Cerebrovascular reactivity in Alzheimer's disease signature regions is associated with mild cognitive impairment in adults with hypertension.

INTRODUCTION: Vascular risk factors contribute to cognitive decline suggesting that maintaining cerebrovascular health could reduce dementia risk. The objective of this study is to evaluate the association of cerebrovascular reactivity (CVR), a measure of brain blood vessel elasticity, with mild cognitive impairment (MCI) and dementia. METHODS: Participants were enrolled in the Systolic Blood Pressure Intervention Trial Memory and Cognition in Decreased Hypertension (SPRINT-MIND) magnetic resonance imaging substudy. Baseline CVR in Alzheimer's disease (AD) signature regions were primary variables of interest. The occipital pole and postcentral gyrus were included as control regions. RESULTS: Higher AD composite CVR was associated with lower MCI risk. No significant associations between inferior temporal gyrus, occipital pole, or postcentral gyrus CVR and MCI risk, or any regional CVR-combined risk associations were observed. DISCUSSION: CVR in AD signature regions is negatively associated with occurrence of MCI, implicating CVR in AD signature regions as a potential mechanism leading to cognitive impairment.

Protective effects of sleep duration and physical activity on cognitive performance are influenced by ß-amyloid and brain volume but not tau burden among cognitively unimpaired older adults.

BACKGROUND AND OBJECTIVES: Sleep and physical activity have gained traction as modifiable risk factors for Alzheimer's disease. Sleep duration is linked to amyloid-ß clearance while physical activity is associated with brain volume maintenance. We investigate how sleep duration and physical activity are associated with cognition by testing if the associations between sleep duration or physical activity to cognition are explained by amyloid-ß burden and brain volume, respectively. Additionally, we explore the mediating role of tau deposition in sleep duration-cognition and physical activity-cognition relationships. METHODS: This cross-sectional study obtained data from participants in the Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4) study, a randomized clinical trial. In trial screening, cognitively unimpaired participants (age 65-85 years) underwent amyloid PET and brain MRI; APOE genotype and lifestyle questionnaire data were obtained. Cognitive performance was assessed using the Preclinical Alzheimer Cognitive Composite (PACC). Self-reported nightly sleep duration and weekly physical activity were the primary predictors. Regional Aß and tau pathologies and volumes were the proposed variables influencing relationships between sleep duration or physical activity and cognition. RESULTS: Aß data were obtained from 4322 participants (1208 with MRI, 59% female, 29% amyloid positive). Sleep duration was associated with a Aß composite score (ß = -0.005, CI: (-0.01, -0.001)) and Aß burden in the anterior cingulate (ACC) (ß = -0.012, CI: (-0.017, -0.006)) and medial orbitofrontal cortices (MOC) (ß = -0.009, CI: (-0.014, -0.005)). Composite (ß = -1.54, 95% CI:(-1.93, -1.15)), ACC (ß = -1.22, CI:(-1.54, -0.90)) and MOC (ß = -1.44, CI:(-1.86, -1.02)) Aß deposition was associated with PACC. Sleep duration-PACC association was explained by Aß burden in path analyses. Physical activity was associated with hippocampal (ß = 10.57, CI: (1.06, 20.08)), parahippocampal (ß = 9.3, CI: (1.69, 16.91)), entorhinal (ß = 14.68, CI: (1.75, 27.61), and fusiform gyral (ß = 38.38, CI: (5.57, 71.18)) volumes, which were positively associated with PACC (p < 0.02 for hippocampus, entorhinal cortex and fusiform gyrus). Physical activity-cognition relationship was explained by regional volumes. PET tau imaging was available for 443 participants. No direct sleep duration-tau burden, physical activity by tau burden, or mediation by regional tau was observed in sleep duration-cognition or physical activity-cognition relationships. DISCUSSION: Sleep duration and physical activity are associated with cognition through independent paths of brain Aß and brain volume, respectively. These findings implicate neural and pathological mechanisms for the relationships between sleep duration and physical activity on cognition. Dementia risk reduction approaches that emphasize the adequate sleep duration and a physically active lifestyle may benefit those with risk for Alzheimer's disease.

Decreased functional connectivity is associated with increased levels of Cerebral Spinal Fluid soluble-PDGFRß, a marker of blood brain barrier breakdown, in older adults.

