Right on Schedule: Improving the Rate of Clinic Appointments Scheduled Prior to Hospital Hospital Discharge.

INTRODUCTION: Children with cancer and blood disorders have many healthcare needs that often require inpatient and outpatient management. There is potential for a lapse in care when patients frequently transition between these settings. We aimed to improve the process and increase the rate of scheduled outpatient follow-up appointments at the time of inpatient discharge for all pediatric hematology-oncology patients from a baseline of 68-80%. METHODS: A multidisciplinary team developed several Plan-Do-Study-Act cycles to standardize and improve the process of scheduling follow-up appointments, communication to schedulers, and discussion of discharge planning. QI Macros for Excel Version 2019.06 was used for statistical analysis. Our primary outcome was displayed over time with a p-chart. RESULTS: Plan-Do-Study-Act interventions had a statistically significant impact in increasing the percentage of patients with follow-up outpatient appointments scheduled at the time of inpatient discharge from a baseline of 68% to consistently over 80%. CONCLUSIONS: This study demonstrates that standardization of care processes and reminders and education of healthcare providers about the new approaches can improve the rates of outpatient follow-up appointments scheduled at the time of hospital discharge from inpatient care.

Retrospective analysis of the effects of Blastomyces antigen concentration in urine and radiographic findings on survival in dogs with blastomycosis.

BACKGROUND: The Blastomyces antigen concentration in urine (BACU) test is used to diagnose blastomycosis and monitor treatment in dogs. It is unknown if a higher BACU is associated with shorter survival. OBJECTIVES: To determine if the magnitude of BACU before treatment is associated with survival in dogs with blastomycosis. ANIMALS: Fifty-two dogs with blastomycosis. METHODS: Retrospective case review. BACU, radiographic lung severity (RLS) score (0-4 scale), and survival time up to 1 year after diagnosis were obtained through medical record review of dogs with Blastomyces dermatitidis. RESULTS: The overall survival was: discharge, 87%; 1 week, 85%; 2 months, 74%; and 6 months, 69%. BACU correlated with RLS score (rs = 0.33, P = .02). BACU and RLS scores were lower in survivors to 2 months than nonsurvivors (average BACU difference of 2.5 ng/mL, 95% confidence interval [CI]: 0.2-4.8 ng/mL, P = .04; median RLS difference of 2; range, 0-4, P = .02). Dogs with BACU <5 ng/mL and dogs with mild (0-1) RLS scores had a greater proportion surviving than those with BACU >5 ng/mL (P = .03) and dogs with severe (3-4) RLS scores (P = .04). All dogs with a BACU <5 ng/mL or mild RLS score were alive at last follow-up (median, 365 days; range, 44-365 days). In all, 68.1% of other dogs survived to 2 months (95% CI, 54.8%-84.8%). CONCLUSIONS AND CLINICAL IMPORTANCE: Dogs with lower BACU and RLS scores have improved survival; however, it is unclear what specific cutoffs should be used for prognosis.

Pneumatosis of the intestines, colon and liver in a young cat.

To describe a case of naturally occurring pneumatosis intestinalis, pneumatosis coli and emphysematous hepatitis in a cat. A 9-month-old, indoors-only, female spayed, domestic medium hair cat presented for vomiting, open-mouth breathing and acute collapse. The initial physical examination identified moderate to severe hypothermia [35°C (95°F)], obtunded mentation, weak femoral pulses, tachycardia (heart rate 240 beats per min), pale pink mucous membranes and significant splenomegaly on abdominal palpation. Immediate diagnostics performed [packed cell volume and total solids (PCV, TS), venous blood gas and electrolytes] revealed severe anaemia (PCV 12%), hypoproteinaemia (TS = 2.2 g/dl), and severe metabolic acidosis (pH 6.956). Additional diagnostics performed included Feline Leukaemia Virus and Feline Immunodeficiency Virus testing (FeLV/FIV), complete blood count (CBC) with pathology review, serum biochemistry profile, prothrombin time (PT) and partial thromboplastin time (PTT), urinalysis, and abdominal radiographs. Abdominal radiographs were consistent with gas within hepatic and splenic veins and parenchyma, small intestinal walls and colonic wall. Due to the guarded prognosis, euthanasia was elected. Necropsy was performed and the most significant gross and histopathological findings included intra-luminal and intra-mural intestinal haemorrhage and vascular congestion with mild neutrophilic hepatitis, and marked hepatic periportal emphysema. Clostridium perfrigens and Escherichia coli were cultured from the bowel wall; no bacterial growth from the liver or spleen was identified. This case report describes idiopathic emphysematous hepatitis, with concurrent emphysema of the spleen and intestinal wall and intestinal haemorrhage. To the authors' knowledge, this type of pathology in a feline patient has not been previously described.

