Evaluation of soft tissue profile changes following autogenous fat or onlay PEEK augmentation versus sliding genioplasty for correction of deficient chin: Randomized controlled clinical trial.

AIM: The study was conducted to evaluate soft tissue profile changes using autogenous fat augmentation or onlay PEEK versus sliding genioplasty for correction of deficient chin in patients with retruded chin. MATERIAL AND METHODS: thirty-three patients with deficient chins were included in the study. The patients were distributed into 3 groups: the fat augmentation group as intervention I, the PEEK augmentation group as intervention II, and the osseous genioplasty group as control group. Preoperative and postoperative CBCT were performed for all patients. With the aid of MIMICS,3-MATIC, and PROPLAN software, diagnosis, virtual planning, and evaluation were performed. The Face-Q questionnaire was used to assess patient satisfaction. RESULTS: there was a statistically significant difference regarding soft tissue relapse in the fat group after 6 months when compared to the control group (mean difference= 0.770), while there was no statistically significant difference regarding soft tissue relapse between PEEK and control group (mean difference= -0.060). Intragroup comparison has shown no statistically significant difference regarding soft tissue relapse within all groups between follow-up periods (P = 0.1389 for the fat group, P = 0.8739 for the peek group, and P = 0.8410 for the control group). All patients showed a statistically significant increase in scores of satisfaction with the chin between follow-up periods (P = 0.0165, P = 0.0150, and P = 0.0293) respectively. CONCLUSIONS: Fat augmentation can be a good intervention choice in mild-moderate deficient cases. PEEK PSI has a stable surgical outcome.

Iron deficiency-induced thrombocytosis presenting with blue toe syndrome.

Although the etiology of blue toe syndrome is varied, the association between blue toe syndrome and iron deficiency-induced thrombocytosis (IDIT) has not been well established. We report the case of a 38-year-old Saudi male who presented with blue toe syndrome and laboratory investigations revealed severe thrombocytosis secondary to iron deficiency. The patient was managed with analgesics, antiplatelets, anticoagulation, intravenous fluids, and iron supplementation. Subsequently, his symptoms resolved within a few days. IDIT is crucial to consider as a possible cause of microvascular thrombosis disorders, especially in patients with severe thrombocytosis.

Effect of SARS-CoV-2 and Toxoplasma gondii co-infection on IFN-γ and TNF-α expression and its impact on disease severity.

The symptomatology of COVID-19 is dependent on the immune status and the cytokine response of the host. The cytokine level of the host is influenced by the presence of chronic persistent or latent infections with co-pathogens. Parasitic diseases are known to induce host immune-modulation which may impact the response to co-infection. Toxoplasmosis is a widespread protozoal infection that remains quiescent in its latent form to be re-activated during states of immune depression. Clinical data on the relation between toxoplasmosis and COVID-19 cytokine profile and symptomatology are still insufficient. Seventy-nine subjects were included in this study. Patients were diagnosed with COVID-19 by PCR. Serological testing for toxoplasmosis was performed by the detection of anti-Toxoplasma IgG antibodies, in addition to IgG avidity testing. IFN-γ and TNF-α levels were determined by RT-PCR. Among patients diagnosed with COVID-19, 67.1% were seronegative for anti-Toxoplasma IgG, while 32.9% were seropositive. High avidity was found in 10 cases (40% of seropositive cases), 4 of whom required ICU administration, while low avidity was found in 15 cases (60%), 7 of which were administered to the ICU. TNF-α and INF-γ levels were significantly higher in COVID-19 patients than in healthy control subjects. No significant association was found between the seroprevalence of toxoplasmosis and the presence of COVID-19 and its severity. Cytokines were significantly higher in both seropositive and seronegative COVID-19 patients than in their control counterparts. The high prevalence of toxoplasmosis merits further exploration of its relation to COVID-19 by mass studies.

Tuberculous Meningitis Presenting with Bilateral Optic Neuritis: A Case Report and Review of Literature.

