Modern theory of tuberculosis: culturomic analysis of its historical origin in Europe and North America.

INTRODUCTION: An historical account of the modern theory of tuberculosis (TB) using a culturomic analysis has not been studied. OBJECTIVE: To analyze, using culturomic methods, the history of our modern understanding of TB as a unitary disease. METHODS: A culturomic analysis of millions of digitized texts was undertaken to quantify 200-year trends in usage of the modern term tuberculosis and pre-modern terms consumptive, phthisis, and scrofula, and to correlate these trends with significant historical events. RESULTS: Our understanding of TB originated with Laënnec in Paris, who proposed that the seemingly disparate wasting conditions phthisis, scrofula, and consumption were each related to the same post-mortem anatomical sign: the tubercle. The term tuberculosis was coined by Schonlein in 1829, but the term's usage remained uncommon until Villemin's 1865 discovery that TB was a communicable disease, Koch's 1882 discovery of Mycobacterium tuberculosis, and Pasteur's 1884 discovery of a vaccine against another communicable disease, smallpox. CONCLUSION: Our modern understanding of TB as a unitary disease was embraced slowly. Acceptance required new terminology describing the idea, scientific confirmation that TB is an infectious disease, and evidence suggesting that it might be prevented. An innovative idea is not enough to induce widespread acceptance. The study illustrates how culturomic methods can be used to study the adoption and diffusion of an innovation, in this case the modern theory of TB.

Comparison of Surface Water Quality and Yields from Organically and Conventionally Produced Sweet Corn Plots with Conservation and Conventional Tillage.

Organic agricultural systems are often assumed to be more sustainable than conventional farming, yet there has been little work comparing surface water quality from organic and conventional production, especially under the same cropping sequence. Our objective was to compare nutrient and sediment losses, as well as sweet corn ( L. var. ) yield, from organic and conventional production with conventional and conservation tillage. The experiment was located in the Appalachian Mountains of North Carolina. Four treatments, replicated four times, had been in place for over 18 yr and consisted of conventional tillage (chisel plow and disk) with conventional production (CT/Conven), conservation no-till with conventional production (NT/Conven), conventional tillage with organic production (CT/Org), and conservation no-till with organic production (NT/Org). Water quality (surface flow volume; nitrogen, phosphorus, and sediment concentrations) and sweet corn yield data were collected in 2011 and 2012. Sediment and sediment-attached nutrient losses were influenced by tillage and cropping system in 2011, due to higher rainfall, and tillage in 2012. Soluble nutrients were affected by the nutrient source and rate, which are a function of the cropping system. Sweet corn marketable yields were greater in conventional systems due to high weed competition and reduced total nitrogen availability in organic treatments. When comparing treatment efficiency (yield kg ha /nutrient loss kg ha ), the NT/Conven treatment had the greatest sweet corn yield per unit of nutrient and sediment loss. Other treatment ratios were similar to each other; thus, it appears the most sustainably productive treatment was NT/Conven.

Prevalence of Adverse Pregnancy Outcomes, by Maternal Diabetes Status at First and Second Deliveries, Massachusetts, 1998-2007.

INTRODUCTION: Understanding patterns of diabetes prevalence and diabetes-related complications across pregnancies could inform chronic disease prevention efforts. We examined adverse birth outcomes by diabetes status among women with sequential, live singleton deliveries. METHODS: We used data from the 1998-2007 Massachusetts Pregnancy to Early Life Longitudinal Data System, a population-based cohort of deliveries. We restricted the sample to sets of parity 1 and 2 deliveries. We created 8 diabetes categories using gestational diabetes mellitus (GDM) and chronic diabetes mellitus (CDM) status for the 2 deliveries. Adverse outcomes included large for gestational age (LGA), macrosomia, preterm birth, and cesarean delivery. We computed prevalence estimates for each outcome by diabetes status. RESULTS: We identified 133,633 women with both parity 1 and 2 deliveries. Compared with women who had no diabetes in either pregnancy, women with GDM or CDM during any pregnancy had increased risk for adverse birth outcomes; the prevalence of adverse outcomes was higher in parity 1 deliveries among women with no diabetes in parity 1 and GDM in parity 2 (for LGA [8.5% vs 15.1%], macrosomia [9.7% vs. 14.9%], cesarean delivery [24.7% vs 31.3%], and preterm birth [7.7% vs 12.9%]); and higher in parity 2 deliveries among those with GDM in parity 1 and no diabetes in parity 2 (for LGA [12.3% vs 18.2%], macrosomia [12.3% vs 17.2%], and cesarean delivery [27.0% vs 37.9%]). CONCLUSIONS: Women with GDM during one of 2 sequential pregnancies had elevated risk for adverse outcomes in the unaffected pregnancy, whether the diabetes-affected pregnancy preceded or followed it.

