Estimating the time-evolving refractivity of a turbulent medium using optical beam measurements: a data assimilation approach.

In applications such as free-space optical communication, a signal is often recovered after propagation through a turbulent medium. In this setting, it is common to assume that limited information is known about the turbulent medium, such as a space- and time-averaged statistic (e.g., root-mean-square), but without information about the state of the spatial variations. It could be helpful to gain more information if the state of the turbulent medium can be characterized with the spatial variations and evolution in time described. Here, we propose to investigate the use of data assimilation techniques for this purpose. A computational setting is used with the paraxial wave equation, and the extended Kalman filter is used to conduct data assimilation using intensity measurements. To reduce computational cost, the evolution of the turbulent medium is modeled as a stochastic process. Following some past studies, the process has only a small number of Fourier wavelengths for spatial variations. The results show that the spatial and temporal variations of the medium are recovered accurately in many cases. In some time windows in some cases, the error is large for the recovery. Finally, we discuss the potential use of the spatial variation information for aiding the recovery of the transmitted signal or beam source.

Scintillation minimization versus intensity maximization in optimal beams.

In free-space optical communications and other applications, it is desirable to design optical beams that have reduced or even minimal scintillation. However, the optimization problem for minimizing scintillation is challenging, and few optimal solutions have been found. Here we investigate the general optimization problem of minimizing scintillation and formulate it as a convex optimization problem. An analytical solution is found and demonstrates that a beam that minimizes scintillation is incoherent light (i.e., spatially uncorrelated). Furthermore, numerical solutions show that beams minimizing scintillation give very low intensity at the receiver. To counteract this effect, we study a new convex cost function that balances both scintillation and intensity. We show through numerical experiments that the minimizers of this cost function reduce scintillation while preserving a significantly higher level of intensity at the receiver.

Rotation of small diatomics in water-ethanol mixture: Multiple breakdowns of hydrodynamic predictions.

We study the rotational and translational dynamics of three small important linear molecules, namely, carbon monoxide (CO), nitric oxide (NO), and cyanide ion (CN-) in water-ethanol mixtures, at different compositions. Here, we report a detailed study of the dynamics of these diatomics in water-ethanol binary mixtures for the first time. We find multiple anomalous results, namely, (i) faster rotational motion of CO and NO than CN-, (ii) larger translational diffusion of CO and NO in pure ethanol than in water but the reverse for CN-, (iii) a pronounced anomaly in the composition dependence of translational-rotational dynamics at low ethanol composition, and (iv) a re-entrant type behavior in the viscosity dependence of orientational relaxation. We compare our simulation result-based observations with the existing experimental results wherever available and find that the simulation results are in reasonably good agreement with the experiments. We implement, for the first time, a calculation of the rotational binary friction following the sophisticated scheme of Evans and co-workers. We also calculate the hydrodynamic predictions for the solute molecules. On comparison with the simulation and experimental results, we find that neither the rotational binary friction nor the hydrodynamic expressions (both stick and slip) can reproduce the results. To rectify the situation, we develop a detailed mode-coupling theory and suggest that such an approach if completely implemented can provide a more reliable description than the hydrodynamic approach. Many of our results could be tested in experimental studies because these linear molecules are amenable to spectroscopic studies, such as 2D-IR.

Relationship Between Pregnancy-Associated Malaria and Adverse Pregnancy Outcomes: a Systematic Review and Meta-Analysis.

BACKGROUND: Pregnancy-associated malaria (PAM) has been associated with adverse pregnancy outcomes like preterm birth (PTB) and low birthweight (LBW), which are among the leading causes of infant mortality globally. Rates of PTB and LBW are high in countries with a high burden of malaria. PAM may be a contributing factor to PTB and LBW, but is not well understood. METHODS: We conducted a systematic review and meta-analysis of studies examining the relationship between PAM and PTB or LBW using PubMed. The title and abstract of all studies were screened by two reviewers, and the full text of selected studies was reviewed to ensure they met inclusion criteria. Information regarding study characteristics and of PTB and LBW births among women with and without PAM was abstracted for included studies. RESULTS: Our search terms yielded 2237 articles, of which 18 met our final inclusion criteria. Eight studies examined associations between PAM and PTB, and 10 examined associations between PAM and LBW (population size ranging from 35 to 9956 women). The overall risk of LBW was 63% higher among women with PAM compared with women without PAM (95% CI = 1.48-1.80) and the risk of PTB was 23% higher among women with PAM compared with women without PAM (95% CI = 1.07-1.41). CONCLUSIONS: These results indicate that infection with PAM is associated with PTB and LBW. Further understanding of the pathogenesis of disease and the immunologic changes that occur during pregnancy is essential for reducing the disproportional effects this disease has on this vulnerable population.

