N-Acetylcysteine reduces hyperacute intermittent hypoxia-induced sympathoexcitation in human subjects.

NEW FINDINGS: What is the central question of this study? This study evaluated the following central question: does N-acetylcysteine (N-AC), an antioxidant that readily penetrates the blood-brain barrier, have the capability to reduce the increase in sympathetic nerve activity observed during hyperacute intermittent hypoxia? What is the main finding and its importance? We demonstrate that N-AC decreases muscle sympathetic nerve activity in response to hyperacute intermittent hypoxia versus placebo control. This finding suggests that antioxidants, such as N-AC, have therapeutic potential in obstructive sleep apnoea. This investigation tested the following hypotheses: that (i) N-acetylcysteine (N-AC) attenuates hyperacute intermittent hypoxia-induced sympathoexcitation, (ii) without elevating superoxide measured in peripheral venous blood. Twenty-eight healthy human subjects were recruited to the study. One hour before experimentation, each subject randomly ingested either 70 mg kg(-1) of N-AC (n = 16) or vehicle placebo (n = 12). Three-lead ECG and arterial blood pressure, muscle sympathetic nerve activity (n = 17) and whole-blood superoxide concentration (using electron paramagnetic resonance spectroscopy; n = 12) were measured. Subjects underwent a 20 min hyperacute intermittent hypoxia training (hAIHT) protocol that consisted of cyclical end-expiratory apnoeas with 100% nitrogen. N-AC decreased muscle sympathetic nerve activity after hAIHT compared with placebo (P < 0.02). However, N-AC did not alter superoxide concentrations in venous blood compared with placebo (P > 0.05). Moreover, hAIHT did not increase superoxide concentrations in the peripheral circulation as measured by electron paramagnetic resonance (P > 0.05). Based on these findings, we contend that (i) hAIHT and (ii) the actions of N-AC in hAIHT are primarily mediated centrally rather than peripherally, although central measurements of reactive oxygen species are difficult to obtain in human subjects, thus making this assertion difficult to verify. This investigation suggests the possibility of developing a pharmaceutical therapy to inhibit the sympathoexcitation associated with obstructive sleep apnoea.

West Nile virus infection incidence based on donated blood samples and neuroinvasive disease reports, Northern Texas, USA, 2012.

During the 2012 outbreak of West Nile virus in the United States, approximately one third of the cases were in Texas. Of those, about half occurred in northern Texas. Models based on infected blood donors and persons with neuroinvasive disease showed, respectively, that ≈0.72% and 1.98% of persons in northern Texas became infected.

Two-week normobaric intermittent hypoxia exposures enhance oxyhemoglobin equilibrium and cardiac responses during hypoxemia.

Intermittent hypoxia (IH) is extensively applied to challenge cardiovascular and respiratory function, and to induce physiological acclimatization. The purpose of this study was to test the hypothesis that oxyhemoglobin equilibrium and tachycardiac responses during hypoxemia were enhanced after 14-day IH exposures. Normobaric-poikilocapnic hypoxia was induced with inhalation of 10% O2 for 5-6 min interspersed with 4 min recovery on eight nonsmokers. Heart rate (HR), arterial O2 saturation (SaO 2), and end-tidal O2 (PetO 2) were continuously monitored during cyclic normoxia and hypoxia. These variables were compared during the first and fifth hypoxic bouts between day 1 and day 14. There was a rightward shift in the oxyhemoglobin equilibrium response following 14-day IH exposures, as indicated by the greater PetO 2 (an index of arterial Po2) at 50% of SaO 2 on day 14 compared with day 1 [33.9 ± 1.5 vs. 28.2 ± 1.3 mmHg (P = 0.005) during the first hypoxic bout and 39.4 ± 2.4 vs. 31.4 ± 1.5 mmHg (P = 0.006) during the fifth hypoxic bout] and by the augmented gains of ΔSaO 2/ΔPetO 2 (i.e., deoxygenation) during PetO 2 from 65 to 40 mmHg in the first (1.12 ± 0.08 vs. 0.80 ± 0.02%/mmHg, P = 0.001) and the fifth (1.76 ± 0.31 vs. 1.05 ± 0.06%/mmHg, P = 0.024) hypoxic bouts. Repetitive IH exposures attenuated (P = 0.049) the tachycardiac response to hypoxia while significantly enhancing normoxic R-R interval variability in low-frequency and high-frequency spectra without changes in arterial blood pressure at rest or during hypoxia. We conclude that 14-day IH exposures enhance arterial O2 delivery and improve vagal control of HR during hypoxic hypoxemia.

