The Untold Story: Early and Mid-Term Results of Subintimal Angioplasty in Superficial Femoral Artery Versus Popliteal Artery Chronic Total Occlusion.

OBJECTIVES: This study aims to compare the immediate and mid-term outcomes of subintimal angioplasty (SIA) of chronic total occlusions (CTOs) of superficial femoral artery (SFA) versus popliteal artery (PA) and to identify possible predictors of loss of limb-based patency (LBP). METHODS: This is a retrospective analysis of chronic lower-limb ischemia (CLI) patients (Rutherford classes 3-6) presenting with CTO of SFA or PA treated by SIA and selective stenting in the period 2018 to 2021. Immediate outcomes were compared between the SFA and PA groups, including technical success, perioperative complications, and 30-day major amputation and mortality rates. Mid-term outcomes for technically successful procedures included limb-based patency (LBP), wound healing rate, amputation-free survival (AFS), and major adverse limb events (MALEs). RESULTS: A total of 450 CLI patients underwent SIA of CTO at the SFA (n=260, 57.8%) and the PA (n=190, 42.2%). The indication for revascularization was chronic limb-threatening ischemia in 80.8% of SFA group and 84.2% of PA group. Technical success rate was higher in the PA group compared to the SFA group (96.3% vs 91.2%; p=0.03). The 30-day amputation rates were comparable between the SFA and PA groups (7.7% vs 6.8%, p=0.7, respectively). No perioperative mortality or systemic major complications occurred in the present study. Kaplan-Meier estimate of the 1-year rates were significantly better for SFA group regarding LBP (82% for SFA group vs 43% for PA group, p=0.006), AFS (88% vs 64%, p=0.02), and wound healing (79% vs 58%, p=0.027), respectively. The number of runoff vessels was the only factor associated with loss of LBP (hazard ratio [HR], 0.055; 95% confidence interval [CI]: 0.001-3.020, p=0.039). CONCLUSIONS: Subintimal angioplasty is an effective and safe endovascular treatment option of CTO at SFA and PA with satisfactory immediate outcomes. The mid-term outcomes, however, are better for SFA lesions in terms of improved LBP, AFS, and wound healing rates. CLINICAL IMPACT: Subintimal angioplasty is a valuable tool in the armamentarium of endovascular surgeons, as re-entry devices aren't always widely accessible. This study aims to assess the technical outcomes of peripheral vascular interventions for infrainguinal chronic total occlusions and identify possible predictors for successful subintimal angioplasty .Subintimal angioplasty is an effective treatment option for infrainguinal CTO with difference in result of immediate outcomes in popliteal lesions and SFA lesions.

Nutritional, antioxidant, and antimicrobial assessment of carrot powder and its application as a functional ingredient in probiotic soft cheese.

Carrots (the main source of carotenoids) have multiple nutritional and health benefits. The objectives of this study were to evaluate the compositional, antioxidant, and antimicrobial properties of carrot powder and to examine its effect on the sensory characteristics, chemical properties, and microbial viability of probiotic soft cheese at a rate of 0.2, 0.4, and 0.6%. The carrot was turned into powder before being analyzed and incorporated as an ingredient in making probiotic soft cheese. Probiotic soft cheese was made from buffalo milk. The buffalo milk (∼6.9% fat, 4.4% protein, 9.2% milk solids not fat, and 0.7% ash) was pasteurized at 75 ± 1°C for 5 min and cooled to 40-42°C. The milk was then divided into 4 aliquots. Sodium chloride (local market, Assiut, Egypt) was added at a ratio of 5% followed by starter cultures. The carrot powder (4.5% moisture, 4.8% ash, 2.7% fat, 8.2% protein, 11.9% fibers, and 72.3% carbohydrate) was added at a rate of 0.2, 0.4, and 0.6%, followed by addition of 0.02 g/kg rennet. The cheese was cut again into cubes, pickled in jars filled with whey, and stored for 28 d at 6 ± 1°C. The results of this study illustrated the nutritional and antioxidant properties of carrot powder. Incorporation of carrot powder in probiotic soft cheese affected the moisture and salt content at 0 d. The total bacteria count decreased from 7.5 to 7.3 log cfu/g in the cheese when carrot powder was used at a rate of 0.6%. The reduction of total bacteria count was noticed during the 28 d of storage by adding carrot powder. Furthermore, lactic acid bacteria and Bifidobacterium longum counts elevated with adding carrot powder during the 28 d of storage.