Dynamics of linear molecules in water: Translation-rotation coupling in jump motion driven diffusion.

We study by computer simulations, and by theory, the coupled rotational and translational dynamics of three important linear diatomic molecules, namely, carbon monoxide (CO), nitric oxide (NO), and cyanide ion (CN-) in water. Translational diffusion of these molecules is found to be strongly coupled to their own rotational dynamics which, in turn, are coupled to similar motions of the surrounding water. In particular, we find that coupled orientational jump motions play an important role in all three cases. While CO and NO show similar features, CN- exhibits certain differences. Our results agree well with the known experimental values of the diffusion coefficient. We examined the validity of hydrodynamic predictions and found them to be inadequate, particularly for rotational diffusion. A mode coupling theory approach is developed and applied to understand the complexity of translation-rotation coupling.

Identification of myeloid-derived suppressor cells in the synovial fluid of patients with rheumatoid arthritis: a pilot study.

BACKGROUND: Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of innate immune cells with a granulocyte-like or monocyte-like phenotype and a unique ability to suppress T-cell responses. MDSCs have been shown to accumulate in cancer patients, but recent studies suggest that these cells are also present in humans and animals suffering from autoimmune diseases. We previously identified MDSCs in the synovial fluid (SF) of mice with experimental autoimmune arthritis. The goal of the present study was to identify MDSCs in the SF of patients with rheumatoid arthritis (RA). METHODS: RA SF cells were studied by flow cytometry using antibodies to MDSC cell surface markers as well as by analysis of cell morphology. The suppressor activity of RA SF cells toward autologous peripheral blood T cells was determined ex vivo. We employed both antigen-nonspecific (anti-CD3/CD28 antibodies) and antigen-specific (allogeneic cells) induction systems to test the effects of RA SF cells on the proliferation of autologous T cells. RESULTS: SF from RA patients contained MDSC-like cells, the majority of which showed granulocyte (neutrophil)-like phenotype and morphology. RA SF cells significantly suppressed the proliferation of anti-CD3/CD28-stimulated autologous T cells upon co-culture. When compared side by side, RA SF cells had a more profound inhibitory effect on the alloantigen-induced than the anti-CD3/CD28-induced proliferation of autologous T cells. CONCLUSION: MDSCs are present among RA SF cells that are commonly regarded as inflammatory neutrophils. Our results suggest that the presence of neutrophil-like MDSCs in the SF is likely beneficial, as these cells have the ability to limit the expansion of joint-infiltrating T cells in RA.

Serum Galactomannan as a Minimally Invasive Diagnostic Tool for Fungal Skull Base Osteomyelitis.

Multidrug resistant strains and fungi add to treatment conundrums in skull base osteomyelitis (SBO). Deep tissue culture in these patients is challenging due to their advanced age and co-morbidities. Besides, fungal culture positivity is seen only in 60% of invasive aspergillosis. To determine the efficacy of a minimally invasive test-Serum Galactomannan (sGM)-for diagnosing fungal SBO. Prospective observational study. Thirty- three patients, clinically diagnosed with SBO were included in this study. Baseline ESR (Erythrocyte Sedimentation Rate), CRP (C- Reactive Protein), pain score, and sGM were noted for all patients. Antifungal Voriconazole was initiated on patients if the sGM values were more than 0.8. At the 12th week of treatment, all parameters were repeated and compared with the baseline values. A significant reduction was noted in ESR, CRP, and pain scores at the 12th week of treatment compared to the baseline values in patients with raised sGM values who were started on Voriconazole. For a culture-proven fungal skull base osteomyelitis with a cut-off value of sGM > / = 0.8, the obtained sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were 81.82, 36.36, 39.13, 80 and 51.52% respectively. At a cut-off value of sGM > / = 01.6, the values of sensitivity/specificity, PPV, NPV and accuracy were 81.82/72.73%, 60%, 88.89% and 75.76%. Culture-negative patients in SBO with sGM value > 0.8 were more likely to be fungal SBO. An sGM cut-off of 1.6 was observed to give maximum accuracy for diagnosing fungal SBO.

