Patterns in benthic macroinvertebrate assemblages in an active region of unconventional shale-gas development in the western Appalachian Plateau of West Virginia, USA.

We sampled headwater streams to characterize impacts of unconventional shale gas development (SGD) on aquatic ecosystems. The study area was relatively un-impacted by confounding activities. Intensity of SGD over the study decreased then increased again but not to levels seen the first year. Shale gas development was associated with increased, but non-impaired, water pH and specific conductance during the latter part of the study. Metrics summarizing macroinvertebrate assemblages were better on average in un-impacted reaches. A genus-level multimetric index of biotic integrity was statistically lower downstream of impacts compared to upstream, but only in the year when SGD activity was most intense. Multivariate analyses indicated that assemblages diverged in similarity downstream compared to upstream of impacts in the first and last years of the study when SGD activity was elevated. Assemblage divergence was related to variation in water quality. Indicator species analysis linked a few key taxa to un-impacted conditions in the first year of the study; tolerant taxa were indicators for impacted conditions later in the study. Our study links SGD to weak negative changes in water quality and benthic macroinvertebrates, which may have negative consequences to food quality for wildlife that rely on aquatic prey within forested systems.

Determinants of attained estradiol levels in response to oral estradiol plus progesterone therapy.

OBJECTIVES: Among postmenopausal women taking hormone therapy (HT), the estradiol (E2) dose and E2 levels were differentially associated with change in metabolic measures. We evaluated determinants of attained E2 levels in response to HT. METHODS: Postmenopausal women from the REPLENISH trial tested four formulations of oral combined E2 and progesterone compared with placebo. Mixed-effects linear models assessed characteristics associated with E2 levels among women with ≥80% HT compliance, adjusted for E2 dose and baseline E2 level. RESULTS: Among 1173 postmenopausal women with mean (standard deviation) age 55 (4.3) years and 5.2 (4.8) years since menopause, higher treated E2 levels were significantly related to younger age, more recent menopause, and current alcohol use, while lower E2 levels were related to current smoking. Both age and time since menopause were significantly inversely associated with E2 levels; time since menopause had a stronger association with E2 levels. In the final multivariable model, E2 levels were positively associated with current alcohol use, and inversely associated with time since menopause and current smoking. CONCLUSION: Adjusting for E2 dose and baseline E2 level, on-trial E2 levels were significantly associated with time since menopause, current smoking, and current alcohol use. Practitioners should consider these factors in individual women to achieve a desirable E2 level during HT.

Subclinical cardiovascular disease in HIV controller and long-term nonprogressor populations.

OBJECTIVES: Elite controllers (ECs), viraemic controllers (VCs), and long-term nonprogressors (LTNPs) control HIV viral replication or maintain CD4 T-cell counts without antiretroviral therapy, but may have increased cardiovascular disease (CVD) risk compared to HIV-uninfected persons. We evaluated subclinical carotid and coronary atherosclerosis and inflammatory biomarker levels among HIV controllers, LTNPs and noncontrollers and HIV-uninfected individuals in the Multicenter AIDS Cohort Study (MACS) and the Women's Interagency HIV Study (WIHS). METHODS: We measured carotid plaque presence and common carotid artery intima-media thickness (IMT) in 1729 women and 1308 men, and the presence of coronary artery calcium and plaque in a subgroup of men. Associations between HIV control category and carotid and coronary plaque prevalences were assessed by multivariable regression analyses adjusting for demographics and CVD risk factors. Serum inflammatory biomarker concentrations [soluble CD163 (sCD163), soluble CD14 (sCD14), galectin-3 (Gal-3), galectin-3 binding protein (Gal-3BP) and interleukin (IL)-6] were measured and associations with HIV control category assessed. RESULTS: We included 135 HIV controllers (30 ECs) and 135 LTNPs in the study. Carotid plaque prevalence and carotid IMT were similar in HIV controllers, LTNPs and HIV-uninfected individuals. HIV controllers and LTNPs had lower prevalences of carotid plaque compared to viraemic HIV-infected individuals. The prevalence of coronary atherosclerosis was similar in HIV controllers/LTNPs compared to HIV-uninfected and viraemic HIV-infected men. Controllers and LTNPs had higher concentrations of sCD163 and sCD14 compared to HIV-uninfected persons. CONCLUSIONS: Subclinical CVD was similar in HIV controllers, LTNPs and HIV-uninfected individuals despite elevated levels of some inflammatory biomarkers. Future studies of HIV controllers and LTNPs are needed to characterize the risk of CVD among HIV-infected persons.

