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1.
Telemed J E Health ; 2024 Apr 02.
Article in English | MEDLINE | ID: mdl-38563767

ABSTRACT

Background: Remote patient monitoring (RPM) has potential in hypertension management, but limited studies have focused on maternal hypertension, especially among vulnerable populations. The objective of this study was to integrate RPM into perinatal care for pregnant patients at elevated risk of hypertensive disorders to show feasibility, acceptability, and safety. Methods: A prospective pilot cohort study was conducted at the University of Mississippi Medical Center 2021-2023. Participants' blood pressure readings were remotely captured and monitored until 8-week postpartum, with timely assessment and intervention. Results: Out of 98 enrollees, 77 utilized RPM, and no maternal or neonatal deaths occurred within 60-day postpartum. High program satisfaction was reported at discharge. Conclusion: This study demonstrates the feasibility and acceptability of RPM for perinatal care in a vulnerable population. Positive outcomes were observed, including high patient satisfaction and no maternal or neonatal deaths. Further research should address patient engagement barriers and develop tailored protocols for improved clinical outcomes.

2.
JMIR Res Protoc ; 13: e55209, 2024 Mar 28.
Article in English | MEDLINE | ID: mdl-38546709

ABSTRACT

BACKGROUND: The rapid expansion of telehealth services, driven by the COVID-19 pandemic, necessitates systematic evaluation to guarantee the quality, effectiveness, and cost-effectiveness of telehealth services and programs in the United States. While numerous evaluation frameworks have emerged, crafted by various stakeholders, their comprehensiveness is limited, and the overall state of telehealth evaluation remains unclear. OBJECTIVE: The overarching goal of this scoping review is to create a comprehensive overview of telehealth evaluation, incorporating perspectives from multiple stakeholder categories. Specifically, we aim to (1) map the existing landscape of telehealth evaluation, (2) identify key concepts for evaluation, (3) synthesize existing evaluation frameworks, and (4) identify measurements and assessments considered in the United States. METHODS: We will conduct this scoping review in accordance with the Joanna Briggs Institute (JBI) methodology for scoping reviews and in line with the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews). This scoping review will consider documents, including reviews, reports, and white papers, published since January 1, 2019. It will focus on evaluation frameworks and associated measurements of telehealth services and programs in the US health care system, developed by telehealth stakeholders, professional organizations, and authoritative sources, excluding those developed by individual researchers, to collect data that reflect the collective expertise and consensus of experts within the respective professional group. RESULTS: The data extracted from selected documents will be synthesized using tools such as tables and figures. Visual aids like Venn diagrams will be used to illustrate the relationships between the evaluation frameworks from various sources. A narrative summary will be crafted to further describe how the results align with the review objectives, facilitating a comprehensive overview of the findings. This scoping review is expected to conclude by August 2024. CONCLUSIONS: By addressing critical gaps in telehealth evaluation, this scoping review protocol lays the foundation for a comprehensive and multistakeholder assessment of telehealth services and programs. Its findings will inform policy makers, health care providers, researchers, and other stakeholders in advancing the quality, effectiveness, and cost-effectiveness of telehealth in the US health care system. TRIAL REGISTRATION: OSF Registries osf.io/aytus; https://osf.io/aytus. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/55209.

