Radiation Exposure Alters Expression of Metabolic Enzyme Genes in Mice

Most administered pharmaceuticals are metabolized by the liver. The health of the liver, especially the rate of its metabolic enzymes, determines the concentration of circulating drugs as well as the duration of their efficacy. Most pharmaceuticals are metabolized by the liver, and clinically-used medication doses are given with normal liver function in mind. A drug overdose can result in the case of a liver that is damaged and removing pharmaceuticals from the circulation at a rate slower than normal. Alternatively, if liver function is elevated and removing drugs from the system more quickly than usual, it would be as if too little drug had been given for effective treatment. Because of the importance of the liver in drug metabolism, we want to understand the effects of spaceflight on the enzymes of the liver and exposure to cosmic radiation is one aspect of spaceflight that can be modeled in ground experiments. Additionally, it has been previous noted that pre-exposure to small radiation doses seems to confer protection against later and larger radiation doses. This protective power of pre-exposure has been called a priming effect or radioadaptation. This study is an effort to examine the drug metabolizing effects of radioadaptation mechanisms that may be triggered by early exposure to low radiation doses

Markers of Inflammation in Bacterial Diarrhea among Travelers, with a Focus on Enteroaggregative Escherichia coli Pathogenicity

The intestinal inflammatory response of traveler's diarrhea acquired in Goa, India, and Guadalajara, Mexico, was studied. Fecal lactoferrin was found in stool samples in which enteroaggregative Escherichia coli (EAEC), enterotoxigenic E. coli, or Salmonella or Shigella species were isolated, with Shigella-positive cases showing the highest level. Samples from cases of Shigella-associated diarrhea had the highest concentrations of fecal cytokines. Travelers to India who had EAEC-associated diarrhea showed elevated levels of interleukin (IL)-8 (median, 341.15 pg/mL) and IL-1β (median, 749.90 pg/mL). Although 15 travelers to Mexico who had EAEC-associated diarrhea had a median concentration of 0 pg/mL for both IL-8 and IL-1β, 2 had high levels of IL-8 (1853 and 11,786 pg/mL), and 5 showed elevated levels of IL-1β (1-1240 pg/mL). Samples from patients in India who had pathogen-negative diarrhea or from patients in Mexico who had asymptomatic EAEC infection were negative for cytokines. Bacterial pathogens causing traveler's diarrhea commonly produce intestinal inflammation, although a subset of patients with EAEC-associated diarrhea fail to develop an inflammatory respons

Association between living near to a non-sanitary landfill, fingernail cadmium level and health symptoms among children in Nilai

Background: Living in proximity to landfill could expose children to heavy metals such as Cadmium that can reduce immune system function and lead to an increased risk of infections. Study was aimed to determine the accumulation of Cd in fingernails and the associated health symptoms among school children living in a proximity to non-sanitary landfill sites. Materials and Methods: A cross-sectional study was performed from November 2013 to February 2014 in Pajam-Nilai, Malaysia. Study involved 70 children aged 7 to 11 years old who reside within 2 to 4 km radius from a non-sanitary landfill. A standard questionnaire was used to determine the socio-demographic background of the respondent, the Cd exposure and the health symptoms. Fingernail samples were collected from the children to indicate metal body burden and the airborne dust was monitored using air sampling pump. Cd in all samples was analyzed using Inductive Coupled Plasma Mass Spectrometry. Result: The mean (SD) of Cd in fingernails of children who lives 2km from landfill (3.19 (0.47) µg/m3). No association was found between Cd in fingernails and Cd in the airborne dust. Reside close to landfill and the levels of Cd in fingernails were not associated with the health symptoms in this study. Conclusion: Although Cd level in fingernail of children living in proximity to landfill was higher than those who lives beyond that, health symptoms had no association with the exposure level

Foot care education and self management behaviors in diverse veterans with diabetes

