Epithelial microRNAs regulate gut mucosal immunity via epithelium-T cell crosstalk.

Colonic homeostasis entails epithelium-lymphocyte cooperation, yet many participants in this process are unknown. We show here that epithelial microRNAs mediate the mucosa-immune system crosstalk necessary for mounting protective T helper type 2 (T(H)2) responses. Abolishing the induction of microRNA by gut-specific deletion of Dicer1 (Dicer1(Δgut)), which encodes an enzyme involved in microRNA biogenesis, deprived goblet cells of RELMß, a key T(H)2 antiparasitic cytokine; this predisposed the host to parasite infection. Infection of Dicer1(Δgut) mice with helminths favored a futile T(H)1 response with hallmarks of inflammatory bowel disease. Interleukin 13 (IL-13) induced the microRNA miR-375, which regulates the expression of TSLP, a T(H)2-facilitating epithelial cytokine; this indicated a T(H)2-amplification loop. We found that miR-375 was required for RELMß expression in vivo; miR-375-deficient mice had significantly less intestinal RELMß, which possibly explains the greater susceptibility of Dicer1(Δgut) mice to parasites. Our findings indicate that epithelial microRNAs are key regulators of gut homeostasis and mucosal immunity.

The proteasome regulator PI31 is required for protein homeostasis, synapse maintenance, and neuronal survival in mice.

Proteasome-mediated degradation of intracellular proteins is essential for cell function and survival. The proteasome-binding protein PI31 (Proteasomal Inhibitor of 31kD) promotes 26S assembly and functions as an adapter for proteasome transport in axons. As localized protein synthesis and degradation is especially critical in neurons, we generated a conditional loss of PI31 in spinal motor neurons (MNs) and cerebellar Purkinje cells (PCs). A cKO of PI31 in these neurons caused axon degeneration, neuronal loss, and progressive spinal and cerebellar neurological dysfunction. For both MNs and PCs, markers of proteotoxic stress preceded axonal degeneration and motor dysfunction, indicating a critical role for PI31 in neuronal homeostasis. The time course of the loss of MN and PC function in developing mouse central nervous system suggests a key role for PI31 in human neurodegenerative diseases.

International questionnaire study on systemic antibiotics in endodontics. Part 1. Prescribing practices for endodontic diagnoses and clinical scenarios.

OBJECTIVES: Part 1 of this two-part study aims to investigate systemic antibiotics (SA) prescribing practices for various endodontic diagnoses and clinical scenarios by general practitioners, post-graduate students and endodontists in Israel and the former Soviet Union (FSU) states. MATERIALS AND METHODS: A total of 7500 dentists from Israel and FSU states were invited to fill in an online questionnaire. The questionnaire consisted the SA prescribing for endodontic diagnoses and clinical scenarios (post operative pain, post apical surgery and post avulsion). The international guidelines of the European Society of Endodontology and the American Association of Endodontists were used as the standard of correct practice. RESULTS: A total of 1310 dentists (response rate of 17.46%, 498 Israeli and 812 FSU dentists) completed the survey. The rates of prescription SA among the Israeli and the FSU respondents for non-recommended diagnoses and clinical scenarios were 24.75% and 11.42% (P>0.05), 16.57% and 16.17% (P>0.05) respectively. The rates of prescription SA among the Israeli and the FSU respondents for recommended diagnoses and clinical scenarios were 63.39% and 62.9% (P>0.05), 27.2% and 13.9% (P>0.05) respectively. CONCLUSIONS: There are gaps between the recommended protocols for prescribing SA for patients with various endodontic diagnoses and clinical scenarios and the actual practices among Israeli and FSU dentists. Continuing education of dentists must be encouraged in order to improve SA prescription practice according to international guidelines. CLINICAL RELEVANCE: When not indicated, prescription of systemic antibiotics might lead to antimicrobial resistance, while non-prescription, when required, might have negative repercussions on the patient's health. Knowledge of the prescription habits of dentists in the endodontic practice will help prevent harmful situations.

Vitamin D and Gastrointestinal Cancers: A Narrative Review.

