The Prevalence of Nephrolithiasis and Associated Risk Factors Among the Population of the Riyadh Province, Saudi Arabia.

Background and objective Kidney stones, also referred to as nephrolithiasis or renal calculi, is a condition where crystal depositions are formed within the kidney and ideally excreted from the body via the urethra with no pain; however, larger calculi may cause significant pain and require further medical assistance. The vast majority of patients who develop renal calculi form calcium stones, which are either a composition of calcium oxalate or calcium phosphate. Other types include uric acid, struvite, and cysteine. While kidney stones are one of the most significant diseases among the Saudi population, which require an acute emergency intervention to prevent serious long-term complications, there are limited studies published regarding this condition in Saudi communities. In light of this, we performed this study to assess the prevalence, incidence, and risk factors of kidney stones among the population of Riyadh, Saudi Arabia. Methods This was a cross-sectional study conducted in Riyadh, Saudi Arabia between August and October 2023, aiming to estimate the prevalence and risk factors of nephrolithiasis among residents of the Riyadh province. Data were collected through an electronic questionnaire in both Arabic and English and distributed via social media in addition to barcode handouts in various selected venues in Riyadh. The questionnaire involved 12 questions categorized into three sections. The first section obtained demographical information while the second section collected data about the past medical history of the participants. Lastly, the third section aimed to assess the prevalence of nephrolithiasis among participants or any history of the condition among their families. Results A total of 1,043 participants were surveyed, of whom 533 were males (51.1%). The prevalence of kidney stones was reported in 98 individuals (9.4%) overall. Individuals in the age groups of 36-50, 51-60, and >60 years showed significantly more renal stone prevalence than those in younger age groups (p<0.001). The prevalence was found to be higher in participants who were smokers, diabetic, hypertensive, and those who suffered from inflammatory bowel disease (IBD), gout, chronic kidney disease (CKD), hyperthyroidism, and hyperparathyroidism. Participants who took calcium supplements or had a positive family history of renal stones were found to have a higher prevalence of renal stones as well. However, only hypertension, gout, and family history showed any statistical significance (p<0.05). Conclusions A direct correlation was observed between hypertension, gout, positive family history, and aging and an increased prevalence of kidney stones among the inhabitants of the Riyadh province. Therefore, we encourage the local authorities to raise awareness of kidney stones and their related risk factors among the general public. Moreover, further local studies need to be conducted to gain deeper insights into kidney stone prevalence, especially pertaining to associated comorbidities and the pattern of the disease itself.

Retrospective Comparative Analysis of Neonatal Mortality and Morbidity in Preterm Singleton and Multiple Births -Single Center Experience.

Objective. To compare mortality and major neonatal morbidities between singleton preterm infants and preterm infants of multiple gestations born <33 weeks' gestation. Method. Case-control study of preterm multiples and singletons <33 weeks' born at King Abdul-Aziz Medical City Riyadh (KAMC-R) between January 2017 and December 2020. Out-born infants and infants with lethal congenital abnormalities were excluded from the study. Mortality and major neonatal morbidities including bronchopulmonary dysplasia (BPD), retinopathy of prematurity (ROP), sepsis and surgical necrotizing enterocolitis (NEC) were compared between preterm singletons and multiples. Results. A total of 803 preterm infants were included: 567 (70.6%) were singletons, 158 (19.6%) were twins and 36 (4.5%) infants were higher multiples. Adjusted mortality before hospital discharge was significantly higher among preterm infants of multiple gestations compared to preterm singletons (12.3% vs 7.9%; P = .003; AOR, 2.2; 95% CI, 1.3-3.7). Retinopathy of prematurity (ROP) needing treatment was significantly higher among preterm infants of multiple pregnancies compared to preterm singletons (11% vs 6.5%, P = .033, AOR 1.1, 95% CI, 1.04-2.99). In addition, the incidence of bronchopulmonary dysplasia (BPD) at 36 weeks post menstrual age (PMA) (29.7% vs 20.5%; P = .003; AOR, 1.7; 95% CI, 1.2-2.5) and culture positive sepsis (24.2% vs 17.5%; P = .044; AOR, 1.5; 95% CI, 1.01-2.2) were significantly higher among preterm infants of multiple pregnancy. There were no differences in mortality and adverse neonatal outcomes between twins and higher multiples. Conclusion. Preterm infants of multiple gestations suffered higher mortality and neonatal morbidities compared to preterm singleton infants despite a higher utilization of maternal antenatal steroids and better antenatal care.

