Chronic inflammatory effects of in vivo irradiation of the murine heart on endothelial cells mimic mechanisms involved in atherosclerosis.

PURPOSE: Radiotherapy is a major pillar in the treatment of solid tumors including breast cancer. However, epidemiological studies have revealed an increase in cardiac diseases approximately a decade after exposure of the thorax to ionizing irradiation, which might be related to vascular inflammation. Therefore, chronic inflammatory effects were examined in primary heart and lung endothelial cells (ECs) of mice after local heart irradiation. METHODS: Long-lasting effects on primary ECs of the heart and lung were studied 20-50 weeks after local irradiation of the heart of mice (8 and 16 Gy) in vivo by multiparameter flow cytometry using antibodies directed against cell surface markers related to proliferation, stemness, lipid metabolism, and inflammation, and compared to those induced by occlusion of the left anterior descending coronary artery. RESULTS: In vivo irradiation of the complete heart caused long-lasting persistent upregulation of inflammatory (HCAM, ICAM­1, VCAM-1), proliferation (CD105), and lipid (CD36) markers on primary heart ECs and an upregulation of ICAM­1 and VCAM­1 on primary ECs of the partially irradiated lung lobe. An artificially induced heart infarction induces similar effects with respect to inflammatory markers, albeit in a shorter time period. CONCLUSION: The long-lasting upregulation of prominent inflammatory markers on primary heart and lung ECs suggests that local heart irradiation induces chronic inflammation in the microvasculature of the heart and partially irradiated lung that leads to cardiac injury which might be related to altered lipid metabolism in the heart.

Quantification of P-glycoprotein function at the human blood-brain barrier using [18F]MC225 and PET.

INTRODUCTION: P-glycoprotein (P-gp) is one of the most studied efflux transporters at the blood-brain barrier. It plays an important role in brain homeostasis by protecting the brain from a variety of endogenous and exogeneous substances. Changes in P-gp function are associated both with the onset of neuropsychiatric diseases, including Alzheimer's disease and Parkinson's disease, and with drug-resistance, for example in treatment-resistant depression. The most widely used approach to measure P-gp function in vivo is (R)-[11C]verapamil PET. (R)-[11C]verapamil is, however, an avid P-gp substrate, which complicates the use of this tracer to measure an increase in P-gp function as its baseline uptake is already very low. [18F]MC225 was developed to measure both increases and decreases in P-gp function. AIM: The aim of this study was (1) to identify the pharmacokinetic model that best describes [18F]MC225 kinetics in the human brain and (2) to determine test-retest variability. METHODS: Five (2 male, 3 female) of fourteen healthy subjects (8 male, 6 female, age 67 ± 5 years) were scanned twice (injected dose 201 ± 47 MBq) with a minimum interval of 2 weeks between scans. Each scanning session consisted of a 60-min dynamic [18F]MC225 scan with continuous arterial sampling. Whole brain grey matter data were fitted to a single tissue compartment model, and to reversible and irreversible two tissue-compartment models to obtain various outcome parameters (in particular the volume of distribution (VT), Ki, and the rate constants K1 and k2). In addition, a reversible two-tissue compartment model with fixed k3/k4 was included. The preferred model was selected based on the weighted Akaike Information Criterion (AIC) score. Test-retest variability (TRTV) was determined to assess reproducibility. RESULTS: Sixty minutes post-injection, the parent fraction was 63.8 ± 4.0%. The reversible two tissue compartment model corrected for plasma metabolites with an estimated blood volume (VB) showed the highest AIC weight score of 34.3 ± 17.6%. The TRVT of the VT for [18F]MC225 PET scans was 28.3 ± 20.4% for the whole brain grey matter region using this preferred model. CONCLUSION: [18F]MC225 VT, derived using a reversible two-tissue compartment model, is the preferred parameter to describe P-gp function in the human BBB. This outcome parameter has an average test-retest variability of 28%. TRIAL REGISTRATION: EudraCT 2020-001564-28 . Registered 25 May 2020.