3.
Telemed J E Health ; 2024 Mar 28.
Article in English | MEDLINE | ID: mdl-38546441

ABSTRACT

Background: Telemental health (TMH) offers a promising approach to managing major depressive disorder (MDD). The objective of our work was to evaluate TMH usage among a vulnerable population of MDD Medicare beneficiaries and its association with health care utilization and expenditures. Methods: This cohort study analyzed 2019 Mississippi Medicare fee-for-service data for adult beneficiaries with MDD. Subjects were matched by the use of TMH following 1:1 propensity score matching. Comparisons between TMH and non-TMH cohorts were made on health care utilization and expenditure outcomes, adjusting for provider types postmatching. Results: Among 7,673 identified beneficiaries, 551 used TMH and 7,122 did not. Prematching, TMH cohort showed greater proportions of dual beneficiaries, rural residents, subjects with income below $40,000, those with disability entitlement, and higher Charlson comorbidity index scores, compared to the non-TMH cohort (all p < 0.001). Moreover, the TMH cohort had fewer outpatient visits, but more inpatient admissions, emergency department (ED) visits, and higher medical, pharmacy, and total expenditures (all p < 0.001). Postmatching, TMH was associated with a 25% reduction in outpatient visits (p < 0.001) and a 20% reduction in pharmacy expenditures (p = 0.01), with no significant effect on inpatient admissions, ED visits, medical expenditures, or total expenditures. Conclusions: These results underscore the potential of TMH in enhancing accessible health care services for vulnerable populations and affordable services for Medicare. Our results provide a robust baseline for future policy discussions concerning TMH. Future studies should consider identifying barriers to TMH use among vulnerable populations and ensuring equitable and high-quality patient care.

4.
Telemed J E Health ; 29(9): 1421-1425, 2023 09.
Article in English | MEDLINE | ID: mdl-36716266

ABSTRACT

During the COVID-19 pandemic and public health emergency, telehealth programs vastly expanded with strong support from various federal and state agencies. However, the uncertainty regarding future reimbursement policies for telehealth services has resulted in concerns about long-term sustainability of innovative health service delivery models beyond the financial support. Given the limited literature on creating telehealth programs with long-term sustainability in consideration, we have developed a framework for gathering appropriate data during various stages of program implementation to evaluate clinical effectiveness and economic sustainability that is applicable across various settings, with additional attention to health equity. Recognizing the difficulty of sustaining telehealth programs solely through a fee-for-service payment model, we encourage all telehealth stakeholders, especially payers and policymakers, to consider cost-effectiveness of telehealth programs and support alternate payment models for ensuring long-term sustainability.


Subject(s)
COVID-19 , Telemedicine , Humans , COVID-19/epidemiology , Pandemics , Telemedicine/methods
5.
Sci Rep ; 12(1): 13691, 2022 Aug 11.
Article in English | MEDLINE | ID: mdl-35953697

ABSTRACT

Localization in underwater wireless sensor network (UWSN) faces an imminent threat when the triangulating anchor node starts to malfunction. Traditional geometric approaches are insufficient to cope with the survivability of UWSN topology. To address these issues, this paper presents a symplectic geometry for identification of the malicious anchor node. Consequently, a geodesic search algorithm (GSA) based Target localization is proposed which reduces the positioning error by exploiting the phase-space constancy of the underwater acoustic sensor network topology to effectively triangulate the target node despite its mobility. First, a malicious anchor node model is presented. The node movement is expressed in the form of "ripple region". GSA is then proposed which effectively frees the node metastasis from anchor node geometry, thereby making the underwater system more survivable and resilient. Simulation results evaluate the survivability of the geodesic formalism in terms of the reduced penalty incurred by node movement, as well as the reduced impact of anchor node malfunction. An improvement of 13.46% and 9.26% reveals the utility of the geodesic technique in aquamarine sensor deployments, which would be beneficial in underwater resource exploration and defense planning.

6.
Am J Crit Care ; 31(1): 73-76, 2022 01 01.
Article in English | MEDLINE | ID: mdl-34972847

ABSTRACT

BACKGROUND: Delirium affects up to 80% of patients in the intensive care unit (ICU) but is missed in up to 75% of cases. Telehealth in the ICU (tele-ICU) has become the standard for providing timely, expert care to remotely located ICUs. OBJECTIVES: This pilot study assessed the feasibility and acceptability of using tele-ICU to increase the accuracy of delirium screening and recognition by ICU nurses. METHODS: The pilot sites included 4 ICUs across 3 hospitals. A geriatrician with delirium expertise remotely observed 13 bedside ICU nurses administering the Confusion Assessment Method for the ICU (CAM-ICU) to patients in real time via the tele-ICU platform and subsequently provided training on CAM-ICU performance and delirium management. Training evaluation consisted of a validated spot check form, a 2-item satisfaction/change-of-practice survey, and a qualitative question on acceptability. RESULTS: Thirteen ICU nurses were observed performing 26 bedside delirium assessments. The top observed barriers to accurate delirium screening were CAM-ICU knowledge deficits, establishment of baseline cognition, and inappropriate use of the "unable to assess" designation. The mean percentage of correct observations improved from 40% (first observation) to 90% (second observation) (P < .001). All 13 nurses strongly agreed that the training was beneficial and practice changing. CONCLUSIONS: The use of tele-ICU to improve the accuracy of delirium screening by ICU nurses appears to be feasible and efficient for leveraging delirium expertise across multiple ICUs. Future studies should evaluate the effects of tele-ICU delirium training on patient-centered outcomes.


