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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.

ObjectiveDescribe the changes in patient population, bed occupancy, severity of illness and ventilator requirements across a large health system in the greater New York City area during the pandemic response in comparison with the 2019 baseline.DesignObservational, descriptive study of ICUs monitored by a tele-ICU system across Northwell Health. Inclusion criteria: All patients admitted to Northwell Health tele-ICUs during 2019 and between March 23, 2020 and April 6, 2020.ExposureA data extract was developed to collect data every hour for each ICU bed in the Northwell tele-critical care program as a quality reporting initiative to understand ICU capacity and resource utilization. A similar extract was developed for each hour of 2019.Main Outcomes and MeasuresAverage of any given hour during the pre-COVID-19 and pandemic periods for the following metrics: proportion of beds occupied, proportion of ventilated patients, severity of illness (measured by the ICU Discharge Readiness Score (DRS)), and length of stay (LOS).ResultsHourly analysis of data from 186 ICU beds from 14 ICUs and 9 hospitals were included, representing 10,714 patients in 2019 and 465 patients between March 23 and April 6, 2020. Average hourly occupancy increased from 64% to 78%, while the proportion of patients invasively ventilated increased from 33.9% to 84.2%. Median DRS (severity of illness score) increased from 1.08 (IQR: 0.24-6.98) to 39.38 (IQR: 12.00-71.28). Proportion of patients with Hispanic ethnicity doubled (7.8% to 16.6%; pConclusions and RelevanceIn addition to the expected increase in ICU occupancy and ventilator requirements, this large group of ICUs in midst of the COVID-19 epidemic are faced with managing a cohort of ICU patients with a dramatically higher severity of illness than their typical census.

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, β-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, β-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.

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.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.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.Number of patients, mobilization/rehabilitation sessions, potential safety events, and events with negative consequences (e.g., requiring intervention or additional therapy).Heterogeneity was assessed by IPatient 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.

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.

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.

Fanconi anemia (FA) is a rare autosomal recessive disorder that results from mutations in at least 11 different genes. Recent studies have demonstrated that clinical progression of the disease may be influenced by inter- and intragenic variations, emphasizing the importance of identifying the complementation groups. In the present study we have employed bicistronic retrovirus vectors that coexpress FA-specific cDNAs for complementation groups A, C, F, and G, together with the enhanced green fluorescence protein (EGFP), allowing for specific analysis of transduced EGFP+ cells within bulk cultures by flow cytometry. In addition, the assay relies on the correction of the characteristic FA-associated G2/M arrest after treatment of cells with DNA-damaging agents, which is analyzed by flow cytometry. Results obtained with this assay matched the complementation groups known for 12 control lymphoblast cell lines tested. We report here the results obtained for 48 FA patients with unknown complementation groups using this new assay. Complementation groups were identified for 24 patients. We have identified mutations in the genes corresponding to the assigned complementation group in 23 samples. This assay has now been established in a standardized fashion for complementation assignments in FA patients and the subsequent directing of rapid mutation analysis in those patients.

Hazardous industrial wastes are inevitable source of environmental pollution. Leachates from these wastes might contaminate the origins of potable water and affect human health. The study was carried out to determine the possible genotoxic effects of leachates from solid waste of a metal and dye industry using the Allium cepa chromosome aberrations assay. The 10% leachates were prepared from solid wastes obtained from both the industries and examined for the presence of heavy metal content and genotoxicity. To simulate the field and laboratory conditions, A. cepa bulbs were exposed through soil and aqueous medium for 48 h to 2.5-10% leachates. The results revealed that both metal waste leachate (MWL) and dye waste leachate (DWL) contained high concentrations of chromium, nickel and iron that significantly induced cytogenetic alterations. Significant inhibition of mitotic index (MI), inductions of chromosomal/mitotic aberrations (CA/MA) and micronuclei (MN) formation were found in all experimental groups exposed to MWL and DWL. The effects observed were concentration dependent and the frequency of aberrations was higher with treatment of MWL than DWL. The MI was severely inhibited at 10% aqueous exposure it was 4.59+/-0.69 (P

