פרסומים

Tissue damage in chronic periodontal disease is driven by the host response to a dysbiotic microbiota, and not by bacteria directly. Among chronic inflammatory diseases of the oral cavity, inflammation and tissue damage around dental implants (peri-implantitis) is emerging as a major clinical challenge, since it is more severe and less responsive to treatment compared to inflammation around natural teeth. We tested whether oral fibroblasts from the periodontal ligament (PDLF), which are present around natural teeth but not around dental implants, actively regulate inflammatory responses to bacterial stimulation. We show that human PDLF down-regulate TNF-α post-transcriptionally in macrophages stimulated with the oral pathogen Porphyromonas gingivalis. Cell contact and secretion of IL-6 and IL-10 contribute to the modulation of inflammatory cytokine production. Although fibroblasts decreased TNF-α secretion, they enhanced the ability of macrophages to phagocytose bacteria. Surprisingly, donor matched oral fibroblasts from gingival tissues, or fibroblasts from peri-implant inflamed tissues were at least as active as PDLF in regulating macrophage responses to bacteria. In addition, priming fibroblasts with inflammatory mediators enhanced PDLF regulatory activity. A further understanding of the spectrum of fibroblast activities in inflammatory lesions is important in order to design ways to control inflammatory tissue damage.

Peri-implantitis is a major health concern, with unclear pathogenesis, and with no accessible animal models. Our aim was to establish a mouse model for peri-implantitis and to investigate mediators of inflammation.\\ Mice were divided into implanted versus non-implanted groups. Implants were inserted immediately following the extraction of the upper first molar. Four weeks following implantation, implanted and non-implanted mice were challenged with either Porphyromonas gingivalis or vehicle (eight mice in each subgroup, 32 mice in total). Alveolar bone loss and expression of inflammatory mediators in the soft tissue were assessed 42 days following infection.\\ Porphyromonas gingivalis infection induced greater bone loss around implants than around teeth. In non-infected animals, the presence of the implant correlated with elevated expression of Il-10, Foxp3 and Rankl/Opg ratio, while Tnf-α levels were decreased relative to tissue around teeth. Six weeks following infection, Tnf-α increased significantly while the expression of Foxp3 decreased in the tissue around the implants. No significant differences in anti- or pro-inflammatory mediators were found around teeth of infected, relative to non-infected mice.\\ Oral infection with P. gingivalis of mice with implants induced bone loss and a shift in gingival cytokine expression. This mouse model enables exploration of the pathogenesis of peri-implantitis and testing of novel treatments.

Book Review:

Vinitzky-Seroussi, Vered (2018) Perpetrator Trauma and Israeli Intifada Cinema Megamot 53.2: 300-303. (in Hebrew)

בספר הזה מוצעים תשעה-עשר עיונים (בפרק המבוא ובפרקים א–יח). רובם עוסקים בלשונות ובמסורות של יהדות המגרב. מקום מרכזי בספר תופסות הקהילות במרוקו, ועמן יש פרקים העוסקים בתעודות מקהילת גרדאיה שבדרום-אלג'יריה. כן מוצעים תיעוד של מנהגים ושל מעשים מקהילות אחדות ועיון נרחב בהם. רוב פרקי הספר מבוססים על כתבי יד ותעודות הנמצאים באוסף כתבי היד היהודיים מצפון-אפריקה בספריית אוניברסיטת ייל. אחרי המבוא ושמונה-עשר הפרקים המוצעים בחמשת השערים הראשונים מובאים בשער השישי שלושה נספחים. אף שאינם מוגשים כפרקי מחקר, יש בהם תיעוד מבורר. שני הנספחים הראשונים מוקדשים לארבעה מסרנים שלא מעט ממחקריו של המחבר התבססו על מסירותיהם בכתב או בעל פה.

