Bacillus Coagulans GBI-30 (BC30) improves indices of Clostridium difficile-Induced colitis in mice

<p>Abstract</p> <p>Background</p> <p>Probiotics have beneficial effects in rodent models of <it>Clostridium difficile </it>(<it>C. diffiicle</it>)-induced colitis. The spore forming probiotic strain <it>Bacillus Coagulans </it>GBI-30, 6086 (BC30) has demonstrated anti-inflammatory and immune-modulating effects <it>in vitro</it>. Our goal was to determine if BC30 improved <it>C. difficile</it>-induced colitis in mice. Starting on study day 0, female C57BL/6 mice were dosed by oro-gastric gavage for 15 days with vehicle (saline) or BC30 (2 × 10⁹CFU per day). Mice in the <it>C. difficile </it>groups received an antibiotic mixture (study days 5 to 8 in the drinking water), and clindamycin (10 mg/kg, i.p., on study day 10). The <it>C. difficile </it>strain VPI 10463 was given by gavage at 10⁴CFU to induce colitis on day 11. On day 16, stools and colons were collected for further analyses.</p> <p>Results</p> <p>All mice treated with BC30 survived on study day 13, while two mice treated with vehicle did not survive. On day 12, a significant difference (p = 0.0002) in the percentage of mice with normal stools (66.7%) was found in the BC30/<it>C. difficile </it>group, as compared to the vehicle/<it>C. diffcile </it>group (13.0%). On study day 16, 23.8% of mice treated with BC30 had normal stools, while this value was 0% with vehicle treatment (p value = 0.0187). On this day, the stool consistency score for the BC30/<it>C. difficile </it>group (1.1 ± 0.2) was significantly lower (p < 0.05) than for the vehicle/<it>C. difficile </it>cohort (1.9 ± 0.2). BC30 modestly attenuated the colonic pathology (crypt damage, edema, leukocyte influx) that was present following <it>C. difficile infection</it>. Colonic MIP-2 chemokine contents (pg/2 cm colon) were: 10.2 ± 0.5 (vehicle/no <it>C. difficile</it>), 24.6 ± 9.5 (vehicle/<it>C. difficile</it>) and 16.3 ± 4.3 (BC30/<it>C. difficle</it>).</p> <p>Conclusion</p> <p>The probiotic BC30 improved some parameters of <it>C. difficile</it>-induced colitis in mice. BC30 prolonged the survival of <it>C. diffiicle </it>infected mice. Particularly, this probiotic improved the stool consistency of mice, in this infectious colitis model.</p

Association between visual impairment and sleep duration: analysis of the 2009 National Health Interview Survey (NHIS)

BACKGROUND: Visual impairment (VI) is associated with increased mortality and health factors such as depression and cardiovascular disease. Epidemiologic studies consistently show associations between sleep duration with adverse health outcomes, but these have not systematically considered the influence of VI. The aim of this study was to ascertain the independent association between VI and sleep duration using the National Health Interview Survey (NHIS) data. We also examined whether race/ethnicity influenced these associations independently of sociodemographic and medical characteristics. METHODS: Our analysis was based on the 2009 NHIS, providing valid sleep and vision data for 29,815 participants. The NHIS is a cross-sectional household interview survey utilizing a multistage area probability design. Trained personnel from the US census bureau gathered data during face-to-face interview and obtained socio-demographic, self-reported habitual sleep duration and physician-diagnosed chronic conditions. RESULTS: The mean age of the sample was 48 years and 56% were female. Short sleep and long sleep durations were reported by 49% and 23% of the participants, respectively. Visual impairment was observed in 10%. Multivariate-adjusted logistic regression models showed significant associations between VI and short sleep (OR = 1.6, 95% CI = 1.5-1.9 and long sleep durations (OR = 1.6, 95% CI = 1.3-1.9). These associations persisted in multivariate models stratified by race-ethnic groups. CONCLUSION: Visual impairment was associated with both short and long sleep durations. Analysis of epidemiologic sleep data should consider visual impairment as an important factor likely to influence the amount of sleep experienced habitually