Using modified approaches on marginal regression analysis of longitudinal data with time-dependent covariates.

Quadratic inference functions (QIFs) and estimating equations using the conjugate gradient method (CGM) for fitting marginal models to longitudinal data show appealing features in improving the efficiency without making assumptions on the correlation structure. However, our simulation study shows that both methods produce biased and inefficient estimates of regression parameters when time-dependent covariates are present. In this paper, we extend both the QIF and CGM methods for fitting marginal models to longitudinal data with time-dependent covariates. The idea is to restrict the moment conditions to the ones that are only valid to certain types of time-dependent covariates. Our simulations show that efficiency on estimating regression parameters is achieved using modified approaches. Furthermore, we apply the modified approach to anthropometric screening data to evaluate the association between body mass index and morbidity in children in the Philippines.

Exposure to Helicobacter pylori-positive siblings and persistence of Helicobacter pylori infection in early childhood.

OBJECTIVES: Cross-sectional studies suggest that Helicobacter pylori may be transmitted between siblings. The present study aimed to estimate the effect of an H pylori-infected sibling on the establishment of a persistent H pylori infection. MATERIALS AND METHODS: The authors used data collected from a Texas-Mexico border population from 1998 to 2005 (the "Pasitos Cohort Study"). Starting at age 6 months, H pylori and factors thought to be associated with H pylori were ascertained every 6 months for participants and their younger siblings. Hazard ratios were estimated from proportional hazards regression models with household-dependent modeling. RESULTS: Persistent H pylori infection in older siblings always preceded persistent infection in younger siblings. After controlling for mother's H pylori status, breast-feeding, antibiotic use, and socioeconomic factors, a strong effect was estimated for persistent H pylori infection in an older sibling on persistent infection in a younger sibling (hazard ratio 7.6, 95% confidence interval 1.6-37], especially when the difference in the age of the siblings was less than or equal to 3 years (hazard ratio 16, 95% confidence interval 2.5-112). CONCLUSIONS: These results suggest that when siblings are close in age, the older sibling may be an important source of H pylori transmission for younger siblings.

Intermittent Hypoxia Training for Treating Mild Cognitive Impairment: A Pilot Study.

Although intermittent hypoxia training (IHT) has proven effective against various clinical disorders, its impact on mild cognitive impairment (MCI) is unknown. This pilot study examined IHT's safety and therapeutic efficacy in elderly patients with amnestic MCI (aMCI). Seven patients with aMCI (age 69 ± 3 years) alternately breathed 10% O2 and room-air, each 5 minutes, for 8 cycles/session, 3 sessions/wk for 8 weeks. The patients' resting arterial pressures fell by 5 to 7 mm Hg (P < .05) and cerebral tissue oxygenation increased (P < .05) following IHT. Intermittent hypoxia training enhanced hypoxemia-induced cerebral vasodilation (P < .05) and improved mini-mental state examination and digit span scores from 25.7 ± 0.4 to 27.7 ± 0.6 (P = .038) and from 24.7 ± 1.2 to 26.1 ± 1.3 (P = .047), respectively. California verbal learning test score tended to increase (P = .102), but trail making test-B and controlled oral word association test scores were unchanged. Adaptation to moderate IHT may enhance cerebral oxygenation and hypoxia-induced cerebrovasodilation while improving short-term memory and attention in elderly patients with aMCI.

Trends in Magnesium Intake among Hispanic Adults, the National Health and Nutrition Examination Survey (NHANES) 1999-2014.

