MyBack - effectiveness and implementation of a behavior change informed exercise programme to prevent low back pain recurrences: a hybrid effectiveness-implementation randomized controlled study protocol.

BACKGROUND: Low back pain (LBP) is a common health condition and the leading cause of years lived with disability worldwide. Most LBP episodes have a favourable prognosis, but recurrences within a year are common. Despite the individual and societal impact related to LBP recurrences, there is limited evidence on effective strategies for secondary prevention of LBP and successful implementation of intervention programmes in a real-world context. The aim of this study is to analyse the effectiveness of a tailored exercise and behavioural change programme (MyBack programme) in the secondary prevention of LBP; and evaluate acceptability, feasibility and determinants of implementation by the different stakeholders, as well as the implementation strategy of the MyBack programme in real context. METHODS: This protocol describes a hybrid type I, randomized controlled trial to evaluate the effectiveness and implementation of MyBack programme in the context of primary health care. The Behaviour Change Wheel framework and FITT-VP principles will inform the development of the behaviour change and exercise component of MyBack programme, respectively. Patients who have recently recovered from an episode of non-specific LBP will be randomly assigned to MyBack and usual care group or usual care group. The primary outcome will be the risk of LBP recurrence. The secondary outcomes will include disability, pain intensity, musculoskeletal health, and health-related quality of life. Participants will be followed monthly for 1 year. Costs data related to health care use and the MyBack programme will be also collected. Implementation outcomes will be assessed in parallel with the effectiveness study using qualitative methods (focus groups with participants and health providers) and quantitative data (study enrolment and participation data; participants adherence). DISCUSSION: To our knowledge, this is the first study assessing the effectiveness and implementation of a tailored exercise and behaviour change programme for prevention of LBP recurrences. Despite challenges related to hybrid design, it is expected that data on the effectiveness, cost-effectiveness, and implementation of the MyBack programme may contribute to improve health care in patients at risk of LBP recurrences, contributing to direct and indirect costs reduction for patients and the health system. TRIAL REGISTRATION NUMBER: NCT05841732.

Exploring barriers and facilitators to the adoption of regular exercise practice in patients at risk of a recurrence of low back pain (MyBack project): a qualitative study.

PURPOSE: This study aimed to explore potential barriers and facilitators to the adoption of regular exercise practice in patients at risk of a recurrence of low back pain (LBP). MATERIALS AND METHODS: Eleven patients, who recovered from a previous episode of LBP, participated in two focus groups. The semi-structured interview schedule was informed by the Behaviour Change Wheel and the Theoretical Domains Framework. Focus groups were held through videoconference, audio and video recorded and transcribed verbatim. A deductive content analysis was performed by two researchers independently. RESULTS: Eighteen barriers and 19 facilitators were identified. The most common barriers included "lack of knowledge on how to manage a recurrence of LBP," "lack of behavioural regulation strategies and having other priorities" and "lack of self-efficacy/confidence to practice exercise autonomously and deal with a new episode of LBP." "Knowledge on exercise and recurrences," "regular exercise habits," "having specific behavioural regulation strategies," "exercise practice with others," "willingness to practice exercise and considering it a priority," and "presence of positive emotions related with exercise practice" were the most common facilitators. CONCLUSIONS: These findings will inform the development of a behaviour change-informed exercise intervention to promote regular exercise practice among patients at risk of a recurrence of LBP.

Exercise interventions are the most effective strategies to reduce the risk of a recurrence of LBP, but patients do not exercise regularly.Exercise interventions targeting specific determinants of behaviour change are needed to support the adoption of this practice.The findings of this study will allow the design of a health intervention to promote the adoption of regular exercise practice for people at risk of having a recurrence of LBP.Researchers, health professionals and policymakers should promote the implementation of evidence- based and theory-driven interventions for the secondary prevention of LBP to reduce its burden on health systems.

Low back pain management in primary healthcare: findings from a scoping review on models of care.

