Dabrafenib for Pilocytic Astrocytoma With BRAF V599ins.

This report highlights the first pediatric case of pilocytic astrocytoma with BRAF V599ins mutation, successfully treated with dabrafenib.

The Cost of Poverty: The Relationship Between Insurance Status, Length of Stay, and Discharge Disposition in Trauma Patients.

INTRODUCTION: Insurance status (IS) is known to be associated with length of stay (LOS). The impact of IS on excess LOS (ELOS), days between medical readiness and discharge date, has not been explored. METHODS: We conducted a retrospective study of patients with pelvic fractures at a level I trauma center. Outcomes included ELOS (primary), discharge disposition (secondary), and ELOS-associated complications (secondary). RESULTS: 185 patients were included. Uninsured patients were the youngest and had the least baseline comorbidities (31.3 years (median), Charlson Comorbidity Index (CCI) .1) while publicly insured patients were the oldest and had the most baseline comorbidities (58.4 years (median), CCI 2.32). Excess LOS and associated complications did not differ among groups. After regression analysis, UIPs had longer LOS than PRPs (2.07 days, 95% CI .28-3.85). UIPs were recommended to go to inpatient rehabilitation 51.6% of the time but were discharged home 93.6% of the time; 81.0% of these changes were attributed to insufficient financial resources. CONCLUSIONS: Excess LOS and complications associated with ELOS were not associated with IS. Although UIPs were younger and had fewer baseline comorbidities, they had longer LOS after regression analysis. While discharge recommendations differed based on insurance status, UIPs had limited access to rehabilitation due to financial disparities. Despite initial treatment team recommendations, UIPs had to be sent home as their lack of insurance precluded inpatient rehabilitation placement.

The Effect of Pharmacist-Led Telemedicine on A1c Reduction During the COVID-19 Pandemic.

Purpose: Diabetes remains a prevalent metabolic chronic condition. The pandemic promoted the use of telemedicine for patients with chronic conditions. Telemedicine offers innovative methods to achieve glycemic control for these patients. This study evaluates the effectiveness of telemedicine with pharmacists in reduction of glycated hemoglobin (A1C) for patients with diabetes. Methods: This study (n = 112) was a single-center, retrospective study that evaluated the effectiveness of patients enrolling in pharmacist-led diabetes management utilizing telemedicine during the COVID-19 pandemic. Patients with an A1C >9 mg/dL were contacted for telemedicine with the pharmacy team. The three groups included: patients agreeing to the telemedicine visit (n = 28), patients that declined the telemedicine visit (n = 42), and patients that did not answer the telephone when offered the telemedicine visit (n = 28). Results: Our study revealed a significant change in the primary endpoint A1C (2.6 + 2.4, p = 0.0144) for the patients who accepted telemedicine visits when compared with the other study groups. The secondary endpoints, changes in A1C (when evaluating employment status, number of clinic visits, number of chronic conditions, gender, race) and changes in body mass index, revealed no significant changes. Conclusion: Diabetes management using telemedicine with pharmacists impacts glycemic control in patients with type 2 diabetes. This study demonstrates patients who accepted pharmacist-led telemedicine had a reduction in A1C. Further research may reveal long-term benefits on clinical outcomes after utilizing this service during the COVID-19 pandemic.

The Impact of Post-Myocardial Infarction (MI) Depression on Cardiovascular-Related Hospitalizations.

Routine depression screening and subsequent treatment in post-myocardial infarction (MI) patients may lead to improved cardiac outcomes. However, screening for depression is not a standard of post-MI care. Though the American Heart Association (AHA) published an advisory recommending routine depression screening in post-MI patients, there is conflicting evidence on the benefit that routine depression screening has on cardiovascular outcomes. The purpose of this study is to compare the occurrence of cardiovascular-related readmissions in post-MI patients diagnosed with depression versus post-MI patients not diagnosed with depression. This retrospective cohort study analyzed the incidence of cardiovascular-related readmissions and mortality in adult post-MI patients diagnosed with depression within 1 year compared to those not diagnosed with depression within a year. Those diagnosed with depression were more likely to experience a subsequent cardiovascular-related hospitalization within 2 years of MI than those not diagnosed with depression (52.6% vs 28.7%; odds ratio [OR], 3.19; 95% CI 2.33-4.38). There was no difference between groups in the incidence of in-hospital mortality.