Introduction: Tuberculosis (TB) is a major global cause of morbidity and mortality. TB meningitis (TBM) is an implication of systemic dissemination of a primary TB infection that indicates a poorer disease prognosis with various long-term neurological sequelae. Consequently, it is crucial to understand the different clinical presentations and manifestations of such condition. In TBM, vision loss, which is one of the most devastating complications, may result from optic nerve inflammation and atrophy. Although unilateral optic neuritis as a primary presenting symptom of TBM has been broadly reported in the literature, there is a paucity of information related to several other rare neuro-ophthalmic features, such as bilateral optic nerve involvement in TBM. Case Presentation: We herein present a case of a 37-year-old Indian male patient presenting with unilateral vision loss that subsequently progressed to bilateral vision loss and was hence diagnosed with bilateral optic neuritis. Additional thorough investigation yielded a diagnosis of TBM with underlying tuberculomas. The patient's condition improved afterward with anti-tuberculous therapy and steroids with follow-up magnetic resonance imaging indicating radiological resolution as well. Conclusion: The differential diagnosis of bilateral optic neuritis is broad but rare, yet an overlooked one would be central nervous system TB in the form of meningitis or tuberculoma. Hence, it is important to identify bilateral optic neuritis as a possible rare presenting symptom of an underlying central nervous system TB infection which could lead to a faster disease diagnosis and treatment to prevent its devastating complications.

Neutrophilic Myeloid-Derived Suppressor Cells and Severity in SARS-CoV-2 Infection.

BACKGROUND: While we strive to live with SARS-CoV-2, defining the immune response that leads to recovery rather than severe disease remains highly important. COVID-19 has been associated with inflammation and a profoundly suppressed immune response. OBJECTIVE: To study myeloid-derived suppressor cells (MDSCs), which are potent immunosuppressive cells, in SARS-CoV-2 infection. RESULTS: Patients with severe and critical COVID-19 showed higher frequencies of neutrophilic (PMN)-MDSCs than patients with moderate illness and control individuals (P = .005). Severe disease in individuals older and younger than 60 years was associated with distinct PMN-MDSC frequencies, being predominantly higher in patients of 60 years of age and younger (P = .004). However, both age groups showed comparable inflammatory markers. In our analysis for the prediction of poor outcome during hospitalization, MDSCs were not associated with increased risk of death. Still, patients older than 60 years of age (odds ratio [OR] = 5.625; P = .02) with preexisting medical conditions (OR = 2.818; P = .003) showed more severe disease and worse outcome. Among the immunological parameters, increased C-reactive protein (OR = 1.015; P = .04) and lymphopenia (OR = 5.958; P = .04) strongly identified patients with poor prognosis. CONCLUSION: PMN-MDSCs are associated with disease severity in COVID-19; however, MDSC levels do not predict increased risk of death during hospitalization.

Outcome of COVID-19 in Egyptian living-donor kidney transplant recipients and relation to maintenance immunosuppressive drugs: a pilot study.

Coronavirus disease 2019 (COVID-19) in kidney transplant recipients is a subject of much debate and became of interest to nephrologists amidst the pandemic. The main concerns are the influence of the chronic use of immunosuppressive drugs, the viral-related risk of acute rejection, and the long-term outcome of allograft function. This single-center prospective study included kidney transplant recipients with COVID-19 infection. Patients were maintained on immunosuppressive regimens. The severity of disease was defined as oxygen saturation < 94%, the need for hospitalization and/or hemodialysis, the occurrence of acute kidney injury (AKI), and mortality. Seventeen patients (54.8%) required hospital admission, four patients needed hemodialysis (12.9%), twelve patients (38.7%) had AKI, and three patients died (9.7%). Oxygen saturation < 94% showed a positive correlation with the presence of diabetes (p value 0.031) and a negative correlation with the maintenance steroid dose (p value 0.046). A negative correlation existed between the need for hemodialysis and average Cyclosporin level (p value 0.019) and between the need for hospitalization and average Tacrolimus level (p value 0.046). Severity of disease was associated with the presence of lymphopenia (p value 0.042), the cumulative steroid dose (p value 0.001), increased serum levels of LDH (p value 0.010), Ferritin (p value 0.020), AST (p value 0.047), and ALT (p value 0.006) and D-dimer levels more than 0.5 mg/L (p value 0.038). This study highlighted that the immunocompromised state of renal transplant recipients may not be regarded as a disadvantage in the setting of COVID-19 infection. Studies on a larger scale are needed to validate these results.

