1. ENDOPHENOTYPE FINDINGS AND PSYCHOSIS PROFILE OF SCHIZOPHRENIA IN MONGOLIA
Oyunchimeg N ; Guljanat E ; Nasantsengel L ; Jablensky A ; Gregory W ; Price
Innovation 2015;9(1):64-67
BACKGROUND: The Western Australian Family Study of Schizophrenia (WAFSS) has conducted genetic epidemiology studies of schizophrenia in Australia for two decades. Recently the WAFSS practices were adopted at the National Centre for for Mental Health in Mongolia, with a view tocollecting comparable data. Like the cited projects (supra), we are cognizant of the dangers of multi site data collection. We replicate common practices, such as training manuals and common site training and refreshment (CCRN WHO training centre). However in international (possibly multilingual) collection and pooling, identical assessment is difficult, it is impossible to replicate endophenotype instructions verbatim (Calkins 2007), and identical recording equipment may not be available indisparate sites. At the very least the data must be compared separately, with the option of weighting,before the pooling for genetic analysis. The use of endophenotypes (Gottesman& Gould) is well established in schizophrenia research for genetic analysis () as well as in more general neuroscience biomarker approaches. The use of electrophysiological markers, and particularly Event-Related Potentials (ERPs) is a well developedaspect of this approach (BraffDL, 2007, TuretskyBI, 2009). Electrophysiological endophenotypes include (inter alia) the Mismatch Negativity (MMN), P50 suppression ratio (P50), auditory oddball P300 (P300), and Antisaccade (AS) tasks. In this study, we seek to follow the multi centre quality assurance examples for pooled data on a smallerscale. This report details the validation of compatibility between the Western Australian Family Study of Schizophrenia (WAFSS) dataset (Perth, Australia), and a pilot dataset from the National Centre for Mental Health (NCMH) in Ulaanbaatar, Mongolia. The working hypothesis is that the psychiatric and endophenotype profiles in the two datasets are sufficiently similar to allow data ompatibility for genetic analysis.METHODS: The Mongolian version of the DIP was developed as part of a joint genetic investigation of schizophrenia between the Centre for Clinical Research in europsychiatry (CCRN) in Perth Western Australia, and the National Center of Mental Health (NCMH) in Ulaanbaatar, Mongolia.The DIP is a semi-structured interview for psychosis for use in epidemiological and clinical settings (CastleD, 2006). It is designed to provide a diagnosis, as well as to assess symptom profiles (present state, past year and lifetime), social functioning, disablement, and service utilisation. It was developed specifically for the National Mental Health Survey – Low Prevalence (Psychotic) Disorders Study(Jablensky et al, 1999, 2000), and has been translated to Italian (RossiA, 2010), Norwegion (SkorvenCS, 2010), and to Mongolian in 2012. The process started with the translation of the original English language version (Castle et al., 2006) by an experienced bilingual psychiatrist (GE) from the NCMH whose native language was Mongolian. Layout and formatting of the document were preserved. It was then back-translated by a non medical,tertiary educated professional, whose native language is Mongolian, but is now resident in Perth. The back-translation was reviewed by an original author (AJ) and experienced practitioners (GP). Grammatical and syntactical discrepancies were resolved directly with the original translator. Event Related Potentials To replicate the WAFSS ERP approach at NCMH, a new portable ERP recording system was deployed. This decision was based on several considerations: a) the WAFSS system could not be taken out of service; b) an identical system could not be replicated due to the age of the components; c) an equivalent system would be too substantial for easy, cost effective transport; d) the system was expected to be used in multiple sites in Mongolia; e) the same system was expected to be used in other Australian projects.The Portable ERP system uses NuAmps, with a hardware selected reference at the FPz location. While the ear references A1 and A2 were recorded, the mathematically re-referenced data is not the same as directly linking ears. (Citation ****). Instead the data was analysed as recorded, with cognizance traces (instead of 20) could not be used. This marks a variation from the original WAFSS processing. Instead of artifact rejection on any trace, only the relevant trace (Fz, Cz, Pz) was used for each ERP (MMN, P50, P300). Endophenotypes The ERP endophenotypes are clearly continous variables, and analysed with general linear modelling. Two tailed significance testing was