Diuron, a persistant substituted urea herbicide, was tested in the root meristem cells of Allium sativum for the possible cytogenetic effects and to compare the sensitivity with Allium cepa. Test concentrations of diuron 22.5, 45.0, and 90.0 ppm were mixed in soil and the cloves of A. sativum were placed over diuron-contaminated soils. Root meristematic cells were sampled at 48 h to score Mitotic/Chromosomal aberrations and to analyze the effect on mitotic index (MI). Microscopic analyses revealed significant and dose-dependent induction of mitotic as well as chromosomal breaks. The frequency of mitotic aberrations was every time found much higher than that of chromosomal aberrations. Mild percentage of Micronucleated and Binucleated cells was observed, as MI also declined during the analysis. Based on the data of valence charge densities on the atoms of herbicide molecule and spectroscopic studies, a possible mechanism of interaction of diuron with DNA molecule for chromosomal aberrations has been proposed.

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.

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.

The contamination of surface- and groundwater by the leaching of solid wastes generated by industrial activities as a result of water runoff and rainfall is a matter of great concern. The leachates from tannery solid waste (TSW), a major environmental pollutant, were examined for their possible genotoxic effects on the somatic cells of Vicia faba. Leachates were prepared from solid wastes procured from leather-tanning industrial sites, and V. faba seedlings were exposed to three test concentrations, 2.5%, 5%, and 10%, through soil and aqueous media for 5 days. The root tips examined for cytogenetic damage revealed that leachate of TSW significantly inhibited the mitotic index and induced significantly frequent chromosomal and mitotic aberrations (CA/MA) in a dose-dependent manner. The chemical analysis of TSW samples revealed that the chief constituents were chromium and nickel, which may cause genetic abnormalities. The frequency of aberrations was found to be higher in the root meristematic cells of Vicia faba exposed through the aqueous medium than those exposed through the soil medium. The results of the present study indicated that contamination of potable water bodies by leachates of TSW may cause genotoxicity. For the biomonitoring of complex mixtures of toxicants with the V. faba bioassay, the use of the aqueous medium seems to be a more promising method than the use of the soil medium.

In order to achieve efficient and safe expression of the promising chemoselection marker, O6-Methylguanine-DNA-methyltransferase (MGMT) P140K, in hematopoietic cells, we designed and compared eight vectors, three gammaretroviral (murine leukemia virus, MLV) and five lentiviral (human immunodeficiency virus, HIV-1). All vectors had monocistronic cassettes as required for clinical studies of MGMT-mediated bone marrow chemoprotection. We compared either LTR-driven or safer SIN (self-inactivating LTR) vectors. In the SIN context, we chose the human phosphoglycerokinase (hPGK), elongation factor 1a (EF1a) or SFFV U3 (MLV-derived) as an internal promoter to reveal different expression strengths. All constructs generated high titers and showed correct processing in target cells, as demonstrated by Northern, Western Blot und immunofluorescence. FACS analysis allowed sensitive detection of MGMT expression in transduced cells and revealed significant differences in MGMT levels, depending on vector design. Expression differences correlated with results of a biochemical alkyltransferase assay. The highest expression levels of MGMT P140K could be achieved using the SFFV promoter, located either in the LTR or in internal position of a SIN backbone. Gammaretroviral and lentiviral SIN vectors with comparable internal cassettes had similar titers and expression levels. An intron did not improve MGMT P140K expression. All vectors were sufficiently strong to mediate polyclonal chemoresistance, which resulted in a chimerism of >95% transduced cells in vitro, following a single exposure to BCNU. However, abundant expression of MGMT P140K, in contrast to the wild-type protein, led to a selective disadvantage of transduced cells in the absence of drug. Use of a less potent SIN vector with an internal expression cassette driven by the human PGK promoter avoided this side effect, and still allowed polyclonal chemoprotection of transduced hematopoietic cells under conditions of a low multiplicity of infection. Thus, to achieve the desired properties of efficiency and safety, less potent expression vectors for MGMT P140K represent a reasonable choice for future in vivo studies. Moreover, our preliminary data suggest that SIN vectors reduce the incidence of insertional genotoxicity in primary murine hematopoietic cells.

