Low pulse pressure and high serum complement C1q are risk factors for hemodialysis headache: A case-control study.

BACKGROUND AND OBJECTIVE: Hemodialysis headache (HDH) is a common complication of dialysis that negatively affects the patient's quality of life. The etiology and triggering factors of HDH are not fully understood. This study aims to assess the prevalence and characteristics of HDH among patients undergoing hemodialysis across multiple centers in China. Furthermore, we conducted a case-control study at one hospital to identify risk factors associated with HDH. METHODS: The study consisted of two phases including a cross-sectional observational study and a case-control study. Participants underwent neurological examinations and interviews. Demographic and medical information were collected from both medical records and patient files. Serum creatinine, uric acid, urea, estimated glomerular filtration rate (eGFR), plasma osmolarity, glucose, C1q, and a variety of electrolytes including potassium, sodium, chloride, calcium, magnesium, and phosphorus were measured before and after dialysis. Blood pressure variables including systolic blood pressure, diastolic blood pressure, pulse pressure (PP), and heart rate were monitored hourly. Serum levels of inflammatory factors, including tumor necrosis factor α (TNF-α), interleukin (IL)-1ß, IL-4, IL-6, and IL-10 were quantified using a double-antibody sandwich enzyme-linked immunosorbent assay (ELISA). RESULTS: The prevalence of HDH was 37.7% (183/485). HDH was characterized by a bilateral tightening headache of moderate intensity and duration of <2 h, occurring in different locations. The case-control study included 50 patients with HDH and 84 control patients, pre-dialysis PP was found to be lower in the HDH group than in the control group (mean ± standard deviation 51.5 ± 18.2 vs. 67.9 ± 14.9, p = 0.027). Furthermore, the pre-dialysis serum complement C1q level was significantly higher for the HDH group than the control group (median and interquartile range 201.5 [179.0-231.5] vs. 189.0 [168.9-209.0], p = 0.021). Pre-dialysis PP was associated with 5.1% decreased odds of HDH (odds ratio [OR] = 0.96; 95% confidence interval [CI], 0.93-0.99, p = 0.026), body weight was associated with a 5.4% decreased risk of HDH (OR = 0.95; 95% CI, 0.91-0.99, p = 0.013), and pre-dialysis C1q levels increased the odds of HDH by 1.9% (OR = 1.02; 95% CI, 1.01-1.03, p = 0.005). CONCLUSION: Low PP, low body weight, and high blood complement C1q may be potential risk factors associated with HDH.

Echocardiography in the Recognition and Management of Mechanical Complications of Acute Myocardial Infarction.

PURPOSE OF REVIEW: Although rare, the development of mechanical complications following an acute myocardial infarction is associated with a high morbidity and mortality. Here, we review the clinical features, diagnostic strategy, and treatment options for each of the mechanical complications, with a focus on the role of echocardiography. RECENT FINDINGS: The growth of percutaneous structural interventions worldwide has given rise to new non-surgical options for management of mechanical complications. As such, select patients may benefit from a novel use of these established treatment methods. A thorough understanding of the two-dimensional, three-dimensional, color Doppler, and spectral Doppler findings for each mechanical complication is essential in recognizing major causes of hemodynamic decompensation after an acute myocardial infarction. Thereafter, echocardiography can aid in the selection and maintenance of mechanical circulatory support and potentially facilitate the use of a percutaneous intervention.

Impact of Opera on Resilience and Thriving in Serious Mental Illness: Pilot Evaluation of The Center Cannot Hold Part 2 and Resilience Workshop.

There are few studies of impacts of arts on recovery in schizphrenia, on audience mood and social connection. We developed a pilot evaluation of opera performances in a university setting on Elyn Saks' journey from psychosis, teaching law and falling in love, coupled with pre-opera workshop on approaches to resilience. Using surveys, primary outcomes were pre and post affect (PANAS-X positive, negative; visual "affect grid" touchscreen for affective valence and arousal) and social connectedness with secondary outcomes of increasing understanding, reducing stigma and willingness to socialize or serve persons with mental illness. Of 107 live and 117 online attendees, 64 completed pre, 24 post, and 22 both surveys. Respondent characteristics were similar for those with pre and pre and post surveys: average age mid 50's, half female, 10% sexual minority, half White/Caucasian, 13% Hispanic/Latino, 11% Black/African American and 20% Asian; of 22 with pre and post, 9 (41%) were providers. There were significant post-pre increases in positive affect (PANAS-X) and arousal (visual grid) and social connectedness (Cohen's d = 0.82 to 1.24, each p < .001); and willingness to socialize with someone with schizophrenia (d = 0.68, p = .011). In this pilot evaluation of opera in a university auditorium, despite small sample sizes, there were significant post-pre increases in audience positive affect and social connection, which could reflect selection (those with positive response completing surveys) or may suggest that arts events promote well-being and connection, issues for future larger studies.

