Catchment-scale biogeography of riverine bacterioplankton

Lotic ecosystems such as rivers and streams are unique in that they represent a continuum of both space and time during the transition from headwaters to the river mouth. As microbes have very different controls over their ecology, distribution and dispersion compared with macrobiota, we wished to explore biogeographical patterns within a river catchment and uncover the major drivers structuring bacterioplankton communities. Water samples collected across the River Thames Basin, UK, covering the transition from headwater tributaries to the lower reaches of the main river channel were characterised using 16S rRNA gene pyrosequencing. This approach revealed an ecological succession in the bacterial community composition along the river continuum, moving from a community dominated by Bacteroidetes in the headwaters to Actinobacteria-dominated downstream. Location of the sampling point in the river network (measured as the cumulative water channel distance upstream) was found to be the most predictive spatial feature; inferring that ecological processes pertaining to temporal community succession are of prime importance in driving the assemblages of riverine bacterioplankton communities. A decrease in bacterial activity rates and an increase in the abundance of low nucleic acid bacteria relative to high nucleic acid bacteria were found to correspond with these downstream changes in community structure, suggesting corresponding functional changes. Our findings show that bacterial communities across the Thames basin exhibit an ecological succession along the river continuum, and that this is primarily driven by water residence time rather than the physiochemical status of the river

Cognitive reserve and Alzheimer's disease biomarkers are independent determinants of cognition

The objective of this study was to investigate how a measure of educational and occupational attainment, a component of cognitive reserve, modifies the relationship between biomarkers of pathology and cognition in Alzheimer's disease. The biomarkers evaluated quantified neurodegeneration via atrophy on magnetic resonance images, neuronal injury via cerebral spinal fluid t-tau, brain amyloid-β load via cerebral spinal fluid amyloid-β1–42 and vascular disease via white matter hyperintensities on T2/proton density magnetic resonance images. We included 109 cognitively normal subjects, 192 amnestic patients with mild cognitive impairment and 98 patients with Alzheimer's disease, from the Alzheimer's Disease Neuroimaging Initiative study, who had undergone baseline lumbar puncture and magnetic resonance imaging. We combined patients with mild cognitive impairment and Alzheimer's disease in a group labelled ‘cognitively impaired’ subjects. Structural Abnormality Index scores, which reflect the degree of Alzheimer's disease-like anatomic features on magnetic resonance images, were computed for each subject. We assessed Alzheimer's Disease Assessment Scale (cognitive behaviour section) and mini-mental state examination scores as measures of general cognition and Auditory–Verbal Learning Test delayed recall, Boston naming and Trails B scores as measures of specific domains in both groups of subjects. The number of errors on the American National Adult Reading Test was used as a measure of environmental enrichment provided by educational and occupational attainment, a component of cognitive reserve. We found that in cognitively normal subjects, none of the biomarkers correlated with the measures of cognition, whereas American National Adult Reading Test scores were significantly correlated with Boston naming and mini-mental state examination results. In cognitively impaired subjects, the American National Adult Reading Test and all biomarkers of neuronal pathology and amyloid load were independently correlated with all cognitive measures. Exceptions to this general conclusion were absence of correlation between cerebral spinal fluid amyloid-β1–42 and Boston naming and Trails B. In contrast, white matter hyperintensities were only correlated with Boston naming and Trails B results in the cognitively impaired. When all subjects were included in a flexible ordinal regression model that allowed for non-linear effects and interactions, we found that the American National Adult Reading Test had an independent additive association such that better performance was associated with better cognitive performance across the biomarker distribution. Our main conclusions included: (i) that in cognitively normal subjects, the variability in cognitive performance is explained partly by the American National Adult Reading Test and not by biomarkers of Alzheimer's disease pathology; (ii) in cognitively impaired subjects, the American National Adult Reading Test, biomarkers of neuronal pathology (structural magnetic resonance imaging and cerebral spinal fluid t-tau) and amyloid load (cerebral spinal fluid amyloid-β1–42) all independently explain variability in general cognitive performance; and (iii) that the association between cognition and the American National Adult Reading Test was found to be additive rather than to interact with biomarkers of Alzheimer's disease pathology