Synovial fluid from patients with early osteoarthritis modulates fibroblast-like synoviocyte responses to toll-like receptor 4 and toll-like receptor 2 ligands via soluble CD14.

OBJECTIVE: Synovial inflammation, a feature of both osteoarthritis (OA) and meniscal injury, is hypothesized to be triggered in part via stimulation of Toll-like receptors (TLRs). We undertook this study to test whether a TLR-2- or TLR-4-stimulating factor in synovial fluid (SF) from patients with early knee OA with meniscal injury could lead to inflammatory activation of synoviocytes. METHODS: SF was obtained from patients with early OA cartilage damage undergoing arthroscopic meniscal procedures. SF was used to stimulate primary cultures of fibroblast-like synoviocytes (FLS) and cell lines transfected with TLR-2 or TLR-4. SF was used either alone or in combination with a TLR-2 stimulus (palmitoyl-3-cysteine-serine-lysine-4 [Pam3CSK4]) or a TLR-4 stimulus (lipopolysaccharide [LPS]). In blocking experiments, SF was preincubated with anti-CD14 antibody. RESULTS: SF from these patients did not stimulate interleukin-8 (IL-8) release from TLR transfectants. Compared with SF on its own, SF (at concentrations of 0.09-25%) in combination with TLR-2 or TLR-4 ligands resulted in significant augmentation of IL-8 release from both transfectants and primary FLS. Soluble CD14 (sCD14), a coreceptor for TLRs, was measured in SF from patients with early OA at levels comparable to those in patients with advanced OA and patients with rheumatoid arthritis. Blockade with anti-CD14 antibody abolished the ability of SF to augment IL-8 production in response to LPS, and diminished Pam3CSK4 responses. CONCLUSION: SF augments FLS responses to TLR-2 and TLR-4 ligands. This effect was largely due to sCD14. Our results demonstrate that sCD14 in the setting of OA and meniscal injury sensitizes FLS to respond to inflammatory stimuli such as TLR ligands.

Metrics for maternity unit staffing in low resource settings: Scoping review and proposed core indicator.

Background: The lack of usable indicators and benchmarks for staffing of maternity units in health facilities has constrained planning and effective program implementation for emergency obstetric and newborn care (EmONC) globally. Objectives: To identify potential indicator(s) and benchmarks for EmONC facility staffing that might be applicable in low resource settings, we undertook a scoping review before proceeding to develop a proposed set of indicators. Eligibility criteria: Population: women attending health facilities for care around the time of delivery and their newborns. Concept: reports of mandated norms or actual staffing levels in health facilities. Context: studies conducted in healthcare facilities of any type that undertake delivery and newborn care and those from any geographic setting in both public and private sector facilities. Sources of evidence and charting: Searches were limited to material published since 2000 in English or French, using Pubmed and a purposive search of national Ministry of Health, non-governmental organization and UN agency websites for relevant documents. A template for data extraction was designed. Results: Data extraction was undertaken from 59 papers and reports including 29 descriptive journal articles, 17 national Ministry of Health documents, 5 Health Care Professional Association (HCPA) documents, two each of journal policy recommendation and comparative studies, one UN Agency document and 3 systematic reviews. Calculation or modelling of staffing ratios was based on delivery, admission or inpatient numbers in 34 reports, with 15 using facility designation as the basis for staffing norms. Other ratios were based on bed numbers or population metrics. Conclusions: Taken together, the findings point to a need for staffing norms for delivery and newborn care that reflect numbers and competencies of staff physically present on each shift. A Core indicator is proposed, "Monthly mean delivery unit staffing ratio" calculated as number of annual births/365/monthly average shift staff census.

Synovial inflammation in patients undergoing arthroscopic meniscectomy: molecular characterization and relationship to symptoms.

