C-reactive protein from dried blood spots: Application to household air pollution field studies.

Household air pollution (HAP) is estimated to be an important risk factor for cardiovascular disease, but little clinical evidence exists and collecting biomarkers of disease risk is difficult in low-resource settings. Among 54 Nicaraguan women with woodburning cookstoves, we evaluated cross-sectional associations between 48-hour measures of HAP (eg, fine particulate matter, PM2.5 ) and C-reactive protein (CRP) via dried blood spots; secondary analyses included seven additional biomarkers of systemic injury and inflammation. We conducted sub-studies to calculate the intraclass correlation coefficient (ICC) in biomarkers collected over four consecutive days in Nicaragua and to assess the validity of measuring biomarkers in dried blood by calculating the correlation with paired venous-drawn samples in Colorado. Measures of HAP were associated with CRP (eg, a 25% increase in indoor PM2.5 was associated with a 7.4% increase in CRP [95% confidence interval: 0.7, 14.5]). Most of the variability in CRP concentrations over the 4-day period was between-person (ICC: 0.88), and CRP concentrations were highly correlated between paired dried blood and venous-drawn serum (Spearman ρ = .96). Results for secondary biomarkers were primarily consistent with null associations, and the sub-study ICCs and correlations were lower. Assessing CRP via dried blood spots provides a feasible approach to elucidate the association between HAP and cardiovascular disease risk.

MC1R Variation in a New Mexico Population.

BACKGROUND: The Melanocortin 1 Receptor (MC1R) contributes to pigmentation, an important risk factor for developing melanoma. Evaluating SNPs in MC1R and association with race/ethnicity, skin type, and perceived cancer risk in a New Mexico (NM) population will elucidate the role of MC1R in a multicultural population. METHODS: We genotyped MC1R in 191 NMs attending a primary care clinic in Albuquerque. We obtained individuals' self-identified race/ethnicity, skin type, and perceived cancer risk. We defined genetic risk as carriage of any one or more of the nine most common SNPs in MC1R. RESULTS: We found that one MC1R SNP, R163Q (rs885479), was identified in 47.6% of self-identified Hispanics and 12.9% of non-Hispanic whites (NHW), making Hispanics at higher "genetic risk" (as defined by carrying one of the MC1R common variants). When we deleted R163Q from analyses, Hispanics were no longer at higher genetic risk (33.3%) compared with NHW (48.3%), consistent with melanoma rates, tanning ability, and lower perceived risk. Hispanics had a perceived risk significantly lower than NHW and a nonsignificant better tanning ability than NHW. CONCLUSIONS: The R163Q variant in MC1R may not be a risk factor for melanoma among NM Hispanics. This suggestion points to the need to carefully interpret genetic risk factors among specific populations. IMPACT: Genetic risk cannot be extrapolated from Northern European populations directly to non-European populations.

Identification and characterization of metabolite quantitative trait loci in tomato leaves and comparison with those reported for fruits and seeds.

INTRODUCTION: To date, most studies of natural variation and metabolite quantitative trait loci (mQTL) in tomato have focused on fruit metabolism, leaving aside the identification of genomic regions involved in the regulation of leaf metabolism. OBJECTIVE: This study was conducted to identify leaf mQTL in tomato and to assess the association of leaf metabolites and physiological traits with the metabolite levels from other tissues. METHODS: The analysis of components of leaf metabolism was performed by phenotypying 76 tomato ILs with chromosome segments of the wild species Solanum pennellii in the genetic background of a cultivated tomato (S. lycopersicum) variety M82. The plants were cultivated in two different environments in independent years and samples were harvested from mature leaves of non-flowering plants at the middle of the light period. The non-targeted metabolite profiling was obtained by gas chromatography time-of-flight mass spectrometry (GC-TOF-MS). With the data set obtained in this study and already published metabolomics data from seed and fruit, we performed QTL mapping, heritability and correlation analyses. RESULTS: Changes in metabolite contents were evident in the ILs that are potentially important with respect to stress responses and plant physiology. By analyzing the obtained data, we identified 42 positive and 76 negative mQTL involved in carbon and nitrogen metabolism. CONCLUSIONS: Overall, these findings allowed the identification of S. lycopersicum genome regions involved in the regulation of leaf primary carbon and nitrogen metabolism, as well as the association of leaf metabolites with metabolites from seeds and fruits.

