United States rural residence is associated with increased acute maternal end-organ injury or mortality after birth: a retrospective multi-state analysis, 2007-2018.

BACKGROUND: Geographic-based healthcare determinants and choice of anesthesia have been shown to be associated with maternal morbidity and mortality. We explored whether differences in maternal outcomes based on maternal residence, and anesthesia type for cesarean and vaginal birth, exist. METHODS: This study was a retrospective multi-state analysis; patient residence was the predictor variable of interest and a composite binary measure of maternal end-organ injury or inpatient mortality was the primary outcome. Our secondary outcomes included a binary measure of anesthesia type for cesarean birth (general vs. neuraxial [NA]) and NA analgesia for vaginal birth (no NA vs. NA). Our predictor variable of interest was patient residency (reference category central metropolitan areas of >1 million population), fringe large metropolitan county, medium metropolitan, small metropolitan, micropolitan, and non-metropolitan or micropolitan county. RESULTS: Women residing in micropolitan (OR 1.17; 95% CI 1.09 to 1.27) and non-metropolitan or micropolitan counties (OR 1.14; 95% CI 1.04 to 1.24) had the highest adjusted increased odds of adverse maternal outcomes. Those residing in suburban, medium, and small metropolitan areas underwent general anesthesia less often during cesarean births than those residing in urban areas. Patients residing in micropolitan rural (OR 2.07; 95% CI 2.02 to 2.12) and non-metropolitan or micropolitan (2.25; 95% CI 2.16 to 2.34) counties underwent vaginal births without NA analgesia more than twice as often as those residing in urban areas. CONCLUSIONS: Rural-urban disparities in maternal end-organ damage and mortality exist and anesthesia choice may play an important role in these disparate outcomes.

Intraoperative ketamine for prevention of depressive symptoms after major surgery in older adults: an international, multicentre, double-blind, randomised clinical trial.

BACKGROUND: Ketamine is a general anaesthetic with anti-depressant effects at subanaesthetic doses. We hypothesised that intraoperative administration of ketamine would prevent or mitigate postoperative depressive symptoms in surgical patients. METHODS: We conducted an international, randomised clinical trial testing the effects of intraoperative administration of ketamine [0.5 mg kg-1 (Lo-K) or 1.0 mg kg-1 (Hi-K)] vs control [saline placebo (P)] in patients ≥60 yr old undergoing major surgery with general anaesthesia. We administered the Patient Health Questionnaire-8 before the operation, on postoperative day (POD) 3 (primary outcome), and on POD30 to assess depressive symptoms, a secondary outcome of the original trial. RESULTS: There was no significant difference on POD3 in the proportion of patients with symptoms suggestive of depression between the placebo [23/156 (14.7%)] and combined ketamine (Lo-K plus Hi-K) [61/349 (17.5%)] groups [difference = -2.7%; 95% confidence interval (CI), 5.0% to -9.4%; P=0.446]. Of the total cohort, 9.6% (64/670; 95% CI, 7.6-12.0%) had symptoms suggestive of depression before operation, which increased to 16.6% (84/505; 95% CI, 13.6-20.1%) on POD3, and decreased to 11.9% (47/395; 95% CI, 9.1-15.5%) on POD30. Of the patients with depressive symptoms on POD3 and POD30, 51% and 49%, respectively, had no prior history of depression or depressive symptoms. CONCLUSIONS: Major surgery is associated with new-onset symptoms suggestive of depression in patients ≥60 yr old. Intraoperative administration of subanaesthetic ketamine does not appear to prevent or improve depressive symptoms. CLINICAL TRIALS REGISTRATION: NCT01690988.

Cerebrospinal-fluid drain-related complications in patients undergoing open and endovascular repairs of thoracic and thoraco-abdominal aortic pathologies: a systematic review and meta-analysis.