Estimating the Recurrence Rate of Gestational Diabetes Mellitus (GDM) in Massachusetts 1998-2007: Methods and Findings.

OBJECTIVES: Women with gestational diabetes mellitus (GDM) may be able to reduce their risk of recurrent GDM and progression to type 2 diabetes mellitus through lifestyle change; however, there is limited population-based information on GDM recurrence rates. METHODS: We used data from a population of women delivering two sequential live singleton infants in Massachusetts (1998-2007) to estimate the prevalence of chronic diabetes mellitus (CDM) and GDM in parity one pregnancies and recurrence of GDM and progression from GDM to CDM in parity two pregnancies. We examined four diabetes classification approaches; birth certificate (BC) data alone, hospital discharge (HD) data alone, both sources hierarchically combined with a diagnosis of CDM from either source taking priority over a diagnosis of GDM, and both sources combined including only pregnancies with full agreement in diagnosis. Descriptive statistics were used to describe population characteristics, prevalence of CDM and GDM, and recurrence of diabetes in successive pregnancies. Diabetes classification agreement was assessed using the Kappa statistic. Associated maternal characteristics were examined through adjusted model-based t tests and Chi square tests. RESULTS: A total of 134,670 women with two sequential deliveries of parities one and two were identified. While there was only slight agreement on GDM classification across HD and BC records, estimates of GDM recurrence were fairly consistent; nearly half of women with GDM in their parity one pregnancy developed GDM in their subsequent pregnancy. While estimates of progression from GDM to CDM across sequential pregnancies were more variable, all approaches yielded estimates of ≤5 %. The development of either GDM or CDM following a parity one pregnancy with no diagnosis of diabetes was <3 % across approaches. Women with recurrent GDM were disproportionately older and foreign born. CONCLUSION: Recurrent GDM is a serious life course public health issue; the inter-pregnancy interval provides an important window for diabetes prevention.

Association of maternal body mass index, excessive weight gain, and gestational diabetes mellitus with large-for-gestational-age births.

OBJECTIVE: To estimate the percentage of large-for-gestational age (LGA) neonates associated with maternal overweight and obesity, excessive gestational weight gain, and gestational diabetes mellitus (GDM)-both individually and in combination-by race or ethnicity. METHODS: We analyzed 2004-2008 linked birth certificate and maternal hospital discharge data of live, singleton deliveries in Florida. We used multivariable logistic regression to assess the independent contributions of mother's prepregnancy body mass index (BMI), gestational weight gain, and GDM status on LGA (birth weight-for-gestational age 90 percentile or greater) risk by race and ethnicity while controlling for maternal age, nativity, and parity. We then calculated the adjusted population-attributable fraction of LGA neonates to each of these exposures. RESULTS: Large-for-gestational age prevalence was 5.7% among normal-weight women with adequate gestational weight gain and no GDM and 12.6%, 13.5% and 17.3% among women with BMIs of 25 or higher, excess gestational weight gain, and GDM, respectively. A reduction ranging between 46.8% in Asian and Pacific Islanders and 61.0% in non-Hispanic black women in LGA prevalence might result if women had none of the three exposures. For all race or ethnic groups, GDM contributed the least (2.0-8.0%), whereas excessive gestational weight gain contributed the most (33.3-37.7%) to LGA. CONCLUSION: Overweight and obesity, excessive gestational weight gain, and GDM all are associated with LGA; however, preventing excessive gestational weight gain has the greatest potential to reduce LGA risk.