OBJECTIVE: Traumatic and degenerative meniscal tears have different anatomic features and different proposed etiologies, yet both are associated with the development or progression of osteoarthritis (OA). In established OA, synovitis is associated with pain and progression, but a relationship between synovitis and symptoms in isolated meniscal disease has not been reported. Accordingly, we sought to characterize synovial pathology in patients with traumatic meniscal injuries and determine the relationships between inflammation, meniscal and cartilage pathology, and symptoms. METHODS: Thirty-three patients without evidence of OA who were undergoing arthroscopic meniscectomy for meniscal injuries were recruited. Pain and function were assessed preoperatively; meniscal and cartilage abnormalities were documented at the time of surgery. Inflammation in synovial biopsy specimens was scored, and associations between inflammation and clinical outcomes were determined. Microarray analysis of synovial tissue was performed, and gene expression patterns in patients with and those without inflammation were compared. RESULTS: Synovial inflammation was present in 43% of the patients and was associated with worse preoperative pain and function scores, independent of age, sex, or cartilage pathology. Microarray analysis and real-time polymerase chain reaction revealed a chemokine signature in synovial biopsy specimens with increased inflammation scores. CONCLUSION: Our findings indicate that in patients with traumatic meniscal injury undergoing arthroscopic meniscectomy without radiographic evidence of OA, synovial inflammation occurs frequently and is associated with increased pain and dysfunction. Synovia with increased inflammation scores exhibit a unique chemokine signature. Chemokines may contribute to the development of synovial inflammation in patients with meniscal pathology; they also represent potential therapeutic targets for reducing inflammatory symptoms.

Efficacy of Gas Combination Cryotherapy in the Management of Odontogenic Keratocyst of the Maxilla and Mandible: A Pilot Study.

Aim: The aim of this study was to evaluate outcome of management of odontogenic keratocyst (OKC) using gas combination cryotherapy (GCC). GCC is a treatment modality where cyst enucleation is followed by applying an adjuvant agent, a spray containing propane, butane and isobutene gas onto the bony bed. Materials and Methods: This was a prospective interventional study which included patients with radiographic and histopathologic evidence of OKC. All patients underwent enucleation of the cysts followed by spraying of the bony cavity with "ENDOFROST ™"(commercially available agent for GCC). Patients were periodically reviewed and the presence of wound dehiscence, infection and neurosensory deficit was noted. After 15 months, a CBCT was taken to assess the amount of bone formation, the presence of any pathologic fracture or recurrence. Comparison of the preoperative and the postoperative size of the defect was also assessed. Results: A total of 10 patients were included in the study of which only 2 presented with neurosensory deficit in the post-op period. One patient of the two patients recovered completely within 12 months, while the other recovered within 15 months. There was no evidence of any patient developing infection, wound dehiscence, recurrence or pathologic fracture. Conclusion: The results of the study show that enucleation followed by GCC is a safe, effective and low-cost therapy for the management of OKC.

Rigid Cations Induce Enhancement of Microheterogeneity and Exhibit Anomalous Ion Diffusion in Water-Ethanol Mixtures.

Because of the amphiphilic nature of ethanol in the aqueous solution, ions cause an interesting microheterogeneity where the water molecules and the hydroxy groups of ethanol preferentially solvate the ions, while the ethyl groups tend to occupy the intervening space. Using computer simulations, we study the dynamics of rigid monovalent cations (Li+, Na+, K+, and Cs+) in aqueous ethanol solutions with chloride as the counterion. We vary both the size of the ions and the composition of the mixture to explore size- and composition-dependent ion diffusion. The relative stability of enhanced microheterogeneous configurations makes ion diffusion slower than what would be surmised by using the bulk properties of the mixture, using the Stokes-Einstein relation. We study the structure through partial radial distribution functions and the stability through coordination number fluctuations. The ion diffusion coefficient exhibits sharp re-entrant behavior when plotted against viscosity varied by composition. Our studies reveal multiple anomalous features of ion motion in this mixture. We formulate a mode-coupling theory (MCT) that takes into account the interaction between different dynamical components; MCT can incorporate the effects of heterogeneous dynamics and nonlinearity in composition dependence that arise from the feedback between mutually dependent ion-solvent dynamics.

Smartphone Usage Among Doctors in the Clinical Setting in Two Culturally Distinct Countries: Cross-sectional Comparative Study.

