Transcriptomic Analysis of Alzheimer's Disease Pathways in a Pakistani Population.

Background: Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder that is most prevalent in elderly individuals, especially in developed countries, and its prevalence is now increasing in developing countries like Pakistan. Objective: Our goal was to characterize key genes and their levels of expression and related molecular transcriptome networks associated with AD pathogenesis in a pilot case-control study in a Pakistani population. Methods: To obtain the spectrum of molecular networks associated with pathogenesis in AD patients in Pakistan (comparing cases and controls), we used high-throughput qRT-PCR (TaqMan Low-Density Array; n = 33 subjects) coupled with Affymetrix Arrays (n = 8) and Ingenuity Pathway Analysis (IPA) to identify signature genes associated with Amyloid processing and disease pathways. Results: We confirmed 16 differentially expressed AD-related genes, including maximum fold changes observed in CAPNS2 and CAPN1. The global gene expression study observed that 61% and 39% of genes were significantly (p-value 0.05) up- and downregulated, respectively, in AD patients compared to healthy controls. The key pathways include, e.g., Amyloid Processing, Neuroinflammation Signaling, and ErbB4 Signaling. The top-scoring networks in Diseases and Disorders Development were Neurological Disease, Organismal Injury and Abnormalities, and Psychological Disorders. Conclusions: Our pilot study offers a non-invasive and efficient way of investigating gene expression patterns by combining TLDA and global gene expression method in AD patients by utilizing whole blood. This provides valuable insights into the expression status of genes related to Amyloid Processing, which could play potential role in future studies to identify sensitive, early biomarkers of AD in general.

Transcriptomics of MASLD Pathobiology in African American Patients in the Washington DC Area †.

Metabolic-dysfunction-associated steatotic liver disease (MASLD) is becoming the most common chronic liver disease worldwide and is of concern among African Americans (AA) in the United States. This pilot study evaluated the differential gene expressions and identified the signature genes in the disease pathways of AA individuals with MASLD. Blood samples were obtained from MASLD patients (n = 23) and non-MASLD controls (n = 24) along with their sociodemographic and medical details. Whole-blood transcriptomic analysis was carried out using Affymetrix Clarion-S Assay. A validation study was performed utilizing TaqMan Arrays coupled with Ingenuity Pathway Analysis (IPA) to identify the major disease pathways. Out of 21,448 genes in total, 535 genes (2.5%) were significantly (p < 0.05) and differentially expressed when we compared the cases and controls. A significant overlap in the predominant differentially expressed genes and pathways identified in previous studies using hepatic tissue was observed. Of note, TGFB1 and E2F1 genes were upregulated, and HMBS was downregulated significantly. Hepatic fibrosis signaling is the top canonical pathway, and its corresponding biofunction contributes to the development of hepatocellular carcinoma. The findings address the knowledge gaps regarding how signature genes and functional pathways can be detected in blood samples ('liquid biopsy') in AA MASLD patients, demonstrating the potential of the blood samples as an alternative non-invasive source of material for future studies.

Insights on the pathogenesis of type 2 diabetes as revealed by signature genomic classifiers in an African American population in the Washington, DC area.

AIMS: African Americans (AA) in the United States have a high risk of type 2 diabetes mellitus (T2DM) and suffer from disparities in the prevalence, mortality, and comorbidities of the disease compared to other Americans. The present study aimed to shed light on the molecular mechanisms of disease pathogenesis of T2DM among AA in the Washington, DC region. METHODS: We performed TaqMan Low Density Arrays (TLDA) on 24 genes of interest that belong to three categories: metabolic disease and disorders, cancer-related genes, and neurobehavioural disorders genes. The 18 genes, viz. ARNT, CYP2D6, IL6, INSR, RRAD, SLC2A2 (metabolic disease and disorders), APC, BCL2, CSNK1D, MYC, SOD2, TP53 (Cancer-related), APBA1, APBB2, APOC1, APOE, GSK3B, and NAE1 (neurobehavioural disorders), were differentially expressed in T2DM participants compared to controls. RESULTS: Our results suggest that factors including gender, smoking habits, and the severity or lack of control of T2DM (as indicated by HbA1c levels) were significantly associated with differential gene expression. APBA1 was significantly (p-value <0.05) downregulated in all diabetes participants. Upregulation of APOE and CYP2D6 genes and downregulation of the INSR gene were observed in the majority of diabetes patients. CONCLUSIONS: Tobacco smoking and gender were significantly associated with case-control differences in expression of the APBA1 and APOE genes (connected with Alzheimer's disease) and the INSR and CYP2D6 (associated with metabolic disorders). The results highlight the need for more effective management of T2DM and for tobacco smoking cessation interventions in this community, and further research on the associations of T2DM with other disease processes, including cancer and neurobehavioral pathways.

