ABSTRACT
OBJECTIVE: This study was undertaken to examine averted stroke in optimized stroke systems. METHODS: This secondary analysis of a multicenter trial from 2014 to 2020 compared patients treated by mobile stroke unit (MSU) versus standard management. The analytical cohort consisted of participants with suspected stroke treated with intravenous thrombolysis. The main outcome was a tissue-defined averted stroke, defined as a final diagnosis of stroke with resolution of presenting symptoms/signs by 24 hours attributed to thrombolysis and no acute infarction/hemorrhage on imaging. An additional outcome was stroke with early symptom resolution, defined as a final diagnosis of stroke with resolution of presenting symptoms/signs by 24 hours attributed to thrombolysis. RESULTS: Among 1,009 patients with a median last known well to thrombolysis time of 87 minutes, 159 (16%) had tissue-defined averted stroke and 276 (27%) had stroke with early symptom resolution. Compared with standard management, MSU care was associated with more tissue-defined averted stroke (18% vs 11%, adjusted odds ratio [aOR] = 1.82, 95% confidence interval [CI] = 1.13-2.98) and stroke with early symptom resolution (31% vs 21%, aOR = 1.74, 95% CI = 1.12-2.61). The relationships between thrombolysis treatment time and averted/early recovered stroke appeared nonlinear. Most models indicated increased odds for stroke with early symptom resolution but not tissue-defined averted stroke with earlier treatment. Additionally, younger age, female gender, hyperlipidemia, lower National Institutes of Health Stroke Scale, lower blood pressure, and no large vessel occlusion were associated with both tissue-defined averted stroke and stroke with early symptom resolution. INTERPRETATION: In optimized stroke systems, 1 in 4 patients treated with thrombolysis recovered within 24 hours and 1 in 6 had no demonstrable brain injury on imaging. ANN NEUROL 2024;95:347-361.
Subject(s)
Brain Ischemia , Stroke , Humans , Female , Tissue Plasminogen Activator/therapeutic use , Fibrinolytic Agents/therapeutic use , Prospective Studies , Stroke/diagnostic imaging , Stroke/drug therapy , Stroke/complications , Hemorrhage/complications , Thrombolytic Therapy/methods , Treatment Outcome , Brain Ischemia/drug therapyABSTRACT
BACKGROUND: Mobile stroke units (MSUs) are ambulances with staff and a computed tomographic scanner that may enable faster treatment with tissue plasminogen activator (t-PA) than standard management by emergency medical services (EMS). Whether and how much MSUs alter outcomes has not been extensively studied. METHODS: In an observational, prospective, multicenter, alternating-week trial, we assessed outcomes from MSU or EMS management within 4.5 hours after onset of acute stroke symptoms. The primary outcome was the score on the utility-weighted modified Rankin scale (range, 0 to 1, with higher scores indicating better outcomes according to a patient value system, derived from scores on the modified Rankin scale of 0 to 6, with higher scores indicating more disability). The main analysis involved dichotomized scores on the utility-weighted modified Rankin scale (≥0.91 or <0.91, approximating scores on the modified Rankin scale of ≤1 or >1) at 90 days in patients eligible for t-PA. Analyses were also performed in all enrolled patients. RESULTS: We enrolled 1515 patients, of whom 1047 were eligible to receive t-PA; 617 received care by MSU and 430 by EMS. The median time from onset of stroke to administration of t-PA was 72 minutes in the MSU group and 108 minutes in the EMS group. Of patients eligible for t-PA, 97.1% in the MSU group received t-PA, as compared with 79.5% in the EMS group. The mean score on the utility-weighted modified Rankin scale at 90 days in patients eligible for t-PA was 0.72 in the MSU group and 0.66 in the EMS group (adjusted odds ratio for a score of ≥0.91, 2.43; 95% confidence interval [CI], 1.75 to 3.36; P<0.001). Among the patients eligible for t-PA, 55.0% in the MSU group and 44.4% in the EMS group had a score of 0 or 1 on the modified Rankin scale at 90 days. Among all enrolled patients, the mean score on the utility-weighted modified Rankin scale at discharge was 0.57 in the MSU group and 0.51 in the EMS group (adjusted odds ratio for a score of ≥0.91, 1.82; 95% CI, 1.39 to 2.37; P<0.001). Secondary clinical outcomes generally favored MSUs. Mortality at 90 days was 8.9% in the MSU group and 11.9% in the EMS group. CONCLUSIONS: In patients with acute stroke who were eligible for t-PA, utility-weighted disability outcomes at 90 days were better with MSUs than with EMS. (Funded by the Patient-Centered Outcomes Research Institute; BEST-MSU ClinicalTrials.gov number, NCT02190500.).