Neurological Examination Frequency and Time-to-Delirium After Traumatic Brain Injury.

BACKGROUND: Frequent neurological examinations in patients with traumatic brain injury (TBI) disrupt sleep-wake cycles and potentially contribute to the development of delirium. OBJECTIVE: To evaluate the risk of delirium among patients with TBI with respect to their neuro-check frequencies. METHODS: A retrospective study of patients presenting with TBI at a single level I trauma center between January 2018 and December 2019. The primary exposure was the frequency of neurological examinations (neuro-checks) assigned at the time of admission. Patients admitted with hourly (Q1) neuro-check frequencies were compared with those who received examinations every 2 (Q2) or 4 (Q4) hours. The primary outcomes were delirium and time-to-delirium. The onset of delirium was defined as the first documented positive Confusion Assessment Method for the Intensive Care Unit score. RESULTS: Of 1552 patients with TBI, 458 (29.5%) patients experienced delirium during their hospital stay. The median time-to-delirium was 1.8 days (IQR: 1.1, 2.9). Kaplan-Meier analysis demonstrated that patients assigned Q1 neuro-checks had the greatest rate of delirium compared with the patients with Q2 and Q4 neuro-checks ( P < .001). Multivariable Cox regression modeling demonstrated that Q2 neuro-checks (hazard ratio: 0.439, 95% CI: 0.33-0.58) and Q4 neuro-checks (hazard ratio: 0.48, 95% CI: 0.34-0.68) were protective against the development of delirium compared with Q1. Other risk factors for developing delirium included pre-existing dementia, tobacco use, lower Glasgow Coma Scale score, higher injury severity score, and certain hemorrhage patterns. CONCLUSION: Patients with more frequent neuro-checks had a higher risk of developing delirium compared with those with less frequent neuro-checks.

Assessment of safety and effectiveness of non-neurosurgical management for minimal traumatic brain injury (TBI).

BACKGROUND: Patients with mild traumatic brain injury (TBI) and intracranial hemorrhage often receive neurosurgical consultation. However, only a small proportion of patients require intervention. Our hypothesis is that low-risk minimal TBI patients managed without immediate neurosurgical consultation will have a reasonable safety and effectiveness outcome profile. METHODS: A non-neurosurgical management protocol for adult minimal TBI was implemented at a level I trauma center as an interdisciplinary quality-improvement initiative in November 2018. Minimal TBI was defined as Glasgow Coma Scale (GCS) of 15 secondary to blunt mechanism, without anticoagulant or antiplatelet therapy, and isolated pneumocephalus and/or traumatic subarachnoid hemorrhage on head CT imaging. Safety was assessed by in-hospital mortality, neurosurgical interventions, and ED revisits within two weeks of discharge. Effectiveness was assessed by neurosurgical consult rate and length of stay. Outcomes were compared 8-months pre- and post-protocol implementation. RESULTS: A total of 97 patients were included, of which 49 were pre-protocol and 48 were post-protocol There was no difference in rates of in-hospital mortality [0 (0%) vs 0 (0%)], neurosurgical procedure [1 (2.1%) vs 0 (0%)], operations [0 (0%) vs 0 (0%)], and ED revisits [1 (2.0%) vs 2 (4.2%), p = 0.985] between the periods. There was a significant reduction in neurosurgical consults post-protocol implementation (92% vs 29%, p<0.001). CONCLUSION: A protocol for minimal TBI patients effectively reduced neurosurgical consultation without changes in safety profile. Such an interdisciplinary management protocol for low-risk neurotrauma can effectively utilize the neurosurgery consult services by stratifying neurologically stable TBI patient.

Decision Support Tool to Judiciously Assign High-Frequency Neurologic Examinations in Traumatic Brain Injury.