INTRODUCTION: Models of care (MoCs) describe evidence-informed healthcare that should be delivered to patients. Several MoCs have been implemented for low back pain (LBP) to reduce evidence-to-practice gaps and increase the effectiveness and sustainability of healthcare services. OBJECTIVE: To synthesise research evidence regarding core characteristics and key common elements of MoCs implemented in primary healthcare for the management of LBP. DESIGN: Scoping review. DATA SOURCES: Searches on MEDLINE (PubMed), EMBASE, Cochrane Central Register of Controlled Trials, PEDro, Scopus, Web of Science and grey literature databases were conducted. ELIGIBILITY CRITERIA: Eligible records included MoCs implemented for adult LBP patients in primary healthcare settings. DATA EXTRACTION AND SYNTHESIS: Data extraction was carried out independently by two researchers and included a summary of the studies, the identification of the MoCs and respective key elements, concerning levels of care, settings, health professionals involved, type of care delivered and core components of the interventions. Findings were investigated through a descriptive qualitative content analysis using a deductive approach. RESULTS: 29 studies reporting 11 MoCs were included. All MoCs were implemented in high-income countries and had clear objectives. Ten MoCs included a stratified care approach. The assessment of LBP patients typically occurred in primary healthcare while care delivery usually took place in community-based settings or outpatient clinics. Care provided by general practitioners and physiotherapists was reported in all MoCs. Education (n=10) and exercise (n=9) were the most common health interventions. However, intervention content, follow-ups and discharge criteria were not fully reported. CONCLUSIONS: This study examines the features of MoCs for LBP, highlighting that research is in its early stages and stressing the need for better reporting to fill gaps in care delivery and implementation. This knowledge is crucial for researchers, clinicians and decision-makers in assessing the applicability and transferability of MoCs to primary healthcare settings.

Physiotherapists' barriers and facilitators to the implementation of a behaviour change-informed exercise intervention to promote the adoption of regular exercise practice in patients at risk of recurrence of low back pain: a qualitative study.

BACKGROUND: Recurrences of low back pain (LBP) are frequent and associated with high levels of disability and medical costs. Regular exercise practice may be an effective strategy to prevent recurrences of LBP, however, the promotion of this behaviour by physiotherapists seems to be challenging. This study aims to explore physiotherapists' perceived barriers and facilitators to the implementation of a behaviour change-informed exercise intervention to promote the adoption of regular exercise practice by patients at risk of recurrence of low back pain. METHODS: Two focus groups with primary healthcare physiotherapists were conducted, based on a semi-structured interview schedule informed by the Behaviour Change Wheel, including the Capability, Opportunity, Motivation-Behaviour (COM-B) model and the Theoretical Domains Framework (TDF). All focus groups were held through videoconference, audio and video recorded and transcribed verbatim. A deductive content analysis, using a coding matrix based on the COM-B and TDF, was performed by two independent researchers. A third researcher was approached to settle disagreements. RESULTS: In total, 14 physiotherapists participated in the focus groups. The analysis revealed a total of 13 barriers (4 COM-B components and 7 TDF domains) and 23 facilitators (5 COM-B and 13 TDF) to physiotherapists' implementation of a behaviour change-informed exercise intervention. The most common barriers were the lack of skills and confidence to implement the proposed intervention. These were explained by the fact that it differs from the usual practice of most participants and requires the learning of new skills applied to their contexts. However, for those who had already implemented other similar interventions or whose rationale is aligned with the new intervention, there seemed to exist more positive determinants, such as potential benefits for physiotherapists and the profession, improvement of quality of care and willingness to change clinical practice. For others who did not previously succeed in implementing these types of interventions, more context-related barriers were mentioned, such as lack of time to implement the intervention, schedule incompatibilities and lack of material and human resources. CONCLUSIONS: This study identified modifiable barriers and facilitators to physiotherapists' implementation of a behaviour change-informed exercise intervention for patients at risk of recurrence of LBP in primary healthcare. The findings of this study will allow the systematic and theory-based development of a behaviour change-informed training programme, aimed at physiotherapists and supporting the successful implementation of the exercise intervention.

Small extracellular vesicles from pregnant women with maternal supraphysiological hypercholesterolemia impair endothelial cell function in vitro.

