A LINE1-Nucleolin Partnership Regulates Early Development and ESC Identity.

Transposable elements represent nearly half of mammalian genomes and are generally described as parasites, or "junk DNA." The LINE1 retrotransposon is the most abundant class and is thought to be deleterious for cells, yet it is paradoxically highly expressed during early development. Here, we report that LINE1 plays essential roles in mouse embryonic stem cells (ESCs) and pre-implantation embryos. In ESCs, LINE1 acts as a nuclear RNA scaffold that recruits Nucleolin and Kap1/Trim28 to repress Dux, the master activator of a transcriptional program specific to the 2-cell embryo. In parallel, LINE1 RNA mediates binding of Nucleolin and Kap1 to rDNA, promoting rRNA synthesis and ESC self-renewal. In embryos, LINE1 RNA is required for Dux silencing, synthesis of rRNA, and exit from the 2-cell stage. The results reveal an essential partnership between LINE1 RNA, Nucleolin, Kap1, and peri-nucleolar chromatin in the regulation of transcription, developmental potency, and ESC self-renewal.

Inheritable Silencing of Endogenous Genes by Hit-and-Run Targeted Epigenetic Editing.

Gene silencing is instrumental to interrogate gene function and holds promise for therapeutic applications. Here, we repurpose the endogenous retroviruses' silencing machinery of embryonic stem cells to stably silence three highly expressed genes in somatic cells by epigenetics. This was achieved by transiently expressing combinations of engineered transcriptional repressors that bind to and synergize at the target locus to instruct repressive histone marks and de novo DNA methylation, thus ensuring long-term memory of the repressive epigenetic state. Silencing was highly specific, as shown by genome-wide analyses, sharply confined to the targeted locus without spreading to nearby genes, resistant to activation induced by cytokine stimulation, and relieved only by targeted DNA demethylation. We demonstrate the portability of this technology by multiplex gene silencing, adopting different DNA binding platforms and interrogating thousands of genomic loci in different cell types, including primary T lymphocytes. Targeted epigenome editing might have broad application in research and medicine.

The developmental control of transposable elements and the evolution of higher species.

Transposable elements (TEs) account for at least 50% of the human genome. They constitute essential motors of evolution through their ability to modify genomic architecture, mutate genes and regulate gene expression. Accordingly, TEs are subject to tight epigenetic control during the earliest phases of embryonic development via histone and DNA methylation. Key to this process is recognition by sequence-specific RNA- and protein-based repressors. Collectively, these mediators are responsible for silencing a very broad range of TEs in an evolutionarily dynamic fashion. As a consequence, mobile elements and their controllers exert a marked influence on transcriptional networks in embryonic stem cells and a variety of adult tissues. The emerging picture is not that of a simple arms race but rather of a massive and sophisticated enterprise of TE domestication for the evolutionary benefit of the host.

KAP1 Is a Chromatin Reader that Couples Steps of RNA Polymerase II Transcription to Sustain Oncogenic Programs.

Precise control of the RNA polymerase II (RNA Pol II) cycle, including pausing and pause release, maintains transcriptional homeostasis and organismal functions. Despite previous work to understand individual transcription steps, we reveal a mechanism that integrates RNA Pol II cycle transitions. Surprisingly, KAP1/TRIM28 uses a previously uncharacterized chromatin reader cassette to bind hypo-acetylated histone 4 tails at promoters, guaranteeing continuous progression of RNA Pol II entry to and exit from the pause state. Upon chromatin docking, KAP1 first associates with RNA Pol II and then recruits a pathway-specific transcription factor (SMAD2) in response to cognate ligands, enabling gene-selective CDK9-dependent pause release. This coupling mechanism is exploited by tumor cells to aberrantly sustain transcriptional programs commonly dysregulated in cancer patients. The discovery of a factor integrating transcription steps expands the functional repertoire by which chromatin readers operate and provides mechanistic understanding of transcription regulation, offering alternative therapeutic opportunities to target transcriptional dysregulation.

