Anti-inflammatory potential of aspergillus unguis SP51-EGY: TLR4-dependent effects & chemical diversity via Q-TOF LC-HRMS.

Inflammation serves as an intricate defense mechanism for tissue repair. However, overactivation of TLR4-mediated inflammation by lipopolysaccharide (LPS) can lead to detrimental outcomes such as sepsis, acute lung injury, and chronic inflammation, often associated with cancer and autoimmune diseases. This study delves into the anti-inflammatory properties of "Aspergillus unguis isolate SP51-EGY" on LPS-stimulated RAW 264.7 macrophages. Through real-time qPCR, we assessed the expression levels of pivotal inflammatory genes, including iNOS, COX-2, TNF-α, and IL-6. Remarkably, our fungal extracts significantly diminished NO production and showed noteworthy reductions in the mRNA expression levels of the aforementioned genes. Furthermore, while Nrf2 is typically associated with modulating inflammatory responses, our findings indicate that the anti-inflammatory effects of our extracts are not Nrf2-dependent. Moreover, the chemical diversity of the potent extract (B Sh F) was elucidated using Q-TOF LC-HRMS, identifying 54 compounds, some of which played vital roles in suppressing inflammation. Most notably, compounds like granisetron, fenofibrate, and umbelliprenin were found to downregulate TNF-α, IL-1ß, and IL-6 through the NF-κB signaling pathway. In conclusion, "Aspergillus unguis isolate SP51-EGY", isolated from the Red Sea, Egypt, has been unveiled as a promising TLR4 inhibitor with significant anti-inflammatory potentials, presenting novel insights for their potential therapeutic use in inflammation.

The impact of wearing complete denture in one or both arches, on eating-related quality of life and patients' perceived need for advice to support eating well: Results from a qualitative study.

BACKGROUND: Wearing complete denture in one or both arches can impact enjoyment of eating and affect quality of life compared with being dentate. Clinicians focus on issuing technically sound dentures but ignore the impact of wearing dentures on the eating-related quality of life which affects the success of treatment. OBJECTIVES: The aim of this research was to qualitatively explore ERQoL in Australian adults wearing complete dentures using a validated questionnaire and through focus groups. METHODS: Complete denture wearers (n = 44) were recruited from dental clinics and invited to complete the self-administered Emotional and Social Issues Related to Eating questionnaire. Responses were categorised under the six questionnaire domains. A subsample of 20 participants who completed the questionnaire were invited to participate in focus groups to identify emerging themes. RESULTS: Twenty-three participants (52.3%) completed the questionnaire. Most participants expressed a decline in enjoyment of eating due to reduced ability to eat, longer chewing times and the need to frequently clean dentures while eating. Focus groups (n = 2 × 4 participants) indicated educational materials on eating with dentures would increase recognition of eating problems with dentures and reduce trial and error approaches to dealing with these. CONCLUSION: ERQoL is adversely affected by wearing complete dentures due to functional limitations, restricted food choices and adaptive eating behaviours. Patient support for eating well with a complete denture/s wearers is required.

Adsorption of azo dye by biomass and immobilized Yarrowia lipolytica; equilibrium, kinetic and thermodynamic studies.

One of the major environmental problems we have today is dye pollution, primarily caused by the textile industry. This pollution has detrimental effects on aquatic life, soil fertility, and human health. Many microbial biosorbents have been documented in the literature for the removal of a wide range of azo dyes commonly employed in the textile industry. However, Yarrowia lipolytica NBRC1658 is firstly used as both free and immobilized sorbents for the removal of Reactive yellow 18 (RY18), acid red 18 (AR18) and basic blue 41 (BB41) in this study. The effect of experimental conditions such as pH, biosorbent quantity, dye concentration, contact time, and temperature on dye removal capacity are examined. The research findings demonstrate that the adsorption capacity is higher in biomass compared to immobilized cells. The highest adsorption capacities are observed at pH 2 for RY18 and AR18, while pH 9 is optimal for BB41. Increasing the adsorbent dosage and initial concentration significantly improves the adsorption capacity. The Langmuir model best describes the adsorption process, indicating that the dye attaches to the biosorbent in a single layer, with a uniform biosorbent surface. The removal of the dye occurs through a chemical process on the biosorbent surface, as evidenced by the pseudo-second-order kinetic model. According to thermodynamic analysis, higher temperatures promote greater adsorption of dyes. Our study shows the effectiveness of Yarrowia lipolyica NBRC1658 as a biosorbent in the removal of a wide range of industrial dyes.

