Comparison of lung function during different phases of the menstrual cycle among young female asthmatics and non-asthmatics

Bronchial asthma is a chronic lung disease that causes significant morbidity and poor quality of life. The incidence of asthma is higher in boys before puberty and higher in females following puberty. Female preponderance is maintained into adulthood and morbidity due to asthma is greater in females. With this background we assessed the lung function with spirometry parameters of young asthmatic and non-asthmatic healthy females during different phases of the menstrual cycle. A case control study was conducted among well controlled asthmatic (N=60) and comparable (age and BMI matched) non – asthmatic healthy females (N=60) between 19 -25 years from June 2017- June 2020. The asthmatics were recruited from the asthma clinic, National Hospital of Sri Lanka, the Family Practice Centre and the medical Centre, University of Sri Jayewardenepura (USJ) while the non-asthmatic females (controls) were recruited from volunteering undergraduates of the university. Although ethnicity was not a criterion for recruitment of participants, the final recruited participants were all from the Sinhalese ethnicity. The sociodemographic data and the relevant information on asthma were obtained through an interviewer administered questionnaire. Forced Expiratory Volume in the first second (FEV1), Forced Vital Capacity (FVC), FEV1/FVC ratio, Peak Expiratory Flow Rate (PEFR) and Forced Expiratory Flow Rates, were measured during menstrual, follicular and luteal phases of the menstrual cycle. Spirometry parameters (means), were compared in asthmatics and non-asthmatics, with independent sample t-test. Analysis of variance (ANOVA) was used to analyze differences within the menstrual cycle within the groups. In all three phases, all spirometry parameters (except FVC) were lower in asthmatics (p<0.05). The spirometry parameters showed a cyclical pattern but did not change significantly between the three phases of the menstrual cycle in both groups. In asthmatics, the mean values of FEV1, FEV1/FVC%, FEF 25-75, FEF50, FEF75 were lowest in the menstrual phase and highest in the luteal phase and in non-asthmatics, the FEV1 was lowest in the menstrual phase and highest in the luteal phase.   KEYWORDS:  menstrual cycle, lung functions, spirometry, asthma, young female

Results of the MRI substudy of the intravenous magnesium efficacy in stroke trial

<p><b>Background and Purpose:</b>Although magnesium is neuroprotective in animal stroke models, no clinical benefit was confirmed in the Intravenous Magnesium Efficacy in Stroke (IMAGES) trial of acute stroke patients. The Magnetic Resonance in IMAGES (MR IMAGES) substudy investigated the effects of magnesium on the imaging surrogate outcome of infarct growth.</p> <p><b>Methods:</b> IMAGES trial patients in participating centers were randomized to receive either intravenous magnesium or placebo within 12 hours of stroke onset. Infarct growth was defined as volume difference between baseline diffusion-weighted imaging and day 90 fluid-attenuated inversion recovery image lesions. Patients who died were imputed the largest infarct growth observed.</p> <p><b>Results:</b> Among the 90 patients included in the primary analysis, there was no difference in infarct growth (median absolute growth, P=0.639; median percentage growth, P=0.616; proportion with any growth, P=0.212) between the 46 treated with magnesium and 44 with placebo. Infarct growth correlated with NIHSS score change from baseline to day 90. There was a trend showing baseline serum glucose correlated with infarct growth with magnesium treatment, but not in the placebo group. The mismatch frequency was reduced from 73% to 47% by increasing the mismatch threshold from >20% to >100% of core volume.</p> <p><b>Conclusions:</b> Infarct growth, confirmed here as a surrogate for clinical progression, was similar between magnesium and placebo treatment, paralleling the main IMAGES trial clinical outcomes. Glucose was a covariate for infarct growth with magnesium treatment. A more stringent mismatch threshold to define penumbra more appropriately would have excluded half of the patients in this 12-hour time window stroke study.</p&gt

Leisure-Time Physical Activity in Pregnancy and Maternal-Child Health: A Systematic Review and Meta-Analysis of Randomized Controlled Trials and Cohort Studies

Background: Evidence suggests that leisure-time physical activity (LTPA) during pregnancy is associated with a reduced risk of preeclampsia, gestational diabetes mellitus (GDM), and preterm birth. However, these results are inconsistent when comparing cohort studies and randomized controlled trials (RCTs). Objective: The purpose of our study was to compare the associations between LTPA in pregnancy and maternal (GDM, preeclampsia, and weight gain during pregnancy) and child health outcomes (preterm birth, birthweight, and fetal growth) between RCTs and cohort studies. Methods: We performed a systematic search in PubMed, Web of Science, and EBSCO up to 31 August 2015. Inclusion criteria for experimental studies required randomized trials with a control group and exposure to a physical activity structured program. The inclusion criteria for cohort studies required information on LTPA during pregnancy as an exposure and at least one maternal–child health outcome. We assessed the methodological quality of all studies and performed a meta-analysis to produce summary estimates of the effects using random models. Results: We included 30 RCTs and 51 cohort studies. The meta-analysis of RCTs indicated that participation in LTPA was associated with lower weight gain during pregnancy, lower likelihood of GDM, and lower likelihood of delivering a large-for-gestational-age infant. Cohort studies indicated that participation in LTPA was associated with lower weight gain during pregnancy, lower likelihood of GDM, and lower risk of preterm delivery. Conclusions: Our findings support the promotion of LTPA in pregnancy as a strategy to improve maternal and child health

How many days are needed to estimate wrist-worn accelerometry-assessed physical activity during the second trimester in pregnancy?