The Asthma Control and Communication Instrument: a clinical tool developed for ethnically diverse populations.

BACKGROUND: Lower levels of quality asthma care among racially diverse populations might be due to inaccurate disease status assessments. The Asthma Control and Communication Instrument (ACCI) is a new tool that captures patient report of disease status during routine care. OBJECTIVE: We sought to test the ACCI's psychometric properties in a racially diverse population. METHODS: We performed a cross-sectional study. Subjects were recruited from specialist and generalist urban outpatient clinics. The ACCI and measures of asthma control, quality of life, lung function, and specialist rating of asthma status were collected. Four ACCI domains were separately validated: Acute Care, Bother, Control, and Direction. Principal component analysis, internal consistency, concurrent, discriminative, known-groups validity, and accuracy were evaluated. RESULTS: Two hundred seventy asthmatic patients (77% female subjects, 55% black) participated. ACCI Control domain internal consistency was 0.80. ACCI Bother, Control, and Direction domains showed strong concurrent validity with asthma control and quality-of-life measures (all P < .001). ACCI Acute Care and Direction domains showed strong concurrent validity with individual validation items (all P < .001). The ACCI Control domain discriminated clinically important levels of disease status measured by asthma control, quality of life (both P < .001), and percent predicted peak expiratory flow rate (P = .005) and was associated with specialist rating of disease status (P < .001), confirming known-groups validity. The accuracy of the ACCI Control domain in classifying patients with uncontrolled asthma was very good (area under the curve, 0.851; 95% CI, 0.742-0.95870). Results were similar for both black and white subjects. CONCLUSION: The ACCI is a promising clinical tool that measures asthma disease status during routine health care and is valid for use in both black and white populations.

Factors that influence quality of life in rural children with asthma and their parents.

INTRODUCTION: Among rural children with asthma and their parents, this study examined the relationship between parental and child reports of quality of life and described the relationship of several factors such as asthma severity, missed days of work, and asthma education on their quality of life. METHODS: Two hundred one rural families with asthma were enrolled in a school-based educational program. Intervention parents and children participated in interactive asthma workshop(s) and received asthma devices and literature. Parent and child quality of life measurements were obtained before and after the intervention using Juniper's Paediatric Caregivers Quality of Life and Juniper's Paediatric Quality of Life Questionnaires. Asthma severity was measured using criteria from the National Asthma Education and Prevention Program guidelines. RESULTS: There was no association between parent and child total quality of life scores, and mean parental total quality of life scores were higher at baseline and follow-up than those of the children. All the parents' quality of life scores were correlated with parental reports of missed days of work. For all children, emotional quality of life (EQOL) was significantly associated with parental reports of school days missed (P = .03) and marginally associated with parental reports of hospitalizations due to asthma (P = .08). Parent's EQOL and activity quality of life (AQOL) were significantly associated with children's asthma severity (EQOL, P = .009; AQOL, P = .03), but not the asthma educational intervention. None of the child quality of life measurements was associated with asthma severity. DISCUSSION: Asthma interventions for rural families should help families focus on gaining and maintaining low asthma severity levels to enjoy an optimal quality of life. Health care providers should try to assess the child's quality of life at each asthma care visit independently of the parents.

Patient factors used by pediatricians to assign asthma treatment.