Subject(s)
Ambulances , Emergency Medical Services , Ischemic Stroke/drug therapy , Mobile Health Units , Time-to-Treatment , Tissue Plasminogen Activator/therapeutic use , Aged , Disability Evaluation , Female , Humans , Ischemic Stroke/complications , Ischemic Stroke/diagnostic imaging , Male , Middle Aged , Odds Ratio , Severity of Illness Index , Tomography, X-Ray ComputedABSTRACT
BACKGROUND: Treatment of patients with acute ischemic stroke on mobile stroke units (MSUs) improves outcomes compared with management by standard emergency medical services ambulances and is associated with more patients treated with intravenous tPA (tissue-type plasminogen activator) in the first golden hour after last known normal. We explored the predictors and outcomes of first-hour treatment (FHT) compared with later treatment in an alternating-week cluster-controlled trial of MSUs. METHODS: We analyzed all patients treated with intravenous tPA in the BEST-MSU Study (Benefits of Stroke Treatment Delivered by a Mobile Stroke Unit Compared to Standard Management by Emergency Medical Services). After stratifying by treatment timeframe, we identified factors associated with FHT. We performed adjusted analyses of the association between FHT and clinical outcome and modeled the shape of the relationship between last known normal-to-treatment time and excellent outcome. RESULTS: Among 941 tPA-treated patients, 206 (21.8%) had lytic started within 60 minutes. Treatment on the MSU, older age, male sex, alert by 911, faster arrival on-scene and imaging, more severe stroke, atrial fibrillation, and absence of heart failure and pretreatment antihypertensive treatment were associated with FHT. Compared with later treatment, FHT was associated with higher adjusted odds ratio for 90-day modified Rankin Scale score of 0 to 1 (odds ratio, 1.87 [95% CI, 1.25-2.84]; P=0.003). Among FHT patients, 68% achieved a 90-day modified Rankin Scale of 0 or 1 or returned to their baseline status. FHT was not associated with higher risk of hemorrhage and was associated with reduced risk of treating neurovascular mimics. CONCLUSIONS: FHT almost doubles the odds of excellent clinical outcome without increased risk compared with later treatment, which supports the use of MSUs.
Subject(s)
Brain Ischemia , Ischemic Stroke , Stroke , Humans , Male , Tissue Plasminogen Activator/therapeutic use , Ischemic Stroke/drug therapy , Treatment Outcome , Stroke/therapy , Ambulances , Thrombolytic Therapy/methods , Fibrinolytic Agents/therapeutic use , Brain Ischemia/drug therapyABSTRACT
BACKGROUND: Neuroinflammation is ubiquitous in acute stroke and worsens outcome. However, the precise timing of the inflammatory response is unknown, hindering the design of acute anti-inflammatory therapeutic interventions. We sought to identify the onset of the neuroinflammatory cascade using a mobile stroke unit. METHODS: The study is a proof-of-concept, cohort investigation of ultra-early blood- and extracellular vesicle-derived markers of neuroinflammation and outcome in acute stroke. Blood was obtained, prehospital, on an mobile stroke unit. Outcomes were biomarker concentrations, modified Rankin Scale score, and National Institutes of Health Stroke Scale score. RESULTS: Forty-one adults were analyzed, including 15 patients treated on the mobile stroke unit between August 2021 and April 2022, and 26 healthy controls to establish biomarker reference levels. Median patient age was 74 (range, 36-97) years, 60% were female, and 80% White. Ten (67%) were diagnosed as stroke, with 8 (53%) confirmed and 2 likely transient ischemic attack or stroke averted by thrombolysis; 5 were stroke mimics. For strokes, median initial National Institutes of Health Stroke Scale score was 11 (range, 4-19) and 6 (75%) received tPA (tissue-type plasminogen activator). Blood was obtained a median of 58 (range, 36-133) minutes after symptom onset. Within 36 minutes after stroke, plasma IL-6 (interleukin-6), neurofilament light chain, UCH-L1 (ubiquitin C-terminal hydrolase L1), and GFAP (glial fibrillary acidic protein) were elevated by as much as 10 times normal. In EVs, MMP-9 (matrix metalloproteinase-9), CXCL4 (chemokine (C-X-C motif) ligand 4), CRP (C-reactive protein), IL-6, OPN (osteopontin), and PECAM1 (platelet and endothelial cell adhesion molecule 1) were elevated. Inflammatory markers increased rapidly in the first 2 hours and continued rising for 24 hours. CONCLUSIONS: The neuroinflammatory cascade was found to be activated within 36 to 133 minutes after stroke and progresses rapidly. This is earlier than observed previously in humans and suggests injury from neuroinflammation occurs faster than had been surmised. These findings could inform development of acute immunomodulatory stroke therapies and lead to new diagnostic tools and improved outcomes.