Calcitriol (1,25(OH)2D3) performs various activities throughout the body. Although low serum 25-hydroxyvitamin D [25(OH)D] levels are associated with several disease processes such as risk of fractures and falls, hypertension, cardiovascular disease, and diabetes mellitus, recent evidence attests that this important hormone also regulates several cellular pathways involved in cancer development and progression. Calcitriol modulates several genes controlling gut physiology and calcium homeostasis and also maintains the integrity of epithelial barriers, regulates the absorption of phosphate and calcium, and modulates host defense against pathogens and inflammatory response by interplaying with several types of secretory and immune cells. Vitamin D deficiency is significantly related to increased risk of developing certain types of cancer. This deficiency can be prevented by vitamin D supplementation which is both economical and safe. This can lower the risk of developing cancer and also improve the prognosis of patients with gastrointestinal malignancy, but epidemiological data remain inconsistent. Several retrospective observational studies have demonstrated the benefits of vitamin D supplementation, but a few randomized controlled trials have not seemingly supported the beneficial role of vitamin D supplementation in gastrointestinal cancers. Therefore, in this literature review, we aimed to examine the possible role of vitamin D in gastrointestinal malignancies, including gastric, esophageal, pancreatic, hepatic, and colorectal cancers.

CBCT analyses of advanced cervical resorption aid in selection of treatment modalities: a retrospective analysis.

OBJECTIVES: The selection of treatment for advanced (classes 3 and 4) invasive cervical resorption (ICR) based on a two-dimensional periapical radiograph is challenging. The purpose of the present study is to describe different treatment approaches for advanced invasive cervical resorption based on cone-beam computed tomography evaluation. MATERIALS AND METHODS: All cases of advanced ICR based on CBCT evaluation in our endodontic department between 2011 and 2016 were included in the study. The dimension, circumferential, and coronal-cervical locations of the entry point of the resorption tissue into the tooth were evaluated. The selected treatment approach for each case was documented, and all the data were summarized and analyzed. RESULTS: Twenty-three cases of advanced ICR were included in the study. Approximately, 74% were diagnosed in stage 4, and 26% were diagnosed in stage 3. The narrow entry point was identified in 43% (10 cases), while in 57% (13) of cases, the entry point was wide. Circumferentially, 70% (16) were located on the proximal side. Coronal-cervically, 43% (10) were located more than 1.5 mm above the crestal bone. All narrow entry point cases were treated using a minimally invasive technique, while different treatment approaches were chosen for cases with a wide entry point. CONCLUSIONS: The present study proposes different treatment approaches for advanced ICR based on CBCT. The CBCT evaluation of the entry point may facilitate choosing the appropriate treatment approach for advanced ICR cases. CLINICAL RELEVANCE: The description of different treatment approaches for advanced invasive cervical resorption based on cone-beam computed tomography evaluation enables the clinician to choose the optimal treatment approach for each advanced ICR case.

A Humanized Monoclonal Antibody against Heat Shock Protein 60 Suppresses Murine Arthritis and Colitis and Skews the Cytokine Balance toward an Anti-Inflammatory Response.

We have previously shown that naturally occurring as well as acquired Abs against the Mycobacterium tuberculosis heat shock protein (HSP)65 protect against the induction of murine autoimmune inflammatory arthritis. In the present work, we have studied the anti-inflammatory effect of prozumab, a humanized anti-HSP mAb in murine inflammatory arthritis and colitis, and its effects on cytokine secretion. Prozumab was shown to bind to HSP60, the highly conserved mammalian homolog of the bacterial protein, and it was found to be effective in protecting and suppressing autoimmune arthritis in the models of adjuvant arthritis and collagen-induced arthritis in rats and mice, respectively, as well as in acute hapten-mediated colitis and chronic, spontaneous colitis models. Mechanistically, prozumab induces IL-10 secretion from naive human PBMCs and suppresses the secretion of IFN-γ and IL-6 from anti-CD3-activated human PBMCs. These findings make prozumab a promising potential drug for treating human rheumatoid arthritis and inflammatory bowel disease, as well as a wide range of autoimmune inflammatory diseases.

Diagnosis of Cytomegalovirus Infection during Exacerbation of Ulcerative Colitis.