Association of oral estradiol dose/levels with coagulation measures in early/late postmenopausal women.

Objective: This study evaluated associations of estradiol (E2) dose and serum E2 levels with coagulation/anti-coagulation measures in early (<6 years) compared with late (≥10 years) postmenopausal women.Methods: Postmenopausal women from the REPLENISH trial tested four formulations of oral combined E2 and progesterone compared with placebo. Mixed-effects linear models tested the association of E2 dose and serum E2 levels with the prothrombin time (PT), the activated partial thromboplastin time (APTT), antithrombin (ATHRM), fibrinogen (FIBRINO), protein C (PROTC), and protein S (PROTS), assessed five times over 12 months.Results: Among 1215 early and 297 late postmenopausal women, the E2 dose was statistically significantly inversely associated with the APTT in early postmenopause, PROTC in late postmenopause, and with the PT, ATHRM, and PROTS in both groups. Serum E2 levels were statistically significantly inversely associated with the APTT, PROTS, and FIBRINO in early postmenopause, the PT in late postmenopause, and ATHRM and PROTC in both groups. With longer time since menopause, the inverse E2 dose effect and serum E2 effects became stronger.Conclusion: Increasing E2 dose and serum E2 levels were associated with changes in coagulation/anti-coagulation measures. The associations were stronger among women ≥10 years since menopause when initiating E2. The timing of E2 therapy, E2 dose, and serum E2 levels relative to time since menopause may modify the venous thromboembolism risk.

Hierarchical measurement structure in the Women's Health Questionnaire: a confirmatory factor analysis.

Purpose: This study conducted confirmatory factor analysis (CFA) to examine the measurement structure of the Women's Health Questionnaire (WHQ) and how its components were organized. Methods: Participants were 448 postmenopausal women, with a mean age of 63.3 years. CFA was conducted to test how well several proposed measurement models fit the data. Results: The single-factor model performed poorly, indicating the presence of multiple factors. The model with seven correlated factors fit the data well, although the varying degrees of inter-factor correlations suggested grouping of similar factors. The hierarchical measurement structure, with seven first-order factors organized under two second-order factors of physical health and mental health functioning, demonstrated a good fit with the data (χ2(367) = 694.05, p < 0.001; root mean square error of approximation = 0.05; comparative fit index = 0.95) and a meaningful pattern. The Mental Health factor was represented by Depressed Mood, Anxiety/Fear, Memory/Concentration Problems, and Sleep Problems. The Physical Health factor was manifested mainly by Somatic Symptoms, Menstrual Symptoms, and Vasomotor Symptoms, and, to a lesser extent, also by Sleep Problems and Memory/Concentration Problems. Conclusion: Findings suggested that, in addition to a global index and subscale scores, the WHQ may produce summary scores of physical health and mental health functioning in evaluation of well-being among postmenopausal women.

Minocycline and matrix metalloproteinase inhibition in acute intracerebral hemorrhage: a pilot study.

BACKGROUND AND PURPOSE: Intracerebral hemorrhage (ICH) is a devastating cerebrovascular disorder with high morbidity and mortality. Minocycline is a matrix metalloproteinase-9 (MMP-9) inhibitor that may attenuate secondary mechanisms of injury in ICH. The feasibility and safety of minocycline in ICH patients were evaluated in a pilot, double-blinded, placebo-controlled randomized clinical trial. METHODS: Patients with acute onset (<12 h from symptom onset) ICH and small initial hematoma volume (<30 ml) were randomized to high-dose (10 mg/kg) intravenous minocycline or placebo. The outcome events included adverse events, change in serial National Institutes of Health Stroke Scale score assessments, hematoma volume and MMP-9 measurements, 3-month functional outcome (modified Rankin score) and mortality. RESULTS: A total of 20 patients were randomized to minocycline (n = 10) or placebo (n = 10). The two groups did not differ in terms of baseline characteristics. No serious adverse events or complications were noted with minocycline infusion. The two groups did not differ in any of the clinical and radiological outcomes. Day 5 serum MMP-9 levels tended to be lower in the minocycline group (372 ± 216 ng/ml vs. 472 ± 235 ng/ml; P = 0.052). Multiple linear regression analysis showed that minocycline was associated with a 217.65 (95% confidence interval -425.21 to -10.10, P = 0.041) decrease in MMP-9 levels between days 1 and 5. CONCLUSIONS: High-dose intravenous minocycline can be safely administered to patients with ICH. Larger randomized clinical trials evaluating the efficacy of minocycline and MMP-9 inhibition in ICH patients are required.

