Elevated lipid oxidation is associated with exceeding gestational weight gain recommendations and increased neonatal anthropometrics: a cross-sectional analysis.

BACKGROUND: Deviations from gestational weight gain (GWG) recommendations are associated with unfavorable maternal and neonatal outcomes. There is a need to understand how maternal substrate metabolism, independent of weight status, may contribute to GWG and neonatal outcomes. The purpose of this study was to explore the potential link between maternal lipid oxidation rate, GWG, and neonatal anthropometric outcomes. METHODS: Women (N = 32) with a lean pre-pregnancy BMI were recruited during late pregnancy and substrate metabolism was assessed using indirect calorimetry, before and after consumption of a high-fat meal. GWG was categorized as follows: inadequate, adequate, or excess. Shortly after delivery (within 48 h), neonatal anthropometrics were obtained. RESULTS: Using ANOVA, we found that fasting maternal lipid oxidation rate (grams/minute) was higher (p = 0.003) among women with excess GWG (0.1019 ± 0.0416) compared to women without excess GWG (inadequate = 0.0586 ± 0.0273, adequate = 0.0569 ± 0.0238). Findings were similar when lipid oxidation was assessed post-meal and also when expressed relative to kilograms of fat free mass. Absolute GWG was positively correlated to absolute lipid oxidation expressed in grams/minute at baseline (r = 0.507, p = 0.003), 2 h post-meal (r = 0.531, p = 0.002), and 4 h post-meal (r = 0.546, p = 0.001). Fasting and post-meal lipid oxidation (grams/minute) were positively correlated to neonatal birthweight (fasting r = 0.426, p = 0.015; 2-hour r = 0.393, p = 0.026; 4-hour r = 0.540, p = 0.001) and also to neonatal absolute fat mass (fasting r = 0.493, p = 0.004; 2-hour r = 0.450, p = 0.010; 4-hour r = 0.552, p = 0.001). CONCLUSIONS: A better understanding of the metabolic profile of women during pregnancy may be critical in truly understanding a woman's risk of GWG outside the recommendations. GWG counseling during prenatal care may need to be tailored to women based not just on their weight status, but other metabolic characteristics.

Cancer outpatients during the COVID-19 pandemic: what Oncoral has to teach us about medical drug use and the perception of telemedicine.

PURPOSE: The COVID-19 pandemic has disrupted healthcare access and telemedicine has been widely deployed. The aim of this study is to assess the impact of this health crisis on treatment consumption and telemedicine development in outpatients treated by oral anti-cancer agents and followed by the Oncoral hospital/community multidisciplinary program where continuity care is maintained by a pharmacist/nurse pair. METHODS: A prospective monocentric study was conducted among cancer patients who received Oncoral telephone follow-up during the 1st lockdown in France using a 56-item questionnaire which covered sociodemographic data, patient medication management, and telehealth. RESULTS: 178 patients received Oncoral follow-up during the 1st lockdown and 67.4% responded to the questionnaire. During lockdown, 9.2% of patients took medication or CAM for fatigue, 6.7% for mood alteration, 10.8% for sleep disorder, 11.7% for stress and anxiety, and 12.5% to get more energy. Homeopathy consumption was triggered by the pandemic. Habits about getting drugs from the pharmacy changed significantly (p < 0.001), while other treatment habits did not. 83% of patients were satisfied by the telephone follow-up established, 69% would be in favor of repeating this in case of a new epidemic wave. Those most in favor of using telemedicine seemed to be the youngest (p < 0.001), with several dependent children (p < 0.007), high school degree or higher education (p = 0.023), and in work (p < 0.001). CONCLUSION: Health system reorganization enables to limit the impact of the crisis on patients' drug use in oncology care. Telemedicine is a promising public health tool.

Carcinogenic potency of perfluorooctane sulfonate (PFOS) on Syrian hamster embryo (SHE) cells.