BACKGROUND/AIMS: The role of cytomegalovirus (CMV) reactivation during exacerbations of ulcerative colitis (UC) is yet a matter of debate, and assessment of CMV infection in UC patients remains an ongoing challenge. We aimed to identify associated parameters and compare detection methods for CMV infection during UC exacerbation. METHODS: Clinical, pathological and virological parameters were retrospectively analyzed in all patients hospitalized in our institution for UC exacerbation between January 2009 and April 2015, who underwent full evaluation for CMV infection in colonic tissue by histopathology, immunohistochemistry (IHC) and CMV-PCR. RESULTS: Of 28 patients who underwent full examination for tissue CMV-infection, 13 (46.4%) were found to be positive for CMV. Tissue CMV-PCR was more sensitive for the detection of CMV infection than histopathology and IHC. CMV-positive patients had a statistically higher frequency of recent steroid treatment and fever, with higher mean partial Mayo scores and lower mean albumin levels. There were no significant differences between CMV-positive and CMV-negative patients in terms of age, severity of colitis and disease duration. In a multivariable model, only recent steroid treatment and fever were independently associated with colonic CMV infection. CONCLUSIONS: This study provides a clinical model to detect the presence of CMV infection in patients hospitalized with UC exacerbation, which could direct proper investigation and facilitate timely empirical therapy.

C-shaped canals-prevalence and root canal configuration by cone beam computed tomography evaluation in first and second mandibular molars-a cross-sectional study.

OBJECTIVES: C-shaped root canal configuration is an unusual root canal morphology and one of the most often anatomical variations in root canal systems of second mandibular molars. The purpose of this study was to assess the prevalence, symmetry and configuration of C-shaped canals in first and second mandibular molars in an Israeli population using cone beam computed tomography (CBCT). MATERIALS AND METHODS: One thousand twenty Israel patients' CBCT scans were screened and evaluated. First and second mandibular molars with C-shaped canals were identified. Prevalence configuration along the root and symmetry were analyzed, and new radicular groove classification was proposed. RESULTS: Total of 1465 mandibular second molars and 1229 mandibular first molars were evaluated. The overall prevalence of C-shaped canals in first and second mandibular molars was 0.16 and 4.6%, respectively. No significant difference was found by gender or side of occurrence. The unilateral prevalence of C-shaped canals in mandibular second molars was 55%. C-shaped canal configuration changed along the root in 63% of the cases. CONCLUSIONS: The prevalence of C-shaped canals in first and second mandibular molars in the Israeli population is low in comparison to other subpopulations. Clinicians should be aware of the possible asymmetry, different configuration along the root, and the location of danger zone of this anatomic variation during clinical work. CLINICAL RELEVANCE: CBCT is an efficient three dimensional radiographic examination for evaluation of C-shape root canal configuration. CBCT may help the clinicians during clinical work for considering appropriate cleaning, shaping, and obturation technique according to the characteristic of C-shape root canal configuration.

Endodontic radiography - what's displaying the radiograph? The yield of commercial computer screens vs. DICOM calibrated medical screens in endodontic radiography.

OBJECTIVE: A comparison between commercial computer screens and DICOM-calibrated medical screens for characterizing anatomy and diagnosing dental pathologies was performed. The aim of this study was to evaluate and compare the ability of each of those screens to identify root apices and widening of the periodontal ligament (PDL) in the posterior maxillary area. MATERIALS AND METHODS: Digital X-ray images of 53 maxillary molar teeth were examined by means of a commercial computer screen and again two months later with a DICOM screen to compare their ability to help identify and diagnose PDL widening and to locate the root apices of those teeth. RESULTS: The DICOM screen had a significantly better ability to identify widened PDLs (from 31.4% to 34.8% of the cases compared to 19% to 26.1% for the commercial screens, P < .001), depending upon the observer. The DICOM screen was also significantly superior in depicting the root apices compared to the commercial screens (from 77.4% to 83.6% of the cases compared to 56% to 66.7% for the commercial screens, P < 0.001), depending upon the observer. CONCLUSION: DICOM-calibrated medical screens were significantly superior to commercial computer screens for identifying widened PDLs and locating the root apex in the posterior maxillary area.