used for between cohort comparisons, since there is no a priori indication which cohort would have the higher values. Single tailed testing was used in comparing Proband (Pb) and Control (Ctl) groups within the same cohort, as thedirection of any difference is well established.RESULTS: DIP The structure of the diagnostic module (DIP-DM) follows the Operational Criteria for Psychosis, OPCRIT, version 3.31 (McGuffin et al., 1991; Williams et al., 1996) 90-item checklist. It can be used to generate diagnoses according to the criteria of ICD-10 (World Health Organization, 1993); DSM-IV (American Psychiatric Association, 1994); the Research Diagnostic Criteria (Spitzer et al., 1978), and others. The summary of diagnoses (ICD-10 and DSM-IV) generated for each cohort are shown in Figure 1. Diagnostic distribution (%) of 30 interviewed cases from NCMH and 201 cases from the WAFSS cohorts, according to the DIP diagnostic algorithm, by diagnostic classification system. To facilitate omparisons between different criteria systems, Castle (2006) escribes aggregated diagnostic classification descriptors (with reservations) that are used in Figure 1. Greater detail of the DIP responses that support these descriptors is shown for similiarly aggregated questions in Figure 2. aMicrovolts for MMNAmp and P300Amp, numeric forothers.bFor MMN, P50, and AS, but not P300, the raw mean (notabsolute value) for the Pb and Fm groups are higher thanthat of the Ctl group. cEqual variances not assumed.Endophenotype values were each significantly “worse” inthe proband group of the NCMH cohort, for MMN (t=1.65;p=0.05), P300 (t=-2.02; p=0.02) and AS (t=2.12; p=0.02).The comparable values from the WAFSS cohort showed thesame behaviour for MMN (t=4.52; p<0.01), P300 (t=-3.35;p<0.01) and AS (t=3.93; p<0.01). The P50 endophenotypedid not show a significant difference between clinical groups in either NCMH (t=0.20) or WAFSS (t=1.12) cohort. DISCUSSION: This comparison has shown that there is not a significant difference (α= 0.05) between the NCMH and WAFSSpopulations (patient and control). This outcome is deemed sufficient to allow pooled analysis of genetic and electrophysiological data in future studies. It is acknowledged that the outcome does not show that the two populations are the same. Questions of international comparison (McGrathJJ, 2006) in incidence and prevalence, of mental illness and particularly of schizophrenia are eschewed. These were not the purpose of the study. Our experience from this study, as distinct from analysis, is that situational variation in equipment, protocol and recruitment likely outweigh any cultural differencesin epidemiology. The absolute value of the lectrophysiologicalendophenotypes was different between the two sites, butthe relative values were the same. The control group showed“better” responses than the patient group, with similareffect size. Moreover, the patient clinical profile was also slightly different. The incidence of neuroleptic medication was a substantial uncontrolled factor. The question becomes how to deal with these differences.In combining population groups, the data can be discarded,equalized, or transformed. Describe each. We seek to standardize comparisons between populations by transforming data by scaling prior to genetic analysis.Absolute value The raw amplitude data for both ERP eatures (MMN, P300) is significantly lower from the Mongolian cohort in both Patient and Control groups. Endophenotype characteristics.ScalingWhile the difference in absolute values precludes directlycombining data from different cohorts, the consistentendophenotype characteristics allows one possiblemethod to further genetic investigation of continuousendophenotype variables. The results are expected toderive from a combination of technical, situational, clinicaland endophenotype factors. Each of these factors could befurther investigated individually. However, if a combinedendophenotype analysis is even theoretically acceptable,then the endophenotypebehaviour in different cohorts hasto be defined as identical, and the standardized measuresfrom equivalent Control groups must be equal. If the WAFSScontrol group is considered as the standard in this study, then the scaling factors for the NCMH cohort are 13.5 (MMN), 1.0 (P50), 2.5 (P300) and 0.6 (AS).SUMMARY: The consistency in endophenotypebehaviour betweencohorts legitimizes the application of the genetic approachin Mongolia. DNA extraction and analysis for this cohort iscontinuing and, although for smaller numbers, preliminaryresults can be compared with the Australian cohort.
2.Corrigendum: Primary Purulent Pericarditis with Cardiac Tamponade due to Oropharyngeal Polymicrobial Infection: A Case Report and Literature Review.