RIF1 and KAP1 differentially regulate the choice of inactive versus active X chromosomes.

The onset of random X chromosome inactivation in mouse requires the switch from a symmetric to an asymmetric state, where the identities of the future inactive and active X chromosomes are assigned. This process is known as X chromosome choice. Here, we show that RIF1 and KAP1 are two fundamental factors for the definition of this transcriptional asymmetry. We found that at the onset of differentiation of mouse embryonic stem cells (mESCs), biallelic up-regulation of the long non-coding RNA Tsix weakens the symmetric association of RIF1 with the Xist promoter. The Xist allele maintaining the association with RIF1 goes on to up-regulate Xist RNA expression in a RIF1-dependent manner. Conversely, the promoter that loses RIF1 gains binding of KAP1, and KAP1 is required for the increase in Tsix levels preceding the choice. We propose that the mutual exclusion of Tsix and RIF1, and of RIF1 and KAP1, at the Xist promoters establish a self-sustaining loop that transforms an initially stochastic event into a stably inherited asymmetric X-chromosome state.

Community and health worker perspectives on malaria in Meghalaya, India: covering the last mile of elimination by 2030.

BACKGROUND: Malaria remains a public health problem in regions of Northeastern India because of favourable bio-geographic transmission conditions, poor access to routine healthcare, and inadequate infrastructure for public health and disease prevention. This study was undertaken to better understand community members' and health workers' perceptions of malaria, as well as their knowledge, attitudes, and prevention practices related to the disease in Meghalaya state. METHODS: The study included participants from three malaria endemic districts: West Khasi Hills, West Jaiñtia Hills, and South Garo Hills from 2019 to 2021. A total of 82 focus group discussions (FGD) involving 694 community members and 63 in-depth interviews (IDI) with health personnel and traditional healers residing within the three districts were conducted. A thematic content analysis approach was employed, using NVivo12 software for data management. RESULTS: Most participants reported a perceived reduction in malaria during recent years, attributing this to changes in attitudes and behaviours in health seeking, and to more effective government interventions. Local availability of testing and treatment, and an improved, more responsive health system contributed to changing attitudes. Long-lasting insecticidal nets (LLINs) were largely preferred over indoor residual spraying (IRS), as LLINs were perceived to be effective and more durable. Community members also reported using personal protective measures such as applying repellents, burning neem tree leaves, straw/egg trays, wearing long sleeve clothes, and applying ointments or oils to protect themselves from mosquito bites. While most participants acknowledged the role of mosquitoes in malaria transmission, other conditions that are not mosquito-borne were also attributed to mosquitoes by some participants. The communities surveyed have largely shifted from seeking treatment for malaria from traditional healers to using public facilities, although some participants reported switching between the two or using both simultaneously. Improved understanding of cerebral malaria, which some participants previously attributed to mental illness due to 'bad spirits', is an example of how cultural and ritualistic practices have changed. CONCLUSION: The findings reveal diverse perceptions among community members regarding malaria, its prevention, practices to prevent mosquito-transmitted diseases, and their opinions about the healthcare system. A key finding was the shift in malaria treatment-seeking preferences of community members from traditional healers to the public sector. This shift highlights the changing dynamics and increasing acceptance of modern healthcare practices for malaria treatment and prevention within tribal and/or indigenous communities. By recognizing these evolving attitudes, policymakers and healthcare providers can better tailor their interventions and communication strategies to more effectively address ongoing needs and concerns as India faces the 'last mile' in malaria elimination.

Epilepsy and education: A case-control analysis of the impact of an intensive epilepsy training program on undergraduate medical students.