Community and federal collaboration to assess pregnancy outcomes in Alaska Native women, 1997-2005.

The objectives are to report the estimated prevalence of pregnancy complications and adverse pregnancy outcomes in a defined population of Alaska Native women and also examine factors contributing to an intensive and successful collaboration between a tribal health center and the Centers for Disease Control and Prevention. Investigators abstracted medical record data from a random sample of singleton deliveries to residents of the study region occurring between 1997 and 2005. We used descriptive statistics to estimate the prevalence and 95% confidence intervals of selected pregnancy complications and adverse pregnancy outcomes. Records were examined for 505 pregnancies ending in a singleton delivery to 469 women. Pregnancy complication rates were 5.9% (95% CI 4.0, 8.4) for gestational diabetes mellitus, 6.1% (95% CI 4.2, 8.6%) for maternal chronic hypertension and 11.5% (95% CI 8.8, 14.6) for pregnancy associated hypertension, and 22.9% (95% CI 19.2-26.5 %) for anemia. The cesarean section rate was 5.5% (95% CI 3.5, 7.5) and 3.8% (95% CI 2.3, 5.8) of newborns weighed >4,500 g. Few previous studies reported pregnancy outcomes among Alaska Native women in a specific geographic region of Alaska and regarding the health needs in this population. We highlight components of our collaboration that contributed to the success of the study. Studies focusing on special populations such as Alaska Native women are feasible and can provide important information on health indicators at the local level.

Are gestational diabetes mellitus and preconception diabetes mellitus less common in non-Hispanic black women than in non-Hispanic white women?

Based on their higher risk of type 2 diabetes, non-Hispanic blacks (NHBs) would be expected to have higher gestational diabetes mellitus (GDM) risk compared to non-Hispanic whites (NHWs). However, previous studies have reported lower GDM risk in NHBs versus NHWs. We examined whether GDM risk was lower in NHBs and NHWs, and whether this disparity differed by age group. The cohort consisted of 462,296 live singleton births linked by birth certificate and hospital discharge data from 2004 to 2007 in Florida. Using multivariable regression models, we examined GDM risk stratified by age and adjusted for body mass index (BMI) and other covariates. Overall, NHBs had a lower prevalence of GDM (2.5 vs. 3.1%, p < 0.01) and a higher proportion of preconception DM births (0.5 vs. 0.3%, p ≤ 0.01) than NHWs. Among women in their teens (risk ratio 0.56, p < 0.01) and 20-29 years of age (risk ratio 0.85, p < 0.01), GDM risk was lower in NHBs than NHWs. These patterns did not change with adjustment for BMI and other covariates. Among women 30-39 years (risk ratio 1.18, p < 0.01) and ≥40 years (risk ratio 1.22, p < 0.01), GDM risk was higher in NHBs than NHWs, but risk was higher in NHWs after adjustment for BMI. Associations between BMI and GDM risk did not vary by race/ethnicity or age group. NHBs have lower risk of GDM than NHWs at younger ages, regardless of BMI. NHBs had higher risk than NHWs at older ages, largely due to racial/ethnic disparities in overweight/obesity at older ages.

Fraction of gestational diabetes mellitus attributable to overweight and obesity by race/ethnicity, California, 2007-2009.

OBJECTIVES: We calculated the racial/ethnic-specific percentages of gestational diabetes mellitus (GDM) attributable to overweight and obesity. METHODS: We analyzed 1 228 265 records of women aged 20 years or older with a live, singleton birth in California during 2007 to 2009. Using logistic regression, we estimated the magnitude of the association between prepregnancy body mass index and GDM and calculated the percentages of GDM attributable to overweight and obesity overall and by race/ethnicity. RESULTS: The overall estimated GDM prevalence ranged from 5.4% among White women to 11.9% among Asian/Pacific Islander women. The adjusted percentages of GDM deliveries attributable to overweight and obesity were 17.8% among Asians/Pacific Islander, 41.2% among White, 44.2% among Hispanic, 51.2% among Black, and 57.8% among American Indian women. Select Asian subgroups, such as Vietnamese (13.0%), Asian Indian (14.0%), and Filipino (14.2%), had the highest GDM prevalence, but the lowest percentage attributable to obesity. CONCLUSIONS: Elevated prepregnancy body mass index contributed to GDM in all racial/ethnic groups, which suggests that decreasing overweight and obesity among women of reproductive age could reduce GDM, associated delivery complications, and future risk of diabetes in both the mother and offspring.