Subject(s)
Delirium , Telemedicine , Critical Care/methods , Delirium/prevention & control , Humans , Intensive Care Units , Pilot Projects
8.
Crit Care Explor ; 3(3): e0363, 2021 Mar.
Article in English | MEDLINE | ID: mdl-33786439

ABSTRACT

OBJECTIVES: Implement a connected network between two Tele-ICU programs to support staffing and rounding during the first wave of the coronavirus disease 2019 pandemic in the United States. DESIGN: Proof of Concept model. SETTING: Northwell Health; a 23 Hospital, 40 ICU (500 ICU beds) healthcare organization serving the downstate NY area. During the initial coronavirus disease 2019 pandemic, Northwell Health rapidly expanded to greater than 1,000 ICU beds. The surge in patients required redeployment of noncritical care providers to the ICU bedside. The Tele-ICU program expanded from covering 176 beds pre pandemic to assisting with care for patients in approximately 450 beds via deployment of Wi-Fi-enabled mobile telehealth carts to the newly formed ICUs. PATIENTS: Critically ill coronavirus disease 2019 patients hospitalized at Northwell Health, NY, at any point from March 2020 to June 2020. INTERVENTIONS: To offset the shortage of critical care physicians, Northwell Health established a collaboration with the Tele-ICU program of Providence, St. Joseph Health in the state of Washington, which enabled the critical care physicians of Providence, St. Joseph Health to participate in virtual rounding on critically ill coronavirus disease 2019 patients at Northwell Health. MAIN RESULTS: We developed an innovative hybrid model that allowed for virtual rounding on an additional 40-60 patients per day by a remote critical care physician at Providence, St. Joseph Health. This was accomplished in approximately 3 weeks and provided remote care to complex patients. CONCLUSIONS: Our findings demonstrate the proof of concept of establishing a network of connected Tele-ICU programs as a rapidly scalable and sustainable paradigm for the provision of support from critical care physicians for noncritical care teams at the bedside.

9.
Toxicol Mech Methods ; 27(5): 376-381, 2017 Jun.
Article in English | MEDLINE | ID: mdl-28325086

ABSTRACT

Non-genotoxic carcinogens may play a significant role in development of cancer. Currently short-term assays for mutagenicity classify genotoxic carcinogens and lack the abilities to detect epigenetic carcinogens. The need to develop an endpoint always remains to recognize potentially carcinogenic agents employing rapid and practical bioassays. For this, the present study utilized TA98 and TA1537 tester strains of Salmonella typhimurium to evaluate four non-genotoxic carcinogenic agents (Coumarin, ß-Myrcene, Bis(2-ethylhexyl) phthalate and trans-anethole). These chemicals were tested individually and in combination with promutagens 2-aminoanthracene (2AA) and benzo(a)pyrene (BP) in presence of metabolic activation system (S9) by plate incorporation method. Exposure to all four test chemicals revealed marked increase of revertant colonies in promutagen combined groups as compared to promutagens alone. However significantly greater fold responses were observed with 2AA combination groups (Coumarin +2AA, ß-Myrcene +2AA, Bis(2-ethylhexyl) phthalate +2AA and trans-anethole +2AA) with TA98 strain as compared with TA1537, which seems to have enhanced the mutagenic response of 2AA in metabolically activated conditions. It is concluded that out of both tester strains TA98 strain of Salmonella typhimurium has the potential to detect non-genotoxic carcinogens when combined with potent promutgens either by inhibiting or modulating activities of liver microsomal enzymes biochemically which may indirectly contribute to neoplastic alterations. Further this simple, short-term alternative assay may provide rapid information during extrapolative toxicology for differentiating genotoxic and non-genotoxic carcinogens.