AIMS: To evaluate the knowledge, attitudes, and practical skills of students submitted to a 6-week intensive training in epilepsy compared to students without any training but mandatory neurology classes. METHODS: It is a case-control study. After completing a 6-week intensive Academic, Clinical, and Research Program in epilepsy, TUMSs answered a validated Knowledge Attitudes and Practices (KAP) questionnaire. The control group, composed of undergraduate students who shared the same age, academic year, and compulsory hours for learning about epilepsy as TUMSs, was also assessed through the KAP instrument. Answers from both groups were submitted to Fisher exact and the χ2 test to observe differences among groups. Descriptive statistics were also performed. RESULTS: TUMSs displayed better results in theoretical knowledge such as the definition and causes of epilepsy, and the application of paraclinical studies essential for diagnosing epilepsy. From their perspective, people with epilepsy encounter restricted opportunities for preserving their social life and employment and they are more prone to workplace accidents. They are convinced that facing epilepsy presents a notable risk due to the difficulties linked with diagnosis, considering epilepsy a challenging disease for general practitioners to identify and follow up. Likewise, they exhibited improvement in treatment adjustment and treatment monitoring of patients with epilepsy, mainly in pregnancy cases. Finally, they had greater knowledge about what to do when they witness a person experiencing a seizure. CONCLUSION: Our study showed that a 6-week intensive education program in epilepsy increased the knowledge and practical skills and changed the attitude toward patients with epilepsy of undergraduate students.

Implementing a cancer survivorship seminar course to non-healthcare professional undergraduate students.

BACKGROUND: At University of California, Irvine (UCI), a seminar course focused on cancer survivorship was developed and offered to non-healthcare professional undergraduate students. Utilizing the knowledge, attitude, and perception (KAP) framework, this study was designed to examine the impact on students who have taken this course, and to clarify the value of this course for undergraduate students. METHODS: This was a cross-sectional survey. Undergraduate students enrolled in the Life After Cancer Freshmen Seminar course (Uni Stu 3) at UCI between 2021 and 2023 were invited to participate. The survey consisted of 4 main sections: (1) demographics, (2) knowledge of cancer survivorship, (3) attitude towards cancer survivorship, and (4) perception and awareness of cancer survivorship. The survey was administered prior to the implementation of the course, and the same survey was administered at the end of the course. RESULTS: A total of 33 students completed the pre-implementation survey and 30 students completed the post-implementation survey. Comparing pre- and post-course implementation, there was an increase of perception and awareness of (i) resources and guidelines for cancer survivors (pre, 9.1% vs. post, 36.7%), (ii) mental health complications among cancer survivors (pre, 36.4% vs. post, 56.7%), (iii) benefits of cancer survivorship care (pre, 15.2% vs. post, 40%), latest research in cancer survivorship (pre, 0% vs. post, 23.3%), and (iv) tailoring survivors' needs according to their age groups (pre, 24.2% vs. post, 66.7%). Knowledge and attitude towards caring of cancer survivors were similar comparing pre- and post-course implementation. CONCLUSION: In an undergraduate seminar course focused on cancer survivorship, we observed an improvement of non-healthcare students' perception and awareness of cancer survivorship-related issues, advocating the value on introducing highly prevalent cancer survivorship topics early to both undergraduate STEM and non-STEM students.

Knowledge, attitude, and practice of breast self-examination is associated with general self-care and cultural factors: a study from Tamil Nadu, India.

AIM: Breast cancer is the most prevalent type of cancer among women. One form of care related to early detection of breast cancer is breast self-examination (BSE). However, evidence on knowledge, attitude, and practice (KAP) of BSE and its determining factors are minuscule in an Indian context. Therefore, the present study primarily examined the prevalence of KAP of BSE. Further, its association with general self-care and cultural factors was determined. METHODS: This cross-sectional study obtained data from 412 women (Mn age = 26.63) from two rural localities of Vellore district, Tamil Nadu, India. Self-reported questionnaires of KAP of BSE, self-care, and cultural factors were applied. Statistical analyses include independent sample t-test and binomial logistic regression. RESULTS: The majority of the sample had inadequate knowledge (58%), unfavourable attitudes (73.8%), and poor practice (89.6%) of BSE. The general self-care among the sample was moderate. Self-care was found to be a significant predictor of knowledge (b = 0.07, p < .05) and attitude (b = 0.092, p < .05) toward BSE. Shyness was identified as a negative predictor of KAP. Discouraged breast health discussions predicted inadequate knowledge, and not being educated by family/friends had a negative impact on knowledge and practice. A preference for same-gender physicians led to an unfavourable attitude toward BSE. CONCLUSION: The observed negative trends in KAP of BSE are concerning. The results imply that girls and women should be educated and encouraged to practice BSE and promote self-care behaviours. At the same time, efforts to reduce cultural barriers may be helpful to promote the KAP of BSE.