Inhibiting PAC1 receptor internalization and endosomal ERK pathway activation may ameliorate hyperalgesia in a chronic migraine rat model.

BACKGROUND: Pituitary adenylate cyclase-activating polypeptide (PACAP) is a multipotent neuropeptide widely distributed in the trigeminovascular system (TVS) and higher brain regions. At present, the underlying mechanism of PACAP/PACAP type1 (PAC1) receptor in migraine generation remains unclear. METHODS: The rat model of chronic migraine (CM) was established by repeated intraperitoneal injection of nitroglycerin (NTG). Von Frey filaments and hot plate tests were used to measure the mechanical and thermal thresholds. The expression levels of c-Fos, calcitonin gene-related peptide (CGRP), PACAP, PAC1, protein kinase A (PKA) and phosphorylated extracellular signal-regulated kinase (ERK) were assessed by western blotting or immunofluorescence staining. The internalization of PAC1 receptor was visualized by fluorescence microscope and laser scanning confocal microscope. RESULTS: The results showed that c-Fos and CGRP expression significantly increased after repeated administrations of NTG or PACAP. Pitstop2 notably improved hyperalgesia in CM rats, while PACAP6-38 offered no benefit. In addition, PACAP-induced PAC1 receptor internalization, PKA and ERK pathways activation were blocked by Pitstop2 instead of PACAP6-38. CONCLUSIONS: Our results demonstrate that inhibition of PAC1 receptor internalization could effectively improve allodynia in CM rats by restraining ERK signaling pathway activation in a chronic migraine rat model. Modulation of receptor internalization may be a novel perspective to explore specific mechanisms of PACAP signaling activation in the trigeminal vascular system.

Aryl hydrocarbon receptors improve migraine-like pain behaviors in rats through the regulation of regulatory T cell/T-helper 17 cell-related homeostasis.

OBJECTIVE: To investigate the effect of the aryl hydrocarbon receptor (AHR)/regulatory T cell (Treg)/T-helper 17 (Th17) cell pathway on the pathogenesis of migraine. BACKGROUND: Migraine is a disabling neurovascular disease that imposes an enormous burden on both individuals and society. The pathophysiological mechanisms of migraine remain controversial. Recent studies have suggested that immune dysfunction may be involved in the pathogenesis of migraine. The AHR, a receptor expressed on most immune cells, has been implicated in the occurrence of many autoimmune diseases; however, whether it is involved in the pathogenesis of migraine is unclear. METHODS: A chronic migraine rat model was established through repeated intraperitoneal injection of nitroglycerin (NTG). The mechanical and thermal pain thresholds were assessed using von Frey filaments and radiant heat. Next, the protein expression levels of AHR in the trigeminal nucleus caudalis (TNC) region of chronic migraine (CM)-like rats were quantified and the changes in Treg/Th17-related transcription factors and inflammatory factors in the TNC were explored. To determine the role of AHR in CM, we examined the effects of the AHR agonist 2-(1'-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE), and AHR antagonist CH-223191 on pain behavior, c-Fos, calcitonin gene-related peptide (CGRP), AHR, and Treg/Th17-related factor expression in CM-like rats. RESULTS: Repeated administration of NTG significantly enhanced nociceptive hypersensitivity and increased expression of c-Fos and CGRP in rats, while AHR was significantly decreased in the TNC. In addition, the expression of the transcription factor forkhead box protein P3 and the signal transducer and activator of transcription 5 decreased significantly. In contrast, the expression of the transcription factor retinoic acid receptor-related orphan receptor γ t and signal transducer and activator of transcription 3 were significantly increased. Moreover, the mRNA level of transforming growth factor beta-1 was decreased, while that of interleukin (IL)-10 and IL-22 was increased in the TNC. The AHR agonist ITE alleviated migraine-like pain behaviors in rats, activated the AHR signaling pathway, and improved the imbalance of Treg/Th17-related transcription factors and inflammatory factors. Conversely, the AHR antagonist CH-223191 did not alleviate migraine-like pain behaviors in rats; and even exacerbated them. CONCLUSIONS: The AHR participates in the development of CM by regulating Treg/Th17-related homeostasis. Therefore, treatments targeting the AHR/Treg/Th17 signaling pathway could be new effective interventions for CM treatment.

