Reprogramming the anti-tumor immune response via CRISPR genetic and epigenetic editing

Precise clustered regularly interspaced short palindromic repeats (CRISPR)-mediated genetic and epigenetic manipulation of the immune response has become a promising immunotherapeutic approach towards combating tumorigenesis and tumor progression. CRISPR-based immunologic reprograming in cancer therapy comprises the locus-specific enhancement of host immunity, the improvement of tumor immunogenicity and the suppression of tumor immunoevasion. To date, the ex vivo re-engineering of immune cells directed to inhibit the expression of immune checkpoints or to express synthetic immune receptors (chimeric antigen receptor therapy) has shown success in some settings, such as in the treatment of melanoma, lymphoma, liver and lung cancer. However, advancements in nuclease-deactivated CRISPR-associated nuclease-9 (dCas9)-mediated transcriptional activation or repression and Cas13-directed gene suppression presents novel avenues for the development of tumor immunotherapies. In this review, the basis for development, mechanism of action and outcomes from recently published Cas9-based clinical trial (genetic editing) and dCas9/Cas13-based pre-clinical (epigenetic editing) data are discussed. Lastly, we review cancer immunotherapy-specific considerations and barriers surrounding use of these approaches in the clinic

The Role of Religion on Suicidal Behavior, Attitudes and Psychological Distress in University Students: A Multinational Study

The purpose of this study was to determine the association of religion to suicidal behavior, attitudes and psychological distress in 5572 students from 12 countries by means of a self-report questionnaire. Our results showed that an affiliation with Islam was associated with reduced risk for suicide ideation, however affiliating with Orthodox Christianity and no religion was related to increased risk for suicide ideation. While affiliating with Buddhism, Catholic religion and no religion associated with lowered risk for attempting suicide, affiliation with Islam was related to heightened risk for attempting suicide. Affiliation with Hinduism, Orthodox Christianity, Protestantism, Catholicism, other religions and with no religion was associated with decreased risk for psychological distress but those reported affiliating with Islam evinced greater risk for psychological distress. The associations of the strength of religious belief to suicidal ideation and attempts were in the expected direction for most but it had a positive relation in respondents affiliating with Catholicism and other religions. Students reporting affiliation with Islam, Orthodox religion and Buddhism were the least accepting of suicide but they displayed a more confronting interpersonal style to an imagined peer with a suicidal decision. It was concluded that the protective function of religion in educated segments of populations (university students) and in university students residing in Muslim countries where freedom from religion is restricted or religion is normative and/or compulsory is likely to be limited. Our findings suggest that public policies supporting religious freedom may augment the protective function of religion against suicide and psychological distress

Three-year survival of single- and two-surface ART restorations in a high-caries child population

The aim of this study was to evaluate the survival of single- and two-surface atraumatic restorative treatment (ART) restorations in the primary and permanent dentitions of children from a high-caries population, in a field setting. The study was conducted in the rainforest of Suriname, South America. ART restorations, made by four Dutch dentists, were evaluated after 6 months, 1, 2, and 3 years. Four hundred seventy-five ART restorations were placed in the primary dentition and 54 in first permanent molars of 194 children (mean age 6.09 ± 0.48 years). Three-year cumulative survivals of single- and two-surface ART restorations in the primary dentition were 43.4 and 12.2%, respectively. Main failure characteristics were gross marginal defects and total or partial losses. Three-year cumulative survival for single-surface ART restorations in the permanent dentition was 29.6%. Main failure characteristics were secondary caries and gross marginal defects. An operator effect was found only for two-surface restorations. The results show extremely low survival rates for single- and two-surface ART restorations in the primary and permanent dentitions. The variable success for ART may initiate further discussion about alternative treatment strategies, especially in those situations where choices have to be made with respect to a well-balanced, cost-effective package of basic oral health care

Absence of carious lesions at margins of glass-ionomer cement and amalgam restorations: An update of systematic review evidence