Evaluation of canine hepatic masses by use of triphasic computed tomography and B-mode, color flow, power, and pulsed-wave Doppler ultrasonography and correlation with histopathologic classification.

OBJECTIVE To determine clinical relevance for quantitative and qualitative features of canine hepatic masses evaluated by use of triphasic CT and B-mode, color flow, power, and pulsed-wave Doppler ultrasonography and to compare diagnostic accuracy of these modalities for predicting mass type on the basis of histopathologic classification. ANIMALS 44 client-owned dogs. PROCEDURES Dogs with histopathologic confirmation (needle core, punch, or excisional biopsy) of a hepatic mass were enrolled. Triphasic CT and B-mode, color flow, power, and pulsed-wave Doppler ultrasonography of each hepatic mass were performed. Seventy quantitative and qualitative variables of each hepatic mass were recorded by 5 separate observers and statistically evaluated with discriminant and stepwise analyses. Significant variables were entered in equation-based predictions for the histopathologic diagnosis. RESULTS An equation that included the lowest delayed-phase absolute enhancement of the mass and the highest venous-phase mass conspicuity was used to correctly classify 43 of 46 (93.5%) hepatic masses as benign or malignant. An equation that included only the lowest delayed-phase absolute enhancement of the mass could be used to correctly classify 42 of 46 (91.3%) masses (with expectation of malignancy if this value was < 37 Hounsfield units). For ultrasonography, categorization of the masses with cavitations as malignant achieved a diagnostic accuracy of 80.4%. CONCLUSIONS AND CLINICAL RELEVANCE Triphasic CT had a higher accuracy than ultrasonography for use in predicting hepatic lesion classification. The lowest delayed-phase absolute enhancement of the mass was a simple calculation that required 2 measurements and aided in the differentiation of benign versus malignant hepatic masses.

Evaluation of 18-F-fluoro-2-deoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) as a staging and monitoring tool for dogs with stage-2 splenic hemangiosarcoma - A pilot study.

Positron Emission Tomography-Computed Tomography (PET-CT) is routinely used for staging and monitoring of human cancer patients and is becoming increasingly available in veterinary medicine. In this study, 18-fluorodeoxyglucose (18FDG)-PET-CT was used in dogs with naturally occurring splenic hemangiosarcoma (HSA) to assess its utility as a staging and monitoring modality as compared to standard radiography and ultrasonography. Nine dogs with stage-2 HSA underwent 18FDG-PET-CT following splenectomy and prior to commencement of chemotherapy. Routine staging (thoracic radiography and abdominal ultrasonography) was performed prior to 18FDG-PET-CT in all dogs. When abnormalities not identified on routine tests were noted on 18FDG-PET-CT, owners were given the option to repeat a PET-CT following treatment with eBAT. A PET-CT scan was repeated on Day 21 in three dogs. Abnormalities not observed on conventional staging tools, and most consistent with malignant disease based on location, appearance, and outcome, were detected in two dogs and included a right atrial mass and a hepatic nodule, respectively. These lesions were larger and had higher metabolic activity on the second scans. 18FDG-PET-CT has potential to provide important prognostic information and influence treatment recommendations for dogs with stage-2 HSA. Additional studies will be needed to precisely define the value of this imaging tool for staging and therapy monitoring in dogs with this and other cancers.