Subject(s)
Brain Ischemia , Ischemic Attack, Transient , Stroke , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Brain Ischemia/drug therapy , Interleukin-6 , Ischemic Attack, Transient/drug therapy , Neuroinflammatory Diseases , Stroke/therapy , Tissue Plasminogen Activator/therapeutic use , Treatment OutcomeABSTRACT
BACKGROUND: UCHealth's Mobile Stroke Unit (MSU) at University of Colorado Hospital is an ambulance equipped with a computed tomography (CT) scanner and tele-stroke capabilities that began clinical operation in Aurora, Colorado January 2016. As one of the first MSU's in the United States, it was necessary to design unique and dynamic information technology infrastructure. This includes high-speed cellular connectivity, Health Insurance Portability and Accountability Act compliance, cloud-based and remote access to electronic medical records (EMR), and reliable and rapid image transfer. Here we describe novel technologies incorporated into the MSU. Technological data-handling aspects of the MSU were reviewed. Functions evaluated include wireless connectivity while in transit, EMR access and manipulation in the field, CT with image transfer from the MSU to the hospital's Picture Archiving Communication System (PACS), and video and audio communication for neurological assessment. METHODS/RESULTS: The MSU wireless system was designed with redundancy to avoid dropped signals during data transfer. Two separate Internet Protocol destinations with split-tunnel architecture are assigned, for videoconferencing and for EMR data transfer. Brain images acquired in the ambulance CT scanner are transferred initially to an onboard laptop, then via Citrix Receiver to the hospital-based PACS server where they can be viewed in PACS or EMR by the stroke neurologist, neuroradiologist, and other providers. PACS and Radiology Information System are 2 of the XenApps utilized by CT technologists on board the MSU. DISCUSSION/CONCLUSIONS: These technologies will serve as a blueprint for development of similar units elsewhere, and as a framework for improvement in this technology.
Subject(s)
Ambulances/organization & administration , Diagnosis, Computer-Assisted , Electronic Health Records/organization & administration , Mobile Health Units/organization & administration , Stroke/diagnostic imaging , Systems Integration , Teleradiology/organization & administration , Tomography, X-Ray Computed , Wireless Technology/organization & administration , Colorado , Delivery of Health Care, Integrated/organization & administration , Diagnosis, Computer-Assisted/instrumentation , Humans , Predictive Value of Tests , Prognosis , Program Evaluation , Stroke/physiopathology , Stroke/therapy , Teleradiology/instrumentation , Time Factors , Time-to-Treatment , Tomography, X-Ray Computed/instrumentation , Wireless Technology/instrumentation , WorkflowABSTRACT
The human distal gut harbours a vast ensemble of microbes (the microbiota) that provide important metabolic capabilities, including the ability to extract energy from otherwise indigestible dietary polysaccharides. Studies of a few unrelated, healthy adults have revealed substantial diversity in their gut communities, as measured by sequencing 16S rRNA genes, yet how this diversity relates to function and to the rest of the genes in the collective genomes of the microbiota (the gut microbiome) remains obscure. Studies of lean and obese mice suggest that the gut microbiota affects energy balance by influencing the efficiency of calorie harvest from the diet, and how this harvested energy is used and stored. Here we characterize the faecal microbial communities of adult female monozygotic and dizygotic twin pairs concordant for leanness or obesity, and their mothers, to address how host genotype, environmental exposure and host adiposity influence the gut microbiome. Analysis of 154 individuals yielded 9,920 near full-length and 1,937,461 partial bacterial 16S rRNA sequences, plus 2.14 gigabases from their microbiomes. The results reveal that the human gut microbiome is shared among family members, but that each person's gut microbial community varies in the specific bacterial lineages present, with a comparable degree of co-variation between adult monozygotic and dizygotic twin pairs. However, there was a wide array of shared microbial genes among sampled individuals, comprising an extensive, identifiable 'core microbiome' at the gene, rather than at the organismal lineage, level. Obesity is associated with phylum-level changes in the microbiota, reduced bacterial diversity and altered representation of bacterial genes and metabolic pathways. These results demonstrate that a diversity of organismal assemblages can nonetheless yield a core microbiome at a functional level, and that deviations from this core are associated with different physiological states (obese compared with lean).