Global analysis of the abundance of AU-rich mRNAs in response to glucocorticoid treatment.

Glucocorticoids (GC) like dexamethasone (Dex) are potent anti-inflammatory agents with diverse cellular functions including the potentiation of the activity of AU-rich elements (AREs). AREs are cis-acting instability sequence elements located in the 3'UTRs of many inflammatory mediator mRNAs. Here, available RNA-seq data were used to investigate the effect of GCs on the ARE-mRNA-transcriptome. At a global scale, ARE-mRNAs had a tendency to be downregulated after GC-treatment of the A549 lung cancer cell-line, but with notable cases of upregulation. mRNA stability experiments indicated that not only the downregulated, but also the upregulated ARE-mRNAs are destabilized by Dex-treatment. Several of the most upregulated ARE-mRNAs code for anti-inflammatory mediators including the established GC targets DUSP1 and ZFP36; both code for proteins that target ARE-containing mRNAs for destruction. GCs are widely used in the treatment of COVID-19 patients; we show that ARE-mRNAs are more likely to regulate in opposite directions between Dex-treatment and SARS-CoV-2 infections compared to non-ARE mRNAs. The effect of GC treatment on ARE-mRNA abundance was also investigated in blood monocytes of COVID-19 patients. The results were heterogeneous; however, in agreement with in vitro observations, ZFP36 and DUSP1 were often amongst the most differentially expressed mRNAs. The results of this study propose a universal destabilization of ARE-mRNAs by GCs, but a diverse overall outcome in vitro likely due to induced transcription or due to the heterogeneity of COVID-19 patient's responses in vivo.

Post-transcriptional regulation of BIRC5/survivin expression and induction of apoptosis in breast cancer cells by tristetraprolin.

Inhibition of apoptosis is one of the hallmarks of cancer and is a target of various therapeutic interventions. BIRC5 is an inhibitor of apoptosis that is aberrantly expressed in cancer leading to sustained growth of tumours. Post-transcriptional control mechanisms involving RNA-binding proteins and AU-rich elements (AREs) are fundamental to many cellular processes and changes in the expression or function of these proteins can promote an aberrant and pathological phenotype. BIRC5 mRNA has an ARE in its 3' UTR making it a candidate for regulation by the RNA binding proteins tristetraprolin (TTP) and HuR (ELAVL1). In this study, we investigated the binding of TTP and HuR by RNA-immunoprecipitation assays and found that these proteins were associated with BIRC5 mRNA to varying extents. Consequently, BIRC5 expression decreased when TTP was overexpressed and apoptosis was induced. In the absence of TTP, BIRC5 mRNA was stabilized, protein expression increased and the number of apoptotic cells declined. As an ARE-mRNA stabilizing protein, recombinant HuR led to upregulation of BIRC5 expression, whereas HuR silencing was concomitant with downregulation of BIRC5 mRNA and protein and increased cell death. Survival analyses demonstrated that increased TTP and low BIRC5 expression predicted an overall better prognosis compared to dysregulated TTP and high BIRC5. Thus, the results present a novel target of ARE-mediated post-transcriptional regulation.

Comparing Thyroidectomy Techniques, Surgical Loupe and Neuromonitoring Between ENT and Endocrine Surgeons-an Observational Study.

Thyroid surgery is performed by ENT head and neck (ENT-HNS), endocrine (ES) and general surgeons (GS). Each modality adopts different surgical techniques causing difference in outcome, operative time and postoperative complication. A retrospective chart review of thyroid surgeries performed by two ENT-HNS, three ES of a single tertiary center was conducted. We compared the use of neuromonitoring and surgical loupe and subsequent patient outcomes between surgeries performed by ENT-HNS versus ES, focusing on parathyroid gland identification, operative duration, vocal cord paralysis and length of hospital stay. A total of 167 patients underwent thyroid surgery. Surgical loupes were used in all the surgeries performed by ENT-HNS vs. 85% by the ES. Parathyroid glands were identified in all the surgeries performed by ENT-HNS versus 95% by ES. Neuromonitoring was used in all the surgeries performed by ENT-HNS, and none by the ES. Vocal cord paralysis developed in two patients of ES versus none in the ENT-HNS. Mean operative duration for total thyroidectomy in ENT-HN surgeries, 183.7 min vs. 151 min in the ES. The mean hospital stay of patients was 3.6 ± 1.6 days for ENT-HNS, and 5.45 ± 3 days for ES. Identification of parathyroid gland and recurrent laryngeal nerve by neuromonitoring and surgical loupes may increase operative time but decrease the rate of vocal cord paralysis and increases the chance of parathyroid gland identification.

