Global evidence on occupational sun exposure and keratinocyte cancers: a systematic review.

Individual studies have suggested that the association between occupational exposure to solar ultraviolet radiation (UVR) and the development of keratinocyte cancers (KCs) may only be valid in populations of European ancestry living in certain geographical regions. Comparative global data are scarce and so this review aimed to summarize current evidence on the association between occupational exposure to solar UVR and the development of KCs, with a specific focus on geographical location and skin colour. Ovid MEDLINE, PubMed, Embase and Web of Science were searched for potentially relevant records. Extracted data were summarized by study, country and region. We included one prospective cohort study and 18 case-control studies (n = 15 233) from 12 countries in regions where the majority of the population is white skinned (Americas, Europe and Oceania). Eighteen of the 19 studies reported effect estimates suggesting an increased risk of basal cell carcinoma (BCC) and/or squamous cell carcinoma (SCC) among outdoor workers. Only 11 studies found a significantly increased risk and many had imprecise estimates. There was a significantly increased risk of BCC and SCC in individual studies in North America, Latin America and the Caribbean, Western Europe and Southern Europe, but not across regions or countries. Overall, 95% of studies reported higher risks among outdoor workers, although the increases in risk were statistically significant in just over half of the studies. Well-designed and sufficiently powered occupational case-control and cohort studies with adequate adjustment for confounding factors and other risk factors are required to provide more accurate risk estimates for occupational KC.

Incidence of occupational contact dermatitis in healthcare workers: a systematic review.

Healthcare workers (HCWs) can be considered at an increased risk of developing occupational contact dermatitis (OCD) due to repetitive hand washing with soaps and disinfectants and extended use of gloves for many hours during the day. The aim of this study was to summarize the incidence of OCD in HCWs. We searched the databases PubMed/MEDLINE (1980-present), EMBASE (1980-present) and Cochrane Library (1992-present) through May 2020 using the search term 'incidence of contact dermatitis in HCWs' according to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Overall, 16 studies (six cohorts; 10 register-based) with follow-up periods between 1987 and 2013 fulfilled the inclusion criteria. The incidence of OCD reported in studies using registers of occupational diseases ranged from 0.6 to 6.7 per 10 000 person-years. The cohort studies reported incidence from 15.9 to 780.0 per 10 000 person-years; the incidence was higher in studies which included apprentice nurses. A higher incidence was also observed amongst dental practitioners, particularly dental technicians and nurses, compared to other HCWs. Studies reporting incidence data are very scarce and results differed by study design, type of contact dermatitis and investigated HCWs. Our study highlighted the dearth of high-quality data on the incidence of OCD and the possible underestimation of disease burden. Prospective cohort studies with harmonized designs, especially exposure assessment and outcome ascertainment, are required to provide more accurate, valid and recent estimates of the incidence of OCD. A high incidence amongst specific occupational groups suggests the need to undertake intervention studies with a focus on prevention, particularly during pandemics such as COVID-19.

Prevalence of and factors associated with burnout among health care professionals in Arab countries: a systematic review.

BACKGROUND: Burnout among healthcare professionals is one of the key challenges affecting health care practice and quality of care. This systematic review aims to (1) estimate the prevalence of burnout among health care professionals (HCP) in Arab countries; and (2) explore individual and work-related factors associated with burnout in this population. METHODS: Multiple electronic databases were searched for studies published in English or Arabic from January 1980 to November 2014 assessing burnout (using the Maslach Burnout Inventory; MBI) amongst health care professionals (HCP) in Arab countries. RESULTS: Nineteen studies (N = 4108; 49.3% females) conducted on HCP in Bahrain, Egypt, Jordan, Lebanon, Palestine, Saudi Arabia and Yemen were included in this review. There was a wide range of prevalence estimates for the three MBI subscales, high Emotional Exhaustion (20.0-81.0%), high Depersonalization (9.2-80.0%), and low Personal Accomplishment (13.3-85.8%). Gender, nationality, service duration, working hours, and shift patterns were all significantly associated with burnout. CONCLUSIONS: Within the constraints of the study and the range of quality papers available, our review revealed moderate-to-high estimates of self-reported burnout among HCP in Arab countries that are similar to prevalence estimates in non-Arabic speaking westernized developed countries. In order to develop culturally appropriate interventions, further research using longitudinal designs is needed to confirm the risk factors for burnout in specific HCP settings and specialties in Arab countries.

