Voices of Older People in Wales: a qualitative study of health and wellbeing among over 50's

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Dynamic fluid shifts induced by fetal bypass

ObjectiveFluid shifts have been suggested to occur with fetal bypass. The degree or mechanisms behind these volume changes (or location) have not been defined. We characterized the preceding and correlated the findings to plasma vasopressin concentrations, the critical peptide of osmoregulation.MethodsSeventeen ovine fetuses (105–111 days' gestation) were started on bypass and followed 2 hours after bypass. Hemodynamics and volume replacements needed to maintain minimum reservoir volume during bypass and normal physiologic parameters after bypass were recorded. Serial blood samples were collected to assess gas exchange and vasopressin levels. Changes in total tissue water content were measured for several organs and the placenta. Plasma volume, fluid shifts, and osmolarity were calculated.ResultsHematocrit values decreased by 15 minutes of bypass to 28% from 33% and then increased to 34% by 120 minutes after bypass, corresponding to a decreased fetal plasma volume of 79 to 72 mL/kg by 120 minutes after bypass. The majority of volume shifts (approximately 100 mL/kg) occurred during bypass, but additional volume replacements were required after bypass to maintain normal hemodynamics, resulting in overall losses of 0.8 mL · kg−1 · min−1. Losses were not accounted for by placental or organ edema. Vasopressin levels increased dramatically with bypass (39–51.5 pg/mL) and were strongly predicted by increased fetal plasma volumes (R2 = 0.90), whereas osmolarity was not significantly associated with plasma volumes.ConclusionFetal bypass leads to significant fluid shifts that correlate strongly with increasing vasopressin levels (but not changes in osmolarity). The placenta is not the primary site of volume loss. Rehydration of the fetus is necessary after bypass

An Evaluation of the All-Wales Dietetic Capacity Grant Scheme: Final Report

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Preliminary Analysis of in Utero Low-Level Arsenic Exposure and Fetal Growth Using Biometric Measurements Extracted from Fetal Ultrasound Reports

Background: Early life exposure to arsenic is associated with decreased birth weight in highly exposed populations but little is known about effects of low-level arsenic exposure on growth in utero. Methods: Using a sample of 272 pregnancies from New Hampshire we obtained biometric measurements directly from fetal ultrasound reports commonly found in electronic medical records. We used information extraction methods to develop and validate an automated approach for mining biometric measurements from the text of clinical reports. As a preliminary analysis, we examined associations between in utero low-level arsenic exposure (as measured by maternal urinary arsenic concentration) and fetal growth measures (converted to Z-scores based on reference populations for estimated fetal weight, head, and other body measures) at approximately 18 weeks of gestation. Results: In a preliminary cross-sectional analysis of 223 out of 272 pregnancies, maternal urinary arsenic concentration (excluding arsenobetaine) was associated with a reduction in head circumference Z-score (Spearman correlation coefficient, rs = -0.08, p-value = 0.21) and a stronger association was observed among female fetuses at approximately 18 weeks of gestation (rs = - 0.21, p-value \u3c 0.05). Although, associations were attenuated in adjusted analyses — among female fetuses a 1 μg/L increase in maternal urinary arsenic concentration was associated with a decrease of 0.047 (95% CI: -0.115, 0.021) in head circumference and 0.072 (95% CI: −0.151, 0.007) decrease in biparietal head diameter Z-score. Conclusions: Our study demonstrates that useful data can be extracted directly from electronic medical records for epidemiologic research. We also found evidence that exposure to low-level arsenic may be associated with reduced head circumference in a sex dependent manner that warrants further investigation

Preliminary Analysis of in Utero Low-Level Arsenic Exposure and Fetal Growth Using Biometric Measurements Extracted from Fetal Ultrasound Reports

Background: Early life exposure to arsenic is associated with decreased birth weight in highly exposed populations but little is known about effects of low-level arsenic exposure on growth in utero. Methods: Using a sample of 272 pregnancies from New Hampshire we obtained biometric measurements directly from fetal ultrasound reports commonly found in electronic medical records. We used information extraction methods to develop and validate an automated approach for mining biometric measurements from the text of clinical reports. As a preliminary analysis, we examined associations between in utero low-level arsenic exposure (as measured by maternal urinary arsenic concentration) and fetal growth measures (converted to Z-scores based on reference populations for estimated fetal weight, head, and other body measures) at approximately 18 weeks of gestation. Results: In a preliminary cross-sectional analysis of 223 out of 272 pregnancies, maternal urinary arsenic concentration (excluding arsenobetaine) was associated with a reduction in head circumference Z-score (Spearman correlation coefficient, rs = -0.08, p-value = 0.21) and a stronger association was observed among female fetuses at approximately 18 weeks of gestation (rs = - 0.21, p-value \u3c 0.05). Although, associations were attenuated in adjusted analyses — among female fetuses a 1 μg/L increase in maternal urinary arsenic concentration was associated with a decrease of 0.047 (95% CI: -0.115, 0.021) in head circumference and 0.072 (95% CI: −0.151, 0.007) decrease in biparietal head diameter Z-score. Conclusions: Our study demonstrates that useful data can be extracted directly from electronic medical records for epidemiologic research. We also found evidence that exposure to low-level arsenic may be associated with reduced head circumference in a sex dependent manner that warrants further investigation

Blood Pressure Changes in Relation to Arsenic Exposure in a U.S. Pregnancy Cohort