Changes in the patterns of respiratory support and incidence of bronchopulmonary dysplasia; a single center experience.

BACKGROUND: With the advances in neonatal intensive care, the survival rate of extremely preterm infants is increasing. However, bronchopulmonary dysplasia (BPD) remains a major cause of morbidity among infants in this group. This study examined the changes in respiratory support modalities, specifically heated humidified high-flow nasal cannula (HHHFNC), and their association with BPD incidence among preterm infants born at < 29 weeks of gestation. METHOD: This population-based retrospective cohort study included infants born at < 29 weeks of gestation between 2016 and 2020. Data regarding the use and duration of respiratory support modalities were obtained, including mechanical ventilation, continuous positive airway pressure, HHHFNC, and low-flow oxygen therapy. Additionally, the incidence of BPD was determined in the included infants. Trend analysis for each respiratory support modality and BPD incidence rate was performed to define the temporal changes associated with changes in BPD rates. In addition, a logistic regression model was developed to identify the association between BPD and severity grade using HHHFNC. RESULTS: Three Hundred and sixteen infants were included in this study. The use and duration of HHHFNC therapy increased during the study period. Throughout the study period, the overall incidence of BPD was 49%, with no significant trends. The BPD rate was significantly higher in the infants who received HHHFNC than in those who did not (52% vs. 39%, P = 0.03). Analysis of BPD severity grades showed that both grade 1 BPD (34% vs. 21%, P = 0.03) and grade 2 BPD (12% vs. 1%, P < 0.01) were significantly more common among infants who received HHHFNC than among those who did not. In contrast, the incidence of grade 3 BPD was lower in infants who received HHFNC (6% vs. 17%, P < 0.01). The duration in days of HHHFNC was found to significantly predict BPD incidence (OR 1.04 [95%CI: 1.01-1.06], P < 0.01) after adjusting for confounding variables. CONCLUSION: The use of HHHFNC in extremely preterm infants born at < 29 weeks of gestation is increasing. There was a significant association between the duration of HHHFNC therapy and the development of BPD in extremely preterm infants born at < 29 weeks of gestation.

Effects of Fogging System and Nitric Oxide on Growth and Yield of 'Naomi' Mango Trees Exposed to Frost Stress.

In years with unfavorable weather, winter frost during the blossoming season can play a significant role in reducing fruit yield and impacting the profitability of cultivation. The mango Naomi cultivar Mangifera indica L. has a low canopy that is severely affected by the effects of frost stress. As a result of the canopy being exposed to physiological problems, vegetative development is significantly inhibited. The current investigation aimed to study the influence of spraying nitric oxide and fogging spray systems on Naomi mango trees grafted on 'Succary' rootstock under frost stress conditions. The treatments were as follows: nitric oxide (NO) 50 and 100 µM, fogging spray system, and control. In comparison to the control, the use of nitric oxide and a fogging system significantly improved the leaf area, photosynthesis pigments of the leaf, the membrane stability index, yield, and physical and chemical characteristics of the Naomi mango cultivar. For instance, the application of 50 µM NO, 100 µM NO, and the fogging spray system resulted in an increase in yield by 41.32, 106.12, and 121.43% during the 2020 season, and by 39.37, 101.30, and 124.68% during the 2021 season compared to the control, respectively. The fogging spray system and highest level of NO decreased electrolyte leakage, proline content, total phenolic content, catalase (CAT), peroxidases (POX), and polyphenol oxidase (PPO) enzyme activities in leaves. Furthermore, the number of damaged leaves per shoot was significantly reduced after the application of fogging spray systems and nitric oxide in comparison to the control. Regarding vegetative growth, our results indicated that the fogging spray system and spraying nitric oxide at 100 µM enhanced the leaf surface area compared to the control and other treatments. A similar trend was noticed regarding yield and fruit quality, whereas the best values were obtained when the fogging spray system using nitric oxide was sprayed at a concentration of 100 µM. The application of fogging spray systems and nitric oxide can improve the production and fruit quality of Naomi mango trees by reducing the effects of adverse frost stress conditions.