Non-invasive kinetic modelling approaches for quantitative analysis of brain PET studies.

Pharmacokinetic modelling with arterial sampling is the gold standard for analysing dynamic PET data of the brain. However, the invasive character of arterial sampling prevents its widespread clinical application. Several methods have been developed to avoid arterial sampling, in particular reference region methods. Unfortunately, for some tracers or diseases, no suitable reference region can be defined. For these cases, other potentially non-invasive approaches have been proposed: (1) a population based input function (PBIF), (2) an image derived input function (IDIF), or (3) simultaneous estimation of the input function (SIME). This systematic review aims to assess the correspondence of these non-invasive methods with the gold standard. Studies comparing non-invasive pharmacokinetic modelling methods with the current gold standard methods using an input function derived from arterial blood samples were retrieved from PubMed/MEDLINE (until December 2021). Correlation measurements were extracted from the studies. The search yielded 30 studies that correlated outcome parameters (VT, DVR, or BPND for reversible tracers; Ki or CMRglu for irreversible tracers) from a potentially non-invasive method with those obtained from modelling using an arterial input function. Some studies provided similar results for PBIF, IDIF, and SIME-based methods as for modelling with an arterial input function (R2 = 0.59-1.00, R2 = 0.71-1.00, R2 = 0.56-0.96, respectively), if the non-invasive input curve was calibrated with arterial blood samples. Even when the non-invasive input curve was calibrated with venous blood samples or when no calibration was applied, moderate to good correlations were reported, especially for the IDIF and SIME (R2 = 0.71-1.00 and R2 = 0.36-0.96, respectively). Overall, this systematic review illustrates that non-invasive methods to generate an input function are still in their infancy. Yet, IDIF and SIME performed well, not only with arterial blood calibration, but also with venous or no blood calibration, especially for some tracers without plasma metabolites, which would potentially make these methods better suited for clinical application. However, these methods should still be properly validated for each individual tracer and application before implementation.

Bile Duct Colonization With Enterococcus sp. Associates With Disease Progression in Primary Sclerosing Cholangitis.

BACKGROUND & AIMS: Primary sclerosing cholangitis (PSC) is characterized by chronic inflammation of the biliary mucosa. Bile ducts in PSC are often colonized with bacteria. Although accumulating evidence demonstrates the importance of microbiota for mucosal immunity, little is known about the impact of bile duct colonization with bacteria on the clinical course of PSC. METHODS: Bile samples were sent to culture during endoscopic retrograde cholangio-pancreatography before the administration of peri-interventional antibiotics. Procedures during overt bacterial cholangitis or with prior antibiotic treatment were excluded. The primary endpoint was defined as a composite clinical endpoint of decompensated cirrhosis and/or liver transplantation or death. RESULTS: A cohort of 189 patients with 591 bile fluid cultures was included. In multivariable Cox regression analysis, the presence of Enterococci (present in 28% of the patients), but not of other bacterial species, conferred risk of disease progression with a hazard ratio of 3.61 (95% confidence interval, 1.6-8.11; P = .002) to reach the composite clinical endpoint. Fungobilia, present in 19.6% of patients, was confirmed to associate with disease progression with a hazard ratio of 3.25 (95% confidence interval, 1.87-5.66; P < .001) to reach the composite clinical endpoint. CONCLUSIONS: The novel association of biliary colonization by Enterococci with disease progression underlines the importance of microbiota-mucosal interplay for the pathogenesis of PSC. These results should stimulate further mechanistic studies on the role of microbiota in PSC and highlight potential new therapeutic targets for a disease without effective treatment options.

Dose-response assessment of cerebral P-glycoprotein inhibition in vivo with [18F]MC225 and PET.

