The changing paradigm of ethics in uterus transplantation: a systematic review

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154399/1/tri13548_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154399/2/tri13548.pd

Concordance of three alternative gestational age assessments for pregnant women from four African countries: A secondary analysis of the MIPPAD trial

Background: At times, ultrasound is not readily available in low resource countries in Africa for accurate determination of gestational age, so using alternative methods is pivotal during pregnancy. These assessments are used to aid the risk analysis for an infant and management strategies for premature delivery, if necessary. Currently, date of last menstrual period, fundal height measurements, and the New Ballard Score are commonly used in resource-limited settings. However, concordance of these measures is unknown for sub-Saharan Africa. We obtained data from an open-label randomized controlled trial, to assess the concordance of these alternative assessment methods. The purpose of our study was to determine the agreement between these alternative methods when used in sub-Saharan African populations. Methods: A total of 4,390 pregnant women from Benin, Gabon, Mozambique and Tanzania were included in our analysis. The assessment methods compared were: 1) reported last menstrual period, 2) symphysis-fundal height measurement, and 3) the New Ballard Score. The Bland-Altman method and intraclass correlation coefficient (ICC) were used to test the degree of agreement. Survival range gestational age, used as an inclusion criterion for further analysis, was from 22 to 44 weeks. Findings: Plots showed a lack of agreement between methods and the 95% limits of agreement too wide to be clinically useful. ICC = 0.25 indicated poor agreement. A post-hoc analysis, restricted from 32 to 42 weeks, was done to check for better agreement in this near-term population. The plots and ICC = 0.16 still confirmed poor agreement. Conclusion: The alternative assessments do not result in comparable outcomes and discrepancies are far beyond the clinically acceptable range. Last menstrual period should not be used as the only estimator of gestational age. In the absence of reliable early ultrasound, symphysis-fundal height measurements may be most useful during pregnancy for fetal risk assessment and the New Ballard Score after delivery as a confirmation of these estimations and for further neonatal management. However, promotion of portable ultrasound devices is required for accurate assessment of gestational age in sub-Sahara Africa

The inwardly rectifying K+ channel KIR7.1 controls uterine excitability throughout pregnancy

Abnormal uterine activity in pregnancy causes a range of important clinical disorders, including preterm birth, dysfunctional labour and post-partum haemorrhage. Uterine contractile patterns are controlled by the generation of complex electrical signals at the myometrial smooth muscle plasma membrane. To identify novel targets to treat conditions associated with uterine dysfunction, we undertook a genome-wide screen of potassium channels that are enriched in myometrial smooth muscle. Computational modelling identified Kir7.1 as potentially important in regulating uterine excitability during pregnancy. We demonstrate Kir7.1 current hyper-polarizes uterine myocytes and promotes quiescence during gestation. Labour is associated with a decline, but not loss, of Kir7.1 expression. Knockdown of Kir7.1 by lentiviral expression of miRNA was sufficient to increase uterine contractile force and duration significantly. Conversely, overexpression of Kir7.1 inhibited uterine contractility. Finally, we demonstrate that the Kir7.1 inhibitor VU590 as well as novel derivative compounds induces profound, long-lasting contractions in mouse and human myometrium; the activity of these inhibitors exceeds that of other uterotonic drugs. We conclude Kir7.1 regulates the transition from quiescence to contractions in the pregnant uterus and may be a target for therapies to control uterine contractility

Uracil DNA N-Glycosylase Promotes Assembly of Human Centromere Protein A

Uracil is removed from DNA by the conserved enzyme Uracil DNA N-glycosylase (UNG). Previously, we observed that inhibiting UNG in Xenopus egg extracts blocked assembly of CENP-A, a histone H3 variant. CENP-A is an essential protein in all species, since it is required for chromosome segregation during mitosis. Thus, the implication of UNG in CENP-A assembly implies that UNG would also be essential, but UNG mutants lacking catalytic activity are viable in all species. In this paper, we present evidence that UNG2 colocalizes with CENP-A and H2AX phosphorylation at centromeres in normally cycling cells. Reduction of UNG2 in human cells blocks CENP-A assembly, and results in reduced cell proliferation, associated with increased frequencies of mitotic abnormalities and rapid cell death. Overexpression of UNG2 induces high levels of CENP-A assembly in human cells. Using a multiphoton laser approach, we demonstrate that UNG2 is rapidly recruited to sites of DNA damage. Taken together, our data are consistent with a model in which the N-terminus of UNG2 interacts with the active site of the enzyme and with chromatin

