Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 70
Filter
1.
Gastric Cancer ; 2024 Apr 17.
Article in English | MEDLINE | ID: mdl-38630317

ABSTRACT

BACKGROUND: While dietary salt intake has been linked with gastric cancer risk in Asian studies, findings from Western populations are sparse and limited to case-control studies. Our aim was to evaluate the frequency of adding salt to food at table in relation to gastric cancer risk among UK adults. METHODS: We evaluated associations between the frequency of adding salt to food and the risk of gastric cancer in the UK Biobank (N = 471,144) using multivariable Cox regression. Frequency of adding salt to food was obtained from a touchscreen questionnaire completed at baseline (2006-2010). 24-h urinary sodium excretion was estimated using INTERSALT formulae. Cancer incidence was obtained by linkage to national cancer registries. RESULTS: During a median follow-up period of 10.9 years, 640 gastric cancer cases were recorded. In multivariable models, the gastric cancer risk among participants reporting adding salt to food at table "always" compared to those who responded "never/rarely" was HR = 1.41 (95% CI: 1.04, 1.90). There was a positive linear association between estimated 24-h urinary sodium levels and the frequency of adding salt to food (p-trend <0 .001). However, no significant association between estimated 24-h urinary sodium with gastric cancer was observed (HR = 1.19 (95% CI: 0.87, 1.61)). CONCLUSIONS: "Always adding salt to food" at table was associated with a higher gastric cancer risk in a large sample of UK adults. High frequency of adding salt to food at table can potentially serve as a useful indicator of salt intake for surveillance purposes and a basis for devising easy-to-understand public health messages.

2.
medRxiv ; 2023 Sep 12.
Article in English | MEDLINE | ID: mdl-37745408

ABSTRACT

Background: Tau pathology is common in age-related neurodegenerative diseases. Tau pathology in primary age-related tauopathy (PART) and in Alzheimer's disease (AD) has a similar biochemical structure and anatomic distribution, which is distinct from tau pathology in other diseases. However, the molecular changes associated with intraneuronal tau pathology in PART and AD, and whether these changes are similar in the two diseases, is largely unexplored. Methods: Using GeoMx spatial transcriptomics, mRNA was quantified in CA1 pyramidal neurons with tau pathology and adjacent neurons without tau pathology in 6 cases of PART and 6 cases of AD, and compared to 4 control cases without pathology. Transcriptional changes were analyzed for differential gene expression and for coordinated patterns of gene expression associated with both disease state and intraneuronal tau pathology. Results: Synaptic gene changes and two novel gene expression signatures associated with intraneuronal tau were identified in PART and AD. Overall, gene expression changes associated with intraneuronal tau pathology were similar in PART and AD. Synaptic gene expression was decreased overall in neurons in AD and PART compared to control cases. However, this decrease was largely driven by neurons lacking tau pathology. Synaptic gene expression was increased in tau-positive neurons compared to tau-negative neurons in disease. Two novel gene expression signatures associated with intraneuronal tau were identified by examining coordinated patterns of gene expression. Genes in the up-regulated expression pattern were enriched in calcium regulation and synaptic function pathways, specifically in synaptic exocytosis. These synaptic gene changes and intraneuronal tau expression signatures were confirmed in a published transcriptional dataset of cortical neurons with tau pathology in AD. Conclusions: PART and AD show similar transcriptional changes associated with intraneuronal tau pathology in CA1 pyramidal neurons, raising the possibility of a mechanistic relationship between the tau pathology in the two diseases. Intraneuronal tau pathology was also associated with increased expression of genes associated with synaptic function and calcium regulation compared to tau-negative disease neurons. The findings highlight the power of molecular analysis stratified by pathology in neurodegenerative disease and provide novel insight into common molecular pathways associated with intraneuronal tau in PART and AD.