Supplemental Oxygen Does Not Influence Self-selected Work Rate at Moderate Altitude.

INTRODUCTION: It is well known that supplemental oxygen can increase aerobic power output during high-intensity and/or maximal efforts at moderate altitude, yet the effects on self-selected work rate during lower-intensity, submaximal exercise are unknown. We reasoned that if the degree of arterial oxygen saturation (SaO2) influences teleoanticipatory regulation of power output, supplemental oxygen given at moderate altitude would increase average power output during exercise performed at self-selected work rates corresponding to RPE 9 (very light) and 13 (somewhat hard). METHODS: Twenty-three subjects (17 males, 6 females) completed one familiarization [fraction of inspired O2 (FIO2) = 0.209] and two blinded, experimental trials (FIO2 = 0.209 and FIO2 = 0.267). In each trial, subjects self-regulated their work rate on a cycle ergometer to maintain RPE 9 for 5 min and RPE 13 for 10 min, before performing an incremental step test to exhaustion (25 W·min). Oxygen consumption (V˙O2) and SaO2 via pulse oximetry (SpO2) were continuously monitored. Subjects were asked to guess the experimental condition after each stage of the protocol. RESULTS: Supplemental oxygen increased SpO2 throughout exercise (~4%; P < 0.001) and was associated with greater peak power output (4% ± 4%; P < 0.001) and V˙O2 (5% ± 10%; P = 0.010) during the incremental test, but did not increase average power output selected during exercise at RPE 9 (P = 0.235) or 13 (P = 0.992). Subjects were unable to perceive the difference in FIO2 at any stage (P > 0.14). CONCLUSIONS: Small increases in inspired oxygen concentration at moderate altitude are imperceptible and do not appear to influence selection of submaximal work rates at RPE ≤ 13.

Alternative stable states and the sustainability of forests, grasslands, and agriculture.

Endangered forest-grassland mosaics interspersed with expanding agriculture and silviculture occur across many parts of the world, including the southern Brazilian highlands. This natural mosaic ecosystem is thought to reflect alternative stable states driven by threshold responses of recruitment to fire and moisture regimes. The role of adaptive human behavior in such systems remains understudied, despite its pervasiveness and the fact that such ecosystems can exhibit complex dynamics. We develop a nonlinear mathematical model of coupled human-environment dynamics in mosaic systems and social processes regarding conservation and economic land valuation. Our objective is to better understand how the coupled dynamics respond to changes in ecological and social conditions. The model is parameterized with southern Brazilian data on mosaic ecology, land-use profits, and questionnaire results concerning landowner preferences and conservation values. We find that the mosaic presently resides at a crucial juncture where relatively small changes in social conditions can generate a wide variety of possible outcomes, including complete loss of mosaics; large-amplitude, long-term oscillations between land states that preclude ecosystem stability; and conservation of the mosaic even to the exclusion of agriculture/silviculture. In general, increasing the time horizon used for conservation decision making is more likely to maintain mosaic stability. In contrast, increasing the inherent conservation value of either forests or grasslands is more likely to induce large oscillations-especially for forests-due to feedback from rarity-based conservation decisions. Given the potential for complex dynamics, empirically grounded nonlinear dynamical models should play a larger role in policy formulation for human-environment mosaic ecosystems.

Landowner perceptions of the value of natural forest and natural grassland in a mosaic ecosystem in southern Brazil.

The forest-grassland mosaics of southern Brazil have been subject to many land use and policy changes over the decades. Like many grasslands around the world, the Campos grasslands are declining with few conservation efforts underway. In contrast, forests receive much attention and many incentives. It is hypothesized that perception of land cover has the potential to shape ecosystems. Here we conduct a questionnaire to further our understanding of decision-making practices that alter landscapes (Campos grassland, Araucaria forest, agriculture and plantation) and direct land policies in the region. Our analysis reveals that plantations are significantly less desirable than the other landscape types. However, plantation land use has increased by 87 % over the past few decades, as a result of industry and government incentives. The proportions of other landscape types have remained consistent over the past two decades. Restoration of native vegetation is not a priority of landowners and restoration would require a financial incentive.