INTRODUCTION: Traumatic brain injury (TBI) management includes serial neurologic examinations to assess for changes dictating neurosurgical interventions. We hypothesized hourly examinations are overassigned. We conducted a decision tree analysis to determine an algorithm to judiciously assign hourly examinations. METHODS: A retrospective cohort study of 1022 patients with TBI admitted to a Level 1 trauma center from January 1, 2019, to December 31, 2019, was conducted. Patients with penetrating TBI or immediate or planned interventions and those with nonsurvivable injuries were excluded. Patients were stratified by whether they underwent an unplanned intervention (e.g., craniotomy or invasive intracranial monitoring). Univariate analysis identified factors for inclusion in chi-square automatic interaction detection technique, classifying those at risk for unplanned procedures. RESULTS: A total of 830 patients were included, 287 (35%) were assigned hourly (Q1) examinations, and 17 (2%) had unplanned procedures, with 16 of 17 (94%) on Q1 examinations. Patients requiring unplanned procedures were more likely to have mixed intracranial hemorrhage pattern (82% versus 39%; P = 0.001), midline shift (35% versus 14%; P = 0.023), an initial poor neurologic examination (Glasgow Comas Scale ≤8, 77% versus 14%; P < 0.001), and be intubated (88% versus 17%; P < 0.001). Using chi-square automatic interaction detection, the decision tree demonstrated low-risk (2% misclassification) and excellent discrimination (area under the curve = 0.915, 95% confidence interval 0.844-0.986; P < 0.001) of patients at risk of an unplanned procedure. By following the algorithm, 167 fewer patients could have been assigned Q1 examinations, resulting in an estimated 6012 fewer examinations. CONCLUSIONS: Using a 4-factor algorithm can optimize the assignment of neuro examinations and substantially reduce neuro examination burden without sacrificing patient safety.

An Examination of Motor Competence Profiles in Preschool Children: A Latent Profile Analysis.

Purpose: Identifying profiles of preschoolers' motor competence (MC) is essential for providing accurate and targeted intervention. However, little is known regarding children's MC profiles, more specifically how skills may present in unique clusters. The purposes of the study were to explore MC profiles of U.S. children ages 3-6 years, quantify the uniqueness of these profiles, and examine differences by age, gender, race, geographic region, socioeconomic status, and Body Mass Index z-scores. Methods: Participants included children (N = 582, ngirls = 296) aged 3-6 years (Mage = 4.97, SD = .75) enrolled in one of seven early childhood education centers (Alabama, Louisiana, Ohio [× 2], South Carolina [× 2], Texas). Each child's MC was assessed with the 12 skills comprising the TGMD-2. Latent profile analysis was performed using the 12 MC skills. Results: Five profiles of MC emerged, three of which show developing MC but in varying combinations. Wald tests revealed possible MC advantages for preschool children who are older, boys, reside in an urban region, and are of higher socioeconomic status, but only for the proficient MC profile. Conclusion: By uncovering five unique latent MC profiles, professionals should consider the presentation/origins of each profile and use such knowledge to create targeted, individualized MC interventions in American preschoolers. From a research perspective, the implications of this study suggest that researchers should consider person-oriented approaches examining individual skill scores (vs. summed subscale scores) whenever possible.

An Innovative Academic Practice Model for Clinical Nursing Education During the COVID-19 Pandemic.

In March of 2020, Columbia University School of Nursing (CUSON) Masters Direct Entry (MDE) program and New York Presbyterian Hospital (NYPH) created an innovative academic partnership to address the clinical needs of students and to help alleviate the burden of surging COVID-19 cases on nurses and the health care system. Through this partnership, students were hired as nurse technicians to assist with patient care during the first wave of the COVID-19 pandemic. As a result of this enhanced relationship, a pipeline of well-qualified graduate nurses with unique skills to adapt to a rapidly changing practice environment was created. Student participants in this opportunity developed an understanding of the organizational and leadership structures of the health care institution. The understanding of organizational and leadership structures will help transform the delivery of care.

Macrophage migration inhibitory factor enhances influenza-associated mortality in mice.

Influenza-associated mortality continues to occur annually despite available antiviral therapies. New therapies that improve host immunity could reduce influenza virus disease burden. Targeting macrophage migration inhibitory factor (MIF) has improved the outcomes of certain inflammatory diseases, but its role in influenza viral infection is unclear. Here, we showed that, during influenza viral infection, Mif-deficient mice have less inflammation, viral load, and mortality compared with WT control mice; conversely, Tg mice, overexpressing Mif in alveolar epithelial cells, had higher inflammation, viral load, and mortality. Antibody-mediated blockade of MIF in WT mice during influenza viral infection improved their survival. Mif-deficient murine lungs showed reduced levels of parkin, a mitophagy protein that negatively regulates antiviral signaling, prior to infection and augmented antiviral type I/III IFN levels in the airspaces after infection as compared with WT lungs. Additionally, in vitro assays with human lung epithelial cells showed that treatment with recombinant human MIF increased the percentage of influenza virus-infected cells. In conclusion, our study reveals that MIF impairs antiviral host immunity and increases inflammation during influenza infection and suggests that targeting MIF could be therapeutically beneficial during influenza viral infection.