Electrocardiographic substrates of arrhythmias in patients with end-stage and chronic kidney diseases: a case-control study.

BACKGROUND: Cardiovascular disease (CVD) is the most common cause of death in patients with renal diseases. Cardiac arrhythmia and sudden cardiac death are particularly important, and the burden is higher in patients on hemodialysis. The aim of this study is to compare specific ECG changes as markers of arrhythmias in patients with CKD and patients with end-stage renal disease (ESRD); all without clinically manifest heart disease, with normal control subjects. RESULTS: Seventy-five ESRD patients on regular hemodialysis, 75 patients with stage 3-5 CKD and 40 healthy control subjects were included. All candidates were subjected to thorough clinical evaluation and laboratory tests including serum creatinine, glomerular filtration rate calculation, serum potassium, magnesium, calcium, phosphorus, iron, parathyroid hormone, and total iron binding capacity (TIBC). Resting twelve-lead ECG was done to calculate P wave dispersion (P-WD), corrected QT interval, QTc dispersion, Tpeak-Tend interval (Tp-e), and Tp-e/QT. Patients with ESRD had a significantly higher QTc dispersion (p < 0.001) and P-WD (p = 0.001) when compared to the other 2 groups. In the ESRD group, males had a significantly higher P-WD (p = 0.045), insignificantly higher QTc dispersion (p = 0.445), and insignificantly lower Tp-e/QT ratio (p = 0.252) as compared to females. Multivariate linear regression analysis for ESRD patients showed that serum creatinine (ß = 0.279, p = 0.012) and transferrin saturation (ß = - 0.333, p = 0.003) were independent predictors of increased QTc dispersion while ejection fraction (ß = 0.320, p = 0.002), hypertension (ß = - 0.319, p = 0.002), hemoglobin level (ß = - 0.345, p = 0.001), male gender (ß = - 0.274, p = 0.009) and TIBC (ß = - 0.220, p = 0.030) were independent predictors of increased P wave dispersion. In the CKD group, TIBC (ß = - 0.285, p = 0.013) was an independent predictor of QTc dispersion while serum calcium (ß = 0.320, p = 0.002) and male gender (ß = - 0.274, p = 0.009) were independent predictors of Tp-e/QT ratio. CONCLUSIONS: Patients with stage 3-5 CKD and those with ESRD on regular hemodialysis exhibit significant ECG changes that are considered substrates for ventricular as well as supraventricular arrhythmias. Those changes were more evident in patients on hemodialysis.

Pathological Features of Recovery or Progression in Acute Tubular Necrosis: Single Centre Study.

Acute tubular necrosis (ATN) is the most important and frequent cause of acute kidney injury (AKI). Controversy exists concerning the role of renal biopsy in the evaluation of ATN prognosis. We aim in our study to evaluate the role of renal biopsy for the detection of recovery and progression and rate of recovery of ATN. The study was designed to include all biopsies with the diagnosis in ATN in adults >21-year-old, from January 2016 to December 2018. Biopsies were recruited retrospectively and were reviewed by three pathologists and quantitated. Four histological ATN features were evaluated. Flattening cells, distension or dilatation, debris, and vacuolation and for each a score were attributed as follows: 0 = less than 5% of section, 1 = 6%-25%, 2 = 26%-50%, 3 = >50%. Thirty-five patients with 35 renal biopsies were analyzed. Flattening was seen <5% in nine patients, 6%-25% in 15 patients, 26%-50% in six patients. and >50% in five patients. Dilatation was seen <5% in 11 patient, 6%-25% in 10 patients, 26%-50% seen in six patients, and >50% in eight patients. The presence of debris was seen in <5% in 12 patients, 6%-25% in 12 patients, 26%-50% seen in six patients, and >50% seen in five patient. Vacuolation was seen in 5% in eight patients, 6%-25% in 14 patients, 26%-50% in seven patients, and >50% in six patients. It was found that flattening <5% and dilatation <5% and dilatation >50% in renal biopsy are the good indicators for recovery and good prognosis of cases of ATN, in addition debris <5% and >50% and vacuolation <5% are also good indicators for recovery and good prognosis of cases of ATN. On the other hand, flattening from 6% to 25% and from 26% to 50%, dilatation from 6% to 25%, debris from 26% to 50% and vacuolation >50% are also indicators for delayed recovery and poor prognosis of cases of ATN. Renal biopsy in AKI with the diagnosis of ATN with scoring system of flattening, dilatation, debris, and vacuolation can point to indication of recovery or progression of these cases.

