In addition to their well characterized role in allergic inflammation, recent data confirm that mast cells play a more extensive role in a variety of immune responses. However, their contribution to autoimmune and neurologic disease processes has not been investigated. Experimental allergic encephalomyelitis (EAE) and its human disease counterpart, multiple sclerosis, are considered to be CD4+ T cell-mediated autoimmune diseases affecting the central nervous system. Several lines of indirect evidence suggest that mast cells could also play a role in the pathogenesis of both the human and murine disease. Using a myelin oligodendrocyte glycoprotein (MOG)-induced model of acute EAE, we show that mast cell-deficient W/W(v) mice exhibit significantly reduced disease incidence, delayed disease onset, and decreased mean clinical scores when compared with their wild-type congenic littermates. No differences were observed in MOG-specific T and B cell responses between the two groups, indicating that a global T or B cell defect is not present in W/W(v) animals. Reconstitution of the mast cell population in W/W(v) mice restores induction of early and severe disease to wild-type levels, suggesting that mast cells are critical for the full manifestation of disease. These data provide a new mechanism for immune destruction in EAE and indicate that mast cells play a broader role in neurologic inflammation.
BACKGROUND AND RESEARCH OBJECTIVE: Approximately 50% of heart failure (HF) patients are thought to be malnourished, and macronutrient and micronutrient deficiencies may potentially aggravate HF symptoms. Thus, concerns have been raised about the overall nutrient composition of diets in HF populations. The purpose of this study was to examine the macronutrient and micronutrient intake by caloric adequacy among community-dwelling adults with HF. PARTICIPANTS AND METHODS: A secondary analysis of baseline data of participants in an HF lifestyle intervention study was conducted. Participants (n = 45) were predominantly male (55.6%), white, and non-Hispanic (64.4%); had a mean age of 61 years (SD, 11 years) and mean body mass index of 31.2 kg/m (SD, 7.3 kg/m); were of New York Heart Association functional classes II and III (77.8%); and had a mean ejection fraction of 31.9% (SD, 13.2%); and 69% had a college or higher level of education. The Block Food Habits Questionnaire was used to assess the intake of macronutrients and micronutrients. Analysis included descriptive statistics and Mann-Whitney U tests. RESULTS AND CONCLUSIONS: Individuals reporting inadequate daily caloric intake reported a lower intake of macronutrients and micronutrients as well as other differences in dietary patterns compared with individuals reporting adequate daily caloric intake. More than half of the individuals reporting adequate caloric intake did not meet the recommended dietary allowance for magnesium and vitamin E. Interventions aimed at increasing overall intake and nutrient density are suggested. Further research is needed to better understand the relationship between dietary factors and outcomes in HF.
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Lori N. Eidson;
George T. Kannarkat;
Christopher J. Barnum;
Jianjun Chang;
Jaegwon Chung;
Chelsea Caspell-Garcia;
Peggy Taylor;
Brit Mollenhauer;
Michael G. Schlossmacher;
Larry Ereshefsky;
Mark Yen;
Catherine Kopil;
Mark Frasier;
Kenneth Marek;
Vicki Hertzberg;
MariadeLourdes Tansey
Background: Efforts to identify fluid biomarkers of Parkinson's disease (PD) have intensified in the last decade. As the role of inflammation in PD pathophysiology becomes increasingly recognized, investigators aim to define inflammatory signatures to help elucidate underlying mechanisms of disease pathogenesis and aid in identification of patients with inflammatory endophenotypes that could benefit from immunomodulatory interventions. However, discordant results in the literature and a lack of information regarding the stability of inflammatory factors over a 24-h period have hampered progress. Methods: Here, we measured inflammatory proteins in serum and CSF of a small cohort of PD (n=12) and age-matched healthy control (HC) subjects (n=6) at 11 time points across 24h to (1) identify potential diurnal variation, (2) reveal differences in PD vs HC, and (3) to correlate with CSF levels of amyloid β (Aβ) and α-synuclein in an effort to generate data-driven hypotheses regarding candidate biomarkers of PD. Results: Despite significant variability in other factors, a repeated measures two-way analysis of variance by time and disease state for each analyte revealed that serum IFNγ, TNF, and neutrophil gelatinase-associated lipocalin (NGAL) were stable across 24h and different between HC and PD. Regression analysis revealed that C-reactive protein (CRP) was the only factor with a strong linear relationship between CSF and serum. PD and HC subjects showed significantly different relationships between CSF Aβ proteins and α-synuclein and specific inflammatory factors, and CSF IFNγ and serum IL-8 positively correlated with clinical measures of PD. Finally, linear discriminant analysis revealed that serum TNF and CSF α-synuclein discriminated between PD and HC with a minimum of 82% sensitivity and 83% specificity. Conclusions: Our findings identify a panel of inflammatory factors in serum and CSF that can be reliably measured, distinguish between PD and HC, and monitor inflammation as disease progresses or in response to interventional therapies. This panel may aid in generating hypotheses and feasible experimental designs towards identifying biomarkers of neurodegenerative disease by focusing on analytes that remain stable regardless of time of sample collection.