Fanconi anemia (FA) is a rare autosomal recessive disorder that results from mutations in at least eleven different genes (A, B, C, D1, D2, E, F, G, I, J, L). Recent studies have demonstrated that clinical progression of the disease may be influenced by inter- and intra-genic variations, underlining the importance of subtyping complementation groups. Previously we have utilized retroviral mediated gene transfer of FA cDNAs and subsequent analysis for the correction of hypersensitivity to Mitomycin C, to develop a valid method for subtyping of groups (Hanenberg et al., 2002). However, for lymphoblastic cell lines (LCL), G418 selection was required to compensate for low transduction efficiencies achieved. In the present study we have utilized RD114/GALV psuedotyped (high titer stable producer clones) bicistronic retroviral vectors that coexpress EGFP. This results in higher transduction efficiencies in LCLs (20–70% for C, F, G and 10–20 % for A vector) and allows for specific analysis of transduced EGFP-positive cells within the bulk cultures, thus obviating the need for selection. In addition, the assay relies on the correction of G2/M arrest that is analyzed by FLOW, further reducing the assay time. After transduction with cDNA-containing vectors for groups A, C, F and G, cells are exposed for 48 hours to the alkylating agent Melphalan, stained with Hoechst 33342 dye and cell cycle analysis for FA-specific G2/M arrest is performed by flow cytometry. The percentage of EGFP-positive cells in the G2/M phase of cell cycle for each vector is calculated and compared using the MODFIT software. A complementation group is identified when correction in the G2/M arrest occurs. Results obtained with the assay matched the complementation group known for 12 control LCLs tested. We report here the results obtained for 39 FA patients with unknown complementation groups using this new assay. Of the 39 cell lines tested, complementation group was identified for 20 lines [FA-A(17), FA-C(1), FA-F(1), FA-G(1)], while 15 lines were typed as Non A/C/F/G. Cells from 4 patients did not undergo G2/M arrest. Mutation analysis by direct sequencing of genomic DNA after DHPLC completed for 11 patients thus far, has detected a mutation in one or both alleles confirming the results of the rapid complementation assay in every case (Table). For the 15 cell lines typed as Non A/C/F/G, additional studies including vectors for the FA genes FANCD2, FANCE, FANCL are underway. In summary, we have developed a rapid and efficient method for the identification of complementation groups in FA patients that also serves as a guide for quick mutational analysis. This methodology can also be applied to myeloid progenitor cells as well as fibroblasts, an advantage in patients with lymphoid mosaicism. Table 1. Mutational analysis of cell lines identified by cell cycle analysis | Cell Line Ref # | Cell cycle analysis | Mutation 1(paternal) | Mutation 2 (maternal) | |:--------------- | ------------------- | -------------------- | --------------------- | | RA2593 | A | c.1471-?_2151+?del | c.1471-?_2151+?del | | RA2483 | A | | c.1901-?_2014+?del | | RA2625 | A | | c.3239G>T(p.R1080L) | | RA2644 | A | c.2806G>A(p.E936K) | c.2806G>A(p.E936K) | | RA2685 | A | c.2678G>A(p.W893X) | | | RA2698 | A | c.337_338delTC | | | RA2704 | A | c.3514-?_3626+?del | c.3520_3522delTGG | | RA2724 | C | c.322delG | c.711+4A>T(IVS4+4A>T) | | RA2191 | A | c.3520_3522dellTGG | | | RA2709 | F | c.484-485delCT | c.219delG | | RA2727 | G | c.908T>C | c.908T>C