3.
Nat Chem ; 14(6): 632-639, 2022 06.
Article in English | MEDLINE | ID: mdl-35655006

ABSTRACT

The controlled isomerization and functionalization of alkenes is a cornerstone achievement in organometallic catalysis that is now widely used throughout industry. In particular, the addition of CO and H2 to an alkene, also known as the oxo-process, is used in the production of linear aldehydes from crude alkene feedstocks. In these catalytic reactions, isomerization is governed by thermodynamics, giving rise to functionalization at the most stable alkylmetal species. Despite the ubiquitous industrial applications of tandem alkene isomerization/functionalization reactions, selective functionalization at internal positions has remained largely unexplored. Here we report that the simple W(0) precatalyst W(CO)6 catalyses the isomerization of alkenes to unactivated internal positions and subsequent hydrocarbonylation with CO. The six- to seven-coordinate geometry changes that are characteristic of the W(0)/W(II) redox cycle and the conformationally flexible directing group are key factors in allowing isomerization to take place over multiple positions and stop at a defined unactivated internal site that is primed for in situ functionalization.


Subject(s)
Alkenes , Tungsten , Catalysis , Isomerism , Oxidation-Reduction
4.
ACS Catal ; 12(19): 12369-12385, 2022 Oct 07.
Article in English | MEDLINE | ID: mdl-37215160

ABSTRACT

Developing strategies to study reactivity and selectivity in flexible catalyst systems has become an important topic of research. Herein, we report a combined experimental and computational study aimed at understanding the mechanistic role of an achiral DABCOnium cofactor in a regio- and enantiodivergent bromocyclization reaction. It was found that electron-deficient aryl substituents enable rigidified transition states via an anion-π interaction with the catalyst, which drives the selectivity of the reaction. In contrast, electron-rich aryl groups on the DABCOnium result in significantly more flexible transition states, where interactions between the catalyst and substrate are more important. An analysis of not only the lowest-energy transition state structures but also an ensemble of low-energy transition state conformers via energy decomposition analysis and machine learning was crucial to revealing the dominant noncovalent interactions responsible for observed changes in selectivity in this flexible system.

5.
Sensors (Basel) ; 21(8)2021 Apr 09.
Article in English | MEDLINE | ID: mdl-33918951

ABSTRACT

Structural cracks are a vital feature in evaluating the health of aging structures. Inspectors regularly monitor structures' health using visual information because early detection of cracks on highly trafficked structures is critical for maintaining the public's safety. In this work, a framework for detecting cracks along with their locations is proposed. Image data provided by an unmanned aerial vehicle (UAV) is stitched using image processing techniques to overcome limitations in the resolution of cameras. This stitched image is analyzed to identify cracks using a deep learning model that makes judgements regarding the presence of cracks in the image. Moreover, cracks' locations are determined using data from UAV sensors. To validate the system, cracks forming on an actual building are captured by a UAV, and these images are analyzed to detect and locate cracks. The proposed framework is proven as an effective way to detect cracks and to represent the cracks' locations.

6.
Article in English | MEDLINE | ID: mdl-33670135

ABSTRACT

The human casualties from simulated nuclear detonation scenarios in New Delhi, India are analyzed, with a focus on the distribution of casualties in urban environments and the theoretical application of a nuclear-specific triage system with significant innovation in interdisciplinary disaster management applicable generally to urban nuclear detonation medical response. Model estimates of nuclear war casualties employed ESRI's ArcGIS 9.3, blast and prompt radiation were calculated using the Defense Nuclear Agency's WE program, and fallout radiation was calculated using the Defense Threat Reduction Agency's (DTRA's) Hazard Prediction and Assessment Capability (HPAC) V404SP4, as well as custom GIS and database software applications. ESRI ArcGISTM programs were used to calculate affected populations from the Oak Ridge National Laboratory's LandScanTM 2007 Global Population Dataset for areas affected by thermal, blast and radiation data. Trauma, thermal burn, and radiation casualties were thus estimated on a geographic basis for New Delhi, India for single and multiple (six) 25 kt detonations and a single 1 mt (1000 kt) detonation. Major issues related to the emergency management of a nuclear incident are discussed with specific recommendations for improvement. The consequences for health management of thermal burn and radiation patients is the worst, as burn patients require enormous resources to treat, and there will be little to no familiarity with the treatment of radiation victims. Of particular importance is the interdisciplinary cooperation necessary for such a large-scale emergency response event, which would be exemplified by efforts such as the application of a Nuclear Global Health Workforce.


