The Alzheimer's Disease Neuroimaging Initiative and the role and contributions of the Private Partners Scientific Board (PPSB).

The Alzheimer's Disease Neuroimaging Initiative (ADNI) Private Partners Scientific Board (PPSB) encompasses members from industry, biotechnology, diagnostic, and non-profit organizations that have until recently been managed by the Foundation for the National Institutes of Health (FNIH) and provided financial and scientific support to ADNI programs. In this article, we review some of the major activities undertaken by the PPSB, focusing on those supporting the most recently completed National Institute on Aging grant, ADNI3, and the impact it has had on streamlining biomarker discovery and validation in Alzheimer's disease. We also provide a perspective on the gaps that may be filled with future PPSB activities as part of ADNI4 and beyond. HIGHLIGHTS: The Private Partners Scientific board (PPSB) continues to play a key role in enabling several Alzheimer's Disease Neuroimaging Initiative (ADNI) activities. PPSB working groups have led landscape assessments to provide valuable feedback on new technologies, platforms, and methods that may be taken up by ADNI in current or future iterations.

The association between adverse childhood experiences, self-silencing behaviours and symptoms in women with fibromyalgia.

Poor adult health has consistently been associated with Adverse Childhood Experiences (ACEs). The process is not fully understood but is likely to involve a complex interaction of biological and psychosocial factors. Early life stress can affect the developing brain resulting in long-term hyper-responses to stress and raised inflammatory biomarkers. Women with fibromyalgia syndrome (FMS) frequently report ACEs and also self-sacrificial behaviours whereby they repress their own needs and emotions to preserve personal relationships. This behavioural profile (termed self-silencing) may develop following ACEs but has not previously been considered in the context of FMS. This study examined whether self-silencing mediates the link between ACEs and FMS symptoms. Women with (N = 539) and without (N = 184) an FMS diagnosis completed measures of Silencing-the-Self, health symptoms and ACEs. Number of ACEs and symptom levels were significantly associated in both groups. One aspect of self-silencing, care and self-sacrifice (putting others needs before your own) mediated the association between ACEs and symptoms in the FMS group only. Externalised self-perception (judging oneself according to perceived external standards) was negatively associated with symptoms but presented no mediating effects. Results present preliminary new information to explain the association between ACEs and FMS. Recognition of the factors which underlie symptomology is important in understanding the condition and supporting patients.

Human Papillomavirus and Vaccination Of Males: Knowledge and Attitudes Of Registered Nurses.

The American Academy of Pediatrics recommends the human papillomavirus (HPV) vaccine for all 11 to 12-year olds as part of the adolescent immunization platform. However, this vaccine has not been universally accepted by health care providers, parents, or the public, and has lower vaccination coverage rates than other recommended vaccines for the same age group. The purpose of this study was to determine registered nurses' knowledge and attitudes about HPV and associated HPV vaccine for males. One hundred eleven (111) RNs participated in a descriptive exploratory study using a survey method. Nurses were knowledgeable about specific HPV information but were less knowledgeable about the extent of HPV infection seen in males or the availability or indications of HPV vaccine for males. This study demonstrates that nurses need more education about HPV and HPV vaccine.

Seroprevalence, Blood Chemistry, and Patterns of Canine Parvovirus, Distemper Virus, Plague, and Tularemia in Free-Ranging Coyotes (Canis latrans) in Northern New Mexico, USA.