Subject(s)
Carcinogens/toxicity , Mutagens/toxicity , Salmonella typhimurium/drug effects , Salmonella typhimurium/genetics , Activation, Metabolic , Acyclic Monoterpenes , Allylbenzene Derivatives , Anisoles/toxicity , Anthracenes/toxicity , Benzo(a)pyrene/toxicity , Coumarins/toxicity , Diethylhexyl Phthalate/toxicity , Dose-Response Relationship, Drug , Drug Synergism , Microsomes, Liver/enzymology , Microsomes, Liver/metabolism , Monoterpenes/toxicity , Mutagenicity Tests
10.
Ann Am Thorac Soc ; 14(5): 766-777, 2017 May.
Article in English | MEDLINE | ID: mdl-28231030

ABSTRACT

BACKGROUND: Early mobilization and rehabilitation of patients in intensive care units (ICUs) may improve physical function, and reduce the duration of delirium, mechanical ventilation, and ICU length of stay. However, safety concerns are an important barrier to widespread implementation. OBJECTIVES: To synthesize safety data regarding patient mobilization and rehabilitation in the ICU, including falls, removal of endotracheal tubes, removal or dysfunction of intravascular catheters, removal of other catheters/tubes, cardiac arrest, hemodynamic changes, and desaturation. DATA SOURCES: Systematic literature review, including searches of five databases. Eligible studies evaluated patients who received mobilization-related interventions in the ICU. Exclusion criteria included: (1) case series with fewer than 10 patients; (2) majority of patients under 18 years of age; and (3) data not reported to permit calculation of incidence of safety events. DATA EXTRACTION: Number of patients, mobilization/rehabilitation sessions, potential safety events, and events with negative consequences (e.g., requiring intervention or additional therapy). SYNTHESIS: Heterogeneity was assessed by I2 statistics, and bias assessed by the Newcastle-Ottawa Scale and Cochrane risk of bias assessment. The literature search identified 20,660 titles. There were 48 eligible publications evaluating 7,546 patients, with 583 potential safety events occurring in 22,351 mobilization/rehabilitation sessions. There was a total of 583 (2.6%) potential safety events with heterogeneity in the definitions for these events. For the safety event types that could be meta-analyzed, pooled incidences per 1,000 mobilization/rehabilitation sessions (95% confidence interval), were: hemodynamic changes, 3.8 (1.3-11.4), and desaturation, 1.9 (0.9-4.3). A total of 24 studies of 3,404 patients reported on any consequences of potential safety events (e.g., needing to increase dose of vasopressor due to mobility-related hypotension), with a frequency of 0.6% in 14,398 mobilization/rehabilitation sessions. CONCLUSIONS: Patient mobilization and physical rehabilitation in the ICU appears safe, with a low incidence of potential safety events, and only rare events having any consequences for patient management. Heterogeneity in the definition of safety events across studies emphasizes the importance of implementing existing consensus-based definitions.


Subject(s)
Critical Illness/rehabilitation , Length of Stay/statistics & numerical data , Patient Safety , Case Management , Critical Illness/therapy , Humans , Intensive Care Units/organization & administration , Randomized Controlled Trials as Topic , Respiration, Artificial/adverse effects
11.
J Endod ; 38(10): 1412-6, 2012 Oct.
Article in English | MEDLINE | ID: mdl-22980190

ABSTRACT

BACKGROUND: The aim of this in vitro study was to evaluate the depth of penetration of 4 different endodontic resin sealers into the radicular dentinal tubules with the aid of confocal microscopy. METHODS: Eighty single-rooted teeth were instrumented and divided into 4 groups composed of 20 teeth each. The samples were obturated with AH Plus, RealSeal, EndoRez, and RoekoSeal resin sealers, respectively. The core material in all the groups was Resilon. The teeth were sectioned at the coronal, middle, and apical thirds and viewed under confocal microscope to determine the depth of penetration of the sealer into the dentinal tubules. RESULTS: The results showed that the maximum penetration was exhibited by RealSeal resin sealer, followed by AH Plus, RoekoSeal, and EndoRez. The coronal third showed the maximum penetration, followed by middle third and least at the apical third. CONCLUSION: Under the parameter of this study, RealSeal resin sealer exhibited the maximum penetration.


