly changed over time were also identified in the lung, indicating key similarities in niche maturation. However, many immune cells at the scaffold had distinct phenotypes, with pro-inflammatory/cytotoxic characteristics. These changes clearly impacted tumor cell phenotype, as cells from the scaffold increased tumor cell migration and apoptosis in vitro. DISCUSSION/SIGNIFICANCE OF IMPACT: Early phenotypic changes at the engineered metastatic niche can identify signs of metastasis prior to colonization of tumor cells. Furthermore, dynamics of immune and stromal cells change throughout niche maturation, influencing tumor cell phenotype and may suggest targeted therapies. CONFLICT OF INTEREST DESCRIPTION: Lonnie Shea, Jacqueline Jeruss, and Grace Bushnell are named inventors on patents or patent applications.
Introduction: Out-of-hospital cardiac arrest (OHCA) constitutes a significant global health burden, with a survival rate of only 10-12%. Early intervention is vital but limited by ambulance response times, low rates of bystander assistance, and access to AEDs. Smartphone technologies have been developed that crowdsource willing volunteers to nearby OHCAs in order to initiate resuscitation prior to ambulance arrival. We performed a scoping review to map the available literature on these crowdsourcing technologies and compared their key operational features. Methods: A search strategy was developed for five online databases: Medline, Cochrane, Embase, and Web of Science, as well as Google Scholar. We searched for primary studies and grey literature describing mobile phone technologies that alerted users of nearby cardiac arrests in the community. Two reviewers independently screened all articles and extracted relevant study information. Subsequently, we performed a search of the Google and Apple app stores, a general internet search, and consulted experts to identify all available technologies that might not be described in literature. We contacted developers for information on technology use and specifications to create a detailed features table. Results: We included 72 articles examining bystander alerting technologies from 15 countries worldwide, owing to the increasing importance of this topic. We identified 25 unique technologies, of which 18 were described in the included literature. Technologies were either text message-based systems (n = 4) or mobile phone applications (n = 21). Most (23/25) used global positioning systems to direct bystanders to victims and nearby AEDs. Response radii for alerts varied widely from 200m to 10km. Some technologies had advanced features such as video-conferencing with ambulance dispatch and detailed alert settings. Not all systems required volunteers to have first aid training. There were 18 studies examining effects on bystander intervention, all of which showed significant improvements using the technologies. However, only six studies assessed impact on survival outcomes. Key barriers discussed included false positive alerts, legal liability, and potential psychological impact on volunteers. Conclusion: Our review provides a comprehensive overview of crowdsourcing technologies for bystander intervention in out-of-hospital cardiac arrest. Future work in this growing field should focus on survival outcomes and methods of addressing barriers to implementation.
Introduction: Time-to-treatment plays a pivotal role in survival from sudden cardiac arrest (SCA). Every minute delay in defibrillation results in a 7-10% reduction in survival. This is particularly problematic in rural and remote regions, where bystander and EMS response is often prolonged and automated external defibrillators (AED) are often not available. Our objective was to examine the feasibility of a novel AED drone delivery method for rural and remote SCA. A secondary objective was to compare times between AED drone delivery and ambulance response to various mock SCA resuscitations. Methods: We conducted 6 simulations in two different rural communities in southern Ontario. During phase 1 (4 simulations) a “mock” call was placed to 911 and a single AED drone and an ambulance were simultaneously dispatched from the same location to a pre-determined destination. Once on scene, trained first responders retrieved the AED from the drone and initiated resuscitative efforts on a manikin. The second phase (2 scenarios) were done in a similar manner save for the drone being dispatched from a regionally optimized location for drone response. Results: Phase 1: The distance from dispatch location to scene varied from 6.6 km to 8.8 km. Mean (SD) response time from 911 call to scene arrival was 11.2 (+/- 1.0) minutes for EMS compared to 8.1 (+/- 0.1) for AED drone delivery. In all four simulations, the AED drone arrived before EMS, ranging from 2.1 to 4.4 minutes faster. The mean time for trained responders to retrieve the AED and apply it to the manikin was 35 (+/- 5) sec. No difficulties were encountered in drone activation by dispatch, drone lift off, landing or removal of the AED from the drone by responders. Phase 2: The ambulance response distance was 20km compared to 9km for the drone. Drones were faster to arrival at the scene by 7 minutes and 8 minutes with AED application 6 and 7 minutes prior to ambulance respectively. Conclusion: This implementation study suggests AED drone delivery is feasible with improvements in response time during a simulated SCA scenario. These results suggest the potential for AED drone delivery to decrease time to first defibrillation in rural and remote communities. Further research is required to determine the appropriate distance for drone delivery of an AED in an integrated EMS system as well as optimal strategies to simplify bystander application of a drone delivered AED.