Salivary gland dysfunction and nasolacrimal duct obstruction: stenotic changes following I-131 therapy.

Radioactive iodine has long been used in the treatment of cancers of the thyroid. While salivary complications secondary to I-131 therapy in association with xerophthalmia are well documented, there is little in the literature addressing simultaneous nasolacrimal duct obstruction with salivary gland dysfunction. The authors present 2 patients with epiphora from bilateral nasolacrimal duct obstruction and concurrent sialadenitis following I-131 ablation therapy for papillary thyroid carcinoma. These cases highlight the lacrimal and salivary duct complications resulting from I-131 therapy, introduce the possibility of a shared mechanism of damage, and demonstrate the availability of effective treatments for both conditions. Ophthalmologists see patients with epiphora from I-131 therapy and should be aware of the possible concurrent symptoms caused by salivary duct stenosis to make timely and appropriate referrals.

Prevention of diseases after menopause.

Women may expect to spend more than a third of their lives after menopause. Beginning in the sixth decade, many chronic diseases will begin to emerge, which will affect both the quality and quantity of a woman's life. Thus, the onset of menopause heralds an opportunity for prevention strategies to improve the quality of life and enhance longevity. Obesity, metabolic syndrome and diabetes, cardiovascular disease, osteoporosis and osteoarthritis, cognitive decline, dementia and depression, and cancer are the major diseases of concern. Prevention strategies at menopause have to begin with screening and careful assessment for risk factors, which should also include molecular and genetic diagnostics, as these become available. Identification of certain risks will then allow directed therapy. Evidence-based prevention for the diseases noted above include lifestyle management, cessation of smoking, curtailing excessive alcohol consumption, a healthy diet and moderate exercise, as well as mentally stimulating activities. Although the most recent publications from the follow-up studies of the Women's Health Initiative do not recommend menopause hormonal therapy as a prevention strategy, these conclusions may not be fully valid for midlife women, on the basis of the existing data. For healthy women aged 50-59 years, estrogen therapy decreases coronary heart disease and all-cause mortality; this interpretation is entirely consistent with results from other randomized, controlled trials and observational studies. Thus. as part of a comprehensive strategy to prevent chronic disease after menopause, menopausal hormone therapy, particularly estrogen therapy may be considered as part of the armamentarium.

Inversion-mediated gene fusions involving NAB2-STAT6 in an unusual malignant meningioma.

BACKGROUND: Meningiomas are the most common primary intracranial tumours, with ∼3% meeting current histopathologic criteria for malignancy. METHODS: In this study, we explored the transcriptome of meningiomas using RNA-Seq. RESULTS: Inversion-mediated fusions between two adjacent genes, NAB2 and STAT6, were detected in one malignant tumour, creating two novel in-frame transcripts that were validated by RT-PCR and Sanger sequencing. CONCLUSION: Gene fusions of NAB2-STAT6 were recently implicated in the pathogenesis of solitary fibrous tumours; our study suggested that similar fusions may also have a role in a malignant meningioma with unusual histopathologic features.

Surgical site infections and cellulitis after abdominal hysterectomy.

OBJECTIVES: To identify risk factors for and outcomes of surgical site infections and cellulitis after abdominal hysterectomies. STUDY DESIGN: We used logistic regression analysis to analyze data from a case-control study of 1104 patients undergoing abdominal hysterectomies at a university hospital between Jan. 1, 2007 and Dec. 30, 2010. RESULTS: Factors significantly associated with surgical site infections and with cellulitis were: pulmonary disease, operations done in Main Operating Room East, and seroma. Body mass index >35, no private insurance, and fluid and electrolyte disorders were risk factors for surgical site infections. The mean prophylactic dose of cefazolin was significantly higher for controls than for patients with surgical site infections. Preoperative showers with Hibiclens (Molnlycke Health Care US, LLC, Norcross, GA) and cefazolin prophylaxis were associated with a significantly decreased cellulitis risk. Surgical site infections and cellulitis were significantly associated with readmissions and return visits and surgical site infections were associated with reoperations. CONCLUSION: Preoperative showers, antimicrobial prophylaxis, surgical techniques preventing seromas, and the operating room environment may affect the risk of surgical site infections and cellulitis after abdominal hysterectomies.