Subject(s)
Dentin Permeability , Dentin , Root Canal Filling Materials , Root Canal Obturation , Bicuspid , Composite Resins , Dental Cements , Dental Pulp Cavity/diagnostic imaging , Dentin/anatomy & histology , Dentinal Fluid , Epoxy Resins , Humans , Microscopy, Confocal , Radiography, Dental, Digital , Root Canal Preparation
12.
Kidney Int ; 80(6): 633-44, 2011 Sep.
Article in English | MEDLINE | ID: mdl-21734638

ABSTRACT

Acute injuries of the kidney or lung each represent serious, complex clinical problems, and their combination drastically decreases patient survival. However, detailed understanding of interactions between these two organs is scarce. To evaluate this further, we used the folic acid (FA) and myohemoglobinuria models of acute kidney injury (AKI) together with Pseudomonas aeruginosa inhalation to study kidney-lung cross-talk in mice during acute kidney and lung injury. Subgroups of mice received antineutrophil antibody or platelet-depleting serum to assess the role of neutrophil and platelets, respectively. AKI by itself did not cause clinically relevant acute lung injury. Pneumonia was neutrophil dependent, whereas pneumonia-induced AKI was platelet dependent. AKI attenuated pulmonary neutrophil recruitment and worsened pneumonia. Mice with AKI had lower oxygen saturations and greater bacterial load than mice without. Neutrophils isolated from mice with FA-induced AKI also had impaired transmigration and F-actin polymerization in vitro. Thus, during acute kidney and pneumonia-induced lung injury, clinically relevant kidney-lung interactions are both neutrophil and platelet dependent.


Subject(s)
Acute Kidney Injury/complications , Acute Kidney Injury/physiopathology , Kidney/physiopathology , Lung/physiopathology , Pneumonia, Bacterial/complications , Pneumonia, Bacterial/physiopathology , Acute Kidney Injury/chemically induced , Animals , Bacterial Load , Blood Platelets/physiology , Disease Models, Animal , Folic Acid/toxicity , Lung/microbiology , Mice , Mice, Inbred C57BL , Models, Biological , Neutrophils/physiology , Organ Specificity , Pneumonia, Bacterial/microbiology , Pseudomonas Infections/complications , Pseudomonas Infections/microbiology , Pseudomonas Infections/physiopathology , Pseudomonas aeruginosa
13.
Article in English | MEDLINE | ID: mdl-21550269

ABSTRACT

OBJECTIVE: Anatomical racial variations are an acknowledged characteristic in permanent molars. Generally, mandibular first molars have 2 roots; however, the presence of a third root, radix entomolaris (RE), is a major anatomic variant among many population groups. This study evaluated the prevalence of permanent mandibular first molars featuring a distolingual root in a South Indian population. STUDY DESIGN: Five hundred patients of South Indian origin possessing bilateral mandibular first molars were selected. The radiographs of these patients were evaluated under optimal conditions. A total of 1000 mandibular first molars were screened and the incidence of 3-rooted mandibular first molars and the correlation between left and right side occurrence and between either gender was recorded. RESULTS: The prevalence of 3-rooted mandibular first molars was 18.6% of the patients examined and 13.3% of the teeth examined. There was no statistically significant difference between genders or side of occurrence (P > .05). The bilateral incidence of a symmetric distribution was 43.01%. CONCLUSIONS: RE is considered an Asiatic trait. The occurrence of this macrostructure in the South Indian population was 13.3%, which was lower than that of other patients of Mongoloid origin. The clinician must thoroughly examine the radiograph before initiation of endodontic therapy.