The Blood-Brain Barrier P-glycoprotein (P-gp) function can be altered in several neurodegenerative diseases and due to the administration of different drugs which may cause alterations in drug concentrations and consequently lead to a reduced effectiveness or increased side-effects. The novel PET radiotracer [18F]MC225 is a weak P-gp substrate that may show higher sensitivity to detect small changes in P-gp function than previously developed radiotracers. This study explores the sensitivity of [18F]MC225 to measure the dose-dependent effect of P-gp inhibitor tariquidar. Twenty-three rats were intravenously injected with different doses of tariquidar ranging from 0.75 to 12 mg/kg, 30-min before the dynamic [18F]MC225-PET acquisition with arterial sampling. Tissue and blood data were fitted to a 1-Tissue-Compartment-Model to obtain influx constant K1 and distribution volume VT, which allow the estimation of P-gp function. ANOVA and post-hoc analyses of K1 values showed significant differences between controls and groups with tariquidar doses >3 mg/kg; while applying VT the analyses showed significant differences between controls and groups with tariquidar doses >6 mg/kg. Dose-response curves were fitted using different models. The four-parameter logistic sigmoidal curve provided the best fit for K1 and VT data. Half-maximal inhibitory doses (ID50) were 2.23 mg/kg (95%CI: 1.669-2.783) and 2.93 mg/kg (95%CI: 1.135-3.651), calculated with K1 or VT values respectively. According to the dose-response fit, differences in [18F]MC225-K1 values could be detected at tariquidar doses ranging from 1.37 to 3.25 mg/kg. Our findings showed that small changes in the P-gp function, caused by low doses of tariquidar, could be detected by [18F]MC225-K1 values, which confirms the high sensitivity of the radiotracer. The results suggest that [18F]MC225 may allow the quantification of moderate P-gp impairments, which may allow the detection of P-gp dysfunctions at the early stages of a disease and potential transporter-mediated drug-drug interactions.

fuPCR as diagnostic method for the detection of rare fungal pathogens, such as Trichosporon, Cryptococcus and Fusarium.

Fungal respiratory tract colonization is a common finding in patients with hematologic neoplasms due to immunosuppression inherent in the diseases and exacerbated by therapy. This greatly increases the risk of fungal infections of the lungs, which is associated with significant mortality. Therefore, reliable diagnostic methods with rapidly available results are needed to administer adequate antifungal therapy. We have established an improved method for fungal DNA extraction and amplification that allows simultaneous detection of fungal families based on a set of multiplexed real-time PCR reactions (fuPCR). We analyzed respiratory rinses and blood of 94 patients with hematological systemic diseases by fuPCR and compared it with the results of culture and serological diagnostic methods. 40 healthy subjects served as controls. Regarding Candida species, the highest prevalence resulted from microbiological culture of respiratory rinses and from detection of antibodies in blood serum in patients (61 and 47%, respectively) and in the control group (29 and 51%, respectively). Detection of other pathogenic yeasts, such as Cryptococcus and Trichosporon, and molds, such as Fusarium, was only possible in patients by fuPCR from both respiratory rinses and whole blood and serum. These fungal species were found statistically significantly more frequent in respiratory rinses collected from patients after myeloablative therapy for stem cell transplantation compared to samples collected before treatment (P < 0.05i). The results show that fuPCR is a valuable complement to culturing and its inclusion in routine mycological diagnostics might be helpful for early detection of pathophysiologically relevant respiratory colonization for patients with hematologic neoplasms.

We validated a set of PCR reactions (fuPCR) for use in routine diagnostic. In contrast to culture and serological methods, only by fuPCR pathogenic yeasts (Cryptococcus and Trichosporon) and molds (Aspergillus and Fusarium) were detected in respiratory rinses and blood of hematological patients.

Introduction of a bead beating step improves fungal DNA extraction from selected patient specimens.

