RESUMEN
BACKGROUND: Peripheral blood transcriptome signatures that distinguish active pulmonary tuberculosis (TB) from control groups have been reported, but correlations of these signatures with sputum mycobacterial load are incompletely defined. METHODS: We assessed the performance of published TB transcriptomic signatures in Haiti, and identified transcriptomic biomarkers of TB bacterial load in sputum as measured by Xpert® MTB/RIF molecular testing. People in Port au Prince, Haiti, with untreated pulmonary TB (n = 51) formed the study cohort: 19 people with low and 32 with high sputum Mycobacterium tuberculosis load. Peripheral whole blood transcriptomes were generated using RNA sequencing. RESULTS: Twenty of the differentially expressed transcripts in TB vs. no TB were differentially expressed in people with low vs. high sputum mycobacterial loads. The difference between low and high bacterial load groups was independent of radiographic severity. In a published data set of transcriptomic response to anti-tuberculosis treatment, this 20-gene subset was more treatment-responsive at 6 months than the full active TB signature. CONCLUSION: We identified genes whose transcript levels in the blood distinguish active TB with high vs. low M. tuberculosis loads in the sputum. These transcripts may reveal mechanisms of mycobacterial control of M. tuberculosis during active infection, as well as identifying potential biomarkers for bacterial response to anti-tuberculosis treatment.
Asunto(s)
Mycobacterium tuberculosis/genética , Esputo/microbiología , Transcriptoma , Tuberculosis Pulmonar/diagnóstico , Adulto , Carga Bacteriana , Biomarcadores/sangre , Estudios de Casos y Controles , Femenino , Haití , Humanos , Masculino , Mycobacterium tuberculosis/aislamiento & purificación , Sensibilidad y Especificidad , Análisis de Secuencia de ARNRESUMEN
OBJECTIVE: To assess sex and ethnic differences in hyperinsulinemia/insulin resistance and to examine the impact of percent body fat on such differences. RESEARCH DESIGN AND METHODS: A cross-sectional epidemiological study was performed in a normoglycemic population of African-Americans (n = 159), Cuban Americans (n = 128), and non-Hispanic whites (n = 207) who resided in Dade County, Florida, from 1990 to 1995. The insulin area under the curve (AUC) in response to a standard 75-g oral glucose tolerance test (OGTT) was used as an indicator of hyperinsulinemia/insulin resistance. Analysis of covariance was performed to compare sex and ethnic differences in the insulin AUC. Multiple linear regression was used to evaluate the independent correlates of the insulin AUC. RESULTS: After covariate adjustment for percent body fat, men displayed a significantly higher insulin AUC than did women (P < 0.001). African-Americans and Cuban-Americans each had a significantly higher insulin AUC than did non-Hispanic white participants (P = 0.01). Alcohol consumption was inversely related to AUC (P = 0.04). CONCLUSIONS: Despite the greater percentage of body fat in women, the insulin AUC was similar in women and men. After adjustment for the sex difference in percent body fat, women displayed a lower insulin AUC than did men, indicating enhanced insulin sensitivity. These differences by sex and ethnicity in insulin resistance are consistent with established differences in heart-disease risk (i.e., higher in men and African-Americans) and suggest that hyperinsulinemia/insulin resistance may partly underlie such differences.
Asunto(s)
Glucemia/análisis , Composición Corporal , Hiperinsulinismo/diagnóstico , Resistencia a la Insulina/fisiología , Insulina/sangre , Adulto , Población Negra , Glucemia/metabolismo , Estudios de Cohortes , Estudios Transversales , Cuba/etnología , Femenino , Florida , Prueba de Tolerancia a la Glucosa , Hispánicos o Latinos , Humanos , Hiperinsulinismo/sangre , Hiperinsulinismo/etnología , Insulina/metabolismo , Modelos Lineales , Masculino , Factores Sexuales , Población BlancaRESUMEN
The South Florida Program on Aging and Health was initiated in 1992 with the aim to assess physical and mental health of the elderly in Dade County and provide a basis for public health policy. This report describes the methodology applied in the study and preliminary screening results in a probability sample of 2,400 African American, Cuban American and white non-Hispanic American elderly men and women. Of 2,013 participants screened by May 1995, 11.5% had cognitive impairment. An increase in prevalence from 4-7% to 25-36% with advancing age was found among men and women of each group, from the youngest (65-74) to the oldest (85+ years). Male and female prevalences were similar but vary by ethnic group and age.
Asunto(s)
Enfermedad de Alzheimer/epidemiología , Etnicidad/estadística & datos numéricos , Negro o Afroamericano/estadística & datos numéricos , Factores de Edad , Anciano , Anciano de 80 o más Años , Envejecimiento , Enfermedad de Alzheimer/prevención & control , Trastornos del Conocimiento/epidemiología , Trastornos del Conocimiento/prevención & control , Cuba/etnología , Femenino , Florida/epidemiología , Salud , Hispánicos o Latinos/estadística & datos numéricos , Humanos , Masculino , Tamizaje Masivo , Prevalencia , Salud Pública , Política Pública , Población Blanca/estadística & datos numéricosRESUMEN
Spectroscopic evidence is presented for the lack of intramolecular hydrogen bonding in a simple peptide derivative of 5,5-dimethylthiazolidine-4-carboxylic acid (Dtc). The infrared spectrum of Boc-Pro-Ile-OMe 1 in nonpolar solvents displays two N-H stretching bands at 3419 and 3330 cm-1 in CCl4 and one at 3417 and 3328 cm-1 in CHCl3. The low frequency band at 3328-3330 cm-1 may be assigned to conformations with an intramolecular hydrogen bond between the Ile N-H and Boc C = O. The band at 3417-3419 cm-1 is the normal Ile N-H stretch. In the polar solvent CH3CN only one NH stretching band at 3365 cm-1 is observed. The IR spectrum of Boc-Dtc-Ile-OMe 2, on the other hand, displays one N-H stretching band at 3423 cm-1 in CCl4 and one at 3418 cm-1 in CHCl3. The IR spectrum of 2 does not display the N-H stretching band that would arise from intramolecular hydrogen bonding between the Boc C = O and Ile N-H. The lack of intramolecular hydrogen bonding for Boc-Dtc-Ile-OMe 2 was evident also in the NMR spectra in nonpolar solvents. The 1H-NMR spectrum of the Pro dipeptide 1 in 50% CDCl3/C6D6 at 20 degrees displayed two Ile-NH signals at 6.58 and 7.74 ppm. The latter signal corresponds to the intramolecularly hydrogen bonded Ile-NH in the trans-Boc isomer of 1 (60% of the total population), while the former signal corresponds to the nonhydrogen bonded Ile-NH in the cis-Boc isomer.(ABSTRACT TRUNCATED AT 250 WORDS)