Subject(s)
Dental Pulp Cavity/anatomy & histology , Molar/anatomy & histology , Tooth Abnormalities/epidemiology , Tooth Root/anatomy & histology , Adolescent , Adult , Aged , Dentition, Permanent , Female , Humans , India/epidemiology , Male , Mandible , Middle Aged , Prevalence , White People , Young Adult
14.
J Endod ; 36(4): 675-8, 2010 Apr.
Article in English | MEDLINE | ID: mdl-20307743

ABSTRACT

INTRODUCTION: The aim of this in vitro study was to evaluate the efficacy of 5.25% sodium hypochlorite (NaOCl), 2% chlorhexidine gluconate (CHX), and 17% EDTA as a final irrigant with and without the inclusion of an antifungal agent (1% clotrimazole) on Candida albicans. METHODS: Sixty-five single-rooted instrumented and inoculated with a suspension of C. albicans. The experimental specimens were divided into two groups. The irrigant group was divided into three subgroups and irrigated with 5.25% NaOCl, 2% CHX, and 17% EDTA, respectively. The irrigant with antifungal group was divided into three subgroups and irrigated with 5.25% NaOCl, 2% CHX, and 17% EDTA respectively followed by 1% clotrimazole. Aliquots from the experimental teeth were plated on 4% Sabouraud agar (Tital Biotech, Delhi, India), and the colony-forming units (CFUs) were evaluated under light microscopy (400x). RESULTS: NaOCl, 5.25%, exhibited superior antifungal efficacy compared with 2% CHX and 17% EDTA (p < 0.001). On inclusion of 1% clotrimazole, there was a significant decrease in the CFU (p < 0.001); 5.25% NaOCl and 2% CHX with clotrimazole showed significantly greater antifungal properties than 17% EDTA with clotrimazole (p < 0.001). CONCLUSION: One percent of clotrimazole proved to be effective against C. albicans when used along with root canal irrigants as a final rinse.


Subject(s)
Antifungal Agents/pharmacology , Candida albicans/drug effects , Chlorhexidine/analogs & derivatives , Clotrimazole/pharmacology , Edetic Acid/pharmacology , Root Canal Irrigants/pharmacology , Sodium Hypochlorite/pharmacology , Analysis of Variance , Chlorhexidine/pharmacology , Colony Count, Microbial , Drug Combinations , Humans , Statistics, Nonparametric
15.
Toxicol Mech Methods ; 20(2): 90-5, 2010 Feb.
Article in English | MEDLINE | ID: mdl-20102296

ABSTRACT

5-aminoisoquinoline (5-AIQ) is an active PARP-1 inhibitor as well as an important functional group various drugs. Quinolines are generally known as mutagenic and carcinogenic in various in vitro and in vivo systems, while both positive and negative findings are available on the mutagenic potential of several isoquinolines. Since no literature is available on the genotoxicity of 5-AIQ, a battery of tests were conducted, in accordance with relevant OECD protocols, such as bacterial reverse mutation test, in vitro chromosomal aberration test, and bone marrow micronucleus test in mouse. These studies demonstrate that 5-AIQ does not possess genotoxic activity both with in vitro and in vivo systems. The findings substantiate the therapeutic value of 5-AIQ.


Subject(s)
Enzyme Inhibitors/toxicity , Isoquinolines/toxicity , Poly(ADP-ribose) Polymerase Inhibitors , Animals , Bone Marrow Cells/drug effects , Bone Marrow Cells/pathology , Cells, Cultured , Chromosome Aberrations/chemically induced , Dose-Response Relationship, Drug , Gene Expression Regulation, Bacterial/drug effects , Humans , Lymphocytes/drug effects , Lymphocytes/pathology , Male , Mice , Mice, Inbred C57BL , Micronuclei, Chromosome-Defective/chemically induced , Mutagenicity Tests , Mutation , Risk Assessment , Salmonella typhimurium/drug effects , Salmonella typhimurium/genetics
16.
Article in English | MEDLINE | ID: mdl-19778737

ABSTRACT

Identification and treatment of extra canals is the cornerstone to successful endodontic practice. Over the years, many diagnostic aids have evolved to facilitate the clinician in detection of hidden canals and to familiarize with the internal radicular anatomy. This case report highlights the rare incidence of 3 canals in the distal root of a permanent mandibular first molar. A spiral computerized tomography scan was used as a noninvasive diagnostic tool to confirm the diagnosis.


