Incidence and risk factors of prostate cancer among the Northern and Eastern parts of the United Arab Emirates population.

BACKGROUND: Prostate cancer (PCa) is a prevalent disease worldwide. However, the incidence and patient-specific risk factors of PCa in the Middle East, specifically in the United Arab Emirates, have not been previously reported. METHODS: We conducted a retrospective cohort study on 2377 men diagnosed with either benign prostatic hyperplasia (BPH) or PCa in the Northern and Eastern regions of the United Arab Emirates, excluding the Western part, which includes Abu Dhabi. The study spanned from January 2012 and December 2021. To calculate the PCa incidence rate, we utilized the world age-standardized incidence rates (W-ASIR) categorized by age groups. Patient-specific risk factors of PCa were identified through a multivariate logistic regression analysis of clinical data. RESULTS: A total of 247 cases of PCa and 2130 cases of BPH were included in the study. In our cohort, the W-ASIR for PCa was 21.3 per 100,000 men. The incidence of PCa showed an increasing trend with age, with the highest incidence observed among men aged 70 years and older. Accordingly, multivariate analysis revealed that age over 70 was associated with an increased risk of PCa (OR: 2.546, 95% confidence interval [CI]: 1.892-3.425, p < 0.01). On the other hand, preexisting conditions such as hypertension and diabetes mellitus were found to lower the risk of PCa (OR: 0.222, 95% CI: 0.163-0.302, p < 0.001) and (OR: 0.364, 95% CI: 0.205-0.648, p < 0.001), respectively. Additionally, metformin intake was associated with a reduced risk of PCa (OR: 0.385, 95% CI: 0.190-0.782, p = 0.008); while insulin usage increased the risk of PCa (OR: 2.586, 95% CI: 1.539-4.344, p < 0.001). Anti-BPH medications such as phosphodiesterase inhibitors (OR: 0.223, 95% CI: 0.069-0.723, p = 0.012) or 5-α reductase (OR: 0.206, 95% CI: 0.110-0.389, p < 0.000), were found to lower the risk of PCa. CONCLUSION: The findings underscore the high incidence of PCa in the United Arab Emirates, with age being a significant factor. Furthermore, the study highlights the influence of certain comorbidities and medications on the risk of developing PCa within the United Arab Emirates population.

Nucleic acid sensor STING drives remodeling and its inhibition enhances steroid responsiveness in chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is progressive and irreversible chronic lung inflammatory disease. Cigarette smoke, the main cause of COPD, is often associated with double-stranded DNA release which potentially activates DNA-sensing pathways, such as STING. This study, therefore, analyzed the role of STING pathway in inducing pulmonary inflammation, steroid resistance, and remodeling in COPD. METHODS: Primary cultured lung fibroblasts were isolated from healthy non-smoker, healthy smoker, and smoker COPD individuals. The expression of STING pathway, remodeling, and steroid resistance signatures were investigated in these fibroblasts upon LPS stimulation and treatment with dexamethasone and/or STING inhibitor, at both mRNA and protein levels using qRT-PCR, western blot, and ELISA. RESULTS: At baseline, STING was elevated in healthy smoker fibroblasts and to a higher extent in smoker COPD fibroblasts when compared to healthy non-smoker fibroblasts. Upon using dexamethasone as monotherapy, STING activity was significantly inhibited in healthy non-smoker fibroblasts but showed resistance in COPD fibroblasts. Treating both healthy and COPD fibroblasts with STING inhibitor in combination with dexamethasone additively inhibited STING pathway in both groups. Moreover, STING stimulation triggered a significant increase in remodeling markers and a reduction in HDAC2 expression. Interestingly, treating COPD fibroblasts with the combination of STING inhibitor and dexamethasone alleviated remodeling and reversed steroid hyporesponsiveness through an upregulation of HDAC2. CONCLUSION: These findings support that STING pathway plays an important role in COPD pathogenesis, via inducing pulmonary inflammation, steroid resistance, and remodeling. This raises the possibility of using STING inhibitor as a potential therapeutic adjuvant in combination with common steroid treatment.

Risks of prostate cancer and mortality in the city of Sharjah, United Arab Emirates.