Mukul BHATARAI ; Gregory YOST ; Christopher W GOOD ; Charles F WHITE ; Hitekshya NEPAL
The Korean Journal of Thoracic and Cardiovascular Surgery 2014;47(3):325-325
There was an error in name of author. Mukul Bhatarai is replaced with Mukul Bhattarai.
3.Primary Purulent Pericarditis with Cardiac Tamponade due to Oropharyngeal Polymicrobial Infection: A Case Report and Literature Review.
Mukul BHATARAI ; Gregory YOST ; Christopher W GOOD ; Charles F WHITE ; Hitekshya NEPAL
The Korean Journal of Thoracic and Cardiovascular Surgery 2014;47(2):155-159
Cardiac tamponade due to purulent pericarditis with a characteristic greenish fluid is rare in this antibiotic era. It is highly fatal despite early diagnosis and advanced treatment. Gram-positive cocci are the leading cause of purulent pericarditis, which usually results from a direct or hematogenous spread of organisms to the pericardium from the primary foci of infection. We describe an index case of rapidly developing pericardial tamponade caused by oropharyngeal polymicrobial infection in the absence of a primary source of infection in a 62-year-old man, who was successfully managed with emergency large-volume pericardiocentesis followed by pericardiectomy.
Cardiac Tamponade*
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Coinfection*
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Early Diagnosis
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Emergencies
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Middle Aged
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Gram-Positive Cocci
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Pericardiectomy
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Pericardiocentesis
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Pericarditis*
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Pericardium
4.Carotid Intima-media Thickness Measurements: Relations with Atherosclerosis, Risk of Cardiovascular Disease and Application in Randomized Controlled Trials.
Michiel L BOTS ; Gregory W EVANS ; Charles H TEGELER ; Rudy MEIJER
Chinese Medical Journal 2016;129(2):215-226
Advances in the field of carotid ultrasound have been incremental, resulting in a steady decrease in measurement variability. Improvements in edge detection algorithms point toward increasing automation of CIMT measurements. The major advantage of CIMT is that it is completely noninvasive and can be repeated as often as required. It provides a continuous measure since all subjects have a measurable carotid wall. It is also relatively inexpensive to perform, and the technology is widely available. A graded relation between raising LDL cholesterol and increased CIMT is apparent. Increased CIMT has been shown consistently to relate the atherosclerotic abnormalities elsewhere in the arterial system. Moreover, increased CIMT predicts future vascular events in both populations from Caucasian ancestry and those from Asian ancestry. Furthermore, lipid‑lowering therapy has been shown to affect CIMT progression within 12–18 months in properly designed trials with results congruent with clinical events trials. In conclusion, when one wants to evaluate the effect of a pharmaceutical intervention that is to be expected to beneficially affect atherosclerosis progression and to reduce CV event risk, the use of CIMT measurements over time is a valid, suitable, and evidence‑based choice.
Atherosclerosis
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diagnosis
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Cardiovascular Diseases
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diagnosis
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Carotid Intima-Media Thickness
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Humans
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Randomized Controlled Trials as Topic
5.Three-Dimensional Modeling of the Structural Microenvironment in Post-Traumatic War Wounds
Gregory T. CHRISTOPHERSON ; Jaira F. de VASCONCELLOS ; John C. DUNN ; Daniel W. GRIFFIN ; Patrick E. JONES ; Leon J. NESTI
Tissue Engineering and Regenerative Medicine 2021;18(6):963-973
BACKGROUND:
The development of post-traumatic heterotopic ossification (HO) is a common, undesirable sequela in patients with high-energy (war-related) extremity injuries. While inflammatory and osteoinductive signaling pathways are known to be involved in the development and progression of post-traumatic HO, features of the structural microenvironment within which the ectopic bone begins to form remain poorly understood. Thus, increasing our knowledge of molecular and structural changes within the healing wound may help elucidate the pathogenesis of post-traumatic HO and aid in the development of specific treatment and/or prevention strategies.
METHODS:
In this study, we performed high-resolution microscopy and biochemical analysis of tissues obtained from traumatic war wounds to characterize changes in the structural microenvironment. In addition, using an electrospinning approach, we modeled this microenvironment to reconstitute a three-dimensional type I collagen scaffold with non-woven, randomly oriented nanofibers where we evaluated the performance of primary mesenchymal progenitor cells.