Subject(s)
Dental Pulp Cavity/diagnostic imaging , Molar/diagnostic imaging , Root Canal Therapy , Tomography, Spiral Computed , Tooth Root/diagnostic imaging , Adult , Dental Pulp Cavity/pathology , Gutta-Percha/therapeutic use , Humans , Male , Periapical Periodontitis/therapy , Pulpitis/therapy , Radiography, Bitewing , Root Canal Filling Materials/therapeutic use , Root Canal Preparation/instrumentation , Root Canal Preparation/methods , Tooth Apex/diagnostic imaging , Tooth Apex/pathology , Tooth Root/pathology
17.
Ecotoxicol Environ Saf ; 66(2): 210-6, 2007 Feb.
Article in English | MEDLINE | ID: mdl-16620981

ABSTRACT

Leachates derived from dry wastes of the metal, tannery, and dye industries of the state of Uttar Pradesh (India) were analyzed for their mutagenic potential using reverse mutation assay. Both the spot and plate incorporation assays were conducted with four tester strains of Salmonella typhimurium (TA97a, TA98, TA100, and TA102). The metal concentrations in the samples were also determined. The result suggests that leachates derived from metal and tannery wastes possess mutagenic properties. The findings are indicative of the type of environmental and health risks posed by improper waste disposal.


Subject(s)
Industrial Waste , Metallurgy , Mutagens/toxicity , Tanning , Water Pollutants, Chemical/toxicity , Coloring Agents , Metals, Heavy/analysis , Metals, Heavy/toxicity , Mutagens/analysis , Refuse Disposal , Salmonella typhimurium/drug effects , Salmonella typhimurium/genetics , Water Pollutants, Chemical/analysis
18.
Exp Hematol ; 34(5): 588-92, 2006 May.
Article in English | MEDLINE | ID: mdl-16647564

ABSTRACT

OBJECTIVE: Lentiviral vectors are increasingly used for preclinical models of gene therapy and other forms of experimental transgenesis. Due to the broad tropism and the ability for concentration by ultracentrifugation, most lentiviral vector preparations are produced using the vesicular stomatitis virus glycoprotein (VSV-g) protein as envelope. Recently, Hanawa and colleagues have demonstrated that the ecotropic envelope protein of murine leukemia viruses allows efficient pseudotyping of HIV-1-derived vector particles. However, this method has found little acceptance, despite potential advantages. MATERIALS AND METHODS: We produced lentiviral vectors pseudotyped with murine ecotropic envelope using a four-plasmid transient transfection system and evaluated their performance in murine fibroblasts and hematopoietic cells. RESULTS: Titers of lentiviral "ecotropic" supernatants were only slightly lower than those produced with VSV-g, could be concentrated by overnight centrifugation (13,000g), and efficiently transduced murine fibroblasts and hematopoietic cells but not human cells. Our Institutional Biosafety Committee agreed on the production and use of replication-defective lentiviral vectors pseudotyped with murine ecotropic envelope under biosafety level 1 (BL1) conditions with additional BL2 practices. We also obtained useful guidelines for the work with human infectious lentiviral vectors. CONCLUSIONS: For the researcher, "ecotropic" lentiviral vectors significantly improve the convenience of daily work, compared to the conditions required for lentiviral pseudotypes that are capable of infecting human cells. High efficiency and superior biosafety in combination with convenient handling will certainly boost the potential applicability of this important vector system.