Wildlife diseases have implications for ecology, conservation, human health, and health of domestic animals. They may impact wildlife health and population dynamics. Exposure rates of coyotes (Canis latrans) to pathogens such as Yersinia pestis, the cause of plague, may reflect prevalence rates in both rodent prey and human populations. We captured coyotes in north-central New Mexico during 2005-2008 and collected blood samples for serologic surveys. We tested for antibodies against canine distemper virus (CDV, Canine morbillivirus), canine parvovirus (CPV, Carnivore protoparvovirus), plague, tularemia (Francisella tularensis), and for canine heartworm (Dirofilaria immitis) antigen. Serum biochemistry variables that fell outside reference ranges were probably related to capture stress. We detected antibodies to parvovirus in 32/32 samples (100%), and to Y. pestis in 26/31 (84%). More than half 19/32 (59%) had antibodies against CDV, and 5/31 (39%) had antibodies against F. tularensis. We did not detect any heartworm antigens (n = 9). Pathogen prevalence was similar between sexes and among the three coyote packs in the study area. Parvovirus exposure appeared to happen early in life, and prevalence of antibodies against CDV increased with increasing age class. Exposure to Y. pestis and F. tularensis occurred across all age classes. The high coyote seroprevalence rates observed for CPV, Y. pestis, and CDV may indicate high prevalence in sympatric vertebrate populations, with implications for regional wildlife conservation as well as risk to humans via zoonotic transmission.

Coping with fibromyalgia during the COVID-19 pandemic: adjustment and wellbeing.

OBJECTIVE: Fibromyalgia syndrome (FMS) is a chronic condition with symptoms known to be exacerbated by stress. Individuals with FMS may be experiencing particular distress under Covid-19 pandemic-related lifestyle restrictions. The present study examined wellbeing, perceived symptom change and coping in individuals with and without FMS during pandemic-related social lockdown in the UK. DESIGN: Participants with a diagnosis of FMS (N = 390) and a general public sample with no FMS (N = 151) completed questionnaires at three time points. MAIN OUTCOME MEASURES: BBC Wellbeing Scale, Cognitive-Emotional Regulation Questionnaire measure of coping, perception of extent to which symptoms have worsened or improved over time. RESULTS: Contrary to expectations, FMS participants reported no worsening of symptoms and an increase in wellbeing over the study period. Non-FMS participants experienced worsening health symptoms and no change in wellbeing. Coping strategies involving positive reappraisal, refocussing and planning were positively associated with wellbeing in the FMS group. CONCLUSION: The unpredictable symptom profile in FMS, and the regular readjustment this necessitates, may support a form of resilience which has been adaptive during the pandemic. The results have implications for supporting people with FMS, and potentially other chronic conditions, especially at times of stress.

System model driven selection of robust tablet manufacturing processes based on drug loading and formulation physical attributes.

Mechanistic process modeling presents an opportunity to reduce experimental burden, enabling relationships between process parameters and product attributes to be mapped out using in-silico experiments. A system model of a pharmaceutical tablet manufacturing process comparing dry granulation with direct compression is developed to answer key material and process design questions. The system model links API physical properties and formulation to process parameters to map out the robust operating space. To demonstrate the application of the model, several drug product formulation design questions were considered:A computational framework was developed using the system models to generate process classification and design space maps to aid robust pharmaceutical formulation and process decision making. Process classification maps were produced to assess the feasibility of roller compaction and direct compression for different material properties and formulations. Constraints on the critical quality attributes of the intermediate and final products were defined using the Manufacturing Classification System. Design space maps presented here demonstrate how system models can be used to support formulation and process design. The design space maps illustrate how the process operating space can be increased or decreased as the API mass fraction is varied. The process design and selection system model demonstrate how an understanding of the API physical properties can be used to model the impact of formulation and process design. Furthermore, these models can be instrumental in the dialogue with colleagues developing the API in order to set the requirements of the API physical properties to ensure successful and robust formulation and process designs.

Clozapine prescribing: comparison of clozapine dosage and plasma levels between White British and Bangladeshi patients.

AIMS AND METHOD: To compare differences in clozapine doses and plasma levels between Bangladeshi and White British patients. Following ethical approval we identified all current Bangladeshi and White British patients on clozapine maintenance in an east London clinic. We carried out univariate and multivariate regression analyses to examine associations between clozapine doses and ethnicity, age, gender, smoking status and weight. We also compared plasma clozapine levels of the two groups. RESULTS: On univariate analysis White British patients had on average 85 mg higher doses than Bangladeshi patients (P = 0.004). Older age, male gender and smoking were also associated with higher dose. On multivariate analysis only age and smoking status remained significant. A greater proportion of Bangladeshi patients had high plasma clozapine levels compared with White British (30.76% v. 20.75%), although the difference was not statistically significant. CLINICAL IMPLICATIONS: Our findings point to the need for the broadening of data collection on ethnic differences in clozapine prescribing within big data-sets such as Prescribing Observatory for Mental Health (POM-UK). Ethnopharmacological variations can inform more person-centred guidance on prescribing.