Stress Factors, Stress Levels, and Coping Mechanisms among University Students.

Aims: To explore university students' levels of stress, stressors, and their coping style. Methods: A cross-sectional correlational design with a convenience sample (n = 676) of university students who completed the Student-Life Stress Inventory (SSI) and Coping Strategies Indicator (CSI) was used. Findings. Overall, two-thirds of the participant reported moderate levels of stress. Students with chronic illness, living alone, low CGPA, and having exams today experienced a statistically higher mean level of stress. Students who are living alone used the "avoidance" method more significantly and the "social support" method significantly less compared with students who are living with their families and friends. Conclusion: This study concurs with others that university students are prone to distress. To our knowledge, this is the first study in the region to explore the students' coping skills. Some of the employed coping and associated factors could be used to lay the groundwork for evidence-based prevention and mitigation.

Mechanical traction from different knee joint angles in patients with knee osteoarthritis: A randomized controlled trial.

OBJECTIVE: To compare the effect of mechanical traction from different knee angles on pain, physical function, and range of motion in patients with knee osteoarthritis. DESIGN: A single-blinded, randomized controlled trial. SETTING: Outpatient public and governmental Hospital clinics. PARTICIPANTS: One hundred and twenty patients with knee osteoarthritis were randomly assigned into 4 equal groups with 30 patients in each group. INTERVENTIONS: Group (A) received conventional physiotherapy(CPT) treatment; group (B) received CPT with knee traction from full extension, group (C) received CPT with knee traction from 90° flexion, while group (D) received CPT with knee traction from 20° flexion. Interventions were applied 3 sessions a week for 4 weeks. OUTCOME MEASUREMENTS: Visual analog scale (VAS), knee passive range of motion and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) were measured at baseline, immediately after 4 weeks of intervention, and after 4 weeks of no intervention as a follow-up. RESULTS: After eight weeks, the mean (SD) for VAS scores were 30.97 ± 8.68, 24.0 ± 8.8, 15.43 ± 6.31, and 16.17 ± 6.11 mm; for total WOMAC scores were 26.77 ± 9.19, 20.3 ± 8.52, 13.27 ± 6.25, and 13.43 ± 7.14 for groups A, B, C and D, respectively. The three traction groups showed statistically significant changes in pain scores, physical function, and total WOMAC, but not for knee passive range of motion, in favor of traction groups C and D than the conventional group (P < 0.05). CONCLUSIONS: Traction from 90°and 20° of knee flexion was found superior to full extension knee in improving pain and physical function, but not for knee passive range of motion, in patients with knee osteoarthritis.

Genetic polymorphisms associated with obesity in the Arab world: a systematic review.

BACKGROUND: Obesity, one of the most common chronic health conditions worldwide, is a multifactorial disease caused by complex genetic and environmental interactions. Several association studies have revealed a considerable number of candidate loci for obesity; however, the genotype-phenotype correlations remain unclear. To date, no comprehensive systematic review has been conducted to investigate the genetic risk factors for obesity among Arabs. OBJECTIVES: This study aimed to systematically review the genetic polymorphisms that are significantly associated with obesity in Arabs. METHODS: We searched four literature databases (PubMed, Science Direct, Scopus, and Google Scholar) from inception until May 2020 to obtain all reported genetic data related to obesity in Arab populations. Quality assessment and data extraction were performed individually by three investigators. RESULTS: In total, 59 studies comprising a total of 15,488 cases and 9,760 controls were included in the systematic review. A total of 76 variants located within or near 49 genes were reported to be significantly associated with obesity. Among the 76 variants, two were described as unique to Arabs, as they have not been previously reported in other populations, and 19 were reported to be distinctively associated with obesity in Arabs but not in non-Arab populations. CONCLUSIONS: There appears to be a unique genetic and clinical susceptibility profile of obesity in Arab patients.

Vitamin D3 supplementation ameliorates ovariectomy-induced cardiac apoptotic and structural changes in adult albino rats.