Subject(s)
Gastrointestinal Tract/microbiology , Metagenome/physiology , Obesity/microbiology , Thinness/microbiology , Adult , Africa/ethnology , Biodiversity , Environment , Europe/ethnology , Feces/microbiology , Female , Genotype , Humans , Metagenome/genetics , Missouri , Molecular Sequence Data , Mothers , RNA, Ribosomal, 16S/analysis , RNA, Ribosomal, 16S/genetics , Twins, Dizygotic , Twins, MonozygoticABSTRACT
Recent investigations have demonstrated that unusually 'hairy' yeti crabs within the family Kiwaidae associate with two predominant filamentous bacterial families, the Epsilon and Gammaproteobacteria. These analyses, however, were based on samples collected from a single body region, the setae of pereopods. To more thoroughly investigate the microbiome associated with Kiwa puravida, a yeti crab species from Costa Rica, we utilized barcoded 16S rRNA amplicon pyrosequencing, as well as microscopy and terminal restriction fragment length polymorphism analysis. Results indicate that, indeed, the bacterial community on the pereopods is far less diverse than on the rest of the body (Shannon indices ranged from 1.30-2.02 and 2.22-2.66, respectively). Similarly, the bacterial communities associated with juveniles and adults were more complex than previously recognized, with as many as 46 bacterial families represented. Ontogenetic differences in the microbial community, from egg to juvenile to adult, included a dramatic under-representation of the Helicobacteraceae and higher abundances of both Thiotrichaceae and Methylococcaceae for the eggs, which paralleled patterns observed in another bacteria-crustacean symbiosis. The degree to which abiotic and biotic feedbacks influence the bacterial community on the crabs is still not known, but predictions suggest that both the local environment and host-derived factors influence the establishment and maintenance of microbes associated with the surfaces of aquatic animals.
Subject(s)
Anomura/microbiology , Bacteria/classification , Microbiota , Phylogeny , Animals , Bacteria/genetics , Costa Rica , DNA Barcoding, Taxonomic , Female , In Situ Hybridization, Fluorescence , Microscopy, Electron, Transmission , Ovum/microbiology , Polymorphism, Restriction Fragment Length , RNA, Ribosomal, 16S/genetics , Sequence Analysis, DNA , SymbiosisABSTRACT
BACKGROUND: The ability to recognize and address bias is an important communication skill not typically addressed during training. We describe the design of an educational curriculum that aims to identify and change behavior related to diversity, equity, and inclusion (DEI). "DEI at the Bedside" uses the existing infrastructure of bedside teaching and provides a tool to normalize DEI discussions and develop skills to address bias during a neurology inpatient rotation. METHODS: As part of traditional clinical rounds, team members on an inpatient service shared experiences with DEI topics, including bias. The team developed potential responses should they encounter a similar situation in the future. We report the results of our needs assessment and curriculum development to evaluate the feasibility of incorporating a DEI educational curriculum in the neurology inpatient setting. RESULTS: Forty-two DEI experiences were recorded. Medical students were the most frequent discussants (44%). Direction of bias occurred between healthcare team members (33%), against patients (31%), and patients against healthcare team members (28%). Experiences ranged from microaggressions to explicit comments of racism, sexism, and homophobia. CONCLUSIONS: Based on needs assessment data, we developed a DEI educational curriculum for the inpatient neurology setting aimed to improve knowledge and skills related to DEI topics as well as to normalize conversation of DEI in the clinical setting. Additional study will demonstrate whether this initiative translates into measurable and sustained improvement in knowledge of how bias and disparity show up in the clinical setting and behavioral intent to discuss and address them.
