Analysis of Clinical Samples of Pancreatic Cyst's Lesions with A Multi-Analyte Bioelectronic Simot Array Benchmarked Against Ultrasensitive Chemiluminescent Immunoassay.

Pancreatic cancer, ranking as the third factor in cancer-related deaths, necessitates enhanced diagnostic measures through early detection. In response, SiMoT-Single-molecule with a large Transistor multiplexing array, achieving a Technology Readiness Level of 5, is proposed for a timely identification of pancreatic cancer precursor cysts and is benchmarked against the commercially available chemiluminescent immunoassay SIMOA (Single molecule array) SP-X System. A cohort of 39 samples, comprising 33 cyst fluids and 6 blood plasma specimens, undergoes detailed examination with both technologies. The SiMoT array targets oncoproteins MUC1 and CD55, and oncogene KRAS, while the SIMOA SP-X planar technology exclusively focuses on MUC1 and CD55. Employing Principal Component Analysis (PCA) for multivariate data processing, the SiMoT array demonstrates effective discrimination of malignant/pre-invasive high-grade or potentially malignant low-grade pancreatic cysts from benign non-mucinous cysts. Conversely, PCA analysis applied to SIMOA assay reveals less effective differentiation ability among the three cyst classes. Notably, SiMoT unique capability of concurrently analyzing protein and genetic markers with the threshold of one single molecule in 0.1 mL positions it as a comprehensive and reliable diagnostic tool. The electronic response generated by the SiMoT array facilitates direct digital data communication, suggesting potential applications in the development of field-deployable liquid biopsy.

Nutritional supplement induced modulations in the functional connectivity of a porcine brain.

BACKGROUND: Functional connectivity (FC) measures statistical dependence between cortical brain regions. Studies of FC facilitate understanding of the brain's function and architecture that underpin normal cognition, behavior, and changes associated with various factors (e.g. nutritional supplements) at a large scale. OBJECTIVE: We aimed to identify modifications in FC patterns and targeted brain anatomies in piglets following perinatal intake of different nutritional diets using a graph theory based approach. METHODS: Forty-four piglets from four groups of pregnant sows, who were treated with nutritional supplements, including control diet, docosahexaenoic acid (DHA), egg yolk (EGG), and DHA + EGG, went through resting-state functional magnetic resonance imaging (rs-fMRI). We introduced the use of differential degree test (DDT) to identify differentially connected edges (DCEs). Simulation studies were first conducted to compare the DDT with permutation test, using three network structures at different noise levels. DDT was then applied to rs-fMRI data acquired from piglets. RESULTS: In simulations, the DDT showed a greater accuracy in detecting DCEs when compared with the permutation test. For empirical data, we found that the strength of internodal connectivity is significantly increased for more than 6% of edges in the EGG group and more than 8% of edges in the DHA and DHA + EGG groups, all compared to the control group. Moreover, differential wiring diagrams between group comparisons provided means to pinpoint brain hubs affected by nutritional supplements. CONCLUSION: DDT showed a greater accuracy of detection of DCEs and demonstrated EGG, DHA, and DHA + EGG supplemented diets lead to an improved internodal connectivity in the developing piglet brain.

Characterization of Resting-State Functional Connectivity Changes in Hypertension by a Modified Difference Degree Test.

Introduction: Hypertension affects over a billion people worldwide, and the application of neuroimaging may elucidate changes brought about by the disease. We have applied a graph theory approach to examine the organizational differences in resting-state functional magnetic resonance imaging (rs-fMRI) data between hypertensive and normotensive participants. To detect these groupwise differences, we performed statistical testing using a modified difference degree test (DDT). Methods: Structural and rs-fMRI data were collected from a cohort of 52 total (29 hypertensive and 23 normotensive) participants. Functional connectivity maps were obtained by partial correlation analysis of participant rs-fMRI data. We modified the DDT null generation algorithm and validated the change through different simulation schemes and then applied this modified DDT to our experimental data. Results: Through a comparative analysis, the modified DDT showed higher true positivity rates (TPR) when compared with the base DDT while also maintaining false positivity rates below the nominal value of 5% in nearly all analytically thresholded trials. Applying the modified DDT to our rs-fMRI data showed differential organization in the hypertension group in the regions throughout the brain including the default mode network. These experimental findings agree with previous studies. Conclusions: While our findings agree with previous studies, the experimental results presented require more investigation to prove their link to hypertension. Meanwhile, our modification to the DDT results in higher accuracy and an increased ability to discern groupwise differences in rs-fMRI data. We expect this to be useful in studying groupwise organizational differences in future studies.