BACKGROUND: Cerebrospinal-fluid (CSF) drainage is recommended by current guidelines for spinal protection during open and endovascular repairs of thoracic and thoraco-abdominal aortic aneurysms. In the published literature, great variability exists in the rate of CSF-related complications and morbidity. Herein, we perform a systematic review and meta-analysis on the incidence of CSF drainage-related complications, and compare the complication rates between open and endovascular repairs. METHODS: The systematic review was conducted according to the Meta-Analysis of Observational Studies in Epidemiology guidelines. Thirty-four studies (4714 patients) were included in the quantitative analysis. The CSF drainage-related complications were categorised as mild, moderate, and severe. Pooled event rates for each complication category were estimated using a random-effect model. Random-effect uni- and multivariable meta-regression analyses were used to assess the effect of aortic-repair approach (open vs endovascular) and the CSF drainage criteria on CSF drainage-related complications. RESULTS: The pooled event rates were 6.5% [95% confidence interval (CI): 4.3-9.8%] for overall complications, 2% (95% CI: 1.1-3.4%) for minor complications, 3.7% (95% CI: 2.5-5.6%) for moderate complications, and 2.5% (95% CI: 1.6-3.8%) for severe complications. The drainage-related-mortality pooled event rate was 0.9% (95% CI: 0.6-1.4%). The uni- and multivariable meta-regression analyses showed no difference in complication rates between the open and endovascular approaches, or between the different CSF drainage protocols. CONCLUSION: The complication rate for CSF drainage is not negligible. Our results help define a more accurate risk-benefit ratio for CSF drain placement at the time of repair of thoracic and thoraco-abdominal aneurysms.

Lunch-time food choices in preschoolers: Relationships between absolute and relative intakes of different food categories, and appetitive characteristics and weight.

Children's appetitive characteristics measured by parent-report questionnaires are reliably associated with body weight, as well as behavioral tests of appetite, but relatively little is known about relationships with food choice. As part of a larger preloading study, we served 4-5year olds from primary school classes five school lunches at which they were presented with the same standardized multi-item meal. Parents completed Child Eating Behavior Questionnaire (CEBQ) sub-scales assessing satiety responsiveness (CEBQ-SR), food responsiveness (CEBQ-FR) and enjoyment of food (CEBQ-EF), and children were weighed and measured. Despite differing preload conditions, children showed remarkable consistency of intake patterns across all five meals with day-to-day intra-class correlations in absolute and percentage intake of each food category ranging from 0.78 to 0.91. Higher CEBQ-SR was associated with lower mean intake of all food categories across all five meals, with the weakest association apparent for snack foods. Higher CEBQ-FR was associated with higher intake of white bread and fruits and vegetables, and higher CEBQ-EF was associated with greater intake of all categories, with the strongest association apparent for white bread. Analyses of intake of each food group as a percentage of total intake, treated here as an index of the child's choice to consume relatively more or relatively less of each different food category when composing their total lunch-time meal, further suggested that children who were higher in CEBQ-SR ate relatively more snack foods and relatively less fruits and vegetables, while children with higher CEBQ-EF ate relatively less snack foods and relatively more white bread. Higher absolute intakes of white bread and snack foods were associated with higher BMI z score. CEBQ sub-scale associations with food intake variables were largely unchanged by controlling for daily metabolic needs. However, descriptive comparisons of lunch intakes with expected amounts based on metabolic needs suggested that overweight/obese boys were at particularly high risk of overeating. Parents' reports of children's appetitive characteristics on the CEBQ are associated with differential patterns of food choice as indexed by absolute and relative intake of various food categories assessed on multiple occasions in a naturalistic, school-based setting, without parents present.

Effect of propofol on the medial temporal lobe emotional memory system: a functional magnetic resonance imaging study in human subjects.

BACKGROUND: Subclinical doses of propofol produce anterograde amnesia, characterized by an early failure of memory consolidation. It is unknown how propofol affects the amygdala-dependent emotional memory system, which modulates consolidation in the hippocampus in response to emotional arousal and neurohumoral stress. We present an event-related functional magnetic resonance imaging study of the effects of propofol on the emotional memory system in human subjects. METHODS: Thirty-five healthy subjects were randomized to receive propofol, at an estimated brain concentration of 0.90 µg ml(-1), or placebo. During drug infusion, emotionally arousing and neutral images were presented in a continuous recognition task, while blood-oxygen-level-dependent activation responses were acquired. After a drug-free interval of 2 h, subsequent memory for successfully encoded items was assessed. Imaging analysis was performed using statistical parametric mapping and behavioural analysis using signal detection models. RESULTS: Propofol had no effect on the stereotypical amygdalar response to emotional arousal, but caused marked suppression of the hippocampal response. Propofol caused memory performance to become uncoupled from amygdalar activation, but it remained correlated with activation in the posterior hippocampus, which decreased in proportion to amnesia. CONCLUSIONS: Propofol is relatively ineffective at suppressing amygdalar activation at sedative doses, but abolishes emotional modulation and causes amnesia via mechanisms that commonly involve hyporesponsiveness of the hippocampus. These findings raise the possibility that amygdala-dependent fear systems may remain intact even when a patient has diminished memory of events. This may be of clinical importance in the perioperative development of fear-based psychopathologies, such as post-traumatic stress disorder. CLINICAL TRIAL REGISTRATION: NCT00504894.