Schistosomicidal, antifibrotic and antioxidant effects of Cucurbita pepo L. seed oil and praziquantel combined treatment for Schistosoma mansoni infection in a mouse model.

Despite the seriousness of schistosomiasis, its treatment depends only on praziquantel (PZQ), which has begun to lose its efficacy against the emergent Schistosoma mansoni-resistant strains. Therefore, the discovery of a novel schistosomicidal drug is an urgent priority. This study was designed to evaluate treatment with Cucurbita pepo L. (pumpkin) seed oil (PSO) alone and combined with PZQ against S. mansoni in experimentally infected mice. The study involved five groups: GI was the normal control; GII was the infected control; GIII was treated with an oral dose of PZQ of 500 mg/kg/day for two successive days, starting in the sixth week post infection; GIV was treated with an oral dose of PSO of 50 mg/kg/day for four weeks, starting in the fourth week post infection; and GV was treated with combined PSO-PZQ. Worm burden, tissue egg load and oogram pattern were estimated, and the ultrastructure alterations were examined. Histopathological examination of granuloma diameters, collagen deposition (Picro Sirius red stain), and angiogenesis (immunohistochemical expression of CD34+) was conducted and serum liver enzymes were measured to assess the liver condition. Moreover, the oxidative stress was evaluated by determining the amounts of malondialdehyde and superoxide dismutase in liver homogenates. The results revealed significant changes in all the assessed parameters with PSO administration. However, PZQ was significantly more effective as an antiparasitic agent, whereas PSO was better in terms of fibrosis and oxidative stress. The most significant results were obtained in group V, which may be attributed to a synergy between PZQ and PSO, with antiparasitic, antioxidant and antifibrotic properties.

Epithelial mesenchymal transition in early invasive breast cancer: an immunohistochemical and reverse phase protein array study.

Epithelial mesenchymal transition (EMT), as defined by loss of epithelial characteristics and gain of a mesenchymal phenotype, has been reported in vivo although the occurrence of events remains unclear. This study aims at exploration of EMT portraits of breast cancer (BC) with relevance to different molecular pathways, especially potential EMT triggers and BC molecular subtypes. Immunohistochemical (IHC) expression of markers/triggers of EMT was studied on a well-defined cohort of invasive non-lobular BC (n = 1,035), prepared as tissue microarrays. IHC panel of biomarkers included cadherins (cad; E-cad and N-cad), TGFß1, PIK3CA, pAkt, and others. Reverse phase protein array (RPPA) was performed for quantitative analysis of proteins extracted from formalin fixed paraffin embedded tissues of a subset of cases from this cohort. Four combinatorial phenotypic groups representing cadherin switch were defined, including E-cad(+)/N-cad(-), E-cad(-)/N-cad(-), E-cad(+)/N-cad(+), and E-cad(-)/N-cad(+). Statistically significant association was noticed between these phenotypes and histological tumour grade, tumour type and size and NPI staging classes. The E-cad/N-cad switch occurred more frequently in the triple negative molecular class, both basal and non-basal, and in the HER2(+) subtype than in luminal BC. Significant outcome differences were observed between cadherin switch combinatorial groups regarding BCSS and DMFS (p < 0.001). Results of RPPA confirm those observed using IHC regarding differential expressions of EMT markers/triggers. EMT/cadherin switch programs in BC appear to occur in synergy with TGFß1 and PIK3/Akt pathways activation. These data explain, at translational proteomic level, the molecular heterogeneity and in turn the varied clinical behaviour of BC molecular subtypes. RPPA is a promising high-throughput technique in monitoring subtle quantitative changes in protein expression in archival material.