Genome-wide gene-environment interaction analysis of pesticide exposure and risk of Parkinson's disease.

INTRODUCTION: Genetic factors and environmental exposures, including pesticides, contribute to the risk of Parkinson's disease (PD). There have been few studies of gene and pesticide exposure interactions in PD, and all of the prior studies used a candidate gene approach. METHODS: We performed the first genome-wide gene-environment interaction analysis of pesticide exposure and risk of Parkinson's disease. Analyses were performed using data on >700,000 single nucleotide polymorphisms (SNPs) in 364 discordant sibling pairs. In addition to testing for SNP-pesticide interaction effects, we also performed exploratory analyses of gene-pesticide interactions at the gene level. RESULTS: None of the gene-environment interaction results were significant after genome-wide correction for multiple testing (α = 1.5E-07 for SNP-level tests; α = 2.1E-06 for gene-level tests). Top results in the SNP-level tests provided suggestive evidence (P < 5.0E-06) that the effect of pesticide exposure on PD risk may be modified by SNPs in the ERCC6L2 gene (P = 2.4E-06), which was also supported by suggestive evidence in the gene-level analysis (P = 4.7E-05). None of the candidate genes assessed in prior studies of gene-pesticide interactions reached statistical support in this genome-wide screen. CONCLUSION: Although no significant interactions were identified, several of the genes with suggestive evidence of gene-environment interaction effects have biological plausibility for PD risk. Further investigation of the role of those genes in PD risk, particularly in the context of pesticide exposure, in large and carefully recruited samples is warranted.

Endoscopic overestimation of colorectal polyp size.

BACKGROUND AND AIMS: Polyp size ≥ 1 cm triggers more frequent colonoscopic surveillance, yet size is typically based on subjective endoscopic estimates. We sought to compare contemporary assessments of polyp size by endoscopic estimation and pathology measurement. METHODS: Colonoscopy and pathology reports were reviewed from the 2012 medical records at a large institution. Only polyps resected in toto with both endoscopic estimates and pathology measurements were included. Pathology measurements were considered the criterion standard. Factors affecting endoscopic miscall rates were assessed by multivariate analyses. RESULTS: From 6067 polyps resected, both endoscopic and pathology sizes were available on 1528. Distribution of polyp size appraised by endoscopy but not by pathology revealed modal clustering, particularly around 1 cm. Among 99 polyps endoscopically called 1 cm, 72% were <1 cm on pathology. Of all 222 polyps estimated as ≥ 1 cm on endoscopy, 46% were <1 cm on pathology; of 1306 polyps estimated as <1 cm, 3.9% were ≥ 1 cm on pathology. By histology, 39% of adenomatous, 59% of sessile serrated, and 73% of hyperplastic polyps were overcalled; P = .008. By configuration, 34% of pedunculated, 49% of sessile, and 61% of flat polyps were overcalled; P = .014. Endoscopic overestimation was more common in women (54%) than in men (40%) (P = .03) and with proximal (56%) than distal (40%) sites; P = .02. Miscall rates were unaffected by endoscopist covariates. CONCLUSIONS: Substantial discordance exists between endoscopic and pathology-based assessments of polyp size. Almost half of polyps called advanced on endoscopic estimates of size ≥ 1 cm fell below this threshold on actual pathology measurements.

Polymer Coatings in 3D-Printed Fluidic Device Channels for Improved Cellular Adherence Prior to Electrical Lysis.