Atypical Presentations of Extraparenchymal Neurocysticercosis.

BACKGROUND: Neurocysticercosis (NCC) is the most common parasitic infection of the central nervous system and is typically diagnosed through visualization of the cysts in the cerebral parenchyma by neuro-imaging. However, neuro-imaging may not detect extraparenchymal neurocysticercosis (EPNCC), which is a rare manifestation of the disease involving the subarachnoid, meningeal, and intraventricular spaces. We report 2 cases of extraparenchymal neurocysticercosis, and discuss the diagnostic challenges and management of this entity. METHODS: Two cases were identified through clinical records. RESULTS: Both patients had an insidious onset with slow progression of disease, and presented with papilledema and cerebrospinal fluid (CSF) eosinophilia. One case was diagnosed with spinal cord biopsy. The other was diagnosed with CSF serology and next-generation sequencing-based pathogen analysis. Both patients were treated with ventriculoperitoneal shunt, systemic antiparasitic agents, and immunosuppression. CONCLUSIONS: EPNCC is less common than parenchymal NCC. A high level of clinical suspicion is required given its rarity, long incubation period, and slow progression. Diagnosis and treatment can be challenging and requires a multidisciplinary approach.

Head Scanning Behavior Predicts Hazard Detection Safety Before Entering an Intersection.

OBJECTIVE: We conducted a driving simulator study to investigate scanning and hazard detection before entering an intersection. BACKGROUND: Insufficient scanning has been suggested as a factor contributing to intersection crashes. However, little is known about the relative importance of the head and eye movement components of that scanning in peripheral hazard detection. METHODS: Eleven older (mean 67 years) and 18 younger (mean 27 years) current drivers drove in a simulator while their head and eye movements were tracked. They completed two city drives (42 intersections per drive) with motorcycle hazards appearing at 16 four-way intersections per drive. RESULTS: Older subjects missed more hazards (10.2% vs. 5.2%). Failing to make a scan with a substantial head movement was the primary reason for missed hazards. When hazards were detected, older drivers had longer RTs (2.6s vs. 2.3s), but drove more slowly; thus, safe response rates did not differ between the two groups (older 83%; younger 82%). Safe responses were associated with larger (28.8° vs. 20.6°) and more numerous (9.4 vs. 6.6) gaze scans. Scans containing a head movement were stronger predictors of safe responses than scans containing only eye movements. CONCLUSION: Our results highlight the importance of making large scans with a substantial head movement before entering an intersection. Eye-only scans played little role in detection and safe responses to peripheral hazards. APPLICATION: Driver training programs should address the importance of making large scans with a substantial head movement before entering an intersection.

PACAP6-38 improves nitroglycerin-induced central sensitization by modulating synaptic plasticity at the trigeminal nucleus caudalis in a male rat model of chronic migraine.

AIMS: Chronic migraine (CM) is a common neurological disorder with complex pathogenesis. Evidence suggests that pituitary adenylate cyclase-activating peptide (PACAP) induces migraine-like attacks and may be potential a new target for migraine treatment, but the therapeutic results of targeting PACAP and its receptors are not uniform. Therefore, the aim of this study was to investigate the regulatory effect of PACAP type I receptor (PAC1R) antagonist, PACAP6-38, on nitroglycerin (NTG)-induced central sensitization in a CM model. METHODS: Sprague-Dawley (SD) rats received repeated injections of NTG to construct a CM model. Mechanical and thermal thresholds were measured using Von Frey filaments and hot plate tests. C-Fos expression was measured by western blotting and immunofluorescence staining to assess the central sensitization. PACAP6-38 was intracerebrally injected into the trigeminal nucleus caudalis (TNC), and then the changes in c-Fos, the synaptic-associated proteins, phospho-ERK1/2 (p-ERK1/2), phosphorylation of cyclic adenosine monophosphate response element-binding protein (p-CREB) and brain-derived neurotrophic factor (BDNF) were detected. Transmission electron microscopy (TEM) and Golgi-Cox staining were used to observe the ultrastructure of synapses and dendritic structures of TNC neurons. RESULTS: The results showed that PACAP and PAC1R expression were significantly raised in the TNC after repeated NTG injections. Additionally, PACAP6-38 treatment alleviated nociceptive sensitization, inhibited NTG-induced overexpression of c-Fos and synaptic-associated proteins in the TNC of CM rat, restored aberrant synaptic structures. Furthermore, the expression of ERK/CREB/BDNF pathway was depressed by PACAP6-38. CONCLUSIONS: Our results demonstrated that abnormal synaptic structure in the TNC of CM, which could be reversed by inhibition of PAC1R via down-regulating the ERK/CREB/BDNF signaling pathway. PACAP6-38 improves NTG-induced central sensitization by regulating synaptic plasticity in the TNC of CM rat, which may provide new insights into the treatments targeting PACAP/PAC1R in migraine.