Effects of gamma irradiation and/or cooking on nutritional quality of faba bean (Vicia faba L.) cultivars seeds.

The effect of gamma irradiation (0.5 and 1.0 kGy) and/or cooking on the proximate composition, mineral content, tannin content, phytic acid content and the in vitro protein digestibility (IVPD) of two Sudanese faba bean cultivars (BB7-S1 and SH-S2) was investigated in the present study. The results obtained revealed that gamma irradiation and/or cooking treatments have slight effect in chemical composition and mineral content, while they caused significant (P ≤ 0.05) reduction on tannin content for both cultivars. Cooking of faba bean seeds also insignificantly (P ≤ 0.05) reduced phytic acid content for both cultivars, while irradiation process and/or cooking had fluctuated effect. For both cultivars, irradiation of seeds and/or cooking increased the in vitro protein digestibility (IVPD), with maximum value of IVPD (79.97%) obtained for cultivar BB7-S1. The results indicate that the treatments used in this study might improve the nutritive quality of faba bean seed due to reduction in antinutritional factors with a concomitant increase in IVPD.

Involvement of CircRNAs in regulating The "New Generation of Cancer Hallmarks": A Special Depiction on Hepatocellular Carcinoma.

The concept of 'Hallmarks of Cancer' is an approach of reducing the enormous complexity of cancer to a set of guiding principles. As the underlying mechanism of cancer are portrayed, we find that we gain insight and additional aspects of the disease arise. The understanding of the tumor microenvironment (TME) brought a new dimension and led to the discovery of novel hallmarks such as senescent cells, non-mutational epigenetic reprogramming, polymorphic microbiomes and unlocked phenotypic plasticity. Circular RNAs (circRNAs) are single-stranded, covalently closed RNA molecules that are ubiquitous across all species. Recent studies on the circRNAs have highlighted their crucial function in regulating the formation of human malignancies through a range of biological processes. The primary goal of this review is to clarify the role of circRNAs in the most common form of liver cancer, hepatocellular carcinoma (HCC). This review also addressed the topic of how circRNAs affect HCC hallmarks, including the new generation hallmarks. Finally, the enormous applications that these rapidly expanding ncRNA molecules serve in the functional and molecular development of effective HCC diagnostic biomarkers and therapeutic targets.

Comparison of high-risk characteristics of non-culprit plaques in relation to plaque severity in acute coronary syndrome.

INTRODUCTION: Patients with acute coronary syndrome (ACS) have high event rates related to non-culprit (NC) lesions, therefore plaque composition of these lesions is of great interest. Although marginal atherosclerotic lesions were studied extensively, more significant lesions might have more high-risk characteristics. AIM: To compare differences in high-risk lesion characteristics between significant versus non-stenotic NC plaques in ACS and the discrepancies with chronic coronary syndrome (CCS) patients. METHODS: Non-culprit vessels of 26 ACS patients with 26 angiographically significant lesions and 37 patients (17 ACS and 20 CCS) with 48 non-stenotic lesions were investigated with intravascular ultrasound (IVUS) and near-infrared spectroscopy (NIRS). Overall, 74 segments of 30 mm length were analyzed in 1 mm intervals. External elastic lamina (EEM), plaque burden (PB), minimal luminal area (MLA), percent atheroma volume (PAV) and lipid core burden index maximum 4 mm (maxLCBI4mm) were determined for each segment. RESULTS: Cardiovascular risk factors were similar in all groups. PB was higher and MLA smaller in significant non-culprit ACS lesions vs non-stenotic lesions: PB 73.5% (IQR 68.7-78.5) vs 59.2 (IQR 49.6-71.5), p = 0.003, MLA 3.0 mm2 (IQR 2.3-3.9) vs 4.0 mm2 (IQR 2.8-4.7). MaxLCBI4mm was similar 308.1 (±155.4) vs 287.8 (±165.7), p = 0.67. Among non-stenotic plaques, MaxLCBI4mm was comparable between ACS and CCS patients, 275.7 (±151.5) in CCS patients vs 287.8 (±165.7) in ACS patients, p = 0.79. CONCLUSION: Although visually significant non-culprit lesions had a higher plaque burden compared to non-stenotic lesions, a significant relation between MaxLCBI4mm and hemodynamic significance of the plaques couldn't be established.