This paper describes the design and fabrication of a polyjet-based three-dimensional (3D)-printed fluidic device where poly(dimethylsiloxane) (PDMS) or polystyrene (PS) were used to coat the sides of a fluidic channel within the device to promote adhesion of an immobilized cell layer. The device was designed using computer-aided design software and converted into an .STL file prior to printing. The rigid, transparent material used in the printing process provides an optically transparent path to visualize endothelial cell adherence and supports integration of removable electrodes for electrical cell lysis in a specified portion of the channel (1 mm width × 0.8 mm height × 2 mm length). Through manipulation of channel geometry, a low-voltage power source (500 V max) was used to selectively lyse adhered endothelial cells in a tapered region of the channel. Cell viability was maintained on the device over a 5 day period (98% viable), though cell coverage decreased after day 4 with static media delivery. Optimal lysis potentials were obtained for the two fabricated device geometries, and selective cell clearance was achieved with cell lysis efficiencies of 94 and 96%. The bottleneck of unknown surface properties from proprietary resin use in fabricating 3D-printed materials is overcome through techniques to incorporate PDMS and PS.

An analysis of fosaprepitant-induced venous toxicity in patients receiving highly emetogenic chemotherapy.

PURPOSE: Fosaprepitant is an antiemetic used for chemotherapy-induced nausea and vomiting. We recently reported increased infusion site adverse events (ISAE) in a cohort of breast cancer patients receiving chemotherapy with doxorubicin and cyclophosphamide (AC). In this current study, we evaluated the venous toxicity of fosaprepitant use with non-anthracycline platinum-based antineoplastic regimens. METHODS: A retrospective review was conducted of the first 81 patients initiated on fosaprepitant among patients receiving highly emetogenic chemotherapy, on or after January 1, 2011 at Mayo Clinic Rochester. None of these regimens included an anthracycline. Data collected included baseline demographics, chemotherapy regimen, type of intravenous access and type, and severity of ISAE. Data from these patients were compared to previously collected data from patients who had received AC. Statistical analysis using χ 2 and univariate logistic regression was used to evaluate the association between treatment regimen, fosaprepitant, and risk of ISAE. RESULTS: Among these 81 patients, the incidence of ISAE was 7.4% in the non-anthracycline platinum group. The most commonly reported ISAE were swelling (3%), extravasation (3%), and phlebitis (3%). When stratified by regimen, fosaprepitant was associated with a statistically significant increased risk of ISAE in the anthracycline group (OR 8.1; 95% CI 2.0-31.9) compared to the platinum group. CONCLUSIONS: Fosaprepitant antiemetic therapy causes significant ISAE that are appreciably higher than previous reports. Patients receiving platinum-based chemotherapy appear to have less significant ISAE than do patients who receive anthracycline-based regimens.

Alpha-synuclein repeat variants and survival in Parkinson's disease.

OBJECTIVES: To determine whether α-synuclein dinucleotide repeat (REP1) genotypes are associated with survival in Parkinson's disease (PD). METHODS: Investigators from the Genetic Epidemiology of Parkinson's Disease Consortium provided REP1 genotypes and baseline and follow-up clinical data for cases. The primary outcome was time to death. Cox proportional hazards regression models were used to assess the association of REP1 genotypes with survival. RESULTS: Twenty-one sites contributed data for 6,154 cases. There was no significant association between α-synuclein REP1 genotypes and survival in PD. However, there was a significant association between REP1 genotypes and age at onset of PD (hazard ratio: 1.06; 95% confidence interval: 1.01-1.10; P value = 0.01). CONCLUSIONS: In our large consortium study, α-synuclein REP1 genotypes were not associated with survival in PD. Further studies of α-synuclein's role in disease progression and long-term outcomes are needed.

Does α-synuclein have a dual and opposing effect in preclinical vs. clinical Parkinson's disease?