Dipeptidyl peptidase-4 inhibitors administered in combination with metformin result in an additive increase in the plasma concentration of active GLP-1.

The aim of the study was to investigate the effects of a dipeptidyl peptidase-4 (DPP-4) inhibitor, of metformin, and of the combination of the two agents, on incretin hormone concentrations. Active and inactive (or total) incretin plasma concentrations, plasma DPP-4 activity, and preproglucagon (GCG) gene expression were determined after administration of each agent alone or in combination to mice with diet-induced obesity (DIO) and to healthy human subjects. In mice, metformin increased Gcg expression in the large intestine and elevated the plasma concentrations of inactive glucagon-like peptide 1 (GLP-1) (9-36) and glucagon. In healthy subjects, a DPP-4 inhibitor elevated both active GLP-1 and glucose dependent insulinotropic polypeptide (GIP), metformin increased total GLP-1 (but not GIP), and the combination resulted in additive increases in active GLP-1 plasma concentrations. Metformin did not inhibit plasma DPP-4 activity either in vitro or in vivo. The study results show that metformin is not a DPP-4 inhibitor but rather enhances precursor GCG expression in the large intestine, resulting in increased total GLP-1 concentrations. DPP-4 inhibitors and metformin have complementary mechanisms of action and additive effects with respect to increasing the concentrations of active GLP-1 in plasma.

Inhibition of dipeptidyl-peptidase IV does not increase circulating IGF-1 concentrations in growing pigs.

The enzyme dipeptidyl peptidase-IV (DPP-IV) inactivates a variety of bioactive peptides, including glucagon-like peptide-1 (GLP-1) and growth hormone releasing hormone (GHRH). Inhibiting DPP-IV in order to increase circulating GLP-1 is of interest as a treatment for Type II diabetes. Inactivation of DPP-IV may also increase circulating GHRH, potentially enhancing growth in domestic animals. To test the hypothesis that inhibition of DPP-IV activity will influence the growth hormone/ IGF-1 axis, growing pigs (Sus scrofa domesticus, 78 kg) were treated with a DPP-IV inhibitor (Compound 1, the 2,5-difluor-ophenyl analog of the triazolopiperazine MK0431, sitagliptin), and plasma concentrations of IGF-1 were monitored. Pigs were administered either sterile saline (0.11 ml/kg followed by a continuous infusion at 2 ml/hr for 72 hrs, controls, n = 2), Compound 1 (2.78 mg/kg followed by a continuous infusion at 0.327 mg/kg x hr for 72 hrs, n = 4) or GHRH (0.11 ml/kg sterile saline, followed by a continuous infusion of GHRH at 2.5 microg/ kg x hr for 48 hrs, n = 4). Plasma concentrations of Compound 1 were maintained at 1 microM, which resulted in a 90% inhibition of circulating DPP-IV activity. Relative to the predose 24-hr period, area under the IGF-1 concentration curve (AUC) tended to be lower (P = 0.062) with Compound 1 (.79 +/- 130 ng/ml x hr) than controls (543 +/- 330 ng/ml x hr). GHRH treatment increased the IGF-1 AUC (1210 +/- 160 ng/ml x hr, P = 0.049 vs. controls and P = 0.001 vs. Compound 1). We conclude that inhibition of DPP-IV does not alter the circulating levels of IGF-1 in the growing pig.

Methodology for worker neutron exposure evaluation in the PDCF facility design.

