Anti-Inflammatory Effect of Dietary Pentadecanoic Fatty Acid Supplementation on Inflammatory Bowel Disease in SAMP1/YitFc Mice.

BACKGROUND/OBJECTIVES: Dietary fats have been linked to the increasing incidence of chronic diseases, including inflammatory bowel diseases (IBD), namely, Crohn's disease (CD). METHODS: This study investigated the impact of pentadecanoic acid (C15:0), a type of an odd-numbered chain saturated fatty acid, for its potential anti-inflammatory properties in different mouse models of experimental IBD using the SAMP1/YitFc (SAMP) mouse line (14- or 24-week-old), including chronic ileitis and DSS-induced colitis. To quantitively assess the effect of C:15, we tested two dosages of C:15 in selected experiments in comparison to control mice. Intestinal inflammation and intestinal permeability were used as primary outcomes. RESULTS: In ileitis, C:15 supplementation showed an anti-inflammatory effect in SAMP mice (e.g., a reduction in ileitis severity vs. control p < 0.0043), which was reproducible when mice were tested in the DSS model of colitis (e.g., reduced permeability vs. control p < 0.0006). Of relevance, even the short-term C:15 therapy prevented colitis in mice by maintaining body weight, decreasing inflammation, preserving gut integrity, and alleviating colitis signs. CONCLUSIONS: Collectively, the findings from both ileitis and colitis in SAMP mice indicate that C:15 may have therapeutic effects in the treatment of IBD (colitis in the short term). This promising effect has major translational potential for the alleviation of IBD in humans.

Microfluidic Detection of SPIONs and Co-Ferrite Ferrofluid Using Amorphous Wire Magneto-Impedance Sensor.

The detection of magnetic nanoparticles in a liquid medium and the quantification of their concentration have the potential to improve the efficiency of several relevant applications in different fields, including medicine, environmental remediation, and mechanical engineering. To this end, sensors based on the magneto-impedance effect have attracted much attention due to their high sensitivity to the stray magnetic field generated by magnetic nanoparticles, their simple fabrication process, and their relatively low cost. To improve the sensitivity of these sensors, a multidisciplinary approach is required to study a wide range of soft magnetic materials as sensing elements and to customize the magnetic properties of nanoparticles. The combination of magneto-impedance sensors with ad hoc microfluidic systems favors the design of integrated portable devices with high specificity towards magnetic ferrofluids, allowing the use of very small sample volumes and making measurements faster and more reliable. In this work, a magneto-impedance sensor based on an amorphous Fe73.5Nb3Cu1Si13.5B9 wire as the sensing element is integrated into a customized millifluidic chip. The sensor detects the presence of magnetic nanoparticles in the ferrofluid and distinguishes the different stray fields generated by single-domain superparamagnetic iron oxide nanoparticles or magnetically blocked Co-ferrite nanoparticles.

Candida tropicalis Affects Candida albicans Virulence by Limiting Its Capacity to Adhere to the Host Intestinal Surface, Leading to Decreased Susceptibility to Colitis in Mice.

Candida (C.) infections represent a serious health risk for people affected by inflammatory bowel disease. An important fungal virulence factor is the capacity of the fungus to form biofilms on the colonized surface of the host. This research study aimed to determine the effect of a C. tropicalis and C. albicans co-infection on dextran sodium sulfate (DSS)-induced colitis in mice. The colitis severity was evaluated using histology and a colonoscopy. The mice were mono-inoculated with C. albicans or C. tropicalis or co-challenged with both species. The mice were administered 3% DSS to induce acute colitis. The biofilm activity was assessed using (2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino)carbonyl] 2H-tetrazoliumhydroxide (XTT) and dry-weight assays. The abundance of C. albicans in the colon tissues was assessed by immunohistochemistry. The co-challenged mice showed a decreased colitis severity compared to the mono-inoculated mice. The dry-weight assay demonstrated a marked decrease in C. albicans biofilm production in a C. albicans culture incubated with C. tropicalis supernatant. Immunohistochemical staining showed that C. albicans was more abundant in the mucosa of C. albicans mono-inoculated mice compared to the co-inoculated group. These data indicate an antagonistic microbial interaction between the two Candida species, where C. tropicalis may produce molecules capable of limiting the ability of C. albicans to adhere to the host intestinal surface, leading to a reduction in biofilm formation.