α-Synuclein gene (SNCA) multiplications cause familial parkinsonism and allele-length polymorphisms within the SNCA dinucleotide repeat REP1 increase the risk for developing Parkinson's disease (PD). Since SNCA multiplications increase SNCA expression, and REP1 genotypes that increase the risk of developing PD show increased SNCA expression in cell-culture systems, animal models, and human blood and brain, PD therapies seek to reduce SNCA expression. We conducted an observational study of 1098 PD cases to test the hypothesis that REP1 genotypes correlated with reduced SNCA expression are associated with better motor and cognitive outcomes. We evaluated the association of REP1 genotypes with survival free of Hoehn and Yahr stages 4 or 5 (motor outcome) and of Modified Telephone Interview for Cognitive Status score ≤27 or Alzheimer's Disease Dementia Screening Interview score ≥2 (cognitive outcome). Median disease duration at baseline was 3.3 years and median lag time from baseline to follow-up was 7.8 years. Paradoxically, REP1 genotypes associated with increased risk of developing PD and increased SNCA expression were associated with better motor (HR = 0.87, p = 0.046, covariate-adjusted age-scale analysis; HR = 0.85, p = 0.020, covariate-adjusted time-scale analysis) and cognitive outcomes (HR = 0.90, p = 0.12, covariate-adjusted age-scale analysis; HR = 0.85, p = 0.023, covariate-adjusted time-scale analysis). Our findings raise the possibility that SNCA has a dual, opposing, and time-dependent role. This may have implications for the development of therapies that target SNCA expression.

The Mayo Clinic Biobank: a building block for individualized medicine.

OBJECTIVE: To report the design and implementation of the first 3 years of enrollment of the Mayo Clinic Biobank. PATIENTS AND METHODS: Preparations for this biobank began with a 4-day Deliberative Community Engagement with local residents to obtain community input into the design and governance of the biobank. Recruitment, which began in April 2009, is ongoing, with a target goal of 50,000. Any Mayo Clinic patient who is 18 years or older, able to consent, and a US resident is eligible to participate. Each participant completes a health history questionnaire, provides a blood sample, and allows access to existing tissue specimens and all data from their Mayo Clinic electronic medical record. A community advisory board provides ongoing advice and guidance on complex decisions. RESULTS: After 3 years of recruitment, 21,736 individuals have enrolled. Fifty-eight percent (12,498) of participants are female and 95% (20,541) of European ancestry. Median participant age is 62 years. Seventy-four percent (16,171) live in Minnesota, with 42% (9157) from Olmsted County, where the Mayo Clinic in Rochester, Minnesota, is located. The 5 most commonly self-reported conditions are hyperlipidemia (8979, 41%), hypertension (8174, 38%), osteoarthritis (6448, 30%), any cancer (6224, 29%), and gastroesophageal reflux disease (5669, 26%). Among patients with self-reported cancer, the 5 most common types are nonmelanoma skin cancer (2950, 14%), prostate cancer (1107, 12% in men), breast cancer (941, 4%), melanoma (692, 3%), and cervical cancer (240, 2% in women). Fifty-six percent (12,115) of participants have at least 15 years of electronic medical record history. To date, more than 60 projects and more than 69,000 samples have been approved for use. CONCLUSION: The Mayo Clinic Biobank has quickly been established as a valuable resource for researchers.

Hospitalizations and emergency department use in Mayo Clinic Biobank participants within the employee and community health medical home.

OBJECTIVE: To evaluate the participants in the Mayo Clinic Biobank for their representativeness to the entire Employee and Community Health program (ECH) primary care population with regard to hospital utilization. PATIENTS AND METHODS: Participants enrolled in the Mayo Clinic Biobank from April 1, 2009, to December 31, 2010, were linked to the ECH population. These individuals were categorized into risk tiers (0-4) on the basis of the number of health conditions present as of December 31, 2010. Outcomes were ascertained through December 31, 2011. Hazard ratios (HRs) and 95% CIs for risk of hospitalization, emergency department (ED) visits, and for risk of hospitalization and emergency department (ED) visits were estimated. RESULTS: The 8927 Biobank participants were part of ECH (N=84,872). Compared with the entire ECH population, the Biobank-ECH participants were more likely to be female (64.3% vs 54.6%), older (median age, 58 years vs 47 years), and categorized to tier 0 (6.4% vs 24.0%). There were strong positive associations between tier (tier 4 vs combined tiers 0 and 1) and risk of hospitalization (HR, 5.8; 95% CI, 4.6-7.5) and ED visits (HR, 5.4; 95% CI, 4.2-6.8) among Biobank-ECH participants. Similar associations for risk of hospitalization (HR, 8.5; 95% CI, 7.8-9.3) and ED visits (HR, 6.9; 95% CI, 6.4-7.5) were observed for the entire ECH population. CONCLUSION: Although the Biobank-ECH participants were older and had more chronic conditions compared with the overall ECH population, the associations of risk tier with utilization outcomes were similar, supporting the use of the Biobank participants to assess biomarkers for health care outcomes in the primary care setting.