The ability of different compositions of calcium silicate and epoxy sealers to withstand gutta percha removal via in vitro pull-out testing.

OBJECTIVE: examination of the influence of chemical composition changes on the ability of sealers to withstand a pull-out test. MATERIALS AND METHODS: Fifty distal or palatal canals of extracted teeth were prepared by Dc Taper files. The teeth were divided into five groups: AH Plus, BJM RCS, Total Fill BC,AH Plus Bioceramic and a group with Gutta Percha with no sealer added. Ten days after obturation, each cone was subjected to the "pull-out test" with the Shimadzo Universal Testing Machine until it was torn or removed from the canal. A force to Stroke graph was generated and the maximum vertex of this graph was recorded. The number of times the cone was torn or removed was recorded. RESULTS: The amount of force needed to remove or rupture the cone was significantly higher in all sealer groups compared to the AH Plus Bioceramic group. The force needed for the AH Plus group was double that needed for the AH Plus Bioceramic group 4 (1.87 ± 0.53 N vs 0.93 ± 0.48 N, respectively, P < 0.001). All of the cones (n = 10) in the AH Plus Bio Ceramic Sealer group were removed in their entirety (P = 0.01 compared to each of the other groups). CONCLUSIONS: The addition of macromolecules to epoxy sealer does not change the material's ability to withstand the pull-out test. Decreasing the amount of tri- and di-calcium silicate compounds combined with increasing amounts of zirconium oxide in a Bioceramic sealer significantly decreased the material's ability to withstand the pull-out test.

Systemic antibiotics in endodontics-International questionnaire study: Choice of types, dosage, loading and duration.

The aim of the study was to investigate the systematic antibiotics (SAs) prescribing practices in the endodontic practice worldwide. 7500 general practitioners, postgraduate students and endodontists from Israel and the former Soviet Union (FSU) states were invited to fill in an online questionnaire. The first-choice SA was amoxicillin (80.12%) among the Israeli (p < 0.05) and amoxicillin + clavulanic acid (88.92%) among the FSU respondents (p < 0.05). The first-choice SA for patients with penicillin allergy was clindamycin (78.2%) among Israeli and azithromycin (35.96%) among the FSU respondents (p < 0.05). Most of the respondents from Israel as well as from the FSU reported prescribing SA for 5-7 days. Only 6.24% of the former and 2.59% of the latter reported prescribing SA until the symptoms disappeared (p > 0.05). The usage of SAs is often not in accordance with existing international guidelines and differs among different dentist's populations.

Delayed fecal incontinence following surgery for anal fissure.

PURPOSE: The surgical treatment of chronic anal fissure is basically done by therapeutic controlled damage to the internal anal sphincter. While fecal incontinence is a well-documented early complication of anal fissure surgery, few data are available about delayed incontinence. The aim of the present study was to assess whether surgical treatment of anal fissures may contribute to the development of delayed anal incontinence. METHODS: A retrospective review of patients referred to the Pelvic Floor Laboratory for physiological evaluation of anal incontinence between 1992 and 2009. All patients, diagnosed with anal fissures, who underwent anal dilatation or partial lateral internal sphincterotomy and developed incontinence at least 4 years after the surgery were included. Controls were patients with delayed anal incontinence after obstetric injury. RESULTS: A total of 21 patients with delayed post-anal fissure surgery incontinence (nine women and 12 men) were identified. The mean (SE) age of incontinence onset in this group of patients was 51.5 (±2), which was 8 years younger than the rest of the 363 incontinent patients (p < 0.001). Time from presumed anal sphincter damage to the onset of incontinence was significantly shorter in the group of past anal-fissure-surgery patients compared to post-obstetric trauma patients (mean difference 15 years, p < 0.001). The severity of incontinence was higher in post-obstetric trauma patients. CONCLUSIONS: Fecal incontinence may present as a late complication of anal fissure surgery. Incontinence may be associated with other cofactors accumulating over time or, more likely, anal fissure surgery may accelerate the physiologic age-related weakening of the anal sphincter mechanism. Candidates for anal fissure surgery should be informed regarding this possible outcome.

Long-term dental implications of infant oral mutilation: a case series.