A Single-Molecule Bioelectronic Portable Array for Early Diagnosis of Pancreatic Cancer Precursors.

A cohort of 47 patients is screened for pancreatic cancer precursors with a portable 96-well bioelectronic sensing-array for single-molecule assay in cysts fluid and blood plasma, deployable at point-of-care (POC). Pancreatic cancer precursors are mucinous cysts diagnosed with a sensitivity of at most 80% by state-of-the-art cytopathological molecular analyses (e.g., KRASmut DNA). Adding the simultaneous assay of proteins related to malignant transformation (e.g., MUC1 and CD55) is deemed essential to enhance diagnostic accuracy. The bioelectronic array proposed here, based on single-molecule-with-a-large-transistor (SiMoT) technology, can assay both nucleic acids and proteins at the single-molecule limit-of-identification (LOI) (1% of false-positives and false-negatives). It comprises an enzyme-linked immunosorbent assay (ELISA)-like 8 × 12-array organic-electronics disposable cartridge with an electrolyte-gated organic transistor sensor array, and a reusable reader, integrating a custom Si-IC chip, operating via software installed on a USB-connected smart device. The cartridge is complemented by a 3D-printed sensing gate cover plate. KRASmut , MUC1, and CD55 biomarkers either in plasma or cysts-fluid from 5 to 6 patients at a time, are multiplexed at single-molecule LOI in 1.5 h. The pancreatic cancer precursors are classified via a machine-learning analysis resulting in at least 96% diagnostic-sensitivity and 100% diagnostic-specificity. This preliminary study opens the way to POC liquid-biopsy-based early diagnosis of pancreatic-cancer precursors in plasma.

Pathogenic mechanisms of post-acute sequelae of SARS-CoV-2 infection (PASC).

COVID-19, with persistent and new onset of symptoms such as fatigue, post-exertional malaise, and cognitive dysfunction that last for months and impact everyday functioning, is referred to as Long COVID under the general category of post-acute sequelae of SARS-CoV-2 infection (PASC). PASC is highly heterogenous and may be associated with multisystem tissue damage/dysfunction including acute encephalitis, cardiopulmonary syndromes, fibrosis, hepatobiliary damages, gastrointestinal dysregulation, myocardial infarction, neuromuscular syndromes, neuropsychiatric disorders, pulmonary damage, renal failure, stroke, and vascular endothelial dysregulation. A better understanding of the pathophysiologic mechanisms underlying PASC is essential to guide prevention and treatment. This review addresses potential mechanisms and hypotheses that connect SARS-CoV-2 infection to long-term health consequences. Comparisons between PASC and other virus-initiated chronic syndromes such as myalgic encephalomyelitis/chronic fatigue syndrome and postural orthostatic tachycardia syndrome will be addressed. Aligning symptoms with other chronic syndromes and identifying potentially regulated common underlining pathways may be necessary for understanding the true nature of PASC. The discussed contributors to PASC symptoms include sequelae from acute SARS-CoV-2 injury to one or more organs, persistent reservoirs of the replicating virus or its remnants in several tissues, re-activation of latent pathogens such as Epstein-Barr and herpes viruses in COVID-19 immune-dysregulated tissue environment, SARS-CoV-2 interactions with host microbiome/virome communities, clotting/coagulation dysregulation, dysfunctional brainstem/vagus nerve signaling, dysautonomia or autonomic dysfunction, ongoing activity of primed immune cells, and autoimmunity due to molecular mimicry between pathogen and host proteins. The individualized nature of PASC symptoms suggests that different therapeutic approaches may be required to best manage specific patients.

Glyphosate in livestock: feed residues and animal health1.