Perfluorooctane sulfonate (PFOS) is the degradation product of many fluoroderivatives and a widespread environmental contaminant. Its persistence, its long half-life in humans and its toxicity explain high concerns on human health side effects in future. PFOS is suspected to be a non-genotoxic carcinogen. In the present work, we assessed carcinogenic potential of PFOS by studying morphological transformation in Syrian hamster embryo (SHE) cells; cell transformation of SHE cells is an in vitro assay recommended by the Organization for Economic Cooperation and Development to detect carcinogens, genotoxic or not. Genotoxicity of PFOS and expression of PPARs genes in SHE cells were also measured. PFOS was shown to induce cell transformation (P < 0.05) at non-cytotoxic concentrations (0.2 and 2 µg/mL) (P ≤ 0.01). No genotoxic effect was recorded in the range of PFOS concentrations tested (2 × 10(-4) to 50 µg/mL) using the single-cell gel electrophoresis (comet) assay after 5 and 24 h of exposure. The expression of PPARs genes was measured by qPCR within the first 24 h and after 7 days of PFOS treatment. Results indicated an increased expression of ppar-ß/δ isoform as early as 24 h. After 7 days, the increase of ppar-ß/δ mRNA was significant at the concentrations inducing cell transformation (0.2 and 2 µg/mL), while overexpression of ppar-γ and ppar-α did not closely relate to effective concentrations. The results indicate that PFOS behave as a non-genotoxic carcinogen and impacted PPARs genes. Its cell transforming potential paralleled an increased expression of ppar-ß/δ.

Real-life drug-drug and herb-drug interactions in outpatients taking oral anticancer drugs: comparison with databases.

PURPOSE: Due to polypharmacy and the rising popularity of complementary and alternative medicines (CAM), oncology patients are particularly at risk of drug-drug interactions (DDI) or herb-drug interactions (HDI). The aims of this study were to assess DDI and HDI in outpatients taking oral anticancer drug. METHOD: All prescribed and non-prescribed medications, including CAM, were prospectively collected by hospital pharmacists during a structured interview with the patient. DDI and HDI were analyzed using four interaction software programs: Thériaque®, Drugs.com®, Hédrine, and Memorial Sloan Kettering Cancer Center (MSKCC) database. All detected interactions were characterized by severity, risk and action mechanism. The need for pharmaceutical intervention to modify drug use was determined on a case-by-case basis. RESULTS: 294 patients were included, with a mean age of 67 years [55-79]. The median number of chronic drugs per patient was 8 [1-29] and 55% of patients used at least one CAM. At least 1 interaction was found for 267 patients (90.8%): 263 (89.4%) with DDI, 68 (23.1%) with HDI, and 64 (21.7%) with both DDI and HDI. Only 13% of the DDI were found in Thériaque® and Drugs.com® databases, and 125 (2.5%) were reported with similar level of risk on both databases. 104 HDI were identified with only 9.5% of the interactions found in both databases. 103 pharmaceutical interventions were performed, involving 61 patients (20.7%). CONCLUSION: Potentially clinically relevant drug interaction were frequently identified in this study, showing that several databases and structured screening are required to detect more interactions and optimize medication safety.

African American Females Are Less Metabolically Flexible Compared with Caucasian American Females following a Single High-Fat Meal: A Pilot Study.

The relationship between metabolic flexibility (MF) and components of metabolic disease has not been well-studied among African American (AA) females and may play a role in the higher incidence of chronic disease among them compared with Caucasian American (CA) females. This pilot study aimed to compare the metabolic response of AA and CA females after a high-fat meal. Eleven AA (25.6 (5.6) y, 27.2 (6.0) kg/m2, 27.5 (9.7) % body fat) and twelve CA (26.5 (1.5) y, 25.7 (5.3) kg/m2, 25.0 (7.4) % body fat) women free of cardiovascular and metabolic disease and underwent a high-fat meal challenge (55.9% fat). Lipid oxidation, insulin, glucose, and interleukin (IL)-8 were measured fasted, 2 and 4 h postprandial. AA females had a significantly lower increase in lipid oxidation from baseline to 2 h postprandial (p = 0.022), and trended lower at 4 h postprandial (p = 0.081) compared with CA females, indicating worse MF. No group differences in insulin, glucose or HOMA-IR were detected. IL-8 was significantly higher in AA females compared with CA females at 2 and 4 h postprandial (p = 0.016 and p = 0.015, respectively). These findings provide evidence of metabolic and inflammatory disparities among AA females compared with CA females that could serve as a predictor of chronic disease in individuals with a disproportionately higher risk of development.