<p>Abstract</p> <p>Background</p> <p>This article aims to update the existing systematic review evidence elicited by Mickenautsch et al. up to 18 January 2008 (published in the European Journal of Paediatric Dentistry in 2009) and addressing the review question of whether, in the same dentition and same cavity class, glass-ionomer cement (GIC) restored cavities show less recurrent carious lesions on cavity margins than cavities restored with amalgam.</p> <p>Methods</p> <p>The systematic literature search was extended beyond the original search date and a further hand-search and reference check was done. The quality of accepted trials was assessed, using updated quality criteria, and the risk of bias was investigated in more depth than previously reported. In addition, the focus of quantitative synthesis was shifted to single datasets extracted from the accepted trials.</p> <p>Results</p> <p>The database search (up to 10 August 2010) identified 1 new trial, in addition to the 9 included in the original systematic review, and 11 further trials were included after a hand-search and reference check. Of these 21 trials, 11 were excluded and 10 were accepted for data extraction and quality assessment. Thirteen dichotomous datasets of primary outcomes and 4 datasets with secondary outcomes were extracted. Meta-analysis and cumulative meta-analysis were used in combining clinically homogenous datasets. The overall results of the computed datasets suggest that GIC has a higher caries-preventive effect than amalgam for restorations in permanent teeth. No difference was found for restorations in the primary dentition.</p> <p>Conclusion</p> <p>This outcome is in agreement with the conclusions of the original systematic review. Although the findings of the trials identified in this update may be considered to be less affected by attrition- and publication bias, their risk of selection- and detection/performance bias is high. Thus, verification of the currently available results requires further high-quality randomised control trials.</p

The Role of Religion on Suicidal Behavior, Attitudes and Psychological Distress in University Students: A Multinational Study

The purpose of this study was to determine the association of religion to suicidal behavior, attitudes and psychological distress in 5572 students from 12 countries by means of a selfreport questionnaire. Our results showed that an affiliation with Islam was associated with reduced risk for suicide ideation, however affiliating with Orthodox Christianity and no religion was related to increased risk for suicide ideation. While affiliating with Buddhism, Catholic religion and no religion associated with lowered risk for attempting suicide, affiliation with Islam was related to heightened risk for attempting suicide. Affiliation with Hinduism, Orthodox Christianity, Protestantism, Catholicism, other religions and with no religion was associated with decreased risk for psychological distress but those reported affiliating with Islam evinced greater risk for psychological distress. The associations of the strength of religious belief to suicidal ideation and attempts were in the expected direction for most but it had a positive relation in respondents affiliating with Catholicism and other religions. Students reporting affiliation with Islam, Orthodox religion and Buddhism were the least accepting of suicide but they displayed a more confronting interpersonal style to an imagined peer with a suicidal decision. It was concluded that the protective function of religion in educated segments of populations (university students) and in university students residing in Muslim countries where freedom from religion is restricted or religion is normative and/or compulsory is likely to be limited. Our findings suggest that public policies supporting religious freedom may augment the protective function of religion against suicide and psychological distress

Chest trauma experience over eleven-year period at al-mouassat university teaching hospital-Damascus: a retrospective review of 888 cases