Shaping Waves of Bone Morphogenetic Protein Inhibition During Vascular Growth.

RATIONALE: The BMPs (bone morphogenetic proteins) are essential morphogens in angiogenesis and vascular development. Disruption of BMP signaling can trigger cardiovascular diseases, such as arteriovenous malformations. OBJECTIVE: A computational model predicted that BMP4 and BMP9 and their inhibitors MGP (matrix gamma-carboxyglutamic acid [Gla] protein) and CV2 (crossveinless-2) would form a regulatory system consisting of negative feedback loops with time delays and that BMP9 would trigger oscillatory expression of the 2 inhibitors. The goal was to investigate this regulatory system in endothelial differentiation and vascular growth. METHODS AND RESULTS: Oscillations in the expression of MGP and CV2 were detected in endothelial cells in vitro, using quantitative real-time polymerase chain reaction and immunoblotting. These organized temporally downstream BMP-related activities, including expression of stalk-cell markers and cell proliferation, consistent with an integral role of BMP9 in vessel maturation. In vivo, the inhibitors were located in distinct zones in relation to the front of the expanding retinal network, as determined by immunofluorescence. Time-dependent changes of the CV2 location in the retina and the existence of an endothelial population with signs of oscillatory MGP expression in developing vasculature supported the in vitro findings. Loss of MGP or its BMP4-binding capacity disrupted the retinal vasculature, resulting in poorly formed networks, especially in the venous drainage areas, and arteriovenous malformations as determined by increased cell coverage and functional testing. CONCLUSIONS: Our results suggest a previously unknown mechanism of temporal orchestration of BMP4 and BMP9 activities that utilize the tandem actions of the extracellular antagonists MGP and CV2. Disruption of this mechanism may contribute to vascular malformations and disease.

FKN/CX3CR1 axis facilitates migraine-Like behaviour by activating thalamic-cortical network microglia in status epilepticus model rats.

BACKGROUND: The incidence of migraines is higher among individuals with epilepsy than in healthy individuals, and these two diseases are thought to shared pathophysiological mechanisms. Excitation/inhibition imbalance plays an essential role in the comorbidity of epilepsy and migraine. Microglial activation is crucial for abnormal neuronal signal transmission. However, it remains unclear whether and how microglia are activated and their role in comorbidities after being activated. This study aimed to explore the characteristics and mechanism of microglial activation after seizures and their effect on migraine. METHODS: Model rats of status epilepticus (SE) induced by intraperitoneal injection of lithium chloride (LiCl)-pilocarpine and migraine induced by repeated dural injections of inflammatory soup (IS) were generated, and molecular and histopathologic evidence of the microglial activation targets of fractalkine (FKN) signalling were examined. HT22-BV2 transwell coculture assays were used to explore the interaction between neurons and microglia. LPS (a microglial agonist) and FKN stimulation of BV2 microglial cells were used to evaluate changes in BDNF levels after microglial activation. RESULTS: Microglia were specifically hyperplastic and activated in the temporal lobe cortex, thalamus, and spinal trigeminal nucleus caudalis (sp5c), accompanied by the upregulation of FKN and CX3CR1 four days after seizures. Moreover, SE-induced increases in nociceptive behaviour and FKN/CX3CR1 axis expression in migraine model rats. AZD8797 (a CX3CR1 inhibitor) prevented the worsening of hyperalgesia and microglial activation in migraine model rats after seizures, while FKN infusion in migraine model rats exacerbated hyperalgesia and microglial activation associated with BDNF-Trkb signalling. Furthermore, in neuron-microglia cocultures, microglial activation and FKN/CX3CR1/BDNF/iba1 expression were increased compared with those in microglial cultures alone. Activating microglia with LPS and FKN increased BDNF synthesis in BV2 microglia. CONCLUSIONS: Our results indicated that epilepsy facilitated migraine through FKN/CX3CR1 axis-mediated microglial activation in the cortex/thalamus/sp5c, which was accompanied by BDNF release. Blocking the FKN/CX3CR1 axis and microglial activation are potential therapeutic strategies for preventing and treating migraine in patients with epilepsy.