Serum Phosphorus, Parathyroid Hormone, and Serum Fibroblast Growth Factor-23 in Egyptian Patients Six Months after Undergoing Living-donor Kidney Transplantation.

End-stage renal disease is a major health problem with many complications. Previous studies emphasized the relationship of cardiovascular disease and mortality among these patients to dysregulated phosphate homeostasis. Even after successful renal transplantation, the risk is not eliminated. Several factors seem to interplay to regulate serum phosphorus levels after renal transplantation. Fibroblast growth factor-23 (FGF-23) is a hormone with the major function of inhibiting the reabsorption of phosphate by the renal tubules. Parathormone reduces the reabsorption of phosphate from the proximal tubule of the kidney. The aim of our study was to explore the changes that occurred in FGF-23 and intact parathyroid hormone (iPTH) levels in a cohort of Egyptian patients undergoing renal transplantation and to examine the effect of these factors on posttransplant serum phosphorus levels. The study was carried out prospectively on 37 candidates for live-donor renal transplantation. Serum levels of calcium, phosphorus, iPTH, and FGF-23 were measured before and 6 months after renal transplantation. Statistically significant differences were detected in serum calcium, phosphorus, FGF-23, and iPTH before and 6 months after transplantation (P < 0.001, P < 0.001, P < 0.001, and P < 0.001, respectively). The results also showed a statistically significant correlation between FGF-23 levels and phosphorus levels before transplantation. The interplay between FGF-23 and iPTH has an impact on posttransplant serum phosphorus levels.

Screening for diabetes and impaired glucose metabolism in Qatar: Models' development and validation.

AIM: To establish two scoring models for identifying individuals at risk of developing Impaired Glucose Metabolism (IGM) or Type two Diabetes Mellitus (T2DM) in Qatari. MATERIALS AND METHODS: A sample of 2000 individuals, from Qatar BioBank, was evaluated to determine features predictive of T2DM and IGM. Another sample of 1000 participants was obtained for external validation of the models. Several scoring models screening for T2DM were evaluated and compared to the model proposed by this study. RESULTS: Age, gender, waist-to-hip-ratio, history of hypertension and hyperlipidemia, and levels of educational were statistically associated with the risk of T2DM and constituted the Qatar diabetes mellitus risk score (QDMRISK). Along with, the 6 aforementioned variables, the IGM model showed that BMI was statistically significant. The QDMRISK performed well with area under the curve (AUC) 0.870 and .815 in the development and external validation cohorts, respectively. The QDMRISK showed overall better accuracy and calibration compared to other evaluated scores. The IGM model showed good accuracy and calibration, with AUCs .796 and .774 in the development and external validation cohorts, respectively. CONCLUSIONS: This study developed Qatari-specific diabetes and IGM risk scores to identify high risk individuals and can guide the development of a nationwide primary prevention program.

Albumin administration in patients with decompensated liver cirrhosis: a meta-analytic update.