Positive correlational shift between crevicular antimicrobial peptide LL-37, pain and periodontal status following non-surgical periodontal therapy. A pilot study.

BACKGROUND: Periodontitis has a high prevalence and uncertain recurrence. Unlike the pro-inflammatory cytokine profile, little is known about the anti-inflammatory cytokine and antimicrobial peptide overview following treatment. The present study aimed to evaluate if any of the antimicrobial peptide LL-37, interleukin (IL) 4, 10 and 6 together with the volume of gingival crevicular fluid (GCF) and total protein concentration in GCF could be used as correlative biomarkers for the severity in periodontitis as well as prognostic factors in the management of the disease. METHODS: Forty-five participants were recruited and allocated to the healthy (15), Stage I-II (15) or Stage III-IV periodontitis (15) group. Along with periodontal examination, GCF samples were obtained at baseline and 4-6 weeks following scaling and root planing (SRP) for the periodontitis groups. GCF samples were analyzed by ELISA kits to quantify LL-37 and IL-4, -6 and - 10. One-way ANOVA followed by Dunnett's test was used to determine differences among the three groups at baseline. Two-way ANOVA followed by Sidak's post-hoc test was used to compare between pre- and post-SRP in the two periodontitis groups. RESULTS: The amount of GCF volume was significantly correlated to the severity of periodontitis and decreased following SRP, particularly in the Stage III-IV group (p < 0.01). The levels of LL-37, IL-6, and pain and periodontal clinical parameters were significantly correlated to the severity of periodontitis. IL-4 and IL-10 in the periodontitis groups were significantly lower than the healthy group (p < 0.0001) and barely improved following SRP up to the level of the healthy group. CONCLUSIONS: With the limitations of this study, crevicular LL-37 may be a candidate for a biomarker of periodontitis and the associated pain upon probing. TRIAL REGISTRATION: The study was registered in clinical trials.gov, with number NCT04404335, dated 27/05/2020.

Hydrocephalus As Possible Prodromal Manifestation of COVID-19: A Report of Two Cases.

Although the etiopathology of normal pressure hydrocephalus (NPH) is still not completely defined, several studies in recent years have highlighted the role of neuro-inflammation mediators in its development. During COVID-19, the infected host develops a multifaceted inflammatory syndrome, that may lead to an uncontrolled immune system response also localized in the host nervous system. In fact, the target of the viral Spike protein, the angiotensin-converting enzyme 2 (ACE2) receptors, is widely expressed in different areas of CNS such as the olfactory epithelium, and the choroid plexus. As for idiopathic NPH, the massive release of inflammatory mediators may result in altered CSF dynamics and consequent sudden clinical decompensation. We report the cases of two patients with a known iNPH condition, in which neurological symptoms suddenly worsened, requiring hospitalization, without any evident precipitating cause. Both patients tested positive for the COVID-19 virus shortly after the neurological impairment, which had occurred, therefore, during the incubation period of the infection. On the basis of our experience we advise, in cases of NPH patients with sudden neurological worsening, to perform a molecular COVID-19 swab at the moment of clinical impairment. We, therefore, recommend considering SARS-CoV-2 infection in the differential diagnosis of a sudden and otherwise unexplainable impairment of hydrocephalic patients. Furthermore, we believe clinicians should invite NPH patients to adopt adequate preventive measures to protect them from SARS-CoV-2 infection.

Modulating the Microbiome for Crohn's Disease Treatment.