Whereas type I interferons (IFNs-I) were proposed to be elevated in human periodontitis, their role in the disease remains elusive. Using a bacterial-induced model of murine periodontitis, we revealed a prolonged elevation in IFN-I expression. This was due to the downregulation of TAM signaling, a major negative regulator of IFN-I. Further examination revealed that the expression of certain TAM components was reduced as a result of prolonged degradation of MYD88 by the infection. As a result of such prolonged IFN-I production, innate immunological functions of the gingiva were disrupted, and CD4+ T cells were constitutively primed by dendritic cells, leading to elevated RANKL expression and, subsequently, alveolar bone loss (ABL). Blocking IFN-I signaling restored proper immunological function and prevented ABL. Importantly, a loss of negative regulation on IFN-I expression by TAM signaling was also evident in periodontitis patients. These findings thus suggest a role for IFN-I in the pathogenesis of periodontitis.

Porphyromonas gingivalis is a gram-negative anaerobic periodontal pathogen that persists in dysbiotic mixed-species biofilms alongside a dense inflammatory infiltrate of neutrophils and other leukocytes in the subgingival areas of the periodontium. Toll-like receptor 2 (TLR2) mediates the inflammatory response to P. gingivalis and TLR2-deficient mice resist alveolar bone resorption following oral challenge with this organism. Although, MyD88 is an adaptor protein considered necessary for TLR2-induced inflammation, we now report for the first time that oral challenge with P. gingivalis leads to alveolar bone resorption in the absence of MyD88. Indeed, in contrast to prototypical TLR2 agonists, such as the lipopeptide Pam3CSK4 that activates TLR2 in a strictly MyD88-dependent manner, P. gingivalis strikingly induced TLR2 signaling in neutrophils and macrophages regardless of the presence or absence of MyD88. Moreover, genetic or antibody-mediated inactivation of TLR2 completely reduced cytokine production in P. gingivalis-stimulated neutrophils or macrophages, suggesting that TLR2 plays a non-redundant role in the host response to P. gingivalis. In the absence of MyD88, inflammatory TLR2 signaling in P. gingivalis-stimulated neutrophils or macrophages depended upon PI3K. Intriguingly, TLR2-PI3K signaling was also critical to P. gingivalis evasion of killing by macrophages, since their ability to phagocytose this pathogen was reduced in a TLR2 and PI3K-dependent manner. Moreover, within those cells that did phagocytose bacteria, TLR2-PI3K signaling blocked phago-lysosomal maturation, thereby revealing a novel mechanism whereby P. gingivalis can enhance its intracellular survival. Therefore, P. gingivalis uncouples inflammation from bactericidal activity by substituting TLR2-PI3K in place of TLR2-MyD88 signaling. These findings further support the role of P. gingivalis as a keystone pathogen, which manipulates the host inflammatory response in a way that promotes bone loss but not bacterial clearance. Modulation of these host response factors may lead to novel therapeutic approaches to improve outcomes in disease conditions associated with P. gingivalis.

The present work reports on the preparation and characterization of progesterone-loaded reverse hexagonal (H-II) mesophase based on a glycerol monooleate (GM0)/tricaprylin (TAG)/water mixture for transdermal application. Several compositions into which progesterone was quantitatively solubilized were selected and used in the present study in order to evaluate the effect of the hormone on structural transitions and characteristics. A GMO/TAG of 90:1 wt ratio with 20 wt% water was found to form H-II mesophases with relative high solubilization capacity of 4 wt% progesterone and a shelf life of over one year. The structures were identified by cross-polarized light microscopy (CPLM). Structural confirmations were obtained from small-angle X-ray scattering (SAXS) measurements. The hormone is solubilized at the interface of the H-II mesophase as confirmed by SAXS, rheology, FTIR, and DSC. The progesterone, which is loaded onto reverse hexagonal cylinders, leads to strengthening the hydrogen bonding and to better packing of the H-II mesophase, suggesting that progesterone is a kosmotropic agent. The reverse hexagonal mesophase seems to be a promising carrier for solubilization of progesterone. (C) 2016 Elsevier B.V. All rights reserved.