P2X7R/NLRP3 signaling pathway-mediated pyroptosis and neuroinflammation contributed to cognitive impairment in a mouse model of migraine.

Migraine is the second most common form of headache disorder and the second leading cause of disability worldwide. Cognitive symptoms ranked second resulting in migraine-related disability, after pain. P2X7 receptor (P2X7R) was recently shown to be involved in hyperalgesia in migraine. However, the role of P2X7R in migraine-related cognitive impairment is still ill-defined. The aim of this study was to explore the molecular mechanisms underlying migraine-related cognitive impairment and the role of P2X7R in it. Here we used a well-established mouse model of migraine that triggered migraine attacks by application of inflammatory soup (IS) to the dura. Our results showed that repeated dural IS stimulation triggered upregulation of P2X7R, activation of NLRP3 inflammasome, release of proinflammatory cytokines (IL-1ß and IL-18) and activation of pyroptotic cell death pathway. Gliosis (microgliosis and astrogliosis), neuronal loss and cognitive impairment also occurred in the IS-induced migraine model. No significant apoptosis or whiter matter damage was observed following IS-induced migraine attacks. These pathological changes occurred mainly in the cerebral cortex and to a less extent in the hippocampus, all of which can be prevented by pretreatment with a specific P2X7R antagonist Brilliant Blue G (BBG). Moreover, BBG can alleviate cognitive impairment following dural IS stimulation. These results identified P2X7R as a key contributor to migraine-related cognitive impairment and may represent a potential therapeutic target for mitigating cognitive impairment in migraine.

Ocular trauma secondary to exercise resistance bands during the COVID-19 pandemic.

OBJECTIVE: To characterize injuries caused by exercise resistance bands. METHOD: Single-site retrospective case series of patients presenting to the Bascom Palmer Eye Institute emergency room with ocular injuries secondary to exercise resistance bands from March through September 2020. RESULTS: Eleven patients (9 males, 2 females, 14 eyes) were reviewed. Eight patients had a unilateral injury (3 right eyes, 5 left eyes) while 3 had bilateral injuries. Iritis was the most common presentation, seen in all 11 patients, followed by hyphema (9 patients, 82%), and vitreous hemorrhage (4 patients, 36%). Among affected eyes, the mean presenting visual acuity was approximately 20/100, improving to 20/40 on the last follow up (p = 0.06). However, 4 eyes (33%) had vision ≤20/60 at last follow up. CONCLUSIONS: Exercise resistance bands can cause a wide spectrum of ocular injuries, some leading to long-term vision loss. As such, we recommend that patients strongly consider using eye protection goggles or glasses while using resistance bands for exercise.

Engaging Community Networks to Improve Depression Services: A Cluster-Randomized Trial of a Community Engagement and Planning Intervention.

This paper explores the effects of a group-randomized controlled trial, Community Partners in Care (CPIC), on the development of interagency networks for collaborative depression care improvement between a community engagement and planning (CEP) intervention and a resources for services (RS) intervention that provided the same content solely via technical assistance to individual programs. Both interventions consisted of a diverse set of service agencies, including health, mental health, substance abuse treatment, social services, and community-trusted organizations such as churches and parks and recreation centers. Participants in the community councils for the CEP intervention reflected a range of agency leaders, staff, and other stakeholders. Network analysis of partnerships among agencies in the CEP versus RS condition, and qualitative analysis of perspectives on interagency network changes from multiple sources, suggested that agencies in the CEP intervention exhibited greater growth in partnership capacity among themselves than did RS agencies. CEP participants also viewed the coalition development intervention both as promoting collaboration in depression services and as a meaningful community capacity building activity. These descriptive results help to identify plausible mechanisms of action for the CPIC interventions and can be used to guide development of future community engagement interventions and evaluations in under-resourced communities.

Automatic processing of gaze movements to quantify gaze scanning behaviors in a driving simulator.

