BackgroundTuberculosis (TB) continues to pose a serious threat to public health despite great efforts. For many years, management and screening for active TB cases have been the main focus of TB ...control programs. Latent TB is a stage where TB can be prevented and controlled. Therefore, designing a comprehensive TB control program that includes latent tuberculosis infection (LTBI) management diseases is needed to be implemented among the healthcare workers (HCWs) who have been found to be at a higher risk for active TB compared to the general population.The objective of the studyThe objective of the study is to assess the knowledge and perceptions of LTBI among HCWs. In addition to estimating the prevalence of LTBI among HCWs using closed-end questions in a self-administered questionnaire.Subjects and methodsThrough a cross-sectional study and non-random sampling technique, 324 (84%) healthcare workers who met the inclusion criteria completed and submitted the electronic questionnaire.ResultsAmong all participants, the study reported a good knowledge about LTBI; however, a third of HCWs had poor knowledge about the difference between LTBI and active TB. Eighteen percent of participants were diagnosed with LTBI, and two-thirds accepted the treatment. Of all participants who started the treatment, 55% completed the treatment course. The compliance rate was high among young HCWs and physicians who had a short course of LTB treatment regimen. ConclusionThe study reported a low acceptance and completion rate of LTBI therapy among HCWs. Low knowledge about some clinical facts of LTBI, the long duration of treatment, and being the treatment optional in Saudi health institutes were all barriers to accepting and completing the treatment of LTBI. All of these factors need to be addressed to increase the compliance rate to LTBI treatment.
Highlights • UV-irradiation for the hydrophilization of dental implants was investigated. • Original, out-of-the-box titanium, zirconia, and PEEK implants were hydrophobic. • UV-A switched solely ...implants with anatase coating into superhydrophilic. • UV-C switched normal titanium and anatase modified implants into superhydrophilic. • Wetting improvements by chairside UV treatments are strongly material dependent.
Titanium dental implants with sandblasted and/or acid-etched surfaces have shown clinical superiority in comparison to their smooth, machined counterparts, and are now state of the art. Sandblasting ...of finished, sintered zirconia implants, however, will damage the surface structure and affect the mechanical properties. To improve osseointegration of zirconia dental implants without impairing the original mechanical strength by crack initiation and partial phase transformation from tetragonal to monoclinic, roughening of the zirconia surface by sandblasting before the final sintering step was employed. Impact of the treatments on cellular reactions of SAOS-2 human osteoblast-like cells was investigated. Sandblasting of Yttrium-stabilized zirconia (Y-TZP) with 120 μm and 250 μm Al2O3 enhanced average roughness (Sa) from 0.28 μm to 4.1 μm and 5.72 μm, respectively. Cell adhesion of SAOS-2 osteoblasts was enhanced up to 175% on sandblasted surfaces, compared to the machined zirconia reference (100%). Metabolic activity and proliferation in the logarithmic growth phase (24-48 h) were not significantly affected. Sample surface coverage by the cells after prolonged incubation (72 h) was markedly decreased on the roughened samples, indicating a shift towards increased differentiation on these surfaces. The approach investigated here to roughen zirconia implants by sandblasting before sintering shows potential to improve the clinical performance of ceramic dental implants.
Summary
Background
The aim of this systematic review was to assess the efficacy of photodynamic therapy (PDT) in the treatment of symptomatic oral lichen planus (OLP).
Methods
This systematic review ...aimed to address the following focused question: “Is PDT effective in the treatment of symptomatic OLP?” Indexed databases such as MEDLINE, EMBASE, and CENTRAL were searched up to and including August 2017.
Results
Six clinical studies were included. The risk of bias was considered high in 5 studies and moderate in one study. Parameters of PDT such as wavelengths, energy fluence, power density and exposure time ranged between 320‐660 nm, 120 J/cm2, 130 mW/cm2, and 70‐150 seconds, respectively. The follow‐up period ranged from 4 to 48 weeks. All included studies reporting clinical scores showed that PDT was effective in the treatment of OLP in adult patients at follow‐up. However, PDT did not show significant improvement when compared with steroid therapy.
Conclusion
Photodynamic therapy appears to have some effect in the symptomatic treatment of OLP in adult patients. However, further randomized controlled trials with long follow‐up period, standardized PDT parameters, and comparing the efficacy of PDT with steroid therapy are warranted to obtain strong conclusions in this regard.