Subject(s)
Disaster Planning , Disasters , Explosions , Humans , India , Triage
7.
J Clin Neurophysiol ; 38(3): 221-225, 2021 May 01.
Article in English | MEDLINE | ID: mdl-32141985

ABSTRACT

INTRODUCTION: Nonconvulsive seizures (NCSs) are common in critically ill adult patients with acute neurologic conditions. However, the effect of NCSs on patient outcome remains unclear. In this study, we aimed to determine the effect of NCSs on short-term outcome and to assess the clinical and EEG factors associated with NCSs. METHODS: We retrospectively identified 219 adult patients from the EEG reporting system who underwent continuous EEG (cEEG) monitoring between January 2018 and June 2018. Patients with anoxic brain injury were excluded from the study. Clinical, laboratory, and EEG data were reviewed to determine potentially predictive factors of NCSs. The impact of NCSs on in-hospital mortality, length of stay, and disability on discharge was measured; an modified Rankin scale of three or greater was considered disabled. RESULTS: Of the 219 patients included in our study, a total of 14% (n = 31) had NCSs on continuous EEG, of which 42% (n = 13) had their first seizure discharge recorded during the first hour of continuous EEG monitoring. The presence of clinical seizures before continuous EEG (odds ratio = 1.787; 95% confidence interval = 1.197-2.667, P = 0.0045), history of epilepsy (odds ratio = 1.508; 95% confidence interval = 1.027-2.215, P = 0.035), and comatose state (29 vs. 16%; P = 0.0006) were associated with NCSs. Among EEG characteristics, the presence of interictal epileptiform discharges (P < 0.0001), lateralized rhythmic delta activity (P = 0.02), and lateralized periodic discharges (P < 0.0001) were associated with NCSs. Nonconvulsive seizures were significantly associated with longer in-hospital stay (23.68 ± 24.84 vs. 17.14 ± 20.52; P = 0.036) and disability on discharge (87% [n = 27] vs. 13% [n = 4], P = 0.02). However, there was no significant association between NCS and in-hospital mortality (9.6% [n = 3] vs. 10.6% [n = 20]; P = 0.1). CONCLUSIONS: Nonconvulsive seizures are associated with longer in-hospital stay and disability on discharge but not with in-hospital mortality in adult patients.


Subject(s)
Seizures/complications , Adult , Critical Illness , Electroencephalography , Female , Hospital Mortality , Humans , Length of Stay , Male , Middle Aged , Retrospective Studies , Seizures/epidemiology
8.
World Neurosurg ; 139: 583-587, 2020 07.
Article in English | MEDLINE | ID: mdl-32360672

ABSTRACT

BACKGROUND: Thermal coagulation is a central principle in surgery, particularly regarding hemostasis, as well as being an integral part of intracranial tumor removal. Traditionally, surgical hemostasis is achieved through application of unipolar or bipolar electrocautery. This method has been contemporized and specialized to treat intracranial tumors through a technique called stereotactic laser ablation (SLA), also known as laser interstitial thermal therapy. CASE DESCRIPTION: In this article, we present this technique as an additional option in the treatment of difficult intracranial tumors. Specifically, we report here a highly vascular and hemorrhagic pineocytoma found in a fragile, elderly patient who underwent a novel combination of procedures: SLA mediated devascularization followed by resection via an endoscopic approach. CONCLUSIONS: SLA-mediated thermal-coagulation is a potential strategy for minimizing hemorrhagic risks in brain tumor resection and may be used in conjunction with other approaches tailored to the patient and their disease.