Resting-state functional connectivity (FC) is suggested to be cross-sectionally associated with both vascular burden and Alzheimer's disease (AD) pathology. For instance, studies in pre-clinical AD subjects have shown increases of cerebral spinal fluid soluble platelet-derived growth factor receptor-ß (CSF sPDGFRß, a marker of BBB breakdown) but have not demonstrated if this vascular impairment affects neuronal dysfunction. It's possible that increased levels of sPDGFRß in the CSF may correlate with impaired FC in metabolically demanding brain regions (i.e. Default Mode Network, DMN). Our study aimed to investigate the relationship between these two markers in older individuals that were cognitively normal and had cognitive impairment. Eighty-nine older adults without dementia from the University of Southern California were selected from a larger cohort. Region of interest (ROI) to ROI analyses were conducted using DMN seed regions. Linear regression models measured significant associations between BOLD FC strength among seed-target regions and sPDGFRß values, while covarying for age and sex. Comparison of a composite ROI created by averaging FC values between seed and all target regions among cognitively normal and impaired individuals was also examined. Using CSF sPDGFRß as a biomarker of BBB breakdown, we report that increased breakdown correlated with decreased functional connectivity in DMN areas, specifically the PCC while the hippocampus exhibited an interaction effect using CDR score. We conclude that BBB breakdown as measured by CSF sPDGFRß affects neural networks resulting in decreased functional connections that leads to cognitive dysfunction.

Modeling ability to resist alcohol in the human laboratory: A pilot study.

Background: Roughly half of patients with alcohol use disorder prefer non-abstinence based approaches to treatment. However, only individuals who can limit their alcohol use after low-risk consumption are most likely to benefit from these approaches. This pilot study developed a laboratory-based intravenous alcohol self-administration paradigm to determine the characteristics of individuals who could successfully resist consuming alcohol after an initial exposure. Methods: Seventeen non-treatment seeking heavy drinkers completed two versions of an intravenous alcohol self-administration paradigm designed to assess impaired control over alcohol use. In the paradigm, participants received a priming dose of alcohol and then entered a 120-min resist phase, in which they received monetary rewards if they resisted self-administering alcohol. We used Cox proportional hazards regression to determine the impact of craving and Impaired Control Scale scores on rate of lapse. Results: 64.7% of participants across both versions of the paradigm were unable to resist alcohol for the duration of the session. Craving at baseline (HR = 1.07, 95% CI 1.01-1.13, p = 0.02) and following priming (HR = 1.08, 95% CI 1.02-1.15, p = 0.01) were associated with rate of lapse. Individuals who lapsed endorsed greater attempts to control their drinking over the prior six months compared to individuals who resisted. Conclusions: This study provides preliminary evidence that craving may be predictive of risk of lapse in individuals who are trying to limit alcohol intake after consuming a small initial amount of alcohol. Future studies should test this paradigm in a larger and more diverse sample.

Efecto del índice enfermera-paciente en la calidad de atención: estudio realizado en pacientes con enfermedades crónicodegenerativas en el servicio de medicina Interna / effect of contents nurse-patient quality of care: study in patients with chronic degenerative in internal medicine diseases

Los indicadores para determinar el número de personal de enfermería necesario deben responder a la demanda epidemiológica que caracteriza a nuestro país, dominada por enfermedades crónico-degenerativas que requieren un cuidado complejo que garantice la calidad de atención en salud y reduzca el riesgo de lesiones, maximizando la salud de los pacientes. La demanda de atención exige a las instituciones realizar la asignación del personal sin considerar la gravedad de la enfermedad, lo que puede alterar la calidad de atención. El objetivo de este trabajo fue evaluar, en un hospital de segundo nivel, la calidad de atención brindada a los pacientes con enfermedades crónico-degenerativas en relación al índice enfermera-paciente en medicina interna de atención. La metodología utilizada fue cuantitativa, longitudinal, prospectiva, no experimental, analítica y correlacional, en 47 pacientes por muestra probabilística. Por día se registró el índice real enfermera-paciente, se aplicó una cédula para valorar el estado integral del paciente a su ingreso y egreso, así como los cuidados de enfermería, utilizando los indicadores de calidad. El análisis se realizó con el Programa SPSS v20.0, e interpretación correlacional de Pearson y Spearman. Resultados: No se encontró ninguna asociación significativa (Rho Spearman = 0.00) entre la calidad de atención y los pacientes recibidos en el servicio, ni entre la calidad de atención y el personal promedio que labora en el Servicio de Medicina Interna. Conclusiones: Los indicadores establecidos por la Comisión Interinstitucional de Enfermería están basados en datos epidemiológicos de 1997, los cuales no responden al estándar de cuidado actualmente requerido