Evidence suggests that healthy older adults with subjective memory complaints are at increased risk of dementia. Subjective Cognitive Impairment (SCI) may precede Mild Cognitive Impairment (MCI) in the clinical continuum of Alzheimer's disease (AD). Attentional deficits may be present early in AD, and associated functional changes have been reported in both MCI and AD. In the present study, activation during divided attention in SCI subjects was investigated using functional magnetic resonance imaging (fMRI). Additionally, amyloid uptake was investigated using 11C-PIB with positron emission tomography (PET).
Brain activation in 11 SCI subjects and 10 controls was compared during a divided attention task using fMRI. Additionally, five SCI subjects and 14 cognitively normal healthy controls underwent 11C-PIB PET scanning. Criteria for diagnosis of SCI were:
1. self-reported memory complaints,
2. objectively normal cognition on detailed neurocognitive testing,
3. absence of psychiatric or causative physical illness,
4. normal activities of daily living and
5. absence of MCI or dementia.
There were no differences in performance between SCI and control groups in terms of cognitive or behavioural measures. However, SCIs had increased activation in left medial temporal lobe, and bilateral thalamus, posterior cingulate and caudate. One SCI subject and one control subject had a pattern of 11C-PIB uptake similar to that seen in AD.
The activation changes identified in SCI may relate to compensatory increased activation in the face of early AD pathology. Larger, longitudinal studies are needed to determine the extent and significance of PIB uptake in SCI.
Some patients with schizophrenia switch medications due to lack of efficacy or side effects; improvement in symptoms and side effects following a switch must be assessed.
In a 12-week, open-label, baseline-controlled, flexible dose switch study, adult outpatients with schizophrenia experiencing suboptimal efficacy or tolerability problems were switched from haloperidol (n=99), olanzapine (n=82), or risperidone (n=104) to ziprasidone (80¬–160 mg/d; dosed bid with food). The primary efficacy evaluation was the BPRS score at Week 12. Safety evaluations included change from baseline in movement disorders (SAS, BAS, AIMS), weight, prolactin, and fasting lipids levels. Statistical tests were 1-sided non-inferiority comparisons with correction for multiple comparisons (0.025/3 significance level), for the primary efficacy endpoint, or 2-sided (0.05 significance level), for secondary endpoints.
BPRS scores improved significantly compared with all 3 preswitch medications at Week 12. Mean change from baseline (SD) for patients switched from haloperidol, olanzapine, and risperidone was –11.3 (16.3), –6.3 (14.2), and –9.9 (13.2), respectively (p < 0.0001 vs baseline). Movement disorders, measured by SAS, BAS, and AIMS, improved significantly for subjects switched from haloperidol and risperidone. Change in weight (kg ± SD) from baseline was 0.4 ± 3.97, –2.0 ± 3.99 (p < 0.001), and –0.6 ± 3.21 for subjects switched from haloperidol, olanzapine, and risperidone, respectively.
Patients switched to ziprasidone demonstrated improvement in symptoms and movement disorders, with a weight neutral effect. Ziprasidone is an appropriate switch option for patients experiencing suboptimal efficacy or poor tolerability with their current treatment.
Quitlines are standard care for smoking cessation; however, retaining clients in services is a problem. Little is known about factors that may predict dropout.
To examine predictors of retention while in-program and at follow-up for clients enrolling in a state quitline.
This was a retrospective analysis of quitline enrolled clients from 2011 to 2017 (N = 49,347). Client retention in-program was categorized as (a) low adherence to treatment (receiving zero coaching calls), moderate (1–2 calls), and high adherence (3+ calls). Dropout at follow-up included participants who were not reached for the 7-month follow-up.