Hydrogel-Forming Microneedles: Current Advancements and Future Trends.

In this focused progress review, the recent developments and trends of hydrogel-forming microneedles (HFMs) and potential future directions are presented. Previously, microneedles (solid, hollow, coated, and dissolving microneedles) have primarily been used to enhance the effectiveness of transdermal drug delivery to facilitate a wide range of applications such as vaccinations and antibiotic delivery. However, the recent trend in microneedle development has resulted in microneedles formed from hydrogels which have the ability to offer transdermal drug delivery and, due to the hydrogel swelling nature, passively extract interstitial fluid from the skin, meaning they have the potential to be used for biocompatible minimally invasive monitoring devices. Thus, in this review, these recent trends are highlighted, which consolidate microneedle design considerations, hydrogel formulations, fabrication processes, applications of HFMs and the potential future opportunities for utilizing HFMs for personalized healthcare monitoring and treatment.

Childhood maltreatment and migraine (part III). Association with comorbid pain conditions.

OBJECTIVE: To evaluate in a headache clinic population the relationship of childhood maltreatment on the prevalence of pain conditions comorbid with migraine. BACKGROUND: Childhood maltreatment is highly prevalent and has been frequently associated with recurrent headache. The relationship of maltreatment and pain has, however, been a subject of some debate. METHODS: Cross-sectional data on self-reported physician-diagnosed pain conditions were electronically collected from persons with migraine (diagnosed according to International Classification of Headache Disorders-2), seeking treatment in headache clinics at 11 centers across the US and Canada. These included irritable bowel syndrome (IBS), chronic fatigue syndrome (CFS), fibromyalgia (FM), interstitial cystitis (IC), arthritis, endometriosis, and uterine fibroids. Other information included demographics, migraine characteristics (frequency, headache-related disability), remote and current depression (The Patient Health Questionnaire-9), and remote and current anxiety (The Beck Anxiety Inventory). Patients also completed the Childhood Trauma Questionnaire regarding sexual, emotional, and physical abuse, and emotional and physical neglect under the age of 18 years old. Statistical analyses accounted for the survey design and appropriate procedures in SAS such as surveymeans, surveyfreq, and surveylogistic were applied to the weighted data. RESULTS: A total of 1348 migraineurs (88% women) were included in this study (mean age 41 years). Based on physician diagnosis or validated criteria, 31% had IBS, 16% had CFS, and 10% had FM. Diagnosis of IC was reported by 6.5%, arthritis by 25%, and in women, endometriosis was reported by 15% and uterine fibroids by 14%. At least 1 comorbid pain condition was reported by 61%, 2 conditions by 18%, and 3 or more by 13%. Childhood maltreatment was reported by 58% of the patients. Emotional abuse was associated with increased prevalence of IBS, CFS, arthritis, and physical neglect with arthritis. In women, physical abuse was associated with endometriosis and physical neglect with uterine fibroids. Emotional abuse, and physical abuse and neglect (P < .0001 for all) were also associated with increased total number of comorbid conditions. In ordinal logistic regression models, adjusted for sociodemographics and current depression (prevalence 28%) and anxiety (prevalence 56%), emotional abuse (odds ratios [OR] = 1.69, 95% confidence intervals [CI]: 1.224-2.33) and physical neglect (OR = 1.73, 95% CI: 1.22-2.46) were independently associated with an increased number of pain conditions. The cohort of women, similarly, had associations of emotional abuse (OR = 1.94, 95% CI: 1.40-2.72) and physical neglect (OR = 1.90, 95% CI: 1.34-2.68) with an increased number of pain comorbidities. CONCLUSION: The association of childhood maltreatment and pain was stronger in those reporting multiple pain conditions and multiple maltreatment types. This finding suggests that in migraineurs childhood maltreatment may be a risk factor for development of comorbid pain disorders.

