CD56 expression in breast cancer induces sensitivity to natural killer-mediated cytotoxicity by enhancing the formation of cytotoxic immunological synapse

We examined the potential value of the natural killer (NK) cell line; NK-92, as immunotherapy tool for breast cancer (BC) treatment and searched for biomarker(s) of sensitivity to NK-92-mediated cytotoxicity. The cytotoxic activity of NK-92 cells towards one breast precancerous and nine BC cell lines was analyzed using calcein-AM and degranulation assays. The molecules associated with NK-92-responsiveness were determined by differential gene expression analysis using RNA-sequencing and validated by RT-PCR, immunostaining and flow cytometry. NK-target interactions and immunological synapse formation were assessed by fluorescence microscopy. Potential biomarker expression was determined by IHC in 99 patient-derived BC tissues and 10 normal mammary epithelial tissues. Most (8/9) BC cell lines were resistant while only one BC and the precancerous cell lines were effectively killed by NK-92 lymphocytes. NK-92-sensitive target cells specifically expressed CD56, which ectopic expression in CD56-negative BC cells induced their sensitivity to NK-92-mediated killing, suggesting that CD56 is not only a biomarker of responsiveness but actively regulates NK function. CD56 adhesion molecules which are also expressed on NK cells accumulate at the immunological synapse enhancing NK-target interactions, cytotoxic granzyme B transfer from NK-92 to CD56-expressing target cells and induction of caspase 3 activation in targets. Interestingly, CD56 expression was found to be reduced in breast tumor tissues (36%) with strong inter- and intratumoral heterogeneity in comparison to normal breast tissues (80%). CD56 is a potential predictive biomarker for BC responsiveness to NK-92-cell based immunotherapy and loss of CD56 expression might be a mechanism of escape from NK-immunity. - 2019, The Author(s).We would like to thank Ms Khaoula Errafii, Dr Kumaran Mande and Dr Richard Thompson for technical support in RNA sequencing. This work was supported by the Qatar Biomedical Research Institute (QBRI), Qatar Foundation.Scopu

Spiritual Well-Being, Depression, and Stress Among Hemodialysis Patients in Jordan

Purpose: The spiritual dimension of a patient’s life is an important factor that may mediate detrimental impacts on mental health. The lack of research investigating spiritual well-being, religiosity, and mental health among Jordanian hemodialysis patients encouraged this research. This study explored levels of spiritual well-being and its associations with depression, anxiety, and stress. Design: A quantitative, cross-sectional correlational study. Method: A sample of 218 Jordanian Muslim hemodialysis patients completed a structured, self-administered questionnaire. The data were analyzed using descriptive statistics and linear multivariate regression models. Findings: The hemodialysis patients had, on average, relatively low levels of spiritual well-being, moderate depression, severe anxiety, and mild to moderate stress. The results of the regression models indicated that aspects of spiritual well-being were negatively associated with depression, anxiety, and stress, but only existential well-being consistently retained significant associations after controlling for religious well-being, religiosity, and sociodemographic variables. Conclusions: Greater spiritual and existential well-being of Jordanian hemodialysis patients were significantly associated with less depression, anxiety, and stress. It appears that these patients use religious and spiritual beliefs and practices as coping mechanisms to overcome their depression, anxiety, and stress. The implications for holistic clinical practice are explored

Diacritics improve comprehension of the Arabic script by providing access to the meanings of heterophonic homographs

The diacritical markers that represent most of the vowels in the Arabic orthography are generally omitted from written texts. Previous research revealed that the absence of diacritics reduces reading comprehension performance even by skilled readers of Arabic. One possible explanation is that many Arabic words become ambiguous when diacritics are missing. Words of this kind are known as heterophonic homographs and are associated with at least two different pronunciations and meanings when written without diacritics. The aim of the two experiments reported in this study was to investigate whether the presence of diacritics improves the comprehension of all written words, or whether the effects are confined to heterophonic homographs. In Experiment 1, adult readers of Arabic were asked to decide whether written words had a living meaning. The materials included heterophonic homographs that had one living and one non-living meaning. Results showed that diacritics significantly increased the accuracy of semantic decisions about ambiguous words but had no effect on the accuracy of decisions about unambiguous words. Consistent results were observed in Experiment 2 where the materials comprised sentences rather than single words. Overall, the findings suggest that diacritics improve the comprehension of heterophonic homographs by facilitating access to semantic representations that would otherwise be difficult to access from print

Synthesis and characterization of phenolic resins based on pyrolysis bio-oil separated by fractional condensation and water extraction

International audienc

IPV Screening and Readiness to Respond to IPV in Ob-Gyn Settings: A Patient-Physician Study

Purpose. Intimate partner violence (IPV) is a serious, preventable public health concern that largely affects women of reproductive age. Obstetrician-gynecologists (ob-gyns) have a unique opportunity to identify and support women experiencing IPV to improve women’s health. Considering recent efforts to increase IPV awareness and intervention, the present study aimed to provide a current evaluation of nationally representative samples to assess ob-gyn readiness to respond to IPV as well as patient IPV-related experiences. Methods. 400 ob-gyns were randomly selected from American College of Obstetricians and Gynecologists’ (ACOG) Collaborative Ambulatory Research Network. Each physician was mailed one physician survey and 25 patient surveys. Results. IPV training/education and IPV screening practices were associated with most measures of ob-gyn readiness to respond to IPV. Among respondents, 36.8% endorsed screening all patients at annual exams; however, 36.8% felt they did not have sufficient training to assist individuals in addressing IPV. Workplace encouragement of IPV response was associated with training, screening, detection, preparation/knowledge, response practices, and resources. Thirty-one percent of patients indicated their ob-gyn had asked about possible IPV experiences during their medical visit. Conclusion. Findings highlight specific gaps in ob-gyns’ IPV knowledge and response practices to be further addressed by IPV training