A Pilot Study on the Impact of the BumptUp® Mobile App on Physical Activity during and after Pregnancy.

To combat maternal morbidity and mortality, interventions designed to increase physical activity levels during and after pregnancy are needed. Mobile phone-based interventions show considerable promise, and BumptUp® has been carefully developed to address the lack of exercise among pregnant and postpartum women. The primary goal of this pilot study was to test the potential efficacy of BumptUp® for improving physical activity among pregnant and postpartum women. A randomized controlled clinical trial was performed (N = 35) with women either receiving access to the mhealth app or an educational brochure. Physical activity and self-efficacy for exercise data were collected at baseline (in mid-pregnancy) and at three additional timepoints (late pregnancy, 6 and 12 weeks postpartum). For moderate-to-vigorous physical activity, a clear trend is observed as the mean estimated difference between groups increases from -0.35 (SE: 1.75) in mid-pregnancy to -0.81 (SE: 1.75) in late pregnancy. For self-efficacy for exercise, the estimated difference of means (control-intervention) changed from 0.96 (SE: 6.53) at baseline to -7.64 (SE: 6.66) in late pregnancy and remained at -6.41 (SE: 6.79) and -6.70 (SE: 6.96) at 6 and 12 weeks postpartum, respectively. When assessing the change in self-efficacy from mid-to -ate pregnancy only, there was a statistically significant difference between groups (p = 0.044). BumptUp® (version 1.0 (3)) shows potential for efficacy. Pilot data suggest key refinements to be made and a larger clinical trial is warranted.

Postpartum Metabolism: How Does It Change from Pregnancy and What are the Potential Implications?

BACKGROUND: Metabolic dysfunction after pregnancy may have serious consequences for a new mother. The purpose of the study was to characterize basic changes that occur in metabolic profiles from late pregnancy through 4-6 months postpartum. A secondary purpose was to determine metabolic factors that may be contributing to postpartum weight retention. METHODS: Participants (n=25) came in for 2 visits: late pregnancy (~34 weeks gestation) and postpartum (4-6 months). Resting metabolic rate (RMR), respiratory quotient (RQ), and substrate oxidation values were assessed for 15 minutes during fasted conditions. Blood was drawn and skinfold anthropometry was performed to assess additional outcomes (inflammation, insulin resistance, lipid profiles, body composition). The participants completed a number of surveys that examined other lifestyle and demographic data of interest. At the postpartum visit, additional assessments regarding sleep and breastfeeding habits were administered. RESULTS: RMR was lower during postpartum (1517.2±225.1 kcal/day) compared to pregnancy (1867.9±302.6 kcal/day) (p<0.001), and remained lower when expressing RMR per kg body weight (postpartum: 22.3±2.7 vs pregnant: 23.7±3.4 kcal/kg, (p=0.034). Relative RMR (RMR per kg body weight) was negatively correlated to insulin resistance (HOMA-IR) during postpartum (r=-.463, p=0.034). Maternal HOMA-IR, inflammation (CRP), triglycerides (TAG), and carbohydrate oxidation were all positively correlated to postpartum weight retention (HOMA-IR: r=0.617, p=0.004; CRP: r=0.477, p=0.039, TAG: r=0.463, p=0.040; Carbohydrate Oxidation: (r=0.469, p=0.018). CONCLUSION: Metabolic rate is lower during postpartum compared to pregnancy, and may be connected to insulin resistance. Maternal insulin resistance, inflammation, blood lipids, and substrate metabolism are all related to postpartum weight retention.