More than half the sample dropped out during treatment; 61% were not reached for follow-up. Women (odds ratio (OR) = 1.21; 95% confidence interval (CI) = [1.16, 127]) and those with high levels of nicotine dependence (OR = 1.03; 95% CI = [1.02, 1.04]) were more likely to have moderate adherence to treatment (1–2 coaching calls). Dropout at follow-up was more likely among clients who used nicotine replacement therapy (OR = 1.14; 95% CI = [1.09, 1.19]) and less likely among those who had high treatment adherence (OR = 0.41; 95% CI = [0.39, 0.42]).
Given the relapsing nature of tobacco use and the harms related to tobacco use, quitlines can improve their impact by offering tailored services to enhance client engagement and retention in-treatment and at follow-up.
The diagnosis of anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis relies on the detection of NMDAR IgG autoantibodies in the serum or cerebrospinal fluid (CSF) of symptomatic patients. Commercial kits are available that allow NMDAR IgG autoantibodies to be measured in local laboratories. However, the performance of these tests outside of reference laboratories is unknown.
To report an unexpectedly low rate of NMDAR autoantibody detection in serum from patients with anti-NMDAR encephalitis tested using a commercially available diagnostic kit in an exemplar clinical laboratory.
Paired CSF and serum samples from seven patients with definite anti-NMDAR encephalitis were tested for NMDAR IgG autoantibodies using commercially available cell-based assays run according to manufacturer’s recommendations. Rates of autoantibody detection in serum tested at our center were compared with those derived from systematic review and meta-analyses incorporating studies published during or before March 2019.
NMDAR IgG autoantibodies were detected in the CSF of all patients tested at our clinical laboratory but not in paired serum samples. Rates of the detection were lower than those previously reported. A similar association was recognized through meta-analyses, with lower odds of NMDAR IgG autoantibody detection associated with serum testing performed in nonreference laboratories.
Commercial kits may yield lower-than-expected rates of NMDAR IgG autoantibody detection in serum when run in exemplar clinical (nonreference) laboratories. Additional studies are needed to decipher the factors that contribute to lower-than-expected rates of serum positivity. CSF testing is recommended in patients with suspected anti-NMDAR encephalitis.
In this paper, we revisit our previous work in which we derive an effective macroscale description suitable to describe the growth of biological tissue within a porous tissue-engineering scaffold. The underlying tissue dynamics is described as a multiphase mixture, thereby naturally accommodating features such as interstitial growth and active cell motion. Via a linearization of the underlying multiphase model (whose nonlinearity poses a significant challenge for such analyses), we obtain, by means of multiple-scale homogenization, a simplified macroscale model that nevertheless retains explicit dependence on both the microscale scaffold structure and the tissue dynamics, via so-called unit-cell problems that provide permeability tensors to parameterize the macroscale description. In our previous work, the cell problems retain macroscale dependence, posing significant challenges for computational implementation of the eventual macroscopic model; here, we obtain a decoupled system whereby the quasi-steady cell problems may be solved separately from the macroscale description. Moreover, we indicate how the formulation is influenced by a set of alternative microscale boundary conditions.
Adolescence is a period of heightened susceptibility to peer influences, and deviant peer affiliation has well-established implications for the development of psychopathology. However, little is known about the role of brain functions in pathways connecting peer contexts and health risk behaviors. We tested developmental cascade models to evaluate contributions of adolescent risk taking, peer influences, and neurobehavioral variables of risk processing and cognitive control to substance use among 167 adolescents who were assessed annually for four years. Risk taking at Time 1 was related to substance use at Time 4 indirectly through peer substance use at Time 2 and insular activation during risk processing at Time 3. Furthermore, neural cognitive control moderated these effects. Greater insular activation during risk processing was related to higher substance use for those with greater medial prefrontal cortex activation during cognitive control, but it was related to lower substance use among those with lower medial prefrontal cortex activation during cognitive control. Neural processes related to risk processing and cognitive control play a crucial role in the processes linking risk taking, peer substance use, and adolescents’ own substance use.