Childhood maltreatment and migraine (part I). Prevalence and adult revictimization: a multicenter headache clinic survey.

OBJECTIVES: To examine the prevalence of childhood maltreatment and adult revictimization in migraineurs and the association with sociodemographic factors, depression and anxiety. BACKGROUND: Population and practice-based studies have demonstrated an association of childhood abuse and headache in adults, although further details on headache diagnoses, characteristics, and comorbid conditions are lacking. There are mounting data suggesting substantial impact of early maltreatment on adult physical and mental health. METHODS: Electronic surveys were completed by patients seeking treatment in 11 headache centers across the United States and Canada. Physicians determined the primary headache diagnoses based on the International Classification of Headache Disorders-2 criteria and average monthly headache frequency. Self-reported information on demographics (including body mass index), social history, and physician-diagnosed depression and anxiety was collected. The survey also included validated screening measures for current depression (Patient Health Questionnaire-9) and anxiety (The Beck Anxiety Inventory). History and severity of childhood (<18 years) abuse (sexual, emotional, and physical) and neglect (emotional and physical) was gathered using the Childhood Trauma Questionnaire. There were also queries regarding adult physical and sexual abuse, including age of occurrence. Analysis includes all persons with migraine with aura, and migraine without aura. RESULTS: A total of 1348 migraineurs (88% women) were included (mean age 41 years). Diagnosis of migraine with aura was recorded in 40% and chronic headache (>or=15 days/month) was reported by 34%. The prevalence of childhood maltreatment types was as follows: physical abuse 21%, sexual abuse 25%, emotional abuse 38%, physical neglect 22%, and emotional neglect 38%. Nine percent reported all 3 categories of childhood abuse (physical, sexual, and emotional) and 17% reported both physical and emotional neglect. Overlap between maltreatment types ranged between 40% and 81%. Of those reporting childhood abuse, 43% reported abuse in adulthood, but infrequently (17%) over the age of 30 years. In logistic regression models adjusted for sociodemographic variables, current depression was associated with physical (P = .003), sexual (P = .007), and emotional abuse (P < .001), and physical and emotional neglect (P = .001 for both). Current anxiety was also associated with all childhood abuse and neglect categories (P < .001 for all). A graded relationship was observed between the number of childhood maltreatment types and remote or current depression and anxiety. In adjusted logistic regression analysis, migraineurs reporting 3 or more categories of childhood trauma were more likely to have received diagnoses of both depression and anxiety (odds ratios [OR] = 6.91, 95% confidence interval [CI]: 3.97-12.03), or either depression or anxiety (OR = 3.66, 95% CI: 2.28-5.88) as compared with those without childhood abuse or neglect. CONCLUSION: Reports of childhood maltreatment, especially emotional abuse and neglect, are prevalent in outpatients with migraine. There is extensive overlap of maltreatment types and a high rate of revictimization in adulthood. All types of childhood abuse and neglect are strongly associated with remote and current depression and anxiety, and the relationship strengthens with an increasing number of maltreatment types.

Childhood maltreatment and migraine (part II). Emotional abuse as a risk factor for headache chronification.