Effects of maternal smokeless tobacco use on selected pregnancy outcomes in Alaska Native women: a case-control study.

OBJECTIVE: To examine the potential effects of prenatal smokeless tobacco use on selected birth outcomes. DESIGN: A population-based, case-control study using a retrospective medical record review. POPULATION: Singleton deliveries 1997-2005 to Alaska Native women residing in western Alaska. METHODS: Hospital discharge codes were used to identify potential case deliveries and a random control sample. Data on tobacco use and confirmation of pregnancy outcomes were abstracted from medical records for 1123 deliveries. Logistic regression was used to examine associations between tobacco use and pregnancy outcomes. Adjusted odds ratios (OR), 95% confidence intervals (95% CI), and p-values were calculated. MAIN OUTCOMES MEASURES: Preterm delivery, pregnancy-associated hypertension, and placental abruption. RESULTS: In unadjusted analysis, smokeless tobacco use was not significantly associated with preterm delivery (OR 1.44, 95% CI 0.97-2.15). After adjustment for parity, pre-pregnancy body mass index, and maternal age, the point estimate was attenuated and remained non-significant. No significant associations were observed between smokeless tobacco use and pregnancy-associated hypertension (adjusted OR 0.92, 95% CI 0.56-1.51) or placental abruption (adjusted OR 1.11, 95% CI 0.53-2.33). CONCLUSIONS: Prenatal smokeless tobacco use does not appear to reduce risk of pregnancy-associated hypertension or to substantially increase risk of abruption. An association between smokeless tobacco and preterm delivery could not be ruled out. Components in tobacco other than nicotine likely play a major role in decreased pre-eclampsia risk in smokers. Nicotine adversely affects fetal neurodevelopment and our results should not be construed to mean that smokeless tobacco use is safe during pregnancy.

Racial/ethnic differences in the prevalence of gestational diabetes mellitus and maternal overweight and obesity, by nativity, Florida, 2004-2007.

OBJECTIVE: We examined the risk of gestational diabetes mellitus (GDM) among foreign-born and U.S.-born mothers by race/ethnicity and BMI category. DESIGN AND METHOD: We used 2004-2007 linked birth certificate and maternal hospital discharge data of live, singleton deliveries in Florida to compare GDM risk among foreign-born and U.S.-born mothers by race/ethnicity and BMI category. We examined maternal BMI and controlled for maternal age, parity, and height. RESULTS: Overall, 22.4% of the women in our study were foreign born. The relative risk (RR) of GDM among women who were overweight or obese (BMI ≥ 25.0 kg m(-2)) was higher than among women with normal BMI (18.5-24.9 kg m(-2)) regardless of nativity, ranging from 1.3 (95% confidence interval (CI) = 1.0, 1.9) to 3.8 (95% CI = 2.1, 7.2).Foreign-born women also had a higher GDM risk than U.S.-born women, with RR ranging from 1.1 (95% CI = 1.1, 1.2) to 2.1 (95% CI = 1.4, 3.1). This finding was independent of BMI, age, parity, and height for all racial/ethnicity groups. CONCLUSIONS: Although we found differences in age, parity, and height by nativity, these differences did not substantially reduce the increased risk of GDM among foreign-born mothers. Health practitioners should be aware of and have a better understanding of how race/ethnicity and nativity can affect women with a high risk of GDM. Although BMI is a major risk factor for GDM, it does not appear to be associated with race/ethnicity or nativity.