Extent of exposure to scented candles and prevalence of respiratory and non-respiratory symptoms amongst young university students.

BACKGROUND: Incense burning such as scented candles are commonly used in Arabian Gulf regions as it is thought to produce relaxing effects on people's mood. This study is conducted to examine the prevalence of scented candles' usage, extent of exposure and its effects on individuals' health based on symptoms prevalence in young university students. MATERIAL AND METHOD: A cross-sectional study was conducted on university students from different regions in Saudi Arabia. Data was collected in March 2020 using an online questionnaire survey adapted from The European Community Respiratory Health Survey-II (ECRHS-II). Inclusion criterion for recruitment was students with non-smoking status. Descriptive statistics were used to report demographic data on the extent of exposure to scented candles (in terms of frequency and duration) and the presence of symptoms. Multiple logistic regression analysis was used to assess the relationship between scented candles exposure and respiratory and other health-related problems. RESULTS: The prevalence of scented candles usage was 65.7% (472/718) among the respondents. However, its pervasiveness was significantly higher in females than in male respondents (74.9% vs. 28.4%; p = 0.0001). Among the scented candle users, 34.8% of the respondents used the scented candles more than 4 times a month and 40.2% of the respondents lit the scented candles for 20-40 min. A total of 117 (24.8%) respondents reported health-related problem and the top three health problems were headache 72 (15.2%), shortness of breath 42 (8.9%) and cough 37 (7.8%). The scented candle usage 5-6 times a week showed significantly lower wheezing (OR = 0.10, 95%CI 0.02-0.54, p = 0.008). The duration of more than 60 min of scented candle exposure showed higher occurrence of headache 1.42 times (95% CI = 0.68-2.96), sneezing 1.29 times (95% CI = 0.42-4.00) and wheezing 1.23 times (95% CI = 0.48-3.13), though the association was not significant. CONCLUSION: The results show that scented candle usage is more prevalent among female university students in Saudi Arabia. The common health-related problems associated with scented candle exposure were headache, shortness of breath and coughing.

Monitoring the effect of TNF-alpha inhibitors on laboratory parameters and adverse effects in different diseases: a retrospective, single-center study.

BACKGROUND: The introduction of biological treatments has revolutionized the management of moderate-to-severe psoriasis. Multiple clinical trials have established the efficacy of biological agents in the treatment of moderate-to-severe psoriasis. Nevertheless, there are no clear indications for optimal monitoring intervals during treatment. OBJECTIVES: Collect and analyze laboratory evaluation data from patients receiving biological therapy to provide a better understanding of the need for laboratory investigations before and during treatment with biological agents, and to analyze adverse events and other factors. DESIGN: Retrospective cohort SETTINGS: Tertiary care center in Riyadh, Saudi Arabia. PATIENTS AND METHODS: Data were collected from the electronic medical records of patients attending the dermatology, rheumatology, and gastroenterology clinics from June 2014 to June 2019. The laboratory parameters of patients who have received one of the TNF-alpha inhibitors (adalimumab, etanercept, or infliximab) were collected starting at baseline and up to at least one year from treatment initiation. MAIN OUTCOME MEASURES: The time points at which patients developed significantly abnormal laboratory results during treatment with one of the TNF-alpha inhibitors. SAMPLE SIZE: 250 patients RESULTS: Most patients were treated with adalimumab (38.4%); a similar proportion (38%) with infliximab, whereas only 23.6% were treated with etanercept. The majority of the significant abnormal laboratory results occurred at baseline, 3-6 and 9-12 months. Most abnormalities were among patients using infliximab, followed by etanercept, and then adalimumab. The median number of laboratory abnormalities for dermatology patients was significantly lower than that for gastroenterology patients (P<.001), and for rheumatology patients (P=.002). CONCLUSIONS: Because dermatology patients showed a lower median number of laboratory abnormalities than patients treated by other specialties in our study, we believe that dermatology patients require less frequent laboratory monitoring. Therefore, we recommend laboratory evaluation at baseline, after 3-6 months, 1 year from the beginning of treatment, and annually thereafter for patients using TNF-alpha inhibitor agents. However, more frequent testing might be warranted according to patient comorbidities, concomitant medications, and physician judgment. LIMITATIONS: Single center and retrospective design. CONFLICT OF INTEREST: None.

