89 research outputs found
Correction to: Choose and stay on one out of two paths: distinction between clinical versus research genetic testing to identify cancer predisposition syndromes among patients with cancer.
No full textFollowing publication of the original article, the author name D Gareth Evans has been processed incorrectly as DGareth Evans.</p
Use of Lean and CAHPS Surgical Care Survey to Improve Patients’ Experiences with Surgical Care
No full textA Neutrophil Phenotype Model for Extracorporeal Treatment of Sepsis
No full textAbstract\ud
\ud
Neutrophils play a central role in eliminating bacterial pathogens, but may also contribute to end-organ damage in sepsis. Interleukin-8 (IL-8), a key modulator of neutrophil function, signals through neutrophil specific surface receptors CXCR-1 and CXCR-2. In this study a mechanistic computational model was used to evaluate and deploy an extracorporeal sepsis treatment which modulates CXCR-1/2 levels. First, a simplified mechanistic computational model of IL-8 mediated activation of CXCR-1/2 receptors was developed, containing 16 ODEs and 43 parameters. Receptor level dynamics and systemic parameters were coupled with multiple neutrophil phenotypes to generate dynamic populations of activated neutrophils which reduce pathogen load, and/or primed neutrophils which cause adverse tissue damage when misdirected. The mathematical model was calibrated using experimental data from baboons administered a two-hour infusion of E coli and followed for a maximum of 28 days. Ensembles of parameters were generated using a Bayesian parallel tempering approach to produce model fits that could recreate experimental outcomes. Stepwise logistic regression identified seven model parameters as key determinants of mortality. Sensitivity analysis showed that parameters controlling the level of killer cell neutrophils affected the overall systemic damage of individuals. To evaluate rescue strategies and provide probabilistic predictions of their impact on mortality, time of onset, duration, and capture efficacy of an extracorporeal device that modulated neutrophil phenotype were explored. Our findings suggest that interventions aiming to modulate phenotypic composition are time sensitive. When introduced between 3–6 hours of infection for a 72 hour duration, the survivor population increased from 31% to 40–80%. Treatment efficacy quickly diminishes if not introduced within 15 hours of infection. Significant harm is possible with treatment durations ranging from 5–24 hours, which may reduce survival to 13%. In severe sepsis, an extracorporeal treatment which modulates CXCR-1/2 levels has therapeutic potential, but also potential for harm. Further development of the computational model will help guide optimal device development and determine which patient populations should be targeted by treatment.\ud
\ud
Author Summary\ud
\ud
Sepsis occurs when a patient develops a whole body immune response due to infection. In this condition, white blood cells called neutrophils circulate in an active state, seeking and eliminating invading bacteria. However, when neutrophils are activated, healthy tissue is inadvertently targeted, leading to organ damage and potentially death. Even though sepsis kills millions worldwide, there are still no specific treatments approved in the United States. This may be due to the complexity and diversity of the body’s immune response, which can be managed well using computational modeling. We have developed a computational model to predict how different levels of neutrophil activation impact survival in an overactive inflammatory conditions. The model was utilized to assess the effectiveness of a simulated experimental sepsis treatment which modulates neutrophil populations and activity. This evaluation determined that treatment timing plays a critical role in therapeutic effectiveness. When utilized properly the treatment drastically improves survival, but there is also risk of causing patient harm when introduced at the wrong time. We intend for this computational model to support and guide further development of sepsis treatments and help translate these preliminary results from bench to bedside
Chronic lead exposure effects in the cynomolgus monkey (Macaca fascicularis) testis