The effect of vitamin D on cardiac dysfunction after menopause is still under investigation. Therefore, we investigated the effect of vitamin D3 on cardiac apoptotic and structural changes in ovariectomized rats. Forty adult female albino rats were divided into 4 equal groups: sham rats, sham rats treated with vitamin D3, ovariectomized rats, and ovariectomized rats treated with vitamin D3 (500 IU/kg per day for 6 weeks, orally). Body mass, blood pressure, heart rate, and whole heart mass (WHM) were measured. Serum soluble receptors of advanced glycation end products (sRAGE), C-reactive protein, malondialdehyde, and total antioxidant capacity were estimated. Cardiac sections were stained with haematoxylin-eosin and Masson's trichrome stain. Fas and FasL apoptosis-related proteins were detected by immunohistochemistry. Vitamin D3 treatment significantly decreased ovariectomy-induced cardiac Fas and FasL apoptosis-related proteins, whole heart mass, body mass, C-reactive protein, and malondialdehyde accompanied by decreased inflammation and reduced collagen deposition between cardiac muscle fibres. However, vitamin D3 significantly increased total antioxidant capacity and sRAGE in ovariectomized and sham treated groups. Our findings suggest that vitamin D3 treatment can prevent ovariectomy-induced cardiac structural and apoptotic changes in rats via increasing sRAGE and antioxidant activity. Our results suggest that vitamin D3 has therapeutic effect against postmenopausal cardiovascular disease.

Comparative study between lutein and its liposomal form on cisplatin-induced retinal injury in rabbits.

Aim: Lutein is a potent antioxidant that is found in ocular tissue. It protects retina against oxidative stress. We aimed to increase lutein efficiency by encapsulating it into liposome and testing its neuroprotective effect against cisplatin-induced retinal injury in rabbits. Materials and methods: Twenty-four male, New Zealand, rabbits weighing 1.5-2 kg were divided into four groups, as follows: group I as a control, group II received cisplatin, group III received free lutein + cisplatin and group IV received liposomal lutein + cisplatin. All treatments were administrated twice per week for 14 days. Electroretinogram (ERG) was recorded for all rabbits just before decapitation. Then, the retinae were subjected to histopathological evaluations and comet assay. Results: Results indicated significant decrease (p ˂ 0.01) in ERG waves, significant increase (p ˂ 0.01) in all parameters of comet assay (% tailed cells, tail length, DNA% in tail and tail moment), severe fragmentation in photoreceptors layer and changes in inner retina after the administration of cisplatin. There were some sort of improvement in ERG, comet assay and the histological results after the administration of lutein with cisplatin, whereas these tests yielded values comparable to control in the liposomal lutein group. Conclusions: Liposomal lutein administration could prevent the detrimental effects of cisplatin on the retina, while avoiding the use any artificial chemicals. The latter might be preferable but with possible highly toxic effects. Results were promising and worse further future investigations.

Optimization of a nano-enzymatic reactor for on-line tryptic digestion of polypeptide conjugates by capillary electrophoresis.

This work aims at studying the optimization of an on-line capillary electrophoresis (CE)-based tryptic digestion methodology for the analysis of therapeutic polypeptides (PP). With this methodology, a mixture of surrogate peptide fragments and amino acid were produced on-line by trypsin cleavage (enzymatic digestion) and subsequently analyzed using the same capillary. The resulting automation of all steps such as injection, mixing, incubation, separation and detection minimizes the possible errors and saves experimental time. In this paper, we first study the differents parameters influencing PP cleavage inside the capillary (plug length, reactant concentration, incubation time, diffusion and electrophoretic plugs mixing). In a second part, the optimization of the electrophoretic separation conditions of generated hydrolysis products (nature, pH and ionic strength (I) of the background electrolyte (BGE)) is described. Using the optimized conditions, excellent repeatability was obtained in terms of separation (migration times) and proteolysis (number of products from enzymatic hydrolysis and corresponding amounts) demonstrating the robustness of the proposed methodology.

Effect of remaining tooth structure on the fracture resistance of endodontically-treated maxillary premolars: An in vitro study.