Analysis of heavy-chain antibody responses and resistance to Parelaphostrongylus tenuis in experimentally infected alpacas.

The parasitic nematode Parelaphostrongylus tenuis is an important cause of neurologic disease of camelids in central and eastern North America. The aim of this study was to determine whether alpacas develop resistance to disease caused by P. tenuis in response to a previous infection or a combination of controlled infection and immunization. Alpacas were immunized with a homogenate of third-stage larvae (L3) and simultaneously implanted subcutaneously with diffusion chambers containing 20 live L3. Sham-treated animals received adjuvant alone and empty chambers. The protocol was not effective in inducing resistance to oral challenge with 10 L3, and disease developed between 60 and 71 days following infection. Immediately following the onset of neurologic disease, affected animals were treated with a regimen of anthelmintic and anti-inflammatory drugs, and all recovered. One year later, a subset of alpacas from this experiment was challenged with 20 L3 and the results showed that prior infection induced resistance to disease. Primary and secondary infections induced production of conventional and heavy-chain IgGs that reacted with soluble antigens in L3 homogenates but did not consistently recognize a recombinant form of a parasite-derived aspartyl protease inhibitor. Thus, the latter antigen may not be a good candidate for serology-based diagnostic tests. Antibody responses to parasite antigens occurred in the absence of overt disease, demonstrating that P. tenuis infection can be subclinical in a host that has been considered to be highly susceptible to disease. The potential for immunoprophylaxis to be effective in preventing disease caused by P. tenuis was supported by evidence of resistance to reinfection.

Racial/ethnic differences in the percentage of gestational diabetes mellitus cases attributable to overweight and obesity, Florida, 2004-2007.

INTRODUCTION: Gestational diabetes mellitus (GDM) affects 3% to 7% of pregnant women in the United States, and Asian, black, American Indian, and Hispanic women are at increased risk. Florida, the fourth most populous US state, has a high level of racial/ethnic diversity, providing the opportunity to examine variations in the contribution of maternal body mass index (BMI) status to GDM risk. The objective of this study was to estimate the race/ethnicity-specific percentage of GDM attributable to overweight and obesity in Florida. METHODS: We analyzed linked birth certificate and maternal hospital discharge data for live, singleton deliveries in Florida from 2004 through 2007. We used logistic regression to assess the independent contributions of women's prepregnancy BMI status to their GDM risk, by race/ethnicity, while controlling for maternal age and parity. We then calculated the adjusted population-attributable fraction of GDM cases attributable to overweight and obesity. RESULTS: The estimated GDM prevalence was 4.7% overall and ranged from 4.0% among non-Hispanic black women to 9.9% among Asian/Pacific Islander women. The probability of GDM increased with increasing BMI for all racial/ethnic groups. The fraction of GDM cases attributable to overweight and obesity was 41.1% overall, 15.1% among Asians/Pacific Islanders, 39.1% among Hispanics, 41.2% among non-Hispanic whites, 50.4% among non-Hispanic blacks, and 52.8% among American Indians. CONCLUSION: Although non-Hispanic black and American Indian women may benefit the most from prepregnancy reduction in obesity, interventions other than obesity prevention may be needed for women from other racial/ethnic groups.

Maternal smokeless tobacco use in Alaska Native women and singleton infant birth size.

OBJECTIVE: To examine the effects of maternal prenatal smokeless tobacco use on infant birth size. DESIGN: A retrospective medical record review of 502 randomly selected deliveries. POPULATION AND SETTING: Singleton deliveries to Alaska Native women residing in a defined geographical region in western Alaska, 1997-2005. METHODS: A regional medical center's electronic records were used to identify singleton deliveries. Data on maternal tobacco exposure and pregnancy outcomes were abstracted from medical records. Logistic models were used to estimate adjusted mean birthweight, length and head circumference for deliveries to women who used no tobacco (n=121), used smokeless tobacco (n=237) or smoked cigarettes (n=59). Differences in mean birthweight, length and head circumference, 95% confidence intervals and p-values were calculated using non-users as the reference group. MAIN OUTCOME MEASURES: Infant birthweight, crown-heel length and head circumference. RESULTS: After adjustment for gestational age and other potential confounders, the mean birthweight of infants of smokeless tobacco users was reduced by 78 g compared with that of infants of non-users (p=0.18) and by 331 g in infants of smokers (p<0.01). No association was found between maternal smokeless tobacco use and infant length or infant head circumference. CONCLUSIONS: We found a modest but non-significant reduction in the birthweight of infants of smokeless tobacco users compared with infants of tobacco non-users. Because smokeless tobacco contains many toxic compounds that could affect other pregnancy outcomes, results of this study should not be construed to mean that smokeless tobacco use is safe during pregnancy.