Influenza virus inoculum volume is critical to elucidate age-dependent mortality in mice.

The elderly exhibit increased mortality to influenza viral infection for unclear reasons. Mice are frequently used to model how aging impacts disease. Several studies have shown that aged mice exhibit an increased mortality to influenza virus, but two recent studies demonstrated the opposite. These two studies administered the virus intranasally in 20 µL, whereas the other studies used a viral inoculum in at least 30 µL. To determine whether the volume of the inoculum could explain the conflicting reports, we infected young and aged mice via intranasal instillation of 40 µL or 20 µL containing 1 x 104 plaque-forming units (PFU) of H1N1 influenza virus. We found that intranasal administration of 40 µL but not 20 µL of inoculum resulted in age-dependent mortality in mice. Compared to aged mice infected with 40 µL inoculum, those infected with 20 µL inoculum showed reduced levels of live virus and IFN-ß in the lung 3 days postinfection. Furthermore, aged mice administered 40 µL of Evans blue intranasally displayed increased dye retention in their bronchoalveolar lavage fluid compared to those administered 20 µL of Evans blue. Our data demonstrate that the inoculating volume of virus is critical for adequate delivery of influenza virus to the lung and thus for efficient infection of aged mice. These findings shed light on discrepant results in the literature regarding aged mice and influenza infection, and establish that mice can be used to examine how aging impacts the response to this biomedically important infection.

Excessive neutrophil levels in the lung underlie the age-associated increase in influenza mortality.

Neutrophils clear viruses, but excessive neutrophil responses induce tissue injury and worsen disease. Aging increases mortality to influenza infection; however, whether this is due to impaired viral clearance or a pathological host immune response is unknown. Here we show that aged mice have higher levels of lung neutrophils than younger mice after influenza viral infection. Depleting neutrophils after, but not before, infection substantially improves the survival of aged mice without altering viral clearance. Aged alveolar epithelial cells (AECs) have a higher frequency of senescence and secrete higher levels of the neutrophil-attracting chemokines CXCL1 and CXCL2 during influenza infection. These chemokines are required for age-enhanced neutrophil chemotaxis in vitro. Our work suggests that aging increases mortality from influenza in part because senescent AECs secrete more chemokines, leading to excessive neutrophil recruitment. Therapies that mitigate this pathological immune response in the elderly might improve outcomes of influenza and other respiratory infections.

Effect of tildrakizumab (MK-3222), a high affinity, selective anti-IL23p19 monoclonal antibody, on cytochrome P450 metabolism in subjects with moderate to severe psoriasis.

AIMS: Tildrakizumab, an interleukin (IL)-23 inhibitor, is indicated for the treatment of moderate to severe chronic plaque psoriasis. Although tildrakizumab is not metabolized by, and does not alter, cytochrome P450 (CYP) expression in vitro, clinically significant pharmacokinetic effects through changes in systemic inflammation, which alters CYP metabolism, have been well documented. At the time of study conduct, the effect of modulation of inflammation/cytokines, including IL-23 inhibition with tildrakizumab, on CYP metabolism, and therefore the potential for disease-drug interactions, in psoriasis patients was unknown. We therefore assessed whether tildrakizumab alters CYP metabolism in subjects with moderate to severe psoriasis. METHODS: This was an open-label, fixed-sequence, two-period trial. In Period 1 (Day 1), subjects received an oral CYP probe cocktail of up to five drugs (midazolam 2 mg [3A4], caffeine 200 mg [1A2], warfarin 10 mg [2C9], omeprazole 40 mg [2C19] and dextromethorphan 30 mg [2D6]), followed by a 7-day washout. In Period 2, subjects received tildrakizumab 200 mg subcutaneously on Days 1 and 29 and a second CYP probe cocktail on Day 57. Substrate or metabolite pharmacokinetics, safety and changes in Psoriasis Severity Area Index (PASI), interleukin-6 (IL-6) and high-sensitivity C-reactive protein (hs-CRP), were assessed. RESULTS: Twenty subjects (13 men, 7 women) were enrolled. Tildrakizumab had no clinically relevant effect on the pharmacokinetics of any of the probe substrates tested. On Day 57 of Period 2, the median percentage decrease from baseline in PASI score following tildrakizumab was ~93%. There were no clinically relevant changes in IL-6 or hs-CRP. Treatment with tildrakizumab was generally well tolerated. CONCLUSION: In subjects with moderate to severe psoriasis, tildrakizumab 200 mg did not have a discernible effect on CYP metabolism. The potential for clinically significant drug-drug interactions (DDIs) with tildrakizumab in patients with psoriasis is low. The difference in the occurrence of DDIs seen with anti-inflammatory agents in rheumatoid arthritis patients compared with psoriasis patients may be due to the much greater extent of systemic inflammation in rheumatoid arthritis as compared to psoriasis.