STATEMENT OF PROBLEM: Assessing the quantity and distribution of residual coronal dentin is important in deciding the restorability of endodontically treated teeth. PURPOSE: The purpose of this in vitro study was to investigate the relationship between the cross-sectional area and location of remaining coronal tooth structure and the fracture resistance of restored teeth after endodontic treatment. MATERIAL AND METHODS: Fifty-five extracted maxillary premolars received endodontic treatment and crown preparations. The teeth were assigned to 11 groups of 5 teeth according to the number and the location of missing axial walls. Impressions of the prepared teeth were made to fabricate dies. Each die was sectioned 1 mm above the finish line, and the dentin surface area was measured. All teeth were restored with composite resin cores and cast metal crowns. The specimens were thermocycled between 5°C and 55°C for 500 cycles before loading until failure with a universal testing machine. The results were analyzed with 1-way ANOVA and post hoc comparisons. RESULTS: Specimens with all axial walls intact around the access cavity had the highest mean fracture strength (1380.5 ±393.9 N). Groups with the palatal and 1 or 2 proximal walls missing showed the lowest mean failure loads (398.4 N ±149.5 N and 344.7 N ±91.2 N). The correlation between the surface area and the fracture resistance was 0.72 CONCLUSIONS: For restored endodontically treated maxillary premolars, a positive linear relationship was found between the remaining coronal dentin surface area and fracture strength. Residual dentin location influences fracture resistance.

Design and implementation of Type-3 intuitionistic fuzzy logic MPPT controller for PV solar system: Comparative study.

The performance of a photovoltaic (PV) solar system is affected by partial shading conditions (PSC) and environmental conditions, such as solar irradiance and ambient temperature, which vary throughout the day. This results in variations in the maximum power point (MPP) on the solar PV output characteristic curve. Therefore, various classical MPP tracking (MPPT) techniques have been used to track the MPP and extract maximum power from PV systems. However, these techniques have drawbacks such as lower stability, increased oscillation around the steady state, and slower convergence to the MPP. To overcome this problem, the newly proposed interval Type-3 intuitionistic fuzzy logic (T3IFL) controller has been proposed. The T3IFL MPPT controller combines the uncertainty of Type-3 fuzzy logic (T3FL) controller with intuitionistic concepts. The T3IFL controller is more accurate and offers faster convergence to the MPP under changing climatic and steady-state conditions than classical techniques and T3FL controller. The T3IFL algorithm provides better performance with excellent MPP tracking by controlling the duty cycle of the DC-DC buck converter. Four cases studied were investigated: uniform radiation conditions, a step change in solar radiation with constant temperature, replacing the battery load with the ohmic load with constant radiation and temperature, and partial shading conditions. Experimental validation of the T3IFL was performed on a DC-DC buck converter using real-time hardware-in-the-loop (HIL). Finally, the simulation and experimental results with comparative studies verified the accuracy of the proposed method in tracking the desired value and disturbance/uncertainty attenuation with better response.

Safety and efficacy of transjugular intrahepatic portosystemic shunts vs endoscopic band ligation plus propranolol in patients with cirrhosis with portal vein thrombosis: a systematic review and meta-analysis.

BACKGROUND: This systematic review and meta-analysis aimed to assess the efficacy and safety of transjugular intrahepatic portosystemic shunts (TIPS) against the combined treatment of endoscopic band ligation (EBL) and propranolol in managing patients with cirrhosis diagnosed with portal vein thrombosis (PVT). METHODS: A literature search from inception to September 2023 was performed using MEDLINE, the Cochrane Library, Web of Science, and Scopus. Independent screening, data extraction, and quality assessment were performed. The main measured outcomes were the incidence and recurrence of variceal bleeding (VB), hepatic encephalopathy, and overall survival. RESULTS: A total of 5 studies were included. For variceal eradication, there was initially no significant difference between the groups; however, after sensitivity analysis, a significant effect emerged (risk ratio [RR], 1.55; P < .0001). TIPS was associated with a significant decrease in the incidence of VB (RR, 0.34; P < .0001) and a higher probability of remaining free of VB in the first 2 years after the procedure (first year: RR, 1.41; P < .0001; second year: RR, 1.58; P < .0001). TIPS significantly reduced the incidence of death due to acute GI bleeding compared with EBL + propranolol (RR, 0.37; P = .05). CONCLUSION: TIPS offers a comprehensive therapeutic advantage over the combined EBL and propranolol regimen, especially for patients with cirrhosis with PVT. Its efficacy in variceal eradication, reducing rebleeding, and mitigating death risks due to acute GI bleeding is evident.

New quinazolin-2,4-dione derivatives incorporating acylthiourea, pyrazole and/or oxazole moieties as antibacterial agents via DNA gyrase inhibition.