Oral contraceptive formulation and risk of breast cancer.

BACKGROUND: While evidence on the association between oral contraceptive (OC) use and breast cancer generally suggests little or no increased risk, the question of whether breast cancer risk varies by OC formulation remains controversial. Few studies have examined this issue because large samples and extensive OC histories are required. STUDY DESIGN: We used data from a multicenter, population-based, case-control investigation. Women aged 35-64 years were interviewed. To explore the association between OC formulation and breast cancer risk, we used conditional logistic regression to derive adjusted odds ratios, and we used likelihood ratio tests for heterogeneity to assess whether breast cancer risk varied by OC formulation. Key OC exposure variables were ever use, current or former use, duration of use and time since last use. To strengthen inferences about specific formulations, we restricted most analyses to the 2282 women with breast cancer and the 2424 women without breast cancer who reported no OC use or exclusive use of one OC. RESULTS: Thirty-eight formulations were reported by the 2674 women who used one OC; most OC formulations were used by only a few women. We conducted multivariable analyses on the 10 formulations that were each used by at least 50 women and conducted supplemental analyses on selected formulations of interest based on recent research. Breast cancer risk did not vary significantly by OC formulation, and no formulation was associated with a significantly increased breast cancer risk. CONCLUSIONS: These results add to the small body of literature on the relationship between OC formulation and breast cancer. Our data are reassuring in that, among women 35-64 years of age, we found no evidence that specific OC formulations increase breast cancer risk.

Percentage of gestational diabetes mellitus attributable to overweight and obesity.

OBJECTIVES: We calculated the percentage of gestational diabetes mellitus (GDM) attributable to overweight and obesity. METHODS: We analyzed 2004 through 2006 data from 7 states using the Pregnancy Risk Assessment Monitoring System linked to revised 2003 birth certificate information. We used logistic regression to estimate the magnitude of the association between prepregnancy body mass index (BMI) and GDM and calculated the percentage of GDM attributable to overweight and obesity. RESULTS: GDM prevalence rates by BMI category were as follows: underweight (13-18.4 kg/m(2)), 0.7%; normal weight (18.5-24.9 kg/m(2)), 2.3%; overweight (25-29.9 kg/m(2)), 4.8%; obese (30-34.9 kg/m(2)), 5.5%; and extremely obese (35-64.9 kg/m(2)), 11.5%. Percentages of GDM attributable to overweight, obesity, and extreme obesity were 15.4% (95% confidence interval [CI] = 8.6, 22.2), 9.7% (95% CI = 5.2, 14.3), and 21.1% (CI = 15.2, 26.9), respectively. The overall population-attributable fraction was 46.2% (95% CI = 36.1, 56.3). CONCLUSIONS: If all overweight and obese women (BMI of 25 kg/m(2) or above) had a GDM risk equal to that of normal-weight women, nearly half of GDM cases could be prevented. Public health efforts to reduce prepregnancy BMI by promoting physical activity and healthy eating among women of reproductive age should be intensified.

Indirect imaging of cardiac-specific transgene expression using a bidirectional two-step transcriptional amplification strategy.