Background: Inorganic arsenic exposure has been related to the risk of increased blood pressure based largely on cross-sectional studies conducted in highly exposed populations. Pregnancy is a period of particular vulnerability to environmental insults. However, little is known about the cardiovascular impacts of arsenic exposure during pregnancy. Objectives: We evaluated the association between prenatal arsenic exposure and maternal blood pressure over the course of pregnancy in a U.S. population. Methods: The New Hampshire Birth Cohort Study is an ongoing prospective cohort study in which \u3e 10% of participant household wells exceed the arsenic maximum contaminant level of 10 μg/L established by the U.S. EPA. Total urinary arsenic measured at 24–28 weeks gestation was measured and used as a biomarker of exposure during pregnancy in 514 pregnant women, 18–45 years of age, who used a private well in their household. Outcomes were repeated blood pressure measurements (systolic, diastolic, and pulse pressure) recorded during pregnancy. Results: Using linear mixed effects models, we estimated that, on average, each 5-μg/L increase in urinary arsenic was associated with a 0.15-mmHg (95% CI: 0.02, 0.29; p = 0.022) increase in systolic blood pressure per month and a 0.14-mmHg (95% CI: 0.02, 0.25; p = 0.021) increase in pulse pressure per month over the course of pregnancy. Conclusions: In our U.S. cohort of pregnant women, arsenic exposure was associated with greater increases in blood pressure over the course of pregnancy. These findings may have important implications because even modest increases in blood pressure impact cardiovascular disease risk

Age-Associated mRNA and miRNA Expression Changes in the Blood-Brain Barrier

Functional and structural age-associated changes in the blood-brain barrier (BBB) may affect the neurovascular unit and contribute to the onset and progression of age-associated neurodegenerative pathologies, including Alzheimer’s disease. The current study interrogated the RNA profile of the BBB in an ageing human autopsy brain cohort and an ageing mouse model using combined laser capture microdissection and expression profiling. Only 12 overlapping genes were altered in the same direction in the BBB of both ageing human and mouse cohorts. These included genes with roles in regulating vascular tone, tight junction protein expression and cell adhesion, all processes prone to dysregulation with advancing age. Integrated mRNA and miRNA network and pathway enrichment analysis of the datasets identified 15 overlapping miRNAs that showed altered expression. In addition to targeting genes related to DNA binding and/or autophagy, many of the miRNAs identified play a role in age-relevant processes, including BBB dysfunction and regulating the neuroinflammatory response. Future studies have the potential to develop targeted therapeutic approaches against these candidates to prevent vascular dysfunction in the ageing brain

Fecal microbiota transfer between young and aged mice reverses hallmarks of the aging gut, eye, and brain

Background: Altered intestinal microbiota composition in later life is associated with inflammaging, declining tissue function, and increased susceptibility to age-associated chronic diseases, including neurodegenerative dementias. Here, we tested the hypothesis that manipulating the intestinal microbiota influences the development of major comorbidities associated with aging and, in particular, inflammation affecting the brain and retina. Methods: Using fecal microbiota transplantation, we exchanged the intestinal microbiota of young (3 months), old (18 months), and aged (24 months) mice. Whole metagenomic shotgun sequencing and metabolomics were used to develop a custom analysis workflow, to analyze the changes in gut microbiota composition and metabolic potential. Effects of age and microbiota transfer on the gut barrier, retina, and brain were assessed using protein assays, immunohistology, and behavioral testing. Results: We show that microbiota composition profiles and key species enriched in young or aged mice are successfully transferred by FMT between young and aged mice and that FMT modulates resulting metabolic pathway profiles. The transfer of aged donor microbiota into young mice accelerates age-associated central nervous system (CNS) inflammation, retinal inflammation, and cytokine signaling and promotes loss of key functional protein in the eye, effects which are coincident with increased intestinal barrier permeability. Conversely, these detrimental effects can be reversed by the transfer of young donor microbiota. Conclusions: These findings demonstrate that the aging gut microbiota drives detrimental changes in the gut–brain and gut–retina axes suggesting that microbial modulation may be of therapeutic benefit in preventing inflammation-related tissue decline in later life. [MediaObject not available: see fulltext.] Graphical abstract: [Figure not available: see fulltext.

Characteristics associated with quality of life among people with drug-resistant epilepsy

Quality of Life (QoL) is the preferred outcome in non-pharmacological trials, but there is little UK population evidence of QoL in epilepsy. In advance of evaluating an epilepsy self-management course we aimed to describe, among UK participants, what clinical and psycho-social characteristics are associated with QoL. We recruited 404 adults attending specialist clinics, with at least two seizures in the prior year and measured their self-reported seizure frequency, co-morbidity, psychological distress, social characteristics, including self-mastery and stigma, and epilepsy-specific QoL (QOLIE-31-P). Mean age was 42 years, 54% were female, and 75% white. Median time since diagnosis was 18 years, and 69% experienced ≥10 seizures in the prior year. Nearly half (46%) reported additional medical or psychiatric conditions, 54% reported current anxiety and 28% reported current depression symptoms at borderline or case level, with 63% reporting felt stigma. While a maximum QOLIE-31-P score is 100, participants’ mean score was 66, with a wide range (25–99). In order of large to small magnitude: depression, low self-mastery, anxiety, felt stigma, a history of medical and psychiatric comorbidity, low self-reported medication adherence, and greater seizure frequency were associated with low QOLIE-31-P scores. Despite specialist care, UK people with epilepsy and persistent seizures experience low QoL. If QoL is the main outcome in epilepsy trials, developing and evaluating ways to reduce psychological and social disadvantage are likely to be of primary importance. Educational courses may not change QoL, but be one component supporting self-management for people with long-term conditions, like epilepsy