Subject(s)
Education, Medical , Neurology , Humans , Diversity, Equity, Inclusion , Inpatients , CommunicationABSTRACT
BACKGROUND: Few data exist on acute stroke treatment in patients with pre-existing disability (PD) since they are usually excluded from clinical trials. A recent trial of mobile stroke units (MSUs) demonstrated faster treatment and improved outcomes, and included PD patients. AIM: To determine outcomes with tissue plasminogen activator (tPA), and benefit of MSU versus management by emergency medical services (EMS), for PD patients. METHODS: Primary outcomes were utility-weighted modified Rankin Scale (uw-mRS). Linear and logistic regression models compared outcomes in patients with versus without PD, and PD patients treated by MSU versus standard management by EMS. Time metrics, safety, quality of life, and health-care utilization were compared. RESULTS: Of the 1047 tPA-eligible ischemic stroke patients, 254 were with PD (baseline mRS 2-5) and 793 were without PD (baseline mRS 0-1). Although PD patients had worse 90-day uw-mRS, higher mortality, more health-care utilization, and worse quality of life than non-disabled patients, 53% returned to at least their baseline mRS, those treated faster had better outcome, and there was no increased bleeding risk. Comparing PD patients treated by MSU versus EMS, 90-day uw-mRS was 0.42 versus 0.36 (p = 0.07) and 57% versus 46% returned to at least their baseline mRS. There was no interaction between disability status and MSU versus EMS group assignment (p = 0.67) for 90-day uw-mRS. CONCLUSION: PD did not prevent the benefit of faster treatment with tPA in the BEST-MSU study. Our data support inclusion of PD patients in the MSU management paradigm.
Subject(s)
Emergency Medical Services , Stroke , Humans , Fibrinolytic Agents/therapeutic use , Quality of Life , Stroke/drug therapy , Tissue Plasminogen Activator/therapeutic use , Treatment Outcome , Clinical Trials as TopicABSTRACT
The MetaPath knowledge base was developed for the purpose of archiving, sharing and analyzing experimental data on metabolism, metabolic pathways and crucial supporting metadata. The MetaPath system grew out of the need to compile and organize the results of metabolism studies into a systematic database to facilitate data comparisons and evaluations. Specialized MetaPath data evaluation tools facilitate the review of pesticide metabolism data submitted for regulatory risk assessments as well as exchange of results of complex analyses used in regulation and research. Customized screen editors called Composers were developed to automate data entry into MetaPath while also streamlining the production of agency specific study summaries such as the Data Evaluation Records (DER) used by the US EPA Office of Pesticide Programs. Efforts are underway through an Organization for Economic Co-operation and Development (OECD) work group to extend the use of DER Composers as harmonized templates for rat metabolism, livestock residue, plant residue and environmental degradation studies.
Subject(s)
Databases, Factual , Knowledge Bases , Xenobiotics/pharmacokinetics , Animals , Environmental Pollutants/pharmacokinetics , Humans , Inactivation, Metabolic , Risk Assessment , SoftwareABSTRACT
BACKGROUND AND PURPOSE: approximately 4% to 17% of all adult strokes have onset in the hospital. Previous research indicates significant in-hospital evaluation delays and lower adherence to some measures of quality care compared to out-of-hospital strokes. METHODS: quality of care for in-hospital ischemic strokes compared to stroke with out-of-hospital onset was examined using cohort analysis of a statewide stroke database maintained by the Colorado Stroke Alliance. RESULTS: one-hundred sixteen in-hospital strokes were compared to 4946 out-of-hospital strokes. Patients with in-hospital strokes were significantly more likely to have history of coronary artery disease (36.7% vs 26.5%; P=0.02), and in-hospital strokes were more severe (NIHSS score 9.5 vs 7.0; P=0.01). Time to brain imaging was not significantly different (54 minutes vs 43 minutes; P=0.13) between groups. Patients with in-hospital stroke were significantly more likely to have documentation of stroke education (90.4% vs 73.1%; P=0.0002) and assessment for rehabilitation (67.7% vs 45.2%; P<0.0001). Total deficit-free care defined as adherence to all Get With the Guidelines Stroke (GWTG-Stroke) measures was better for in-hospital strokes compared to strokes in the community (52.8% vs 32.3%; P<0.0001). CONCLUSIONS: adherence to GWTG-Stroke performance measures was better for in-hospital strokes in this statewide registry. Variability in reporting by participating hospitals suggests in-hospital strokes are under-recognized or under-reported. In-hospital stroke evaluation times remain more than twice the recommended benchmark of 25 minutes, representing an opportunity for process improvement.