In immunocompromised patients a colonisation with fungi carries the risk to develop serious invasive fungal infection. An early detection is therefore important, but not optimal hitherto. Fortunately, molecular genetic methods have increased the sensitivity of fungal detection and limited the time, until results are available. However, their success depends on an efficient extraction of genomic DNA from the fungal cell in the given diagnostic specimen. To improve the routine DNA preparation method for yeasts and moulds, the impact of bead beating on fungal DNA release was evaluated. PBS, blood and respiratory rinse were spiked with Candida glabrata or Aspergillus fumigatus. DNA was extracted by mechanical bead beating in addition to the different steps of the DNA preparation protocol, which comprised liquid nitrogen treatment, proteinase K digestion and DNA isolation using the EZ1 DNA Tissue Kit and Workstation. In every method variant tested, treatment with liquid nitrogen did not improve the DNA release. Bead beating once followed by proteinase K digestion and EZ1-work-up led to the highest DNA release from fungus, spiked in PBS, and increased the extracted DNA amount of C. glabrata about 100-fold and of A. fumigatus about 10-fold in relation to sole EZ1-work-up. In fungus-spiked respiratory rinse and blood, highest increase in DNA release was measured after triple bead beating with simultaneous proteinase K digestion. Fungal DNA release of C. glabrata increased for >100-fold in respiratory rinse and for >1000-fold in blood and of A. fumigatus for >10-fold in respiratory rinse and about 5- to 10-fold in blood. The data of this study clearly demonstrate that preparation of fungal DNA from human specimens is optimized by introduction of a bead beating step to the conventional DNA-preparation method without the necessity of a liquid nitrogen step.

The Effectiveness of Deep Brain Stimulation in Dystonia: A Patient-Centered Approach.

Background: To systematically evaluate the effectiveness of deep brain stimulation of the globus pallidus internus (GPi-DBS) in dystonia on pre-operatively set functional priorities in daily living. Methods: Fifteen pediatric and adult dystonia patients (8 male; median age 32y, range 8-65) receiving GPi-DBS were recruited. All patients underwent a multidisciplinary evaluation before and 1-year post DBS implantation. The Canadian Occupational Performance Measure (COPM) first identified and then measured changes in functional priorities. The Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) was used to evaluate dystonia severity. Results: Priorities in daily functioning substantially varied between patients but showed significant improvements on performance and satisfaction after DBS. Clinically significant COPM-score improvements were present in 7/8 motor responders, but also in 4/7 motor non-responders. Discussion: The use of a patient-oriented approach to measure GPi-DBS effectiveness in dystonia provides an unique insight in patients' priorities and demonstrates that tangible improvements can be achieved irrespective of motor response. Highlights: Functional priorities in life of dystonia patients and their caregivers vary greatlyThe effect of DBS on functional priorities did not correlate with motor outcomeHalf of the motor 'non-responder' patients reported important changes in their prioritiesThe effect of DBS in dystonia should not be measured by motor outcome alone.

The Genomics Research and Innovation Network: creating an interoperable, federated, genomics learning system.

PURPOSE: Clinicians and researchers must contextualize a patient's genetic variants against population-based references with detailed phenotyping. We sought to establish globally scalable technology, policy, and procedures for sharing biosamples and associated genomic and phenotypic data on broadly consented cohorts, across sites of care. METHODS: Three of the nation's leading children's hospitals launched the Genomic Research and Innovation Network (GRIN), with federated information technology infrastructure, harmonized biobanking protocols, and material transfer agreements. Pilot studies in epilepsy and short stature were completed to design and test the collaboration model. RESULTS: Harmonized, broadly consented institutional review board (IRB) protocols were approved and used for biobank enrollment, creating ever-expanding, compatible biobanks. An open source federated query infrastructure was established over genotype-phenotype databases at the three hospitals. Investigators securely access the GRIN platform for prep to research queries, receiving aggregate counts of patients with particular phenotypes or genotypes in each biobank. With proper approvals, de-identified data is exported to a shared analytic workspace. Investigators at all sites enthusiastically collaborated on the pilot studies, resulting in multiple publications. Investigators have also begun to successfully utilize the infrastructure for grant applications. CONCLUSIONS: The GRIN collaboration establishes the technology, policy, and procedures for a scalable genomic research network.

Correction: The Genomics Research and Innovation Network: creating an interoperable, federated, genomics learning system.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Myoclonus-dystonia: Distinctive motor and non-motor phenotype from other dystonia syndromes.