The central role of the gut microbiota in the regulation of health and disease has been convincingly demonstrated. Polymicrobial interkingdom interactions between bacterial (the bacteriome) and fungal (the mycobiome) communities of the gut have become a prominent focus for development of potential therapeutic approaches. In addition to polymicrobial interactions, the complex gut ecosystem also mediates interactions between the host and the microbiota. These interactions are complex and bidirectional; microbiota composition can be influenced by host immune response, disease-specific therapeutics, antimicrobial drugs, and overall ecosystems. However, the gut microbiota also influences host immune response to a drug or therapy by potentially transforming the drug's structure and altering bioavailability, activity, or toxicity. This is especially true in cases where the gut microbiota has produced a biofilm. The negative ramifications of biofilm formation include alteration of gut permeability, enhanced antimicrobial resistance, and alteration of host immune response effectiveness. Natural modulation of the gut microbiota, using probiotic and prebiotic approaches, may also be used to affect the host microbiome, a type of "natural" modulation of the host microbiota composition. In this review, we discuss potential bidirectional interactions between microbes and host, and we describe the changes in gut microbiota induced by probiotic and prebiotic approaches as well as their potential clinical consequences, including biofilm formation. We outline a systematic approach to designing probiotics capable of altering the host microbiota in disease states, using Crohn's disease as a model chronic disease. Understanding how the effective changes in the microbiome may enhance treatment efficacy may unlock the possibility of modulating the gut microbiome to improve treatment using a natural approach.

A Novel Probiotic Combination Ameliorates Crohn's Disease-Like Ileitis by Increasing Short-Chain Fatty Acid Production and Modulating Essential Adaptive Immune Pathways.

BACKGROUND: Crohn's disease (CD) represents a significant public health challenge. We identified a combination of beneficial probiotic strains (Saccharomyces boulardii, Lactobacillus rhamnosus, Lactobacillus acidophilus, and Bifidobacterium breve) and amylase that may antagonize elevated bacterial pathogens in the inflamed gut. Our aim was to characterize the effect(s) of this novel probiotic supplement in SAMP1/YitFc (SAMP) mice with CD-like ileitis. METHODS: Three groups of 7-week-old SAMP mice were used in this study. The first experimental group was administered 1 dose of the probiotic supplement (probiotic strains + amylase) diluted in sterile phosphate-buffered saline (PBS) (0.25 mg in 100 µL of PBS) every day for 56 days through the gavage technique, the second group had a probiotic supplement (probiotic strains without amylase), and the third group was a control group in which animals were administered sterile PBS. At the end of the treatment, mice were sacrificed and ilea were collected for histological scoring of ileitis and NanoString analysis. Stool samples were evaluated by 16S ribosomal RNA and gas chromatography-mass spectrometry analyses. RESULTS: Histology scores showed that mice treated with probiotics + amylase had a significant decrease of ileitis severity compared with the other 2 groups. 16S ribosomal RNA and gas chromatography-mass spectrometry analysis showed that abundance of species belonging to genus Lachnoclostridium and Mucispirillum schaedleri were significantly increased compared with the other 2 groups, and this increase was associated with augmented production of short-chain fatty acids. NanoString data showed that 21 genes involved in B memory cell development and T cell infiltration were significantly upregulated in probiotic-treated mice and that 3 genes were significantly downregulated. CONCLUSIONS: Our data provide experimental proof for a beneficial effect of the designed probiotic formulation on the severity of CD-like ileitis in the SAMP mouse model, involving both alteration of intestinal genetic pathways and microbial rearrangements. Thus, we propose that this novel probiotic mixture should be further tested as an adjuvant therapy in the treatment of biofilm-associated disorders such as CD, in which it has been proven that polymicrobial imbalance plays a critical role in dysbiosis and gut inflammation.

In this study, we report that consumption of a novel probiotic and amylase mixture reduced intestinal inflammation in SAMP1/YitFc mice. These findings provide the rationale for clinical testing of the designed probiotic as an adjuvant therapy for Crohn's disease treatment.

Mycobiome and Inflammatory Bowel Disease: Role in Disease Pathogenesis, Current Approaches and Novel Nutritional-based Therapies.