<p>Abstract</p> <p>Background</p> <p>Thoracic trauma is one of the leading causes of morbidity and mortality in developing countries. In this study, we present our 11-year experience in the management and clinical outcome of 888 chest trauma cases as a result of blunt and penetrating injuries in our university hospital in Damascus, Syria.</p> <p>Methods</p> <p>We reviewed files of 888 consequent cases of chest trauma between January 2000 and January 2011. The mean age of our patients was 31 ± 17 years mostly males with blunt injuries. Patients were evaluated and compared according to age, gender, etiology of trauma, thoracic and extra-thoracic injuries, complications, and mortality.</p> <p>Results</p> <p>The leading cause of the trauma was violence (41%) followed by traffic accidents (33%). Pneumothorax (51%), Hemothorax (38%), rib fractures (34%), and lung contusion (15%) were the most common types of injury. Associated injuries were documented in 36% of patients (extremities 19%, abdomen 13%, head 8%). A minority of the patients required thoracotomy (5.7%), and tube thoracostomy (56%) was sufficient to manage the majority of cases. Mean hospital LOS was 4.5 ± 4.6 days. The overall mortoality rate was 1.8%, and morbidity (n = 78, 8.7%).</p> <p>Conclusions</p> <p>New traffic laws (including seat belt enforcement) reduced incidence and severity of chest trauma in Syria. Violence was the most common cause of chest trauma rather than road traffic accidents in this series, this necessitates epidemiologic or multi-institutional studies to know to which degree violence contributes to chest trauma in Syria. The number of fractured ribs can be used as simple indicator of the severity of trauma. And we believe that significant neurotrauma, traffic accidents, hemodynamic status and GCS upon arrival, ICU admission, ventilator use, and complication of therapy are predictors of dismal prognosis.</p

Two years survival rate of class II composite resin restorations prepared by ART with and without a chemomechanical caries removal gel in primary molars

The aim was to test the null hypotheses that there is no difference: (1) in carious lesion development at the restoration margin between class II composite resin restorations in primary molars produced through the atraumatic restorative treatment (ART) with and without a chemomechanical caries removal gel and (2) in the survival rate of class II composite resin restorations between two treatment groups after 2 years. Three hundred twenty-seven children with 568 class II cavitated lesions were included in a parallel mouth study design. Four operators placed resin composite (Filtek Z 250) restorations bonded with a self-etch adhesive (Adper prompt L pop). Two independent examiners evaluated the restorations after 0.5, 1, and 2 years using the modified Ryge criteria. The Kaplan–Meier survival method was applied to estimate survival percentages. A high proportion of restorations were lost during the study period. Therefore, the first hypothesis could not be tested. No statistically significant difference was observed between the cumulative survival percentages of restorations produced by the two treatment approaches over the 2-year period (ART, 54.1 ± 3.4%; ART with Carisolv™, 46.0 ± 3.4%). This hypothesis was accepted. ART with chemomechanical gel might not provide an added benefit increasing the survival percentages of ART class II composite resin restorations in primary teeth

Survival of atraumatic restorative treatment (ART) sealants and restorations: a meta-analysis

The purpose of this study is to perform a systematic investigation plus meta-analysis into survival of atraumatic restorative treatment (ART) sealants and restorations using high-viscosity glass ionomers and to compare the results with those from the 2005 ART meta-analysis. Until February 2010, four databases were searched. Two hundred four publications were found, and 66 reported on ART restorations or sealant survival. Based on five exclusion criteria, two independent reviewers selected the 29 publications that accounted for the meta-analysis. Confidence intervals (CI) and or standard errors were calculated and the heterogeneity variance of the survival rates was estimated. Location (school/clinic) was an independent variable. The survival rates of single-surface and multiple-surface ART restorations in primary teeth over the first 2 years were 93% (CI, 91–94%) and 62% (CI, 51–73%), respectively; for single-surface ART restorations in permanent teeth over the first 3 and 5 years it was 85% (CI, 77–91%) and 80% (CI, 76–83%), respectively and for multiple-surface ART restorations in permanent teeth over 1 year it was 86% (CI, 59–98%). The mean annual dentine lesion incidence rate, in pits and fissures previously sealed using ART, over the first 3 years was 1%. No location effect and no differences between the 2005 and 2010 survival rates of ART restorations and sealants were observed. The short-term survival rates of single-surface ART restorations in primary and permanent teeth, and the caries-preventive effect of ART sealants were high. Clinical relevance: ART can safely be used in single-surface cavities in both primary and permanent teeth. ART sealants have a high caries preventive effect