A 3D printed fluidic device that enables integrated features.

Fluidic devices fabricated using conventional soft lithography are well suited as prototyping methods. Three-dimensional (3D) printing, commonly used for producing design prototypes in industry, allows for one step production of devices. 3D printers build a device layer by layer based on 3D computer models. Here, a reusable, high throughput, 3D printed fluidic device was created that enables flow and incorporates a membrane above a channel in order to study drug transport and affect cells. The device contains 8 parallel channels, 3 mm wide by 1.5 mm deep, connected to a syringe pump through standard, threaded fittings. The device was also printed to allow integration with commercially available membrane inserts whose bottoms are constructed of a porous polycarbonate membrane; this insert enables molecular transport to occur from the channel to above the well. When concentrations of various antibiotics (levofloxacin and linezolid) are pumped through the channels, approximately 18-21% of the drug migrates through the porous membrane, providing evidence that this device will be useful for studies where drug effects on cells are investigated. Finally, we show that mammalian cells cultured on this membrane can be affected by reagents flowing through the channels. Specifically, saponin was used to compromise cell membranes, and a fluorescent label was used to monitor the extent, resulting in a 4-fold increase in fluorescence for saponin treated cells.

Genetic susceptibility loci, environmental exposures, and Parkinson's disease: a case-control study of gene-environment interactions.

BACKGROUND: Prior studies causally linked mutations in SNCA, MAPT, and LRRK2 genes with familial Parkinsonism. Genome-wide association studies have demonstrated association of single nucleotide polymorphisms (SNPs) in those three genes with sporadic Parkinson's disease (PD) susceptibility worldwide. Here we investigated the interactions between SNPs in those three susceptibility genes and environmental exposures (pesticides application, tobacco smoking, coffee drinking, and alcohol drinking) also associated with PD susceptibility. METHODS: Pairwise interactions between environmental exposures and 18 variants (16 SNPs and two variable number tandem repeats, or "VNTRs") in SNCA, MAPT and LRRK2, were investigated using data from 1098 PD cases from the upper Midwest, USA and 1098 matched controls. Environmental exposures were assessed using a validated telephone interview script. RESULTS: Five pairwise interactions had uncorrected P-values < 0.05. These included pairings of pesticides × SNCA rs3775423 or MAPT rs4792891, coffee drinking × MAPT H1/H2 haplotype or MAPT rs16940806, and alcohol drinking × MAPT rs2435211. None of these interactions remained significant after Bonferroni correction. Secondary analyses in strata defined by type of control (sibling or unrelated), sex, or age at onset of the case also did not identify significant interactions after Bonferroni correction. CONCLUSIONS: This study documented limited pairwise interactions between established genetic and environmental risk factors for PD; however, the associations were not significant after correction for multiple testing.

Integration of multiple components in polystyrene-based microfluidic devices part I: fabrication and characterization.