Prevalence and factors associated with infectious intestinal diseases in Ras Al Khaimah, United Arab Emirates, 2017: A population-based cross-sectional study.

BACKGROUND: The United Arab Emirates (UAE) is a rapidly developing high-income country that has experienced significant population growth, urbanization, and improvements in the standard of living since its formation in 1971. Published estimates on the prevalence of infectious intestinal diseases (IID) in the UAE are scarce and exclusively based on hospital data. The aim of this study was to provide the first prevalence estimates of IID in the UAE. METHODS: A population-based cross-sectional study design using a telephone-based questionnaire was used to estimate the IID prevalence in the previous 4 weeks in a representative sample of the Ras Al Khaimah (RAK) population from January to September 2017. RESULTS: Data were collected from 1254 participants (57.3% male; 25.2% <18 years). The prevalence of IID was 4.2% in the 4 weeks prior to the interview. Multivariate logistic regression analysis identified that being female (odds ratio (OR) 2.4, 95% confidence interval (CI) 1.2-5.1) and having a middle-range monthly household income (approx. USD 4080-<6800: OR 5.42, 95% CI 1.15-25.48; approx. USD 6800-<9530: OR 7.13, 95% CI 1.47-34.57) were positively associated with IID. Age ≥6 years was negatively associated with IID (OR 0.95, 95% CI 0.90-0.99). Forty-nine percent of participants with an IID sought medical care and 20.8% took over-the-counter medication. CONCLUSIONS: This study provides the first population-based prevalence estimates of IID in the UAE, which are similar to those reported in China (4%), but lower than those reported in Canada (10%), the Netherlands (7%), and the USA (6%).

Fluoropyrimidine-mediated radiosensitization depends on cyclin E-dependent kinase activation.

Fluoropyrimidines radiosensitize human colon cancer cells that progress into S phase in the presence of drug (M.A. Davis, H-Y. Tang, J. Maybaum, and T.S. Lawrence. Int. J. Radiat. Biol. 67. 509-512, 1995). We hypothesized that progression occurs in cells that generate elevated levels of cyclin E-dependent kinase activity despite the presence of the fluoropyrimidine. To test this hypothesis, we treated HT29 and SW620 human colon cancer cells with fluorodeoxyuridine under conditions that produced nearly complete inhibition of thymidylate synthase but which sensitized only the HT29 cells. We found that, whereas HT29 cells progressed into S phase and demonstrated increased cyclin E-dependent kinase activity, SW620 cells arrested just past the G1-S boundary and showed no change in kinase activity. Because these cell lines have the same p53 mutation, these findings suggest that there is a p53-independent G1-S checkpoint that mediates radiosensitization produced by fluorodeoxyuridine.

Expression of wild-type p53 stimulates an increase in both Bax and Bcl-xL protein content in HT29 cells.

It has been shown previously that wild-type p53 activity can simultaneously up-regulate Bax, a protein which predisposes cells to programmed cell death (PCD), and down-regulate Bcl-2, a protein which antagonizes PCD. These findings have been interpreted to suggest that correction of the mutant p53 status of some tumor cells may be a means of increasing their sensitivity to chemotherapeutic agents, by increasing their likelihood of undergoing PCD. We show here that when wild-type p53 activity is expressed in HT29 human colon cancer cells by use of a temperature sensitive p53 mutant, Bax levels rise, but so do levels of Bcl-xL protein. These observations indicate that Bcl-2 and Bcl-xL are regulated differently in response to wild-type p53 activity and that, while correction of mutant p53 phenotype may effectively kill cells having Bcl-2 as their major defense against PCD, this is not necessarily the case in cells using Bcl-xL as their primary defense.

Mechanism and pharmacological specificity of dUTPase-mediated protection from DNA damage and cytotoxicity in human tumor cells.