OBJECTIVES: To assess in a headache clinic population the relationship of childhood abuse and neglect with migraine characteristics, including type, frequency, disability, allodynia, and age of migraine onset. BACKGROUND: Childhood maltreatment is highly prevalent and has been associated with recurrent headache. Maltreatment is associated with many of the same risk factors for migraine chronification, including depression and anxiety, female sex, substance abuse, and obesity. METHODS: Electronic surveys were completed by patients seeking treatment in headache clinics at 11 centers across the United States and Canada. Physician-determined data for all participants included the primary headache diagnoses based on the International Classification of Headache Disorders-2 criteria, average monthly headache frequency, whether headaches transformed from episodic to chronic, and if headaches were continuous. Analysis includes all persons with migraine with aura, and migraine without aura. Questionnaire collected information on demographics, social history, age at onset of headaches, migraine-associated allodynic symptoms, headache-related disability (The Headache Impact Test-6), current depression (The Patient Health Questionnaire-9), and current anxiety (The Beck Anxiety Inventory). History and severity of childhood (<18 years) abuse (sexual, emotional, and physical) and neglect (emotional and physical) was gathered using the Childhood Trauma Questionnaire. RESULTS: A total of 1348 migraineurs (88% women) were included (mean age 41 years). Diagnosis of migraine with aura was recorded in 40% and chronic headache (>or=15 days/month) was reported by 34%. Transformation from episodic to chronic was reported by 26%. Prevalence of current depression was 28% and anxiety was 56%. Childhood maltreatment was reported as follows: physical abuse 21%, sexual abuse 25%, emotional abuse 38%, physical neglect 22%, and emotional neglect 38%. In univariate analyses, physical abuse and emotional abuse and neglect were significantly associated with chronic migraine and transformed migraine. Emotional abuse was also associated with continuous daily headache, severe headache-related disability, and migraine-associated allodynia. After adjusting for sociodemographic factors and current depression and anxiety, there remained an association between emotional abuse in childhood and both chronic (odds ratio [OR] = 1.77, 95% confidence intervals [CI]: 1.19-2.62) and transformed migraine (OR = 1.89, 95% CI: 1.25-2.85). Childhood emotional abuse was also associated with younger median age of headache onset (16 years vs 19 years, P = .0002). CONCLUSION: Our findings suggest that physical abuse, emotional abuse, and emotional neglect may be risk factors for development of chronic headache, including transformed migraine. The association of maltreatment and headache frequency appears to be independent of depression and anxiety, which are related to both childhood abuse and chronic daily headache. The finding that emotional abuse was associated with an earlier age of migraine onset may have implications for the role of stress responses in migraine pathophysiology.

Robotic microscopy for everyone: the OpenFlexure microscope.

Optical microscopes are an essential tool for both the detection of disease in clinics, and for scientific analysis. However, in much of the world access to high-performance microscopy is limited by both the upfront cost and maintenance cost of the equipment. Here we present an open-source, 3D-printed, and fully-automated laboratory microscope, with motorised sample positioning and focus control. The microscope is highly customisable, with a number of options readily available including trans- and epi- illumination, polarisation contrast imaging, and epi-florescence imaging. The OpenFlexure microscope has been designed to enable low-volume manufacturing and maintenance by local personnel, vastly increasing accessibility. We have produced over 100 microscopes in Tanzania and Kenya for educational, scientific, and clinical applications, demonstrating that local manufacturing can be a viable alternative to international supply chains that can often be costly, slow, and unreliable.

Migraine and biomarkers of endothelial activation in young women.

BACKGROUND AND PURPOSE: There is mounting evidence of endothelial activation and dysfunction in migraine. Our objectives were to determine in a population of premenopausal women whether endothelial activation markers are associated with migraine. METHODS: Women (18 to 50 years) with and without migraine and free from cardiovascular disease were evaluated with tests of coagulation (von Willebrand factor activity, prothrombin fragment), fibrinolysis (tissue-type plasminogen activator antigen), inflammation (high-sensitivity C-reactive protein), and oxidative stress (homocysteine, total nitrate/nitrite concentrations, thiobarbituric acid-reactive substances). RESULTS: Sixty-one participants had migraine with aura (MA), 64 had migraine without aura (MO), and 50 were controls. Compared with controls, women with migraine had higher adjusted odds ratios for elevated von Willebrand factor activity of 6.51 (95% CI, 1.94 to 21.83) in those with MA and of 4.59 (95% CI, 1.37 to 15.38) in those with MO, elevated high-sensitivity C-reactive protein of 7.99 (95% CI, 2.32 to 27.61) in those with MA and of 2.63 (95% CI, 0.73 to 9.45) in those with MO, and for lower nitrate/nitrite levels of 6.60 (95% CI, 2.06 to 21.16) in those with MA and of 3.03 (95% CI, 0.90 to 10.15) in those with MO. Within the migraine group, von Willebrand factor activity was correlated with tissue-type plasminogen activator antigen (P=0.035) and nitrate/nitrite (P=0.024). There was a trend with high-sensitivity C-reactive protein (P=0.09). CONCLUSIONS: In premenopausal women with migraine, particularly in those with MA, there is evidence of increased endothelial activation, a component of endothelial dysfunction.