The objective of this study was to examine differences in self-reported diabetes foot care education, self management behaviors, and barriers to good foot care among veterans with diabetes by race and ethnicity. Data was collected using the Veterans Health Administration Footcare Survey, a validated tool that assessed demographic, general health, diabetes and foot self-care information, barriers to foot self-care, receipt of professional foot care, and satisfaction with current care. We mailed surveys to a random sample of patients with diabetes from eight VA medical centers. Study participants were 81% White; 13% African American; 4% Asian, and 2% American Indian and Pacific Islanders. The majority of respondents felt that they did not know enough about foot self-care. There were large gaps between self-reported knowledge and actual foot care practices, even among those who reported “knowing enough” on a given topic. There were significant differences in self-reported foot care behaviors and education by race and ethnicity. These findings document the need for culturally-specific self-management education to address unique cultural preferences and barriers to care

Assessing respiratory inflammation among children living near to non-sanitary landfill using interleukin-6 (IL-6)

Aims: To determine the respiratory inflammation among children living near to non-sanitary municipal solid waste landfill area and the concentration of Interleukin-6 cytokine. Study Design: A cross-sectional comparative study design. Place and Duration of Study: Sample: Pajam, Negeri Sembilan, Malaysia, between September 2013 and April 2014. Methodology: A total of 72 children were randomly selected based on the inclusive and exclusive criteria. A set of pre-tested questionnaires were utilized to obtain socio-demographic information and to predict health risk faced by the respondents. Saliva samples of the respondents were collected and analyzed using Human Interleukin-6 (IL-6) Platinum ELISA (Enzyme-Linked Immunosorbent Assay) kit. Results: The PM10 concentration for the exposed group was higher than the unexposed group with the mean ± standard deviation (SD) of 152.31±31.07 μg/m3 and 87.77±30.77 μg/m3 respectively. The mean ± SD of the Interleukin-6 for the exposed group was slightly higher than the unexposed group with the mean ± SD of 6.34±1.95 pg/ml and 5.77±1.08 pg/ml respectively. The most common symptoms reported was sneezing and sore throat. There was no significant correlation between PM10 concentration and IL-6 in this study. Conclusion: The findings exhibit that there was no association between Interleukin-6 and PM10 concentration of the respondent. However, there are likely potential adverse health impacts arising from particulates exposure among exposed children in this study. Respondents are advised to have a medical check-up in order to determine respiratory health status thus elimination the risks of acquiring respiratory inflammation

Changes in SARS-CoV-2 viral load and mortality during the initial wave of the pandemic in New York City

Funding: This work was partially supported by the National Center for Advancing Translational Sciences of the National Institutes of Health (UL1 TR0023484 to Julianne Imperato-McGinley) and the National Institute of Allergy and Infectious Diseases (UM1 AI069470 to M.E.S).Public health interventions such as social distancing and mask wearing decrease the incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, but it is unclear whether they decrease the viral load of infected patients and whether changes in viral load impact mortality from coronavirus disease 2019 (COVID-19). We evaluated 6923 patients with COVID-19 at six New York City hospitals from March 15-May 14, 2020, corresponding with the implementation of public health interventions in March. We assessed changes in cycle threshold (CT) values from reverse transcription-polymerase chain reaction tests and in-hospital mortality and modeled the impact of viral load on mortality. Mean CT values increased between March and May, with the proportion of patients with high viral load decreasing from 47.7% to 7.8%. In-hospital mortality increased from 14.9% in March to 28.4% in early April, and then decreased to 8.7% by May. Patients with high viral loads had increased mortality compared to those with low viral loads (adjusted odds ratio 2.34). If viral load had not declined, an estimated 69 additional deaths would have occurred (5.8% higher mortality). SARS-CoV-2 viral load steadily declined among hospitalized patients in the setting of public health interventions, and this correlated with decreases in mortality.Peer reviewe