No full textAlthough reproductive consequences of high circulating blood lead levels (greater than or equal to 60 mu g/dL) have been reported, potential adverse effects of chronic lead exposure in males that result in low to moderate blood lead levels (10-25 and 26-60 mu g/dL, respectively) are unknown. Effects of chronic lead exposure to testis ultrastructure were determined in the cynomolgus monkey after oral administration of lead acetate (1500 mu g/kg BW/day) in a vehicle in the following groups: from birth to 10 years (lifetime), postnatal day 300 to 10 years (postinfancy), and postnatal day 0-400 (infancy); monkeys in the control group received only the vehicle (95% glycerol and 5% distilled water). At age 10 years, circulating lead concentrations in lifetime and postinfancy-dosed monkeys were approximately 35 mu g/dL, and in control and infancy animals the concentrations were <1.0 mu g/dL. Sertoli and spermatogenic cells of dosed monkeys from the infancy and lifetime groups revealed injuries. Chronic exposure to lead that results in moderate blood lead concentrations induced persistent ultrastructural alterations in the cynomolgus monkey testis. Results of this study on the primate, following extrapolation to humans, could influence further refining of the impact of environmental lead contamination concentrations vis-a-vis the health of children, adults, and aged human beings.PT: J; CR: *ATSDR, 1988, NAT EXT LEAD EXP CHI ASSENNATO G, 1987, ARCH ENVIRON HEALTH, V42, P124 BABINEAU KA, 1991, J SUBMICR CYTOL PATH, V23, P457 BOSCOLO P, 1988, TOXICOL LETT, V41, P129 BRAUNSTEIN GD, 1978, INFERTILITY, V1, P33 BRODY DJ, 1994, JAMA-J AM MED ASSOC, V272, P277 CHOWDHURY AR, 1984, BIOMED BIOCHIM ACTA, V43, P95 CHOWDHURY AR, 1986, FOLIA HISTOCHEM CYTO, V24, P233 CHOWDHURY AR, 1986, IND HLTH, V25, P55 CULLEN MR, 1984, ARCH ENVIRON HEALTH, V39, P431 FOSTER WG, 1993, REPROD TOXICOL, V7, P203 GENNART JP, 1992, AM J EPIDEMIOL, V135, P1208 GHELBERG NW, 1981, J APPL TOXICOL, V1, P284 HAMILTON A, 1974, IND TOXICOLOGY, P119 HERMESLIMA M, 1991, BIOCHIM BIOPHYS ACTA, V1056, P57 HILDERBRAND DC, 1973, AM J OBSTET GYNECOL, V115, P1058 JIUN YS, 1994, ARCH ENVIRON HEALTH, V49, P256 LANCRANJAN I, 1975, ARCH ENVIRON HEALTH, V30, P396 MAIZLISH N, 1990, AM J PUBLIC HEALTH, V80, P931 MALKIN R, 1992, ENVIRON RES, V59, P265 MCGREGOR AJ, 1990, HUM EXP TOXICOL, V9, P371 MURTHY RC, 1991, EXP PATHOL-JENA, V42, P95 MURTHY RC, 1995, REPROD TOXICOL, V9, P483 NORDSTROM S, 1978, HEREDITAS, V88, P51 PANIAGUA R, 1991, J ELECTRON MICR TECH, V19, P241 PIRKLE JL, 1994, JAMA-J AM MED ASSOC, V272, P284 QUINLAN GJ, 1988, BIOCHIM BIOPHYS ACTA, V962, P196 RICE DC, 1990, TOXICOL APPL PHARM, V102, P101 RICE DC, 1990, TOXICOL APPL PHARM, V106, P327 SAXENA DK, 1989, FOLIA HISTOCHEM CYTO, V1, P57 SKINNER MK, 1990, REPROD FERT DEVELOP, V2, P237 SOKOL RZ, 1990, J ANDROL, V11, P521 SUNDARAM K, 1995, REPROD TOXICOL, P99 TEPPER A, 1992, AM J PUBLIC HEALTH, V82, P275 VALERIO DA, 1969, LAB ANIM CARE, V19, P250 VALERIO DA, 1970, LAB ANIM CARE, V20, P734 WALLER K, 1992, AM J PUBLIC HEALTH, V82, P1669 YASSI A, 1991, AM J PUBLIC HEALTH, V81, P736; NR: 38; TC: 3; J9: ULTRASTRUCT PATHOL; PG: 9; GA: YR370Source type: Electronic(1
Trauma Induced Complete Sinonasal Separation and Subsequent Frontoethmoid Mucocele Formation
No full text
Facial nerve paresis caused by benign parotid neoplasms: A case report and review of the literature
No full textIntroduction
No full textAlmost 70 years since its establishment, the European Union (EU) is still confronted with the deep problem of the perceived gap between the EU institutions and the EU citizens. Relevant research shows that the majority of the Europeans do not trust the EU (European Commission, 2021; Pew Research Center, 2012; 2013; Inglehart et al., 2014) and they think of it as an inefficient institution that does not listen to them and does not understand their needs (Wike et al., 2019; Pew Research Center, 2014; Manchin, 2014). In addition, a large percentage of the EU citizens express their dissatisfaction with the way by which democracy works in the EU (European Parliament, 2018) while among the most popular reasons for abstention from the 2009, 2014, and 2019 European Parliament (EP) elections was the feeling of the EU citizens that their vote has no consequences and does not change anything (European Parliament, 2012, 2014, 2018). The steadily growing support for Eurosceptic and far right parties across member states (e.g. Italy, Germany, Austria, the Netherlands) (Oltermann, 2017; Mudde, 2017a, b; Henley & Malkin, 2017), the desire of citizens in different EU member states to have their voice heard through referendums on their own EU membership and their desire to have some of the EU key powers returned back to their national governments (Stokes, 2016; Pew Research Center, 2017) are also some of the facts that indicate the gap between the EU and its citizens. © 2022, The Author(s), under exclusive license to Springer Nature Switzerland AG
Healing environment: a contribution to the interior design and decor features in single occupancy hospital rooms in Libya.
No full text- …