This study aimed at examining trends in magnesium intake among U.S. Hispanic adults stratified by gender, Hispanic origins, age, and poverty income ratio (PIR) level. Data on 9304 Hispanic adults aged ≥20 years from eight National Health and Nutrition Examination Survey (NHANES) cycles (1999-2014) were included in this study. For each cycle, survey-weighted mean dietary and total magnesium intakes were estimated. The prevalence of dietary and total magnesium intake below the Recommended Dietary Allowance (RDA) was further estimated stratified by gender and age groups. Linear regression was used to test trend. Over the survey cycles, both dietary and total magnesium intakes were significantly increased among Hispanic adults. In the study period, magnesium intake tended to be lower in females, adults in other Hispanic-origin group, those aged ≥65 years old, and those with a PIR <1.0. The prevalence of magnesium intake inadequacy decreased among Hispanic adults; however, more than 70% of Hispanic males and females continued to have magnesium intake below the RDA in 2013-2014. From 1999/2000 to 2013/2014, despite several improvements in magnesium intake having been identified, additional findings showed insufficient intake in Hispanic males and females, suggesting the need to improve magnesium intake through diet and dietary supplementation for U.S. Hispanics.

Comparison of Dietary Micronutrient Intakes by Body Weight Status among Mexican-American and Non-Hispanic Black Women Aged 19-39 Years: An Analysis of NHANES 2003-2014.

The objective of the current study was to examine micronutrient intake from foods in women of childbearing age and to better understand potential nutritional problems varied by body weight status in minority women. A sample of women aged 19-39 years from the National Health and Nutrition Examination Surveys (NHANES) 2003-2014 was analyzed. Dietary intakes of 13 micronutrients were estimated using the National Cancer Institute method. Mexican-American and non-Hispanic Black women were categorized into normal/under-weight, overweight, or obese groups according to their body mass index (BMI). Mexican-American and non-Hispanic Black women had lower dietary intakes for vitamins A, B2, B6, B12, and D, folate, calcium, and magnesium than non-Hispanic Whites. Among Mexican-Americans, obese women had the lowest dietary intake of vitamins A, B2, C and D. Obese non-Hispanic Black women had significantly lower dietary intakes of iron and zinc than their normal/under-weight counterparts. Comparable percentages (>30%) of Mexican-American and non-Hispanic Black women had dietary intake less than the Estimated Average Requirements (EARs) for several key nutrients including vitamin A, C and D, folate, calcium and magnesium, and the percentages varied by body weight status. These results indicate micronutrient inadequacies persist among and within racial/ethnic and body weight groups.

Physically active lifestyle enhances vagal-cardiac function but not central autonomic neural interaction in elderly humans.

UNLABELLED: The cause of the age-related impairment of arterial baroreflex function remains ill-defined; moreover, it is unknown whether this impairment results from aging per se or from an inactive lifestyle associated with aging. In this study, we sought to: 1) determine whether elderly individuals who maintained an active lifestyle had an enhanced carotid baroreflex function as compared with their sedentary counterparts; and 2) determine whether this difference was due in part to altered function of the arterial baroreceptor and/or altered central modulation. Eight healthy, sedentary (SED, 68+/-2 yr) and eight physically active (ACT, 68+/-1 yr) elderly men with peak O(2) consumption 25.5+/-1.2 vs 35.7+/-2.4 ml/min/kg (P<0.01), respectively, were assessed with carotid baroreceptor (CBR) function using 5s pulses of neck pressure or suction (ranging from +40 to -80 Torr) delivered to the carotid sinus region at rest and during lower body negative pressure (LBNP) of -15 and -40 Torr. Changes in heart rate (HR) and mean arterial pressure (MAP) were assessed for CBR-HR and CBR-MAP gains, respectively. Overall CBR-HR gains in a range of approximately 120 mmHg of carotid sinus pressure were greater (P<0.01) in ACT than SED at rest and during LBNP. The derived peak CBR-HR slopes between ACT and SED at rest were -0.32+/-0.07 vs -0.11+/-0.02 bpm/mmHg (P=0.007), respectively. However, there was no statistical difference (P=0.37) in CBR-MAP gains between the groups. Neither CBR-MAP (P=0.08) nor CBR-HR (P=0.41) gain was augmented by LBNP in the elderly. CONCLUSION: Active lifestyle enhances the CBR-HR reflex sensitivity as a result of the improved vagal-cardiac function in elderly people. Aging is associated with an absence of central autonomic interaction in the control of blood pressure regardless of physical fitness.