Artificial Intelligence, Surveillance, and Big Data

The most important resource to improve technologies in the field of artificial intelligence is data. Two types of policies are crucial in this respect: privacy and data-sharing regulations, and the use of surveillance technologies for policing. Both types of policies vary substantially across countries and political regimes. In this paper, we examine how authoritarian and democratic political institutions can influence the quality of research in artificial intelligence, and the availability of large-scale datasets to improve and train deep learning algorithms. We focus mainly on the Chinese case, and find that – ceteris paribus – authoritarian political institutions continue to have a negative effect on innovation. They can, however, have a positive effect on research in deep learning, via the availability of large-scale datasets that have been obtained through government surveillance. We propose a research agenda to study which of the two effects might dominate in a race for leadership in artificial intelligence between countries with different political institutions, such as the United States and China.210

A Transparency Checklist for Carbon Footprint Calculations Applied within a Systematic Review of Virtual Care Interventions

Increasing concerns about climate change imply that decisions on the digitization of healthcare should consider evidence about its carbon footprint (CF). This study aims to develop a transparency catalogue for reporting CF calculations, to compare results, and to assess the transparency (reporting quality) of the current evidence of virtual care (VC) intervention. We developed a checklist of transparency criteria based on the consolidation of three established standards/norms for CF calculation. We conducted a systematic review of primary studies written in English or German on the CF of VC interventions to check applicability. Based on our checklist, we extracted methodological information. We compared the results and calculated a transparency score. The checklist comprises 22 items in the aim, scope, data and analysis categories. Twenty-three studies out of 1466 records were included, mostly addressing telemedicine. The mean transparency score was 38% (minimum 14%, maximum 68%). On average, 148 kg carbon dioxide equivalents per patient were saved. Digitization may have co-benefits, improving care and reducing the healthcare CF. However, the evidence for this is weak, and CF reports are heterogeneous. Our transparency checklist may serve as a reference for developing a standard to assess the CF of virtual and other healthcare and public health services

A retrospective chart review to identify perinatal factors associated with food allergies

Abstract Background Gut flora are important immunomodulators that may be disrupted in individuals with atopic conditions. Probiotic bacteria have been suggested as therapeutic modalities to mitigate or prevent food allergic manifestations. We wished to investigate whether perinatal factors known to disrupt gut flora increase the risk of IgE-mediated food allergies. Methods Birth records obtained from 192 healthy children and 99 children diagnosed with food allergies were reviewed retrospectively. Data pertaining to delivery method, perinatal antibiotic exposure, neonatal nursery environment, and maternal variables were recorded. Logistic regression analysis was used to assess the association between variables of interest and subsequent food allergy diagnosis. Results Retrospective investigation did not find perinatal antibiotics, NICU admission, or cesarean section to be associated with increased risk of food allergy diagnosis. However, associations between food allergy diagnosis and male gender (66 vs. 33; p=0.02) were apparent in this cohort. Additionally, increasing maternal age at delivery was significantly associated with food allergy diagnosis during childhood (OR, 1.05; 95% CI, 1.017 to 1.105; p=0.005). Conclusions Gut flora are potent immunomodulators, but their overall contribution to immune maturation remains to be elucidated. Additional understanding of the interplay between immunologic, genetic, and environmental factors underlying food allergy development need to be clarified before probiotic therapeutic interventions can routinely be recommended for prevention or mitigation of food allergies. Such interventions may be well-suited in male infants and in infants born to older mothers.</p