Maternal physiological hypercholesterolemia MPH, maternal total cholesterol (TC) levels at term of pregnancy ≤280 mg/dL) occurs to assure fetal development. Maternal supraphysiological hypercholesterolemia (MSPH, TC levels >280 mg/dL) is a pathological condition associated with maternal, placental, and fetal endothelial dysfunction and early neonatal atherosclerosis development. Small extracellular vesicles (sEVs) are delivered to the extracellular space by different cells, where they modulate cell functions by transporting active signaling molecules, including proteins and miRNA. AIM: To determine whether sEVs from MSPH women could alter the function of endothelial cells (angiogenesis, endothelial activation and nitric oxide synthesis capacity). METHODS: This study included 24 Chilean women (12 MPH and 12 MSPH). sEVs were isolated from maternal plasma and characterized by sEV markers (CD9, Alix and HSP70), nanoparticle tracking analysis, transmission electron microscopy, and protein and cholesterol content. The endothelial cell line HMEC-1 was used to determine the uptake of labeled sEVs and the effects of sEVs on cell viability, endothelial tube formation, endothelial cell activation, and endothelial nitric oxide expression and function. RESULTS: In MSPH women, the plasma concentration of sEVs was increased compared to that in MPH women. MSPH-sEVs were highly taken up by HMEC-1 cells and reduced angiogenic capacity and the expression and activity of eNOS without changing cell viability or endothelial activation compared to MPH-sEVs. CONCLUSION: sEVs from MSPH women impair angiogenesis and nitric oxide synthesis in endothelial cells, which could contribute to MSPH-associated endothelial dysfunction.

Models of care for low back pain patients in primary healthcare: a scoping review protocol.

INTRODUCTION: Low back pain (LBP) is the most prevalent musculoskeletal condition worldwide and it is responsible for high healthcare costs and resources consumption. It represents a challenge for primary care services that struggle to implement evidence-based practice. Models of care (MoCs) are arising as effective solutions to overcome this problem, leading to better health outcomes. Although there is growing evidence regarding MoCs for the management of LBP patients, an analysis of the existing body of evidence has not yet been carried out. Therefore, this scoping review aims to identify and map the current evidence about the implementation of MoCs for LBP in primary healthcare. Findings from this study will inform policy makers, health professionals and researchers about their characteristics and outcomes, guiding future research and best practice models. METHODS AND ANALYSIS: This protocol will follow the Joanna Briggs Institute methodological guidelines for scoping reviews. Studies that implemented an MoC for LBP patients in primary healthcare will be included. Searches will be conducted on PubMed, EMBASE, Cochrane Central Register of Controlled Trials, PEDro, Scopus, Web of Science, grey literature databases and relevant organisations websites. This review will consider records from 2000, written in English, Portuguese or Spanish. Two researchers will independently screen all citations and full-text articles and abstract data. Data extracted will include the identification of the MoC, key elements of the intervention, organisational components, context-specific factors and patient-related, system-related and implementation-related outcomes. ETHICS AND DISSEMINATION: As a secondary analysis, this study does not require ethical approval. It will provide a comprehensive understanding on existing MoCs for LBP, outcomes and context-related challenges that may influence implementation in primary healthcare, which is meaningful knowledge to inform future research in this field. Findings will be disseminated through research papers in peer-reviewed journals, presentations at relevant conferences and documentation for professional organisations and stakeholders.

Does the Aged Simulation Suit help nursing students provide better care? - A phenomenological study.

BACKGROUND: The use of simulation in the training of nurses has increased in the last decades, allowing the acquisition and development of several competencies. OBJECTIVE: Understand the experiences of nursing students who used the aged simulation suit. METHODOLOGY: Qualitative study of a phenomenological nature. The participants were nursing students, who used the aged simulation suit. Data collection was made through the interview, and the data analysis was performed following the Giorgi phenomenological method. RESULTS: Three themes reflect the essence of the experience: Wear the skin of the elderly; Confrontation with their own ageing process; Skills development. CONCLUSION: If, on the one hand, the students who used the aged simulation suit experienced sensory and motor impairment and consequent confrontation with their own ageing process, on the other hand, they experienced the development of scientific, relational and citizenship skills. It is expected that the results of this work will foster the use of the aged simulation suit as a complementary methodology, with potential impact on the quality of care and health gains.