Infant oral mutilation (IOM) is a ritual ceremony practised mostly in African cultures, in which the primary tooth bud of the deciduous canine is extracted. Complications and risks of IOM include pain, heavy bleeding and infection that may deteriorate to life-threating conditions. The main long-term consequence of IOM is future dental abnormalities. The scientific literature lacks in-depth analyses of the dental sequelae of this practice among adults who underwent it, and particularly of the aspect of dental treatment. Eight new cases of IOM are presented in this case series, with emphasis on dental diagnosis and treatment modalities. We describe different outcomes of this practice, such as enamel hypoplasia and crown deformations with later necrosis and infection of the root canal system, severe discolouration, immature root apex, impaction of a canine, failure of development and missing lower permanent incisors and canines, an odontoma-like structure, severe periodontal defect and root dilaceration. Familiarity with the practice of IOM is vital in order to identify its manifestations and arrive at the correct diagnosis and optimal course of treatment.

Weight disorders and associated morbidity among young adults in Israel 1990-2003.

BACKGROUND: The aim of this study was to evaluate the change in prevalence of weight disorders and associated morbidity among young adults. METHODS: Records of 1,021,211 subjects aged 17, who underwent a medical examination, were included. RESULTS: Among female subjects the prevalence of underweight increased steadily from 13.2% to 15.6%. No statistically significant trend was found among male subjects. Among male subjects a twofold increase in the prevalence of obesity was observed, while among female subjects there was an increase of 57%. In obese versus normal-weight male subjects the OR, adjusted for origin, education and year of recruitment, of having high blood pressure, diabetes type 2 and type 1 and hyperlipidemia were 4.1 (95%CI 3.89-4.34), 5.56 (5.09-6.07), 1.00 (0.30-3.27) and 16.07 (8.29-31.15), respectively. For obese female nominees the OR were 5.56 (95%CI 5.09-6.07), 4.42 (3.90-5.00), 3.59 (0.77-16.87) and 9.00 (4.36-18.60), respectively. CONCLUSION: A significant increase in prevalence of obesity was observed with an increased risk of having diabetes type 2, hyperlipidemia and high blood pressure. An increase in the prevalence of being underweight was observed in female subjects. Policy makers have to plan appropriate effective interventions that will promote a healthy lifestyle in adolescents and reduce obesity on the one hand, and avoid the fashion for being underweight, with its possible development to anorexia, on the other.

Accuracy and stability of electronic apex locator length measurements in root canals with wide apical foramen: an ex vivo study.

The aim of the current study was to determine the accuracy of electronic apex locator (EAL) measurements when using files of different sizes in roots with wide apical foramina while considering a new parameter of stability of EAL reading. Ten teeth with straight roots were subjected to a sequential widening of the apical foramen to 0.6, 0.7, and 0.8 mm. The roots were embedded after each enlargement stage in an alginate mold and subjected to EAL readings. Measurements were done using sequential K-file sizes and the self-adjusting file (SAF). Measurement stability was introduced as a new additional parameter. As the difference between the file size used and the apical diameter of the canal decreases, the results obtained were more accurate and stable. The stability and accuracy of the measurements coincided with each other in a statistically significant manner. Within the limitations of the present ex vivo study, it may be concluded that in straight canals with wide apical foramina of 0.6-0.8 mm, both SS K-files which fit snugly to the walls of apical foramen and the SAF file may offer both accurate and stable EAL measurements.

Elderly bedridden patients with dementia use over one quarter of resources in internal medicine wards in an Israeli hospital.