Background: Prostatic hyperplasia (BPH) and prostate cancer (PCa) are common age-related diseases in men. According to World Health Organization (WHO), PCa is the second most common cancer among Emirati men. This study aimed to identify the risk factors associated with PCa and mortality in a cohort diagnosed with PCa between 2012 and 2021 in Sharjah, United Arab Emirates (UAE). Methods: The data collected in this retrospective case-control study included patient demographics and comorbidities, as well as PCa markers such as prostate-specific antigen (PSA), prostate volume, prostate-specific antigen density (PSAD), and Gleason scores. Risk factors for PCa were assessed using multivariate logistic regression analysis, and factors associated with all-cause mortality in PCa patients were evaluated using Cox-proportional hazard analysis. Results: Of the 192 cases analyzed in this study, 88 were diagnosed with PCa and 104 were diagnosed with BPH. Regarding risk factors for PCa, a higher risk of PCa was associated with age 65 or older (OR=2.76, 95% confidence interval (CI): 1.04-7.30; P=0.038) and serum PSAD greater than 0.1 ng/mL2 (OR=3.48, 95% CI:1.66-7.32; P=0.001), whereas being of UAE nationals (OR=0.40, 95% CI:0.18-0.88; P=0.029) were associated with lower risk of PCa, after adjusting for patient demographics and comorbidities. Moreover, regarding cancer markers, higher serum PSA level (P=0.003) and smaller prostate volume (P=0.028) were associated with a higher risk of PCa, after adjusting with patients' age and BMI. Additionally, a high-grade Gleason score was associated with an increased risk of all-cause mortality after adjusting for patient's age and BMI (hazard ratio, aHR= 2.3, 95% CI:1.3-4.1; P= 0.016). Conclusion: This study found that age 65 or older and serum PSAD greater than 0.1 ng/mL2 are risk factors for PCa, while UAE nationality is associated with a lower risk. PSAD may be a better screening marker for PCa compared to traditional markers such as PSA and prostate volume.

Early administration of remdesivir to COVID-19 patients associates with higher recovery rate and lower need for ICU admission: A retrospective cohort study.

OBJECTIVES: Remdesivir is one of the most widely recommended and used medications for COVID-19 treatment. However, different outcomes have been reported for hospitalized patients with COVID-19 treated with remdesivir. Specifically, the effect of the timing of remdesivir initiation (from patient's symptom onset) on clinical outcomes in COVID-19 patients has not been investigated. METHODS: This is a retrospective cohort study of patients hospitalized with COVID-19 and treated with or without remdisivir. The primary outcome was patient's recovery rate, defined as clinical improvement and patient's discharge by day 14 of symptom onset. The secondary outcome was the need for intensive care unit (ICU) admission, mechanical ventilation, and mortality within 28 days of patient's symptom onset. RESULTS: Out of 323 hospitalized adults with COVID-19, 107 (33.1%) received no remdesivir during their hospital stay, 107 (33.1%) received remdesivir early within 7 days of the symptom onset, and 109 (33.7%) received it at 8 days or later of symptom onset. At day 14 following symptom onset, higher proportion of patients recovered in the early remdesivir compared to the late remdesivir cohort, or patients who did not receive remdesivir (adjusted odds ratio, aOR, 2.65; 95% confidence interval [CI], 1.31 to 5.35). Moreover, early administration of remdesivir was associated with lower admission to intensive care unit (adjusted hazard ratio [aHR], 0.31; 95% CI, 0.15 to 0.64), less need for mechanical ventilation (aHR, 0.22; 95% CI, 0.10 to 0.51), and lower mortality at 28 days (aHR, 0.15; 95% CI, 0.04 to 0.53), as compared to the late remdesivir cohort or patients who did not receive remdesivir. CONCLUSION: Early administration of remdesivir within 7 days of symptom onset is associated with less need for mechanical ventilation and lower 28-days mortality.

The psychological impact of the COVID-19 pandemic on adults and children in the United Arab Emirates: a nationwide cross-sectional study.

BACKGROUND: The psychosocial impact of previous infectious disease outbreaks in adults has been well documented, however, there is limited information on the mental health impact of the COVID-19 pandemic on adults and children in the United Arab Emirate (UAE) community. The aim of this study was to explore anxiety levels among adults and children in the UAE and to identify potential risk and protective factors for well-being during the COVID-19 pandemic. METHODS: Using a web-based cross-sectional survey we collected data from 2200 self-selected, assessed volunteers and their children. Demographic information, knowledge and beliefs about COVID-19, generalized anxiety disorder (GAD) using the (GAD-7) scale, emotional problems in children using the strengths and difficulties questionnaire (SDQ), worry and fear about COVID-19, coping mechanisms and general health information were collected. Descriptive analysis was carried out to summarize demographic and participant characteristics, Chi-square analysis to explore associations between categorical variables and anxiety levels and multivariable binary logistic regression analysis to determine predictors of anxiety levels in adults and emotional problems in children. RESULTS: The overall prevalence of GAD in the general population was 71% with younger people (59.8%) and females (51.7%) reporting highest levels of anxiety. Parents who were teachers reported the highest percentage of emotional problems in children (26.7%). Adjusted multivariable logistic regression for GAD-7 scores showed that being female, high levels of worry associated with COVID-19, intention to take the COVID-19 vaccine and smoking were associated with higher levels of anxiety. Adjusted multivariable logistic regression for SDQ showed that higher emotional problems were reported for children in lower and higher secondary education, and parents who had severe anxiety were seven times more likely to report emotional problems in their children. CONCLUSIONS: This study reports the psychological impact of COVID-19 among adults and children in the UAE and highlights the significant association between parental and child anxiety. Findings suggest the urgency for policy makers to develop effective screening and coping strategies for parents and especially children.