RESULTS:
We found that traumatic war wounds are characterized by a disorganized, densely fibrotic collagen I matrix that influences progenitor cells adhesion, proliferation and osteogenic differentiation potential.
CONCLUSION
Altogether, these results suggest that the structural microenvironment present in traumatic war wounds has the potential to contribute to the development of post-traumatic HO. Our findings may support novel treatment strategies directed towards modifying the structural microenvironment after traumatic injury.
6.Urodynamic Mechanisms Underlying Overactive Bladder Symptoms in Patients With Parkinson Disease
Gregory VURTURE ; Benoit PEYRONNET ; Jose Alberto PALMA ; Rachael D SUSSMAN ; Dominique R MALACARNE ; Andrew FEIGIN ; Ricardo PALMEROLA ; Nirit ROSENBLUM ; Steven FRUCHT ; Horacio KAUFMANN ; Victor W NITTI ; Benjamin M BRUCKER
International Neurourology Journal 2019;23(3):211-218
PURPOSE: To assess the urodynamic findings in patients with Parkinson disease (PD) with overactive bladder symptoms. METHODS: We performed a retrospective chart review of all PD patients who were seen in an outpatient clinic for lower urinary tract symptoms (LUTS) between 2010 and 2017 in a single-institution. Only patients who complained of overactive bladder (OAB) symptoms and underwent a video-urodynamic study for these symptoms were included. We excluded patients with neurological disorders other than PD and patients with voiding LUTS but without OAB symptoms. RESULTS: We included 42 patients (29 men, 13 women, 74.5±8.1 years old). Seven patients (16.7%) had a postvoid residual (PVR) bladder volume >100 mL and only one reported incomplete bladder emptying. Detrusor overactivity (DO) was found in all 42 patients (100%) and was terminal in 19 (45.2%) and phasic in 22 patients (52.4%). Eighteen patients had detrusor underactivity (DU) (42.3%). Later age of PD diagnosis was the only parameter associated with DU (P=0.02). Patients with bladder outlet obstruction (BOO) were younger than patients without BOO (70.1 years vs. 76.5 years, P=0.004), had later first sensation of bladder filling (173.5 mL vs. 120.3 mL, P=0.02) and first involuntary detrusor contraction (226.4 mL vs. 130.4 mL, P=0.009). CONCLUSIONS: DO is almost universal in all patients with PD complaining of OAB symptoms (97.1%). However, a significant percentage of patients also had BOO (36.8%), DU (47%), and increased PVR (16.7%) indicating that neurogenic DO may not be the only cause of OAB symptoms in PD patients.
Ambulatory Care Facilities
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Diagnosis
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Female
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Humans
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Lower Urinary Tract Symptoms
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Male
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Nervous System Diseases
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Parkinson Disease
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Parkinsonian Disorders
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Retrospective Studies
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Sensation
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Urinary Bladder
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Urinary Bladder Neck Obstruction
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Urinary Bladder, Overactive
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Urinary Incontinence
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Urodynamics
7.Venous Outflow Profiles Are Linked to Clinical Outcomes in Ischemic Stroke Patients with Extensive Baseline Infarct
Laurens WINKELMEIER ; Gabriel BROOCKS ; Helge KNIEP ; Vincent GEEST ; Jonathan REINWALD ; Lukas MEYER ; Noel VAN HORN ; Adrien GUENEGO ; Kamil ZELEŇÁK ; Gregory W. ALBERS ; Maarten LANSBERG ; Peter SPORNS ; Max WINTERMARK ; Jens FIEHLER ; Jeremy J. HEIT ; Tobias D. FAIZY
Journal of Stroke 2022;24(3):372-382
Background:
and Purpose The benefit of endovascular thrombectomy (EVT) treatment is still unclear in stroke patients presenting with extensive baseline infarct. The use of additional imaging biomarkers could improve clinical outcome prediction and individualized EVT selection in this vulnerable cohort. We hypothesized that cerebral venous outflow (VO) may be associated with functional outcomes in patients with low Alberta Stroke Program Early CT Score (ASPECTS).