Cytokines and tumor metastasis gene variants in oral cancer and precancer in Puerto Rico.

OBJECTIVES: A cross-sectional epidemiological study explored genetic susceptibility to oral precancer and cancer in Puerto Rico (PR). MATERIALS AND METHODS: Three hundred three individuals with a benign oral condition, oral precancer (oral epithelial hyperplasia/hyperkeratosis, oral epithelial dysplasia), or oral squamous cell carcinoma (SCCA) were identified via PR pathology laboratories. A standardized, structured questionnaire obtained information on epidemiological variables; buccal cells were collected for genetic analysis. Genotyping was performed using Taqman® assays. Allelic frequencies of single nucleotide polymorphisms (SNPs) were evaluated in cytokine genes and genes influencing tumor metastasis. Risk estimates for a diagnosis of oral precancer or SCCA while having a variant allele were generated using logistic regression. Adjusted models controlled for age, gender, ancestry, education, smoking and alcohol consumption. RESULTS: Relative to persons with a benign oral lesion, individuals with homozygous recessive allelic variants of tumor necrosis factor (TNF-α) -238 A/G SNP had a reduced odds of having an oral precancer (ORadjusted = 0.15; 95% CI 0.03-0.70). The transforming growth factor beta-1 (TGFß-1 -509 C/T) polymorphism was inversely associated with having an oral SCCA among persons homozygous for the recessive variant (ORcrude = 0.27; 95% CI 0.09-0.79). The matrix metalloproteinase gene (MMP-1) variant, rs5854, was associated with oral SCCA; participants with even one variant allele were more likely to have oral SCCA (ORadjusted = 2.62, 95% CI 1.05-6.53) compared to people with ancestral alleles. CONCLUSION: Our exploratory analyses suggest that genetic alterations in immune system genes and genes with metastatic potential are associated with oral precancer and SCCA risk in PR.

Toll-like receptor 4-dependent microglial activation mediates spinal cord ischemia-reperfusion injury.

BACKGROUND: Paraplegia continues to complicate thoracoabdominal aortic interventions. The elusive mechanism of spinal cord ischemia-reperfusion injury has delayed the development of pharmacological adjuncts. Microglia, the resident macrophages of the central nervous system, can have pathological responses after a variety of insults. This can occur through toll-like receptor 4 (TLR-4) in stroke models. We hypothesize that spinal cord ischemia-reperfusion injury after aortic occlusion results from TLR-4-mediated microglial activation in mice. METHODS AND RESULTS: TLR-4 mutant and wild-type mice underwent aortic occlusion for 5 minutes, followed by 60 hours of reperfusion when spinal cords were removed for analysis. Spinal cord cytokine production and microglial activation were assessed at 6 and 36 hours after surgery. Isolated microglia from mutant and wild-type mice were subjected to oxygen and glucose deprivation for 24 hours, after which the expression of TLR-4 and proinflammatory cytokines was analyzed. Mice without functional TLR-4 demonstrated decreased microglial activation and cytokine production and had preserved functional outcomes and neuronal viability after thoracic aortic occlusion. After oxygen and glucose deprivation, wild-type microglia had increased TLR-4 expression and production of proinflammatory cytokines. CONCLUSIONS: The absence of functional TLR-4 attenuated neuronal injury and microglial activation after thoracic aortic occlusion in mice. Furthermore, microglial upregulation of TLR-4 occurred after oxygen and glucose deprivation, and the absence of functional TLR-4 significantly attenuated the production of proinflammatory cytokines. In conclusion, TLR-4-mediated microglia activation in the spinal cord after aortic occlusion is critical in the mechanism of paraplegia after aortic cross-clamping and may provide targets for pharmacological intervention.