This article contributes to the search for new therapeutic agents for treatment of diseases caused by bacterial pathogens. In this study, a new series of compounds incorporating numerous bioactive moieties such as quinazolin-2,4-dione, acylthiourea linkage, and/or five membered nitrogen heterocycles (pyrazole and oxazole) 2-5a-c was described to identify new antibacterial drug candidates via inhibition of DNA gyrase enzyme. The precursor N-[N'-(2-cyano-acetyl)-hydrazinocarbothioyl]-4-(2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)-benzamide 2 was prepared by treatment of compound 1 with ammonium thiocyanate and cyanoacetic acid hydrazide through multicomponent reaction (MCR). In addition, compounds 3a-d and 4a-b were synthesized by treatment of 2 with aromatic aldehydes and/or ketones through Knoevenagel reaction, affording high purity products in satisfactory yields. Moreover, new heterocyclic moieties such as pyrazole and/or oxazole attached to quinazolin-2,4-dione core 5a-c were synthesized by treatment of 3c with different nucleophilic reagents like hydrazine, phenyl hydrazine and hydroxyl amine, respectively. Subsequently, the obtained products were structurally characterized by IR, 1H-, 13C-NMR, and MS analyses. The minimum inhibitory concentration (MIC) and antibacterial potency of all compounds were estimated against two G-ve (E. coli and P. aeruginosa), and two G+ve bacteria (B. subtilis and S. aureus). Encouragingly, compound 3c demonstrated the best antibacterial activity against all the strains of the tested pathogenic bacteria at low concentrations compared with the standard drug, Ciprofloxacin. Electron withdrawing groups such as -NO2 and -Cl enhance the antibacterial activity. Next, a molecular docking study between the synthesized derivatives and the target enzyme, DNA gyrase enzyme (PDB: 2xct) was undertaken to investigate intermolecular interactions between the compounds and target enzyme.

Comparing Left Ventricular Structure and Functions in End-Stage Renal Disease Using Conventional Echocardiography and 2D Speckle Tracking Echocardiography.

BACKGROUND: Patients on hemodialysis (HD) are prone to various cardiovascular complications. Two-dimensional speckle tracking echocardiography (2D STE) is an innovative technique for early myocardial dysfunction detection, even with normal ejection fraction (EF). OBJECTIVE: We aim to detect left ventricle (LV) dysfunction in regular hemodialysis patients using 2D STE compared to traditional echocardiography. METHODS: The study comprised 30 patients with end-stage renal disease (ESRD), subdivided according to left ventricular mass index (LVMI) into group 1 with left ventricular hypertrophy (LVH) (n=19) and group 2 without LVH (n=11). Another 30 healthy control subjects were recruited as group 3. The EF, average systolic velocity (Sa), and 2D LV strain were taken as measures of LV systolic function. The indicators for diastolic function included the E/A ratio and E velocity/peak early diastolic velocity. RESULTS: Regarding the parameters of LV systolic and diastolic functions assessed by traditional echocardiography, we found no significant difference between groups 1 and 2. However, using 2D STE, we observed significant differences in the average Sa velocity (p=0.025), average LV strain (p=0.03), 2D global longitudinal strain (GLS) (p=0.03), E/Ea (p=0.003), and LV myocardial performance index (MPI) (p=0.006). Also, a significant positive correlation was found between LVMI and left ventricular end-diastolic diameter (LVEDD) (p<0.01, r=0.63), EF measured by 2D (p=0.034, r=0.39), mitral E/A ratio (p=0.03, r=0.49), and mitral E/Ea (p<0.01, r=0.72). There was a significantly strong negative correlation between LVMI and 2D average LV strain (p=0.034, r=-0.39). CONCLUSION: We concluded that 2D STE is more sensitive than a conventional echo in detecting early LV systolic and diastolic dysfunction even in patients with normal EF.

Size and charge characterization of polymeric drug delivery systems by Taylor dispersion analysis and capillary electrophoresis.

In this work, Taylor dispersion analysis and capillary electrophoresis were used to characterize the size and charge of polymeric drug delivery nanogels based on polyglutamate chains grafted with hydrophobic groups of vitamin E. The hydrophobic vitamin E groups self-associate in water to form small hydrophobic nanodomains that can incorporate small drugs or therapeutic proteins. Taylor dispersion analysis is well suited to determine the weight average hydrodynamic radius of nanomaterials and to get information on the size polydispersity of polymeric samples. The effective charge was determined either from electrophoretic mobility and hydrodynamic radius using electrophoretic modeling (three different approaches were compared), or by indirect UV detection in capillary electrophoresis. The influence of vitamin E hydrophobicity on the polymer effective charge has been studied. The presence of vitamin E leads to a drastic decrease in polymer effective charge in comparison to non-modified polyglutamate. Finally, the electrophoretic behavior of polyglutamate backbone grafted with hydrophobic vitamin E (pGVE) nanogels according to the ionic strength was investigated using the recently proposed slope plot approach. It was deduced that the pGVE nanogels behave electrophoretically as polyelectrolytes which is in good agreement with the high water content of the nanogels.