Older adult care in nursing education: How have curricula been developed?

Given the rapidly growing older adult population, future nurses should increase their knowledge and skills in gerontological nursing to deliver high-quality care to older adults. The aim of this national survey (n = 40 nursing schools) was to analyse the status of gerontology education in Portuguese baccalaureate nursing programmes. Data were collected using a 51-item questionnaire about baccalaureate nursing education programmes and gerontology-related topics. Descriptive analysis was used. A total of 18 nursing schools returned the questionnaire (response rate = 45%). Results showed that 66.7% (n = 12) of nursing schools integrated gerontology content into several courses, 38.9% (n = 7) of them had stand-alone courses, and 11.1% (n = 2) of them had both options. The most significant factor inhibiting the development of the gerontological nursing curriculum was the negative image of gerontological nursing (44.4%). Gerontological-related competencies were identified in only two nursing programmes. Thirteen schools reported needing help to strengthen the gerontological content in the nursing curriculum. This study has demonstrated that gerontological content is covered in the nursing curriculum of all nursing schools. The increase of knowledge and skills in gerontological nursing and the development of a standard gerontological curriculum could contribute to enhancing gerontological nursing education and practice.

Knowledge and Myths about Palliative Care among the General Public and Health Care Professionals in Portugal.

Background: International research has shown that healthcare professionals (HCPs) and nonhealthcare professionals (NHCPs) are unaware of the goals and purposes of palliative care. This study evaluates the knowledge of palliative care among a sample of Portuguese adults and correlates their level of knowledge with age, gender, profession, and experience of family member's palliative care. Method: A cross-sectional online survey was carried out on a sample of 152 HCPs and 440 NHCPs who completed an anonymous questionnaire of sociodemographic, family, and professional data, and an instrument of 26 dichotomous (true or false) questions focusing on palliative care goals and purposes. Results: The 592 participants had a mean age of 31.3 ± 11.1 years, and most were female. Statistically significant differences between statements considered as correct by HCPs and NHCPs were found in 24 statements; HCPs had the highest percentage of correct answers. The terms most frequently associated with palliative care mentioned by NHCPs were chronic and progressive disease (n = 76), while HCPs mostly mentioned quality-of-life promotion (n = 29). Women, the elderly, and HCPs had a higher level of knowledge regarding palliative care (p < 0.001). Conclusions: Results clearly show gaps in knowledge of palliative care, especially among NHCPs. An integrated approach is needed to inform and clarify the philosophy and goals of palliative care in different settings in order to improve knowledge.

Interferon-γ and high glucose-induced opening of Cx43 hemichannels causes endothelial cell dysfunction and damage.

Both IFN-γ or high glucose have been linked to systemic inflammatory imbalance with serious repercussions not only for endothelial function but also for the formation of the atherosclerotic plaque. Although the uncontrolled opening of connexin hemichannels underpins the progression of various diseases, whether they are implicated in endothelial cell dysfunction and damage evoked by IFN-γ plus high glucose remains to be fully elucidated. In this study, by using live cell imaging and biochemical approaches, we demonstrate that IFN-γ plus high glucose augment endothelial connexin43 hemichannel activity, resulting in the increase of ATP release, ATP-mediated Ca2+ dynamics and production of nitric oxide and superoxide anion, as well as impaired insulin-mediated uptake and intercellular diffusion of glucose and cell survival. Based on our results, we propose that connexin 43 hemichannel inhibition could serve as a new approach for tackling the activation of detrimental signaling resulting in endothelial cell dysfunction and death caused by inflammatory mediators during atherosclerosis secondary to diabetes mellitus.

Cholesterol uptake and efflux are impaired in human trophoblast cells from pregnancies with maternal supraphysiological hypercholesterolemia.