Self-reported ethnicity and genetic ancestry in relation to oral cancer and pre-cancer in Puerto Rico.

BACKGROUND: Hispanics are known to be an extremely diverse and genetically admixed ethnic group. The lack of methodologies to control for ethnicity and the unknown admixture in complex study populations of Hispanics has left a gap in understanding certain cancer disparity issues. Incidence rates for oral and pharyngeal cancer (OPC) in Puerto Rico are among the highest in the Western Hemisphere. We conducted an epidemiological study to examine risk and protective factors, in addition to possible genetic susceptibility components, for oral cancer and precancer in Puerto Rico. METHODOLOGY/PRINCIPAL FINDINGS: We recruited 310 Puerto Rico residents who had been diagnosed with either an incident oral squamous cell carcinoma, oral precancer, or benign oral condition. Participants completed an in-person interview and contributed buccal cells for DNA extraction. ABI Biosystem Taqman™ primer sets were used for genotyping 12 ancestry informative markers (AIMs). Ancestral group estimates were generated using maximum likelihood estimation software (LEADMIX), and additional principal component analysis was carried out to detect population substructures. We used unconditional logistic regression to assess the contribution of ancestry to the risk of being diagnosed with either an oral cancer or precancer while controlling for other potential confounders. The maximum likelihood estimates showed that study participants had a group average ancestry contribution of 69.9% European, 24.5% African, and 5.7% detectable Native American. The African and Indigenous American group estimates were significantly higher than anticipated. Neither self-identified ethnicity nor ancestry markers showed any significant associations with oral cancer/precancer risk in our study. CONCLUSIONS/SIGNIFICANCE: The application of ancestry informative markers (AIMs), specifically designed for Hispanics, suggests no hidden population substructure is present based on our sampling and provides a viable approach for the evaluation and control of ancestry in future studies involving Hispanic populations.

Seroprevalencia de los virus de las hepatitis A y B en grupos etarios de Costa Rica / Seroprevalence of viral hepatitis A y b in age groups of Costa Rica

Justificación y Objetivos: Debido a la persistencia de casos y brotes de hepatitis viral A y B en el país, junto a la observación de un aumento importante de infecciones por el tipo A en la población de adultos, se planteó la necesidad de establecer la prevalencia de estos dos tipos de hepatitis en diferentes grupos etarios en nuestro país. Métodos: La seroprevalencia de los virus de la hepatitis A (VHA) y de hepatitis B (VHB), fueron investigadas en 873 muestras de niños pre-escolares menores de 7 años de la encuesta nacional de nutrición en 1996; 614 niños escolares de 9 a 15 años de una encuesta de nutrición de la Universidad de Costa Rica realizada en 1997 y 996 muestras de adultos, estudiantes y funcionarios de esta misma universidad recolectadas en 1994. Las muestras se realizaron por anticuerpos totales contra el VHA (anti-VHA total), VHB antígeno de superficie (HBsAg) y anticuerpos totales contra la proteína del núcleo o "core" (anti-HBc total). Resultados: Se encontró un 6.8 por ciento, 13.2 por ciento y 71.7 por ciento de anti-VHA total en los preescolares, escolares y adultos, respectivamente, con una creciente prevalencia en relación con la edad. La prevalencia de estos anticuerpos en los escolares estuvo asociada con la escolaridad de los padres y su condición socioeconómica; siendo mayor cuando los padres tenían un menor nivel de escolaridad (24 por ciento con secundaria incompleta versus 7.6 por ciento con nivel educativo superior) y entre padres sin capacitación técnica o profesionales (16 por ciento versus 8.7 por ciento en los padres con estudios superiores). También se encontró una diferencia en la prevalencia de anti-VHA entre estudiantes de escuelas públicas (19.5 por ciento) versus privadas (6.9 por ciento). En los preescolares, el único grupo con representación estadística geográfica; la provincia de Guanacaste presentó un riesgo de 2 a 3 veces mayor de tener anticuerpos contra el VHA (21 por ciento) que los niños procedentes de otras provincias, lo cual es concordante con los datos relacionados con condiciones socioeconómicas más bajas, falta de agua potable, letrinización y hacinamiento en las áreas rurales. En cuanto a los marcadores de VHB, se encontró una prevalencia de 0.5 por ciento, 0.2 por ciento y 0.2 por ciento para HBsAg y 2.8 por ciento, 0.3 por ciento y 4.0 por ciento para el anti-HBc total en preescolares, escolares y adultos, respectivamente...