Subject(s)
Genetic Vectors/adverse effects , Lentivirus/genetics , Leukemia Virus, Murine/genetics , Animals , Base Sequence , DNA Primers , Genetic Therapy , Mice , Polymerase Chain Reaction
19.
Environ Mol Mutagen ; 47(5): 325-33, 2006 Jun.
Article in English | MEDLINE | ID: mdl-16586500

ABSTRACT

Contamination of ground water by industrial waste poses potential health hazards for man and his environment. The improper disposal of toxic wastes could allow genotoxic chemicals to percolate into ground waters, and these contaminated ground waters may produce toxicity, including mutation and eventually cancer, in exposed individuals. In the present study, we evaluated the in vivo genotoxic potential of leachates made from three different kinds of industrial waste (tannery waste, metal-based waste, and waste containing dyes and pigments) that are disposed of in areas adjoining human habitation. Three different doses of test leachates were administered by oral gavage for 15 consecutive days to Swiss albino mice; their bone marrow cells were examined for chromosome aberrations (CAs), micronucleated polychromatic erythrocytes (MNPCEs), and DNA damage using the alkaline Comet assay. Exposure to the leachates resulted in significant (P < 0.05 or P < 0.001) dose-dependent increases in chromosome and DNA damage. Fragmented chromosomes and chromatid breaks were the major CAs observed. Chemical analysis of the leachates indicated that chromium and nickel were elevated above the limits established by health organizations. The highest levels of genotoxicity were produced by the metal-based leachate and the tannery-waste leachate, while the dye-waste leachate produced weaker genotoxic responses. The cytogenetic abnormalities and DNA damage produced by the leachates indicate that humans consuming water contaminated with these materials are at increased risk of developing adverse health consequences.


Subject(s)
Bone Marrow Cells/drug effects , Industrial Waste/adverse effects , Water Pollutants, Chemical/toxicity , Administration, Oral , Animals , Chromosome Aberrations/chemically induced , Coloring Agents , Comet Assay , DNA Damage , Industrial Waste/analysis , Male , Metallurgy , Metals, Heavy/analysis , Metals, Heavy/toxicity , Mice , Micronuclei, Chromosome-Defective/chemically induced , Micronucleus Tests , Tanning , Water Pollutants, Chemical/analysis
20.
Mol Ther ; 13(2): 391-400, 2006 Feb.
Article in English | MEDLINE | ID: mdl-16226060

ABSTRACT

Severe adverse events related to insertional mutagenesis have reinforced interest in self-inactivating (SIN) retroviral vectors lacking enhancer-promoter sequences in the long terminal repeats (LTRs). Here, we have compared the potency of gammaretroviral and lentiviral vectors expressing the P140K mutant of O(6)-methylguanine-DNA methyltransferase (MGMT). MGMT-P140K is a clinically relevant selection marker that mediates a strong survival advantage in hematopoietic cells exposed to alkylating agents. We designed gammaretroviral and lentiviral vectors that contained identical enhancer-promoter sequences located either in the LTR or downstream of the packaging region, for internal initiation of transcription from SIN backbones. Gammaretroviral vectors with intact LTRs containing enhancer-promoter sequences showed both higher titers and higher expression levels than the lentiviral counterparts, likely a result of suboptimal RNA processing of the lentiviral leader region. In the SIN context, gammaretroviral and lentiviral vectors with comparable internal cassettes had similar expression properties. Interestingly, gammaretroviral SIN vectors pseudotyped with RD114/TR had a higher transduction efficiency on proliferating human CD34(+) cells than lentiviral counterparts. These results encourage further investigations into the formation of retroviral hybrid vectors that combine the desired properties of high efficiency and increased biosafety.


Subject(s)
Gene Expression Regulation, Viral/physiology , Genetic Vectors , Hematopoietic Stem Cells/enzymology , Lentivirus/genetics , Leukemia Virus, Murine/genetics , O(6)-Methylguanine-DNA Methyltransferase/biosynthesis , O(6)-Methylguanine-DNA Methyltransferase/genetics , Transduction, Genetic , Animals , Cells, Cultured , Hematopoietic Stem Cells/virology , Humans , Mice , Mice, Inbred C57BL , Mutagenesis, Insertional , O(6)-Methylguanine-DNA Methyltransferase/physiology , RNA Processing, Post-Transcriptional
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