Incidence and Clinicopathological Features of Breast Cancer in the Northern Emirates: Experience from Sharjah Breast Care Center.

BACKGROUND: Breast cancer is the most frequently reported cancer among women in the Middle East and North Africa (MENA) region. However, the available data about women breast cancer from the MENA and particularly from the Northern Emirates region of the United Arab Emirates (UAE) are scarce and inconsistent. Therefore, this study estimated the incidence, patient-specific factors including 25(OH)D levels, and clinicopathological features of breast cancer in women from the Northern Emirates. METHODS: We conducted this retrospective case-control study on 1,048 women who were referred to the Sharjah Breast Care Centre at University Hospital Sharjah between March 2016 and July 2018. Multivariate logistic regression was used for the statistical analysis of clinical data. RESULTS: Out of 1048 women with breast-related conditions referred to our canter, 94 (10%) were diagnosed with breast cancer (1 in 11), and approximately 1 in 5 of these women was younger than 40 years. After adjusting for age, body mass index and menopause status, women with serum 25-hydroxyvitamin D [25(OH)D] levels lower than 20 ng/mL were found to be at higher risk of breast cancer (odd ratio, 4.63; 95% CI, 2.61-8.23). The majority of breast cancer cases had invasive-ductal carcinoma with hormone-positive receptor molecular subtype (78 cases out of 94, 83%). HER2 overexpressing tumor (3+ by immunohistochemistry (IHC) or by fluorescence in situ hybridization (FISH)) was seen more in women younger than 40 years as compared to older women (7 cases out of 19 HER2 expressed tumors, p=0.007). CONCLUSION: Our study cohort showed a mean age of diagnosis of breast cancer in women a decade earlier than in the developed countries. Furthermore, women with breast cancer tend to be serum 25(OH)D deficient at diagnosis and to have luminal A tumors.

Airways Expression of SARS-CoV-2 Receptor, ACE2, and TMPRSS2 Is Lower in Children Than Adults and Increases with Smoking and COPD.

It has been reported that angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) are the main cell entry proteins for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and play a critical role in causing coronavirus disease 2019 (COVID-19). To investigate the expression level of these SARS-CoV-2 host cell entry genes in the lung airway, we used public gene expression datasets. We have found a differential expression of ACE2 and TMPRSS2 in nasal and bronchial airways relative to age and diseases status. Children were found to have significantly lower expression of COVID-19 receptors in the upper and lower airways (nasal and bronchial). Moreover, the lung airway expression of both ACE2 and TMPRSS2 was found to be significantly upregulated in smokers compared with non-smokers, and in patients with chronic obstructive pulmonary disease (COPD) compared with healthy subjects. No difference was observed in the blood expression levels of ACE2 and TMPRSS2 between children and adults, or in COPD or diabetic patients. However, a significant increase in blood expression levels of these genes was observed in patients with essential hypertension, whereas only ACE2 was upregulated in the blood of asthmatics. These results suggest that the observed difference in COVID-19 severity between children and adults could, in part, be attributed to the difference in ACE2 and TMPRSS2 airways tissue expression levels.

Low Vitamin D Serum Level Is Associated with HDL-C Dyslipidemia and Increased Serum Thrombomodulin Levels of Insulin-Resistant Individuals.