Aerobic Exercise Training Improves Orthostatic Tolerance in Aging Humans.

PURPOSE: This study was designed to test the hypothesis that aerobic exercise training of the elderly will increase aerobic fitness without compromising orthostatic tolerance (OT). METHODS: Eight healthy sedentary volunteers (67.0 ± 1.7 yr old, four women) participated in 1 yr of endurance exercise training (stationary bicycle and/or treadmill) program at the individuals' 65%-75% of HRpeak. Peak O2 uptake (V˙O2peak) and HRpeak were determined by a maximal exercise stress test using a bicycle ergometer. Carotid baroreceptor reflex (CBR) control of HR and mean arterial pressure (MAP) were assessed by a neck pressure-neck suction protocol. Each subject's maximal gain (Gmax), or sensitivity, of the CBR function curves were derived from fitting their reflex HR and MAP responses to the corresponding neck pressure-neck suction stimuli using a logistic function curve. The subjects' OT was assessed using lower-body negative pressure (LBNP) graded to -50 mm Hg; the sum of the product of LBNP intensity and time (mm Hg·min) was calculated as the cumulative stress index. RESULTS: Training increased V˙O2peak (before vs after: 22.8 ± 0.92 vs 27.9 ± 1.33 mL·min·kg, P < 0.01) and HRpeak (154 ± 4 vs 159 ± 3 bpm, P < 0.02) and decreased resting HR (65 ± 5 vs 59 ± 5 bpm, P < 0.02) and MAP (99 ± 2 vs 87 ± 2 mm Hg, P < 0.05). CBR stimulus-response curves identified a leftward shift with an increase in CBR-HR Gmax (from -0.13 ± 0.02 to -0.27 ± 0.04 bpm·mm Hg, P = 0.01). Cumulative stress index was increased from 767 ± 68 mm Hg·min pretraining to 946 ± 44 mm Hg·min posttraining (P < 0.05). CONCLUSION: Aerobic exercise training improved the aerobic fitness and OT in elderly subjects. An improved OT is likely associated with an enhanced CBR function that has been reset to better maintain cerebral perfusion and cerebral tissue oxygenation during LBNP.

Enhanced cerebral perfusion during brief exposures to cyclic intermittent hypoxemia.

Cerebral vasodilation and increased cerebral oxygen extraction help maintain cerebral oxygen uptake in the face of hypoxemia. This study examined cerebrovascular responses to intermittent hypoxemia in eight healthy men breathing 10% O2 for 5 cycles, each 6 min, interspersed with 4 min of room air breathing. Hypoxia exposures raised heart rate ( P < 0.01) without altering arterial pressure, and increased ventilation ( P < 0.01) by expanding tidal volume. Arterial oxygen saturation ([Formula: see text]) and cerebral tissue oxygenation ([Formula: see text]) fell ( P < 0.01) less appreciably in the first bout (from 97.0 ± 0.3% and 72.8 ± 1.6% to 75.5 ± 0.9% and 54.5 ± 0.9%, respectively) than the fifth bout (from 94.9 ± 0.4% and 70.8 ± 1.0% to 66.7 ± 2.3% and 49.2 ± 1.5%, respectively). Flow velocity in the middle cerebral artery ( VMCA) and cerebrovascular conductance increased in a sigmoid fashion with decreases in [Formula: see text] and [Formula: see text]. These stimulus-response curves shifted leftward and upward from the first to the fifth hypoxia bouts; thus, the centering points fell from 79.2 ± 1.4 to 74.6 ± 1.1% ( P = 0.01) and from 59.8 ± 1.0 to 56.6 ± 0.3% ( P = 0.002), and the minimum VMCA increased from 54.0 ± 0.5 to 57.2 ± 0.5 cm/s ( P = 0.0001) and from 53.9 ± 0.5 to 57.1 ± 0.3 cm/s ( P = 0.0001) for the [Formula: see text]- VMCA and [Formula: see text]- VMCA curves, respectively. Cerebral oxygen extraction increased from prehypoxia 0.22 ± 0.01 to 0.25 ± 0.02 in minute 6 of the first hypoxia bout, and remained elevated between 0.25 ± 0.01 and 0.27 ± 0.01 throughout the fifth hypoxia bout. These results demonstrate that cerebral vasodilation combined with enhanced cerebral oxygen extraction fully compensated for decreased oxygen content during acute, cyclic hypoxemia. NEW & NOTEWORTHY Five bouts of 6-min intermittent hypoxia (IH) exposures to 10% O2 progressively reduce arterial oxygen saturation ([Formula: see text]) to 67% without causing discomfort or distress. Cerebrovascular responses to hypoxemia are dynamically reset over the course of a single IH session, such that threshold and saturation for cerebral vasodilations occurred at lower [Formula: see text] and cerebral tissue oxygenation ([Formula: see text]) during the fifth vs. first hypoxia bouts. Cerebral oxygen extraction is augmented during acute hypoxemia, which compensates for decreased arterial O2 content.