Prenatal Yoga and Mental Health During the COVID-19 Pandemic: A Randomized-Control Trial.

Studies have demonstrated that new and expectant mothers experience increased levels of stress and anxiety during the COVID-19 pandemic. Though prenatal yoga is an effective mode of improving mental health during pregnancy, no research has evaluated its effect on mental health during times of extreme stress, such as a global pandemic. The purpose of this study was to determine the influence of a single session and a 10-week prenatal yoga intervention on the mental health of pregnant women during the COVID-19 pandemic. Women (n = 19; 28.52 ± 3.74 years; 20.94 ± 4.69 weeks gestation; BMI 29.33 ± 9.08) were randomized into a yoga or a non-yoga control group. There were no differences in demographic factors or depression/anxiety scores between groups at baseline. Baseline levels of anxiety and depression were high, with an average depression score of 8.10 ± 4.85 (scores > 8 represent possible depression) and an average anxiety score of 39.26 ± 12.99 (scores ≥ 39 represent a clinically significant anxiety). After just one session of yoga, women reported feeling less depressed (p = 0.028), tense (p < 0.001), and fatigued (p = 0.004). After 10 weeks, the yoga group had lower anxiety (p = 0.002), depression (p = 0.032), and total mood disturbance (p = 0.002) scores when compared to the control group. Yoga appears to benefit the mental health of expectant mothers, even in times of extreme stress. The findings of this study provide clinicians with valuable information regarding alternative exercise options for mental health during pregnancy during the COVID-19 pandemic.

High-fat meal increases peripheral blood mononuclear cell pro-inflammatory cytokine expression in African-American women.

African-American (AA) women have elevated predominance of inflammatory diseases concurrent with local inflammation resulting in compromised metabolic function. The purpose of the study was 2-fold: 1) to examine the gene and protein expression of pro- and anti-inflammatory cytokine secretion by peripheral blood mononuclear cells (PBMC) obtained from AA and Caucasian-American (CA) women in response to an acute high-fat meal; and 2) to explore the influence of race (AA vs. CA) on PBMC reactivity. Ten AA and 11 CA women consumed a high-fat meal with baseline and 4 h postprandial venous blood draws. PBMCs were incubated for 3 h then messenger RNA expression and supernatant protein concentration was used to examine inflammatory profiles. All women had a postprandial increase in interleukin (IL)-8 gene expression, IL-8 protein concentration, and tumor necrosis factor alpha (TNF-α) protein concentration (P < 0.05). AA women had a postprandial increase in IL-6, IL-8, and TNF-α protein concentration (P < 0.05). AA women had higher postprandial IL-1ß protein concentration and IL-8 gene expression compared with CA women (P < 0.05). Our data uncovers the specific impact of race and time on pro-inflammatory PBMC (IL-1ß, IL-6, IL-8, and TNF-α) expression profiles in response to an acute high-fat meal challenge. Novelty: African Americans have higher predominance of inflammatory disease. We explored the potential race impact on peripheral blood mononuclear cell reactivity in response to a meal. A pro-inflammatory response to an acute high-fat meal with race impact was observed possibly contributing to health disparities impacting African-American women.

Metabolic flexibility during late pregnancy is associated with neonatal adiposity.

The aim of this study was to determine the relationships between maternal metabolic flexibility during pregnancy and neonatal health outcomes. Percent change in lipid oxidation (before and after a high-fat meal) was calculated as the measure of "metabolic flexibility". Neonatal adiposity was assessed within 48 h of delivery by skinfold anthropometry. Metabolic flexibility (r = -0.271, p = 0.034), maternal HOMA-IR (r = 0.280, p = 0.030), and maternal body mass index (r = 0.299, p = 0.018) were correlated with neonatal subscapular skinfold (i.e., measure of neonatal adiposity). Clinical Trail Registration Number: NCT03504319. Novelty: This is the first study to link maternal metabolic flexibility, body mass index, and insulin resistance during pregnancy to neonatal adiposity at parturition.