Background Objective methods to measure physical activity (PA) can lead to better cross-cultural comparisons, monitoring temporal PA trends, and measuring the effect of interventions. However, when applying this technology in field-work, the accelerometer data processing is prone to methodological issues. One of the most challenging issues relates to standardizing total wear time to provide reliable data across participants. It is generally accepted that at least 4 complete days of accelerometer wear represent a week for adults. It is not known if this same assumption holds true for pregnant women. Aim We assessed the optimal number of days needed to obtain reliable estimates of overall PA and moderate-to-vigorous physical activity (MVPA) during the 2nd trimester in pregnancy using a raw triaxial wrist-worn accelerometer. Methods Cross-sectional analyses were carried out in the antenatal wave of the 2015 Pelotas (Brazil) Birth Cohort Study. Participants wore the wrist ActiGraph wGT3X-BT accelerometer for seven consecutive days. The daily average acceleration, which indicated overall PA, was measured as milli-g (mg), and time spent in MVPA (minutes/day) was analyzed in 5-minute bouts. ANOVA and Kruskal-Wallis tests were used to compare variability across days of the week. Bland-Altman plots and the Spearman-Brown Prophecy Formula were applied to determine the reliability coefficient associated with one to seven days of measurement. Results Among 2,082 pregnant women who wore the accelerometer for seven complete days, overall and MVPA were lower on Sundays compared to other days of the week. Reliability of > = 0.80 to evaluate overall PA was reached with at least three monitoring days, whereas seven days were needed to estimate reliable measures of MVPA. Conclusions Our findings indicate that obtaining one week of accelerometry in adults is appropriate for pregnant women, particularly to obtain differences on weekend days and reliably estimate overall PA and MVPA

Correlates of accelerometer-assessed physical activity in pregnancy—The 2015 Pelotas (Brazil) Birth Cohort Study

Objective methods to measure physical activity (PA) have become available and widely used given the high degree of precision to evaluate PA. However, few studies have used accelerometers to measure PA during pregnancy, especially in low- and middle-income countries. We assessed overall PA, moderate, vigorous, and moderate-to-vigorous physical activity (MVPA) objectively measured among pregnant women and their correlates in a population-based study. PA was assessed for seven consecutive days using a raw triaxial wrist-worn accelerometer in women interviewed around 16 and 24 weeks of gestation in the 2015 Pelotas (Brazil) Birth Cohort Study. The average acceleration, which expresses overall PA, was presented in milli-g (1 mg = 0.001 g), and average time (min/day) spent in MVPA (>100 mg) was also analyzed in 5- and 10-min bouts. Analyses were performed using linear regression. In total, 2317 women were included in the analyses. Overall PA was 27.6 mg. Pregnant women spent on average 14 min/day in MVPA and 0.4 min in vigorous PA. Time spent in MVPA and total PA were inversely associated with years in school and income, and were lower among women receiving advice to not exercise. MVPA was also inversely associated with age, lower among women living with a partner, and higher among non-white women. The study indicated low levels of PA among pregnant women. The identified correlates may provide a framework to better understand factors influencing PA during pregnancy and thus inform future interventions

Theoretical description of phase coexistence in model C60

We have investigated the phase diagram of the Girifalco model of C60 fullerene in the framework provided by the MHNC and the SCOZA liquid state theories, and by a Perturbation Theory (PT), for the free energy of the solid phase. We present an extended assessment of such theories as set against a recent Monte Carlo study of the same model [D. Costa et al, J. Chem. Phys. 118:304 (2003)]. We have compared the theoretical predictions with the corresponding simulation results for several thermodynamic properties. Then we have determined the phase diagram of the model, by using either the SCOZA, or the MHNC, or the PT predictions for one of the coexisting phases, and the simulation data for the other phase, in order to separately ascertain the accuracy of each theory. It turns out that the overall appearance of the phase portrait is reproduced fairly well by all theories, with remarkable accuracy as for the melting line and the solid-vapor equilibrium. The MHNC and SCOZA results for the liquid-vapor coexistence, as well as for the corresponding critical points, are quite accurate. All results are discussed in terms of the basic assumptions underlying each theory. We have selected the MHNC for the fluid and the first-order PT for the solid phase, as the most accurate tools to investigate the phase behavior of the model in terms of purely theoretical approaches. The overall results appear as a robust benchmark for further theoretical investigations on higher order C(n>60) fullerenes, as well as on other fullerene-related materials, whose description can be based on a modelization similar to that adopted in this work.Comment: RevTeX4, 15 pages, 7 figures; submitted to Phys. Rev.