Calcium plus vitamin D supplementation and lung cancer incidence among postmenopausal women in the Women's Health Initiative.

BACKGROUND: Magnesium and calcium are antagonistic in many physiologic processes. However, few studies have investigated the associations of supplemental calcium with lung cancer risk taking this antagonism into account. We evaluated the effect of calcium and vitamin D supplementation on lung cancer incidence and explored whether the ratio of baseline calcium to magnesium (Ca:Mg) intake modifies the association in the Women's Health Initiative (WHI) calcium plus vitamin D supplementation (CaD) trial. METHODS: The intervention phase of the WHI CaD was a double-blinded, randomized, placebo-controlled trial in 36,382 postmenopausal women aged 50-79 years, recruited at 40U.S. centers. Post-intervention follow-up continued among 29,862 (86%) of the surviving participants. Risk of lung cancer in association with CaD supplementation was evaluated using proportional hazard regression models. RESULTS: After 11 years' cumulative follow-up, there were 207 lung cancers (incidence 0.11% per year) in the supplement arm and 241 (0.12%) in the placebo arm (hazard ratio (HR) for the intervention, 0.91; 95% confidence interval (CI), 0.71-1.17). Subgroup analyses suggested that the HR for lung cancer varied by baseline Ca:Mg intake ratio among women who were current smokers at enrollment (p=0.04 for interaction). CONCLUSIONS: Over the entire follow-up period, calcium and vitamin D supplementation did not reduce lung cancer incidence among postmenopausal women. In exploratory analyses, an interaction was found for the baseline Ca:Mg intake ratio on lung cancer among current smokers at the trial entry. This findings need to be further studied for the role of calcium with magnesium in lung carcinogenesis in current smokers.

Amplification and overexpression of topoisomerase IIalpha predict response to anthracycline-based therapy in locally advanced breast cancer.

PURPOSE: The putative association between erbB-2 overexpression and favorable response to anthracyline-based therapy in breast cancer is controversial, and the mechanism unclear. We sought to determine whether coamplification and overexpression of the topoisomerase IIalpha gene, near erbB-2 on chromosome 17, and a known anthracycline target, may underlie the association. EXPERIMENTAL DESIGN: Thirty-five patients who had locally advanced breast cancer (LABC) and who had received neoadjuvant, anthracycline-based therapy were studied. Copy number of topoisomerase IIalpha and erbB-2 was determined by fluorescence in situ hybridization, and expression by immunohistochemistry. RESULTS: Of 8 patients with erbB-2 amplification, 5 had a complete response (CR) or minimal residual disease (MRD), 3 had a partial response (PR), and none had stable (StD) or progressive disease (PD) at the time of mastectomy, versus 3 CR or MRD, 16 PR, and 8 StD or PD for patients without amplification (P = 0.008). In contrast, erbB-2 overexpression was not significantly associated with response (P = 0.114). Of 6 patients with topoisomerase IIalpha amplification, 4 had CR or MRD, 2 PR, and none StD or PD, versus 4 CR or MRD, 17 PR, and 8 StD or PD for patients without amplification (P = 0.034). All of the tumors with topoisomerase IIalpha amplification also had erbB-2 amplification, but not vice versa. Overexpression of topoisomerase IIalpha (9 patients) was also associated with favorable response (P = 0.021). CONCLUSIONS: Coamplification of erbB-2 and topoisomerase IIalpha is significantly associated with favorable local response to anthracycline-based therapy in LABC. The expression data favor a plausible mechanism based on topoisomerase IIalpha biology.