Baseline Findings of PreventE4: A Double-Blind Placebo Controlled Clinical Trial Testing High Dose DHA in APOE4 Carriers before the Onset of Dementia.

INTRODUCTION: Lower blood levels of the omega-3 polyunsaturated fatty acid docosahexaenoic acid (DHA) are correlated with worse cognitive functions, particularly among APOE ε4 carriers. Whether DHA supplementation in APOE ε4 carriers with limited DHA consumption and dementia risk factors can delay or slow down disease progression when started before the onset of clinical dementia is not known. METHODS: PreventE4 is a double-blind, single site, randomized, placebo-controlled trial in cognitively unimpaired individuals with limited omega-3 consumption and dementia risk factors (n=368). Its objectives are to determine (1) whether carrying the APOE ε4 allele is associated with lower delivery of DHA to the brain; and (2) whether high dose DHA supplementation affects brain imaging biomarkers of AD and cognitive function. RESULTS: 365 cognitively unimpaired individuals between 55 and 80 (mean age 66) were randomized to 2 grams of DHA per day or identically appearing placebo for a period of 2 years. Half the participants were asked to complete lumbar punctures at baseline and 6-month visits to obtain cerebrospinal fluid (CSF). The primary trial outcome measure is the change in CSF DHA to arachidonic acid ratio after 6 months of the intervention (n=181). Secondary trial outcomes include the change in functional and structural connectivity using resting state functional MRI at 24 months (n=365). Exploratory outcomes include the change in Repeatable Battery of the Assessment of Neuropsychological Status at 24 months (n=365). CONCLUSIONS: Findings from PreventE4 will clarify the brain delivery of DHA in individuals carrying the APOE ε4 allele with implications for dementia prevention strategies. Trial was registered as NCT03613844.

The timing hypothesis for coronary heart disease prevention with hormone therapy: past, present and future in perspective.

Over the past decade, two informative events in primary prevention of coronary heart disease (CHD) have occurred for women's health. The first concerns hormone replacement therapy (HRT) where data have come full circle from presumed harm to consistency with observational data that HRT initiation in close proximity to menopause significantly reduces CHD and overall mortality. The other concerns sex-specific efficacy of CHD primary prevention therapies where lipid-lowering and aspirin therapy have not been conclusively shown to significantly reduce CHD and, more importantly, where there is lack of evidence that either therapy reduces overall mortality in women. Cumulated data support a 'window-of-opportunity' for maximal reduction of CHD and overall mortality and minimization of risks with HRT initiation before 60 years of age and/or within 10 years of menopause and continued for 6 years or more. There is a substantial increase in quality-adjusted life-years over a 5-30-year period in women who initiate HRT in close proximity to menopause, supporting HRT as a highly cost-effective strategy for improving quality-adjusted life. Although primary prevention therapies and HRT contrast in their efficacy to significantly reduce CHD and especially overall mortality in postmenopausal women, the magnitude and types of risks associated with HRT are similar to those associated with other medications commonly used in women's health. The cumulated data highlight the importance of studying the HRT cardioprotective hypothesis in women representative of those from whom the hypothesis was generated.

Effect of statins on estrogen and androgen levels in postmenopausal women treated with estradiol.

OBJECTIVE: A considerable number of postmenopausal women who receive estrogen therapy are also treated for hypercholesterolemia with cholesterol-lowering statins. Statins and steroid hormones can compete for the same steroid-metabolizing enzymes. We investigated whether long-term administration of statins had an effect on serum estrogen and androgen levels in postmenopausal women receiving and not receiving oral estrogen therapy. METHODS: A subgroup analysis from the Estrogen in the Prevention of Atherosclerosis Trial, a randomized, double-blind, placebo-controlled trial, was performed. A total of 222 women were randomized to receive either placebo or 1 mg of oral micronized 17ß-estradiol daily for 2 years. In both the placebo and treatment groups, participants with low density lipoprotein cholesterol levels >160 mg/dl were treated with statins. Blood samples were obtained at baseline and every 6 months during the trial. Serum levels of dehydroepiandrosterone, androstenedione, testosterone, estrone and 17ß-estradiol were measured by radioimmunoassay. RESULTS: Among 86 placebo- and 90 estradiol-treated subjects with baseline and on-trial hormone measurements, no significant differences were observed between the statin-free and statin-treated groups in mean changes from baseline to on-trial levels in any of the androgens or estrogens, whether or not the postmenopausal women were treated with estrogen. CONCLUSION: The results suggest that estrogen therapy and statins can be used simultaneously with no deleterious effects on circulating hormone levels.