Cardiovascular disease is the leading cause of morbidity/mortality worldwide. Metformin is the first therapy offering cardioprotection in type 2 diabetes and non-diabetic animals with unknown ...mechanism. We have shown that metformin improves angiogenesis via affecting expression of growth factors/angiogenic inhibitors in CD34⁺ cells under hyperglycemia-hypoxia. Now we studied the direct effect of physiological dose of metformin on human umbilical vein endothelial cells (HUVEC) under conditions mimicking hypoxia-hyperglycemia. HUVEC migration and apoptosis were studied after induction with euglycemia or hyperglycemia and/or CoCl₂ induced hypoxia in the presence or absence of metformin. HUVEC mRNA was assayed by whole transcript microarrays. Genes were confirmed by qRT-PCR, proteins by western blot, ELISA or flow cytometry. Metformin promoted HUVEC migration and inhibited apoptosis via upregulation of vascular endothelial growth factor (VEGF) receptors (VEGFR1/R2), fatty acid binding protein 4 (
), ERK/mitogen-activated protein kinase signaling, chemokine ligand 8, lymphocyte antigen 96, Rho kinase 1 (
), matrix metalloproteinase 16 (
) and tissue factor inhibitor-2 under hyperglycemia-chemical hypoxia. Therefore, metformin's dual effect in hyperglycemia-chemical hypoxia is mediated by direct effect on VEGFR1/R2 leading to activation of cell migration through
and
upregulation, and inhibition of apoptosis by increase in phospho-ERK1/2 and
, components of VEGF signaling cascades.
Hepatitis B virus (HBV) infection is a leading cause of liver diseases including cirrhosis and hepatocellular carcinoma. Human leukocyte antigens (HLAs) play an important role in the regulation of ...immune response against infectious organisms, including HBV. Recently, several genome-wide association (GWAS) studies have shown that genetic variations in HLA genes influence disease progression in HBV infection. The aim of this study was to investigate the role of HLA genetic polymorphisms and their possible role in HBV infection in Saudi Arabian patients. Variations in HLA genes were screened in 1672 subjects who were divided according to their clinical status into six categories as follows; clearance group, inactive carriers, active carriers, cirrhosis, hepatocellular carcinoma (HCC) patients and uninfected healthy controls. Three single nucleotide polymorphisms (SNPs) belonged to HLA-DQ region (rs2856718, rs7453920 and rs9275572) and two SNPs belonged to HLA-DP (rs3077 and rs9277535) were studied. The SNPs were genotyped by PCR-based DNA sequencing (rs2856718) and allele specific TaqMan genotyping assays (rs3077, rs7453920, rs9277535 and rs9275572). The results showed that rs2856718, rs3077, rs9277535 and rs9275572 were associated with HBV infection (p = 0.0003, OR = 1.351, CI = 1.147-1.591; p = 0.041, OR = 1.20, CI = 1.007-1.43; p = 0.045, OR = 1.198, CI = 1.004-1.43 and p = 0.0018, OR = 0.776, CI = 0.662-0.910, respectively). However, allele frequency of rs2856718, rs7453920 and rs9275572 were found more in chronically infected patients when compared to clearance group infection (p = 0.0001, OR = 1.462, CI = 1.204-1.776; p = 0.0178, OR = 1.267, CI = 1.042-1.540 and p = 0.010, OR = 0.776, CI = 0.639-0.942, respectively). No association was found when polymorphisms in HLA genes were compared in active carriers versus cirrhosis/HCC patients. In conclusion, these results suggest that variations in HLA genes could affect susceptibility to and clearance of HBV infection in Saudi Arabian patients.
Breast cancer brain metastases (BCBM) develop in about 20-30% of breast cancer (BC) patients. BCBM are associated with dismal prognosis not at least due to lack of valuable molecular therapeutic ...targets. The aim of the study was to identify new molecular biomarkers and targets in BCBM by using complementary state-of-the-art techniques.
We compared array expression profiles of three BCBM with 16 non-brain metastatic BC and 16 primary brain tumors (prBT) using a false discovery rate (FDR) p < 0.05 and fold change (FC) > 2. Biofunctional analysis was conducted on the differentially expressed probe sets. High-density arrays were employed to detect copy number variations (CNVs) and whole exome sequencing (WES) with paired-end reads of 150 bp was utilized to detect gene mutations in the three BCBM.
The top 370 probe sets that were differentially expressed between BCBM and both BC and prBT were in the majority comparably overexpressed in BCBM and included, e.g. the coding genes BCL3, BNIP3, BNIP3P1, BRIP1, CASP14, CDC25A, DMBT1, IDH2, E2F1, MYCN, RAD51, RAD54L, and VDR. A number of small nucleolar RNAs (snoRNAs) were comparably overexpressed in BCBM and included SNORA1, SNORA2A, SNORA9, SNORA10, SNORA22, SNORA24, SNORA30, SNORA37, SNORA38, SNORA52, SNORA71A, SNORA71B, SNORA71C, SNORD13P2, SNORD15A, SNORD34, SNORD35A, SNORD41, SNORD53, and SCARNA22. The top canonical pathway was entitled, role of BRCA1 in DNA damage response. Network analysis revealed key nodes as Akt, ERK1/2, NFkB, and Ras in a predicted activation stage. Downregulated genes in a data set that was shared between BCBM and prBT comprised, e.g. BC cell line invasion markers JUN, MMP3, TFF1, and HAS2. Important cancer genes affected by CNVs included TP53, BRCA1, BRCA2, ERBB2, IDH1, and IDH2. WES detected numerous mutations, some of which affecting BC associated genes as CDH1, HEPACAM, and LOXHD1.