Subject(s)
Brain Neoplasms/surgery , Cerebral Hemorrhage/surgery , Laser Therapy/methods , Neuroendoscopy/methods , Pineal Gland/surgery , Pinealoma/surgery , Aged , Brain Neoplasms/diagnostic imaging , Cerebral Hemorrhage/diagnostic imaging , Female , Humans , Pineal Gland/diagnostic imaging , Pinealoma/diagnostic imaging , Proof of Concept Study
9.
Int J Mol Sci ; 21(3)2020 Jan 30.
Article in English | MEDLINE | ID: mdl-32019190

ABSTRACT

Lymphoma, a group of widely prevalent hematological malignancies of lymphocyte origin, has become the focus of significant clinical research due to their high propensity for refractory/relapsed (R/R) disease, leading to poor prognostic outcomes. The complex molecular circuitry in lymphomas, especially in the aggressive phenotypes, has made it difficult to find a therapeutic option that can salvage R/R disease. Furthermore, the association of lymphomas with the Bone Marrow (BM) microenvironment has been found to portend worse outcomes in terms of heightened chances of relapse and acquired resistance to chemotherapy. This review assesses the current therapy options in three distinct types of lymphomas: diffuse large B-cell lymphoma, follicular lymphoma and mantle cell lymphoma. It also explores the role of the BM tumor microenvironment as a secure 'niche' for lymphoma cells to grow, proliferate and survive. It further evaluates potential mechanisms through which the tumor cells can establish molecular connections with the BM cells to provide pro-tumor benefits, and discusses putative therapeutic strategies for disrupting the BM-lymphoma cell communication.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/pharmacology , Bone Marrow/pathology , Drug Resistance, Neoplasm , Lymphoma, B-Cell/pathology , Tumor Microenvironment/immunology , Bone Marrow/drug effects , Bone Marrow/immunology , Humans , Lymphoma, B-Cell/drug therapy , Lymphoma, B-Cell/immunology , Tumor Microenvironment/drug effects
10.
Curr Res Pharmacol Drug Discov ; 1: 19-29, 2020 Apr.
Article in English | MEDLINE | ID: mdl-34909639

ABSTRACT

Delivering glial cell line-derived neurotrophic factor (GDNF) to the brain is a potential treatment for Parkinson's Disease (PD). Here we use an implantable encapsulated cell technology that uses modified human clonal ARPE-19 â€‹cells to deliver of GDNF to the brain. In vivo studies demonstrated sustained delivery of GDNF to the rat striatum over 6 months. Anatomical benefits and behavioral efficacy were shown in 6-OHDA lesioned rats where nigral dopaminergic neurons were preserved in neuroprotection studies and dopaminergic fibers were restored in neurorecovery studies. When larger, clinical-sized devices were implanted for 3 months into the putamen of Göttingen minipigs, GDNF was widely distributed throughout the putamen and caudate producing a significant upregulation of tyrosine hydroxylase immunohistochemistry. These results are the first to provide clear evidence that implantation of encapsulated GDNF-secreting cells deliver efficacious and biologically relevant amounts of GDNF in a sustained and targeted manner that is scalable to treat the large putamen in patients with Parkinson's disease.

11.
Epilepsy Behav ; 94: 124-130, 2019 05.
Article in English | MEDLINE | ID: mdl-30909075

ABSTRACT

OBJECTIVES: Children with temporal lobe epilepsy (TLE) exhibit executive dysfunction on traditional neuropsychological tests. There is limited evidence of different functional network alterations associated with this clinical executive dysfunction. This study investigates working memory deficits in children with TLE by assessing deactivation of the default mode network (DMN) on functional Magnetic Resonance Imaging (fMRI) and the relationship of DMN deactivation with fMRI behavioral findings and neuropsychological test performance. EXPERIMENTAL DESIGN: fMRI was conducted on 15 children with TLE and 15 healthy controls (age: 8-16 years) while performing the N-back task in order to assess deactivation of the DMN. N-back accuracy, N-back reaction time, and neuropsychological tests of executive function (Delis-Kaplan Executive Function System [D-KEFS] Color-Word Interference and Card Sort tests) were also assessed. PRINCIPAL OBSERVATIONS: During the N-back task, children with TLE exhibited significantly less deactivation of the DMN, primarily in the precuneus/posterior cingulate cortex compared with controls. These alterations significantly correlated with N-back behavioral findings and D-KEFS results. CONCLUSIONS: Children with TLE exhibit executive dysfunction which correlates with DMN alterations. These findings suggest that the level of deactivation of specific functional networks may contribute to cognitive impairment in children with TLE. The findings also indicate that children with TLE have network alterations in extratemporal lobe brain regions.