Admission temperature and neonatal outcomes - single-centre experience in Saudi Arabia.

Objective: This study aimed to investigate the association between admission hypothermia (AH), neonatal mortality and major neonatal morbidities in preterm infants <33 weeks' gestation. An additional aim of the study was to examine changes in the prevalence of admission hypothermia after the initiation of a thermoregulation quality improvement (QI) project. Method: This is a retrospective cohort study of preterm infants < 33 weeks' gestation born at King AbdulAziz Medical City Riyadh (KAMC-R) between January 2017 to December 2020. Results: Eight-hundred infants were born during the study period. Four hundred and one infants (50.1%) had an admission temperature of <36.5 °C and a further 399 (49.9%) had an admission temperature of >36.5 °C. The mortality before discharge was 15.7% in infants with AH compared to 4.8% among those with an admission temperature above 36.5 °C. This remained statistically significant after adjustments for gestational age and maternal PET status on a multivariate analysis (P = .001, OR 2.7,95%CI 1.5-4.7). The need for mechanical ventilation (P = .005) and incidence of surgical NEC (P = .030) were significantly different between the two temperature groups. Mean (SD) admission temperature increased from 36.3 °C to 36.6 °C following the thermoregulation intervention program (P <.001). Admission temperature <36 °C is associated with higher mortality in the first week (P = .001, OR 3.3,95% CI (1.7-6.6)) and increased incidence of cystic PVL (P = .04, OR 2.1, CI (1.03-4.3)). Conclusion: Preterm infants with AH suffered higher mortality and greater neonatal morbidities.

Axillary Recurrence in Breast Cancer Patients After Negative Sentinel Lymph Node Biopsy: Retrospective Cohort Study From Riyadh, Saudi Arabia.

Breast cancer (BC) is among the most prevalent cancers globally. For minimally invasive axillary staging in early breast cancer, sentinel lymph node biopsy (SLNB) is commonly regarded as the gold standard. Historically, axillary lymph node dissection (ALND) was used as a staging procedure, but the less morbid SLNB has now replaced it. This retrospective cohort study, undertaken with patients at King Saud University Medical City in Riyadh, Saudi Arabia, evaluates mid-term follow-up data on axillary recurrences and outcomes for breast cancer patients with negative SLNB. The results indicate that the five-year risk of developing regional recurrence following negative SLNB is 0% in breast cancer patients. The low relapse rate further contributes to the evidence base suggesting the efficacy of SLNB and the higher morbidity associated with ALND. Future researchers should conduct a nationwide and long-term follow-up study to offer additional insights into the efficacy of SLNB.

Biological Control of Celery Powdery Mildew Disease Caused by Erysiphe heraclei DC In Vitro and In Vivo Conditions.

The present study aimed to investigate the potentiality of certain biocontrol agents, namely Bacillus subtilis, B. pumilus, B. megaterium, Pseudomonas fluorescens, Serratia marcescens, Trichoderma album, T. harzianum and T. viride, as well as the synthetic fungicide difenoconazole to control celery powdery mildew caused by Erysiphe heraclei DC, in vitro (against conidia germination and germ tube length of E. heraclei) and in vivo (against disease severity and AUDPC). In vitro, it was found that the antifungal activity of the tested biocontrol agents significantly reduced the germination percentage of the conidia and germ tube length of the pathogen. The reduction in conidia germination ranged between 88.2% and 59.6% as a result of the treatment with B. subtilis and T. album, respectively compared with 97.1% by the synthetic fungicide difenoconazole. Moreover, the fungicide achieved the highest reduction in germ tube length (92.5%) followed by B. megaterium (82.0%), while T. album was the least effective (62.8%). Spraying celery plants with the tested biocontrol agents in the greenhouse significantly reduced powdery mildew severity, as well as the area under the disease progress curve (AUDPC), after 7, 14, 21 and 28 days of application. In this regard, B. subtilis was the most efficient followed by B. pumilus, S. marcescens and B. megaterium, with 80.1, 74.4, 73.2 and 70.5% reductions in disease severity, respectively. In AUDPC, reductions of those microorganisms were 285.3, 380.9, 396.7 and 431.8, respectively, compared to 1539.1 in the control treatment. On the other hand, the fungicide difenoconazole achieved maximum efficacy in reducing disease severity (84.7%) and lowest AUDPC (219.3) compared to the other treatments. In the field, all the applied biocontrol agents showed high efficiency in suppressing powdery mildew on celery plants, with a significant improvement in growth and yield characteristics. In addition, they caused an increase in the concentration of leaf pigments, and the activities of defense-related enzymes such as peroxidase (PO) and polyphenol oxidase (PPO) and total phenol content (TPC). In conclusion, the results showed the possibility of using tested biocontrol agents as eco-friendly alternatives to protect celery plants against powdery mildew.