Evaluating knowledge, attitude, and physical activity levels related to cardiovascular disease in Egyptian adults with and without cardiovascular disease: a community-based cross-sectional study.

BACKGROUND: Cardiovascular disease (CVD) represents a significant health challenge in Egypt, yet there exists limited understanding regarding the knowledge, attitudes, and physical activity levels associated with CVD. These factors play a pivotal role in developing effective prevention and management strategies. Hence, this cross-sectional study aimed to evaluate Egyptian adults' knowledge, attitudes, and physical activity (KAP) levels. METHODS: Data were collected using a previously validated questionnaire encompassing demographic characteristics, CVD knowledge (including risk factors and symptoms), attitudes toward CVD, and self-reported physical activity levels. The survey was distributed among social media channels, and trained researchers administered the questionnaire via face-to-face interviews with adult patients with and without CVD admitted to Cairo University Hospital clinics. RESULTS: The study involved 591 participants, of whom 21.7% had CVD. Overall, participants exhibited poor knowledge regarding CVD, with a mean score of 21 ± 7 out of 40, equivalent to 52.5%. Attitudes toward CVD were moderate, with a mean score of 66.38 ± 8.7 out of 85, approximately 78%. Physical activity levels per week were also moderate, averaging 1188 MET-min with a range of 1121-18,761. Subgroup analysis revealed that individuals with CVD had lower average knowledge, attitude, and physical activity levels than those without CVD. Working in the healthcare field was a predictor of higher knowledge score (standard error (SE) 5.89, 95% confidence interval (CI) 4.61 to 7.17, P < 0.001), while those with CVD and smokers were predictors of lower attitude score (SE -4.08, 95% CI -6.43 to -1.73, P < 0.001) and (SE -2.54, 95% CI -4.69 to -0.40, P = 0.02), respectively. CONCLUSION: The study findings highlight a significant disparity in knowledge, attitudes, and physical activity levels related to CVD in Egypt. Targeted interventions aimed at improving awareness, fostering positive attitudes, and promoting physical activity among individuals at risk for CVD are crucial for effective prevention and management.

Culturally adapted training for community volunteers to improve their knowledge, attitude and practice regarding non-communicable diseases in Vietnam.

BACKGROUND: The burden of non-communicable diseases is becoming unmanageable by primary healthcare facilities in low- and middle-income countries. Community-based approaches are promising for supporting healthcare facilities. In Vietnam, community health volunteers are trained in providing health promotion and screening in a culturally adapted training. This study aims to assess the change in knowledge, attitude and practice regarding NCD prevention and management after a culturally adapted training, and the potential mechanisms leading to this change. METHODS: The Knowledge Attitude and Practice survey was assessed before and after an initial training, and before and after a refresher training (n = 37). We used a focus group discussion with community health volunteers (n = 8) to map potential mechanisms of the training and applying learned knowledge in practice. Data were collected in the districts Le Chan and An Duong of Hai Phong, Vietnam, in November 2021 and May 2022. RESULTS: We found that knowledge increased after training (mean = 5.54, 95%-confidence interval = 4.35 to 6.74), whereas attitude and practice did not improve. Next, knowledge decreased over time (m=-12.27;-14.40 to -10.11) and did not fully recover after a refresher training (m=-1.78;-3.22 to -0.35). As potential mechanisms for change, we identified the use of varying learning methods, enough breaks, efficient coordination of time located for theory and practice, handout materials, large group size and difficulty in applying a digital application for screening results. CONCLUSION: Culturally adapted trainings can improve knowledge among community health volunteers which is important for the support of primary healthcare in low- and middle-income countries. Using a digital screening application can be a barrier for the improvement of knowledge, attitude and practice and we suggest using an intergenerational or age-friendly approach, with the supervision of primary healthcare professionals. Future research on behavioral change should include additional components such as self-efficacy and interrelationships between individuals.