A multicenter study of noninvasive cardiac output by bioreactance during symptom-limited exercise.

BACKGROUND: Hemodynamic responses to exercise were assessed in patients with varying degrees of chronic heart failure (CHF) to determine the feasibility of using bioreactance during exercise testing in multicenter studies of CHF. METHODS AND RESULTS: A total of 210 symptomatic CHF patients and 22 subjects without heart failure were subjected to symptom-limited exercise testing on a bicycle (105) or treadmill (127) while measuring gas exchange for VO(2), cardiac output (CO) noninvasively by a bioreactance technique, heart rate, and blood pressure. Peak CO (pCO) and VO(2) (pVO(2)) during exercise were lower in patients with higher New York Heart Association (NYHA) class, in females and in older patients. Multiple linear regression analysis showed that pCO (L/min)=19.6+4.M -2.1.NYHA+1.9.G -0.09.Age, where M=1 for treadmill and 0 for bicycle and G=1 for males and 0 for females. Similarly, pVO(2) (mL/kg/min)=24+2.1.M -2.9.NYHA+1.26.G -0.08.Age. VO(2) and CO were also highly correlated to each other: pCO (mL/kg/min)=0.059+0.007.pVO(2)+0.036.M -0.025.G. Similar correlations were determined for other parameters of exercise, including left ventricular power, and the ratio of peak/resting VO(2) (cardiovascular reserve), the ratio of peak/resting CO (cardiac reserve), and total peripheral vascular resistance. CONCLUSION: Bioreactance-based noninvasive measurements of CO at rest and during exertion identified abnormalities of cardiovascular function consistent with those identified by pVO(2) and in prior studies using invasive CO measurements. This technique might therefore be useful for indexing disease severity, prognostication, and for tracking responses to treatment in clinical practice and in clinical trials.

Allodynia in migraine: association with comorbid pain conditions.

BACKGROUND: Cutaneous allodynia (CA) in migraine is a clinical manifestation of central nervous system sensitization. Several chronic pain syndromes and mood disorders are comorbid with migraine. In this study we examine the relationship of migraine-associated CA with these comorbid conditions. We also evaluate the association of CA with factors such as demographic profiles, migraine characteristics, and smoking status that may have an influence on the relationships of CA to pain and mood. METHODS: Data are from a cross-sectional multicenter study of comorbid conditions in persons seeking treatment in headache clinics. Diagnosis of migraine was determined by a physician based on the International Classification of Headache Disorders-II criteria. Participants completed a self-administered questionnaire ascertaining sociodemographics, migraine-associated allodynia, physician-diagnosed comorbid medical and psychiatric disorders, headache-related disability, current depression, and anxiety. RESULTS: A total of 1413 migraineurs (mean age = 42 years, 89% women) from 11 different headache treatment centers completed a survey on the prevalence of comorbid conditions. Aura was reported by 38% and chronic headache by 35% of the participants. Sixty percent of the study population reported at least one migraine-related allodynic symptom, 10% reported > or =4 symptoms. Symptoms of CA were associated with female gender, body mass index, current smoking, presence of aura, chronic headaches, transformed headaches, severe headache-related disability, and duration of migraine illness from onset. The prevalence of self-reported physician diagnosis of comorbid pain conditions (irritable bowel syndrome, chronic fatigue syndrome, fibromyalgia) and psychiatric conditions (current depression and anxiety) was also associated with symptoms of CA. Adjusted ordinal regression indicated a significant association between number of pain conditions and severity of CA (based on symptom count). Adjusting for sociodemographics, migraine characteristics, and current depression and anxiety, the likelihood of reporting symptoms of severe allodynia was much higher in those with 3 or more pain conditions (odds ratio = 3.03, 95% confidence interval: 1.78-5.17), and 2 pain conditions (odds ratio = 2.67, 95% confidence interval: 1.78-4.01) when compared with those with no comorbid pain condition. CONCLUSION: Symptoms of CA in migraine were associated with current anxiety, depression, and several chronic pain conditions. A graded relationship was observed between number of allodynic symptoms and the number of pain conditions, even after adjusting for confounding factors. This study also presents the novel association of CA symptoms with younger age of migraine onset, and with cigarette smoking, in addition to confirming several previously reported findings.