OBJECTIVE: Although asthma is often inappropriately treated in children, little is known about what information pediatricians use to adjust asthma therapy. The purpose of this work was to assess the importance of various dimensions of patient asthma status as the basis of pediatrician treatment decisions. PATIENTS AND METHODS: We conducted a cross-sectional, random-sample survey, between November 2005 and May 2006, of 500 members of the American Academy of Pediatrics using standardized case vignettes. Vignettes varied in regard to (1) acute health care use (hospitalized 6 months ago), (2) bother (parent bothered by the child's asthma status), (3) control (frequency of symptoms and albuterol use), (4) direction (qualitative change in symptoms), and (5) wheezing during physical examination. Our primary outcome was the proportion of pediatricians who would adjust treatment in the presence or absence of these 5 factors. RESULTS: Physicians used multiple dimensions of asthma status other than symptoms to determine treatment. Pediatricians were significantly more likely to increase treatment for a recently hospitalized patient (45% vs 18%), a bothered parent (67% vs 18%), poorly controlled symptoms (4-5 times per week; 100% vs 18%), or if there was wheezing on examination (45% vs 18%) compared with patients who only had well-controlled symptoms. Pediatricians were significantly less likely to decrease treatment for a child with well-controlled symptoms and recent hospitalization (28%), parents who reported being bothered (43%), or a child whose symptoms had worsened since the last doctor visit (10%) compared with children with well-controlled symptoms alone. CONCLUSIONS: Pediatricians treat asthma on the basis of multiple dimensions of asthma status, including hospitalization, bother, symptom frequency, direction, and wheezing but use these factors differently to increase and decrease treatment. Tools that systematically assess multiple dimensions of asthma may be useful to help further improve pediatric asthma care.

Patient factors that physicians use to assign asthma treatment.

BACKGROUND: Asthma guidelines recommend severity assessment to assign treatment, often quantified as current control. It is unknown how strongly control assessment affects clinician treatment decisions, nor if control is sufficient. METHODS: To determine patient factors used by physicians to assign treatment, we surveyed pulmonary specialists (PSs) and family physicians (FPs) using vignettes. We tested whether recent acute care (hospitalization 6 months ago), bother (patient bothered by asthma), control (symptom or reliever medication frequency), and direction (change since last visit) influence treatment decisions. Factors used for stepping up and stepping down were assessed. RESULTS: A total of 461 physicians participated (236 PSs and 225 FPs). As expected, physicians indicated a greater likelihood of stepping up treatment for persistent (4-5 times per week) than for intermittent (1 time per 2 weeks) symptoms (PSs 97% vs 24%, P < .001; FPs 97% vs 33%, P < .001). All else being equal, physicians were more likely to step up treatment of a patient with intermittent symptoms if the patient reported recent acute care (PSs 49% vs 24%; FPs 72% vs 33%), was bothered (PSs 81% vs 24%; FPs 80% vs 33%), or was worse since the last visit (PSs 68% vs 24%; FPs 66% vs 33%) (all P < .001). These factors were also predictive of stepping down from high-intensity therapy and remained significant in multivariate analyses (all P < .05). CONCLUSIONS: Asthma control greatly influences physician decisions about asthma treatments. However, recent acute care, bother, and direction of illness also influence decisions, particularly those that involve increasing the amount of medication prescribed. Further work is needed to determine if use of these additional indicators leads to better asthma outcomes.

Asthma education for rural school nurses: resources, barriers, and outcomes.

This paper describes a school-based asthma education program for rural elementary school nurses. The program was designed to teach school nurses in 7 rural counties in Maryland how to implement and to reinforce asthma management behaviors in children with asthma and their caregivers. Rural nurses who participated in this program increased their mean asthma knowledge scores more than nurses who did not take the program. The program also increased self-efficacy among intervention school nurses, but the difference in self-efficacy between intervention and control nurses was not statistically significant at follow-up. No effects on documentation or communication behaviors were noted. Only 25% of the nurses reported an interest in implementing future asthma educational programs for children with asthma. This study indicates the importance of understanding the unique characteristics of rural school nurses, the resources they need, and the barriers and challenges they face in their practice.

A+ Asthma Rural Partnership coloring for health: an innovative rural asthma teaching strategy.

Asthma is the leading chronic illness in children, affecting about 4.8 million children in the United States. Recent reports indicate a lack of asthma educational resources for rural school health nurses to use in their practice. This article describes the development of the My Asthma Coloring Book educational tool for children and their families living in rural communities. My Asthma Coloring Book was developed to provide asthma information in a short-story format for children with asthma. The coloring book content is described, including its utilization as part of the A+ Asthma Rural Partnership research project funded by the National Institute of Nursing Research (R01NR05062-01).