Prevalencia de marcadores de la hepatitis B en Zarcero / Prevalence of the hepatitis B in Zarcero

Se realiza una investigación en 105 pacientes cuyo lugar de nacimiento y residencia es el distrito de Zarcero con el objetivo fundamental de conocer la incidencia de positividad de marcadores contral la hepatitis B en el mes de agosto de 1994. Los pacientes que se sangraron para estas determinaciones realizadas por medio de EIA en los laboratorios de ICMRT-LSU fueron quienes consultaron al servicio de endoscopía digestiva. De los 105 pacientes, el 6,8 por ciento mencionaron antecedentes de transfusión y un 5,6 por ciento antecedentes de hepatitis, un 15 por ciento se declaró alcohólico. Dos terceras partes de los pacientes fueron mujeres y un 58 por ciento comprendidos entre las edades de 40 a 84 años. De los 105 pacientes el 0 por ciento mostró positividad para el HBsAg

Respuesta inmune humoral contra la vacuna del virus de hepatitis B H-B-Vax en el personal hospitalario / Immuno-Humoral response to Hepatitis B H-B-Vax vaccine in health care workers

Se hizo un estudio con 201 individuos sanos, trabajadores en el campo de la salud, para evaluar un programa de vacunación por hepatitis B en un hospital metropolitano. Para evaluar el contacto previo con el virus se hizo en forma concomitante a la primera dosis un examen serológico, encontrando una prevalencia de 12,4 por ciento de hepatitis B. De los 176 seronegativos, 68 completaron el esquema de tres dosis, a los 0,1 y 4 ó 6 meses. Un control efectuado a los 7 meses de la administración de la primera dosis reveló que 88,2 por ciento tenía niveles protectores (>10 mlU/ml) de anti-HBs, algunos alcanzando hasta 19.000 mlU/ml. A los tres años se controlan 11 que quedaron con el esquema incompleto (1 ó 2 dosis), y 9 de ellos presentaron niveles de 50 a 1041 mlU/ml, proporcional al número de dosis recibidas. Se reveló una respuesta protectora adecuada con el esquema de tres dosis, aunque 11,8 por ciento de los vacunados no respondieron. Se recomienda la administración de la vacuna a todo personal hospitalario con el esquema de tres dosis

Respuesta inmunehumoral contra la vacuna del virus de hepatitis B H-B-VAX en el personal hospitalario / Inmunehumoral response againt hepatitis B vaccines H-B-VAX in the hospital personnel

Se hizo un estudio con 201 individuos sanos, trabajadores en el campo de la salud, para evaluar un programa de vacunación por hepatitis B en un hospital metropolitano. Para evaluar el contacto previo con el virus se hizo en forma concomitante a la primera dosis un examen serológico, encontrando una prevalencia de 12,4 por ciento de hepatitis B. De los 176 seronegativos, 68 complementaron el esquema de tres dosis, a los 0,1 y 4 ó 6 meses. Un control efectuado a los 7 meses de la administración de la primera dosis reveló que 88, 2 por ciento tenía niveles protectores (>10 mlU/ml) de anti-HBs, algunos alcanzando hasta 19.000 mlU/ml. A los tres años se controlaron 11 que quedaron con el esquema incompleto (1 ó 2 dosis), y 9 de ellos presentaron niveles de 50 a 1041 mlU/ml, proporcional al número de dosis recibidas. Se reveló una respuesta protectora adecuada con el esquema de tres dosis, aunque 11, 8 por ciento de los vacunados no respondieron. Se recomienda la administración de la vacuna a todo personal hospitalario con el esquema de tres dosis (Rev. Cost. Cienc. Méd. 1988; 9(4): 41-7)