A project headed by Washington Group International is meant to design the Pit Disassembly and Conversion Facility (PDCF) to convert the plutonium pits from excessed nuclear weapons into plutonium oxide for ultimate disposition. Battelle staff are performing the shielding calculations that will determine appropriate shielding so that the facility workers will not exceed target exposure levels. The target exposure levels for workers in the facility are 5 mSv y(-1) for the whole body and 100 mSv y(-1) for the extremity, which presents a significant challenge to the designers of a facility that will process tons of radioactive material. The design effort depended on shielding calculations to determine appropriate thickness and composition for glove box walls, and concrete wall thicknesses for storage vaults. Pacific Northwest National Laboratory (PNNL) staff used ORIGEN-S and SOURCES to generate gamma and neutron source terms, and Monte Carlo (computer code for) neutron photon (transport) (MCNP-4C) to calculate the radiation transport in the facility. The shielding calculations were performed by a team of four scientists, so it was necessary to develop a consistent methodology. There was also a requirement for the study to be cost-effective, so efficient methods of evaluation were required. The calculations were subject to rigorous scrutiny by internal and external reviewers, so acceptability was a major feature of the methodology. Some of the issues addressed in the development of the methodology included selecting appropriate dose factors, developing a method for handling extremity doses, adopting an efficient method for evaluating effective dose equivalent in a non-uniform radiation field, modelling the reinforcing steel in concrete, and modularising the geometry descriptions for efficiency. The relative importance of the neutron dose equivalent compared with the gamma dose equivalent varied substantially depending on the specific shielding conditions and lessons were learned from this effect. This paper addresses these issues and the resulting methodology.

Enhanced visual memory effect for negative versus positive emotional content is potentiated at sub-anaesthetic concentrations of thiopental.

BACKGROUND: Emotional information has the ability to alter the formation and strength of a memory ('memory modulation'). Memory modulation by negative emotion is mediated by the amygdala. It is not known how gamma aminobutyric acid (GABA)ergic drugs affect the processes involved in memory modulation. This study investigates whether memory for negative emotional stimuli is more refractory to the effects of GABAergic drugs. METHODS: Eighty-three healthy volunteers were shown a randomized sequence of 60 visual stimuli consisting of negative, positive and neutral emotive pictures, while receiving a controlled infusion of thiopental (n=31), propofol (n=31), dexmedetomidine (n=10) or placebo (n=11). After a 5 h retention interval, when drug concentration was negligible, subjects performed a recognition task with 'old' pictures randomly mixed with 'new' pictures. Drug effect was calculated as the proportionate reduction in recognition for images of each emotional valence. RESULTS: Forty-eight subjects were included in a within-subject logistic dose-response model analysis. In the thiopental group there was a smaller drug effect seen for negative vs positive images (proportional memory reduction from baseline 0.27 (SD 0.20) vs 0.56 (0.25), P<0.001, n=20 included in analysis). A similar trend was seen in the propofol group (0.25 (0.28) vs 0.54 (0.30), n=10), but this did not attain statistical significance. No trend was seen in the dexmedetomidine group (0.33 (0.26) vs 0.24 (0.22), n=7). CONCLUSIONS: Over a specific dose range of thiopental (target serum concentration 2-7 micro g ml(-1)), impairment of explicit memory for images with negative emotional valence is less than that for images with positive emotional valence. There is a strong possibility that propofol (target serum concentration 0.3-2.4 micro g ml(-1)) causes a similar effect. Modulation of visual memory by negative emotional content continues at sub-anaesthetic concentrations of GABAergic drugs associated with explicit memory impairment.

Diversity, genetic structure and evidence of outcrossing in British populations of the rock fern Adiantum capillus-veneris using microsatellites.

Microsatellites were isolated and a marker system was developed in the fern Adiantum capillus-veneris. Polymorphic markers were then used to study the genetic diversity and structure of populations within the UK and Ireland where this species grows at the northern edge of its range, requiring a specific rock habitat and limited to a few scattered populations. Three dinucleotide loci detected a high level of diversity (23 alleles and 28 multilocus genotypes) across the UK and Ireland, with nearly all variation partitioned among rather than within populations. Of 17 populations represented by multiple samples, all except four were monomorphic. Heterozygosity was detected in three populations, all within Glamorgan, Wales (UK), showing evidence of outcrossing. We make inferences on the factors determining the observed levels and patterns of genetic variation and the possible evolutionary history of the populations.