Single-cell developmental classification of B cell precursor acute lymphoblastic leukemia at diagnosis reveals predictors of relapse.

Insight into the cancer cell populations that are responsible for relapsed disease is needed to improve outcomes. Here we report a single-cell-based study of B cell precursor acute lymphoblastic leukemia at diagnosis that reveals hidden developmentally dependent cell signaling states that are uniquely associated with relapse. By using mass cytometry we simultaneously quantified 35 proteins involved in B cell development in 60 primary diagnostic samples. Each leukemia cell was then matched to its nearest healthy B cell population by a developmental classifier that operated at the single-cell level. Machine learning identified six features of expanded leukemic populations that were sufficient to predict patient relapse at diagnosis. These features implicated the pro-BII subpopulation of B cells with activated mTOR signaling, and the pre-BI subpopulation of B cells with activated and unresponsive pre-B cell receptor signaling, to be associated with relapse. This model, termed 'developmentally dependent predictor of relapse' (DDPR), significantly improves currently established risk stratification methods. DDPR features exist at diagnosis and persist at relapse. By leveraging a data-driven approach, we demonstrate the predictive value of single-cell 'omics' for patient stratification in a translational setting and provide a framework for its application to human cancer.

Correlation of serum biomarkers in adults with single ventricles with strain and strain rate using 2D speckle tracking.

BACKGROUND: With advances in cardiac care, patients with congenital heart disease, including single ventricle (SV) physiology, now survive into adulthood. These patients often suffer from congestive heart failure (CHF) with overexpression of serum biomarkers. Strain and strain rate (SR) may better describe the myocardial mechanics of a failing SV. Our objective was to determine the correlation between strain/SR and biomarkers in adult patients with SV and CHF. METHODS: Adult patients (age ≥8 years) with a SV were enrolled. Strain/SR in a 16-segment model of a SV was measured using 2D speckle echocardiography. Serum levels of interleukin 6, interleukin 8, matrix metalloproteinase 9, procollagen I C-terminal peptide (PCIP), cross-linked carboxy-terminal telopeptide of type I collagen (ICTP), pro-B-type natriuretic peptide, nitrotryrosine, tissue growth factor beta (TGF-ß), tumor necrosis factor alpha, vascular endothelial growth factor, and creatinine (Cr) were measured. Patients underwent a complete 6 Minute Walk Test (MWT). Pearson correlation coefficient was used. P <.05 was considered significant. RESULTS: Ten patients with SV (LV = 7, RV = 3) were enrolled. Mean age was 35.5 years (25-42 years). Mean single ventricular ejection fraction (SVEF) was 47%. ICTP correlated with the basal, mid, and apical anterolateral SR, as well as apical anterior and inferior SR. PCIP correlated with mid anterolateral, basal anteroseptal, and mid inferolateral SR. TGF-ß correlated with apical inferior SR. Cr correlated with mid inferior-septal and apical lateral SR. 6 MWT negatively correlated with the apical anterior septum SR. CONCLUSIONS: ICTP, Cr, and PCIP correlated best with segmental SR values. Our results provide a preliminary platform for future studies to follow the results of treatment modalities using strain/SR and biomarkers for CHF in this population.