Aging Impairs Alveolar Macrophage Phagocytosis and Increases Influenza-Induced Mortality in Mice.

Influenza viral infections often lead to increased mortality in older people. However, the mechanisms by which aging impacts immunity to influenza lung infection remain unclear. We employed a murine model of influenza infection to identify these mechanisms. With aging, we found reduced numbers of alveolar macrophages, cells essential for lung homeostasis. We also determined that these macrophages are critical for influenza-induced mortality with aging. Furthermore, aging vastly alters the transcriptional profile and specifically downregulates cell cycling pathways in alveolar macrophages. Aging impairs the ability of alveolar macrophages to limit lung damage during influenza infection. Moreover, aging decreases alveolar macrophage phagocytosis of apoptotic neutrophils, downregulates the scavenging receptor CD204, and induces retention of neutrophils during influenza infection. Thus, aging induces defective phagocytosis by alveolar macrophages and increases lung damage. These findings indicate that therapies that enhance the function of alveolar macrophages may improve outcomes in older people infected with respiratory viruses.

Aging and the immune response to organ transplantation.

An increasing number of older people receive organ transplants for various end-stage conditions. Although organ transplantation is an effective therapy for older patients (i.e., older than 65 years of age), such as in end-stage renal disease, this therapy has not been optimized for older patients because of our lack of understanding of the effect of aging and the immune response to organ transplantation. Here, we provide an overview of the impact of aging on both the allograft and the recipient and its effect on the immune response to organ transplantation. We describe what has been determined to date, discuss existing gaps in our knowledge, and make suggestions on necessary future studies to optimize organ transplantation for older people.

Gold nanoparticles to improve HIV drug delivery.

BACKGROUND: Antiretroviral therapy (ART) has improved lifespan and quality of life of patients infected with the HIV-1. However, ART has several potential limitations, including the development of drug resistance and suboptimal penetration to selected anatomic compartments. Improving the delivery of antiretroviral molecules could overcome several of the limitations of current ART. RESULTS & CONCLUSION: Two to ten nanometer diameter inorganic gold crystals serve as a base scaffold to combine molecules with an array of properties in its surface. We show entry into different cell types, antiviral activity of an HIV integrase inhibitor conjugated in a gold nanoparticle and penetration into the brain in vivo without toxicity. Herein, gold nanoparticles prove to be a promising tool to use in HIV therapy.

Controlled exposure of humans with metabolic syndrome to concentrated ultrafine ambient particulate matter causes cardiovascular effects.

Many studies have reported associations between air pollution particles with an aerodynamic diameter <2.5 µm (fine particulate matter (PM)) and adverse cardiovascular effects. However, there is an increased concern that so-called ultrafine PM which comprises the smallest fraction of fine PM (aerodynamic diameter <0.1 µm) may be disproportionately toxic relative to the 0.1-2.5 µm fraction. Ultrafine PM is not routinely measured in state monitoring networks and is not homogenously dispersed throughout an airshed but rather located in hot spots such as near combustion sources (e.g., roads), making it difficult for epidemiology studies to associate exposure to ultrafine PM with adverse health effects. Thirty four middle-aged individuals with metabolic syndrome were exposed for 2 h while at rest in a randomized crossover design to clean air and concentrated ambient ultrafine particles (UCAPS) for 2 h. To further define potential risk, study individuals carrying the null allele for GSTM1 (a prominent antioxidant gene) were identified by genotyping. Blood was obtained immediately prior to exposure, and at 1 and 20 h afterward. Continuous Holter monitoring began immediately prior to exposure and continued for 24 h. Based on changes we observed in previous CAPS studies, we hypothesized that ultrafine CAPS would cause changes in markers of blood inflammation and fibrinolysis as well as changes in heart rate variability and cardiac repolarization. GSTM1 null individuals had altered cardiac repolarization as seen by a change in QRS complexity following exposure to UCAPS and both the entire study population as well as GSTM1 null individuals had increased QT duration. Blood plasminogen and thrombomodulin were decreased in the whole population following UCAPS exposure, whereas C-reactive protein (CRP) and SAA were increased. This controlled human exposure study is the first to show that ambient ultrafine particles can cause cardiovascular changes in people with metabolic syndrome, which affects nearly a quarter of the U.S. adult population.