BACKGROUND: Myoclonus-dystonia (M-D) due to a pathogenic variant of SGCE is an autosomal dominant inherited movement disorder. Apart from motor symptoms, psychiatric disorders are highly prevalent in patients with M-D. Previous studies suggest, but never tested directly, that the type of psychiatric disorder differs between dystonia syndromes, probably related to disease specific pathology. Little is known about other non-motor symptoms (NMS) in M-D. Here, we systematically study NMS in M-D in direct comparison to other types of dystonia and healthy controls. METHODS: Standardized questionnaires were used to assess type and severity of psychiatric co-morbidity, sleep problems, fatigue and quality of life. Results of M-D patients with a pathogenic variant of SGCE were compared to results of idiopathic cervical dystonia (CD) patients, dopa-responsive dystonia (DRD) patients with a pathogenic variant of GCH1 and controls. RESULTS: We included 164 participants: 41 M-D, 51 CD, 19 DRD patients, 53 controls. Dystonia patients (M-D, CD and DRD) had an increased prevalence of psychiatric disorders compared to controls (56-74% vs. 29%). In M-D we found a significantly increased prevalence of obsessive-compulsive disorder (OCD) and psychosis compared to CD and DRD. All dystonia patients had more sleep problems (49-68% vs. 36%) and fatigue (42-73% vs. 15%) than controls. Compared to other dystonia subtypes, M-D patients reported less excessive daytime sleepiness and fatigue. CONCLUSION: Psychiatric comorbidity is frequent in all dystonia types, but OCD and psychosis are more common in M-D patients. Further research is necessary to elucidate underlying pathways.

Relationships between Serotonin Transporter Binding in the Raphe Nuclei, Basal Ganglia, and Hippocampus with Clinical Symptoms in Cervical Dystonia: A [11C]DASB Positron Emission Tomography Study.

PURPOSE: Alterations of the central serotonergic system have been implicated in the pathophysiology of dystonia. In this molecular imaging study, we assessed whether altered presynaptic serotonin transporter (SERT) binding contributes to the pathophysiology of cervical dystonia (CD), concerning both motor and non-motor symptoms (NMS). METHODS: We assessed the non-displaceable binding potential (BPND) using the selective SERT tracer [11C]DASB and positron emission tomography (PET) in 14 CD patients and 12 age- and gender-matched controls. Severity of motor symptoms was scored using the Toronto Western Spasmodic Torticollis Rating Scale and Clinical Global Impression jerks/tremor scale. NMS for depressive symptoms, anxiety, fatigue, and sleep disturbances were assessed with quantitative rating scales. The relationship between SERT binding and clinical patient characteristics was analyzed with the Spearman's rho test and multiple regression. RESULTS: When comparing the CD patients with controls, no significant differences in BPND were found. Higher BPND in the dorsal raphe nucleus was statistically significantly correlated (p < 0.001) with motor symptom severity (rs = 0.65), pain (rs = 0.73), and sleep disturbances (rs = 0.73), with motor symptom severity being the most important predictor of SERT binding. Furthermore, fatigue was negatively associated with the BPND in the medial raphe nucleus (rs = -0.61, p = 0.045), and sleep disorders were positively associated with the BPND in the caudate nucleus (rs = 0.58, p = 0.03) and the hippocampus (rs = 0.56, p = 0.02). CONCLUSION: Motor symptoms, as well as pain, sleep disturbances, and fatigue in CD showed a significant relationship with SERT binding in the raphe nuclei. Moreover, fatigue showed a significant relationship with the medial raphe nucleus and sleep disorders with the caudate nucleus and hippocampus. These findings suggest that an altered serotonergic signaling in different brain areas in CD is related to different motor as well as NMS, which will further stimulate research on the role of serotonin in the pathogenesis of dystonia.

Reactivation of the Nkx2.5 cardiac enhancer after myocardial infarction does not presage myogenesis.