Maternal physiological (MPH) or supraphysiological hypercholesterolaemia (MSPH) occurs during pregnancy. Cholesterol trafficking from maternal to foetal circulation requires the uptake of maternal LDL and HDL by syncytiotrophoblast and cholesterol efflux from this multinucleated tissue to ApoA-I and HDL. We aimed to determine the effects of MSPH on placental cholesterol trafficking. Placental tissue and primary human trophoblast (PHT) were isolated from pregnant women with total cholesterol <280 md/dL (MPH, n = 27) or ≥280 md/dL (MSPH, n = 28). The lipid profile in umbilical cord blood from MPH and MSPH neonates was similar. The abundance of LDL receptor (LDLR) and HDL receptor (SR-BI) was comparable between MSPH and MPH placentas. However, LDLR was localized mainly in the syncytiotrophoblast surface and was associated with reduced placental levels of its ligand ApoB. In PHT from MSPH, the uptake of LDL and HDL was lower compared to MPH, without changes in LDLR and reduced levels of SR-BI. Regarding cholesterol efflux, in MSPH placentas, the abundance of cholesterol transporter ABCA1 was increased, while ABCG1 and SR-BI were reduced. In PHT from MSPH, the cholesterol efflux to ApoA-I was increased and to HDL was reduced, along with reduced levels of ABCG1, compared to MPH. Inhibition of SR-BI did not change cholesterol efflux in PHT. The TC content in PHT was comparable in MPH and MSPH cells. However, free cholesterol was increased in MSPH cells. We conclude that MSPH alters the trafficking and content of cholesterol in placental trophoblasts, which could be associated with changes in the placenta-mediated maternal-to-foetal cholesterol trafficking.

Gestational Diabetes Mellitus Treatment Schemes Modify Maternal Plasma Cholesterol Levels Dependent to Women´s Weight: Possible Impact on Feto-Placental Vascular Function.

: Gestational diabetes mellitus (GDM) associates with fetal endothelial dysfunction (ED), which occurs independently of adequate glycemic control. Scarce information exists about the impact of different GDM therapeutic schemes on maternal dyslipidemia and obesity and their contribution to the development of fetal-ED. The aim of this study was to evaluate the effect of GDM-treatments on lipid levels in nonobese (N) and obese (O) pregnant women and the effect of maternal cholesterol levels in GDM-associated ED in the umbilical vein (UV). O-GDM women treated with diet showed decreased total cholesterol (TC) and low-density lipoproteins (LDL) levels with respect to N-GDM ones. Moreover, O-GDM women treated with diet in addition to insulin showed higher TC and LDL levels than N-GDM women. The maximum relaxation to calcitonin gene-related peptide of the UV rings was lower in the N-GDM group compared to the N one, and increased maternal levels of TC were associated with even lower dilation in the N-GDM group. We conclude that GDM-treatments modulate the TC and LDL levels depending on maternal weight. Additionally, increased TC levels worsen the GDM-associated ED of UV rings. This study suggests that it could be relevant to consider a specific GDM-treatment according to weight in order to prevent fetal-ED, as well as to consider the possible effects of maternal lipids during pregnancy.

Maternal Dyslipidaemia in Pregnancy with Gestational Diabetes Mellitus: Possible Impact on Foetoplacental Vascular Function and Lipoproteins in the Neonatal Circulation.

Dyslipidaemia occurs in pregnancy to secure foetal development. The mother shows a physiological increase in plasma total cholesterol and Triglycerides (TG) as pregnancy progresses (i.e. maternal physiological dyslipidaemia in pregnancy). However, in some women pregnancy-associated dyslipidaemia exceeds this physiological adaptation. The consequences of this condition on the developing fetus include endothelial dysfunction of the foetoplacental vasculature and development of foetal aortic atherosclerosis. Gestational Diabetes Mellitus (GDM) associates with abnormal function of the foetoplacental vasculature due to foetal hyperglycaemia and hyperinsulinaemia, and associates with development of cardiovascular disease in adulthood. Supraphysiological dyslipidaemia is also detected in GDM pregnancies. Although there are several studies showing the alteration in the maternal and neonatal lipid profile in GDM pregnancies, there are no studies addressing the effect of dyslipidaemia in the maternal and foetal vasculature. The literature reviewed suggests that dyslipidaemia in GDM pregnancy should be an additional factor contributing to worsen GDM-associated endothelial dysfunction by altering signalling pathways involving nitric oxide bioavailability and neonatal lipoproteins.