Association between dietary saturated fat with cardiovascular disease risk markers and body composition in healthy adults- findings from the cross-sectional BODYCON study

Background: Diets high in saturated fatty acids (SFAs) and greater abdominal obesity are both associated with raised low-density lipoprotein cholesterol (LDL-C) concentrations, an independent cardiovascular disease (CVD) risk marker. Although reducing SFA intake is a public health strategy for CVD prevention, the role of body fat distribution on the relationship between SFA and LDL-C is unclear. Therefore, our objective was to investigate whether the association between dietary SFAs and LDL-C concentrations is related to body composition. Methods: In the BODYCON (impact of physiological and lifestyle factors on body composition) study, 409 adults (mean age 42±16y and median BMI of 23.5 (21.5-25.9) kg/m2) underwent a measure of body composition by dual energy x-ray absorptiometry, assessment of habitual dietary intake using a 4-day weighed food diary and physical activity level using a tri-axial accelerometer. Blood pressure was measured, and a fasting blood sample was collected to determine cardiometabolic disease risk markers. Correlations between body composition, circulating risk markers and dietary macronutrients were assessed prior to multivariate regression analysis. The effect of increasing intakes of dietary SFA on outcome measures was assessed using ANCOVA after adjusting for covariates. Results: Abdominal visceral adipose tissue (VAT) mass was moderately positively correlated with total cholesterol (TC), LDL-C, systolic blood pressure (SBP), diastolic blood pressure and HOMA-IR (rs=0.25-0.44, p<0.01). In multiple regression analysis, 18.3% of the variability in LDL-C was explained by SFA intake (% total energy (TE)), abdominal VAT mass, carbohydrate%TE and fat%TE intakes. When data were stratified according to increasing SFA%TE intakes, fasting TC, LDL-C and non-high-density lipoprotein-cholesterol were higher in Q4 compared with Q2 (p≤0.03). SBP was higher in Q4 versus Q3 (p=0.01). Android lean mass was also higher in Q3 versus Q1 (p=0.02). Other anthropometric and CVD risk markers were not different across quartile groups. Conclusions: Although dietary SFA was found to explain 9% of the variability in LDL-C, stratification of data according to quartiles of SFA intake did not reveal a dose-dependent relationship with LDL-C concentration. Furthermore, this association appeared to be independent of abdominal obesity in this cohort

Taller “Pescando Oportunidades 2022” – Sesión 2

Claudia Rada, Moderadora Ray Rosales Gonzales, representante de la empresa ECOSOLARTEC Samantha Montenegro, representante Armo SolarLos impactos del cambio climático ponen en peligro el desarrollo económico de las naciones, por lo tanto, los países deben adoptar medidas de adaptación para reducir los potenciales impactos negativos de este. Sin embargo, estos impactos pueden ser mitigados reduciendo las emisiones de GEI mediante el acceso y el uso eficiente de energías alternativas, la promoción de servicios y tecnologías con bajo uso de carbono, y otras prácticas con baja huella de carbono. A corto plazo, las estrategias para llevar adelante acciones de eficiencia energética es una de las maneras más eficaces para reducir estas emisiones en función de los costos, a la vez que produce otros beneficios socioeconómicos y ambientales

Effects of Recycled Rubber Particles Incorporated as Partial Sand Replacement on Fresh and Hardened Properties of Cement-Based Concrete: Mechanical, Microstructural and Life Cycle Analyses