Gastrointestinal bleeding after liver transplantation

To investigate the causes of gastrointestinal bleeding (GIB) and its impact on patient and graft survival after orthotopic liver transplantation (OLTx), the first 1000 consecutive OLTx using tacrolimus were studied. Our patient population consisted of 834 adults. The bleeding episodes of patients with GIB (n=74) were analyzed, and patients without GIB (n=760) were used as controls. The mean age, gender, and United Network for Organ Sharing status were similar in both groups. Endoscopy was done in 73 patients with GIB and yielded a diagnosis in 60 patients (82.2%): 39 with a single, and 21 with multiple GIB episodes. In the remaining 13 patients (17.8%), the bleeding source was not identified. Of 92 GIB episodes with endoscopic diagnoses, ulcers (n=25) were the most common cause of bleeding, followed by enteritis (n=24), portal hypertensive lesions (n=15), Roux-en-Y bleeds, and other miscellaneous events (n=28). The majority (73%) of the GIB episodes occurred during the first postoperative trimester. The patient and graft survival rates were statistically lower in the GIB group compared with the control group. The adjusted relative risk of mortality and graft failure was increased by bleeding. In summary, the cumulative incidence of GIB was 8.9%. Endoscopy identified the source of GIB in most cases. Ulcers were the most common cause of GIB after OLTx. The onset of GIB after OLTx was an indicator of decreased patient and graft survival

Multicore liquid perfluorocarbon-loaded multimodal nanoparticles for stable ultrasound and ¹⁹ F MRI applied to in vivo cell tracking

Ultrasound is the most commonly used clinical imaging modality. However, in applications requiring cell-labeling, the large size and short active lifetime of ultrasound contrast agents limit their longitudinal use. Here, 100 nm radius, clinically applicable, polymeric nanoparticles containing a liquid perfluorocarbon, which enhance ultrasound contrast during repeated ultrasound imaging over the course of at least 48 h, are described. The perfluorocarbon enables monitoring the nanoparticles with quantitative 19 F magnetic resonance imaging, making these particles effective multimodal imaging agents. Unlike typical core–shell perfluorocarbon-based ultrasound contrast agents, these nanoparticles have an atypical fractal internal structure. The nonvaporizing highly hydrophobic perfluorocarbon forms multiple cores within the polymeric matrix and is, surprisingly, hydrated with water, as determined from small-angle neutron scattering and nuclear magnetic resonance spectroscopy. Finally, the nanoparticles are used to image therapeutic dendritic cells with ultrasound in vivo, as well as with 19 F MRI and fluorescence imaging, demonstrating their potential for long-term in vivo multimodal imaging. </p

Therapeutic Targeting of ATP7B in Ovarian Carcinoma.

PURPOSE: Resistance to platinum chemotherapy remains a significant problem in ovarian carcinoma. Here, we examined the biological mechanisms and therapeutic potential of targeting a critical platinum resistance gene, ATP7B, using both in vitro and in vivo models. EXPERIMENTAL DESIGN: Expression of ATP7A and ATP7B was examined in ovarian cancer cell lines by real-time reverse transcription-PCR and Western blot analysis. ATP7A and ATP7B gene silencing was achieved with targeted small interfering RNA (siRNA) and its effects on cell viability and DNA adduct formation were examined. For in vivo therapy experiments, siRNA was incorporated into the neutral nanoliposome 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine (DOPC). RESULTS: ATP7A and ATP7B genes were expressed at higher levels in platinum-resistant cells compared with sensitive cells; however, only differences in ATP7B reached statistical significance. ATP7A gene silencing had no significant effect on the sensitivity of resistant cells to cisplatin, but ATP7B silencing resulted in 2.5-fold reduction of cisplatin IC(50) levels and increased DNA adduct formation in cisplatin-resistant cells (A2780-CP20 and RMG2). Cisplatin was found to bind to the NH(2)-terminal copper-binding domain of ATP7B, which might be a contributing factor to cisplatin resistance. For in vivo therapy experiments, ATP7B siRNA was incorporated into DOPC and was highly effective in reducing tumor growth in combination with cisplatin (70-88% reduction in both models compared with controls). This reduction in tumor growth was accompanied by reduced proliferation, increased tumor cell apoptosis, and reduced angiogenesis. CONCLUSION: These data provide a new understanding of cisplatin resistance in cancer cells and may have implications for therapeutic reversal of drug resistance