Genetic Variants Associated With Unexplained Sudden Cardiac Death in Adult White and African American Individuals.

Importance: Unexplained sudden cardiac death (SCD) describes SCD with no cause identified. Genetic testing helps to diagnose inherited cardiac diseases in unexplained SCD; however, the associations between pathogenic or likely pathogenic (P/LP) variants of inherited cardiomyopathies (CMs) and arrhythmia syndromes and the risk of unexplained SCD in both White and African American adults living the United States has never been systematically examined. Objective: To investigate cases of unexplained SCD to determine the frequency of P/LP genetic variants of inherited CMs and arrhythmia syndromes. Design, Setting, and Participants: This genetic association study included 683 African American and White adults who died of unexplained SCD and were included in an autopsy registry. Overall, 413 individuals had DNA of acceptable quality for genetic sequencing. Data were collected from January 1995 to December 2015. A total of 30 CM genes and 38 arrhythmia genes were sequenced, and variants in these genes, curated as P/LP, were examined to study their frequency. Data analysis was performed from June 2018 to March 2021. Main Outcomes and Measures: The frequency of P/LP variants for CM or arrhythmia in individuals with unexplained SCD. Results: The median (interquartile range) age at death of the 413 included individuals was 41 (29-48) years, 259 (62.7%) were men, and 208 (50.4%) were African American adults. A total of 76 patients (18.4%) with unexplained SCD carried variants considered P/LP for CM and arrhythmia genes. In total, 52 patients (12.6%) had 49 P/LP variants for CM, 22 (5.3%) carried 23 P/LP variants for arrhythmia, and 2 (0.5%) had P/LP variants for both CM and arrhythmia. Overall, 41 P/LP variants for hypertrophic CM were found in 45 patients (10.9%), 9 P/LP variants for dilated CM were found in 11 patients (2.7%), and 10 P/LP variants for long QT syndrome were found in 11 patients (2.7%). No significant difference was found in clinical and heart characteristics between individuals with or without P/LP variants. African American and White patients were equally likely to harbor P/LP variants. Conclusions and Relevance: In this large genetic association study of community cases of unexplained SCD, nearly 20% of patients carried P/LP variants, suggesting that genetics may contribute to a significant number of cases of unexplained SCD. Our findings regarding both the association of unexplained SCD with CM genes and race-specific genetic variants suggest new avenues of study for this poorly understood entity.

Effect of bolus enteral tube feeding on body weight in ambulatory adults with obesity and type 2 diabetes: a feasibility pilot randomized trial.

BACKGROUND/OBJECTIVES: To ascertain the effect on body weight of 14 days of bolus enteral feeding with mixed meal (MM) and electrolyte solution (ES) in ambulatory adults with type 2 diabetes and obesity, and also the safety and feasibility of using a modified, intraorally anchored enteral feeding tube for this purpose. SUBJECTS/METHODS: We conducted a randomized, crossover pilot trial with 16 participants. A 140 cm, 8-French feeding tube was placed in the jejunum under electromagnetic guidance and anchored intraorally. Participants were randomized to self-administer 120 mL 523 kJ (125 kcal) MM, or 50 kJ (12 kcal) ES four times/day for 14 days. After ≥14 days without the tube, participants crossed over to the other treatment. The primary outcome compared weight change between treatments. Thereafter, participants could elect to undergo additional MM cycles. Participants were encouraged to continue with all usual activities including eating ad lib throughout the study. RESULTS: Ten participants withdrew prior to completing two randomized 14-day cycles (4 social, 3 intolerant of anchor, and 3 intolerant of tube). Six participants were assessed for the primary outcome and showed no significant difference in weight loss between MM and ES (p = 0.082). For the secondary outcome of within-group weight loss, average weight loss from baseline was significant for MM but not for ES: -2.40 kg (95% CI: -3.78, -1.02; p = 0.008) vs. -0.64 kg (95% CI: -2.01, 0.74; p = 0.27). A total of 23 2-week cycles were completed (12 paired, 2 unpaired, and 9 additional), with no significant adverse events for 334 days of tube use. CONCLUSIONS: Repeated bolus nutrient administration via enteral feeding tube is associated with weight loss in adults with obesity and type 2 diabetes, with no significant difference seen between MM and ES feeds. The prototype device was safe, but requires development for further investigation into the effect of bolus jejunal feeding on weight and to improve acceptability.