Glyphosate is a nonselective systemic herbicide used in agriculture since 1974. It inhibits 5-enolpyruvylshikimate-3-phosphate (EPSP) synthase, an enzyme in the shikimate pathway present in cells of plants and some microorganisms but not human or other animal cells. Glyphosate-tolerant crops have been commercialized for more than 20 yr using a transgene from a resistant bacterial EPSP synthase that renders the crops insensitive to glyphosate. Much of the forage or grain from these crops are consumed by farm animals. Glyphosate protects crop yields, lowers the cost of feed production, and reduces CO2 emissions attributable to agriculture by reducing tillage and fuel usage. Despite these benefits and even though global regulatory agencies continue to reaffirm its safety, the public hears conflicting information about glyphosate's safety. The U.S. Environmental Protection Agency determines for every agricultural chemical a maximum daily allowable human exposure (called the reference dose, RfD). The RfD is based on amounts that are 1/100th (for sensitive populations) to 1/1,000th (for children) the no observed adverse effects level (NOAEL) identified through a comprehensive battery of animal toxicology studies. Recent surveys for residues have indicated that amounts of glyphosate in food/feed are at or below established tolerances and actual intakes for humans or livestock are much lower than these conservative exposure limits. While the EPSP synthase of some bacteria is sensitive to glyphosate, in vivo or in vitro dynamic culture systems with mixed bacteria and media that resembles rumen digesta have not demonstrated an impact on microbial function from adding glyphosate. Moreover, one chemical characteristic of glyphosate cited as a reason for concern is that it is a tridentate chelating ligand for divalent and trivalent metals; however, other more potent chelators are ubiquitous in livestock diets, such as certain amino acids. Regulatory testing identifies potential hazards, but risks of these hazards need to be evaluated in the context of realistic exposures and conditions. Conclusions about safety should be based on empirical results within the limitations of model systems or experimental design. This review summarizes how pesticide residues, particularly glyphosate, in food and feed are quantified, and how their safety is determined by regulatory agencies to establish safe use levels.

Assessing the Safety of Pesticides in Food: How Current Regulations Protect Human Health.

Understanding the magnitude and impact of dietary pesticide exposures is a concern for some consumers. However, the ability of consumers to obtain and understand state-of-the-science information about how pesticides are regulated and how dietary exposure limits are set can be limited by the complicated nature of the regulations coupled with an abundance of sources seeking to cast doubt on the reliability of those regulations. Indeed, these regulations are sometimes not well understood within health care professions. As such, the objective of this review is to provide a historical perspective as to how modern pesticides were developed, current trends in pesticide use and regulation, and measures taken to reduce the risk of pesticide use to the consumer. Throughout the review, we provide specific examples for some of the concepts as they apply to glyphosate-a pesticide commonly used by both farmers and consumers. In addition, we describe current efforts to monitor pesticide use. We are confident that this succinct, yet thorough, review of this topic will be of interest to myriad researchers, public health experts, and health practitioners as they help communicate information about making healthful and sustainable food choices to the public.

Calorimetric Biosensing System for Quantification of Urinary Creatinine.

In this work, we demonstrate the quantification of creatinine in human urine samples using a microcalorimetric sensing system. The calorimetric sensor is based on an array of microfabricated Y-cut quartz resonators. The piezoelectric quartz is etched down to a thickness of 10 µm and exhibits a bulk acoustic resonance of 166 MHz. The temperature sensitivity of this high-frequency quartz resonator is 14 600 Hz/K due to the high phenomenological sensitivity of quartz. Most importantly, the quartz sensors and the analyte fluidics are decoupled providing a significantly more robust calorimetric sensing system than directly contacted chip calorimeters. A reference resonator, consisting of a suspended structure held by four arms, was realized to thermal isolation from the bulk quartz by using focused ion beam etching. We employ alginate entrapped creatinine deiminase to transduce urinary creatinine into temperature signatures, permitting the quantification of creatinine. Fairly good agreement with the measured creatinine values in the 5 urine samples using calorimetric and HPLC methods is obtained.

Physiological responses related to increased grain yield under drought in the first biotechnology-derived drought-tolerant maize.

Maize (Zea mays ssp. mays L.) is highly susceptible to drought stress. This work focused on whole-plant physiological mechanisms by which a biotechnology-derived maize event expressing bacterial cold shock protein B (CspB), MON 87460, increased grain yield under drought. Plants of MON 87460 and a conventional control (hereafter 'control') were tested in the field under well-watered (WW) and water-limited (WL) treatments imposed during mid-vegetative to mid-reproductive stages during 2009-2011. Across years, average grain yield increased by 6% in MON 87460 compared with control under WL conditions. This was associated with higher soil water content at 0.5 m depth during the treatment phase, increased ear growth, decreased leaf area, leaf dry weight and sap flow rate during silking, increased kernel number and harvest index in MON 87460 than the control. No consistent differences were observed under WW conditions. This indicates that MON 87460 acclimated better under WL conditions than the control by lowering leaf growth which decreased water use during silking, thereby eliciting lower stress under WL conditions. These physiological responses in MON 87460 under WL conditions resulted in increased ear growth during silking, which subsequently increased the kernel number, harvest index and grain yield compared to the control.