Inflammatory bowel disease (IBD), a disorder characterized by chronic inflammation of the gastrointestinal (GI) tract and a range of adverse health effects including diarrhea, abdominal pain, vomiting, and bloody stools, affects nearly 3.1 million genetically susceptible adults in the United States today. Although the etiology of IBD remains unclear, genetics, stress, diet, and gut microbiota dysbiosis- especially in immunocompromised individuals- have been identified as possible causes of disease. Although previous research has largely focused on the role of bacteria in IBD pathogenesis, recently observed alterations of fungal load and biodiversity in the GI tract of afflicted individuals suggest interkingdom interactions amongst different gut microbial communities, particularly between bacteria and fungi. These discoveries point to the potential utilization of treatment approaches such as antibiotics, antifungals, probiotics, and postbiotics that target both bacteria and fungi in managing IBD. In this review, we discuss the impact of specific fungi on disease pathogenesis, with a focus on the highly virulent genus Candida and how the presence of certain co-enzymes impacts its virulence. In addition, we evaluate current gut microbiome-based therapeutic approaches with the intention of better understanding the mechanisms behind novel therapies.

Recently observed alterations of fungal load in the gastrointestinal tract of IBD patients suggest interkingdom interactions amongst different gut microbial communities. These discoveries point to the potential utilization of antifungals and probiotics that target bacteria and fungi in managing IBD.

Effectiveness of mRNA COVID-19 Vaccines in Adolescents Over 6 Months.

BACKGROUND AND OBJECTIVES: On June 4, 2021, Italy launched the coronavirus disease 2019 (COVID-19) vaccination of adolescents to slow down the COVID-19 spread. Although clinical trials have evaluated messenger ribonucleic acid (mRNA) vaccine effectiveness in adolescents, there is limited literature on its real-world effectiveness. Accordingly, this study aimed to estimate the effectiveness of mRNA COVID-19 vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and mild or severe COVID-19 in a cohort of Sicilian adolescents within a 6 month observation period. METHODS: A retrospective cohort study was conducted with adolescents aged 12 to 18 years, residents of Sicily, who were followed from July 15 to December 31, 2021. SARS-CoV-2 infections, mild and severe COVID-19, and COVID-19-related intubation or deaths during the study period were compared between subjects vaccinated with 2 doses of mRNA vaccines and unvaccinated individuals. The Cox regression analysis, adjusted for age and sex, was performed to compare the 2 groups. RESULTS: Overall, the study included a total at-risk population of 274 782 adolescents with 61.4% of them having completed the vaccination cycle by the end of the study. Unvaccinated subjects had higher incidence rates of SARS-CoV-2 (1043 × 10 000 vs 158.7 × 10 000 subjects), mild COVID-19 (27.7 × 10 000 vs 1.8 × 10 000 subjects) and severe COVID-19 (1.41 × 10 000 vs 0 subjects) compared with the vaccinated population. The estimated adjusted vaccine effectiveness against SARS-CoV-2 infection was 71.2%, reaching 92.1% and 97.9% against mild and severe COVID-19, respectively. CONCLUSIONS: This study provides rigorous evidence of mRNA COVID-19 vaccines' effectiveness in protecting adolescents from both SARS-CoV-2 infection and COVID-19.

Design and Characterization of an RF Applicator for In Vitro Tests of Electromagnetic Hyperthermia.

The evaluation of the biological effects of therapeutic hyperthermia in oncology and the precise quantification of thermal dose, when heating is coupled with radiotherapy or chemotherapy, are active fields of research. The reliable measurement of hyperthermia effects on cells and tissues requires a strong control of the delivered power and of the induced temperature rise. To this aim, we have developed a radiofrequency (RF) electromagnetic applicator operating at 434 MHz, specifically engineered for in vitro tests on 3D cell cultures. The applicator has been designed with the aid of an extensive modelling analysis, which combines electromagnetic and thermal simulations. The heating performance of the built prototype has been validated by means of temperature measurements carried out on tissue-mimicking phantoms and aimed at monitoring both spatial and temporal temperature variations. The experimental results demonstrate the capability of the RF applicator to produce a well-focused heating, with the possibility of modulating the duration of the heating transient and controlling the temperature rise in a specific target region, by simply tuning the effectively supplied power.