Transcriptional targeting for cardiac gene therapy is limited by the relatively weak activity of most cardiac-specific promoters. We have developed a bidirectional plasmid vector, which uses a two-step transcriptional amplification (TSTA) strategy to enhance the expression of two optical reporter genes, firefly luciferase (fluc) and Renilla luciferase (hrluc), driven by the cardiac troponin T (cTnT) promoter. The vector was characterized in vitro and in living mice using luminometry and bioluminescence imaging to assess its ability to mediate strong, correlated reporter gene expression in a cardiac cell line and the myocardium, while minimizing expression in non-cardiac cell lines and the liver. In vitro, the TSTA system significantly enhanced cTnT-mediated reporter gene expression with moderate preservation of cardiac specificity. After intramyocardial and hydrodynamic tail vein delivery of an hrluc-enhanced variant of the vector, long-term fluc expression was observed in the heart, but not in the liver. In both the cardiac cell line and the myocardium, fluc expression correlated well with hrluc expression. These results show the vector's ability to effectively amplify and couple transgene expression in a cardiac-specific manner. Further replacement of either reporter gene with a therapeutic gene should allow non-invasive imaging of targeted gene therapy in living subjects.

Neural, metabolic, and performance adaptations to four weeks of high intensity sprint-interval training in trained cyclists.

The purpose of this study was to investigate the effects of short-term, high-intensity sprint training on the root mean squared (RMS) and median frequency (MF) derived from surface electromyography (EMG), as well as peak power, mean power, total work, and plasma lactate levels in trained cyclists when performed concurrently with endurance training. Seventeen trained cyclists were randomly assigned to a sprint training (S) group (n = 10, age 25 +/- 2.0 y) or a control (C) group (n = 7, age 25 +/- 0.5 y). Sprint training was performed bi-weekly for four weeks, comprising a total of 28 min over the training period. EMG measurements were taken before and after training during a series of four 30-s sprints separated by four minutes of active recovery. Plasma lactate, peak power, mean power, and total work were measured during each sprint bout. Following sprint training a significant increase occurred in the RMS of the vastus lateralis with a decrease in MF of the same muscle. Values for the vastus medialis did not change. Pre training exercising plasma lactate values were higher (p < 0.05) in C compared to S, but did not change with training. Exercising plasma lactate values increased (p < 0.05) from pre to post training in S, but were not different from C post training. Total work output increased from pre to post in S (p = 0.06). Peak power, mean power, and V.O (2)max increased (p < 0.05) pre to post training in S and C, indicating C was not a true control. In conclusion, these data suggest that four weeks of high-intensity sprint training combined with endurance training in a trained cycling population increased motor unit activation, exercising plasma lactate levels, and total work output with a relatively low volume of sprint exercise compared to endurance training alone.

Do thyroid disorders increase the risk of breast cancer?

The objective of this study was to determine whether thyroid disorders or treatment of such disorders affects the risk of breast cancer. Subjects aged 35-64 years were participants in the National Institute of Child Health and Human Development Women's Contraceptive and Reproductive Experiences Study, a population-based, case-control study of invasive breast cancer that was carried out at five sites in the United States. In-person interviews were completed for 4575 women (cases) with breast cancer (2953 white and 1622 black) and 4682 control women (3021 white and 1661 black). Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using multiple logistic regression methods. Models included adjustment for age (5-year age groups), race (white or black), and site. A history of any thyroid disorder (OR = 1.1, 95% CI = 0.9-1.2) was not associated with breast cancer risk. Only women with a history of thyroid cancer had an increased risk, but this was restricted to parous women (parous OR = 3.4, 95% CI = 1.5-8.1; nulliparous OR = 0.5, 95% CI = 0.04-5.1). Breast cancer risk was not associated with treatment for thyroid disorders. There was no statistical interaction between thyroid disorders, thyroid treatments, and race, menopausal status, or parity. We found no association between thyroid disorders or their associated treatments and the risk of breast cancer.

Reproductive health indicators and outcomes among refugee and internally displaced persons in postemergency phase camps.