End-stage liver disease and its related complications exert a huge disease burden and reduce the survival rates of many patients. Albumin administration for patients with decompensated liver cirrhosis has been a controversial topic of discussion. The aim of this study is to investigate whether albumin reduces the mortality and complications of liver cirrhosis compared to standard medical therapy (SMT) alone. Clinical trials in which albumin administration was compared to SMT in patients with liver cirrhosis were included in this meta-analysis. The primary outcome of this study was to evaluate the effect on reducing all-cause mortality. Ascites control, renal failure and hepatic encephalopathy were evaluated as secondary outcomes. Nine clinical trials with 1231 patients were recruited and analyzed using the quality effect model. Mortality rate was significantly reduced in the albumin group [relative risk (RR) 0.73, 95% confidence interval (CI) 0.56-0.96]. Heterogeneity was mild across all studies (I2 23.3%). Studies reporting long-term albumin (LTA) administration were found to have a significant decrease in mortality (RR 0.57, 95% CI 0.44-0.73). However, studies reporting short-term albumin administration were found to have no effect on mortality (RR 0.90, 95% CI 0.56-1.45). Furthermore, there was a significant decrease in the incidence of all secondary outcomes. This meta-analysis provides evidence that LTA administration is significantly effective in reducing the mortality of liver cirrhosis compared to SMT. Albumin administration was also shown to reduce the occurrence of ascites, renal failure and hepatic encephalopathy as complications of liver cirrhosis.

Evaluation of serum presepsin, procalcitonin, copeptin, and high-sensitivity C-reactive protein for differentiating bacterial infection from disease activity in Egyptian patients with systemic lupus erythematosus.

OBJECTIVES: Several biological markers have been studied for the differentiation of infection from disease activity in systemic lupus erythematosus (SLE) patients with discrepant results. We aimed to evaluate the role of serum presepsin, hs-CRP, procalcitonin (PCT), and copeptin (CPP) in differentiating bacterial infections from disease activity in SLE patients. METHODS: This study is a cross-sectional observational study in which 94 Egyptian patients were recruited from June 2017 to January 2018. Our patients were divided into two groups: group (1) included 48 patients with active SLE hospitalized with any sort of lupus activity and group (2) included 46 patients with active SLE admitted with a proven bacterial infection. Hs-CRP, presepsin, PCT, and CPP were measured using enzyme-linked immune sorbent assay technique. RESULTS: Hs-CRP, presepsin, PCT, and CPP were highly significantly higher among group (2) patients compared to group (1) patients (p < 0.001). Serum presepsin expressed higher specificity than hs-CRP (87.5% vs 60.4%) but the same sensitivity (80.4%) in the detection of bacterial infection in SLE patients. Serum PCT expressed higher specificity than hs-CRP (100% vs 60.4%) but lower sensitivity (73.9% vs 80.4%). Serum CPP expressed higher specificity than hs-CRP (65.9% vs 60.4%) but lower sensitivity (65.9% vs 80.4%). CONCLUSION: Our study suggests that increased serum levels of hs-CRP, presepsin and PCT levels are useful in differentiating bacterial infections from disease activity in SLE patients. Serum CPP could be used as an adjunct with more specific inflammatory biomarkers in making better diagnostic judgments. KEY POINTS: • The increased serum levels of hs-CRP, presepsin and PCT levels are useful in differentiating bacterial infections from disease activity in SLE patients. • Serum Presepsin expressed higher specificity than hs-CRP but the same sensitivity in the detection of bacterial infection in SLE patients. • Serum CPP expressed higher specificity than hs-CRP but lower sensitivity.

Urine albumin and serum uric acid are important determinants of serum 25 hydroxyvitamin D level in pre-dialysis chronic kidney disease patients.

Low serum 25 hydroxyvitamin D (25 OH D) is common among chronic kidney disease (CKD) patients. This cross-sectional study is looking for the different factors associated with serum 25 OH D among pre-dialysis CKD. 1624 adult stage 3-5 CKD patients were studied beside 200 normal control subjects. All candidates were tested for body mass index (BMI), estimated glomerular filtration rate (eGFR), calcium (Ca), phosphorus (P), parathormone (PTH), 25 OH D, albumin, and uric acid (UA), and urine albumin/creatinine ratio (ACR). Multivariate linear regression analysis was done to determine predictors of 25 OH D. 98.6% of CKD patients have inadequate level of 25 OH D vs 48% of normal subjects. Serum 25 OH D was significantly lower in CKD patients (mean ± S.D = 16.54 ± 5.8 vs 37.79 ± 3.58 ng/mL for CKD vs control group respectively, p < .001). Serum level of 25 OH D has significant positive correlation with Ca (r = 0.337, p < .001), and significant negative correlation with P, PTH, UA, and ACR (r = -0.440, -0. 679, -0.724, and -0.781respectively, p < .001 in all). The independent predictors of 25 OH D were Ca, P, UA, PTH, and ACR (R square = 0.7, ß = -0.087, -0.226, -0.313, -0.253, and -0.33 respectively, p < .001 in all). In conclusion, pre-dialysis CKD patients frequently suffer low 25 OH D. Among the different abnormalities related to CKD, urine albumin excretion rate and UA are the most important predictors of 25 OH D in these patients.