Knowledge, Attitudes and Practices About Zika Virus Infection Among Women of Reproductive Age in Central Brooklyn, New York City, USA.

Zika virus (ZIKV) is spread by mosquitos, sexual intercourse and vertically during pregnancy. The 2015-2016 ZIKV epidemic infected millions in the Americas and resulted in thousands of infants born with malformations. Though the clusters of severe birth defects have subsided since 2017, ZIKV transmission remains a concern throughout Latin America and the Caribbean. Travel-associated and sexually-transmitted Zika, therefore, remain potential routes of transmission for women of reproductive age and their partners. This is particularly true for communities with high immigrant and foreign-born populations in Central Brooklyn, New York. Limited information has been collected on the perception by this population of ZIKV and how high-risk women engage in preventive practices. Using a survey adapted from the WHO, we assessed engagement in mosquito-related preventive practices while traveling. Data from 483 respondents on knowledge and perceived ZIKV concern, along with demographics as correlates of engagement in preventive practices were collected using a convenience sample between September 2020 and January 2021. Data were collected via a multipronged approach using social media in REDCap. Our findings show that being white/not Hispanic, pregnant, knowledgeable and concerned about ZIKV, and having enough information about ZIKV were all significantly associated with an increased likelihood of engaging in preventive practices while traveling. Multivariable logistic modeling revealed that knowledge was significantly associated with an increased likelihood of engaging in preventive practices while traveling (AOR = 1.90, 95% CI [1.28-2.83]). These findings underscore the importance of directing tailored health education efforts to vulnerable populations.

Zika Virus Infection Knowledge and Communication Preferences Among Women of Reproductive Age in Central Brooklyn, New York: A Thematic Analysis.

The 2016 outbreak of Zika virus (ZIKV) infected millions and resulted in thousands of infants born with malformations. Though the clusters of severe birth defects resulting from this outbreak have subsided, ZIKV continues to be a concern throughout much of Latin America and the Caribbean. Travel and sexual intercourse remain the dominant transmission risk factors for women of reproductive age and their partners. This is particularly true for communities in Brooklyn, New York, that comprise large immigrant and foreign-born populations. Practitioners of public health understand little about how women at risk for ZIKV are most likely to receive information about the virus or who they trust most to provide that information. In the context of five focus group discussions, this study explored the knowledge and communication preferences of 20 women of reproductive age in Central Brooklyn. Results derived from a thematic analysis suggest that while most women are familiar with mosquitos as ZIKV vectors, knowledge of sexual transmission is considerably lower. Many respondents believe that only women who are pregnant or trying to become pregnant are at risk, and public health agencies, such as the U.S. Centers for Disease Control and Prevention, remain the most trusted sources of information. These findings can support more effective communication about the risks of ZIKV infection and other vector-borne diseases to women in New York City and similar urban communities.

Knowledge, attitude, and practice of dental health professionals toward dental impression disinfection protocol during the COVID-19 pandemic in Saudi Arabia- a cross-sectional study.