Analogs design, synthesis and biological evaluation of peptidomimetics with potential anti-HCV activity.

Two series of peptidomimetics were designed, prepared and evaluated for their anti-HCV activity. One series possesses a C-terminal carboxylate functionality. In the other series, the electrophilic vinyl sulfonate moiety was introduced as a novel class of HCV NS3/4A protease inhibitors. In vitro based studies were then performed to evaluate the efficacies of the inhibitors using Human hepatoma cells, with the vinyl sulfonate ester (10) in particular, found to have highly potent anti-HCV activity with an EC(50) = 0.296 µM. Finally, molecular modeling studies were performed through docking of the synthesized compounds in the HCV NS3/4A protease active site to assess their binding modes with the enzyme and gain further insight into their structure-activity relationships.

Molecular modelling design, synthesis and cytotoxic evaluation of certain substituted 2-(3,4,5-triacetoxybenzoylamino)benzo[d]thiazole and 2-(galloylamino)benzo[d]thiazole derivatives having potential topoisomerase-I inhibitory activity.

New 2-(3,4,5-triacetoxybenzoylamino)benzothiazoles (4a~5f) and 2-(galloylamino)benzothiazoles (6a~7f), were designed as topoisomerase-I inhibitors. Compare/fit studies between these molecules and the generated topoisomerase-I inhibitors hypothesis revealed that 4a~5f have higher fitting values than (6a~7f). Also, docking of 4a~7f with the topoisomerase-I enzyme prioritized the higher activity of (4a~5f) than (6a~7f). These molecules were synthesized and biologically evaluated for their in vitro cytotoxic activity against Hela and MCF7 human cancer cell lines in comparison to Camptothecin (topo-I inhibitor) and doxorubicin (topo-II inhibitors) as reference drugs. Such screening revealed that compounds 4d, 4e, 4h, 5b, 5c and 5e have comparable higher cytotoxic activity in both cultures than these reference drugs. The highest active molecule was 5f that gave 1.5 folds higher cytotoxic activity against Hela cell cultures and 1.9 folds higher activity against MCF7 cell lines than doxorubicin and 1.6 folds and 2.2 folds higher activity towards the two respective cultures than Camptothecin.

Clinical characteristics and short-term outcomes of adult patients with urolithiasis: first report from Somalia.

OBJECTIVE: This study aimed to investigate the data of adult patients admitted to the only tertiary care center in Somalia with the diagnosis of urolithiasis and to present the first report from this Sub-Saharan African country. PATIENTS AND METHODS: This study was designed as a retrospective single-center study conducted in Somalia Turkiye Training and Research Hospital. Adult patients who received the diagnosis of urolithiasis and who were admitted to the urology department constituted the target population. Reviewed data included demographic parameters, stone features, type of surgical procedure, intraoperative and early postoperative complications, and inpatient mortality. RESULTS: Overall, 3,680 patients were admitted during the study period. Among these, 620 (17%) patients were admitted due to urolithiasis. There was a significant male predominance with a male-to-female ratio of 3.4:1. Urinary bladder was the most common stone location (n=253, 40.8%), followed by the kidney (n=223, 35.9%). The mean stone diameter was 22.41 (5-64); most (39.4%) of the patients had a stone diameter between 20 and 30 mm, while 27.5% had stones with diameters between 10 and 20 mm. Minimally invasive procedures were the primary surgical modality in 52.6% (n=326) of our patients. However, 45.9% (n=285) of the patients underwent open surgery. CONCLUSIONS: The rate of adults with urolithiasis is relatively high in Somalia, as in many other African countries, with a significant male predominance. Although open surgery is rarely used for treating adult urolithiasis in industrialized countries, this approach is still commonly used in Somalia, similar to other parts of Africa.