Indicators to determine the number of nurses needed, must respond to the epidemiological demand that characterizes our country that is dominated by chronic degenerative diseases requiring complex care, to ensure the quality of health care, reduce the risk of injuries, maximizing the health of patients. The demand for care requires institutions make the assignment of staff regardless of disease severity, such a situation may alter the quality of care provided to patients. The objective was to evaluate the quality of care provided to patients with chronic degenerative diseases relating to nurse patient ratio of internal medicine at a hospital in secondary care. The methodology used was quantitative, longitudinal, prospective, non-experimental, analytical and correlational, in 47 patients by probabilistic sample. By day the actual nurse-patient ratio were recorded,a charter was applied to assess the overall condition of the patient at admission and discharge, as well as nursing care, using quality indicators. The analysis was performed using SPSS v20.0 program, interpretation and correlation of Pearson and Spearman. Results: No significant association (Spearman Rho = 0.00) was not found between the quality of patient care and service received, or between quality of care and the average staff working in the Department of Internal Medicine. Conclusions: The indicators established by the Inter Nursing Facility, are based on epidemiological data from 1997, which do not respond to standard of care currently required

Occupational rhinoconjunctivitis and bronchial asthma due to Acalypha wilkesiana allergy.

BACKGROUND: Acalypha wilkesiana, or copperleaf, is a plant of the Euphorbiaceae family. Although it is widely known as an outdoor ornamental plant, no cases of A. wilkesiana allergy have been reported to date. OBJECTIVE: To describe a patient with occupational respiratory allergy to A. wilkesiana. METHODS: Extracts from A. wilkesiana leaves and flowers were used for skin prick testing, specific conjunctival and bronchial challenge tests, and in vitro studies. These studies range from A. wilkesiana specific IgE determination to sodium dodecyl sulfate-polyacrylamide gel electrophoresis immunodetection of A. wilkesiana protein bands in patient serum samples and immunoblot inhibition by preincubation with Salsola kali and Chenopodium album pollen extracts. RESULTS: Our patient had positive skin prick test reactions to A. wilkesiana leaf and flower extracts; negative reactions were found in a control group of 20 atopic patients. On immunodetection of A. wilkesiana extracts in patient serum samples, as many as 9 different IgE-binding proteins, with apparent molecular weights of 16 to 86 kDa, were revealed. Preincubation with S. kali and C. album pollen extracts completely inhibited IgE binding to the A. wilkesiana extract. Specific bronchial challenge resulted in a spirometric 30% decline in forced expiratory volume in 1 second with respect to baseline 1 minute after 1:100 (vol/vol) A. wilkesiana extract solution inhalation; 2 atopic controls had negative bronchial challenge test results. CONCLUSION: Acalypha wilkesiana is a new etiologic agent for IgE-mediated occupational respiratory allergy.

Safety of the new selective cyclooxygenase type 2 inhibitors rofecoxib and celecoxib in patients with anaphylactoid reactions to nonsteroidal anti-inflammatory drugs.

BACKGROUND: Controlled oral challenge with nonsteroidal anti-inflammatory drugs (NSAIDs) is the only definite way to detect safe NSAIDs in patients with NSAID-induced anaphylactoid reactions. OBJECTIVE: To evaluate the safety of the selective cyclooxygenase (COX) type 2 inhibitors rofecoxib and celecoxib in patients with single-reactive, NSAID-induced anaphylactoid reactions. METHODS: We prospectively conducted single-blind, placebo-controlled oral challenges (SBPCOCs) with rofecoxib and celecoxib in 33 patients with single-reactive, NSAID-induced anaphylactoid reactions. RESULTS: Nineteen women and 14 men (age range, 20-78 years; mean age, 44.8 years) exhibited anaphylactoid reactions on emergency department admission. Symptoms involved the skin (100%), laryngeal edema (73%), systolic hypotension (39%), and the gastrointestinal system (15%). The NSAIDs most frequently involved in the episodes were dipyrone (64%), propyphenazone (12%), and diclofenac (12%). In all patients, tolerance to a potent, nondiscriminatory COX inhibitor (except those reported as being responsible for the reaction) was noted. The SBPCOCs with the selective COX-2 inhibitors celecoxib and rofecoxib were well tolerated in all cases. Twenty-three patients who had an anaphylactoid reaction involving dipyrone and propyphenazone showed good tolerance to celecoxib (which contains a pyrazole group in its structure) on challenge. CONCLUSIONS: The SBPCOCs with highly selective COX-2 inhibitors were safe in patients with single-reactive, NSAID-induced anaphylactoid reactions, even in cases that involved pyrazole derivatives.