Medication adherence and management in older people: identify and intervene

Medication non-adherence rates in older people range between 45 and 75% due to several reasons. A descriptive, quantitative study is being conducted with the purpose of identifying older people's knowledge about medication management, their difficulties, and strategies used. The sample is composed of older people (aged 65 years or over) who use day care centers in Coimbra. Data are collected using a questionnaire designed by the authors. The AGITE (Adesão e Gestão por Idosos da Terapêutica, Older People's Medication Adherence and Management) tool has 4 open-ended questions and 26 closed-ended questions. It is used in combination with the 6-item Cognitive Impairment Test (6CIT) and the Graffar scale. The study was approved by the Ethics Committee of the Health Sciences Research Unit: Nur-sing, Nursing School of Coimbra. The final version of the questionnaire was applied to a sample composed of 128 older adults with a mean age of 78.24 years. The preliminary results show that the questionnaire is easy to apply. With regard to its psychometric properties, and based on the exploratory factor analysis, three dimensions emerged with an acceptable internal consistency (0.6-0.8). The AGITE tool may be an adequate tool for identifying older people's difficulties and designing nursing strategies to help them overcome these difficulties. For this reason, the study should continue being developed

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High density lipoprotein cholesterol and proteome in SR-B1 KO mice: lost in precipitation.

Scavenger receptor class B type 1 (SR-B1) plays an essential role in high density lipoprotein (HDL) metabolism. SR-B1 deficient (SR-B1 KO) mice are prone to atherosclerosis and exhibit abnormally large, cholesterol-rich, dysfunctional HDL. In a recent issue of J Transl Med, Cao et al. described results of proteomics analyses of HDL isolated from wild-type (WT) and SR-B1 KO mice using precipitation of large lipoproteins with polyethylene glycol (PEG). They report abnormalities in SR-B1 KO HDL protein components that correlate with HDL function. In this commentary, we describe and discuss the differences in the results published by Cao et al. and those obtained in a recent study from our laboratory using shotgun proteomics of HDL of SR-B1 KO mice isolated by ultracentrifugation. We propose that different HDL purification procedures used may account for the discrepancies observed. We show that SR-B1 KO HDL purification using either PEG or dextran sulfate precipitation results in enrichment of small HDL subclasses, and may therefore underestimate alterations in lipoprotein composition or function. Compared to HDL obtained by ultracentrifugation, HDL isolated by PEG precipitation show a lower ApoE/ApoA-I proportion and reduced cholesterol content. HDL protein components described by Cao et al. or our laboratory are mostly inconsistent: only 33 HDL proteins were detected in both datasets, whereas a significant number of proteins were only identified by Cao et al. (n = 43) or Contreras-Duarte et al. (n = 26) datasets. The relative abundance of HDL-associated peptide and protein levels in WT vs SR-B1 HDL were also highly different in both datasets. This study indicates that caution must be taken when interpreting results from HDL isolated by chemical precipitation.

Connexin 43 Hemichannel Activity Promoted by Pro-Inflammatory Cytokines and High Glucose Alters Endothelial Cell Function.