Endometriosis is associated with prevalence of comorbid conditions in migraine.

OBJECTIVE: To examine the headache characteristics of women with migraine and endometriosis (EM), and differences in the prevalence of comorbid conditions between female migraineurs with EM, without EM and nonheadache controls. BACKGROUND: Migraine and EM are common conditions in women of reproductive age, and both are influenced by ovarian hormones. The comorbidity of migraine and EM is newly recognized, but reasons for the association are uncertain. METHODS: This is a cross-sectional study of female headache outpatients and healthy controls conducted at University of Toledo and Duke University in 2005 and 2006. After a headache specialist determined headache frequency and diagnosis (based on criteria of the second International Classification of Headache Disorders), patients completed a self-administered electronic survey with information on demographics, headache-related disability, menstrual disorders, premenstrual dysphoric disorder (PMDD), vascular event risk, and comorbid conditions, including irritable bowel syndrome (IBS), fibromyalgia (FM), chronic fatigue syndrome (CFS), interstitial cystitis (IC), depression, and anxiety. RESULTS: Study enrolled 171 women with migraine and 104 controls. EM was reported more commonly in migraineurs than in controls (22% vs 9.6%, P < .01). Frequency of chronic headache was higher in migraineurs with EM compared to without EM (P= .002) and median headache-related disability scores were also higher in the EM group (P= .025). Symptoms of PMDD were more common in migraineurs, but frequency did not differ by EM status. Migraineurs with EM reported more menorrhagia, dysmenorrhea, and infertility compared to the migraine cohort without EM and to controls. Depression, anxiety, IBS, FM, CFS, and IC were more common in migraine with EM group than in controls. Anxiety (OR = 2.2, 95% CI 1.0-4.7), IC (OR = 10.6, 95% CI 1.9-56.5), and CFS (OR = 3.6, 95% CI 1.1-11.5) were more common in migraine with EM group, than in the cohort with migraine without EM. CONCLUSION: Prevalence of EM is higher in women with migraine than in nonheadache controls. Migraineurs with EM have more frequent and disabling headaches, and are more likely to have other comorbid conditions affecting mood and pain, compared to migraineurs without EM.

Migraine comorbidity constellations.

OBJECTIVES: To identify distinct constellations of comorbid disorders occurring in migraineurs, and to examine differences in demographics, headache profiles, and psychosocial features between the comorbidity constellations. METHODS: This is a retrospective electronic chart review of consecutive new female outpatients diagnosed with migraine (n = 223) using International Classification of Headache Disorders (ICHD)-II criteria. Questionnaire collected information on comorbid diagnoses, current depression, somatic symptoms, psychosocial stressors, and antidepressant use, social and abuse history. Cluster analysis, based on nonheadache disorders, was performed and differences between the resulting groups were examined. RESULTS: We identified 3 groups. Group 1 (n = 55) was defined by hypertension, hyperlipidemia, diabetes mellitus, and hypothyroidism; Group 2 (n = 83) by depression, anxiety, and fibromyalgia; Group 3 (n = 85) by the absence of defining comorbidities. Group 1 had more males (22% vs 5% vs 12%, P < .05), was older (median years: 52 vs 36 vs 32, P < .01), and had later age of headache onset (median years: 22 vs 16 vs 18, P < .05). Group 2 had the greatest disability (P < .05), and the lowest quality of life (P < .001). Persons in Group 2 more commonly reported sexual abuse (OR = 2.7, 95% CI: 1.1 to 6.5), physical abuse (OR = 2.5, 95% CI: 1.2 to 5.1), and emotional abuse (OR = 4.3, 95% CI: 1.9 to 8.9). CONCLUSION: Within a headache clinic population, we identified 3 different migraine comorbidity constellations, with differing headache and psychosocial profiles, suggesting heterogeneity of genetic and environmental factors. This may have implications for diagnosis and disease management.