Report on G4-Med, a Geant4 benchmarking system for medical physics applications developed by the Geant4 Medical Simulation Benchmarking Group.

BACKGROUND: Geant4 is a Monte Carlo code extensively used in medical physics for a wide range of applications, such as dosimetry, micro- and nanodosimetry, imaging, radiation protection, and nuclear medicine. Geant4 is continuously evolving, so it is crucial to have a system that benchmarks this Monte Carlo code for medical physics against reference data and to perform regression testing. AIMS: To respond to these needs, we developed G4-Med, a benchmarking and regression testing system of Geant4 for medical physics. MATERIALS AND METHODS: G4-Med currently includes 18 tests. They range from the benchmarking of fundamental physics quantities to the testing of Monte Carlo simulation setups typical of medical physics applications. Both electromagnetic and hadronic physics processes and models within the prebuilt Geant4 physics lists are tested. The tests included in G4-Med are executed on the CERN computing infrastructure via the use of the geant-val web application, developed at CERN for Geant4 testing. The physical observables can be compared to reference data for benchmarking and to results of previous Geant4 versions for regression testing purposes. RESULTS: This paper describes the tests included in G4-Med and shows the results derived from the benchmarking of Geant4 10.5 against reference data. DISCUSSION: Our results indicate that the Geant4 electromagnetic physics constructor G4EmStandardPhysics_option4 gives a good agreement with the reference data for all the tests. The QGSP_BIC_HP physics list provided an overall adequate description of the physics involved in hadron therapy, including proton and carbon ion therapy. New tests should be included in the next stage of the project to extend the benchmarking to other physical quantities and application scenarios of interest for medical physics. CONCLUSION: The results presented and discussed in this paper will aid users in tailoring physics lists to their particular application.

Patient and Provider Communication Regarding Exercise during Pregnancy in a Rural Setting.

Women in rural settings are at increased risk for adverse pregnancy outcomes. One potential way to improve pregnancy outcomes in rural settings is through physical activity promotion. However, given the disparities in prenatal care, women in rural areas may not receive information from their health care provider regarding physical activity during pregnancy. Therefore, the purpose of this study was to examine patient and provider communication in a rural setting (both patients' and providers' perspectives) regarding physical activity during pregnancy. A mixed methods study was performed among patients and providers in an obstetrical practice in a rural setting. During early pregnancy, patients were asked questions about their current physical activity levels and intentions for physical activity during their pregnancy. During late pregnancy, patients completed a survey regarding communication from their obstetric provider about exercise during pregnancy. Providers responsible for the patients' prenatal care were surveyed regarding communication with patients about physical activity. Seventy-one pregnant women and five providers participated. 58.2% of patients reported their provider did not discuss physical activity during pregnancy with them at all. Meanwhile, all providers (100%) reported discussing physical activity with all of their patients. Similarly, only 21.8% of patients reported their provider discussed the benefits of exercise during pregnancy, while 100% of providers reported telling their patients about the benefits of exercise during pregnancy. Our study suggests ineffective patient-provider communication regarding physical activity during pregnancy in a rural setting. Improved communication strategies could reduce disparities in health outcomes among pregnant women in rural settings.

Metabolic Flexibility and Weight Status May Contribute to Inter-Individual Changes in Breastmilk Lipid Content in Response to an Acute Bout of Exercise: Preliminary Findings from a Pilot Study.