Aims: The contribution of resident stem or progenitor cells to cardiomyocyte renewal after injury in adult mammalian hearts remains a matter of considerable debate. We evaluated a cell population in the adult mouse heart induced by myocardial infarction (MI) and characterized by an activated Nkx2.5 enhancer element that is specific for multipotent cardiac progenitor cells (CPCs) during embryonic development. We hypothesized that these MI-induced cells (MICs) harbour cardiomyogenic properties similar to their embryonic counterparts. Methods and results: MICs reside in the heart and mainly localize to the infarction area and border zone. Interestingly, gene expression profiling of purified MICs 1 week after infarction revealed increased expression of stem cell markers and embryonic cardiac transcription factors (TFs) in these cells as compared to the non-mycoyte cell fraction of adult hearts. A subsequent global transcriptome comparison with embryonic CPCs and fibroblasts and in vitro culture of MICs unveiled that (myo-)fibroblastic features predominated and that cardiac TFs were only expressed at background levels. Conclusions: Adult injury-induced reactivation of a cardiac-specific Nkx2.5 enhancer element known to specifically mark myocardial progenitor cells during embryonic development does not reflect hypothesized embryonic cardiomyogenic properties. Our data suggest a decreasing plasticity of cardiac progenitor (-like) cell populations with increasing age. A re-expression of embryonic, stem or progenitor cell features in the adult heart must be interpreted very carefully with respect to the definition of cardiac resident progenitor cells. Albeit, the abundance of scar formation after cardiac injury suggests a potential to target predestinated activated profibrotic cells to push them towards cardiomyogenic differentiation to improve regeneration.

Fatigue, Sleep Disturbances, and Their Influence on Quality of Life in Cervical Dystonia Patients.

BACKGROUND: Nonmotor symptoms (NMS) are highly prevalent in cervical dystonia (CD). In general, fatigue and sleep are important NMS that determine a decreased health-related quality of life (HR-QoL), but their influence in CD is unknown. The authors systematically investigated fatigue, excessive daytime sleepiness (EDS), and sleep quality in patients with CD and controls and assessed the influence of psychiatric comorbidity, pain, and dystonia motor severity. They also examined the predictors of HR-QoL. METHODS: The study included 44 patients with CD and 43 matched controls. Fatigue, EDS, and sleep quality were assessed with quantitative questionnaires and corrected for depression and anxiety using analysis of covariance. The Toronto Western Spasmodic Torticollis Rating Scale and the Clinical Global Impression Scale-jerks/tremor subscale were used to score motor severity and to assess whether motor characteristics could explain an additional part of the variation in fatigue and sleep-related measures. HR-QoL was determined with the RAND-36 item Health Survey, and predictors of HR-QoL were assessed using multiple regression. RESULTS: Fatigue scores were increased independently from psychiatric comorbidity (4.0 vs. 2.7; P < 0.01), whereas EDS (7.3 vs. 7.4; P = 0.95) and sleep quality (6.5 vs. 6.1; P = 0.73) were highly associated with depression and anxiety. In patients with CD, motor severity did not explain the variations in fatigue (change in the correlation coefficient [ΔR2] = 0.06; P = 0.15), EDS (ΔR2 = 0.00; P = 0.96), or sleep quality (ΔR2 = 0.04; P = 0.38) scores. Fatigue, EDS, psychiatric comorbidity, and pain predicted a decreased QoL. CONCLUSION: Independent from psychiatric comorbidity and motor severity, fatigue appeared to be a primary NMS. Sleep-related measures were highly associated with psychiatric comorbidity, but not with motor severity. Only NMS predicted HR-QoL, which emphasizes the importance of attention to NMS in patients with CD.

The Frequency and Self-perceived Impact on Daily Life of Motor and Non-motor Symptoms in Cervical Dystonia.