Community-Level Responses to Iron Availability in Open Ocean Plankton Ecosystems

Predicting responses of plankton to variations in essential nutrients is hampered by limited in situ measurements, a poor understanding of community composition, and the lack of reference gene catalogs for key taxa. Iron is a key driver of plankton dynamics and, therefore, of global biogeochemical cycles and climate. To assess the impact of iron availability on plankton communities, we explored the comprehensive bio-oceanographic and bio-omics data sets from Tara Oceans in the context of the iron products from two state-of-the-art global scale biogeochemical models. We obtained novel information about adaptation and acclimation toward iron in a range of phytoplankton, including picocyanobacteria and diatoms, and identified whole subcommunities covarying with iron. Many of the observed global patterns were recapitulated in the Marquesas archipelago, where frequent plankton blooms are believed to be caused by natural iron fertilization, although they are not captured in large-scale biogeochemical models. This work provides a proof of concept that integrative analyses, spanning from genes to ecosystems and viruses to zooplankton, can disentangle the complexity of plankton communities and can lead to more accurate formulations of resource bioavailability in biogeochemical models, thus improving our understanding of plankton resilience in a changing environment

Geriatric High-Energy Polytrauma With Orthopedic Injuries

Background: The impact of orthopedic injuries in the elderly patient with multi-trauma and the effect of operative fixation on these injuries have not been thoroughly evaluated. Methods: We reviewed geriatric patients (aged 65 and older) between 2004 and 2010 at a level 1 trauma center who sustained high-energy polytrauma (injury and severity score [ISS] ≥ 16) with associated orthopedic injuries. Patients were excluded if they had severe head and spine injuries, died on arrival, or had low-energy mechanisms of injury. Logistic regression was conducted to identify factors that predict mortality. Results: There were 154 patients who comprised our study group with an average age of 76 years and an ISS of 23. There were 96 males and 58 females. Overall, 52 patients died within 1 year of their admission: 21 patients during their initial hospital stay and 31 patients within 1 year following admission. In all, 64 (42%) patients underwent operative stabilization of their orthopedic injuries. Increased mortality was seen ( P < .05) in female patients, those with lower admission Glasgow coma score, and those who underwent orthopedic surgery. Patients had worse outcomes if they sustained femur ( P = .014), clavicle, or scapular fractures ( P = .027). Other factures associated with higher mortality included pelvic/acetabular injury requiring surgery ( P = .019) or spine fractures treated nonoperatively ( P = .014). Conclusion: The effect of orthopedic injuries on this geriatric polytrauma group contribute to worse outcomes when they included clavicle, scapula, and femur fractures. We also found that pelvic/acetabular fractures treated operatively and nonoperative spine fractures were associated with higher mortality rates. Risk/benefit consideration is suggested when contemplating operative intervention in these patients

Decreased expression of vitamin D receptors in neointimal lesions following coronary artery angioplasty in atherosclerotic swine.

Inflammatory cytokines, such as TNF-α, play a key role in the pathogenesis of occlusive vascular diseases. Activation of vitamin D receptors (VDR) elicits both growth-inhibitory and anti-inflammatory effects. Here, we investigated the expression of TNF-α and VDR in post-angioplasty coronary artery neointimal lesions of hypercholesterolemic swine and examined the effect of vitamin D deficiency on the development of coronary restenosis. We also examined the effect of calcitriol on cell proliferation and effect of TNF-α on VDR activity and expression in porcine coronary artery smooth muscle cells (PCASMCs) in-vitro.Expression of VDR and TNF-α and the effect of vitamin D deficiency in post-angioplasty coronary arteries were analyzed by immunohistochemistry and histomorphometry. Cell proliferation was examined by thymidine and BrdU incorporation assays in cultured PCASMCs. Effect of TNF-α-stimulation on the activity and expression of VDR was analyzed by luciferase assay, immunoblotting and immunocytochemistry. In-vivo, morphometric analysis of the tissues revealed typical lesions with significant neointimal proliferation. Histological evaluation showed expression of smooth muscle α-actin and significantly increased expression of TNF-α in neointimal lesions. Interestingly, there was significantly decreased expression of VDR in PCASMCs of neointimal region compared to normal media. Indeed, post-balloon angioplasty restenosis was significantly higher in vitamin D-deficient hypercholesterolemic swine compared to vitamin D-sufficient group. In-vitro, calcitriol inhibited both serum- and PDGF-BB-induced proliferation in PCASMCs and TNF-α-stimulation significantly decreased the expression and activity of VDR in PCASMCs.These data suggest that significant downregulation of VDR in proliferating smooth muscle cells in neointimal lesions could be due to atherogenic cytokines, including TNF-α. Vitamin D deficiency potentiates the development of coronary restenosis. Calcitriol has anti-proliferative properties in PCASMCs and these actions are mediated through VDR. This could be a potential mechanism for uncontrolled growth of neointimal cells in injured arteries leading to restenosis

Vitamin D Supplementation Reduces Intimal Hyperplasia and Restenosis following Coronary Intervention in Atherosclerotic Swine.