Subject(s)
Brain/physiopathology , Epilepsy, Temporal Lobe/physiopathology , Executive Function/physiology , Memory, Short-Term/physiology , Adolescent , Brain/diagnostic imaging , Child , Cognitive Dysfunction/physiopathology , Cognitive Dysfunction/psychology , Epilepsy, Temporal Lobe/diagnostic imaging , Epilepsy, Temporal Lobe/psychology , Female , Functional Neuroimaging , Gyrus Cinguli/diagnostic imaging , Gyrus Cinguli/physiopathology , Humans , Magnetic Resonance Imaging/methods , Male , Neuropsychological Tests , Parietal Lobe/diagnostic imaging , Parietal Lobe/physiopathology , Reaction Time
12.
J Neurosci ; 39(11): 2144-2156, 2019 03 13.
Article in English | MEDLINE | ID: mdl-30665947

ABSTRACT

Neurotrophic factors are candidates for treating epilepsy, but their development has been hampered by difficulties in achieving stable and targeted delivery of efficacious concentrations within the desired brain region. We have developed an encapsulated cell technology that overcomes these obstacles by providing a targeted, continuous, de novo synthesized source of high levels of neurotrophic molecules from human clonal ARPE-19 cells encapsulated into hollow fiber membranes. Here we illustrate the potential of this approach for delivering glial cell line-derived neurotrophic factor (GDNF) directly to the hippocampus of epileptic rats. In vivo studies demonstrated that bilateral intrahippocampal implants continued to secrete GDNF that produced high hippocampal GDNF tissue levels in a long-term manner. Identical implants robustly reduced seizure frequency in the pilocarpine model. Seizures were reduced rapidly, and this effect increased in magnitude over 3 months, ultimately leading to a reduction of seizures by 93%. This effect persisted even after device removal, suggesting potential disease-modifying benefits. Importantly, seizure reduction was associated with normalized changes in anxiety and improved cognitive performance. Immunohistochemical analyses revealed that the neurological benefits of GDNF were associated with the normalization of anatomical alterations accompanying chronic epilepsy, including hippocampal atrophy, cell degeneration, loss of parvalbumin-positive interneurons, and abnormal neurogenesis. These effects were associated with the activation of GDNF receptors. All in all, these results support the concept that the implantation of encapsulated GDNF-secreting cells can deliver GDNF in a sustained, targeted, and efficacious manner, paving the way for continuing preclinical evaluation and eventual clinical translation of this approach for epilepsy.SIGNIFICANCE STATEMENT Epilepsy is one of the most common neurological conditions, affecting millions of individuals of all ages. These patients experience debilitating seizures that frequently increase over time and can associate with significant cognitive decline and psychiatric disorders that are generally poorly controlled by pharmacotherapy. We have developed a clinically validated, implantable cell encapsulation system that delivers high and consistent levels of GDNF directly to the brain. In epileptic animals, this system produced a progressive and permanent reduction (>90%) in seizure frequency. These benefits were accompanied by improvements in cognitive and anxiolytic behavior and the normalization of changes in CNS anatomy that underlie chronic epilepsy. Together, these data suggest a novel means of tackling the frequently intractable neurological consequences of this devastating disorder.