Background Patient's knowledge about heart failure (HF) contributes to successful HF self-care, but less is known about shared patient-caregiver knowledge. Objectives The purpose of this analysis was to: 1) identify configurations of shared HF knowledge in patient-caregiver dyads; 2) characterize dyads within each configuration by comparing sociodemographic factors, HF characteristics, and psychosocial factors; and 3) quantify the relationship between configurations and patient self-care adherence to managing dietary sodium and HF medications. Methods This was a secondary analysis of cross-sectional data (N = 114 dyads, 53% spousal). Patient and caregiver HF knowledge was measured with the Atlanta Heart Failure Knowledge Test. Patient dietary sodium intake was measured by 3-day food record and 24 h urine sodium. Medication adherence was measured by Medication Events Monitoring System caps. Patient HF-related quality of life was measured by the Minnesota Heart Failure Questionnaire; caregiver health-related quality of life was measured by the Short Form-12 Physical Component Summary. Patient and caregiver depression were measured with the Beck Depression Inventory-II. Patient and caregiver perceptions of caregiver-provided autonomy support to succeed in heart failure self-care were measured by the Family Care Climate Questionnaire. Multilevel and latent class modeling were used to identify dyadic knowledge configurations. T-tests and chi-square tests were used to characterize differences in sociodemographic, clinical, and psychosocial characteristics by configuration. Logistic/linear regression were used to quantify relationships between configurations and patient dietary sodium and medication adherence. Results Two dyadic knowledge configurations were identified: “Knowledgeable Together” (higher dyad knowledge, less incongruence; N = 85, 75%) and “Knowledge Gap” (lower dyad knowledge, greater incongruence; N = 29, 25%). Dyads were more likely to be in the “Knowledgeable Together” group if they were White and more highly educated, if the patient had a higher ejection fraction, fewer depressive symptoms, and better autonomy support, and if the caregiver had better quality of life. In unadjusted comparisons, patients in the “Knowledge Gap” group were less likely to adhere to HF medication and diet. In adjusted models, significance was retained for dietary sodium only. Conclusions Dyads with higher shared HF knowledge are likely more successful with select self-care adherence behaviors.
Vascular endothelial dysfunction is associated with increased risk for adverse cardiovascular (CV) events. However, less is known about sex differences in the endothelial function of untreated hypertensive individuals. The purpose of this study was to assess endothelial function in women and men with untreated hypertension. Ninety participants (35 women, 55 men), aged 40 to 60years (mean age, 46.1±8.2years), with untreated stage 1 hypertension (systolic blood pressure 140-159mmHg and/or diastolic blood pressure 90-99mmHg) underwent brachial artery endothelial-dependent flow-mediated dilation and endothelial-independent glyceryl trinitrate dilation. Women had a smaller flow-mediated dilation response than men (adjusted mean±standard error of the mean [SEM]; 1.8±0.6% vs 3.9±0.4%, P=.036), adjusting for baseline arterial diameter (P=.004), age (P=.596), ethnicity (P=.496), log shear stress ratio (P<.001), body mass index (P=.009), 24-hour diastolic blood pressure (P=.169), high-density lipoprotein (P=.225), log creatinine (P=.927), and log physical activity (P=.682). Glyceryl trinitrate dilation did not differ by sex in adjusted models. Women between the ages of 40 and 60years with untreated stage 1 hypertension exhibited a greater impairment of endothelial function compared with their male counterparts. These findings raise the possibility that female sex may impart a greater risk of CV events in patients with untreated stage 1 hypertension potentially due to poorer endothelial function.
Objective: (i) To compare the prevalence and severity of depressive symptoms between men and women enrolled in a large heart failure (HF) registry. (ii) To determine gender differences in predictors of depressive symptoms from demographic, behavioral, clinical, and psychosocial factors in HF patients. Methods: In 622 HF patients (70% male, 61 ± 13 years, 59% NYHA class III/IV), depressive symptoms were assessed by the Patient Health Questionnaire (PHQ-9). Potential correlates were age, ethnicity, education, marital and financial status, smoking, exercise, body mass index (BMI), HF etiology, NYHA class, comorbidities, functional capacity, anxiety, and perceived control. To identify gender-specific correlates of depressive symptoms, separate logistic regression models were built by gender. Results: Correlates of depressive symptoms in men were financial status (p = 0.027), NYHA (p = 0.001); functional capacity (p < 0.001); health perception (p = 0.043); perceived control (p = 0.002) and anxiety (p < 0.001). Correlates of depressive symptoms in women were BMI (p = 0.003); perceived control (p = 0.013) and anxiety (p < 0.001). Conclusions: In HF patients, lowering depressive symptoms may require gender-specific interventions focusing on weight management in women and improving perceived functional capacity in men. Both men and women with HF may benefit from anxiety reduction and increased control.
Background: This study evaluated 1-year linear trajectories of patient-reported dimensions of quality of life among patients receiving dialysis.
Study Design: Longitudinal observational study.
Setting & Participants: 227 patients recruited from 12 dialysis centers.