Our kidneys and teeth may be closer than we think: relationship between dental calculi and renal stone burden grading in a patient series from Somalia.

OBJECTIVE: This study investigated the correlation between dental calculi grading and renal stone burden grading. PATIENTS AND METHODS: This study was designed as an observational single-center study and included consecutive patients with radiologically confirmed renal stones at our center between January 2022 and July 2022. These patients were referred to the dentistry clinic for a dental examination to assess dental calculi and oral hygiene. Investigated parameters included demographic characteristics, renal stone location and diameter, urine pH, and dental evaluation findings (teeth brushing habits, oral hygiene, and dental calculi). Renal stone burden grade and dental calculi grade were calculated, and Spearman's rank-order correlation analysis was used for correlation analyses. RESULTS: Overall, 204 patients were included. The mean patient age was 36.3±15.2. Approximately half of the patients (49.2%) had multiple stones. About 36% of the participants had high-grade dental calculi, while 29.4% had intermediate low-grade dental calculi. Oral hygiene was significantly associated with dental calculi grade (p<0.001). The dental calculi grade was positively and moderately correlated with the renal stone diameter (Spearman's rho=0.493, p<0.001). Among patients with a renal stone diameter greater than 20 mm, intermediate to high-grade dental calculi were found in 88.4%. This proportion was 49.1% for those with a renal stone diameter smaller than 20 mm. CONCLUSIONS: Dentists should consider the presence of undiagnosed kidney stones in patients with especially intermediate or high-grade dental calculi. Urologists should know that patients with large and multiple kidney stones may have dental calculi.

Geotechnical and environmental radioactivity investigations at Al Sadis Min Uktober city, Cairo municipality (Egypt), for the high-speed railway construction.

The present study aims to evaluate the possibility of constructing a new high-speed railway (HSR) at Al Sadis Min Uktober city, Cairo (Egypt): geotechnical and environmental radiological hazards are estimated from several collected soil and water samples. A variety of laboratory geotechnical tests such as grain size, free swelling test, liquid and plastic limits, chemical analysis and uniaxial compression strength are applied to sixty-one drill holes. A geotechnical examination of the coarse-grained soil at the foundation level classified it as poorly graded soil. The results of the investigation of fine-grained soil at the foundation level shown that the liquid limit ranges from 22% to 55%, the plastic limit ranges from 12% to 28%, the plasticity index varies from 11% to 33%, free swelling varies from 51% to 71%. Mechanically, the uniaxial compressive strength values on rock samples range from 6.96 MPa to 142.39 MPa. The radioactive study is performed to detect the 226Ra, 232Th, and 40 K activity concentrations of the soil samples: their mean values are 34 ± 10 Bq·kg-1, 14 ± 5 Bq·kg-1 and 552 ± 20 Bq·kg-1, respectively. The values of radiological hazard indexes are not exceeded the permissible limits: e.g. the mean value of absorbed dose rate is 47 ± 6 nGy h-1; the annual gonadal dose equivalent is 0.3 ± 0.04 mSv·y-1; the lifetime cancer risk is 02 ± 0.2·10-3. Thus, the soil in the studied railway area is safe to use in building materials and infrastructure applications: the radiological hazards and the geotechnical studies confirmed the studied area is suitable to construct a new community having a HSR. According to the SWOT-PEST and environmental impact analyses, the construction of the HSR meets the criteria of the Kyoto Protocol, the EU Climate and Energy policy, and other international treaties.

Biosynthesized Silver Nanoparticles from Cyperus Conglomeratus Root Extract Inhibit Osteogenic Differentiation of Immortalized Mesenchymal Stromal Cells.