Cement is one of the most valuable materials in today’s society, as it is used in most construction developments known to mankind. However, the energy intensive process and significant environmental impacts related to the production of Ordinary Portland Cement have shown the importance of searching for more sustainable materials. Concrete uses different aggregates added to the cement binder to lower, not only cost, but other factors like environmental burden, while maintaining good mechanical properties. This study analyzes the properties of fresh and hardened concrete incorporating recycled rubber to replace fine aggregate. Locally sourced 2 mm diameter rubber was incorporated in a regular strength concrete matrix into three different replacement levels, i.e., 3%, 5%, and 10%. Compression, tensile, flexural, and modulus of elasticity of hardened concrete were carried out in specimens aged 7, 14, and 28 days. In addition, non-destructive ultrasonic pulse velocity and rebound number tests were only performed on specimens aged 28 days. Once the tests were carried out, the fresh and hardened concrete properties were obtained. Similarly, the compressive and flexural strengths had the exact relationship between the values obtained. On the other hand, the modulus of elasticity tends to decrease due to the presence of the rubber. Consequently, it is recommended not to develop mix designs with more than 5% rubber because it is not meaningfully affected. The fine aggregate can be partially replaced by the rubber, keeping almost the same performance compared with sand-only counterparts. In addition, the life cycle assessment showed a reduction of up to 40% in the global warming potential. In fact, the 15% recycled rubber concrete mix has a climate change indicator of approximately 245 kg of CO2 eq

Combination of Mycobacterium tuberculosis RS Ratio and CFU Improves the Ability of Murine Efficacy Experiments to Distinguish between Drug Treatments.

Murine tuberculosis drug efficacy studies have historically monitored bacterial burden based on CFU of Mycobacterium tuberculosis in lung homogenate. In an alternative approach, a recently described molecular pharmacodynamic marker called the RS ratio quantifies drug effect on a fundamental cellular process, ongoing rRNA synthesis. Here, we evaluated the ability of different pharmacodynamic markers to distinguish between treatments in three BALB/c mouse experiments at two institutions. We confirmed that different pharmacodynamic markers measure distinct biological responses. We found that a combination of pharmacodynamic markers distinguishes between treatments better than any single marker. The combination of the RS ratio with CFU showed the greatest ability to recapitulate the rank order of regimen treatment-shortening activity, providing proof of concept that simultaneous assessment of pharmacodynamic markers measuring different properties will enhance insight gained from animal models and accelerate development of new combination regimens. These results suggest potential for a new era in which antimicrobial therapies are evaluated not only on culture-based measures of bacterial burden but also on molecular assays that indicate how drugs impact the physiological state of the pathogen

Concordance of three alternative gestational age assessments for pregnant women from four African countries: A secondary analysis of the MIPPAD trial

Background: At times, ultrasound is not readily available in low resource countries in Africa for accurate determination of gestational age, so using alternative methods is pivotal during pregnancy. These assessments are used to aid the risk analysis for an infant and management strategies for premature delivery, if necessary. Currently, date of last menstrual period, fundal height measurements, and the New Ballard Score are commonly used in resource-limited settings. However, concordance of these measures is unknown for sub-Saharan Africa. We obtained data from an open-label randomized controlled trial, to assess the concordance of these alternative assessment methods. The purpose of our study was to determine the agreement between these alternative methods when used in sub-Saharan African populations. Methods: A total of 4,390 pregnant women from Benin, Gabon, Mozambique and Tanzania were included in our analysis. The assessment methods compared were: 1) reported last menstrual period, 2) symphysis-fundal height measurement, and 3) the New Ballard Score. The Bland-Altman method and intraclass correlation coefficient (ICC) were used to test the degree of agreement. Survival range gestational age, used as an inclusion criterion for further analysis, was from 22 to 44 weeks. Findings: Plots showed a lack of agreement between methods and the 95% limits of agreement too wide to be clinically useful. ICC = 0.25 indicated poor agreement. A post-hoc analysis, restricted from 32 to 42 weeks, was done to check for better agreement in this near-term population. The plots and ICC = 0.16 still confirmed poor agreement. Conclusion: The alternative assessments do not result in comparable outcomes and discrepancies are far beyond the clinically acceptable range. Last menstrual period should not be used as the only estimator of gestational age. In the absence of reliable early ultrasound, symphysis-fundal height measurements may be most useful during pregnancy for fetal risk assessment and the New Ballard Score after delivery as a confirmation of these estimations and for further neonatal management. However, promotion of portable ultrasound devices is required for accurate assessment of gestational age in sub-Sahara Africa