Potential role of blood constituents in pain-relief associated with fibromyalgia treatment with extremely low magnetic field: Spectroscopic investigation.

Magnetic field is used as an adjunct therapy for pain control and relief of musculoskeletal pain conditions as Fibromyalgia. It is regarded as more natural and less harmful alternative to analgesic compounds. The exact mechanism underlying these positive effects is still to be determined. Twenty-three patients diagnosed with Fibromyalgia condition were included in this study, and subjected to extremely low magnetic field treatment sessions. The treatment protocol based on exposing patients to gradually increased magnetic field strength that starts with 0.1 µT at the beginning, and increased gradually to 100 µT (3.33 µT/min). UV-Visible, mid-IR and fluorescence characteristics of whole blood, erythrocytes and hemoglobin were investigated; in addition to RBCs-osmotic fragility measurements. The obtained results were analyzed according to control-sham exposed patients. We observed marked changes in the blood (and/or its constituents) absorption spectra of fibromyalgia patients that indicate an enhancement in the energetic pathways and increased hemoglobin-oxygen affinity; in addition, the osmotic fragility measurements show that erythrocytes were characterized by increased elasticity and rehydration. The analyses of infrared spectra show that magnetic field treatment was associated with changes in the erythrocytes skeleton where α-helix component of protein secondary structure is dominant. This study provides scientific evidence that pain relief associated with extremely low magnetic field treatment can be directly related to its systemic effects as well as the enhancement of the cellular activities.

Adding Weight Shift Training to Weight Reduction Decreases the Risk of Falling in Obese Women: A Prospective Randomized Controlled Trial.

OBJECTIVE: The aim of this study was to examine the effect of adding weight shift training to a weight loss program on the risk of falling, fear of falling, overall stability, anteroposterior stability, mediolateral stability, and isometric knee torque in young obese women. DESIGN: A single-blinded, randomized controlled study was performed. Sixty women, 18 to 46 yrs old, were randomly assigned either to the study or the control group. The participants in the study group were given weight-shifting training plus a weight reduction program; the control group received only a weight-reduction program. The interventions were performed for 12 wks. At baseline and after 12 wks of training, the risk of falling, fear of falling, overall stability, anteroposterior stability, mediolateral stability, and isometric knee torque were all examined. RESULTS: There were statistically significant differences in risk of falling, fear of falling, isometric knee torque, and overall, anteroposterior, and mediolateral stability indices, in favor of the study group, after 3 mos of training ( P < 0.001). CONCLUSIONS: Weight shift training combined with weight reduction was more beneficial than weight reduction alone in decreasing the risk of falling and fear of falling and improving isometric knee torque and overall, anteroposterior, and mediolateral stability indices. It could be used for treating balance problems and weakness around the knee joint in obese women. TO CLAIM CME CREDITS: Complete the self-assessment activity and evaluation online at http://www.physiatry.org/JournalCME. CME OBJECTIVES: Upon completion of this article, the reader should be able to: (1) Determine the impact of weight shift training on risk of falling and postural stability in obese women; (2) Identify the effect of weight shift training on fear of falling in adult women with obesity; and (3) Verify the additive effect of weight shift training to weight reduction program vs. weight reduction program alone on muscle strength in young obese women. LEVEL: Advanced. ACCREDITATION: The Association of Academic Physiatrists is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.The Association of Academic Physiatrists designates this Journal-based CME activity for a maximum of 1.0 AMA PRA Category 1 Credit(s) ™. Physicians should only claim credit commensurate with the extent of their participation in the activity.

Novel 3-phenylquinazolin-2,4(1H,3H)-diones as dual VEGFR-2/c-Met-TK inhibitors: design, synthesis, and biological evaluation.