BACKGROUND: Silver nanoparticles (AgNPs) are a focus of huge interest in biological research, including stem cell research. AgNPs synthesized using Cyperus conglomeratus root extract have been previously reported but their effects on mesenchymal stromal cells have yet to be investigated. OBJECTIVES: The aim of this study is to investigate the effects of C. conglomeratus-derived AgNPs on adipogenesis and osteogenesis of mesenchymal stromal cells. METHODS: AgNPs were synthesized using C. conglomeratus root extract, and the phytochemicals involved in AgNPs synthesis were analyzed using gas chromatography-mass spectrometry (GC-MS). The cytotoxicity of the AgNPs was tested on telomerase-transformed immortalized human bone marrow-derived MSCs-hTERT (iMSC3) and human osteosarcoma cell line (MG-63) using MTT and apoptosis assays. The uptake of AgNPs by both cells was confirmed using inductively coupled plasma-optical emission spectrometry (ICP-OES). Furthermore, the effect of AgNPs on iMSC3 adipogenesis and osteogenesis was analyzed using stain quantification and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). RESULTS: The phytochemicals predominately identified in both the AgNPs and C. conglomeratus root extract were carbohydrates. The AgNP concentrations tested using MTT and apoptosis assays (0.5-64 µg/ml and 1,4 and 32 µg/ml, respectively) showed no significant cytotoxicity on iMSC3 and MG-63. The AgNPs were internalized in a concentration-dependent manner in both cell types. Additionally, the AgNPs exhibited a significant negative effect on osteogenesis but not on adipogenesis. CONCLUSION: C. conglomeratus-derived AgNPs had an impact on the differentiation capacity of iMSC3. Our results indicated that C. conglomeratus AgNPs and the associated phytochemicals could exhibit potential medical applications.

TOMM34 expression in early invasive breast cancer: a biomarker associated with poor outcome.

Appropriate mitochondrial functioning in normal cells depends on proper functioning of mitochondrial translocation machinery, of which translocase of the outer membrane of mitochondria (TOMM) plays important role. The aim of this study was to explore the expression of TOMM34 in invasive breast cancer (BC) with relevance to BC molecular subtypes and patients' outcome. Gene expression data of 128 BC were analysed using artificial neuronal network (ANN) analysis to identify differentially expressed genes between BC with distant metastases and that without distant metastases. TOMM34 expression was assessed in a large series of BC (n = 1,061) with long-term follow-up using tissue microarray and immunohistochemistry. TOMM34 protein expression was quantitatively measured using the novel reverse phase protein microarray (RPPA) technique. ANN analysis revealed TOMM34 gene transcript as one of the top differentially expressed gene correlated with BC distant metastasis. Protein expression of TOMM34 was associated with features of aggressive behaviour including higher tumour grade, advanced nodal stage, larger tumour size and lymphovascular invasion. TOMM34 over-expression was significantly associated with shorter BC-specific survival and metastasis-free survival independent of standard prognostic parameters. TOMM34 protein expression was quantified by RPPA which showed that the mean expression values of TOMM34 were higher in samples demonstrating features of poor outcome. This study demonstrates at translational protein expression level that TOMM34 is a marker of poor prognosis in BC. Our findings underscore the role played by mitochondrial machinery in BC progression and warrant their validation on a prospective basis.

A CD44⁻/CD24⁺ phenotype is a poor prognostic marker in early invasive breast cancer.