The role of matrix metalloproteinases 2 in atherosclerosis of patients with chronic kidney disease in type 2 diabetes.

Matrix metalloproteinase-2 (MMP2) has been implicated in chronic disease and cardiovascular disease. However, there is no knowledge about the correlations between serum levels of MMP-2, proteinuria and atherosclerosis in patients with diabetic nephropathy (DN). We investigated whether serum MMP-2 levels were associated with proteinuria, intima-media thickness (IMT) in DN patients. Diabetic patients not on hemodialysis (n = 50) were enrolled for the study. MMP-2 levels were measured using an ELISA system. IMT was evaluated by highresolution ultrasonography. Univariate analyses revealed that MMP-2 (P = 0.013) were independent correlates of proteinuria. Further, multivariate analyses revealed that MMP-2 levels (P = 0.001) were independent correlates of IMT. MMP-2 levels were significantly (P = 0.001) higher in patients with atherosclerosis than those without it. The present study demonstrates that serum levels of MMP-2 were one of the independent correlates of proteinuria and IMT in patients with DN. Our results suggest that serum MMP-2 levels may be one of the risk factors for renal damage and atherosclerosis in DN patients.

Association of insulin growth factor-1 and growth hormone levels in elderly renal transplant recipients with cardiac dysfunction.

Insulin growth factor-1 (IGF-1) and growth hormone (GH) have cardiac protective effects through many mechanisms; they can directly oppose endothelial dysfunction in a number of ways. Many studies assessed the effect of GH or IGF-like growth factor 1 in patients with cardiac dysfunction, but no previous study assessed the GH and insulin-like growth factor-1 in renal transplant recipients with and without cardiac dysfunction, especially elderly. Eighty patients with renal transplantation and age limit above 75 years. They were subdivided into two groups according to the presence or absence of cardiac dysfunction based on medical history, clinical findings, electrocardiogram, and echocardiography. Serum GH and insulin-like growth factor-1 were studied by immunoradiometric assay. The echocardiography study was performed. M-mode two-dimensional and Doppler measurements were taken to obtain the four- and five-chamber views, chambers' dimensions, left ventricular end-diastolic dimensions, left ventricular end-systolic dimensions, septal wall thickness (SWT), distance between leading edges of the endocardial and pericardial echoes of left ventricular posterior wall (posterior wall thickness), aortic root and left atrial dimensions (LAD), fractional shortening and ejection fraction. IGF-1 is lower in patients with cardiac dysfunction with renal transplantation with mean value of 61 ± 30.05 than those control group with mean value 145.52 ± 70.5. Level of human growth factor is higher in patients with dysfunction with renal transplantation with mean value 2.62 ± 3.05 than those control group after renal transplantation with mean value 0.85 ± 0.9. No correlations were found between IGF-1 and various echocardiographic parameters. Only SWT and LAD were negatively correlated with GH, r = -0.08, P <0.02, r = -0.37, P <0.03, respectively. No correlation was found between IGF-1 and various echocardiographic parameters. Only SWT and LAD were negatively correlated with GH.

Effect of reducing medication regimen complexity on glycaemic control in patients with diabetes.