BACKGROUND: Evidence suggests that non-motor symptoms (NMS) are the most important predictors of decreased health-related quality of life (HR-QoL) in patients with cervical dystonia (CD). In this study, we evaluate an NMS screening list and examine the influence of motor symptoms and NMS on HR-QoL. METHODS: In 40 patients with CD, the frequency of NMS was evaluated using an extended NMS questionnaire. Furthermore, patients composed a list of their 5 most burdensome motor symptoms and NMS and scored the severity of predefined symptoms. HR-QoL was examined with the RAND 36-item Health Survey. RESULTS: Of 40 patients, 38 experienced NMS (median number of NMS, 6.5; range, 0-13; maximum, 15). The self-perceived most burdensome symptoms were tremor/jerks, pain, sleep disturbances, daily-life limitations, and fatigue. Also, of the predefined symptom list, tremor and fatigue were identified as the most disturbing. Several domains of HR-QoL were significantly influenced by NMS, whereas motor symptoms had only a small influence on the physical functioning domain of HR-QoL. CONCLUSION: Our findings highlight the impact of NMS on HR-QoL and emphasize the importance of a standardized, validated NMS questionnaire for patients with dystonia. This would enable us to monitor the effect of treatment for motor symptoms and NMS on an individual basis and improve treatment options.

Can a healthy youth development clinic serving latino families be youth friendly and family oriented? A mixed-methods evaluation.

BACKGROUND: Parenting adolescents poses challenges that are exacerbated by immigration. Aqui Para Ti [Here for You] (APT) is a clinic-based, healthy youth development program that provides family-centered care for Latino youth and their families who are mostly immigrants from Mexico and Latin America. OBJECTIVES: To present the APT model of care and report the experiences of youth and their parents. SUBJECTS: APT patients between 11 and 24 years (n=30) and parents (n=15). Most youth patients were female, between 11 and 17 years, and from Mexico. Most parents were female, 40 years or younger, and from Mexico. METHODS: Youth participants completed a survey and participated in an individual semi-structured interview, and parent participants attended focus groups. Descriptive statistics summarized survey data. Interviews and focus groups were transcribed and analyzed in Spanish using content analysis by two independent coders. Quantitative and qualitative findings were integrated using side-by-side comparisons. Researchers not involved in the coding process contributed with the interpretation of the findings. RESULTS: Youth and parents were satisfied with the services received at APT. Youth felt listened to by their providers (100%), felt they could trust them (100%) and valued comprehensive care. Eighty-seven percent reported that their experiences at APT were better than at other clinics. Parents valued the family parallel care, confidentiality, family-centeredness, and the cultural inclusivity of the APT services. CONCLUSION: Patients and parents were satisfied with the services offered at APT. Family parallel care could be a positive alternative to deliver confidential and family-centered services to immigrant families.

Development of project wings home visits, a mental health intervention for Latino families using community-based participatory research.

As the Latino population in the United States experiences rapid growth, the well-being of Latino adolescents is a growing concern because of their high rates of mental health problems. Latino adolescents have higher rates of mental health problems than their peers, including depressive symptoms, suicide attempts, and violence. Sophisticated, realistic health promotion efforts are needed to reduce these risk behaviors and enhance protective factors. Parents and schools can be key protective factors, or assets, in adolescents' lives. This article details the steps undertaken to develop Project Wings Home Visits, a collaborative school-based, community-linked mental health promotion intervention for Latino adolescents and their families. Core to the intervention is the use of a community health worker model to provide home-based outreach and education to parents of Latino adolescents. The intervention was developed using a community-based participatory research approach that involved the cooperation of a community health care system, a public high school, and a university. Our process demonstrates the benefits, strengths, and challenges of using community-based participatory research in creating and implementing health promotion interventions.

Handedness and dominant side of symptoms in Parkinson's disease.

The aim of this retrospective study was to assess the presence of a possible association between handedness and the side of symptom dominance in 963 patients with Parkinson's disease (PD). In only 287 patients the hand dominance was registered. Out of 254 right-handed patients, 158 (62%) had a right-side dominance of PD symptoms, while 96 patients (38%) had left-lateralized symptom dominance (p < 0.001). For the 33 left-handed subjects, 18 (55%) had left- and 15 (45%) had right-sided symptom dominance (p = 0.602). Right-handedness thus appeared to be associated with right-sided dominance of PD symptoms, while the group of left-handed patients was too small to draw conclusions from. Possible explanations are discussed.