Mental illness in metropolitan, urban and rural Georgia populations.

BACKGROUND: Mental illness represents an important public health problem. Local-level data concerning mental illness in different populations (e.g., socio-demographics and residence--metropolitan/urban/rural) provides the evidence-base for public health authorities to plan, implement and evaluate control programs. This paper describes prevalence and covariates of psychiatric conditions in Georgia populations in three defined geographic areas. METHODS: Data came from the Georgia population-based random-digit-dialing study investigating unwellness and chronic fatigue syndrome (CFS) in Georgia populations of three defined geographic areas (metropolitan, urban, and rural). Respondents were screened for symptoms of fatigue, sleep, cognition, and pain at household screening interviews, and a randomly selected sample completed detailed individual phone interviews. Based on the detailed phone interviews, we conducted one-day clinical evaluations of 292 detailed interview participants classified as unwell with a probable CFS (i.e. CFS-like; a functional somatic syndrome), 268 classified as other unwell, and 223 well (matched to CFS-like). Clinical evaluation included psychiatric classification by means of the Structured Clinical Interview for DSM (SCID). To derive prevalence estimates we used sample weighting to account for the complexity of the multistage sampling design. We used 2- and 3-way table analyses to examine socio-demographic and urbanicity specific associations and multiple logistic regression to calculate adjusted odds ratios. RESULTS: Anxiety and mood disorders were the most common psychiatric conditions. Nineteen percent of participants suffered a current anxiety disorder, 18% a mood disorder and 10% had two or more conditions. There was a significant linear trend in occurrence of anxiety or mood disorders from well to CFS-like. The most common anxiety disorders were post-traumatic stress disorder (PTSD) (6.6%) and generalized anxiety disorder (GAD) (5.8%). Logistic regression showed that lower education and female sex contributed significantly to risk for both PTSD and GAD. In addition, rural/urban residence and Hispanic ethnicity were associated with PTSD. We defined moderate to severe depression as Major Depressive Disorder or a Zung score>60 and logistic regression found lower education to be significantly associated but sex, age and urbanicity were not. CONCLUSIONS: Overall occurrence of anxiety and mood disorders in Georgia mirrored national findings. However, PTSD and GAD occurred at twice the published national rates (3.6 and 2.7%, respectively). State and local prevalence and associations with education, sex and urbanicity comprise important considerations for developing control programs. The increased prevalence of anxiety and mood disorders in people with a functional somatic syndrome (or CFS-like illness) is important for primary care providers, who should consider additional psychiatric screening or referral of individuals presenting with somatoform symptoms.

Prevalence, incidence, and classification of chronic fatigue syndrome in Olmsted County, Minnesota, as estimated using the Rochester Epidemiology Project.

OBJECTIVE: To estimate the prevalence and incidence of chronic fatigue syndrome in Olmsted County, Minnesota, using the 1994 case definition and describe exclusionary and comorbid conditions observed in patients who presented for evaluation of long-standing fatigue. PATIENTS AND METHODS: We conducted a retrospective medical record review of potential cases of chronic fatigue syndrome identified from January 1, 1998, through December 31, 2002, using the Rochester Epidemiology Project, a population-based database. Patients were classified as having chronic fatigue syndrome if the medical record review documented fatigue of 6 months' duration, at least 4 of 8 chronic fatigue syndrome-defining symptoms, and symptoms that interfered with daily work or activities. Patients not meeting all of the criteria were classified as having insufficient/idiopathic fatigue. RESULTS: We identified 686 potential patients with chronic fatigue, 2 of whom declined consent for medical record review. Of the remaining 684 patients, 151 (22%) met criteria for chronic fatigue syndrome or insufficient/idiopathic fatigue. The overall prevalence and incidence of chronic fatigue syndrome and insufficient/idiopathic fatigue were 71.34 per 100,000 persons and 13.16 per 100,000 person-years vs 73.70 per 100,000 persons and 13.58 per 100,000 person-years, respectively. The potential cases included 482 patients (70%) who had an exclusionary condition, and almost half the patients who met either criterion had at least one nonexclusionary comorbid condition. CONCLUSION: The incidence and prevalence of chronic fatigue syndrome and insufficient/idiopathic fatigue are relatively low in Olmsted County. Careful clinical evaluation to identify whether fatigue could be attributed to exclusionary or comorbid conditions rather than chronic fatigue syndrome itself will ensure appropriate assessment for patients without chronic fatigue syndrome.