Post-transcriptional screen of cancer amplified genes identifies ERBB2/Her2 signaling as AU-rich mRNA stability-promoting pathway.

Amplification of specific cancer genes leads to their over-expression contributing to tumor growth, spread, and drug resistance. Little is known about the ability of these amplified oncogenes to augment the expression of cancer genes through post-transcriptional control. The AU-rich elements (ARE)-mediated mRNA decay is compromised for many key cancer genes leading to their increased abundance and effects. Here, we performed a post-transcriptional screen for frequently amplified cancer genes demonstrating that ERBB2/Her2 overexpression was able to augment the post-transcriptional effects. The ERBB1/2 inhibitor, lapatinib, led to the reversal of the aberrant ARE-mediated process in ERBB2-amplified breast cancer cells. The intersection of overexpressed genes associated with ERBB2 amplification in TCGA datasets with ARE database (ARED) identified ERBB2-associated gene cluster. Many of these genes were over-expressed in the ERBB2-positive SKBR3 cells compared to MCF10A normal-like cells, and were under-expressed due to ERBB2 siRNA treatment. Lapatinib accelerated the ARE-mRNA decay for several ERBB2-regulated genes. The ERBB2 inhibitor decreased both the abundance and stability of the phosphorylated inactive form of the mRNA decay-promoting protein, tristetraprolin (ZFP36/TTP). The ERBB2 siRNA was also able to reduce the phosphorylated ZFP36/TTP form. In contrast, ectopic expression of ERBB2 in MCF10A or HEK293 cells led to increased abundance of the phosphorylated ZFP36/TTP. The effect of ERBB2 on TTP phosphorylation appeared to be mediated via the MAPK-MK2 pathway. Screening for the impact of other amplified cancer genes in HEK293 cells also demonstrated that EGFR, AKT2, CCND1, CCNE1, SKP2, and FGFR3 caused both increased abundance of phosphorylated ZFP36/TTP and ARE-post-transcriptional reporter activity. Thus, specific amplified oncogenes dysregulate post-transcriptional ARE-mediated effects, and targeting the ARE-mediated pathway itself may provide alternative therapeutic approaches.

Kinome inhibition reveals a role for polo-like kinase 1 in targeting post-transcriptional control in cancer.

Dysfunctions in post-transcriptional control are observed in cancer and chronic inflammatory diseases. Here, we employed a kinome inhibitor library (n = 378) in a reporter system selective for 3'-untranslated region-AU-rich elements (ARE). Fifteen inhibitors reduced the ARE-reporter activity; among the targets is the polo-like kinase 1 (PLK1). RNA-seq experiments demonstrated that the PLK1 inhibitor, volasertib, reduces the expression of cytokine and cell growth ARE mRNAs. PLK1 inhibition caused accelerated mRNA decay in cancer cells and was associated with reduced phosphorylation and stability of the mRNA decay-promoting protein, tristetraprolin (ZFP36/TTP). Ectopic expression of PLK1 increased abundance and stability of high molecular weight of ZFP36/TTP likely of the phosphorylated form. PLK1 effect was associated with the MAPK-MK2 pathway, a major regulator of ARE-mRNA stability, as evident from MK2 inhibition, in vitro phosphorylation, and knockout experiments. Mutational analysis demonstrates that TTP serine 186 is a target for PLK1 effect. Treatment of mice with the PLK1 inhibitor reduced both ZFP36/TTP phosphorylation in xenograft tumor tissues, and the tumor size. In cancer patients' tissues, PLK1/ARE-regulated gene cluster was overexpressed in solid tumors and associated with poor survival. The data showed that PLK1-mediated post-transcriptional aberration could be a therapeutic target.

Synthesis, Cytotoxic Analysis, and Molecular Docking Studies of Tetrazole Derivatives via N-Mannich Base Condensation as Potential Antimicrobials.

