Evaluation of the cell viability of human Wharton's jelly stem cells for use in cell therapy

Human umbilical cord Wharton's jelly stem cells (HWJSCs) are gaining attention as a possible clinical source of mesenchymal stem cells for cell therapy and tissue engineering due to their high accessibility, expansion potential, and plasticity. We employed a combination of highly sensitive techniques to determine the average cell viability levels and proliferation capabilities of 10 consecutive cell passages of cultured HWJSCs and then used RNA microarrays to identify genes associated with changes in cell viability levels. We found an initial decrease in cell viability from the first to the third cell passage followed by an increase until the sixth passage and a final decrease from the sixth to tenth cell passages. The highest cell viability levels corresponded to the fifth and sixth passages. The intracellular ionic contents of potassium, sodium, and chlorine suggest that the lower cell viability levels at passages 2, 3, and 8-10 may be associated with apoptotic cell death. In fact, gene expression analysis revealed that the average cell viability was significantly associated with genes with a function in apoptotic cell death, especially pro-apoptotic FASTKD2, BNIP3L genes and anti-apoptotic TNFAIP8 and BCL2L2 genes. This correlation with both pro-apoptotic and anti-apoptotic genes suggests that there may be a complex live-death equilibrium in cultured HWJSCs kept in culture for multiple cell passages. In this study, the highest cell viability levels corresponded to the fifth and sixth HWJSC passages, suggesting that these passages should be preferentially employed in cell therapy or tissue engineering protocols using this cell type

Comparing passive leg raising and suprasystolic ankle occlusion responses to quantify age-related microcirculatory status

The skin provides an easy accessible vascular network to assess microcirculation by laser Doppler flowmetry (LDF), and transcutaneous (tc) gasometry, widely known techniques used for this purpose. the objective of this study was to assess and compare the microcirculation status of different age subjects, knowing that the ageing process progressively affects macro and microcirculatory vessels. We’ve chosen to compare dynamical responses to two provocation tests – passive leg raising (PLR) and ankle occlusion - in 59 healthy subjects, 35 young (22.1 ± 3.7 years old.) in Group 1, and 24 older (50.8 ± 7.6 years old.) in Group 2, selected after informed consent. Local blood flow, tcpO2 and transepidermal water loss (TEWL) were measured in distal locations of the lower limb. PLR and ankle occlusion significantly reduced blood flow and tcpO2 in both groups, while no changes were found for TEWL. While the magnitude of the hyperemic response was found to be significantly reduced in group 2, no differences were found during ankle occlusion. tcpO2-dependent parameters were also significantly different between groups. These results seem to confirm the usefulness of these experimental models to distinguish the microcirculatory function of subjects with different ages, with PLR being more sensible in detecting age-related changes

Development of an in vivo method to better understand the obese skin

The impact of obesity in the pathophysiology of human skin seems to be related to various dermatoses, basically resulting from the change in its normal physiology, including changes in the “barrier” and the “envelope" functions as well . However, the available information is still scarce due to the many complexities of the subject. This work aims to define an experimental methodology approach to objectively study the functional changes that characterize the obese skin. This transversal study included 28 healthy volunteers, female (mean age 23 ± 5 years old), after informed consent. Skin functional characterization was obtained in one single measurement by non-invasive techniques, under controlled conditions. Relevant variables were hydration (superficial and deep), barrier function and biomechanical behavior, measured at four different anatomical areas. Through the SPSS (v 20.0) a univariate statistical analysis was performed to calculate central tendency and dispersion measures. The Pearson's and the Spearman's tests were chosen for those variables that followed , or not, a normal distribution, respectively, assuming a confidence level of 95%. Results allow us to propose a methodology for the study of the skin applied to obese patients, including the choice of the anatomical areas and variables appropriate to the intended goal

Relationship between the dietary intake of water and skin hydration

Several studies about the importance of water in the hydration of the human skin suggest that higher water intake might have a positive impact on the skin. When measuring water consumption, it must be taken into account that the water comes from various sources. With this in mind, we evaluated the impact of an increased inflow of 2L of water per day, on two groups with different daily water intakes. Results suggest that there is an improvement in the epidermal and dermal hydration obtained by standard methods. The magnitude of this impact on skin hydration is greater in the group that regularly consumes less water. This suggests that an increase in water consumption has more beneficial effects on the skin health of those individuals that consume less water per day. These data are consistent with the published literature, which therefore justifies further research into this topic