Subject(s)
Brain Ischemia/epidemiology , Guideline Adherence , Hospitals , Quality of Health Care , Stroke/epidemiology , Aged , Aged, 80 and over , Brain Ischemia/etiology , Brain Ischemia/pathology , Colorado/epidemiology , Coronary Artery Disease/complications , Coronary Artery Disease/epidemiology , Coronary Artery Disease/pathology , Female , Humans , Male , Middle Aged , Stroke/etiology , Stroke/pathologyABSTRACT
BACKGROUND/AIMS: Undiagnosed stroke is a major public health problem. The Questionnaire for Verifying Stroke-Free Status (QVSS) includes eight items and was originally designed to detect stroke-free individuals. Its six symptom-related questions could potentially be used to screen for undiagnosed stroke or transient ischemic attack (TIA), but the sensitivity and specificity of just the six symptom-related questions are unknown. METHODS: A research assistant administered the QVSS to outpatients from Veterans Administration stroke and general medicine clinics. Neurologists, blinded to QVSS scores, interviewed and examined all subjects to determine stroke status. Responses to the six symptom questions of the QVSS were compared against the neurologist-determined stroke/TIA status. RESULTS: The sensitivity of the individual symptom questions ranged from 0.22 to 0.60, and the specificity ranged from 0.79 to 0.95. The sensitivity of any of the six symptom questions was 0.82, and the specificity was 0.62. CONCLUSION: The six symptom-related questions of the QVSS demonstrate a high sensitivity and moderate specificity for the diagnosis of stroke or TIA compared with neurological exam. Though these findings should be validated in a more representative general population, these questions have potential for meeting the public health objective of detecting clinically unrecognized but symptomatic stroke.
Subject(s)
Ambulatory Care/standards , Ischemic Attack, Transient/diagnosis , Neurologic Examination/standards , Stroke/diagnosis , Surveys and Questionnaires/standards , Adult , Aged , Aged, 80 and over , Female , Humans , Ischemic Attack, Transient/psychology , Male , Middle Aged , Neurologic Examination/methods , Risk Factors , Sensitivity and Specificity , Stroke/psychologyABSTRACT
An inpatient stroke alert program is effective in decreasing evaluation time for in-hospital strokes, although response times remain significantly longer than those in the emergency department. It is capable of increasing the percentage of ischemic strokes identified by the hospital's stroke team, at the cost of an increased percentage of false alarms.
Subject(s)
Brain Ischemia/diagnosis , Hospital Communication Systems/organization & administration , Inpatients , Patient Care Team/organization & administration , Stroke/diagnosis , Adult , Aged , Aged, 80 and over , Attitude of Health Personnel , Brain Ischemia/complications , Brain Ischemia/therapy , Colorado , Early Diagnosis , Female , Health Knowledge, Attitudes, Practice , Humans , Male , Middle Aged , Predictive Value of Tests , Prognosis , Program Evaluation , Retrospective Studies , Stroke/etiology , Stroke/therapy , Time FactorsABSTRACT
The Yeti crab, Kiwa hirsuta Macpherson et al., is the single known species in a recently discovered crab family Kiwaidae (Decapoda: Galatheoidea) from deep-sea hydrothermal vents. Its chelipeds, walking legs and the ventral surface of its cephalothorax are covered with dense setae that, in turn, are covered with clusters of filamentous bacteria, making the crab appear extraordinarily 'hairy'. Electron microscopy revealed dense bacterial clusters attached to the chitinous outer layer of the setae. Molecular phylogenetic analyses revealed the setae-associated bacteria to be dominated by epsilon-Proteobacteria ( approximately 56% of the recovered ribotypes), gamma-Proteobacteria ( approximately 25%) and Bacteroidetes ( approximately 10%). Fluorescence in situ microscopy confirmed the attachment of filamentous epsilon-Proteobacteria on setae, but no specialized morphological structures appeared to exist for bacterial attachment. Key enzymes involved in the reductive tricarboxylic acid cycle (ATP-dependent citrate lyase) and sulfite oxidation or dissimilatory sulfate reduction (bidirectional APS reductase) were detected. Consequently, the potential for carbon fixation and cycling of reduced and oxidized sulfur appear to exist in the dense microflora that grows on the crab's setae.