Subject(s)
Epilepsy/drug therapy , Glial Cell Line-Derived Neurotrophic Factor/administration & dosage , Neuroprotective Agents/administration & dosage , Seizures/drug therapy , Animals , Cell Encapsulation , Cell Line , Drug Delivery Systems/methods , Epilepsy/chemically induced , Humans , Male , Pilocarpine/administration & dosage , Rats, Sprague-Dawley , Seizures/chemically induced
13.
Mol Ther Methods Clin Dev ; 9: 211-224, 2018 Jun 15.
Article in English | MEDLINE | ID: mdl-29766029

ABSTRACT

Brain-derived neurotrophic factor (BDNF) may represent a therapeutic for chronic epilepsy, but evaluating its potential is complicated by difficulties in its delivery to the brain. Here, we describe the effects on epileptic seizures of encapsulated cell biodelivery (ECB) devices filled with genetically modified human cells engineered to release BDNF. These devices, implanted into the hippocampus of pilocarpine-treated rats, highly decreased the frequency of spontaneous seizures by more than 80%. These benefits were associated with improved cognitive performance, as epileptic rats treated with BDNF performed significantly better on a novel object recognition test. Importantly, long-term BDNF delivery did not alter normal behaviors such as general activity or sleep/wake patterns. Detailed immunohistochemical analyses revealed that the neurological benefits of BDNF were associated with several anatomical changes, including reduction in degenerating cells and normalization of hippocampal volume, neuronal counts (including parvalbumin-positive interneurons), and neurogenesis. In conclusion, the present data suggest that BDNF, when continuously released in the epileptic hippocampus, reduces the frequency of generalized seizures, improves cognitive performance, and reverts many histological alterations associated with chronic epilepsy. Thus, ECB device-mediated long-term supplementation of BDNF in the epileptic tissue may represent a valid therapeutic strategy against epilepsy and some of its co-morbidities.

14.
JAMA Neurol ; 74(6): 637-639, 2017 06 01.
Article in English | MEDLINE | ID: mdl-28384710
15.
Acta Neuropathol ; 133(6): 923-931, 2017 06.
Article in English | MEDLINE | ID: mdl-28332094

ABSTRACT

Abnormal accumulation of TDP-43 into cytoplasmic or nuclear inclusions with accompanying nuclear clearance, a common pathology initially identified in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), has also been found in Alzheimer' disease (AD). TDP-43 serves as a splicing repressor of nonconserved cryptic exons and that such function is compromised in brains of ALS and FTD patients, suggesting that nuclear clearance of TDP-43 underlies its inability to repress cryptic exons. However, whether TDP-43 cytoplasmic aggregates are a prerequisite for the incorporation of cryptic exons is not known. Here, we assessed hippocampal tissues from 34 human postmortem brains including cases with confirmed diagnosis of AD neuropathologic changes along with age-matched controls. We found that cryptic exon incorporation occurred in all AD cases exhibiting TDP-43 pathology. Furthermore, incorporation of cryptic exons was observed in the hippocampus when TDP-43 inclusions was restricted only to the amygdala, the earliest stage of TDP-43 progression. Importantly, cryptic exon incorporation could be detected in AD brains lacking TDP-43 inclusion but exhibiting nuclear clearance of TDP-43. These data supports the notion that the functional consequence of nuclear depletion of TDP-43 as determined by cryptic exon incorporation likely occurs as an early event of TDP-43 proteinopathy and may have greater contribution to the pathogenesis of AD than currently appreciated. Early detection and effective repression of cryptic exons in AD patients may offer important diagnostic and therapeutic implications for this devastating illness of the elderly.


Subject(s)
Alzheimer Disease/metabolism , Alzheimer Disease/pathology , Brain/metabolism , Brain/pathology , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , Aged , Aged, 80 and over , Alzheimer Disease/genetics , Cell Nucleus/metabolism , Cell Nucleus/pathology , Cohort Studies , Exons , Female , Humans , Immunohistochemistry , Male , Neurons/metabolism , Neurons/pathology , TDP-43 Proteinopathies/metabolism , TDP-43 Proteinopathies/pathology
16.
Clin EEG Neurosci ; 47(3): 247-50, 2016 Jul.
Article in English | MEDLINE | ID: mdl-25326288