INTRODUCTION: Medication Regimen complexity is an important issue of patients care that needs to be addressed. The aim of this study is the safe reduction of regimens complexities. The effect of this intervention on glycemic control was assessed in this study. METHODS: Seventy eight patients were recruited to the study. The entry criteria were non optimal glycemic, non-adherence (as demonstrated by indirect tools), and polypharmacy. The only intervention was the safe reduction of medication regimen complexity. This was done in view of the best practice guidelines; to ensure that all comorbidities are treated with the optimum number of medications for the optimum duration. There was no change to hypoglycemic regimen. All patients, whose hypoglycemic regimen has changed after the recruitment, were excluded. The primary outcome measure was the change in HbA1c three months after the intervention. RESULTS: Reducing medications regimen complexities led to a significant improvement of HbA1c in the after phase compared to the before phase (mean HbA1c in the before phase was 7.7 ± 0.43% compared to 6.93 ± 0.4% in the after phase. Mean reduction in the HbA1c was 0.77 ± 0.23%, p values < 0.001). CONCLUSION: Medications regimen complexity constitutes a burden for patients with diabetes. Reducing such regimens might improve glycemic control in those patients. Further studies are needed to confirm this favourable effect on the glycemic control.

Water-pipe smoking promotes epithelial-mesenchymal transition and invasion of human breast cancer cells via ERK1/ERK2 pathways.

BACKGROUND: With the increasing popularity of water-pipe smoking (WPS), it is critical to comprehend how WPS may affect women's health. The main goal of this study is to identify the potential outcome of WPS on human breast cancer progression. METHODS: Two breast cancer cell lines, MCF7 and BT20, were used in this investigation. We explored the outcome of WPS on cell morphology and cell invasion using inverted microscope and Biocoat Matrigel invasion chambers. On the other hand, Western blot was employed to study the expression patterns of key control genes of cell adhesion and invasion. RESULTS: Our data reveal that WPS induces epithelial-mesenchymal transition (EMT) of MCF7 and BT20 breast cancer cell lines; thus, WPS enhances cell invasion ability of both cell lines in comparison with their matched controls. More significantly, WPS provokes a down- and up-regulation of E-cadherin and focal adhesion kinase (FAK), respectively, which are important key regulators of cancer progression genes. Finally, our data point out that WPS incites the activation of Erk1/Erk2, which could be behind the stimulation of EMT and invasion as well as the deregulation of E-cadherin and FAK expression. CONCLUSION: Our data show, for the first time, that WPS initiates EMT and stimulates cell invasion of breast cancer cells, which could incite metastatic development in breast cancer patients. Thus, we believe that further studies, both in vitro and in vivo, are required to elucidate the pathogenic outcome of WPS on cancer progression of several human carcinomas including breast.

Substantial Toxic Effect of Water-Pipe Smoking on the Early Stage of Embryonic Development.

Background: Water-pipe smoking (WPS) is the most widespread tobacco use in the Middle-East, and is rapidly spreading globally. Smoke from WP contains most of the compounds present in cigarette smoke, although in different proportions. WPS is associated with the risk of several human diseases; however, its impact on the early stage of normal development has not been investigated yet. Thus, in this investigation, we assess the effect of WPS on the embryo at the early stage of development. Methods: Chicken embryos at 3 days of incubations were used in this study. Meanwhile, we explored the outcome of WPS on angiogenesis using the chorioallantoic membrane (CAM) of the chicken embryos. Finally, quantitative real-time polymerase chain reaction was used to study the regulation of some key control genes of cell proliferation, apoptosis, and migration. Results: Our data reveal that WPS inhibits angiogenesis of the CAM and in embryos in comparison with their matched controls; in addition, WPS-exposed embryos show slight reduction in their sizes. We also noted that around 80% of WPS-exposed embryos die before 10 days of incubation. More significantly, WPS induces upregulations of BCL-2, Caspase-8, ATF-3, INHIB-A, and Cadherin 6 genes, which are important key regulators of cell apoptosis, proliferation, and migration. Conclusion: Our data reveal, for the first time, that WPS has very toxic effects during the early stage of embryogenesis. Thus, we believe that further studies are required to elucidate the pathogenic effect of WPS on human health especially on the embryo at the early stage of its development. Implications: This investigation addresses an important gap on the outcome of WPS during the early stage of embryogenesis. Data of this study point out that WPS can have a very toxic effect on the embryo at this stage. Additionally, results from this report display for the first time that WPS can damage normal angiogenesis of the embryo thus provoking a significant number of embryonic death. Moreover, this study reveals that this effect can occur via the deregulation of several genes related to cell apoptosis, proliferation, and migration.