Eye and head movements are used to scan the environment when driving. In particular, when approaching an intersection, large gaze scans to the left and right, comprising head and multiple eye movements, are made. We detail an algorithm called the gaze scan algorithm that automatically quantifies the magnitude, duration, and composition of such large lateral gaze scans. The algorithm works by first detecting lateral saccades, then merging these lateral saccades into gaze scans, with the start and end points of each gaze scan marked in time and eccentricity. We evaluated the algorithm by comparing gaze scans generated by the algorithm to manually marked "consensus ground truth" gaze scans taken from gaze data collected in a high-fidelity driving simulator. We found that the gaze scan algorithm successfully marked 96% of gaze scans and produced magnitudes and durations close to ground truth. Furthermore, the differences between the algorithm and ground truth were similar to the differences found between expert coders. Therefore, the algorithm may be used in lieu of manual marking of gaze data, significantly accelerating the time-consuming marking of gaze movement data in driving simulator studies. The algorithm also complements existing eye tracking and mobility research by quantifying the number, direction, magnitude, and timing of gaze scans and can be used to better understand how individuals scan their environment.

Maternal health services utilisation among primigravidas in Uganda: what did the MDGs deliver?

BACKGROUND: Achieving maternal health outcomes in the SDGs requires the implementation of more targeted policies and strategies. While the MDGs may have deepened our understanding in this regard, we know little about the trends in maternal health services utilisation among primigravidas, and how age and geographical regions could have influenced these trends. In this study, we examined utilisation of antenatal and skilled delivery services among primigravidas in Uganda, a country with one of the highest maternal mortality ratios, and where early childbearing and its attendant challenges are common. METHODS: Guided by Andersen's Behavioural Model, we fitted multivariate regression models to a pooled dataset of the 2006, 2011 and 2016 Ugandan Demographic and Health Survey (n = 3477) to understand the dynamics in Antenatal Care (ANC) and Skilled Birth Attendance (SBAs) utilisation among primigravidas. Post-estimation margins were employed to further highlight the effect of age and geographical regions. RESULTS: The analyses show an improvement in access to maternal health services among primigravidas from 2006 to 2016. Compared to 2006, primigravidas in 2016 were 48%, 24% and 2.98 times more likely to have early ANC, four or more ANC visits, and SBAs, respectively. Altogether, a primigravida in 2016 relative to 2006 was 42% more likely to meet all three maternal health service indicators. Post-estimation margins analyses on age and geographical disparities revealed that younger primigravidas have lower probability, while primigravidas in Eastern Region, one of the most deprived in the country, have the lowest probability of accessing maternal health services. Also, the study found education, wealth, women's household decision-making power, place of residence as important determinants of ANC visits and SBAs. CONCLUSIONS: Based on our findings, it is important to address the vulnerabilities of primigravidas, particularly younger individuals, in accessing early ANC. Uganda should scale-up decentralisation and integration of maternal health delivery in local communities as a strategy of addressing lingering geographical disparities, and ultimately improve maternal health outcomes in the SDGs period.

The effects of age on the contributions of head and eye movements to scanning behavior at intersections.

The current study was aimed at evaluating the effects of age on the contributions of head and eye movements to scanning behavior at intersections. When approaching intersections, a wide area has to be scanned requiring large lateral head rotations as well as eye movements. Prior research suggests older drivers scan less extensively. However, due to the wide-ranging differences in methodologies and measures used in prior research, the extent to which age-related changes in eye or head movements contribute to these deficits is unclear. Eleven older (mean 67 years) and 18 younger (mean 27 years) current drivers drove in a simulator while their head and eye movements were tracked. Scans, analyzed for 15 four-way intersections in city drives, were split into two categories: eye-only (consisting only of eye movements) and head+eye (containing both head and eye movements). Older drivers made smaller head+eye scans than younger drivers (46.6° vs. 53°), as well as smaller eye-only scans (9.2° vs. 10.1°), resulting in overall smaller all- gaze scans. For head+eye scans, older drivers had both a smaller head and a smaller eye movement component. Older drivers made more eye-only scans than younger drivers (7 vs. 6) but fewer head+eye scans (2.1 vs. 2.7). This resulted in no age effects when considering all-gaze scans. Our results clarify the contributions of eye and head movements to age-related deficits in scanning at intersections, highlight the importance of analyzing both eye and head movements, and suggest the need for older driver training programs that emphasize the importance of making large scans before entering intersections.