Clinical and Neuropsychological Correlates of Prefrailty Syndrome

Physical frailty is closely associated with cognitive impairment. We aim to investigate the neuropsychological profiles of prefrail and non-frail dementia-free community-dwelling older adults using a comprehensive neuropsychological evaluation, and to examine the association between specific frailty criteria and clinical and neuropsychological scores. Participants completed a comprehensive standardized neuropsychological evaluation (covering cognitive domains such as memory, executive functions, language and attention), and frailty assessment. Frailty was assessed according to biological criteria: unintentional weight loss, exhaustion, low physical activity, slowness, and weakness. The sample comprised 60 dementia-free community-dwelling adults, aged 65 years or older (range 65-89 years; 60.0% women). Forty-two participants were classified as robust (no frailty criteria present), and 18 as prefrail (1 or 2 frailty criteria present). We explored neurocognitive differences between the groups and examined the association between specific criteria of frailty phenotype and clinical and neuropsychological outcomes with bivariate tests and multivariate models. Prefrail participants showed poorer cognitive performance than non-frail participants in both memory and non-memory cognitive domains. However, delayed episodic memory was the only cognitive subdomain that remained significant after controlling for age, gender, and educational level. Gait speed was significantly associated with general cognitive performance, immediate memory, and processing speed, while grip strength was associated with visual episodic memory and visuoconstructive abilities. Both gait speed and grip strength were negatively associated with depressive scores. Our results suggest that prefrailty is associated with cognitive dysfunction. The fact that specific cognitive domains may be susceptible to subclinical states of physical frailty may have important clinical implications. Indeed, early detection of specific cognitive dysfunctions may allow opportunities for reversibility

Relationship between skin hydration and elasticity in normal weighted subjects and the influence of age

Skin is the largest organ of the human body. It is a protective organ and of all its known functions, the most significant is the capacity to adapt itself to the contours of the body. The current study aims to determine the extent to which hydration influences or is influenced by elasticity, by comparing the parameters of hydration and elasticity. A convenience sample of 42 volunteers was selected all of whom were female, healthy and with normal BMI according to WHO. The “barrier” function was characterized by the transepidermal water loss (Tewameter TM300); the superficial epidermal hydration was measured by Moisturemeter SC and Corneometer and the “envelope” function was assessed by the Cutometer MPA580 and by the reviscometer RV600. Measurements were taken on the face (zygomatic and frontal areas), in the breast and in the abdominal areas. The most significant results show that almost all hydration and elasticity parameters fluctuate with age, which corresponds to previous studies. Moreover, there is some interaction between hydration parameters and some elasticity descriptors that should be investigated in future studies

Brain-Derived Neurotrophic Factor Levels in Cord Blood from Growth Restricted Fetuses with Doppler Alteration Compared to Adequate for Gestational Age Fetuses

Background and Objectives: Fetal growth restriction (FGR) is a severe obstetric disease characterized by a low fetal size entailing a set of undesired consequences. For instance, previous studies have noticed a worrisome association between FGR with an abnormal neurodevelopment. However, the precise link between FGR and neurodevelopmental alterations are not yet fully understood yet. Brain-derived neurotrophic factor (BDNF) is a critical neurotrophin strongly implicated in neurodevelopmental and other neurological processes. In addition, serum levels of BDNF appears to be an interesting indicator of pathological pregnancies, being correlated with the neonatal brain levels. Therefore, the aim of this study is to analyze the blood levels of BDNF in the cord blood from fetuses with FGR in comparison to those with weight appropriate for gestational age (AGA). Materials and Methods: In this study, 130 subjects were recruited: 91 in group A (AGA fetuses); 39 in group B (16 FGR fetuses with exclusively middle cerebral artery (MCA) pulsatility index (PI) 95th percentile). Serum levels of BDNF were determined through ELISA reactions in these groups. Results: Our results show a significant decrease in cord blood levels of BDNF in FGR and more prominently in those with UA PI >95th percentile in comparison to AGA. FGR fetuses with exclusively decreased MCA PI below the 5th percentile also show reduced levels of BDNF than AGA, although this difference was not statistically significant. Conclusions: Overall, our study reports a potential pathophysiological link between reduced levels of BDNF and neurodevelopmental alterations in fetuses with FGR. However, further studies should be conducted in those FGR subjects with MCA PI < 5th percentile in order to understand the possible implications of BDNF in this group.Depto. de Salud Pública y Materno - InfantilFac. de MedicinaTRUEUnión EuropeaComunidad de MadridInstituto de Salud Carlos IIIHalekulani S.LFundación Santiago Dexeus Fontpu

Newborns of Mothers with Venous Disease during Pregnancy Show Increased Levels of Lipid Peroxidation and Markers of Oxidative Stress and Hypoxia in the Umbilical Cord