The purposes of this pilot study were to describe changes in breastmilk lipid content in response to an acute bout of moderate intensity exercise and to explore maternal metabolic health factors, including metabolic flexibility, which may impact this change. A cross-sectional, observational, pilot study design was performed in 14 women between 4 and 6 months postpartum. Whole body fasting lipid oxidation was assessed, a standardized high-fat breakfast was consumed, and lipid oxidation was again measured 120-minutes post-meal. Metabolic flexibility was determined by comparing the change in lipid oxidation before and after the meal. Women completed 30-minutes of moderate intensity treadmill walking 150-minutes post-meal. Breastmilk was expressed and analyzed for lipid content before and after exercise. Overall, there was no significant difference between pre- and post-exercise breastmilk lipid content (pre-exercise 59.4±36.1 g/L vs. post-exercise 52.5±20.7 g/L, p=0.26). However, five (36%) women had an increase in breastmilk lipid content in response to the exercise bout, compared to nine (64%) that had a decrease in breastmilk lipid content suggesting inter-individual variability. The change in breastmilk lipid content from pre- to post-exercise was positively correlated to metabolic flexibility (r=0.595, p=0.03). Additionally, post-exercise lipid content was positively correlated with body mass index (BMI), body composition, and postpartum weight retention. Preliminary findings from this pilot study suggest that metabolic flexibility and maternal weight status may help explain the inter-individual changes in breastmilk lipid content in response to an acute bout of moderate intensity exercise.

Metabolic flexibility is impaired in women who are pregnant and overweight/obese and related to insulin resistance and inflammation.

CONTEXT: Maternal obesity is a significant public health concern that contributes to unfavorable outcomes such as inflammation and insulin resistance. Women with obesity may have impaired metabolic flexibility (i.e. an inability to adjust substrate metabolism according to fuel availability). Impaired metabolic flexibility during pregnancy may mediate poor pregnancy outcomes in women with obesity. PURPOSE: The purposes of this study were to: 1) compare metabolic flexibility between overweight/obese and lean women; and 2) determine the relationships between metabolic flexibility, inflammation following a high-fat meal, and maternal metabolic health outcomes (i.e. gestational weight gain and insulin resistance). PROCEDURES: This interventional physiology study assessed lipid oxidation rates via indirect calorimetry before and after consumption of a high-fat meal. The percent change in lipid metabolism was calculated to determine 'metabolic flexibility.' Maternal inflammatory profiles (CRP, IL-6, IL-8, IL-10, IL-12, TNF-α) and insulin resistance (HOMA-IR) were determined via plasma analyses. MAIN FINDINGS: 64 women who were pregnant (lean = 35, overweight/obese = 29) participated between 32 and 38 weeks gestation. Lean women had significantly higher metabolic flexibility compared to overweight/obese women (lean 48.0 ±â€¯34.1% vs overweight/obese 29.3 ±â€¯34.3%, p = .035). Even when controlling for pre-pregnancy BMI, there was a negative relationship between metabolic flexibility and percent change in CRP among the overweight/obese group (r = -0.526, p = .017). Metabolic flexibility (per kg fat free mass) was negatively correlated with postprandial HOMA-IR (2 h: r = -0.325, p = .016; 4 h: r = -0.319, p = .019). CONCLUSIONS: Overweight and obese women who are pregnant are less 'metabolically flexible' than lean women, and this is related to postprandial inflammation and insulin resistance.

Two forms of elongation factor 1 alpha (EF-1 alpha O and 42Sp50), present in oocytes, but absent in somatic cells of Xenopus laevis.

We have purified and partially sequenced the EF-1 alpha protein from Xenopus laevis oocytes (EF-1 alpha O). We show that the two cDNA clones isolated by Coppared et al. (Coppard, N. J., K. Poulsen, H. O. Madsen, J. Frydenberg, and B. F. C. Clark. 1991. J. Cell Biol. 112:237-243) do not encode 42Sp50, as claimed by these authors, but two very similar forms of EF-1 alpha O (EF-1 alpha O and EF-1 alpha O1). 42Sp50 is the major protein component of a 42S nucleoprotein particle that is very abundant in previtellogenic oocytes of X. laevis, 42Sp50 differs from EF-1 alpha O not only by its amino acid sequence, but also by several properties already reported. In particular, 42Sp50 has a low EF-1 alpha activity. It is distributed uniformly in the cytoplasm of previtellogenic oocytes, in contrast to EF-1 alpha O which is concentrated in a small region of the cytoplasm, known as the mitochondrial mass or Balbiani body.