Coronary heart disease and hormone replacement therapy after the menopause.

The discordance in coronary heart disease (CHD) outcome between randomized, controlled trials and observational studies of hormone replacement therapy (HRT) is likely the result of the dissimilar cohorts studied. This observation led to the formation of the timing hypothesis that benefits and risks of HRT depend upon age of HRT initiation and/or time of HRT initiation in relation to menopause. This hypothesis has been supported with data from large, randomized, controlled trials that have studied HRT and selective estrogen receptor modulators (SERMs) in the prevention of CHD. Initiation of HRT in women <60 years of age and/or within 10 years of menopause reduces both CHD and total mortality; SERMs have been shown to reduce CHD in women <60 years. What has become clear from the cumulated literature is that in young postmenopausal women who initiate HRT in close proximity to menopause, the adverse effects of HRT are rare and no greater than those of other commonly used pharmacological agents and that the primary prevention benefits for CHD are at least equivalent to those of other commonly used therapies. Additionally, the literature indicates that the duration of HRT confers greater CHD benefit especially in women <60 years who initiate therapy. The cumulated literature dispels misperceptions concerning HRT and CHD.

Effect of HAART on salivary gland function in the Women's Interagency HIV Study (WIHS).

OBJECTIVE: To determine the impact of highly active antiretroviral therapy (HAART) on salivary gland function in human immunodeficiency virus (HIV) positive women from the Women's Interagency HIV Study (WIHS). DESIGN: Longitudinal cohort study. SUBJECTS AND METHODS: A total of 668 HIV positive women from the WIHS cohort with an initial and at least one follow-up oral sub-study visit contributed 5358 visits. Salivary gland function was assessed based on a dry mouth questionnaire, whole unstimulated and stimulated salivary flow rates, salivary gland enlargement or tenderness and lack of saliva on palpation of the major salivary glands. MAIN OUTCOME MEASURES: Changes in unstimulated and stimulated flow rates at any given visit from that of the immediate prior visit (continuous variables). The development of self-reported dry mouth (present/absent), enlargement or tenderness of salivary glands (present/absent), and absence of secretion on palpation of the salivary glands were binary outcomes (yes/no). RESULTS: Protease Inhibitor (PI) based HAART was a significant risk factor for developing decreased unstimulated (P = 0.01) and stimulated (P = 0.0004) salivary flow rates as well as salivary gland enlargement (P = 0.006) as compared with non-PI based HAART. CONCLUSIONS: PI-based HAART therapy is a significant risk factor for developing reduced salivary flow rates and salivary gland enlargement in HIV positive patients.

Elevation of monocyte chemoattractant protein-1 in patients experiencing neurocognitive decline following carotid endarterectomy.

BACKGROUND: Previous studies have demonstrated that elevated pre-operative monocyte count is an independent predictor of acute neurocognitive decline following carotid endarterectomy (CEA). Monocyte chemoattractant protein-1 (MCP-1), secreted by human endothelial and monocyte-like cells, is a potent mediator of inflammation and mononuclear cell trafficking. This study examines the relationship between peri-operative serum MCP-1 elevation and post-operative neurocognitive injury following CEA. METHODS: Fifty-two patients undergoing CEA and 67 lumbar laminectomy (LL) controls were administered a battery of five neuropsychological tests pre-operatively and on post-operative day 1 (POD 1). Change in individual test scores from baseline to POD 1 were converted into Z-score and used to develop a point system quantifying the degree of neurocognitive dysfunction relative to change within the LL group. Neurocognitive injury following CEA was defined as a score greater than 2 standard deviations above mean total deficit scores of LL controls. Serum MCP-1 levels were measured pre-operatively and on POD 1 by enzyme-linked immunosorbent assay. FINDINGS: Mean percent MCP-1 elevation was higher for the 13 injured CEA patients (147.7 +/- 32.4%) in our cohort compared to 39 age- and sex-matched uninjured CEA patients (76.0 +/- 16.5%). In unconditional multivariate logistic regression analysis, percent elevation in serum MCP-1 level was associated with neurocognitive injury one day after CEA (OR = 2.19, 95% CI = 1.13-4.26, P = 0.021, for a 100% elevation from pre-operative levels). CONCLUSIONS: Peri-operative elevations in serum MCP-1 levels correlate with acute neurocognitive dysfunction following CEA. These data implicate an inflammatory mechanism in the pathogenesis of Ischaemic neurocognitive decline.