BACKGROUND: Insulin-resistant individuals are known to have dyslipidemia and are predicted to be at high risk of cardiovascular events. Vitamin D deficiency was shown to be associated with dyslipidemia; however, the type of dyslipidemia associated with vitamin D deficiency in insulin-resistant individuals is not determined. Furthermore, there is evidence linking insulin resistance with low-grade inflammation suggesting levels of pro-inflammatory cytokines to be increased in insulin-resistant states. OBJECTIVE: This study was performed to evaluate the impact of vitamin D deficiency, defined as serum level of 25(OH)D below 20 ng/mL, on lipid profile and inflammatory markers such as interleukin (IL-6) and IL-8, as well as soluble thrombomodulin (TM) in the serum of insulin-resistant individuals. METHODS: A total of 4114 individuals had simultaneous serum 25(OH)D, insulin, and lipid panel testing during 2013 as part of the United Arab Emirates National Diabetes and Lifestyle (UAEDIAB) study. Multivariate logistic regression analysis was used to assess the association between serum level of 25(OH)D and lipid profile in insulin-sensitive versus -resistant individuals. The lipid panel was stratified into high total cholesterol (TC: >6.2 mmol/L), high low-density lipoprotein-cholesterol (LDL-C: >2.59 mmol/L), high triglycerides (TG: >2.3 mmol/L), and low high-density lipoprotein-cholesterol (HDL-C: <1.55 mmol/L) dyslipidemia. Furthermore, the immunomodulatory and vasculoprotective effects of 25(OH)D were assessed by measuring the levels of IL-6, IL-8, and soluble TM in serum using ELISA. RESULTS: More than half of the 4114 individuals were insulin resistant (n=2760, 67%) and around one-fifth of them were vitamin D-deficient (n=796, 19%). After adjusting for age, gender, body mass index, smoking, ethnicity, and educational level, the only dyslipidemia associated with vitamin D-deficient-insulin-resistant individuals (OR 2.09 [95]; P=0.009) was lower HDL-C. Furthermore, deficient 25(OH)D individuals with low HDL-C levels had higher circulatory IL-6 and IL-8 levels, and higher serum soluble TM compared to individuals with sufficient 25(OH)D and normal lipid profiles (median, IL-6 pg/mL 0.82 vs 1.71, P=0.001; median, IL-8 pg/mL 51.31 vs 145.6, P=0.003; and median, soluble TM ng/mL 5.19 vs 7.38, P<0.0001; in sufficient vs deficient groups, respectively). CONCLUSION: The results of our study showed that in insulin-resistant individuals, vitamin D deficiency status is associated with HDL-C dyslipidemia and higher serum inflammatory and endothelial damage markers.

Integrative systematic review meta-analysis and bioinformatics identifies MicroRNA-21 and its target genes as biomarkers for colorectal adenocarcinoma.

BACKGROUND: Advanced colorectal has poor survival and are difficult to treat. Therefore, there is an urgent need for biomarkers to diagnose this cancer at earlier manageable stages. Micro-RNAs (miRNAs) are amongst the most significant biomarkers that have shown promise in improving management and early detection of different types of cancers. However, since MiRNAs are non-coding, the main limitation of using them as biomarkers is that they do not have associated phenotype and therefore difficult to validate using other techniques. This makes it difficult to understand the mechanism of miRNA is disease initiation and progression, therefore any methodology that can provide semantics to miRNA expression would enhance the understanding of the role of miRNA in disease. METHODS: Here we report an integrative meta-analysis and bioinformatics methodology that showed microRNA-21 and its associated target mRNA to be the most significant predictive biomarkers for colorectal adenoma and adenocarcinoma. After drawing key inferences by meta-analysis, the authors then developed a bioinformatics method to identify mir-21 gene targeting in a specific tissue using two different bioinformatics approaches; absolute GSEA (Gene Set Enrichment Analysis) and LIMMA (Linear Models for MicroArray data) to identify differentially expressed genes of miRNA-21. RESULTS: Results from GSEA intersection with mir-21 gene targets was a subset of longer gene list that was obtained from the GEO2R intersect. In our study, both of longer GEO2R gene target list and the more focused GSEA list established the fact that mir-21 target numerous functional pathways that are mostly interconnected. Our three steps bioinformatics approach identified ABCB1, HPGD, BCL2, TIAM1, TLR3, and PDCD4 as common targets for mir-21 in both of adenoma as well as adenocarcinoma suggesting they are biomarkers for early CRC. CONCLUSIONS: The approach in this study proposed combining the big data from the scientific literature together with novel bioinformatics to bring about a methodology that can be used to first identify which microRNAs are involved in a specific disease, and then to identify a panel of biomarkers derived from the microRNAs target genes, and from these target genes the functional significance of these microRNAs can be inferred providing better clinical value for the surgeon.

Incidence of bladder cancer in Benghazi, Libya over the past three decades.

There are limited data on the disease of bladder cancer in Libya. The objective of this study was to assess the pattern of incidence and clinical presentation of bladder cancer in Benghazi, Libya. This study was a retrospective cohort analysis conducted among consecutive individuals who were diagnosed and/or were treated for bladder cancer from January 1st 1983 to December 31st 2009. A total of 835 cases of bladder tumour were recorded. The world age-standardized incidence rate was 13.1 and 1.9 per 100,000 for males and females, respectively. The mean (standard deviation) age of all patients was 63.7 (14.7). The majority of patients (n = 750, 89.8%) were male, two-thirds of which (n = 594, 79.2%) were smokers while all female patients were non-smokers. Hematuria was the most frequent presenting symptom. Most tumours were well differentiated, and transitional cell carcinoma was the most frequent histological type. The incidence of bladder cancer in Libya is lower than most developed countries, increases by aging, and is more prevalent among males. The incidence of this disease is expected to grow in developing countries such as Libya because of increase in smoking popularity, the shift to sedentary life, diabetes mellitus, and obesity.