Targeting the TGF-β1 Pathway to Prevent Normal Tissue Injury After Cancer Therapy

Evidence supporting the critical role of transforming growth factor β1 in the development of normal tissue injury after cancer therapy is reviewed and the results of recent research aimed at preventing normal tissue injury by targeting the transforming growth factor β1 pathway are presented

Aerobic Exercise during Pregnancy and Presence of Fetal-Maternal Heart Rate Synchronization

It has been shown that short-term direct interaction between maternal and fetal heart rates may take place and that this interaction is affected by the rate of maternal respiration. The aim of this study was to determine the effect of maternal aerobic exercise during pregnancy on the occurrence of fetal-maternal heart rate synchronization.In 40 pregnant women at the 36th week of gestation, 21 of whom exercised regularly, we acquired 18 min. RR interval time series obtained simultaneously in the mothers and their fetuses from magnetocardiographic recordings. The time series of the two groups were examined with respect to their heart rate variability, the maternal respiratory rate and the presence of synchronization epochs as determined on the basis of synchrograms. Surrogate data were used to assess whether the occurrence of synchronization was due to chance.In the original data, we found synchronization occurred less often in pregnancies in which the mothers had exercised regularly. These subjects also displayed higher combined fetal-maternal heart rate variability and lower maternal respiratory rates. Analysis of the surrogate data showed shorter epochs of synchronization and a lack of the phase coordination found between maternal and fetal beat timing in the original data.The results suggest that fetal-maternal heart rate coupling is present but generally weak. Maternal exercise has a damping effect on its occurrence, most likely due to an increase in beat-to-beat differences, higher vagal tone and slower breathing rates

A Population-Based Evaluation of a Publicly Funded, School-Based HPV Vaccine Program in British Columbia, Canada: Parental Factors Associated with HPV Vaccine Receipt

Analysis of a telephone survey by Gina Ogilvie and colleagues identifies the parental factors associated with HPV vaccine uptake in a school-based program in Canada

Biomarkers of hepatic injury and function in neonatal hypoxic ischemic encephalopathy and with therapeutic hypothermia

Therapeutic hypothermia (TH) is now provided as standard care to infants with moderate-severe hypoxic ischemic encephalopathy (HIE). The role of TH in limiting neuronal injury is well recognized, but its effect on hepatic injury which occurs frequently in neonatal HIE is not known. Our objective was to characterize biomarkers of liver injury and function in the setting of neonatal HIE and to describe whether HIE severity and provision of TH influence these hepatic biomarkers. We performed a multicenter retrospective study and compared hepatic biomarkers obtained during the first postnatal week, according to the severity of HIE and whether treated with TH. Of a total of 361 infants with HIE, 223 (62%) received TH and 138 (38%) were managed at normal temperature. Most hepatic biomarkers and C-reactive protein (CRP) were significantly associated with the severity of HIE (p<0.001). Infants treated with TH had lower peak Alanine aminotransferase (ALT) concentrations (p=0.025) and delay in reaching peak CRP concentration (p<0.001).  Conclusion: We observed a significant association between the clinical grade of HIE and biomarkers of liver metabolism and function. Therapeutic hypothermia was associated with delayed CRP responses and with lower ALT concentrations and so may have the potential to modulate hepatic injury

Training and expertise in undertaking assisted vaginal delivery (AVD): a mixed methods systematic review of practitioners views and experiences

Abstract: Background: During childbirth, complications may arise which necessitate an expedited delivery of the fetus. One option is instrumental assistance (forceps or a vacuum-cup), which, if used with skill and sensitivity, can improve maternal/neonatal outcomes. This review aimed to understand the core competencies and expertise required for skilled use in AVD in conjunction with reviewing potential barriers and facilitators to gaining competency and expertise, from the point of view of maternity care practitioners, funders and policy makers. Methods: A mixed methods systematic review was undertaken in five databases. Inclusion criteria were primary studies reporting views, opinions, perspectives and experiences of the target group in relation to the expertise, training, behaviours and competencies required for optimal AVD, barriers and facilitators to achieving practitioner competencies, and to the implementation of appropriate training. Quality appraisal was carried out on included studies. A mixed-methods convergent synthesis was carried out, and the findings were subjected to GRADE-CERQual assessment of confidence. Results: 31 papers, reporting on 27 studies and published 1985–2020 were included. Studies included qualitative designs (3), mixed methods (3), and quantitative surveys (21). The majority (23) were from high-income countries, two from upper-middle income countries, one from a lower-income country: one survey included 111 low-middle countries. Confidence in the 10 statements of findings was mostly low, with one exception (moderate confidence). The review found that AVD competency comprises of inter-related skill sets including non-technical skills (e.g. behaviours), general clinical skills; and specific technical skills associated with particular instrument use. We found that practitioners needed and welcomed additional specific training, where a combination of teaching methods were used, to gain skills and confidence in this field. Clinical mentorship, and observing others confidently using the full range of instruments, was also required, and valued, to develop competency and expertise in AVD. However, concerns regarding poor outcomes and litigation were also raised. Conclusion: Access to specific AVD training, using a combination of teaching methods. Complements, but does not replace, close clinical mentorship from experts who are positive about AVD, and opportunities to practice emerging AVD skills with supportive supervision. Further research is required to ascertain effective modalities for wider training, education, and supportive supervision for optimal AVD use

Enhanced growth and improved vascular function in offspring from successive pregnancies in endothelial nitric oxide synthase knockout mice

Objective: Transgenic mice that lack endothelial nitric oxide synthase have offspring with growth deficiency and abnormal vascular reactivity in later life. Our objective was to evaluate the role of parity in the modulation of the fetal programming of growth and vascular responses in these transgenic mice. Study design: Oligoparous (0-2 previous pregnancies) and multiparous (5-9 previous pregnancies) nitric oxide synthase knockout (-/-KO) female mice were bred with nitric oxide synthase(-/-KO) and wild type (+/+WT) male mice to produce nitric oxide synthase-/-KO and maternally derived heterozygous (+/-Mat) litters. The pups were weighed weekly. Carotid arteries of the adult females from these litters were used for in vitro vascular reactivity studies. Results: Nitric oxide synthase knockout and nitric oxide synthase maternal litters that were born to oligoparous mothers had significant growth lag compared with corresponding multiparous litters. Length-tension characteristics were not different between the groups. However, optimal diameter, which is a measure of vascular tensile properties and resistance, was decreased in oligoparous compared with multiparous female offspring. Acetylcholine-mediated vasorelaxation was abolished, and contraction by phenylephrine and Ca++ was increased in oligoparous, but not multiparous, female offspring (P <.05). Conclusion: These data support the role of abnormal uterine environment in the fetal programming of postnatal growth and vascular function in later life. Successive pregnancies may lead to maternal uterine adaptations that bypass the lack of a functional nitric oxide synthase, which leads to improvement in postnatal growth and vascular function in the offspring. Given the reported effect of parity on the risk of preeclampsia, similar mechanisms may be operative in human pregnancy. (C) 2004 Elsevier Inc. All rights reserved