Subject(s)
Anomura/microbiology , Bacteria/classification , Bacteria/isolation & purification , Biodiversity , Animal Structures/microbiology , Animals , Bacteria/genetics , Citric Acid Cycle/genetics , DNA, Bacterial/chemistry , DNA, Bacterial/genetics , DNA, Ribosomal/chemistry , DNA, Ribosomal/genetics , Genes, rRNA , Hot Springs , Microscopy, Electron , Molecular Sequence Data , Oxidoreductases Acting on Sulfur Group Donors/genetics , Phylogeny , RNA, Bacterial/genetics , RNA, Ribosomal, 16S/genetics , Seawater , Sequence Analysis, DNA , Sequence Homology, Nucleic AcidABSTRACT
Bone-eating worms of the genus Osedax colonized and grew on cow bones deployed at depths ranging from 385 to 2893m in Monterey Bay, California. Colonization occurred as rapidly as two months following deployment of the cow bones, similar to the time it takes to colonize exposed whalebones. Some Osedax females found on the cow bones were producing eggs and some hosted dwarf males in their tubes. Morphological and molecular examinations of these worms confirmed the presence of six Osedax species, out of the eight species presently known from Monterey Bay. The ability of Osedax species to colonize, grow and reproduce on cow bones challenges previous notions that these worms are 'whale-fall specialists.'
Subject(s)
Annelida/physiology , Bone and Bones , Ecosystem , Feeding Behavior/physiology , Animals , Annelida/genetics , Base Sequence , Cattle , DNA, Mitochondrial/genetics , Molecular Sequence Data , Pacific Ocean , Sequence Analysis, DNA , Species SpecificityABSTRACT
Rationale Mobile stroke units speed treatment for acute ischemic stroke, thereby possibly improving outcomes. Aim To compare mobile stroke unit and standard management clinical outcomes, healthcare utilization, and cost-effectiveness in tissue plasminogen activator-eligible acute ischemic stroke patients calling 911. Sample size 693. Eighty percent power with 0.05 type I error rate to detect a difference of 0.09 in mean utility-weighted modified Rankin scale between groups. Design Phase III, multicenter, prospective cluster-randomized (mobile stroke unit versus standard management weeks) comparative effectiveness study in tissue plasminogen activator-eligible patients. Outcomes Primary: Ninety-day mean utility-weighted modified Rankin scale. Coprimary: cost-effectiveness based on EQ5D quality of life and one year poststroke costs. Analysis Two-sample t-test and linear regression adjusting for covariates; incremental cost-effectiveness ratio and net benefit regression. Results As of March 2017, 288 tissue plasminogen activator-eligible patients have been enrolled (173 in the mobile stroke unit arm and 115 in the standard management arm). Two new centers start in early 2017 with target end of recruitment September 2019. Conclusion This is the first randomized study to test for disability, healthcare utilization, and cost-effectiveness of a mobile stroke unit. The progress of the study suggests that it is feasible. Management of tissue plasminogen activator eligible acute ischemic stroke patients by a mobile stroke unit could potentially result in less disability and healthcare utilization, and be cost effective. Mobile stroke units are very costly. This trial may determine if the fixed cost can be justified by a reduction in disability and healthcare utilization. Clinical Trial Registration NCT02190500.