Candida tropicalis Infection Modulates the Gut Microbiome and Confers Enhanced Susceptibility to Colitis in Mice.

BACKGROUND & AIMS: We previously showed that abundance of Candida tropicalis is significantly greater in Crohn's disease patients compared with first-degree relatives without Crohn's disease. The aim of this study was to determine the effects and mechanisms of action of C tropicalis infection on intestinal inflammation and injury in mice. METHODS: C57BL/6 mice were inoculated with C tropicalis, and colitis was induced by administration of dextran sodium sulfate in drinking water. Disease severity and intestinal permeability subsequently were evaluated by endoscopy, histology, quantitative reverse-transcription polymerase chain reaction, as well as 16S ribosomal RNA and NanoString analyses (NanoString Technologies, Seattle, WA). RESULTS: Infected mice showed more severe colitis, with alterations in gut mucosal helper T cells (Th)1 and Th17 cytokine expression, and an increased frequency of mesenteric lymph node-derived group 2 innate lymphoid cells compared with uninfected controls. Gut microbiome composition, including changes in the mucin-degrading bacteria, Akkermansia muciniphila and Ruminococcus gnavus, was altered significantly, as was expression of several genes affecting intestinal epithelial homeostasis in isolated colonoids, after C tropicalis infection compared with uninfected controls. In line with these findings, fecal microbiome transplantation of germ-free recipient mice using infected vs uninfected donors showed altered expression of several tight-junction proteins and increased susceptibility to dextran sodium sulfate-induced colitis. CONCLUSIONS: C tropicalis induces dysbiosis that involves changes in the presence of mucin-degrading bacteria, leading to altered tight junction protein expression with increased intestinal permeability and followed by induction of robust Th1/Th17 responses, which ultimately lead to an accelerated proinflammatory phenotype in experimental colitic mice.

Replacing Animal Protein with Soy-Pea Protein in an "American Diet" Controls Murine Crohn Disease-Like Ileitis Regardless of Firmicutes: Bacteroidetes Ratio.

BACKGROUND: The current nutritional composition of the "American diet" (AD; also known as Western diet) has been linked to the increasing incidence of chronic diseases, including inflammatory bowel disease (IBD), namely Crohn disease (CD). OBJECTIVES: This study investigated which of the 3 major macronutrients (protein, fat, carbohydrates) in the AD has the greatest impact on preventing chronic inflammation in experimental IBD mouse models. METHODS: We compared 5 rodent diets designed to mirror the 2011-2012 "What We Eat in America" NHANES. Each diet had 1 macronutrient dietary source replaced. The formulated diets were AD, AD-soy-pea (animal protein replaced by soy + pea protein), AD-CHO ("refined carbohydrate" by polysaccharides), AD-fat [redistribution of the ω-6:ω-3 (n-6:n-3) PUFA ratio; ∼10:1 to 1:1], and AD-mix (all 3 "healthier" macronutrients combined). In 3 separate experiments, 8-wk-old germ-free SAMP1/YitFC mice (SAMP) colonized with human gut microbiota ("hGF-SAMP") from CD or healthy donors were fed an AD, an AD-"modified," or laboratory rodent diet for 24 wk. Two subsequent dextran sodium sulfate-colitis experiments in hGF-SAMP (12-wk-old) and specific-pathogen-free (SPF) C57BL/6 (20-wk-old) mice, and a 6-wk feeding trial in 24-wk-old SPF SAMP were performed. Intestinal inflammation, gut metagenomics, and MS profiles were assessed. RESULTS: The AD-soy-pea diet resulted in lower histology scores [mean ± SD (56.1% ± 20.7% reduction)] in all feeding trials and IBD mouse models than did other diets (P < 0.05). Compared with the AD, the AD-soy-pea correlated with increased abundance in Lactobacillaceae and Leuconostraceae (1.5-4.7 log2 and 3.0-5.1 log2 difference, respectively), glutamine (6.5 ± 0.8 compared with 3.9 ± 0.3 ng/µg stool, P = 0.0005) and butyric acid (4:0; 3.3 ± 0.5 compared with 2.54 ± 0.4 ng/µg stool, P = 0.006) concentrations, and decreased linoleic acid (18:2n-6; 5.4 ± 0.4 compared with 8.6 ± 0.3 ng/µL plasma, P = 0.01). CONCLUSIONS: Replacement of animal protein in an AD by plant-based sources reduced the severity of experimental IBD in all mouse models studied, suggesting that similar, feasible adjustments to the daily human diet could help control/prevent IBD in humans.