BACKGROUND: Smartphones and mobile applications have seen a surge in popularity in recent years, a pattern that has also been reflected in the health care system. Despite increased reliance among clinicians however, limited research has been conducted on the uptake and impact of smartphone usage in medical practice, especially outside the Western world. OBJECTIVE: This study aimed to identify the usage of smartphones and medical apps by doctors in the clinical setting in 2 culturally distinct countries: King Hamad University Hospital (KHUH), Bahrain and Queen Mary Hospital (QMH), Hong Kong. METHODS: A cross-sectional, comparative study was conducted where doctors in both hospitals were asked to take part in a 15-item online survey. The questions were categorized into the following groups: demographics of the study population, ownership and main use of smartphones, number and names of medical apps currently owned, rating usage of smartphones for medical purposes, time spent on a smartphone related to clinical use, clinical reliance on smartphones, and views on further integration of smartphones. The results were then tabulated and analyzed using SPSS Statistics 25 for Mac (IBM Corp Inc, Armonk, NY). RESULTS: A total of 200 doctors were surveyed, with a total of 99.0% (99/100) of the doctors owning a smartphone in both KHUH and QMH; 58% (57/99) and 55% (54/99) of the doctors from KHUH and QMH, respectively, identified communication as their main use of smartphones in the clinical setting (P=.004). Doctors from KHUH were likely to spend more time on medical apps than doctors from QMH (P=.002). According to the overall results of both hospitals, 48% (32/67) of the junior doctors claimed high reliance on smartphones, whereas only 32.3% (41/127) of the senior doctors said the same (P=.03). Of doctors in KHUH and QMH, 78.0% (78/100) and 69.0% (69/100), respectively, either strongly agreed or agreed that smartphones need to be integrated into the clinical setting. In terms of preferences for future apps, 48% (48/100) and 56% (56/100) of the doctors in KHUH and QMH, respectively, agreed that more medical applications need to be created in order to support smartphone use in the clinical setting. CONCLUSIONS: These results suggest a substantial acceptance of smartphones by doctors in the clinical setting. It also elicits the need to establish policies to officially integrate smartphone technology into health care in accordance with ethical guidelines. More emphasis should be placed on creating medical applications that aid health care professionals in attaining their information from accurate sources and also regulate a system to monitor the usage of mobile devices within hospitals to prevent a breach of patient privacy and confidentiality.

The Impact of Challenge and Hindrance Demands on Burnout, Work Engagement, and Presenteeism. A Cross-Sectional Study Using the Job Demands-Resources Model.

OBJECTIVE: The present study used the Job Demands-Resources (JD-R) model to understand how perceiving job demands as a hindrance or a challenge can influence an individual's exhaustion and motivation and its effect on presenteeism. METHOD: A sample of 171 working Australians was used to test the relationships between job demands and job resources with presenteeism via burnout and work engagement. FINDINGS: The results suggested that challenge demands were positively related to burnout and work engagement, while hindrance demands were positively related to burnout and negatively related to work engagement. Most direct and indirect pathways predicted in earlier work incorporating the JD-R model to understand presenteeism were replicated. CONCLUSION: Future research on larger nation-wide samples is needed to further explore the differentiating effects of job demands on presenteeism via burnout and work engagement.

IL-15 and IL15RA in Osteoarthritis: Association With Symptoms and Protease Production, but Not Structural Severity.

Objective: Interleukin-15 (IL-15) is a pro-inflammatory cytokine that is increased in joint fluids of early-stage osteoarthritis (OA) patients, and has been associated with expression of proteases that can damage cartilage, and the development of neuropathic pain-like symptoms (NP) after nerve injury. The objective of this study was to further explore the role of IL-15 in the pathogenesis of OA cartilage degeneration and test genetic variation in the IL-15 receptor α gene (IL15RA) for an association with OA with radiographic severity and symptoms. Methods: Cartilage samples from donors (n = 10) were analyzed for expression of the IL15 receptor α-chain using immunohistochemistry, and for responses to IL-15 in vitro using explant cultures. Data from two independent Nottinghamshire-based studies (n = 795 and n = 613) were used to test genetic variants in the IL15RA gene (rs2228059 and rs7097780) for an association with radiographic severity, symptomatic vs. asymptomatic OA and NP. Results: IL-15Rα was expressed in chondrocytes from cartilage obtained from normal and degenerative knees. IL-15 significantly increased the release of matrix metalloproteinase-1 and -3 (MMP-1 and -3), but did not affect loss of proteoglycan from the articular matrix. Genetic variants in the IL15RA gene are associated with risk of symptomatic vs. asymptomatic OA (rs7097780 OR = 1.48 95% 1.10-1.98 p < 0.01) and with the risk of NP post-total joint replacement (rs2228059 OR = 0.76 95% 0.63-0.92 p < 0.01) but not with radiographic severity. Conclusions: In two different cohorts of patients, we show an association between genetic variation at the IL15 receptor and pain. Although ex vivo cartilage explants could respond to IL-15 with increased protease production, we found no effect of IL-15 on cartilage matrix loss and no association between IL15RA variants and radiographic severity. Together, these results suggest that IL-15 signaling may be a target for pain, but may not impact structural progression, in OA.

