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 toward 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 present 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 in Suicidal Behavior, Attitudes and Psychological Distress Among University Students: A Multinational Study.

The purpose of this study was to determine the associations between religion, 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 was associated with lowered risk for attempting suicide, affiliation with Islam was related to heightened risk for attempting suicide. Affiliation with Hinduism, Orthodox Christianity, 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 had a positive relation in respondents affiliating with Catholicism and other religions. Students reporting affiliation with Islam, the Christian 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.

Suicidal Behavior and Psychological Distress in University Students: A 12-nation Study.

This study investigated the prevalence of suicidal behavior and psychological distress in university students across 12 nations. A total of 5,572 university students from 12 countries were surveyed about suicide ideation, suicide attempts, and psychological distress by means of a self-administered questionnaire. Almost 29% of the samples reported having contemplated suicide and 7% reported attempting suicide. Of the total sample, 51.1% scored above the General Health Questionnaire-12 ≥ 3 cut-off points, 41.6% above the GHQ-12 ≥ 4 cut-off points, and 33.8% scored above the GHQ-12 ≥ 5 cut-off points. While odds of suicide ideation were elevated in Austria and the UK, reduced ORs were detected for China, Italy, Saudi Arabia, Tunisia, and Turkey. Similarly, while odds of suicide attempt were high in Jordan, Palestine, Saudi Arabia, and to some extent in Turkey, reduced ORs were observed for Austria, China, Italy, Japan and the United States. Elevated ORs for psychological distress were seen in Japan, Jordan, Palestine, Saudi Arabia, Tunisia, and Turkey but reduced ORs were noted in Austria, China, Iran, Italy, and the United States. Psychological distress was strongly associated with reports of suicide ideation and attempts. Suicide ideation, suicide attempt, and psychological distress are common in university students but their rates vary depending on the sociocultural context. Due attention should be devoted to the mental health needs of young adults enrolled in higher educational institutions and more cross-cultural research is warranted to better understand the etiology of the observed intersocietal variations in suicidal behavior and psychological distress.

Knowledge and attitudes of Saudi dental undergraduates on oral cancer.

Oral cancer awareness among future dental practitioners may have an impact on the early detection and prevention of oral cancer. A cross-sectional survey was undertaken to assess the current knowledge of future Saudi dentists on oral cancer and their opinions on oral cancer prevention. A pretested questionnaire was sent to 550 undergraduate dental students in the fourth, fifth, and sixth year of the Al-Farabi College for Dentistry and Nursing, Riyadh, Saudi Arabia. Questions relating to knowledge of oral cancer, risk factors, and opinions on oral cancer prevention and practices were posed. Four hundred seventy-nine students returned the questionnaire (87.1 %). Eighty-one percent of respondents correctly answered questions relating to oral cancer awareness. Eighty-seven percent of respondents felt confident in performing a systematic oral examination to detect changes consistent with oral malignancy. Interestingly, 57 % of respondents had seen the use of oral cancer diagnostics aids. Thirty-seven percent of respondents felt inadequately trained to provide tobacco and alcohol cessation advice. There is a need to reinforce the undergraduate dental curriculum with regards to oral cancer education; particularly in its prevention and early detection. Incorporating the use of oral cancer diagnostic aids should be made mandatory.

An unusual side effect of Ibuprofen post dental therapy: increased erectile and libido activity.

Nonsteroidal anti-inflammatory drugs are the most commonly used medications for pain control in dentistry. The reported adverse effects include gastrointestinal and cardiovascular events, alterations in renal function, and effects on blood pressure, hepatic injury, and platelet inhibition which can lead to increased bleeding. This case report describes an unusual rare adverse event of the use of ibuprofen for pain control post restorative treatment. A 26-year-old, otherwise healthy Saudi male reported an unusual side effect of increased libido and erectile function post use of ibuprofen. The medical and laboratory tests have failed to identify a link between this rare adverse event and either underlying conditions or possibly related etiology. This case represented a puzzling challenge with no clear explanation.