Demographic characteristics of an avian predator, Louisiana Waterthrush (Parkesia motacilla), in response to its aquatic prey in a Central Appalachian USA watershed impacted by shale gas development.

We related Louisiana Waterthrush (Parkesia motacilla) demographic response and nest survival to benthic macroinvertebrate aquatic prey and to shale gas development parameters using models that accounted for both spatial and non-spatial sources of variability in a Central Appalachian USA watershed. In 2013, aquatic prey density and pollution intolerant genera (i.e., pollution tolerance value <4) decreased statistically with increased waterthrush territory length but not in 2014 when territory densities were lower. In general, most demographic responses to aquatic prey were variable and negatively related to aquatic prey in 2013 but positively related in 2014. Competing aquatic prey covariate models to explain nest survival were not statistically significant but differed annually and in general reversed from negative to positive influence on daily survival rate. Potential hydraulic fracturing runoff decreased nest survival both years and was statistically significant in 2014. The EPA Rapid Bioassessment protocol (EPA) and Habitat Suitability Index (HSI) designed for assessing suitability requirements for waterthrush were positively linked to aquatic prey where higher scores increased aquatic prey metrics, but EPA was more strongly linked than HSI and varied annually. While potential hydraulic fracturing runoff in 2013 may have increased Ephemeroptera, Plecoptera, and Trichoptera (EPT) richness, in 2014 shale gas territory disturbance decreased EPT richness. In 2014, intolerant genera decreased at the territory and nest level with increased shale gas disturbance suggesting the potential for localized negative effects on waterthrush. Loss of food resources does not seem directly or solely responsible for demographic declines where waterthrush likely were able to meet their foraging needs. However collective evidence suggests there may be a shale gas disturbance threshold at which waterthrush respond negatively to aquatic prey community changes. Density-dependent regulation of their ability to adapt to environmental change through acquisition of additional resources may also alter demographic response.

Postmenopausal oral estrogen therapy affects hemostatic factors, but does not account for reduction in the progression of subclinical atherosclerosis.

BACKGROUND: Hemostatic factors influenced by postmenopausal hormone therapy may contribute to atherosclerosis. The Estrogen in the Prevention of Atherosclerosis Trial (EPAT), a 2-year, randomized, double-blind, placebo-controlled trial, demonstrated reduced subclinical atherosclerosis progression measured by change in common carotid artery intima-media thickness (CIMT) with unopposed oral 17beta-estradiol. OBJECTIVES: To assess the effect of postmenopausal hormone therapy on the levels of several hemostatic factors, and the relationship between these factors and the progression of subclinical atherosclerosis. PATIENTS AND METHODS: We measured tissue plasminogen activator (t-PA) antigen, factor (F) VII, D-dimer and albumin longitudinally, and plasminogen activator inhibitor type 1 (PAI-1) and fibrinogen at trial-end, in 186 postmenopausal women. RESULTS: Estradiol vs. placebo was associated with greater FVII and lower t-PA, albumin, PAI-1 and fibrinogen (all P < or = 0.001), with no estradiol effect on D-dimer (P = 0.42). Only mean on-trial t-PA was positively associated with the absolute level of CIMT on-trial (r = 0.29, P < 0.0001), but this was attenuated with age and body mass index adjustment. No longitudinally measured hemostatic factor was associated with CIMT progression. However, higher CIMT during the trial was significantly related to increases in t-PA. CONCLUSIONS: These results confirm previous findings regarding estrogen's effect on hemostatic factors and show that albumin is negatively associated with estrogen therapy. These hemostatic factors did not account for the reduction of CIMT progression with 17beta-estradiol seen in EPAT. Atherosclerosis itself may affect levels of hemostatic factors (reverse causality), with subsequent involvement in atherosclerosis-associated thrombosis.