BACKGROUND: Elderly bedridden patients with dementia (EBRPD) are a growing segment of the population. We aimed to describe acute care hospitalization of EBRPD in internal medicine wards: the prevalence of EBRPD, their impact on hospital resources and hospital ecology, one-year survival, and one-year readmission-free survival. METHODS: The study setting was the internal medicine division of one tertiary care hospital in Israel. We conducted a point-prevalence survey to measure the prevalence of EBRPD and the prevalence of multidrug-resistant organism (MDRO) carriage. We also conducted a retrospective chart review of EBRPD who were hospitalized in the internal medicine division in order to assess resource use, survival, and readmission. RESULTS: In the point prevalence surveys (N = 1667 patients), EBRPD comprised 24.3% of patients and 59.0% of mechanically ventilated patients. EBRPD were twice as likely to be colonized or infected by MDROs as other patients (39.3% vs. 18%, p < 0.001); thus, 41% of MDRO carriers during the survey days were EBRPD. In the retrospective study (N = 517 EBRPD), 80% of EBRPD received antibiotics; on average, they received an antibiotic on 87.7% of their hospital days. One-year survival was 35.6% and one-year readmission-free survival was 16.4%. CONCLUSIONS: Acute care hospitalization of EBRPD accounted for a high proportion of bed occupancy and ventilator use in internal medicine wards. EBRPD significantly increase the potential for MDRO transmission. Policymakers should seek alternatives to acute care hospitalization for EBRPD.

Factors associated with bleeding in elderly hospitalized patients treated with enoxaparin sodium : a prospective, open-label, observational study.

BACKGROUND: Despite a lack of clear recommendations to guide decision-making, reductions in enoxaparin sodium dosage in the elderly and in patients with mild and moderate renal dysfunction are common in patients with acute coronary syndrome. OBJECTIVE: To evaluate whether weight, age and renal function are associated with anti-factor Xa activity and with bleeding in elderly patients treated with enoxaparin sodium. METHOD: This was a prospective observational study of 156 elderly patients admitted consecutively to a general internal medicine ward with creatinine clearance >30 mL/min who were treated with enoxaparin sodium twice daily. Anti-factor Xa activity and bleeding events were documented in all patients. Statistical analyses were conducted to determine the effects of clinical characteristics such as renal dysfunction, age and bodyweight on these parameters. RESULTS: 156 patients (60% males, mean age 71.0 +/- 15.98 years) were studied. Therapeutic anti-factor Xa was observed in 85.3% of patients treated with enoxaparin sodium 0.61-0.8 mg/kg/12h, and in 82.6% of patients treated with enoxaparin sodium 0.81-1.1 mg/kg/12h. Minor or major bleeding was observed in 5.8% of patients, and was associated with a lower mean bodyweight (61.89 +/- 13.35 vs 74.30 +/- 13.24 kg for patients with no bleeding; p = 0.014). Bodyweight < or =55 kg was associated with bleeding with an odds ratio of 5.63 (95% CI 1.2, 25, p = 0.025). CONCLUSION: Low bodyweight is associated with a greater risk of bleeding despite a reduction in enoxaparin sodium dose according to weight. This finding supports the possibility that low bodyweight is an independent risk factor for enoxaparin sodium-related bleeding.

External invasive resorption: Possible coexisting factors and demographic and clinical characteristics.

The purpose of this retrospective study was to identify the coexisting factors for EIR and to characterise EIR clinically and demographically. All cases of EIR that were referred to the endodontic department between 2011 to 2016 and diagnosed by an endodontist were evaluated. Demographic and clinical characteristics were collected and evaluated. Thirty-eight cases of EIR diagnosed between 2011 and 2016 were included in the study. Seventy-one percent of EIR cases were misdiagnosed by general practitioners. The most affected teeth were the maxillary central incisors (29% of cases) and mandibular molars (26%). Sixty-eight percent of EIR cases were diagnosed in teeth with clinically normal pulp. Pulp necrosis was observed mainly in the advanced stages (class 3 and class 4) of EIR (75%) and in teeth with a history of trauma (63%). Histories of previous trauma and orthodontic treatment were reported in 29% and 23% of cases, respectively.

Toll-like receptors in inflammatory bowel disease-stepping into uncharted territory.

Ulcerative colitis and Crohn's disease are chronic relapsing-remitting inflammatory processes of the intestinal tract. The etiology of these diseases is currently unknown. However, inflammation is hypothesized to result from inappropriate activation of mucosal immunity by luminal antigens in genetically susceptible individuals. Toll-like receptors (TLRs) are a family of transmembrane proteins that act as microbial pattern recognition receptors. They are crucial initiators of innate immune responses. The role of TLRs in the pathogenesis of inflammatory bowel disease (IBD) has not been fully elucidated. In this review, we aim to analyze the available data connecting individual TLRs to intestinal inflammation and IBD.