Statistical learning and Gestalt-like principles predict melodic expectations.

Expectation, or prediction, has become a major theme in cognitive science. Music offers a powerful system for studying how expectations are formed and deployed in the processing of richly structured sequences that unfold rapidly in time. We ask to what extent expectations about an upcoming note in a melody are driven by two distinct factors: Gestalt-like principles grounded in the auditory system (e.g.a preference for subsequent notes to move in small intervals), and statistical learning of melodic structure. We use multinomial regression modeling to evaluate the predictions of computationally implemented models of melodic expectation against behavioral data from a musical cloze task, in which participants hear a novel melodic opening and are asked to sing the note they expect to come next. We demonstrate that both Gestalt-like principles and statistical learning contribute to listeners' online expectations. In conjunction with results in the domain of language, our results point to a larger-than-previously-assumed role for statistical learning in predictive processing across cognitive domains, even in cases that seem potentially governed by a smaller set of theoretically motivated rules. However, we also find that both of the models tested here leave much variance in the human data unexplained, pointing to a need for models of melodic expectation that incorporate underlying hierarchical and/or harmonic structure. We propose that our combined behavioral (melodic cloze) and modeling (multinomial regression) approach provides a powerful method for further testing and development of models of melodic expectation.

Formulation of a nasogastric liquid feed and shelf-life extension using gamma radiation.

Nasogastric liquid feed formulation (NGLF) was developed for immunocompromised patients who are vulnerable targets of pathogenic assault. NGLF consisted of cereals, pulses, vegetables, and milk powder to provide balanced nutrients; however, the shelf life was only a few hours because this product was highly prone to microbial contamination and proliferation due to its high water content and rich nutrients. Postpreparation storage and distribution was very difficult, even at chilled temperatures. To overcome this problem, the NGLF was irradiated at various doses (2.5 to 10 kGy). Gamma irradiation at 10 kGy reduced the microbial load to nondetectable levels, and the product could be stored up to 1 month without any detectable increase in microbial load. The sensory evaluation did not indicate differences between the nonirradiated fresh, irradiated fresh, and stored samples. Nutritional quality in terms of total carbohydrates, dietary fiber, proteins, calories, vitamins A and C, and the micronutrients calcium, iron, and zinc was not affected by irradiation. NGLF also possessed antimutagenic potential against ethylmethanesulphonate-induced mutagenesis in Escherichia coli cells as evaluated by the rifampin resistance assay. This property of NGLF remained unchanged even after exposure to a 10-kGy dose of gamma radiation. Thus, irradiated NGLF seemed to be a safe and wholesome food for immunocompromised patients.

Enhanced virulence of Chlamydia muridarum respiratory infections in the absence of TLR2 activation.

Chlamydia trachomatis is a common sexually transmitted pathogen and is associated with infant pneumonia. Data from the female mouse model of genital tract chlamydia infection suggests a requirement for TLR2-dependent signaling in the induction of inflammation and oviduct pathology. We hypothesized that the role of TLR2 in moderating mucosal inflammation is site specific. In order to investigate this, we infected mice via the intranasal route with C. muridarum and observed that in the absence of TLR2 activation, mice had more severe disease, higher lung cytokine levels, and an exaggerated influx of neutrophils and T-cells into the lungs. This could not be explained by impaired bacterial clearance as TLR2-deficient mice cleared the infection similar to controls. These data suggest that TLR2 has an anti-inflammatory function in the lung during Chlamydia infection, and that the role of TLR2 in mucosal inflammation varies at different mucosal surfaces.

Innate immune pathways in virus-induced autoimmune diabetes.

We recently hypothesized that Toll-like receptor-induced innate upregulation by Kilham rat virus (KRV) in the BioBreeding diabetes-resistant (BBDR) rat model plays a key role in the mechanism of diabetes induction. To address this hypothesis, we analyzed innate immune signaling pathways upregulated by KRV in vitro and in vivo. We demonstrate that KRV activates the signal transducer and activator of transcription (STAT)-1 in spleen cells in vitro and that this activation can be blocked by TLR9 inhibition. We also show that KRV upregulates STAT-1 in pancreatic lymph nodes early after virus infection. Our data may implicate TLR9-induced STAT-1 signaling pathways in KRV-induced innate immune activation in the BBDR rat and raise the possibility that these pathways are involved in mediating autoimmune diabetes.