Utilization of two web-based continuing education courses evaluated by Markov chain model.

OBJECTIVES: To evaluate the web structure of two web-based continuing education courses, identify problems and assess the effects of web site modifications. DESIGN: Markov chain models were built from 2008 web usage data to evaluate the courses' web structure and navigation patterns. The web site was then modified to resolve identified design issues and the improvement in user activity over the subsequent 12 months was quantitatively evaluated. MEASUREMENTS: Web navigation paths were collected between 2008 and 2010. The probability of navigating from one web page to another was analyzed. RESULTS: The continuing education courses' sequential structure design was clearly reflected in the resulting actual web usage models, and none of the skip transitions provided was heavily used. The web navigation patterns of the two different continuing education courses were similar. Two possible design flaws were identified and fixed in only one of the two courses. Over the following 12 months, the drop-out rate in the modified course significantly decreased from 41% to 35%, but remained unchanged in the unmodified course. The web improvement effects were further verified via a second-order Markov chain model. CONCLUSIONS: The results imply that differences in web content have less impact than web structure design on how learners navigate through continuing education courses. Evaluation of user navigation can help identify web design flaws and guide modifications. This study showed that Markov chain models provide a valuable tool to evaluate web-based education courses. Both the results and techniques in this study would be very useful for public health education and research specialists.

Therapeutic Modalities in Diabetic Nephropathy: Future Approaches.

Diabetes mellitus is the leading cause of end stage renal disease and is responsible for more than 40% of all cases in the United States. Several therapeutic interventions for the treatment of diabetic nephropathy have been developed and implemented over the past few decades with some degree of success. However, the renal protection provided by these therapeutic modalities is incomplete. More effective approaches are therefore urgently needed. Recently, several novel therapeutic strategies have been explored in treating DN patients including Islet cell transplant, Aldose reductase inhibitors, Sulodexide (GAC), Protein Kinase C (PKC) inhibitors, Connective tissue growth factor (CTGF) inhibitors, Transforming growth factor-beta (TGF-ß) inhibitors and bardoxolone. The benefits and risks of these agents are still under investigation. This review aims to summarize the utility of these novel therapeutic approaches.

Mental illness surveillance among adults in the United States.

Mental illnesses account for a larger proportion of disability in developed countries than any other group of illnesses, including cancer and heart disease. In 2004, an estimated 25% of adults in the United States reported having a mental illness in the previous year. The economic cost of mental illness in the United States is substantial, approximately $300 billion in 2002. Population surveys and surveys of health-care use measure the occurrence of mental illness, associated risk behaviors (e.g., alcohol and drug abuse) and chronic conditions, and use of mental health-related care and clinical services. Population-based surveys and surveillance systems provide much of the evidence needed to guide effective mental health promotion, mental illness prevention, and treatment programs. This report summarizes data from selected CDC surveillance systems that measure the prevalence and impact of mental illness in the U.S. adult population. CDC surveillance systems provide several types of mental health information: estimates of the prevalence of diagnosed mental illness from self-report or recorded diagnosis, estimates of the prevalence of symptoms associated with mental illness, and estimates of the impact of mental illness on health and well-being. Data from the CDC 2005-2008 National Health and Nutrition Examination Survey indicate that 6.8% of adults had moderate to severe depression in the 2 weeks before completing the survey. State-specific data from the CDC 2006 Behavioral Risk Factor Surveillance System (BRFSS), the most recent BRFSS data available, indicate that the prevalence of moderate to severe depression was generally higher in southeastern states compared with other states. Two other CDC surveys on ambulatory care services, the National Ambulatory Medical Care Survey and the National Hospital Ambulatory Medical Care Survey, indicate that during 2007-2008, approximately 5% of ambulatory care visits involved patients with a diagnosis of a mental health disorder, and most of these were classified as depression, psychoses, or anxiety disorders. Future surveillance should pay particular attention to changes in the prevalence of depression both nationwide and at the state and county levels. In addition, national and state-level mental illness surveillance should measure a wider range of psychiatric conditions and should include anxiety disorders. Many mental illnesses can be managed successfully, and increasing access to and use of mental health treatment services could substantially reduce the associated morbidity.

Cumulative life stress in chronic fatigue syndrome.