BACKGROUND: Despite the updated guidelines on dental impression disinfection protocols during the COVID-19 pandemic, adherence to such procedures has not been studied among dental health professionals in Saudi Arabia. Understanding DHPs' knowledge, attitudes, and practices regarding COVID-19 is crucial in assessing a willingness to adhere to the recommendations provided by health authorities in mitigating the spread of COVID-19 via dental impressions impacting patient safety and infection control measures. Hence, this study aimed to assess dental health professionals' (DHPs) knowledge, attitudes, and practices (KAP) toward dental impression disinfection protocol during the COVID-19 pandemic in Saudi Arabia. METHODS: A cross-sectional study using an online survey was conducted from 14 December 2022 to 21 March 2023 among practicing dentists, dental assistants (DA), dental laboratory technicians (DT), and dental hygienists in Saudi Arabia. A validated and reliable questionnaire that consisted of 38 items along with demographic variables was prepared to collect the data. Using Google Forms, a questionnaire link was prepared and shared on the social media platforms of DHPs in Saudi Arabia. A descriptive analysis was conducted to report the percentages and frequencies. The mean knowledge, attitude, and practice scores were analyzed using an Independent t-test, ANOVA, and Pearson's correlation tests. RESULTS: A total of 718 DHPs voluntarily participated in the survey. Most of the DHPs exhibited average knowledge 392 (54.6%), neutral attitudes 393(54.7%), and adequate 549 (76.5%) practice towards dental impression disinfection protocol. The mean knowledge score differed significantly across nationality (p = 0.013), type of DHPs (p < 0.001), qualification (p = 0.045), and experience (p = 0.028) of the study participants. Significant differences in attitude towards impression disinfection were observed in different age groups (p = 0.002), qualifications (p = 0.015), and experiences (p = 0.024) of the DHPs. Similarly, practice varied across different age groups (p = 0.010), nationality (p = 0.013), type of DHPs (p = 0.019), qualification (p = 0.044), experience (p = 0.041), and COVID-19 Infection (p = 0.006). Moreover, a significant positive correlation between knowledge-attitude (r = 0.258, p < 0.01), knowledge-practice (r = 0.283, p < 0.01), and attitude-practice (r = 0.196, p < 0.01) was observed. CONCLUSION: DHPs considered in this study demonstrated average knowledge and attitudes toward impression disinfection, requiring improvement through continuous dental education and training. However, they displayed acceptable dental impression disinfection practices during the COVID-19 pandemic. It is highly recommended that continuing education programs should mainly reinforce the knowledge of sodium hypochlorite, iodophor, and phenolics and their concentrations to be used as an impression disinfectant. Additionally, it should focus on techniques of disinfecting elastomeric, hydrocolloid, zinc oxide and eugenol, and impression compound materials to mitigate the spread of COVID-19 based on Saudi ministry of health guidelines.

Attitudes, knowledge and practices concerning delirium among paediatric intensive care unit nurses: a multisite cross-sectional study in Sichuan, China.

BACKGROUND: Delirium is an acute mental state associated with poor outcomes. The incidence of delirium is high, especially in the paediatric intensive care unit (PICU). It is important for staff, particularly nurses, to understand delirium and implement interventions to prevent it. We performed a survey with the aim of evaluating and analysing the factors influencing the knowledge, attitudes and behaviour of PICU nurses towards delirium. METHODS: This cross-sectional descriptive study included 215 PICU nurses in 6 PICUs from five teaching hospitals in Sichuan Province, China. An online survey about the knowledge, attitudes and practices related to delirium care was conducted among PICU nurses used a self-made and validated questionnaire. The data were analysed using descriptive statistics; differences between groups were compared using t tests, ANOVA and rank-sum tests. Variables with a significance level of 0.05 in the univariate analysis were entered into the multivariable regression analysis to identify predictors. RESULTS: Only 14.4% of the nurses had a good understanding of delirium, and 40.9% had received relevant training. The mean knowledge score was 9.01 ± 3.86, and the overall passing rate of knowledge was 49.8%. The mean attitude and behaviour scores were 40.95 ± 5.62 and 40.33 ± 8.01, respectively. Among the hospitals, different delirium assessments for children and specific training were performed, explaining approximately 10% of the variability in knowledge scores (F = 6.152), approximately 10% of the variability in attitude/belief scores (F = 5.908), and approximately 17% of the variability in practice scores (F = 10.767). CONCLUSIONS: PICU nurses have poor knowledge of delirium, particularly regarding its clinical manifestations, influencing factors and medications used, and they have adequate attitudes and confidence and good behaviour regarding delirium in children. To better prevent delirium, we suggest that PICU departments routinely assess delirium and conduct delirium training for nurses. TRIAL REGISTRATION: Not applicable.

Determinants of dietary behaviors among dental professionals: insights across educational levels.