ABSTRACT

Periodic lateralized epileptiform discharges (PLEDs) are an electroencephalographic pattern recorded in the setting of a variety of brain abnormalities. It is best recognized for its association with acute viral encephalitis, stroke, tumor, or latestatus epilepticus. However, there are other conditions that have been recognized as the underlying pathology for PLEDs such as alcohol withdrawal, Creutzfeldt-Jacob disease, anoxic brain injury, and hemiplegic migraine. However, there are only rare case reports of PLEDs in patients with neurosyphilis. Here, we report 2 patients presenting with encephalopathy and seizures with PLEDs, ipsilateral or contralateral to their main brain magnetic resonance imaging abnormalities. Further workup revealed neurosyphilis in both patients, one in association with human immunodeficiency virus (HIV) infection. Given the increasing incidence of neurosyphilis with or without HIV infection, these cases suggest neurosyphilis as a consideration in the differential for patients presenting with PLEDs.


Subject(s)
Brain/physiopathology , Encephalitis, Viral/diagnosis , Encephalitis, Viral/physiopathology , Epilepsy/physiopathology , HIV Infections/physiopathology , Neurosyphilis/physiopathology , Aged , Biological Clocks , Electroencephalography/methods , Encephalitis, Viral/complications , Epilepsy/diagnosis , Epilepsy/etiology , Female , HIV Infections/complications , HIV Infections/diagnosis , Humans , Middle Aged , Neurosyphilis/complications , Neurosyphilis/diagnosis
17.
PLoS One ; 10(12): e0145799, 2015.
Article in English | MEDLINE | ID: mdl-26714315

ABSTRACT

Any release of anthrax spores in the U.S. would require action to decontaminate the site and restore its use and operations as rapidly as possible. The remediation activity would require environmental sampling, both initially to determine the extent of contamination (hazard mapping) and post-decon to determine that the site is free of contamination (clearance sampling). Whether the spore contamination is within a building or outdoors, collecting and analyzing what could be thousands of samples can become the factor that limits the pace of restoring operations. To address this sampling and analysis bottleneck and decrease the time needed to recover from an anthrax contamination event, this study investigates the use of composite sampling. Pooling or compositing of samples is an established technique to reduce the number of analyses required, and its use for anthrax spore sampling has recently been investigated. However, use of composite sampling in an anthrax spore remediation event will require well-documented and accepted methods. In particular, previous composite sampling studies have focused on sampling from hard surfaces; data on soil sampling are required to extend the procedure to outdoor use. Further, we must consider whether combining liquid samples, thus increasing the volume, lowers the sensitivity of detection and produces false negatives. In this study, methods to composite bacterial spore samples from soil are demonstrated. B. subtilis spore suspensions were used as a surrogate for anthrax spores. Two soils (Arizona Test Dust and sterilized potting soil) were contaminated and spore recovery with composites was shown to match individual sample performance. Results show that dilution can be overcome by concentrating bacterial spores using standard filtration methods. This study shows that composite sampling can be a viable method of pooling samples to reduce the number of analysis that must be performed during anthrax spore remediation.


Subject(s)
Bacillus anthracis/isolation & purification , Soil Microbiology , Specimen Handling/methods , Anthrax/microbiology , Dust , Spores, Bacterial/isolation & purification
18.
Disaster Med Public Health Prep ; 9(6): 681-9, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26545189

ABSTRACT

OBJECTIVE: We designed and conducted a regional full-scale exercise in 2007 to test the ability of Atlanta-area hospitals and community partners to respond to a terrorist attack involving the coordinated release of 2 dangerous chemicals (toluene diisocyanate and parathion) that were being transported through the area by tanker truck. METHODS: The exercise was designed to facilitate the activation of hospital emergency response plans and to test applicable triage, decontamination, and communications protocols. Plume modeling was conducted by using the Defense Threat Reduction Agency's (DTRA) Hazard Prediction and Assessment Capability (HPAC) V4 program. The scenario went through multiple iterations as exercise planners sought to reduce total injuries to a manageable, but stressful, level for Atlanta's health care infrastructure. RESULTS: Atlanta-area hospitals rapidly performed multiple casualty triage and were able to take in a surge of victims from the simulated attack. However, health care facilities were reticent to push the perceived manageable numbers of victims, and scenarios were modified significantly to lower the magnitude of the simulated attack. Additional coordination with community response partners and incident command training is recommended. Security at health care facilities and decontamination of arriving victims are two areas that will require continued review. CONCLUSION: Atlanta-area hospitals participated in an innovative regional exercise that pushed facilities beyond traditional scopes of practice and brought together numerous health care community response partners. Using lessons learned from this exercise coupled with subsequent real-world events and training exercises, participants have significantly enhanced preparedness levels and increased the metropolitan region's medical surge capacity in the case of a multiple casualty disaster.