Methods:
We conducted a retrospective multicenter cohort study of patients with acute ischemic stroke due to large vessel occlusion (AIS-LVO). Extensive baseline infarct was defined by an ASPECTS of ≤5 on admission computed tomography (CT). VO profiles were assessed on admission CT angiography using the Cortical Vein Opacification Score (COVES). Favorable VO was defined as COVES ≥3. Multivariable logistic regression was used to determine the association between cerebral VO and good clinical outcomes (90-day modified Rankin Scale score of ≤3).
Results:
A total of 98 patients met the inclusion criteria. Patients with extensive baseline infarct and favorable VO achieved significantly more often good clinical outcomes compared to patients with unfavorable VO (45.5% vs. 10.5%, P<0.001). Higher COVES were strongly associated with good clinical outcomes (odds ratio, 2.17; 95% confidence interval, 1.15 to 4.57; P=0.024), independent of ASPECTS, National Institutes of Health Stroke Scale, and success of EVT.
Conclusions
Cerebral VO profiles are associated with good clinical outcomes in AIS-LVO patients with extensive baseline infarct. VO profiles could serve as a useful additional imaging biomarker for treatment selection and outcome prediction in low ASPECTS patients.
8.Association of Unfavorable Social Determinants of Health With Stroke/Transient Ischemic Attack and Vascular Risk Factors in Hispanic/Latino Adults: Results From Hispanic Community Health Study/Study of Latinos
Gabriela TRIFAN ; Linda C. GALLO ; Melissa LAMAR ; Olga GARCIA-BEDOYA ; Krista M. PERREIRA ; Amber PIRZADA ; Gregory A. TALAVERA ; Sylvia W. SMOLLER ; Carmen R. ISASI ; Jianwen CAI ; Martha L. DAVIGLUS ; Fernando D. TESTAI
Journal of Stroke 2023;25(3):361-370
Background:
and Purpose Social determinants of health (SDOH) are non-medical factors that may contribute to the development of diseases, with a higher representation in underserved populations. Our objective is to determine the association of unfavorable SDOH with self-reported stroke/transient ischemic attack (TIA) and vascular risk factors (VRFs) among Hispanic/Latino adults living in the US.
Methods:
We used cross-sectional data from the Hispanic Community Health Study/Study of Latinos. SDOH and VRFs were assessed using questionnaires and validated scales and measurements. We investigated the association between the SDOH (individually and as count: ≤1, 2, 3, 4, or ≥5 SDOH), VRFs and stroke/TIA using regression analyses.
Results:
For individuals with stroke/TIA (n=388), the mean age (58.9 years) differed from those without stroke/TIA (n=11,210; 46.8 years; P<0.0001). In bivariate analysis, income <$20,000, education less than high school, no health insurance, perceived discrimination, not currently employed, upper tertile for chronic stress, and lower tertiles for social support and language- and social-based acculturation were associated with stroke/TIA and retained further. A higher number of SDOH was directly associated with all individual VRFs investigated, except for at-risk alcohol, and with number of VRFs (β=0.11, 95% confidence interval [CI]=0.09–0.14). In the fully adjusted model, income, discrimination, social support, chronic stress, and employment status were individually associated with stroke/TIA; the odds of stroke/TIA were 2.3 times higher in individuals with 3 SDOH (95% CI 1.6–3.2) and 2.7 times (95% CI 1.9–3.7) for those with ≥5 versus ≤1 SDOH.
Conclusion
Among Hispanic/Latino adults, a higher number of SDOH is associated with increased odds for stroke/TIA and VRFs. The association remained significant after adjustment for VRFs, suggesting involvement of non-vascular mechanisms.
9.Perfusion Profiles May Differ Between Asymptomatic Versus Symptomatic Internal Carotid Artery Occlusion
Ting-Yu CHANG ; Soren CHRISTENSEN ; Michael MLYNASH ; Jeremy J. HEIT ; Michael P. MARKS ; Sarah LEE ; Margy E. MCCULLOUGH-HICKS ; Lili Velickovic OSTOJIC ; Stephanie KEMP ; Gregory W. ALBERS ; Aditya SRIVATSAN ; Tsong-Hai LEE ; Maarten G. LANSBERG
Journal of Stroke 2024;26(1):108-111