BACKGROUND: Healthy dietary behaviors are fundamental for maintaining optimal health. Understanding the dietary behaviors of dentists is vital for designing effective interventions to foster healthier behaviors. However, investigations into dietary behaviors and their associations among dental professionals have been limited. OBJECTIVE: To investigate the dietary behaviors of dental professionals, along with the associated factors influencing their dietary options. MATERIALS AND METHODS: A self-administered online questionnaire was constructed to collect data from three groups of dental professionals: undergraduates (UG), postgraduates (PG), and practicing dentists (DT). The questionnaire encompassed inquiries regarding demographic characteristics, knowledge assessment, evaluation of attitudes, and examination of dietary behaviors. Data analysis procedures included descriptive statistics, Spearman's rank correlation, and multiple linear regression. RESULTS: A total of 842 individuals participated in the study (UG: 264, PG: 247, DT: 331). Attitude emerged as the strongest association of healthy dietary behaviors across all groups (UG: ß=0.370, PG: ß=0.512, DT: ß=0.642; P < 0.001), while alcohol consumption showed a negative correlation with healthy dietary behaviors (UG: ß=-0.135, PG: ß=-0.220, DT: ß=-0.216; P < 0.001). CONCLUSION: Significant variations in dietary behaviors across diverse educational levels of dental professionals were observed. Attitude emerged as the predominant factor influencing dietary behaviors, while knowledge was found to have a weak association. Tailored interventions addressing individual challenges at different career stages should be considered to enhance dietary behaviors and overall well-being in dental practice settings.

How sizeable are the knowledge, attitude and perception of food risks among young adults? An Italian survey.

BACKGROUND: in recent years, food safety has become increasingly important and a public health priority, especially in developed and rich countries. OBJECTIVES: to investigate knowledge and perception of food risk among young adults and the related behaviours. DESIGN: observational study conducted from March to October 2022 through the administration of an anonymous questionnaire based on multiple-choice questions spread online through social networks. SETTING AND PARTICIPANTS: 317 men and women with a mean age of 23.6 ± 6.7 (71% F, 29% M), mainly students, who filled the questionnaire and gave their consent to the use of personal data for the purpose of scientific research. MAIN OUTCOMES MEASURES: knowledge, attitudes, and perception of food risk in the target population. RESULTS: the majority think that food safety is very important to their health. The most perceived food risks are the presence of pesticides, bacterial and viral contamination, residuals of antibiotics and/or hormones, and microplastics. More than half believes to be poorly informed about the risk associated with food consumption. There is a high level of trust in data from scientific evidence and physicians and a low level of trust in data from European institutions and the Italian government. Almost everyone thinks that public authorities should provide more information. CONCLUSIONS: these data show a good knowledge of the importance of food safety for health; nevertheless, the majority does not feel well informed. The evaluation of the risk perception and of the factors influencing it is important for the success of the information/communication about food safety and for the consumer empowerment.

Indoor air pollution: an Italian Knowledge, Attitude and Practice (KAP) study among the general population.

Background: Indoor air pollution negatively affects population health and the national health services in terms of socio-economic costs. The presence of indoor pollutants depends a lot on lifestyles. Study design: The aim of this work is to evaluate knowledge, daily habits and the preventive behaviors in order to contrast the effects on health caused by indoor pollutants. Methods: The study was conducted through the administration of questionnaires to the population resident in the metropolitan city of Messina (Italy), asking about sociodemographic characteristics, knowledge, daily habits and preventive behaviors. Results: The questionnaire was filled by 894 subjects (46.8% M; 53.2% F). Regarding knowledge, 66.8% had heard of indoor air pollution and 94.9% knew what the most common indoor pollutants are; regarding daily habits they often aired out the house (91.9% in the morning and 71.4% after cleaning), 24.8% were smokers and 36.7 of them smoked indoors; regarding preventive behaviors, 41.6% chose the cleaning products based on habit and only 32.9% bought plants able to purify environments. Conclusions: Although the analyzed population had adequate knowledge of indoor air pollution, this did not strongly impact on the adoption of healthy lifestyles. Therefore, it becomes necessary to intervene on a social level with environmental education activities, starting from school age.