A Survey of Active Learning for Quantifying Vegetation Traits from Terrestrial Earth Observation Data.

The current exponential increase of spatiotemporally explicit data streams from satellitebased Earth observation missions offers promising opportunities for global vegetation monitoring. Intelligent sampling through active learning (AL) heuristics provides a pathway for fast inference of essential vegetation variables by means of hybrid retrieval approaches, i.e., machine learning regression algorithms trained by radiative transfer model (RTM) simulations. In this study we summarize AL theory and perform a brief systematic literature survey about AL heuristics used in the context of Earth observation regression problems over terrestrial targets. Across all relevant studies it appeared that: (i) retrieval accuracy of AL-optimized training data sets outperformed models trained over large randomly sampled data sets, and (ii) Euclidean distance-based (EBD) diversity method tends to be the most efficient AL technique in terms of accuracy and computational demand. Additionally, a case study is presented based on experimental data employing both uncertainty and diversity AL criteria. Hereby, a a simulated training data base by the PROSAIL-PRO canopy RTM is used to demonstrate the benefit of AL techniques for the estimation of total leaf carotenoid content (Cxc ) and leaf water content (Cw ). Gaussian process regression (GPR) was incorporated to minimize and optimize the training data set with AL. Training the GPR algorithm on optimally AL-based sampled data sets led to improved variable retrievals compared to training on full data pools, which is further demonstrated on a mapping example. From these findings we can recommend the use of AL-based sub-sampling procedures to select the most informative samples out of large training data pools. This will not only optimize regression accuracy due to exclusion of redundant information, but also speed up processing time and reduce final model size of kernel-based machine learning regression algorithms, such as GPR. With this study we want to encourage further testing and implementation of AL sampling methods for hybrid retrieval workflows. AL can contribute to the solution of regression problems within the framework of operational vegetation monitoring using satellite imaging spectroscopy data, and may strongly facilitate data processing for cloud-computing platforms.

Specific Loss Power of Co/Li/Zn-Mixed Ferrite Powders for Magnetic Hyperthermia.

An important research effort on the design of the magnetic particles is increasingly required to optimize the heat generation in biomedical applications, such as magnetic hyperthermia and heat-assisted drug release, considering the severe restrictions for the human body's exposure to an alternating magnetic field. Magnetic nanoparticles, considered in a broad sense as passive sensors, show the ability to detect an alternating magnetic field and to transduce it into a localized increase of temperature. In this context, the high biocompatibility, easy synthesis procedure and easily tunable magnetic properties of ferrite powders make them ideal candidates. In particular, the tailoring of their chemical composition and cation distribution allows the control of their magnetic properties, tuning them towards the strict demands of these heat-assisted biomedical applications. In this work, Co0.76Zn0.24Fe2O4, Li0.375Zn0.25Fe2.375O4 and ZnFe2O4 mixed-structure ferrite powders were synthesized in a 'dry gel' form by a sol-gel auto-combustion method. Their microstructural properties and cation distribution were obtained by X-ray diffraction characterization. Static and dynamic magnetic measurements were performed revealing the connection between the cation distribution and magnetic behavior. Particular attention was focused on the effect of Co2+ and Li+ ions on the magnetic properties at a magnetic field amplitude and the frequency values according to the practical demands of heat-assisted biomedical applications. In this context, the specific loss power (SLP) values were evaluated by ac-hysteresis losses and thermometric measurements at selected values of the dynamic magnetic fields.

Human Gut Microbiome Transplantation in Ileitis Prone Mice: A Tool for the Functional Characterization of the Microbiota in Inflammatory Bowel Disease Patients.