SERCA1 truncated proteins unable to pump calcium reduce the endoplasmic reticulum calcium concentration and induce apoptosis.

By pumping calcium from the cytosol to the ER, sarco/endoplasmic reticulum calcium ATPases (SERCAs) play a major role in the control of calcium signaling. We describe two SERCA1 splice variants (S1Ts) characterized by exon 4 and/or exon 11 splicing, encoding COOH terminally truncated proteins, having only one of the seven calcium-binding residues, and thus unable to pump calcium. As shown by semiquantitative RT-PCR, S1T transcripts are differentially expressed in several adult and fetal human tissues, but not in skeletal muscle and heart. S1T proteins expression was detected by Western blot in nontransfected cell lines. In transiently transfected cells, S1T homodimers were revealed by Western blot using mildly denaturing conditions. S1T proteins were shown, by confocal scanning microscopy, to colocalize with endogenous SERCA2b into the ER membrane. Using ER-targeted aequorin (erAEQ), we have found that S1T proteins reduce ER calcium and reverse elevation of ER calcium loading induced by SERCA1 and SERCA2b. Our results also show that SERCA1 variants increase ER calcium leakage and are consistent with the hypothesis of a cation channel formed by S1T homodimers. Finally, when overexpressed in liver-derived cells, S1T proteins significantly induce apoptosis. These data reveal a further mechanism modulating Ca(2+) accumulation into the ER of nonmuscle cells and highlight the relevance of S1T proteins to the control of apoptosis.

Fucoidan/VEGF-based surface modification of decellularized pulmonary heart valve improves the antithrombotic and re-endothelialization potential of bioprostheses.

Decellularized porcine heart valves offer promising potential as biocompatible prostheses. However, this procedure alter matrix fibres and glycans, leading to lower biomechanical resistance and increased their thrombotic potential. Therefore, their durability is limited due to calcification and weak regeneration in vivo. Surface modifications are highly requested to improve the scaffolds re-endothelialization required to restore functional and haemocompatible heart valve. Fucoidan, a natural sulphated polysaccharide, carries antithrombotic and anti-inflammatory properties and is known to enhance endothelial adhesion and proliferation when associated with vascular endothelial growth factor (VEGF). Based on these features, we constructed fucoidan/VEGF polyelectrolyte multilayer film (PEM) coated valve scaffold in an attempt to develop functional heart valve bioprosthesis. We investigated the haemocompatibility of the PEM coated valve scaffolds, the adhesion and growth potential of endothelial cells (HUVECs) in flow, as well as long term culture with stem cells. Fucoidan/VEGF PEM coated scaffolds demonstrated antithrombotic and non-calcifying properties. The PEM application increased HUVECs adhesion in flow (6 h) and HUVECs viability over time (72 h). HUVECs were well spread and aligned in flow direction. Interestingly, stem cells infiltration was improved by the PEM coating at 21 days. Thus, the fucoidan/VEGF PEM is a promising surface modification to obtain valve bioprostheses for clinical applications with increased antithrombotic and re-endothelialization potential.

Assessment of endpoint criteria and perceived barriers during maximal cardiorespiratory fitness testing among pregnant women.