CONTEXT: Despite increasing awareness of the importance of reproductive health programs and services for refugee and internally displaced populations, there is a paucity of basic epidemiological data on reproductive health outcomes. OBJECTIVES: To collect data on reproductive health outcomes among refugees and internally displaced persons in postemergency phase camps and compare these outcomes with those of host country and country-of-origin populations. To determine programmatic factors that may affect reproductive health outcomes. DESIGN, SETTING, AND PARTICIPANTS: Retrospective study of data collected from August 1998 through March 2000 of 688,766 persons living in 52 postemergency phase camps in 7 countries. Reproductive health outcomes of refugee and internally displaced populations were compared with available data of reference populations within their respective host country and country of origin. MAIN OUTCOME MEASURES: Crude birth rate (CBR), neonatal mortality rate (NNMR), maternal mortality ratio (MMR), percentage of newborns with low birth weight (LBW), and incidence of complications of unsafe or spontaneous abortions. RESULTS: Six of 11 groups had lower CBRs than their country of origin and 5 of 9 groups had lower CBRs than their host country. Four of 5 had lower NNMRs than their country of origin and 6 of 9 had lower NNMRs than the host country. Four of 6 had lower MMRs than their country of origin, and 5 of 6 had lower MMRs than their host country. Seven of 9 had lower percentages of LBWs than in the country of origin and 5 of 9 had lower percentages of LBWs than the host country. Higher CBRs were associated with more recently established camps and higher numbers of local health staff per 1000 persons; and higher percentages of LBW newborns were associated with rainy season, more recently established camps, lower numbers of community health workers per 1000 persons, and camps without supplementary feeding programs. CONCLUSIONS: Refugees and internally displaced persons in most postemergency phase camps had better reproductive health outcomes than their respective host country and country-of-origin populations.

Regulation of matrix metalloproteinases and effect of MMP-inhibition in heart transplant related reperfusion injury.

PURPOSE: Metalloproteinases (MMPs) regulate extracellular matrix turnover and degrade basal lamina. Aim of the study was to examine the regulation of MMPs and the effect of an MMP inhibitor in transplant related ischemia/reperfusion injury. METHODS: Heterotopic cardiac transplantation was performed after 4 h of ischemia in three groups of six rats: allografts (black hooded inbred strain, PVG donor/August Copenhagen Irish inbred strain recipient); allografts treated with a competitive MMP-inhibitor (Batimastat) 15 mg/kg every 24 h; isografts (PVG donor and recipient). Normal PVG hearts served as a control. Hearts were explanted after 72 h of reperfusion. Expression of MMP-2 and -9 was measured using gelatin zymography. Proteolytic activity was measured using a gelatinase activity assay. Myeloperoxidase activity and tumor necrosis factor-alpha (TNF-alpha) were measured as markers of inflammatory response. Immunostaining for collagen IV and laminin was used to study degradation of basal lamina. RESULTS: There was a significant increase of MMP-2 expression in allografts (2271+/-571 microg/ml) as compared to normal (683+/-139 microg/ml) and the Batimastat-treated (259+/-140 microg/ml, P<0.05) groups. Although pro-MMP-2 expression was equally high in the untreated iso- and allograft group (75+/-23 versus 62+/-30 microg/ml) MMP-2 expression in the isograft hearts was significantly lower (359+/-267 microg/ml) suggesting activation of the pro-form by an immunologic mechanism. Pro-MMP-9 levels were significantly higher in the untreated iso- and allograft groups as opposed to normal hearts and MMP-inhibited hearts. MMP-9 was completely inhibited by Batimastat treatment. Collagenolytic activity was lower in the treated group as compared to untreated allografts (538+/-140 versus 384+/-97 microg/ml, P<0.05), demonstrating effective inhibition of MMPs by Batimastat. In the treated group a lesser extent of basement membrane component alterations could be demonstrated by laminin and collagen IV staining. There was a significant reduction in myeloperoxidase activity (P=0.027) as well as lower TNF-alpha levels (ns) in the in the Batimastat treated group. CONCLUSION: Ischemia leads to an increase in MMP expression and degradation of basal lamina. This process is enhanced in allografts as compared to isografts suggesting additional activation of MMPs by immunologic mechanisms. MMP-inhibition is effective in preventing the proteolytic activity of MMPs and may alter the host rejection response by preserving extracellular matrix components and basement membranes.