BACKGROUND: Inflammatory bowel disease (IBD) is a lifelong digestive disease characterized by periods of severe inflammation and remission. To our knowledge, this is the first study showing a variable effect on ileitis severity from human gut microbiota isolated from IBD donors in remission and that of healthy controls in a mouse model of IBD. METHODS: We conducted a series of single-donor intensive and nonintensive fecal microbiota transplantation (FMT) experiments using feces from IBD patients in remission and healthy non-IBD controls (N = 9 donors) in a mouse model of Crohn's disease (CD)-like ileitis that develops ileitis in germ-free (GF) conditions (SAMP1/YitFC; N = 96 mice). RESULTS: Engraftment studies demonstrated that the microbiome of IBD in remission could have variable effects on the ileum of CD-prone mice (pro-inflammatory, nonmodulatory, or anti-inflammatory), depending on the human donor. Fecal microbiota transplantation achieved a 95% ± 0.03 genus-level engraftment of human gut taxa in mice, as confirmed at the operational taxonomic unit level. In most donors, microbiome colonization abundance patterns remained consistent over 60 days. Microbiome-based metabolic predictions of GF mice with Crohn's or ileitic-mouse donor microbiota indicate that chronic amino/fatty acid (valine, leucine, isoleucine, histidine; linoleic; P < 1e-15) alterations (and not bacterial virulence markers; P > 0.37) precede severe ileitis in mice, supporting their potential use as predictors/biomarkers in human CD. CONCLUSION: The gut microbiome of IBD remission patients is not necessarily innocuous. Characterizing the inflammatory potential of each microbiota in IBD patients using mice may help identify the patients' best anti-inflammatory fecal sample for future use as an anti-inflammatory microbial autograft during disease flare-ups.

Comparative analysis of atmospheric radiative transfer models using the Atmospheric Look-up table Generator (ALG) toolbox (version 2.0).

Atmospheric radiative transfer models (RTMs) are software tools that help researchers in understanding the radiative processes occurring in the Earth's atmosphere. Given their importance in remote sensing applications, the intercomparison of atmospheric RTMs is therefore one of the main tasks used to evaluate model performance and identify the characteristics that differ between models. This can be a tedious tasks that requires good knowledge of the model inputs/outputs and the generation of large databases of consistent simulations. With the evolution of these software tools, their increase in complexity bears implications for their use in practical applications and model intercomparison. Existing RTM-specific graphical user interfaces are not optimized for performing intercomparison studies of a wide variety of atmospheric RTMs. In this paper, we present the Atmospheric Look-up table Generator (ALG) version 2.0, a new software tool that facilitates generating large databases for a variety of atmospheric RTMs. ALG facilitates consistent and intuitive user interaction to enable the running of model executions and storing of RTM data for any spectral configuration in the optical domain. We demonstrate the utility of ALG in performing intercomparison studies of radiance simulations from broadly used atmospheric RTMs (6SV, MODTRAN, and libRadtran) through global sensitivity analysis. We expect that providing ALG to the research community will facilitate the usage of atmospheric RTMs to a wide range of applications in Earth observation.

TWEAK/Fn14 Is Overexpressed in Crohn's Disease and Mediates Experimental Ileitis by Regulating Critical Innate and Adaptive Immune Pathways.