IL-12 Enhances the Antitumor Actions of Trastuzumab via NK Cell IFN-γ Production

The antitumor effects of therapeutic mAbs may depend on immune effector cells that express FcRs for IgG. IL-12 is a cytokine that stimulates IFN-γ production from NK cells and T cells. We hypothesized that coadministration of IL-12 with a murine anti-HER2/neu mAb (4D5) would enhance the FcR-dependent immune mechanisms that contribute to its antitumor activity. Thrice-weekly therapy with IL-12 (1 μg) and 4D5 (1 mg/kg) significantly suppressed the growth of a murine colon adenocarcinoma that was engineered to express human HER2 (CT-26(HER2/neu)) in BALB/c mice compared with the result of therapy with IL-12, 4D5, or PBS alone. Combination therapy was associated with increased circulating levels of IFN-γ, monokine induced by IFN-γ, and RANTES. Experiments with IFN-γ–deficient mice demonstrated that this cytokine was necessary for the observed antitumor effects of therapy with IL-12 plus 4D5. Immune cell depletion experiments showed that NK cells (but not CD4(+) or CD8(+) T cells) mediated the antitumor effects of this treatment combination. Therapy of HER2/neu-positive tumors with trastuzumab plus IL-12 induced tumor necrosis but did not affect tumor proliferation, apoptosis, vascularity, or lymphocyte infiltration. In vitro experiments with CT-26(HER2/neu) tumor cells revealed that IFN-γ induced an intracellular signal but did not inhibit cellular proliferation or induce apoptosis. Taken together, these data suggest that tumor regression in response to trastuzumab plus IL-12 is mediated through NK cell IFN-γ production and provide a rationale for the coadministration of NK cell-activating cytokines with therapeutic mAbs

Dopamine 5 receptor mediates Ang II type 1 receptor degradation via a ubiquitin-proteasome pathway in mice and human cells

Hypertension is a multigenic disorder in which abnormal counterregulation between dopamine and Ang II plays a role. Recent studies suggest that this counterregulation results, at least in part, from regulation of the expression of both the antihypertensive dopamine 5 receptor (D5R) and the prohypertensive Ang II type 1 receptor (AT1R). In this report, we investigated the in vivo and in vitro interaction between these GPCRs. Disruption of the gene encoding D5R in mice increased both blood pressure and AT1R protein expression, and the increase in blood pressure was reversed by AT1R blockade. Activation of D5R increased the degradation of glycosylated AT1R in proteasomes in HEK cells and human renal proximal tubule cells heterologously and endogenously expressing human AT1R and D5R. Confocal microscopy, Förster/fluorescence resonance energy transfer microscopy, and fluorescence lifetime imaging microscopy revealed that activation of D5R initiated ubiquitination of the glycosylated AT1R at the plasma membrane. The regulated degradation of AT1R via a ubiquitin/proteasome pathway by activation of D5R provides what we believe to be a novel mechanism whereby blood pressure can be regulated by the interaction of 2 counterregulatory GPCRs. Our results therefore suggest that treatments for hypertension might be optimized by designing compounds that can target the AT1R and the D5R

NK Cell–Mediated Antitumor Effects of a Folate-Conjugated Immunoglobulin Are Enhanced by Cytokines

Optimally effective antitumor therapies would not only activate immune effector cells, but engage them at the tumor. Folate-conjugated to immunoglobulin (F-IgG) could direct innate immune cells with Fc receptors to folate receptor–expressing cancer cells. F-IgG bound to human KB and HeLa cells, as well as murine L1210JF, a folate receptor (FR) overexpressing cancer cell line, as determined by flow cytometry. Recognition of F-IgG by NK cell Fc receptors led to phosphorylation of the ERK transcription factor and increased NK cell expression of CD69. Lysis of KB tumor cells by NK cells increased about 5-fold after treatment with F-IgG, an effect synergistically enhanced by treatment with IL2, IL12, IL15, or IL21 (P < 0.001). F-IgG also enhanced the lysis of chronic lymphocytic leukemia cells by autologous NK cells. NK cells significantly increased production of IFNγ, MIP-1α, and RANTES in response to F-IgG–coated KB target cells in the presence of the NK cell–activating cytokine IL12, and these coculture supernatants induced significant T cell chemotaxis P < 0.001). F-IgG–coated targets also stimulated FcR-mediated monocyte effector functions. Studies in a murine leukemia model confirmed the intratumoral localization and antitumor activity of F-IgG, as well as enhancement of its effects by IL12 (P = 0.05). The antitumor effect of this combination was dependent on NK cells and led to decreased tumor cell proliferation in vivo. Thus, F-IgG can induce an immune response against FR-positive tumor cells that is mediated by NK cells and can be augmented by cytokine therapy