MSurvPow: a FORTRAN program to calculate the sample size and power for cluster-randomized clinical trials with survival outcomes.

Manatunga and Chen [A.K. Manatunga, S. Chen, Sample size estimation for survival outcomes in cluster-randomized studies with small cluster sizes, Biometrics 56 (2000) 616-621] proposed a method to estimate sample size and power for cluster-randomized studies where the primary outcome variable was survival time. The sample size formula was constructed by considering a bivariate marginal distribution (Clayton-Oakes model) with univariate exponential marginal distributions. In this paper, a user-friendly FORTRAN 90 program was provided to implement this method and a simple example was used to illustrate the features of the program.

Risky behaviors and factors associated with suicide attempt in adolescents.

The objective of this study was to identify the behavior risk factors associated with suicide attempt in adolescents and to determine gender-specific patterns of risk factors. In 2001, the Center for Disease Control and Prevention (CDC) conducted National Youth Risk Behavior Survey for 13,601 high school students in the U.S. Data were analyzed with logistic regressions to identify the risk behaviors. New significant risk factors (being offered illegal drugs at school, being abused by a boyfriend/girlfriend, gender, and ethnicity) were identified for suicidal attempt in adolescents. Patterns of risk behaviors differed among male and female groups. Several new risk behaviors associated with suicide attempt in adolescents were identified. There were notable differences in risk behaviors between two gender groups, especially in the area of depression. These findings could have potentially important implications for preventing adolescent suicide attempts.

Data quality assurance and quality control measures in large multicenter stroke trials: the African-American Antiplatelet Stroke Prevention Study experience.

Data quality assurance and quality control are critical to the effective conduct of a clinical trial. In the present commentary, we discuss our experience in a large, multicenter stroke trial. In addition to standard data quality control techniques, we have developed novel methods to enhance the entire process. Central to our methods is the use of clinical monitors who are trained in the techniques of data monitoring.

Associations of physical activity and dietary behaviors with children's health and academic problems.

BACKGROUND: We examined the associations of physical activities and dietary behaviors with children's health and academic-behavioral problems. METHODS: We employed a Community-wide Children's Health Assessment and Planning Survey to examine physical activity, healthy meals, health status, and academic-behavioral problems in 3708 children 7 to 14 years of age. Statistical associations were examined with chi-square test and logistic regression analysis; we calculated odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Among these children, 30.2% were overweight-obese, 11.0% had academic problems, and 7.9% had behavioral problems. Children classified as healthy eaters were more likely to exercise ≥4 days/week (79.1% vs 64.6%, OR: 2.08, 95% CI: 1.14 to 2.49), less likely to be overweight-obese (27.7% vs 44.6%, OR: 0.48, CI: 0.31 to 0.73), less likely to have academic problems (9.1% vs 16.1%, OR: 0.57, 95% CI: 0.41 to 0.79) and behavioral problems (6.9% vs 13.9%, OR: 0.46, 95% CI: 0.32 to 0.66) compared with their less healthy eating peers. Physical activity and healthy meals were associated with an improved health status (p < .001). However, the proportions of children taking unhealthy meals or choosing sedentary lifestyle increased as the cohorts progressed (p < .05) from childhood (7 to 8 years) to adolescence (13 to 14 years). CONCLUSIONS: Healthy (or unhealthy) lifestyle behaviors are significantly interrelated. Children who take healthy meals and exercise often are associated with better health and fewer academic and behavioral problems. Unfortunately, taking unhealthy meals and sedentary lifestyle characterize a growing proportion of young adolescents. Thus, curbing unhealthy lifestyle behaviors should start in early childhood.

Aging induced decline in T-lymphopoiesis is primarily dependent on status of progenitor niches in the bone marrow and thymus.