PURPOSE: A new series of tetrazole derivatives, which are renowned antimicrobials possessing a five-membered aromatic heterocyclic group, are synthesized herein and subjected to antimicrobial and cytotoxicity screening. METHODS: The tetrazole derivatives were synthesized via ultrasonication using Mannich base condensation. Structural verification of the products was performed using IR, 1H NMR, and 13C NMR spectroscopy, as well as mass spectroscopic and elemental analyses. The compounds were then screened for antimicrobial and cytotoxic activity against HepG2 (liver), MCF-7 (breast), and HeLa (cervical) cell lines. Inter- and intra-molecular binding interactions were determined using molecular docking studies. The exact binding mode between the most active tetrazole derivatives (ie, 1b, 2a, and 2b) and the proteins (ie, 4OR7, 1AI9, and 4FM9) was established using Autodock Vina 1.1.2 software and compared to the binding mode of the reference compounds (ie, cefazolin, clotrimazole, and fluorouracil). RESULTS: Compound 1b was extremely active against Enterococcus faecalis relative to the positive control cefazolin. Compounds 1b and 1e were active against Candida albicans and Microsporum audouinii compared to the positive control clotrimazole in antifungal screening. The HepG2 (liver) and MCF-7 (breast) cancer cell lines were particularly susceptible to the synthesized compounds. Compared to the control compound fluorouracil, 2a and 2b were extremely active against all three cancer cell lines. Molecular docking studies showed that 2b exhibited higher binding affinity (-7.8 kcal/mol) to the 4OR7 protein than the control cefazolin (-7.2 kcal/mol). CONCLUSION: Generally, 1b, 2a, and 2b exhibited impressive inhibitory capabilities in antibacterial, antifungal, and cytotoxic screenings relative to the reference compounds. The results of the molecular docking studies and both the microbial and anticancer screenings indicate that these novel derivatives could be developed into potential therapeutic agents for medical applications.

Validating candidate biomarkers for different stages of non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is a common chronic condition caused by the accumulation of fat in the liver. NAFLD may range from simple steatosis to advanced cirrhosis, and affects more than 1 billion people around the world. To date, there has been no effective treatment for NAFLD. In this study, we evaluated the expression of 4 candidate NAFLD biomarkers to assess their possible applicability in the classification and treatment of the disease.Twenty-six obese subjects, who underwent bariatric surgery, were recruited and their liver biopsies obtained. Expression of 4 candidate biomarker genes, PNPLA3, COL1A1, PPP1R3B, and KLF6 were evaluated at gene and protein levels by RT-qPCR and enzyme-linked immunosorbent assay (ELISA), respectively.A significant increase in the levels of COL1A1 protein (P = .03) and PNPLA3 protein (P = .03) were observed in patients with fibrosis-stage NAFLD compared to that in patients with steatosis-stage NAFLD. However, no significant differences were found in abundance of PPP1R3B and KLF6 proteins or at the gene level for any of the candidate.This is the first study, to our knowledge, to report on the expression levels of candidate biomarker genes for NAFLD in the Saudi population. Although PNPLA3 and PPP1R3B had been previously suggested as biomarkers for steatosis and KLF6 as a possible marker for the fibrosis stage of NAFLD, our results did not support these findings. However, other studies that had linked PNPLA3 to fibrosis in advanced NAFLD supported our current finding of high PNPLA3 protein in patients with fibrosis. Additionally, our results support COL1A1 protein as a potential biomarker for the fibrosis stage of NAFLD, and indicate its use in the screening of patients with NAFLD. Further studies are required to validate the use of COL1A1 as a biomarker for advanced NAFLD in a larger cohort.

Clinical and functional significance of tumor/stromal ATR expression in breast cancer patients.

BACKGROUND: Most breast cancer-associated fibroblasts (CAFs) are active and important cancer-promoting cells, with significant impact on patient prognosis. Therefore, we investigated here the role of the protein kinase ATR in breast stromal fibroblasts in the prognosis of locally advanced breast cancer patients. METHODS: We have used immunohistochemistry to assess the level of ATR in breast cancer tissues and their adjacent normal tissues. Immunoblotting as well as quantitative RT-PCR were utilized to show the role of breast cancer cells and IL-6 as well as AUF-1 in downregulating ATR in breast stromal fibroblasts. Engineered human breast tissue model was also used to show that ATR-deficient breast stromal fibroblasts enhance the growth of breast cancer cells. RESULTS: We have shown that the protein kinase ATR is downregulated in cancer cells and their neighboring CAFs in breast cancer tissues as compared to their respective adjacent normal tissues. The implication of cancer cells in ATR knockdown in CAFs has been proven in vitro by showing that breast cancer cells downregulate ATR in breast fibroblasts in an IL-6/STAT3-dependent manner and via AUF-1. In another cohort of 103 tumors from locally advanced breast cancer patients, we have shown that absence or reduced ATR expression in tumoral cells and their adjacent stromal fibroblasts is correlated with poor overall survival as well as disease-free survival. Furthermore, ATR expression in CAFs was inversely correlated with tumor recurrence and progression. CONCLUSION: ATR downregulation in breast CAFs is frequent, procarcinogenic, and correlated with poor patient survival.