Nanoscale structure-activity relationships, mode of action, and biocompatibility of gold nanoparticle antibiotics.

The emergence of resistance to multiple antimicrobial agents by pathogenic bacteria has become a significant global public health threat. Multi-drug-resistant (MDR) Gram-negative bacteria have become particularly problematic, as no new classes of small-molecule antibiotics for Gram-negative bacteria have emerged in over two decades. We have developed a combinatorial screening process for identifying mixed ligand monolayer/gold nanoparticle conjugates (2.4 nm diameter) with antibiotic activity. The method previously led to the discovery of several conjugates with potent activity against the Gram-negative bacterium Escherichia coli. Here we show that these conjugates are also active against MDR E. coli and MDR Klebsiella pneumoniae. Moreover, we have shown that resistance to these nanoparticles develops significantly more slowly than to a commercial small-molecule drug. These results, combined with their relatively low toxicity to mammalian cells and biocompatibility in vivo, suggest that gold nanoparticles may be viable new candidates for the treatment of MDR Gram-negative bacterial infections.

Reduced nitrogen losses after conversion of row crop agriculture to perennial biofuel crops.

Current biofuel feedstock crops such as corn lead to large environmental losses of N through nitrate leaching and NO emissions; second-generation cellulosic crops have the potential to reduce these N losses. We measured N losses and cycling in establishing miscanthus (), switchgrass ( L. fertilized with 56 kg N ha yr), and mixed prairie, along with a corn ( L.)-corn-soybean [ (L.) Merr.] rotation (corn fertilized at 168-202 kg N ha). Nitrous oxide emissions, soil N mineralization, mid-profile nitrate leaching, and tile flow and nitrate concentrations were measured. Perennial crops quickly reduced nitrate leaching at a 50-cm soil depth as well as concentrations and loads from the tile systems (year 1 tile nitrate concentrations of 10-15 mg N L declined significantly by year 4 in all perennial crops to <0.6 mg N L, with losses of <0.8 kg N ha yr). Nitrous oxide emissions were 2.2 to 7.7 kg N ha yr in the corn-corn-soybean rotation but were <1.0 kg N ha yr by year 4 in the perennial crops. Overall N balances (atmospheric deposition + fertilization + soybean N fixation - harvest, leaching losses, and NO emissions) were positive for corn and soybean (22 kg N ha yr) as well as switchgrass (9.7 kg N ha yr) but were -18 and -29 kg N ha yr for prairie and miscanthus, respectively. Our results demonstrate rapid tightening of the N cycle as perennial biofuel crops established on a rich Mollisol soil.

Gastrointestinal bioavailability of 2.0 nm diameter gold nanoparticles.

The use of gold nanoparticles as imaging agents and therapeutic delivery systems is growing rapidly. However, a significant limitation of gold nanoparticles currently is their low absorption efficiencies in the gastrointestinal (GI) tract following oral administration. In an attempt to identify ligands that facilitate gold nanoparticle absorption in the GI tract, we have studied the oral bioavailability of 2.0 nm diameter gold nanoparticles modified with the small molecules p-mercaptobenzoic acid and glutathione, and polyethylene glycols (PEG) of different lengths and charge (neutral and anionic). We show that GI absorption of gold nanoparticles modified with the small molecules tested was undetectable. However, the absorption of PEGs depended upon PEG length, with the shortest PEG studied yielding gold nanoparticle absorptions that are orders-of-magnitude larger than observed previously. As the oral route is the most convenient one for administering drugs and diagnostic reagents, these results suggest that short-chain PEGs may be useful in the design of gold nanoparticles for the diagnosis and treatment of disease.