The present work was done to elucidate whether hemichannels of a cell line derived from endothelial cells are affected by pro-inflammatory conditions (high glucose and IL-1ß/TNF-α) known to lead to vascular dysfunction. We used EAhy 926 cells treated with high glucose and IL-1ß/TNF-α. The hemichannel activity was evaluated with the dye uptake method and was abrogated with selective inhibitors or knocking down of hemichannel protein subunits with siRNA. Western blot analysis, cell surface biotinylation, and confocal microscopy were used to evaluate total and plasma membrane amounts of specific proteins and their cellular distribution, respectively. Changes in intracellular Ca2+ and nitric oxide (NO) signals were estimated by measuring FURA-2 and DAF-FM probes, respectively. High glucose concentration was found to elevate dye uptake, a response that was enhanced by IL-1ß/TNF-α. High glucose plus IL-1ß/TNF-α-induced dye uptake was abrogated by connexin 43 (Cx43) but not pannexin1 knockdown. Furthermore, Cx43 hemichannel activity was associated with enhanced ATP release and activation of p38 MAPK, inducible NO synthase, COX2, PGE2 receptor EP1, and P2X7/P2Y1 receptors. Inhibition of the above pathways prevented completely the increase in Cx43 hemichannel activity of cells treated high glucose and IL-1ß/TNF-α. Both synthetic and endogenous cannabinoids (CBs) also prevented the increment in Cx43 hemichannel opening, as well as the subsequent generation and release of ATP and NO induced by pro-inflammatory conditions. The counteracting action of CBs also was extended to other endothelial alterations evoked by IL-1ß/TNF-α and high glucose, including increased ATP-dependent Ca2+ dynamics and insulin-induced NO production. Finally, inhibition of Cx43 hemichannels also prevented the ATP release from endothelial cells treated with IL-1ß/TNF-α and high glucose. Therefore, we propose that reduction of hemichannel activity could represent a strategy against the activation of deleterious pathways that lead to endothelial dysfunction and possibly cell damage evoked by high glucose and pro-inflammatory conditions during cardiovascular diseases.

Maternal supraphysiological hypercholesterolemia associates with endothelial dysfunction of the placental microvasculature.

Maternal physiological or supraphysiological hypercholesterolemia (MPH, MSPH) occurs during pregnancy. MSPH is associated with foetal endothelial dysfunction and atherosclerosis. However, the potential effects of MSPH on placental microvasculature are unknown. The aim of this study was to determine whether MSPH alters endothelial function in the placental microvasculature both ex vivo in venules and arterioles from the placental villi and in vitro in primary cultures of placental microvascular endothelial cells (hPMEC). Total cholesterol < 280 mg/dL indicated MPH, and total cholesterol ≥280 mg/dL indicated MSPH. The maximal relaxation to histamine, calcitonin gene-related peptide and adenosine was reduced in MSPH venule and arteriole rings. In hPMEC from MSPH placentas, nitric oxide synthase (NOS) activity and L-arginine transport were reduced without changes in arginase activity or the protein levels of endothelial NOS (eNOS), human cationic amino acid 1 (hCAT-1), hCAT-2A/B or arginase II compared with hPMEC from MPH placentas. In addition, it was shown that adenosine acts as a vasodilator of the placental microvasculature and that NOS is active in hPMEC. We conclude that MSPH alters placental microvascular endothelial function via a NOS/L-arginine imbalance. This work also reinforces the concept that placental endothelial cells from the macro- and microvasculature respond differentially to the same pathological condition.

Foetoplacental epigenetic changes associated with maternal metabolic dysfunction.

Metabolic-related diseases are attributed to a sedentary lifestyle and eating habits, and there is now an increased awareness regarding pregnancy as a preponderant window in the programming of adulthood health and disease. The developing foetus is susceptible to the maternal environment; hence, any unfavourable condition will result in foetal physiological adaptations that could have a permanent impact on its health. Some of these alterations are maintained via epigenetic modifications capable of modifying gene expression in metabolism-related genes. Children born to mothers with dyslipidaemia, pregestational or gestational obesity, and gestational diabetes mellitus, have a predisposition to develop metabolic alterations during adulthood. CpG methylation-associated alterations to the expression of several genes in the human placenta play a crucial role in the mother-to-foetus transfer of nutrients and macromolecules. Identification of epigenetic modifications in metabolism-related tissues of offspring from metabolic-altered pregnancies is essential to obtain insights into foetal programming controlling newborn, childhood, and adult metabolism. This review points out the importance of the foetal milieu in the programming and development of human disease and provides evidence of this being the underlying mechanism for the development of adulthood metabolic disorders in maternal dyslipidaemia, pregestational or gestational obesity, and gestational diabetes mellitus.