BACKGROUND: A plateau in volume of oxygen consumption (VO2) is the primary indicator for determining if an individual has reached their maximal aerobic capacity. However, secondary criteria can also be used to identify maximal effort (i.e. lactate level, rating of perceived exertion [RPE], percent of age-predicted maximal heart rate [HR] and respiratory exchange ratio [RER]). Age and gender-specific secondary criteria have been developed for the general population, but no secondary criteria have been established for pregnant women. The primary purpose of this study was to analyze secondary endpoint criteria during VO2max testing among pregnant women. A secondary purpose was to identify emotional and physical barriers pregnant women have that may prevent them from reaching maximal effort. METHODS: Twenty-five pregnant women (age= 30.0±3.6 years; gestation age= 22.1±1.4 weeks, pre-pregnancy BMI= 23.68±4.04 kg/m2) participated. Each participant completed a Bruce protocol treadmill test and maximal HR, RER, lactate, and RPE were assessed and compared to standards. Barriers were assessed immediately postexercise via open-ended questions. RESULTS: The mean VO2max was 32.9±8.8 mL/kg/min. Mean RPEmax was 17.6±1.8 versus the standard of RPE≥17 (P=0.12). Percent of age-predicted HRmax was 88.0±6.8% versus the standard of ≥95% (P<0.001). Immediate postexercise lactate was 6.8±2.4mM versus the standard of ≥8 mM (P=0.03). Maximal RER was 1.2±0.2 versus the standard of RERmax ≥1.1 (P=0.08). CONCLUSIONS: Our data provide preliminary evidence that secondary criteria may need to be adjusted for pregnant women. Additionally, physical and emotional barriers may be enhanced by pregnancy (e.g. pain, discomfort, anxiety, health concerns), and may limit the performance of pregnant women during maximal exercise.

Structural requirements of 5S rRNA for nuclear transport, 7S ribonucleoprotein particle assembly, and 60S ribosomal subunit assembly in Xenopus oocytes.

Structural requirements of 5S rRNA for nuclear transport and RNA-protein interactions have been studied by analyzing the behavior of oocyte-type 5S rRNA and of 31 different in vitro-generated mutant transcripts after microinjection into the cytoplasm of Xenopus oocytes. Experiments reveal that the sequence and secondary and/or tertiary structure requirements of 5S rRNA for nuclear transport, storage in the cytoplasm as 7S ribonucleoprotein particles, and assembly into 60S ribosomal subunits are complex and nonidentical. Elements of loops A, C, and E, helices II and V, and bulged and hinge nucleotides in the central domain of 5S rRNA carry the essential information for these functional activities. Assembly of microinjected 5S rRNA into 60S ribosomal subunits was shown to occur in the nucleus; thus, the first requirement for subunit assembly is nuclear targeting. The inhibitory effects of ATP depletion, wheat germ agglutinin, and chilling on the nuclear import of 5S rRNA indicate that it crosses the nuclear envelope through the nuclear pore complex by a pathway similar to that used by karyophilic proteins.

2,4-Dichlorophenoxyacetic acid: effects on Syrian hamster embryo (SHE) cell transformation, c-Myc expression, DNA damage and apoptosis.

2,4-Dichlorophenoxyacetic acid (2,4-D) is a selective, systemic auxin-type herbicide extensively used throughout the world. The present research was aimed at studying effects of low and non-cytotoxic concentrations of 2,4-D on SHE cells in relation with carcinogenicity. Effects were studied on Syrian hamster morphological cell transformation, c-Myc expression - both at the gene and protein level - DNA damage and apoptosis. 2,4-D significantly induced cell transformation at 11.5 microM and 23 microM (i.e. 2.5 microg/mL and 5 microg/mL). An increase in the expression of the transcription factor c-Myc, measured by use of RT-PCR with respect to mRNA level and by Western blotting for protein level was registered at these concentrations, as well as genotoxic effects evaluated with the single-cell gel electrophoresis (Comet) assay. Consequences for apoptosis of 2,4-D treatment were also investigated. The fluorochrome acridine orange was used to study DNA fragmentation as a marker of apoptosis. No effect on apoptosis was found at 2,4-D concentrations that induced cell transformation. This was confirmed by the unchanged expression of Bcl-2 and Bax, two regulator genes of the mitochondrial pathway of apoptosis. Our results demonstrate the transforming and genotoxic effects of low concentrations of 2,4-D in mammalian cells. This information contributes to a better understanding of the mechanism of 2,4-D toxicity in mammalian cells and demonstrates that 2,4-D should be considered as potentially hazardous to humans.