Subject(s)
Mobile Health Units , Stroke/therapy , Telemedicine/methods , Telemedicine/trends , Female , Follow-Up Studies , Humans , Male , Mobile Health Units/trends , Statistics, Nonparametric , Tissue Plasminogen Activator/therapeutic use , Treatment OutcomeABSTRACT
The ecological patterns of many invertebrate larvae remain an ongoing mystery, in large part owing to the difficult task of detecting them in the water column. The development of nucleic-acid-based technology has the potential to resolve this issue by direct identification and monitoring of embryonic and larval forms in situ. We report herein on the successful development and application of nucleic-acid-based sandwich hybridization assays that detect barnacles using rRNA-targeted probes with both group-(order Thoracica) and species-(Balanus glandula) specificity. Primary results include the determination of target 18S rRNA sequences and the construction of "capture" probes for detection of larvae using hybridization techniques. In addition, we modified existing protocols for whole cell hybridization of invertebrate larvae as confirmation of the sandwich hybridization results. We used both hybridization techniques successfully in the laboratory on a plankton time series collected over 3 months, as well as a week-long in situ deployment of the technique in Monterey Bay, CA. The adaptability of this technology promises to be further applicable to various organisms and could be used to enhance our understanding of larval presence in the world's oceans.
Subject(s)
Environmental Monitoring/methods , Nucleic Acid Hybridization/methods , Plankton/classification , Thoracica/classification , Air Pressure , Animals , DNA Primers/chemistry , DNA Probes/chemistry , Female , In Situ Hybridization, Fluorescence/methods , Larva/classification , Larva/genetics , Plankton/genetics , RNA, Ribosomal, 18S/genetics , Sensitivity and Specificity , Spectrum Analysis/methods , Temperature , Thoracica/geneticsABSTRACT
The pharmacokinetics and drug disposition of 14C 1-[3-[[4-[2-(1-methylethoxy)phenyl]-1-piperazinyl]methyl]benzoy]piperidine succinate (RWJ-37796, mazapertine, Mz) have been investigated in male and female Sprague-Dawley rats. Approximately 93% of the orally administered radioactive dose (30 mg/kg) was recovered after 7 days. Fecal elimination accounted for approximately 63% of the dose while urine accounted for 30%. The rate of elimination of 14C Mz was rapid with 81% of the total fecal and 94% of the total urinary radioactivity being excreted within 24 h. There were no significant gender differences in the overall excretion pattern. The maximal plasma concentration of Mz and total radioactivity occurred at 0.5h after dosing and plasma concentrations were consistently higher in female rats. The Mz concentration declined rapidly in plasma with a terminal half-life<2 h. The total radioactive dose in plasma displayed a considerably longer terminal half-life of 9-13 h. Mz and a total of 15 metabolites were isolated and identified in these samples. Unchanged Mz accounted for <5% of the radioactive dose in excreta samples and <8% of the sample in plasma (0-24 h). Metabolites were formed by phenyl hydroxylation, piperidyl oxidation, O-dealkylation, N-dephenylation, oxidative N-debenzylation and glucuronide conjugation.
Subject(s)
Antipsychotic Agents/pharmacokinetics , Piperazines/pharmacokinetics , Administration, Oral , Animals , Antipsychotic Agents/administration & dosage , Antipsychotic Agents/urine , Biotransformation , Feces/chemistry , Female , Glucuronides/metabolism , Male , Oxidation-Reduction , Piperazines/administration & dosage , Piperazines/urine , Rats , Rats, Sprague-Dawley , Tissue DistributionABSTRACT
The Sovanco Fracture Zone and Blanco Transform Fault separate the Explorer, Juan de Fuca, and Gorda ridge systems of the northeastern Pacific Ocean. To test whether such offsets in the ridge axis create barriers to along-axis dispersal of the endemic hydrothermal vent animals, we examined the genetic structure of limpet populations previously identified as Lepetodrilus fucensis McLean, 1988 (Gastropoda, Lepetodrilidae). Mitochondrial DNA sequences and patterns of allozyme variation revealed no evidence that the 150-km-long Sovanco Fracture Zone impeded gene flow between the Explorer and Juan de Fuca populations. In contrast, the 450-km-long Blanco Transform Fault separates the limpets into highly divergent northern and southern lineages that we recognize as distinct species. We describe southern populations from the Gorda Ridge (Seacliff) and Escanaba Trough as Lepetodrilus gordensis new species and refer northern populations from the Explorer and Juan de Fuca ridge systems to L. fucensis sensu stricto. The species are similar morphologically, but L. gordensis lacks a sensory neck papilla and has a more tightly coiled teleconch. To assess the degree of isolation between these closely related species, we used the Isolation with Migration method to estimate the time of population splitting, effective sizes of the ancestral and derived populations, and rates of migration across the Blanco Transform Fault.