Multitarget anticancer drugs are more superior than single target drugs regarding patient compliance, drug adverse effects, drug-drug interactions, drug resistance as well as pharmaceutical industry economics. Dysregulation of both VEGFR-2 and c-Met tyrosine kinases (TKs) could result in development and progression of different human cancers. Herein, we reported a novel series of 3-phenylquinazolin-2,4(1H,3H)-diones with thiourea moiety as dual VEGFR-2/c-Met TKs. Compared to sorafenib, cabozantinib went behind VEGFR-2 inhibition to target c-Met TK. The dual VEGFR-2/c-Met inhibitory activity of cabozantinib is due to a longer HB domain than that of sorafenib. Based on pharmacophore of cabozantinib analogues, we designed new dual VEGFR-2/c-Met TKs. We synthesized the target compounds via a new single pot three-component reaction. The cytotoxic activity of synthesized compounds was conducted against HCT-116 colorectal cancer cell line. Compounds 3c and 3e exhibited the highest cytotoxic activity against HCT-116 cell line (IC50 1.184 and 3.403 µM, respectively). The in vitro enzyme inhibitory activity was carried out against both VEGFR-2 and c-Met TKs. Compound 3e has the highest inhibitory activity against both VEGFR-2/c-Met (IC50 = 83 and 48 nM, respectively). Docking studies showed that α-oxo moiety in quinazoline ring formed hydrogen bond HB with Met1160 residue in the adenine region of c-Met TK.

Use of Basilic vein in arteriovenous fistulas construction for hemodialysis access. Is it a good option alternative to prosthetic arteriovenous grafts?

PURPOSE: For patients with a failed forearm autogenous fistula (AF) and an exhausted cephalic vein, there is controversy about whether a brachial basilic AF with transposition or an arteriovenous prosthetic bridging graft (BG) must be the second vascular access option. This work measured and compared these two modalities according to patency rates, complications, and revisions. PATIENTS AND METHODS: A retrospective study of 104 cases that had either a brachial basilic AF (72) or an Arteriovenous BG (32). Technical success, operative complications, procedurerelated mortality, maturation time, functional primary, secondary, and overall patency rates were all assessed. RESULTS: Technical success was obtained in all participants. No procedure-linked mortality. Maturation time for BGs was significantly shorter than AFs. The complication rate was significantly higher in BGs than in AFs. The most prevalent complication was access thrombosis. The functional primary patency rate was significantly higher in AF than in BG at 12-month followup: 77.7% vs 53.1% (p < 0.012). secondary patency rate was higher in AF than in BG at 1-year follow-up 62.5% vs 42.8% (p = 0.063), respectively. In addition, BGs required more interventions to preserve patency. CONCLUSIONS: AF had higher primary, secondary and overall functional patency rates and needed fewer procedures to keep patency than BGs. Cases that need early vascular access as a result of central venous catheter complications or who have a reduced life expectancy may benefit from BGs.

Relation between myostatin levels and malnutrition and muscle wasting in hemodialysis patients.

BACKGROUND AND AIM: Malnutrition is one of the most troublesome comorbidities among hemodialysis patients (HD). Myostatin (MSTN) belongs to the transforming growth factor-ß superfamily. In HD patients, MSTN effects are not limited to skeletal muscle growth. The present study aimed to assess MSTN levels in HD patients and its relation to various clinical and biochemical parameters. PATIENTS AND METHODS: The present case control study included 60 patients on HD for at least three years. In addition, there were age and sex-matched healthy subjects who constitutes the control group. Nutritional status was evaluated using the malnutrition inflammation score (MIS). Muscle wasting in the present study was evaluated using the lean tissue index (LTI) as assessed by the body composition monitor (BCM). Rectus Femoris Muscle (RFM) thickness was also measured as indicator for nutritional status of patient. RESULTS: The present study included 60 HD patients, and ageand sex-matched healthy controls. Patients expressed significantly higher myostatin levels when compared to controls [median (IQR): 221.3 (153.5-688.2) versus 144.8 (97.0-281.7), p < 0.001]. According to MIS, patients were classified into those with no/mild malnutrition (n = 22) and others with moderate/severe malnutrition (n = 38). Comparison between the two subgroups revealed that the former group had significantly lower myostatin levels [167.7 (150.3-236.3) versus 341.7 (160.9-955.9), p = 0.004]. According to LTI, patients were classified into those with muscle wasting (n = 23) and others without muscle wasting (n = 37). Comparative analysis showed that patients in the former group had significantly higher myostatin levels [775.1 (325.1-2133.7) versus 161.8 (142.6-302.3), p < 0.001]. CONCLUSIONS: Myostatin seems to be a promising marker for identification of malnutrition and muscle wasting in HD patients.