Subject(s)
Chemical Hazard Release , Hospitals/standards , Surge Capacity/standards , Chemical Terrorism , Decontamination/methods , Disaster Planning/methods , Georgia , Hospital Planning/standards , Humans , Mass Casualty Incidents , Motor Vehicles , Triage/statistics & numerical data
19.
J Org Chem ; 80(15): 7530-5, 2015 Aug 07.
Article in English | MEDLINE | ID: mdl-26153720

ABSTRACT

Amine photobase generators (PBGs) are uncommon yet useful compounds. Rarer still are examples of PBGs that are active at visible wavelengths. We report the synthesis and characterization of new photolabile amine protecting groups that are active under visible light. The new chromophore, benzothiophene imino-phenylacetonitrile (BTIPA), was synthesized in four steps without use of chromatography and found to release any one of several amines upon exposure to 405 nm light. The chromophore was also demonstrated to be useful as a Merrifield synthesis protecting group. Experimental evidence suggests a sequential, two stage photolysis mechanism which leads to a nonlinear response to dose.

20.
J Infect Dev Ctries ; 7(7): 533-40, 2013 Jul 15.
Article in English | MEDLINE | ID: mdl-23857388

ABSTRACT

INTRODUCTION: Vibrio vulnificus infection, an uncommon but life-threatening illness, manifests as two main types, primary septicemia and primary wound infections.  Little information regarding the seasonality of V. vulnificus infections in tropical areas and prognostic factors of primary V. vulnificus wound infections is available. METHODOLOGY: This retrospective study was conducted to include 159 V. vulnificus-infected admissions at our institution in southern Taiwan, 63 with primary septicemia (Group 1) and 96 with primary wound infections (Group 2), from 1999 to 2008, for analysis. RESULTS: The case-fatality rate was 24%. Eighty-eight percent of these cases occurred during April to November. During December to March, patients in Group 2 were less likely to have acquired the infection compared with those in Group 1. Group 1 was more likely to have comorbidities and a higher case-fatality rate compared to Group 2. In multivariate analysis, hemorrhagic bullous skin lesions/necrotizing fasciitis (P=0.024), lesions involving two or more limbs (P=0.043), and shock on admission (P=0.015) were related to an increased mortality risk, while surgery < 24 hours after admission (P=0.001) was related to a decreased mortality risk in Group 1; however, hemorrhagic bullous skin lesions/necrotizing fasciitis (P=0.045) was the only prognostic factor in Group 2. CONCLUSION: The presence of hemorrhagic bullous lesion/necrotizing fasciitis is the main prognostic factor for primary septicemia or primary wound infections caused by V. vulnificus. Persons with an underlying immunocompromised status should avoid consuming raw/undercooked seafood or exposing wounds to seawater and should wear clothing during handling of seafood/fishing, especially in warmer months.


Subject(s)
Vibrio Infections/epidemiology , Vibrio Infections/pathology , Adult , Aged , Clinical Medicine/methods , Female , Humans , Male , Middle Aged , Prognosis , Retrospective Studies , Seasons , Sepsis/diagnosis , Sepsis/epidemiology , Sepsis/mortality , Sepsis/pathology , Survival Analysis , Taiwan , Vibrio Infections/diagnosis , Vibrio Infections/mortality , Wound Infection/diagnosis , Wound Infection/epidemiology , Wound Infection/mortality , Wound Infection/pathology
SELECTION OF CITATIONS
SEARCH DETAIL
...