A CD44(-)/CD24(+) phenotype is a poor prognostic marker in early invasive breast cancer. Breast cancer cells with high CD44 and low or absent CD24 (i.e. CD44(+)CD24(-)/low phenotype) are reported to have stem cell features. However, the clinical impact of CD24 and CD44 expression in tumours remains unclear. To explore the immunohistochemical expression of CD44 and CD24 (individually and combined) and their clinical value as prognostic and predictive markers. Immunohistochemical expression of CD24 and CD44 was studied in a large series of early primary invasive breast cancer tumours (n = 1036) prepared as a tissue microarray. Associations between the expression of each marker individually and in combination and clinico-pathological, molecular variables and patients' outcome were investigated. CD24 cytoplasmic expression was significantly associated with poor prognostic variables including high tumour grade, ER-, PR-, HER2(+), p53+ and triple negative (TN) phenotype; P < 0.05. However, CD24 expression was not significantly associated with patients' outcome. Conversely, CD44 expression was associated with favourable prognostic criteria including lower Nottingham prognostic index, ER+, HER2- and luminal phenotype; P < 0.05. Moreover, CD44 expression was found to be an independent predictor of good prognosis. In combination, the CD44(+)/CD24(-) phenotype was associated with the most favourable outcome (84 and 80% 10 year breast cancer survival [BCSS] and metastasis free survival [MFS], respectively). Contrasting this, the CD44(-)/CD24(+) phenotype was associated with the most dismal outcome (62 and 60% 10 years BCSS and MFS, respectively). CD24 and CD44 expression can individually yield prognostic data in breast cancer, but importantly, when both markers are considered; the CD44(+)/CD24(-) phenotype had the best prognosis, while the CD44(-)/CD24(+) phenotype had the worst prognosis. This shows that the relationship between basic cell biology and clinical behaviour is not always straightforward and warrants further investigations of the true clinical impact of breast cancer stem cells.

Integrated structure-based activity prediction model of benzothiadiazines on various genotypes of HCV NS5b polymerase (1a, 1b and 4) and its application in the discovery of new derivatives.

This work presents the first structure-based activity prediction model for benzothiadiazines against various genotypes of HCV NS5b polymerase (1a, 1b and 4).The model is a comprehensive workflow of structure-based field template followed by guided docking. The field template was used as a pre-filter and a tool to provide hits in good orientation and position. It was created based on detailed molecular interaction field analysis which includes Topomer CoMFA, grid independent analysis and Superstar. On the other hand, Guided docking was used as a refinement and assessment tool. It was actively directed by two scores: Moldock score as an interaction descriptor (r(2)=0.65) and a template similarity score as a measure for accurate binding-mode compliance. The docking template was based on energy-based pharmacophore analysis. The whole procedure was formulated and tweaked for both screening (ROC of AUC=0.91) and activity prediction (r(2) of 0.8) for the genotype 1a. In order to widen the model scope, linear interaction energy was used as a tool for predicting activities of other genotypes based on the docked ligand poses while mutation binding energy was used to investigate the effect of each amino acid mutation in genotype 4. The model was applied for structure-based fragment hopping by screening a library designed by reaction enumeration. A top scoring hit was used to generate a focused library such that it has lower TPSA than the original class ligands and thus better pharmacokinetic properties. After that, experimental validation was carried out by the synthesis of this library and its biological evaluation which yielded compounds that exhibit EC(50) ranging from 1.86 to 23 µM.

Association between Vitamin D Deficiency and Vitamin D Receptor Gene Polymorphism (FokI-rs2228570) among Men with Anemia in Babylon Province, Iraq.

Vitamin D or calciferol is a fat-soluble vitamin that has a unique feature of synthesizing in the body mainly by exposure to UV from the sunlight and then transformed to 25 (OH) D by the liver and finally to a vital form 1,25-dihydroxyvitamin D by the kidneys. Vitamin D receptor gene polymorphism (FokI-rs2228570) has been proposed as the major cause of anemia. The present study aimed to discover the association between vitamin D deficiency and vitamin D receptor gene polymorphism (FokI-rs2228570) in patients with anemia. A total of 120 men with anemia and no kidney disorders have been compared with 60 healthy controls in the present case-control study. A single nucleotide polymorphism (SNP) FokI-rs2228570 was detected by PCR and PCR-RFLP techniques. Levels of serum vitamin D, erythropoietin, and some biochemical parameters were detected by the ELISA assay technique. The mutant homozygous genotype ff was more frequent in patients with anemia (45%) than in the controls (15%). Also, the frequency of the f allele was associated with a significant decrease in the levels of vitamin D and hemoglobin in patients (0.62%); therefore, the mutant allele is a risk factor for developing anemia compared with genetic patterns FF and Ff. Vitamin D deficiency is common in those with anemia which is often associated with low hemoglobin and high levels of erythropoietin. Additionally, the genetic frequencies also affect the level of vitamin D which is indicated by low levels of mutant patterns (Ff, ff) in which patients suffer from severe anemia.