Mining multi-site clinical data to develop machine learning MRI biomarkers: application to neonatal hypoxic ischemic encephalopathy.

BACKGROUND: Secondary and retrospective use of hospital-hosted clinical data provides a time- and cost-efficient alternative to prospective clinical trials for biomarker development. This study aims to create a retrospective clinical dataset of Magnetic Resonance Images (MRI) and clinical records of neonatal hypoxic ischemic encephalopathy (HIE), from which clinically-relevant analytic algorithms can be developed for MRI-based HIE lesion detection and outcome prediction. METHODS: This retrospective study will use clinical registries and big data informatics tools to build a multi-site dataset that contains structural and diffusion MRI, clinical information including hospital course, short-term outcomes (during infancy), and long-term outcomes (~ 2 years of age) for at least 300 patients from multiple hospitals. DISCUSSION: Within machine learning frameworks, we will test whether the quantified deviation from our recently-developed normative brain atlases can detect abnormal regions and predict outcomes for individual patients as accurately as, or even more accurately, than human experts. Trial Registration Not applicable. This study protocol mines existing clinical data thus does not meet the ICMJE definition of a clinical trial that requires registration.

Comparative Effectiveness of Coalitions Versus Technical Assistance for Depression Quality Improvement in Persons with Multiple Chronic Conditions.

Significance: Prior research suggests that Community Engagement and Planning (CEP) for coalition support compared with Resources for Services (RS) for program technical assistance to implement depression quality improvement programs improves 6- and 12-month client mental-health related quality of life (MHRQL); however, effects for clients with multiple chronic medical conditions (MCC) are unknown. Objective: To explore effectiveness of CEP vs RS in MCC and non-MCC subgroups. Design: Secondary analyses of a cluster-randomized trial. Setting: 93 health care and community-based programs in two neighborhoods. Participants: Of 4,440 clients screened, 1,322 depressed (Patient Health Questionnaire, PHQ8) provided contact information, 1,246 enrolled and 1,018 (548 with ≥3 MCC) completed baseline, 6- or 12-month surveys. Intervention: CEP or RS for implementing depression quality improvement programs. Outcomes and Analyses: Primary: depression (PHQ9 <10), poor MHRQL (Short Form Health Survey, SF-12<40); Secondary: mental wellness, good physical health, behavioral health hospitalization, chronic homelessness risk, work/workloss days, services use at 6 and 12 months. End-point regressions were used to estimate intervention effects on outcomes for subgroups with ≥3 MCC, non-MCC, and intervention-by-MCC interactions (exploratory). Results: Among MCC clients at 6 months, CEP vs RS lowered likelihoods of depression and poor MHRQL; increased likelihood of mental wellness; reduced work-loss days among employed and likelihoods of ≥4 behavioral-health hospitalization nights and chronic homelessness risk, while increasing faith-based and park community center depression services; and at 12 months, likelihood of good physical health and park community center depression services use (each P<.05). There were no significant interactions or primary outcome effects for non-MCC. Conclusions: CEP was more effective than RS in improving 6-month primary outcomes among depressed MCC clients, without significant interactions.

Age and amyloid effects on human central nervous system amyloid-beta kinetics.

OBJECTIVE: Age is the single greatest risk factor for Alzheimer's disease (AD), with the incidence doubling every 5 years after age 65. However, our understanding of the mechanistic relationship between increasing age and the risk for AD is currently limited. We therefore sought to determine the relationship between age, amyloidosis, and amyloid-beta (Aß) kinetics in the central nervous system (CNS) of humans. METHODS: Aß kinetics were analyzed in 112 participants and compared to the ages of participants and the amount of amyloid deposition. RESULTS: We found a highly significant correlation between increasing age and slowed Aß turnover rates (2.5-fold longer half-life over five decades of age). In addition, we found independent effects on Aß42 kinetics specifically in participants with amyloid deposition. Amyloidosis was associated with a higher (>50%) irreversible loss of soluble Aß42 and a 10-fold higher Aß42 reversible exchange rate. INTERPRETATION: These findings reveal a mechanistic link between human aging and the risk of amyloidosis, which may be owing to a dramatic slowing of Aß turnover, increasing the likelihood of protein misfolding that leads to deposition. Alterations in Aß kinetics associated with aging and amyloidosis suggest opportunities for diagnostic and therapeutic strategies. More generally, this study provides an example of how changes in protein turnover kinetics can be used to detect physiological and pathophysiological changes and may be applicable to other proteinopathies.