[Expression and prognostic significance of KAP1 gene in malignant pleural mesothelioma].

Objective: To explore the expression of KAP1 (KRAB-associated protein 1, KAP1) in Malignant pleural mesothelioma (MPM) based on the cancer genome atlas (TCGA) and clinical trials. And elucidate the correlation between the expression of KAP1 and the clinical pathological parameters of patients with MPM and its prognosis. Methods: In April 2022, Based on the second generation KAP1mRNA sequencing data and clinicopathological data of MPM patients downloaded from TCGA database, the correlation between KAP1mRNA expression and clinical parameters was analyzed, and the correlation between KAP1 protein expression and clinicopathological parameters and its prognostic value were analyzed based on Chuxiong data set cohort clinical samples. The expression of KAP1 mRNA in MPM samples and matched normal tumor adjacent tissues was detected by qRT-PCR, and the expression of KAP1 protein in MPM and normal pleural tissues was detected by immunohistochemistry and Westernblotting. To construct a Kaplan-Meier model to explore the effect of KAP1 expression on the prognosis of MPM patients, and to analyze the prognostic factors of MPM patients by Cox regression. Results: qRT-PCR and Western blotting detection showed that the expression levels of KAP1 gene in four different MPM cells (NCI-H28, NCI-H2052, NCI-H2452, and MTSO-211H) were significantly higher than those in normal pleural mesothelial cells Met-5A. qRT-PCR, Western blotting and IHC results demonstrated that the mRNA and protein expression levels of KAP1 in MPM tissues was significantly higher than that in matching normal mesothelial tissues, and the expression level of KAP1 protein was correlated with TP 53 protein expression levels and serum CEA levels (P<0.05) . The mRNA expression level was significantly correlated with the prognosis, The overall survival time of mesothelioma patients with high KAP1mRNA expression was significantly shorter (HR=3.7, Logrank P<0.001) . Tumor type, age and the mRNA expression were related to the prognosis of MPM patients (P<0.05) . Multivariate analysis showed that tumor type and KAP1 mRNA expression level were independent prognostic factors of MPM patients (P<0.05) . Conclusion: In this study, TCGA database and Chuxiong cohort experiment samples were used to collect the relevant information of KAP1 expression in malignant melanoma tissues. It was confirmed that KAP1 is highly expressed in MPM tissues. The mRNA expression level and pathological type are correlated with the prognosis of patients.

DNA polymerase η promotes nonhomologous end joining upon etoposide exposure dependent on the scaffolding protein Kap1.

DNA polymerase eta (Pol η) is a eukaryotic member of the Y-family of DNA polymerase involved in translesion DNA synthesis and genome mutagenesis. Recently, several translesion DNA synthesis polymerases have been found to function in repair of DNA double-strand breaks (DSBs). However, the role of Pol η in promoting DSB repair remains to be well defined. Here, we demonstrated that Pol η could be targeted to etoposide (ETO)-induced DSBs and that depletion of Pol η in cells causes increased sensitivity to ETO. Intriguingly, depletion of Pol η also led to a nonhomologous end joining repair defect in a catalytic activity-independent manner. We further identified the scaffold protein Kap1 as a novel interacting partner of Pol η, the depletion of which resulted in impaired formation of Pol η and Rad18 foci after ETO treatment. Additionally, overexpression of Kap1 failed to restore Pol η focus formation in Rad18-deficient cells after ETO treatment. Interestingly, we also found that Kap1 bound to Rad18 in a Pol η-dependent manner, and moreover, depletion of Kap1 led to a significant reduction in Rad18-Pol η association, indicating that Kap1 forms a ternary complex with Rad18 and Pol η to stabilize Rad18-Pol η association. Our findings demonstrate that Kap1 could regulate the role of Pol η in ETO-induced DSB repair via facilitating Rad18 recruitment and stabilizing Rad18-Pol η association.