Using complementary molecular genetic techniques, this study identified shared and unshared molecular events in three highly aberrant BCBM emphasizing the challenge to detect new molecular biomarkers and targets with translational implications. Among new findings with the capacity to gain clinical relevance is the detection of overexpressed snoRNAs known to regulate some critical cellular functions as ribosome biogenesis.
Introduction. Obesity is becoming the most common health problem of the 21st century, as it will contribute significantly to the high prevalence of cardiovascular disease in developing countries. The ...main objective of our study was to estimate the prevalence of obesity and overweight among adults attending primary health care settings, southwestern region of the Kingdom of Saudi Arabia. Methods. The studied population was composed of adults visiting primary health care centres in the southwestern region of Saudi Arabia. A cross-sectional study was carried out on a representative sample of 1681 adult patients. Obesity and overweight were defined according to the WHO standards. Statistical analysis was conducted using the statistical package SPSS 17.0. Logistic regression analysis was used to identify independent predictors of obesity and overweight in the studied population. Results. Data on body mass index (BMI) measurement was recorded for 1649 out of 1681 participants (98.1%). The overall mean weight was 74.1 ± 15.81 kg; and that for men was 77.69 ± 16.14 kg vs. 69.37 ± 14.02 kg for women with significant statistical difference of p < 0.001. The overall prevalence of overweight and obesity was, respectively, 38.3% and 27.6%. Smoking was not significantly associated with obesity, whereas hypertension was significantly associated with obesity. The risk of overweight or obesity significantly increased from the highest to the lowest monthly income; it passed from 1.67 CI 95% = 1.24-2.25 within the category 5000-7000 SAR to 2.23 CI 95% = 1.71-2.90 within the category less than 5000 SAR. Conclusion. Our study showed high prevalence of overweight and obesity which should be considered as a public health concern to be followed by specific interventions at the community level with multidisciplinary activities starting from childhood as a primordial prevention program.
Breast cancer (BC) is one of the most common female cancers. Clinical and histopathological information is collectively used for diagnosis, but is often not precise. We applied machine learning (ML) ...methods to identify the valuable gene signature model based on differentially expressed genes (DEGs) for BC diagnosis and prognosis.
A cohort of 701 samples from 11 GEO BC microarray datasets was used for the identification of significant DEGs. Seven ML methods, including RFECV-LR, RFECV-SVM, LR-L1, SVC-L1, RF, and Extra-Trees were applied for gene reduction and the construction of a diagnostic model for cancer classification. Kaplan-Meier survival analysis was performed for prognostic signature construction. The potential biomarkers were confirmed via qRT-PCR and validated by another set of ML methods including GBDT, XGBoost, AdaBoost, KNN, and MLP.
We identified 355 DEGs and predicted BC-associated pathways, including kinetochore metaphase signaling, PTEN, senescence, and phagosome-formation pathways. A hub of 28 DEGs and a novel diagnostic nine-gene signature (
,
,
,
,
,
, and
) were identified using stringent filter conditions. Similarly, a novel prognostic model consisting of eight-gene signatures (
,
,
,
,
,
,
, and
) was also identified using disease-free survival and overall survival analysis. Gene signatures were validated by another set of ML methods. Finally, qRT-PCR results confirmed the expression of the identified gene signatures in BC.
The ML approach helped construct novel diagnostic and prognostic models based on the expression profiling of BC. The identified nine-gene signature and eight-gene signatures showed excellent potential in BC diagnosis and prognosis, respectively.
Background/Aims: The hepatitis B virus X protein (HBx) is a viral trans-activator that plays a crucial role in pathogenesis of hepatocellular carcinoma (HCC) via an unknown mechanism. The role of HBx ...in modulating cell proliferation and programmed cell death is replete with controversies. Thus, the goal of this study was to elucidate the effect of HBx and its deletion mutants on cell cycle progression in human hepatoma cells. Methods: Huh7 cells transfected with either full-length or truncated HBx were tested for their mitogenic potential based on their effect on the expression of key cell cycle-related proteins (p27, cyclin D1, p21, and p53) and pro-apoptotic proteins such as cleaved poly (ADP-ribose) polymerase (PARP) and Bax. Western blotting and immunofluorescence techniques were applied to detect changes in the expression levels and intracellular localization, respectively, of the investigated proteins. Also, Quantitative real-time PCR (qRT-PCR) was used to detect changes in RNA levels. Results: An increased anchorage-independent growth of cells transfected with HBx-WT and its deletion mutants was observed. The cell cycle regulatory molecules were differentially modulated by full-length HBx (1-154) and its different N- and C-terminal truncated forms (HBx (31-154), HBx (61-154), HBx (1-94), and HBx (61-124)). An enhanced modulation of p27, p21, and cyclin D1 was associated with HBx (1-154), whereas p53 expression was significantly inhibited by HBx (61-124). Similarly, the expression of cleaved PARP and Bax was efficiently suppressed by HBx (1-94) and HBx (61-154). Conclusion: The HBx-WT and its mutants play a critical role in the pathogenesis and progression of HCC by modulating cell cycle regulatory proteins.
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