Factors: Sociodemographic and clinical characteristics.
Measurements/Outcomes: Participants completed an hour-long interview monthly for 12 months. Each interview included patient-reported outcome measures of overall symptoms (Edmonton Symptom Assessment System), physical functioning (Activities of Daily Living/Instrumental Activities of Daily Living), cognitive functioning (Patient's Assessment of Own Functioning Inventory), emotional well-being (Center for Epidemiologic Studies Depression Scale, State Anxiety Inventory, and Positive and Negative Affect Schedule), and spiritual well-being (Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being Scale). For each dimension, linear and generalized linear mixed-effects models were used. Linear trajectories of the 5 dimensions were jointly modeled as a multivariate outcome over time.
Results: Although dimension scores fluctuated greatly from month to month, overall symptoms, cognitive functioning, emotional well-being, and spiritual well-being improved over time. Older compared with younger participants reported higher scores across all dimensions (all P < 0.05). Higher comorbidity scores were associated with worse scores in most dimensions (all P < 0.01). Nonwhite participants reported better spiritual well-being compared with their white counterparts (P < 0.01). Clustering analysis of dimension scores revealed 2 distinctive clusters. Cluster 1 was characterized by better scores than those of cluster 2 in nearly all dimensions at baseline and by gradual improvement over time.
Limitations: Study was conducted in a single region of the United States and included mostly patients with high levels of function across the dimensions of quality of life studied.
Conclusions: Multidimensional patient-reported quality of life varies widely from month to month regardless of whether overall trajectories improve or worsen over time. Additional research is needed to identify the best approaches to incorporate patient-reported outcome measures into dialysis care.
Background: Kenya's human resources for health shortage is well documented, yet in line with the new constitution, responsibility for health service delivery will be devolved to 47 new county administrations. This work describes the public sector nursing workforce likely to be inherited by the counties, and examines the relationships between nursing workforce density and key indicators.
Methods: National nursing deployment data linked to nursing supply data were used and analyzed using statistical and geographical analysis software. Data on nurses deployed in national referral hospitals and on nurses deployed in non-public sector facilities were excluded from main analyses. The densities and characteristics of the public sector nurses across the counties were obtained and examined against an index of county remoteness, and the nursing densities were correlated with five key indicators.
Results: Of the 16,371 nurses in the public non-tertiary sector, 76% are women and 53% are registered nurses, with 35% of the nurses aged 40 to 49 years. The nursing densities across counties range from 1.2 to 0.08 per 1,000 population. There are statistically significant associations of the nursing densities with a measure of health spending per capita (P value = 0.0028) and immunization rates (P value = 0.0018). A higher county remoteness index is associated with explaining lower female to male ratio of public sector nurses across counties (P value < 0.0001).
Conclusions: An overall shortage of nurses (range of 1.2 to 0.08 per 1,000) in the public sector countrywide is complicated by mal-distribution and varying workforce characteristics (for example, age profile) across counties. All stakeholders should support improvements in human resources information systems and help address personnel shortages and mal-distribution if equitable, quality health-care delivery in the counties is to be achieved.
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Kathleen L. Withers;
Judith White;
Grace Carolan-Rees;
Hannah Patrick;
Peter O'Callaghan;
Stephen Murray;
David Cunningham;
Kathryn Wood;
Mauro Lencioni;
Michael Griffith
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Stephen M. Vindigni;
Patricia L. Riley;
Francis Kimani;
Rankesh Willy;
Patrick Warutere;
Jennifer F. Sabatier;
Rose Kiriinya;
Michael Friedman;
Martin Osumba;
Agnes N. Waudo;
Chris Rakuom;
Martha Rogers
Objective: To assess the feasibility of utilizing a small-scale, low-cost, pilot evaluation in assessing the short-term impact of Kenya's emergency-hire nursing programme (EHP) on the delivery of health services (outpatient visits and maternal-child health indicators) in two underserved health districts with high HIV/AIDS prevalence.Methods: Six primary outcomes were assessed through the collection of data from facility-level health management forms-total general outpatient visits, vaginal deliveries, caesarean sections, antenatal care (ANC) attendance, ANC clients tested for HIV, and deliveries to HIV-positive women. Data on outcome measures were assessed both pre-and post-emergency-hire nurse placement. Informal discussions were also conducted to obtain supporting qualitative data.Findings: The majority of EHP nurses were placed in Suba (15.5%) and Siaya (13%) districts. At the time of the intervention, we describe an increase in total general outpatient visits, vaginal deliveries and caesarean sections within both districts. Similar significant increases were seen with ANC attendance and deliveries to HIV-positive women. Despite increases in the quantity of health services immediately following nurse placement, these levels were often not sustained. We identify several factors that challenge the long-term sustainability of these staffing enhancements.Conclusions: There are multiple factors beyond increasing the supply of nurses that affect the delivery of health services. We believe this pilot evaluation sets the foundation for future, larger and more comprehensive studies further elaborating on the interface between interventions to alleviate nursing shortages and promote enhanced health service delivery. We also stress the importance of strong national and local relationships in conducting future studies.