Genetic basis of the latex-fruit syndrome: association with HLA class II alleles in a Spanish population.

BACKGROUND: The latex-fruit syndrome is a well-defined disorder whose genetic background has not been elucidated. OBJECTIVE: To study the genetic basis of the latex-fruit syndrome. METHODS: In a case-control study, we have investigated a carefully selected group of patients allergic to latex, searching for association between latex-fruit allergy and HLA class I and II genes, HLA-DR functional groups, and markers IL4-R1 and FcepsilonRI-betaca . RESULTS: Seventy-eight patients allergic to latex without spina bifida, 33% of them also allergic to fruits, were included in our protocol. Skin prick test results with both a commercial latex extract and purified hevein were significantly greater in patients allergic to latex and fruit than in patients allergic to latex and not fruit. A cutoff point of >7 mm for commercial latex skin prick test diagnosed latex-fruit allergy with a sensitivity of 66.7% (95% CI, 41.0-86.6) and a specificity of 83.3% (95% CI, 68.6-93.0) in our series of patients. No significant differences were found regarding HLA class I, IL4-R1 , or FcepsilonRI-betaca allele distributions. However, comparison of HLA class II allelic frequencies between patients allergic to latex and fruit and patients allergic to latex and not fruit showed significant associations of latex-fruit allergy with DQB1 *0201 (corrected P value, .001; odds ratio, 7.3; 95% CI, 2.6-20.0), as well as with HLA-DR functional group E (corrected P value, .028; odds ratio, 16.0; 95% CI, 1.9-134.1). When comparing allelic distribution among different subgroups of patients allergic to latex, additional significant associations of latex-fruit allergy with DRB1 *0301 and *0901, and of latex and not fruit allergy with DQB1 *0202, DRB1 *0701 and *1101, were demonstrated. CONCLUSIONS: Latex-fruit allergy is associated with HLA-DQB1 *0201, DRB1 *0301, and *0901, as well as with HLA-DR functional group E, whereas latex-not-fruit allergy is associated with DQB1 *0202, and with both DRB1 *0701 and *1101 alleles.

Sputum eosinophilia and maximal airway narrowing in Dermatophagoides pteronyssinus allergic rhinitis patients: only rhinitis or rhinitis plus mild asthma?

STUDY OBJECTIVE: To study the existence of bronchial disease among rhinitis patients. To evaluate the laboratory test or set of tests (ie, symptoms, exposure, and sensitization to the allergen, and the provocative dose of methacholine [Mth] causing a 20% fall in FEV(1) [PD(20)] and the maximal response plateau [MRP] to Mth) that best identifies a case of mild asthma. DESIGN: Cross-sectional analysis in 52 Dermatophagoides pteronyssinus-monosensitized patients who were consulting a physician for perennial rhinitis. SETTING: Allergy Department, Hospital Doctor Negrín, Las Palmas, Grand Canary Island, Spain. INTERVENTIONS AND MEASUREMENTS: Patients filled out a standardized asthma symptom questionnaire, and underwent sputum induction and Mth challenge in which 40% falls in FEV(1) were attained. Dose-response curves were expressed in terms of both PD(20) values and the level of the MRP. D pteronyssinus allergen exposure was assessed in dust samples from patients' beds. RESULTS: No difference between patients who positively responded to the questionnaire and those who did not was observed. Mth-PD(20) values were not detected in 13% of the patients reporting bronchial symptoms, and an MRP was not identified in 59% of the subjects who did not respond positively. A higher degree of allergen sensitization (ascertained from skin test results, and total and specific serum IgE levels) and higher degree of sputum eosinophilia were detected in subjects in whom an MRP had not been identified. The presence of sputum eosinophilia provided the best differentiation between those patients who presented with an MRP and those who did not. CONCLUSION: The individual perception of bronchial symptoms is highly variable among perennial allergic rhinitis patients. The lack of a maximal airway-narrowing plateau is related to the presence of sputum eosinophilia, which might be useful in the detection of patients susceptible to anti-inflammatory therapy. Prospective studies evaluating whether these patients are more likely to develop symptomatic asthma in the future and if the early anti-inflammatory treatment prevents its development are needed.