Age-related decline in the generation of T cells is associated with two primary lymphoid organs, the bone marrow (BM) and thymus. Both organs contain lympho-hematopoietic progenitor/stem cells (LPCs) and non-hematopoietic stromal/niche cells. Murine model showed this decline is not due to reduced quantities of LPCs, nor autonomous defects in LPCs, but rather defects in their niche cells. However, this viewpoint is challenged by the fact that aged BM progenitors have a myeloid skew. By grafting young wild-type (WT) BM progenitors into aged IL-7R-/- hosts, which possess WT-equivalent niches although LPCs are defect, we demonstrated that these young BM progenitors also exhibited a myeloid skew. We, further, demonstrated that aged BM progenitors, recruited by a grafted fetal thymus in the in vivo microenvironment, were able to compete with their young counterparts, although the in vitro manipulated old BM cells were not able to do so in conventional BM transplantation. Both LPCs and their niche cells inevitably get old with increasing organismal age, but aging in niche cells occurred much earlier than in LPCs by an observation in thymic T-lymphopoiesis. Therefore, the aging induced decline in competence to generate T cells is primarily dependent on status of the progenitor niche cells in the BM and thymus.

The impact of the 2002 Delaware smoking ordinance on heart attack and asthma.

In the United States, smoking is the leading cause of death - having a mortality rate of approximately 435,000 people in 2000-accounting for 8.1% of all US deaths recorded that year. Consequently, we analyzed the Delaware Hospital Discharge Database, and identified state and non-state residents discharged with AMI or asthma for the years 1999 to 2004. Statistical data analysis compared the incidence of AMI or asthma for each group before (1999-2002) and after (2003-2004) the amendment. As a result, we found that pre-ordinance and post-ordinance quarterly rates of AMI for Delaware residents were 451 (se = 21) and 430 (se = 21) respectively, representing a 4.7% reduction. Over the same time period, there was negligible change in the incidence of AMI for non-Delaware residents. After adjusting for population growth, the Risk Ratio (RR) for asthma in Delaware residents post-ordinance was 0.95 (95% CI, 0.90 to 0.999), which represented a significant reduction (P = 0.046). By comparison, non-Delaware residents had an increased RR for asthma post-ordinance of 1.62 (95% CI, 1.46 to 1.86; P < 0.0001).The results suggest that Delaware's comprehensive non-smoking ordinance effectively was associated with a statistically significant decrease in the incidence of AMI and asthma in Delaware residents when compared to non-Delaware residents.

Latent TB infection treatment acceptance and completion in the United States and Canada.

BACKGROUND: Treatment of latent TB infection (LTBI) is essential for preventing TB in North America, but acceptance and completion of this treatment have not been systematically assessed. METHODS: We performed a retrospective, randomized two-stage cross-sectional survey of treatment and completion of LTBI at public and private clinics in 19 regions of the United States and Canada in 2002. RESULTS: At 32 clinics that both performed tuberculin skin testing and offered treatment, 123 (17.1%; 95% CI, 14.5%-20.0%) of 720 subjects tested and offered treatment declined. Employees at health-care facilities were more likely to decline (odds ratio [OR], 4.74; 95% CI, 1.75-12.9; P = .003), whereas those in contact with a patient with TB were less likely to decline (OR, 0.19; 95% CI, 0.07-0.50; P = .001). At 68 clinics starting treatment regardless of where skin testing was performed, 1,045 (52.7%; 95% CI, 48.5%-56.8%) of 1,994 people starting treatment failed to complete the recommended course. Risk factors for failure to complete included starting the 9-month isoniazid regimen (OR, 2.08; 95% CI, 1.23-3.57), residence in a congregate setting (nursing home, shelter, or jail; OR, 2.94; 95% CI, 1.58-5.56), injection drug use (OR, 2.13; 95% CI, 1.04-4.35), age >or= 15 years (OR, 1.49; 95% CI, 1.14-1.94), and employment at a health-care facility (1.37; 95% CI, 1.00-1.85). CONCLUSIONS: Fewer than half of the people starting treatment of LTBI completed therapy. Shorter regimens and interventions targeting residents of congregate settings, injection drug users, and employees of health-care facilities are needed to increase completion.