Clinicopathological concordance in the diagnosis of skin diseases: a retrospective analysis of 5000 histopathology reports.

BACKGROUND: The accuracy of clinical diagnoses of skin diseases has not been researched in Saudi Arabia. OBJECTIVES: Assess concordance between the histopathological and clinical diagnosis in skin diseases. DESIGN: Retrospective. SETTING: Academic tertiary care center. METHODS: Demographic, clinical and pathological data were collected from the medical record for the period 1997-2013. MAIN OUTCOME MEASURES: Concordance between the pathological and clinical diagnosis. SAMPLE SIZE: 4268 cases. RESULTS: Of 4268 biopsies, 2440 (58.1%) were females. The mean age (SD) of patients was 36.9 (17.8) years. The three most common locations from which skin biopsies were retrieved in descending order were the lower extremity (1123; 29.1%), head, neck, scalp and hair (1033; 26.7%) and trunk (853; 22.1%). Overall concordance was 75.9% (partial concordance 47.6%, full concordance 28.3%). Biopsies from the oral mucosa and lips had the lowest concordance (overall 58.5%, full 26.4%) at P=.004. Overall concordance was highest for the following three diagnoses: malignant neoplasms, 88%; vesiculobullous diseases 87%; urticarias, erythemas, and purpuras 87%. CONCLUSION: There is considerable variability in concordance among different histopathological diagnoses. The full concordance between the clinical diagnosis and the pathological diagnosis is low. This is a reflection of the fact that the biopsies were obtained only in cases where the clinical diagnosis was a dilemma. LIMITATIONS: Single center, retrospective, incomplete medical records, low percentage of biopsies were assessed by dermatopathologists. CONFLICT OF INTEREST: None.

Gene therapy of hematological disorders: current challenges.

Recent advances in genetic engineering technology and stem cell biology have spurred great interest in developing gene therapies for hereditary, as well as acquired hematological disorders. Currently, hematopoietic stem cell transplantation is used to cure disorders such as hemoglobinopathies and primary immunodeficiencies; however, this method is limited by the availability of immune-matched donors. Using autologous cells coupled with genome editing bypasses this limitation and therefore became the focus of many research groups aiming to develop efficient and safe genomic modification. Hence, gene therapy research has witnessed a noticeable growth in recent years with numerous successful achievements; however, several challenges have to be overcome before gene therapy becomes widely available for patients. In this review, I discuss tools used in gene therapy for hematological disorders, choices of target cells, and delivery vehicles with emphasis on current hurdles and attempts to solve them, and present examples of successful clinical trials to give a glimpse of current progress.

Comparison study between open and laparoscopic liver resection in a Saudi tertiary center.

OBJECTIVES: To compare King Saud University Medical City experience in laparoscopic liver resection with our previously established database for open resections. METHODS: A retrospective study was conducted at King Saud University Medical City, Riyadh, Saudi Arabia. All adult patients who underwent liver resection from 2006 to 2017 were included. Patients who had their procedure converted to open were excluded. RESULTS: Among the 111 liver resections included, 22 (19.8%) were performed laparoscopically and 89 (80.1%) were performed using the open technique. Malignancy was the most common indication in both groups (78.5%). The mean operative time was 275 min (SD 92.2) in the laparoscopic group versus 315 min (SD 104.3) in the open group. Intraoperative blood transfusion was required in the laparoscopic (9%) and open groups (31.4%). The morbidity rate was 13.6% in the laparoscopic group and 31.4% in the open group, and the mortality rate was 0% in the laparoscopic group and 5.6% in the open group. CONCLUSION: Laparoscopic liver resection appears to be a safe technique and can be performed in various benign and malignant cases.