PURPOSE: We have reported previously that the expression of E. coli dUTPase (dutE) can protect HT29 cells from 5-fluorodeoxyuridine (FdUrd)-induced DNA fragmentation and cytotoxicity. In the study reported here, we further characterized the ability of dutE expression in one HT29 clone, dutE7, to alter the effects of treatment with FdUrd and other thymidylate synthase (TS) inhibitors. In addition, we developed two HuTu80 dutE-expressing clones using a pLNCX-dutE retroviral construct and tested their sensitivity to FdUrd-induced DNA fragmentation and cytotoxicity. METHODS: Both a dutE retroviral expression system and a dutE antibody were developed to facilitate the generation and screening of dutE-expressing clones. HT29 and HuTu80 clones expressing dutE were tested for drug-induced DNA damage with either alkaline elution or pulsed field gel electrophoresis and drug-induced loss of clonogenicity. RESULTS: Following a 24-h treatment with 100 microM CB3717 or 500 nM methotrexate (MTX), dutE7 cells were significantly less sensitive to drug-induced loss of clonogenicity than con3 cells. DutE7 cells were also resistant to CB3717-induced DNA fragmentation at 24 h. However, following a 48-h treatment with CB3717 or MTX there was no difference in survival between con3 and dutE7 cells, even though DNA damage was still greatly attenuated in the dutE7 cell line. In addition, expression of dutE in two HuTu80 clones, 80 C and 80 K, did not protect these cells from FdUrd-induced DNA damage or cytotoxicity. CONCLUSIONS: We conclude that the role of uracil misincorporation and subsequent DNA damage in cytotoxicity induced by TS inhibitors, in HT29 cells, is time dependent, and that cytotoxicity caused by long-term exposure to these drugs is largely independent of resultant DNA damage, in this cell line. The inability of dutE to protect HuTu80 cells from FdUrd further suggests that the significance of uracil misincorporation resulting from TS inhibition varies among cell lines.

Prevention of fluorodeoxyuridine-induced cytotoxicity and DNA damage in HT29 colon carcinoma cells by conditional expression of wild-type p53 phenotype.

We have examined the effects of conditionally expressing wild-type p53 activity in HT29 cells on DNA damage and cytotoxicity caused by exposure to fluorodeoxyuridine (FdUrd). Expression of wild-type p53 phenotype for 24 hr before FdUrd treatment provided HT29 cells with virtually complete protection from cytotoxicity caused by this drug. In addition, wild-type p53 expression also prevented FdUrd-induced DNA double-strand breaks and, unexpectedly, single-strand breaks in parental (mature) DNA. Temporary expression of wild-type p53 activity in the absence of drug treatment caused some loss of clonogenicity, although the magnitude of this cytotoxic effect was small compared with the level of cell kill obtained by treatment with cytotoxic drugs for similar periods of time, indicating that HT29 cells are not highly sensitive to induction of programmed cell death by wild-type p53. Because these observations conflict with previously suggested models for FdUrd-induced damage to parental DNA, we propose an alternative model to explain how incorporation of uracil into nascent DNA might result in single-strand breaks in the opposite (parental) strand and how these breaks might be converted to the double-strand breaks that produce cell death.

Identifying potential tumor markers and antigens by database mining and rapid expression screening.

Genes expressed specifically in malignant tissue may have potential as therapeutic targets but have been difficult to locate for most cancers. The information hidden within certain public databases can reveal RNA transcripts specifically expressed in transformed tissue. To be useful, database information must be verified and a more complete pattern of tissue expression must be demonstrated. We tested database mining plus rapid screening by fluorescent-PCR expression comparison (F-PEC) as an approach to locate candidate brain tumor antigens. Cancer Genome Anatomy Project (CGAP) data was mined for genes highly expressed in glioblastoma multiforme. From 13 mined genes, seven showed potential as possible tumor markers or antigens as determined by further expression profiling. Now that large-scale expression information is readily available for many of the commonly occurring cancers, other candidate tumor markers or antigens could be located and evaluated with this approach.