A mouse model featuring tissue-specific deletion of p53 and Brca1 gives rise to mammary tumors with genomic and transcriptomic similarities to human basal-like breast cancer

Purpose and methods: In human basal-like breast cancer, mutations and deletions in TP53 and BRCA1 are frequent oncogenic events. Thus, we interbred mice expressing the CRE-recombinase with mice harboring loxP sites at TP53 and BRCA1 (K14-Cre; p53 f/f Brca1 f/f ) to test the hypothesis that tissue-specific deletion of TP53 and BRCA1 would give rise to tumors reflective of human basal-like breast cancer. Results: In support of our hypothesis, these transgenic mice developed tumors that express basal-like cytokeratins and demonstrated intrinsic gene expression features similar to human basal-like tumors. Array comparative genomic hybridization revealed a striking conservation of copy number alterations between the K14-Cre; p53 f/f Brca1 f/f mouse model and human basal-like breast cancer. Conserved events included MYC amplification, KRAS amplification, and RB1 loss. Microarray analysis demonstrated that these DNA copy number events also led to corresponding changes in signatures of pathway activation including high proliferation due to RB1 loss. K14-Cre; p53 f/f Brca1 f/f also matched human basal-like breast cancer for a propensity to have immune cell infiltrates. Given the long latency of K14-Cre; p53 f/f Brca1 f/f tumors (~ 250 days), we created tumor syngeneic transplant lines, as well as in vitro cell lines, which were tested for sensitivity to carboplatin and paclitaxel. These therapies invoked acute regression, extended overall survival, and resulted in gene expression signatures of an anti-tumor immune response. Conclusion: These findings demonstrate that this model is a valuable preclinical resource for the study of human basal-like breast cancer

Chronic treatment with ivabradine does not affect cardiovascular autonomic control in rats

A low resting heart rate (HR) would be of great benefit in cardiovascular diseases. Ivabradine-a novel selective inhibitor of hyperpolarization-activated cyclic nucleotide gated (HCN) channels- has emerged as a promising HR lowering drug. Its effects on the autonomic HR control are little known. This study assessed the effects of chronic treatment with ivabradine on the modulatory, reflex and tonic cardiovascular autonomic control and on the renal sympathetic nerve activity (RSNA). Male Wistar rats were divided in 2 groups, receiving intraperitoneal injections of vehicle (VEH) or ivabradine (IVA) during 7 or 8 consecutive days. Rats were submitted to vessels cannulation to perform arterial blood pressure (AP) and HR recordings in freely moving rats. Time series of resting pulse interval and systolic AP were used to measure cardiovascular variability parameters. We also assessed the baroreflex, chemoreflex and the Bezold-Jarish reflex sensitivities. To better evaluate the effects of ivabradine on the autonomic control of the heart, we performed sympathetic and vagal autonomic blockade. As expected, ivabradine-treated rats showed a lower resting (VEH: 362 \ufffd 16 bpm vs. IVA: 260 \ufffd 14 bpm, p = 0.0005) and intrinsic HR (VEH: 369 \ufffd 9 bpm vs. IVA: 326 \ufffd 11 bpm, p = 0.0146). However, the chronic treatment with ivabradine did not change normalized HR spectral parameters LF (nu) (VEH: 24.2 \ufffd 4.6 vs. IVA: 29.8 \ufffd 6.4; p > 0.05); HF (nu) (VEH: 75.1 \ufffd 3.7 vs. IVA: 69.2 \ufffd 5.8; p > 0.05), any cardiovascular reflexes, neither the tonic autonomic control of the HR (tonic sympathovagal index; VEH: 0.91\ufffd 0.02 vs. IVA: 0.88 \ufffd 0.03, p = 0.3494). We performed the AP, HR and RSNA recordings in urethane-anesthetized rats. The chronic treatment with ivabradine reduced the resting HR (VEH: 364 \ufffd 12 bpm vs. IVA: 207 \ufffd 11 bpm, p < 0.0001), without affecting RSNA (VEH: 117 \ufffd 16 vs. IVA: 120 \ufffd 9 spikes/s, p = 0.9100) and mean arterial pressure (VEH: 70 \ufffd 4 vs. IVA: 77 \ufffd 6 mmHg, p = 0.3293). Our results suggest that, in health rats, the long-term treatment with ivabradine directly reduces the HR without changing the RSNA modulation and the reflex and tonic autonomic control of the heart