Using Rosemary Essential Oil as a Potential Natural Preservative during Stirred-like Yogurt Making.

The popularity of rosemary has grown as a natural alternative over the synthetic supplements due to its potential health benefits. The rosemary plant has been utilized to preserve food due to its ability to prevent oxidation and microbial contamination. The reason for this study was to determine the phytochemical components and antimicrobial activity of rosemary essential oil (REO) and the effect of REO addition (0.5 and 0.7%) on the chemical, microbiological, and sensory properties of stirred-like yogurt (SLY) during 16 days of storage at 4 °C. The obtained data observed that REO exhibited antimicrobial action against Escherichia coli, Staphylococcus aureus, and Salmonella marcescens, as well as fungi (Aspergillus flavus) and yeasts (Candida albicans). Increased REO to 0.7% accelerated (p < 0.05) the development of lactic acid bacteria (LAB) in SLY (8.3 log cfu/g) and delayed yeast growth up to 12 days. Molds and coliforms were also not found in the SLY samples with REO. In comparison to control samples, sensory results showed that the addition of REO improves the overall acceptance of SLY (p < 0.05). In conclusion, the current study found that REO could be used as a natural preservative during the production of SLY to extend shelf-life and promote LAB development.

A clinical guide to deep venous stenting for chronic iliofemoral venous obstruction.

BACKGROUND: An increase in endovenous interventions for deep venous pathologies has been observed. This article aims to provide an overview of the role of venous stenting in the management of chronic conditions affecting the deep venous system of the lower limbs, with a focus on intervention relating to the vena cava and iliofemoral venous segments. METHODS: An overview of the literature on the minimally invasive venous stenting procedures that are being increasingly used in the management of chronic conditions affecting the deep venous system of the lower limbs. RESULTS: We discuss key areas of interest to a venous specialist practicing in this area, including diagnostic imaging in chronic deep venous disease, with a focus on the use of intravascular ultrasound examination in this context; the treatment of chronic venous outflow obstruction, including the rationale and structural indications for stenting, current guidance regarding stent placement, and fundamental points to consider during decision-making (endophlebectomy and stenting, stenting across the inguinal ligament, optimal sizing of venous stents, extension of venous stenting to beyond the common femoral vein confluence, the role of thrombolysis useful in chronic venous disease, and arteriovenous fistulae); outcomes and initial reports of stenting; and the future of venous stents. CONCLUSIONS: Deep venous stenting has become a key treatment option for chronic (thrombotic or nonthrombotic) obstructive venous disease. Dedicated venous stents and intravascular ultrasound examination represent important technological advances in the minimally invasive treatment of symptomatic chronic deep venous obstruction, which previously required open surgical reconstruction.

A possible role for ticks in the transmission of Madurella mycetomatis in a mycetoma-endemic village in Sudan.

BACKGROUND: Currently there is a wide knowledge gap in our understanding of mycetoma epidemiological characteristics, including the infection route. METHODS: A cross-sectional descriptive epidemiological study was carried out to determine the role of exposure to animals and insects such as ticks in the transmission of eumycetoma in two adjacent villages at eastern Sudan. RESULTS: Significant differences were found between the two villages in the level of contact and exposure to animals and ticks, the percentages of people bitten by ticks, participation in cleaning animal pens and knowledge of the medical importance of ticks. In the village with a high mycetoma prevalence rate, there were high infestation rates of ticks in domestic animals. Hyalomma and Rhipicephalus species were the most prevalent species in houses with mycetoma patients and together they constituted 83% of the total collection. Pool screening of vectors for the detection of Madurella mycetomatis recombinant RNA genes showed one positive pool from Rhipicephalus evertsi following amplification of the universal fungal primer and one positive sample from Hyalomma rufipes following the use of a specific primer. CONCLUSION: The findings indicate a possible role of ticks in the transmission of eumycetoma causative agents. However, further in-depth studies are needed to verify this.