BACKGROUND & AIMS: Crohn's disease (CD) is a debilitating inflammatory disorder that affects more than 1.6 million people in North America alone. Members of the tumor necrosis factor superfamily are key regulators of intestinal inflammation; specifically, tumor necrosis factor-like weak inducer of apoptosis (TWEAK) and its receptor, fibroblast growth factor-inducible 14 (Fn14), are involved in normal and pathologic tissue remodeling. Our aim was to determine the role of TWEAK/Fn14 in CD and a murine model of CD-like ileitis (ie, SAMP1/YitFc [SAMP] strain). METHODS: SAMP mice deficient in Fn14 (SAMP × Fn14-/-) were developed and a detailed time-course study was performed evaluating ileal tissues by histology and stereomicroscopy, as well as quantitative polymerase chain reaction and NanoString technology (Seattle, WA). Reciprocal bone marrow chimeras were generated to assess the relevance of Fn14 in hematopoietic vs nonhematopoietic compartments. Surgically resected intestinal tissues and mucosal biopsy specimens from patients with CD, ulcerative colitis, and healthy controls were analyzed for the expression of TWEAK/Fn14 by quantitative polymerase chain reaction, Western blot, immunohistochemistry, and immunofluorescence. RESULTS: SAMP × Fn14-/- showed a marked decrease in ileitis severity at 20 weeks of age compared with SAMP WT controls. Bone marrow chimeras showed that Fn14 was required in both hematopoietic and nonhematopoietic compartments for ileitis to develop. Transcriptome data showed multiple cellular pathways regulated by Fn14 signaling. Finally, increased expression of TWEAK and Fn14 was observed in tissue lesions from CD patients compared with ulcerative colitis and healthy controls. CONCLUSIONS: TWEAK/Fn14 are up-regulated in CD, and also mediate experimental CD-like ileitis, by regulation of multiple innate and adaptive cellular pathways. Therefore, TWEAK/Fn14 may represent a novel therapeutic target for the treatment of small intestinal inflammation in CD.

Lipocalin 24p3 Induction in Colitis Adversely Affects Inflammation and Contributes to Mortality.

Recognition of microorganism associated molecular patterns by epithelial cells elicits signaling cascades resulting in the production of host defense proteins. Lipocalin 24p3 is purported to be one such protein. 24p3 binds prokaryotic and eukaryotic siderophores and by sequestering iron laden bacterial siderophores it was believed to restrict bacterial replication. As such mice deficient for 24p3 are susceptible to systemic infections. However, it is not clear whether deficiency of 24p3 on the gut mucosa contributes to inflammation. In line with 24p3's function as a bacteriostat, it would be reasonable to assume that deficiencies in the control of intestinal flora from 24p3 absence play a role in inflammatory intestinal diseases. Surprisingly, we show 24p3 is a contributor of inflammation and 24p3 deficiency protects mice from dextran sodium sulfate (DSS)-induced colitis. 24p3 was found to be a negative regulator of platelet-derived growth factor (PDGF), which helps maintain the integrity of the gut mucosa. Neutralization of PDGF-BB abrogated resistance of 24p3 null mice to DSS confirming the direct link between 24p3 and PDGF-BB. Finally, iron handling in wild-type and 24p3-null mice upon DSS treatment also differed. In summary, differential iron levels and enhanced expression of PDGF-BB in 24p3 null mice confers resistance to DSS.

Gradient-Based Automatic Lookup Table Generator for Radiative Transfer Models.

Physically based radiative transfer models (RTMs) are widely used in Earth observation to understand the radiation processes occurring on the Earth's surface and their interactions with water, vegetation, and atmosphere. Through continuous improvements, RTMs have increased in accuracy and representativity of complex scenes at expenses of an increase in complexity and computation time, making them impractical in various remote sensing applications. To overcome this limitation, the common practice is to precompute large lookup tables (LUTs) for their later interpolation. To further reduce the RTM computation burden and the error in LUT interpolation, we have developed a method to automatically select the minimum and optimal set of input-output points (nodes) to be included in an LUT. We present the gradient-based automatic LUT generator algorithm (GALGA), which relies on the notion of an acquisition function that incorporates: 1) the Jacobian evaluation of an RTM and 2) the information about the multivariate distribution of the current nodes. We illustrate the capabilities of GALGA in the automatic construction and optimization of MODTRAN-based LUTs of different dimensions of the input variables space. Our results indicate that when compared with a pseudorandom homogeneous distribution of the LUT nodes, GALGA reduces:1) the LUT size by >24%; 2) the computation time by 27%; and 3) the maximum interpolation relative errors by at least 10%. It is concluded that an automatic LUT design might benefit from the methodology proposed in GALGA to reduce interpolation errors and computation time in computationally expensive RTMs.