Vitamin D is a fat-soluble steroid hormone that activates vitamin D receptor to regulate multiple downstream signaling pathways and transcription of various target genes. There is an association between vitamin D deficiency and increased risk for cardiovascular disease. However, most of the studies are observational and associative in nature with limited data on clinical application. Thus, there is a need for more prospective randomized controlled studies to determine whether or not vitamin D supplementation provides cardiovascular protection. In this study, we examined the effects of the deficiency and supplementation of vitamin D on coronary restenosis following coronary intervention in atherosclerotic Yucatan microswine. Twelve Yucatan microswine were fed vitamin D-deficient (n = 4) or -sufficient (n = 8) high cholesterol diet for 6-months followed by coronary intervention. Post-intervention, swine in the vitamin D-sufficient high cholesterol diet group received daily oral supplementation of either 1,000 IU (n = 4) or 3,000 IU (n = 4) vitamin D3. Six months later, optical coherence tomography (OCT) was performed to monitor the development of intimal hyperplasia and restenosis. Animals were euthanized to isolate arteries for histomorphometric and immunohistochemical studies. Animals had graded levels of serum 25(OH)D; vitamin D-deficient (15.33 ± 1.45 ng/ml), vitamin D-sufficient + 1,000 IU oral vitamin D post-intervention (32.27 ± 1.20 ng/ml), and vitamin D-sufficient + 3,000 IU oral vitamin D post-intervention (51.00 ± 3.47 ng/ml). Findings from the OCT and histomorphometric studies showed a decrease in intimal hyperplasia and restenosis in vitamin D-supplemented compared to vitamin D-deficient swine. Vitamin D supplementation significantly decreased serum levels of TNF-α and IFN-γ, upregulated serum levels of IL-10, and had no effect on serum IL-6 levels. These findings suggest that vitamin D supplementation limits neointimal formation following coronary intervention in atherosclerotic swine and provide the support for vitamin D supplementation to protect against the development of coronary restenosis

Outcomes of surgical versus transcatheter aortic valve replacement in nonagenarians- a systematic review and meta-analysis

Introduction: Since the approval of transcatheter aortic valve replacement (TAVR), nonagenarian group patients are being increasingly considered for TAVR. Therefore, we compared the clinical outcomes of surgical aortic valve replacement (SAVR) vs TAVR in nonagenarians with severe aortic stenosis. Methods: A literature search was performed using MEDLINE, Embase, Web of Science, Cochrane, and Clinicaltrials.gov for studies reporting the comparative outcomes of TAVR versus SAVR in nonagenarians. The primary endpoint was short-term mortality. Secondary endpoints were post-operative incidences of stroke or transient ischemic attack (TIA), vascular complications, acute kidney injury (AKI), transfusion requirement, and length of hospital stay. Results: Four retrospective studies qualified for inclusion with a total of 8,389 patients (TAVR = 3,112, SAVR = 5,277). Short-term mortality was similar between the two groups [RR = 0.91 (95% CI: 0.76–1.10), p = 0.318]. The average length of hospital stay was shorter by 3 days in the TAVR group (p = 0.037). TAVR was associated with a significantly lower risk of AKI [RR = 0.72 (95% CI: 0.62–0.83), p < 0.001] and a lower risk of transfusion [RR = 0.71 (95% CI: 0.62–0.81), p < 0.001]. There was no difference in risk of stroke/TIA[RR = 1.01 (95% CI: 0.70–1.45), p = 0.957]. The risk of vascular complications was significantly higher in the TAVR group [RR = 3.39 (95% CI: 2.65–4.333), p < 0.001]. Conclusion: In this high-risk population, TAVR compared to SAVR has similar short-term mortality benefit but has lower risks of perioperative complications and a higher number of patients being discharged to home

Effect of calcitriol stimulation on VDR mRNA transcript, VDR protein expression, cell proliferation in PCASMCs.

<p>Calcitriol-stimulated PCASMCs were subjected to RNA and protein isolation for qPCR (A) and Western blot (B) and data was normalized against GAPDH. Quiescent PCASMCs were incubated with calcitriol in SMCM with 10% FBS for 24 h followed by [³H] thymidine incorporation assay (C). Quiescent PCASMCs were stimulated with 20 ng/ml PDGF-BB with calcitriol for 24 h, and BrdU incorporation was analyzed (D). Representative Western blot and quantification of VDR protein in PCASMCs transfected with scrambled and VDR-specific siRNA (E). The relative expression of VDR protein was analyzed using GAPDH as a control. VDR knocked-down PCASMCs were stimulated with 20 ng/ml PDGF-BB with calcitriol for 24 h, and BrdU incorporation was analyzed (F). Data is mean± SEM (N = 3). *P<0.05, **P<0.01, ***P<0.001 all compared to control.</p