The study (FIS-PI18/00912) was supported by the Instituto de Salud Carlos III (grant no. Estatal de I + D + I 2013–2016) and co-financed by the European Development Regional Fund “A way to achieve Europe” and B2017/BMD-3804 MITIC-CM (Comunidad de Madrid), and Halekulani S.L.Chronic venous disease (CVD) encompasses a set of disorders of the venous system that have a high prevalence in Western societies and are associated with significant sociohealth costs. Pregnancy is a period in which different hormonal and haemodynamic changes occur that lead to significant changes in the cardiovascular system, increasing the risk of developing venous problems, especially during the third trimester of gestation. In turn, CVD involves a series of local and systemic alterations that can have negative repercussions in pregnancy. In this context, the role of oxidative stress in the pathophysiology of this condition has been shown to significantly affect other vascular structures during pregnancy, such as the placenta. However, the effects of oxidative stress on the umbilical cord in women with CVD have not yet been fully elucidated. Thus, the objective of this study was to analyse the gene and protein expression of the enzymes NOX-1, NOX-2 and iNOS, which are involved in the production of reactive oxygen and nitrogen species, respectively. Similarly, the presence of hypoxia-inducible factor 1-alpha (HIF-1α) in the umbilical cord in women with CVD was compared to that of pregnant control women, and the levels of the lipid peroxidation marker malonyldialdehyde (MDA) in cord tissue and blood was also analysed. Our results support a significant increase in the enzymes NOX-1, NOX-2 and iNOS and HIF-1α and MDA in the umbilical cord tissue and blood of women with CVD. For the first time, our work demonstrates an increase in oxidative stress and cellular damage in the umbilical cords of pregnant women who develop this condition, deepening the understanding of the consequences of CVD during pregnancy.Depto. de Salud Pública y Materno - InfantilFac. de MedicinaTRUEUnión EuropeaComunidad de MadridInstituto de Salud Carlos IIIHalekulanipu

Factors Associated with Failure of Bakri Balloon Tamponade for the Management of Postpartum Haemorrhage. Case Series Study and Systematic Review

Background: Postpartum haemorrhage (PPH) is an unpredictable obstetric emergency that requires a multidisciplinary approach. Bakri balloon tamponade (BBT) is recommended when PPH does not respond to medical treatment. Nowadays few published studies have performed a multivariate analysis to determine the variables independently associated with BBT failure. Methods: Our study purpose was to determine the variables independently associated with BBT failure: first, in a large single-centre cohort study between 2010 and 2020, and second, in a systematic literature review using Medline and the Cochrane Library. Maternal and perinatal variables, PPH characteristics, technique-related variables and complications were recorded in the case series study, comparing between successful and failed BBT patients. Study characteristic and variables significantly associated with BBT failure were recorded in the systematic review. All studies used a logistic regression test. Results: The case series included 123 patients. The profile of these patients were primiparous, with vaginal delivery and a full-term new-born. BBT was successful in 81.3% of cases. Five studies were included in the systematic review, providing data from 551 patients. BBT was successful in 79.5% of cases. Conclusions: Maternal age, caesarean delivery, ≥7 red blood cells units (RBCU) transfused and curettage before BBT insertion, history of caesarean section, pre-pregnancy obesity, anteriorly placed placenta, placenta accreta, caesarean delivery, estimated blood loss before insertion of BBT, long operation duration, and coagulopathy were independent factors for BBT failure

A New Multiplatform Model for Outpatient Prenatal and Postpartum Care in a Cohort of COVID-19-Affected Obstetric Patients

Spain was one of the epicenters of the first wave of the COVID-19 pandemic. We describe in this article the design and results of a new telephone-and-telematic multiplatform model of systematic prenatal and postpartum follow-up for COVID-19-affected women implemented in a tertiary reference hospital in Madrid. We included patients with RT-PCR-confirmed COVID-19 during pregnancy or delivery from 10 March 2020 to 15 December 2020. We had a total of 211 obstetric patients: 148 (70.1%) were tested at the onset of suspicious clinical manifestations and 62 (29.4%) were tested in the context of routine screening. Of all the patients, 60 women (28.4%) were asymptomatic and 97 (46%) presented mild symptoms. Fifty-one women (24.2%) were admitted to our hospital for specific treatment because of moderate or severe symptoms. We had no missed cases and a good adherence. The mean number of calls per patient was 2.3. We performed 55 in-person visits. We analyzed the complexity of our program over time, showing a two-wave-like pattern. One patient was identified as needing hospitalization and we did not record major morbidity. Telemedicine programs are a strong and reproducible tool to reach to pregnant population affected by COVID-19, to assess its symptoms and severity, and to record for pregnancy-related symptoms both in an outpatient regime and after discharge from hospital