Previous studies suggest that the link between obsessive–compulsive (OC) symptoms and moral thought–action fusion (TAF) depends on religion; however, no study has compared Muslim and Jewish samples. We examined the relationships between OC symptoms, scrupulosity, religiosity, and moral TAF in Israeli Muslims and Jews. Religiosity was not associated with elevations in OC symptoms, although religiosity correlated with scrupulosity across the entire sample after controlling for depression and anxiety. Moral TAF was related to scrupulosity across the entire sample. The Muslim group had higher levels of OC symptoms, scrupulosity, and depressive symptoms than did the Jewish group, but the groups were equally religious. In addition, Muslims scored higher than did Jews on moral TAF even after controlling for symptoms; however, moral TAF was not related to scrupulosity within the Muslim group. In combination, these results imply that moral TAF depends on cultural and religious factors and does

Background Previous studies have indicated that obsessive-compulsive disorder (OCD) might have a reduced placebo response compared to other anxiety-related disorders including generalized anxiety disorder, panic disorder, post-traumatic stress disorder, and social anxiety disorder. No previous analysis has directly compared antidepressant and placebo responses between OCD and these conditions.

The quantification of spatial rainfall is critical for distributed hydrological modeling. Rainfall spatial patterns generated by similar weather conditions can be extremely diverse. This variability can have a significant impact on hydrological processes. Stochastic simulation allows generating multiple realizations of spatial rainfall or filling missing data. The simulated data can then be used as input for numerical models to study the uncertainty on hydrological forecasts. In this paper, we use the direct sampling technique to generate stochastic simulations of high-resolution (1 km) daily rainfall fields, conditioned by elevation and weather state. The technique associates historical radar estimates to variables describing the daily weather conditions, such as the rainfall type and mean intensity, and selects radar images accordingly to form a con- ditional training image set of each day. Rainfall fields are then generated by resampling pixels from these images. The simulation at each location is conditioned by neighbor patterns of rainfall amount and eleva- tion. The technique is tested on the simulation of daily rainfall amount for the eastern Mediterranean. The results show that it can generate realistic rainfall fields for different weather types, preserving the temporal weather pattern, the spatial features, and the complex relation with elevation. The concept of conditional training image provides added value to multiple-point simulation techniques dealing with extremely non- stationary heterogeneities and extensive data sets.

We prove that ω-categorical dp-minimal groups are nilpotent-by-finite, a small step in the general direction of proving this for NIP ω-categorical groups. We also show that in dp-minimal definably amenable groups, f-generic global types are strongly f-generic.

Insulin loading into the Hu mesophases was examined as a function of its concentration, with addition of glycerol as a cosolvent and with addition of phosphatidylcholine (PC) as a structural stabilizer. The structural properties, the molecular interactions, the viscoelastic properties, and the dynamic behavior were investigated by SAXS, ATR-FTIR, and rheological measurements. Insulin release was then monitored and analyzed. Insulin incorporation into the Hu systems shrank the cylinders as it competed with the lipids in water-bonding. Insulin interrupted the interface while increasing tmax and creating a more solid-like response. Upon addition of PC, cooperative flow behavior was detected, which is probably the reason for increase in insulin cumulative release from 28% to 52% after 300 min. In the presence of glycerol, the system was less cooperative but insulin was more compactly folded, resulting in a slight improvement in insulin release (up to 6%). Addition of both PC and glycerol caused the maximum release (55%). The addition of additives into the H-11 system demonstrates how structural modifications can improve insulin release, and influence future design of encapsulated drug delivery systems. (C) 2016 Elsevier Inc. All rights reserved.

Objective: Individuals with schizophrenia demonstrate cognitive, social cognitive, and motivational deficits that contribute to impairment in real-world functioning. In the current study, we investigated the effects of supplementing computerized neurocognitive training with social cognitive exercises, as compared with neurocognitive training alone. Method: In this ongoing, double-blind, randomized controlled trial of 111 participants with psychosis, we compare the effects of supplementing intensive targeted cognitive training with social cognitive training exercises (TCT + SCT) with the effects of targeted cognitive training alone (TCT-only). Participants were assessed on cognition, symptoms, functional capacity, and functional outcomes, as well as social cognition and measures related to reward processing. Results: Both treatment groups showed significant improvement in multiple cognitive domains and improvement in functional capacity. However, as predicted, TCT + SCT group participa