In Part I of a two-part series, we describe a simple and inexpensive approach to fabricate polystyrene devices that is based upon melting polystyrene (from either a Petri dish or powder form) against PDMS molds or around electrode materials. The ability to incorporate microchannels in polystyrene and integrate the resulting device with standard laboratory equipment such as an optical plate reader for analyte readout and pipets for fluid propulsion is first described. A simple approach for sample and reagent delivery to the device channels using a standard, multi-channel micropipette and a PDMS-based injection block is detailed. Integration of the microfluidic device with these off-chip functions (sample delivery and readout) enables high-throughput screens and analyses. An approach to fabricate polystyrene-based devices with embedded electrodes is also demonstrated, thereby enabling the integration of microchip electrophoresis with electrochemical detection through the use of a palladium electrode (for a decoupler) and carbon-fiber bundle (for detection). The device was sealed against a PDMS-based microchannel and used for the electrophoretic separation and amperometric detection of dopamine, epinephrine, catechol, and 3,4-dihydroxyphenylacetic acid. Finally, these devices were compared against PDMS-based microchips in terms of their optical transparency and absorption of an anti-platelet drug, clopidogrel. Part I of this series lays the foundation for Part II, where these devices were utilized for various on-chip cellular analysis.

Integration of multiple components in polystyrene-based microfluidic devices part II: cellular analysis.

In Part II of this series describing the use of polystyrene (PS) devices for microfluidic-based cellular assays: various cellular types and detection strategies are employed to determine three fundamental assays often associated with cells. Specifically, using either integrated electrochemical sensing or optical measurements with a standard multi-well plate reader, cellular uptake, production, or release of important cellular analytes are determined on a PS-based device. One experiment involved the fluorescence measurement of nitric oxide (NO) produced within an endothelial cell line following stimulation with ATP. The result was a four-fold increase in NO production (as compared to a control), with this receptor-based mechanism of NO production verifying the maintenance of cell receptors following immobilization onto the PS substrate. The ability to monitor cellular uptake was also demonstrated by optical determination of Ca(2+) into endothelial cells following stimulation with the Ca(2+) ionophore A20317. The result was a significant increase (42%) in the calcium uptake in the presence of the ionophore, as compared to a control (17%) (p < 0.05). Finally, the release of catecholamines from a dopaminergic cell line (PC 12 cells) was electrochemically monitored, with the electrodes being embedded into the PS-based device. The PC 12 cells had better adherence on the PS devices, as compared to use of PDMS. Potassium-stimulation resulted in the release of 114 ± 11 µM catecholamines, a significant increase (p < 0.05) over the release from cells that had been exposed to an inhibitor (reserpine, 20 ± 2 µM of catecholamines). The ability to successfully measure multiple analytes, generated in different means from various cells under investigation, suggests that PS may be a useful material for microfluidic device fabrication, especially considering the enhanced cell adhesion to PS, its enhanced rigidity/amenability to automation, and its ability to enable a wider range of analytes to be investigated, even analytes with a high degree of hydrophobicity.

Genomic determinants of motor and cognitive outcomes in Parkinson's disease.

BACKGROUND: Little is known regarding genetic factors associated with motor or cognitive outcomes in Parkinson's disease (PD). OBJECTIVE: To identify common genetic variants associated with motor and cognitive outcomes in PD. METHODS: The sample consisted of 443 PD cases included in the first genome-wide association study (GWAS) of PD. Methods included telephone interview assessments of motor and cognitive outcomes, a median 9 years following the initial clinical assessments. Analyses included Cox proportional hazard models to study the association of 198,345 single nucleotide polymorphisms (SNPs) with survival free of Hoehn and Yahr stage ≥ 4 (motor outcome), and either TICS-M ≤ 27 or AD-8 ≥ 2 (cognitive outcomes). RESULTS: The SNP rs10958605 in the C8orf4 gene had the smallest p value in analyses of the motor outcome (HR = 1.81; 95% CI = 1.42-2.31; p = 1.51 × 10(-6)). The SNP rs6482992 in the CLRN3 gene had the smallest p value in analyses of the cognitive outcome (HR = 2.03, 95% CI 1.47-2.79, p = 4.08 × 10(-6)). However, no SNP associations were significant after Bonferroni correction. The C8orf4 gene had small p values for both motor and cognitive outcomes, highlighting inflammation as a possible pathogenesis mechanism for progression in PD. CONCLUSIONS: This study suggests that common variants in several genes may be associated with motor and cognitive outcomes in PD, with biological plausibility.