We studied the impact of cumulative life stress on CFS in a population-based study. We found that exposure to stressors was significantly more common in persons with CFS compared to NF controls; those with CFS reported experiencing significantly higher levels of psychological distress. Also, post-traumatic stress disorder was significantly more common in people with CFS. These results not only corroborate findings from other studies but, importantly, extend those by: a) measuring a comprehensive spectrum of stress variables, b) for the first time presenting data on stress in a population-based study, thus minimizing the effects of recruitment bias, and c) diagnosing CFS by means of standardized, validated scales, thus allowing replication and extension of our findings. Stress may be an important factor in the pathophysiology of CFS. Consequently, future studies should provide a more detailed understanding of the processes that lead from stress to CFS using longitudinal designs.

Gynecological history in chronic fatigue syndrome: a population-based case-control study.

BACKGROUND: Chronic fatigue syndrome (CFS) affects disproportionately more women than men, and the condition is more common at perimenopause. We examined gynecological history events as risk factors for CFS. METHODS: In a case-control study from a randomly selected population sample from Wichita, Kansas, 36 women with CFS and 48 nonfatigued controls, of similar age, race, and body mass index (BMI), answered a structured gynecological history questionnaire. RESULTS: CFS cases and controls had the same mean age (51 years) and age at menarche (12 years). Overall, a greater proportion of women with CFS than controls reported pelvic pain unrelated to menstruation (22.2% vs. 1.7%, p = 0.004), endometriosis (36.1% vs. 16.7, %, p = 0.046), and periods of amenorrhea (53.9 % vs. 46.2%, p = 0.06). Compared to controls, women in the CFS group had a higher mean number of pregnancies (2.8 vs 2.0, p = 0.05) and gynecological surgeries (1.8 vs. 1.1, p = 0.05). Similar proportions of the CFS (69.4%) and control (72.9%) groups were menopausal. Although menopausal women in the CFS and control groups had similar mean age (55.5 and 55.8, respectively), menopause occurred about 4.4 years earlier in the CFS group (41.7 years vs. 46.1 years, respectively, p = 0.11). Among menopausal women, 76% of the CFS group reported hysterectomy vs. 54.6% of controls (p = 0.09), and 56% of women with CFS reported oophorectomy vs. 34.3% of controls (p = 0.11). CONCLUSIONS: The higher prevalence of gynecological conditions and gynecological surgeries in women with CFS highlights the importance of evaluating gynecological health in these patients and the need for more research to clarify the chronologic and the pathophysiological relationships between these conditions and CFS.

Endogenous IL-10 attenuates cisplatin nephrotoxicity: role of dendritic cells.

Sterile inflammation is associated with tissue injury and organ failure. Recent studies indicate that certain endogenous cytokines and immune cells may limit tissue injury by reducing immune-mediated inflammatory responses. Cisplatin is a commonly used anticancer chemotherapeutic agent but causes acute kidney injury and dysfunction. In a recent study, we showed that renal dendritic cells attenuate cisplatin-induced kidney injury by reducing inflammation. In this study, we investigated the effect of endogenous IL-10 and dendritic cell IL-10 in cisplatin-mediated kidney injury. Cisplatin treatment caused increases in renal IL-10R1 expression and STAT3 phosphorylation. In response to cisplatin treatment, IL-10 knockout mice showed more rapid and greater increases in blood urea nitrogen and serum creatinine compared with wild-type mice, indicating that endogenous IL-10 ameliorates kidney injury in cisplatin nephrotoxicity. Renal infiltration of IFN-γ-producing neutrophils was markedly increased in IL-10 knockout mice compared with wild-type mice. However, IFN-γ neutralization had no impact on renal dysfunction, suggesting IFN-γ-independent mechanisms of tissue injury in cisplatin nephrotoxicity. Renal dendritic cells showed high expression of IL-10 in response to cisplatin treatment. We further investigated the effect of dendritic cell-derived IL-10 in cisplatin nephrotoxicity using a conditional cell ablation approach. Mixed bone marrow chimeric mice lacking IL-10 in dendritic cells showed moderately greater renal dysfunction than chimeric mice positive for IL-10 in dendritic cells. These data demonstrate that endogenous IL-10 reduces cisplatin nephrotoxicity and associated inflammation. Moreover, IL-10 produced by dendritic cells themselves accounts for a portion of the protective effect of dendritic cells in cisplatin nephrotoxicity.