Microstructural Evolutions and its Impact on the Corrosion Behaviour of Explosively Welded Al/Cu Bimetal

In this study, the microstructural evolutions and corrosion resistance of aluminium/copper joint fabricated through explosive welding process have been thoroughly investigated, while stand-off distance was variable. Microstructural analyses demonstrate that, regardless of grain refinement in the welding boundary, increasing the stand-off space is followed by a higher thickness of the localized melting pool. X-Ray diffraction (XRD) and energy-dispersive X-ray spectroscopy (EDS) analyses recognized the binary intermetallic layers as a combination of Al2Cu and AlCu. Polarization and electrochemical impedance spectroscopy (EIS) corrosion tests revealed that a higher stand-off distance resulted in the increment of corrosion potential, current rate, and concentration gradient at the interface owing to the remarkable kinetic energy of the collision, which impaired corrosion resistance

Alveolar rhabdomyosarcoma of the left hand with bilateral breast metastases in an adolescent female

Rhabdomyosarcoma is a common extramammary malignancy in pediatric age groups, but it rarely metastasizes to the breast. Breast rhabdomyosarcomas are commonly metastatic, with possible primary locations at the head and neck, trunk, extremities, retroperitoneum and perianal region. We report a case of primary alveolar rhabdomyosarcoma of the upper extremities in a 17-year-old adolescent female who presented with bilateral lower limb weakness and bilateral breast lumps

Pharmacokinetic Parameters and Over-Responsiveness of Iranian Population to Propranolol

Purpose: Propranolol is the most widely used treatment for cardiovascular diseases. Dosage range in our patients is usually less than the amount mentioned in references. The aim of the present study was to clarify whether pharmacokinetic differences are able to justify the need for the fewer doses in our patients or not. Methods: Twenty healthy volunteers (10 male) at heart center of Mazandaran University of Medical Sciences were studied. Samples of blood were collected before a single oral dose (40 mg) of Propranolol. Blood samples were taken up to 9 hours after dose. Total plasma concentration of Propranolol was measured by HPLC. Population Pharmacokinetic analysis was performed using population pharmacokinetics modeling software P-Pharm. Results: The mean value for oral plasma clearance (CL/F) was 126.59 ml/hr. The corresponding values for apparent volume of distribution (V/F), t1/2 beta, maximum blood concentration (C max), and time to reach the maximum blood concentration (T max) were 334.12 Lit, 1.98 hr, 40.25 ng/ml, and 1.68 hr, respectively. The observed mean values of V/F of propranolol in the present study were comparable with those reported in the literature. However, the mean values of CL/F of propranolol in current study was significantly higher than those reported in other population (P-value<0.001). Conclusion: This study has confirmed that the pharmacokinetic differences are not able to justify over-responsiveness of Iranian population to propranolol. Pharmacodynamic differences in responding to beta blocker drugs by Renin secretion or having a different sensibility to beta receptors might play a role in making our population have a different response to propranolol

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

The global retinoblastoma outcome study : a prospective, cluster-based analysis of 4064 patients from 149 countries

DATA SHARING : The study data will become available online once all analyses are complete.BACKGROUND : Retinoblastoma is the most common intraocular cancer worldwide. There is some evidence to suggest that major differences exist in treatment outcomes for children with retinoblastoma from different regions, but these differences have not been assessed on a global scale. We aimed to report 3-year outcomes for children with retinoblastoma globally and to investigate factors associated with survival. METHODS : We did a prospective cluster-based analysis of treatment-naive patients with retinoblastoma who were diagnosed between Jan 1, 2017, and Dec 31, 2017, then treated and followed up for 3 years. Patients were recruited from 260 specialised treatment centres worldwide. Data were obtained from participating centres on primary and additional treatments, duration of follow-up, metastasis, eye globe salvage, and survival outcome. We analysed time to death and time to enucleation with Cox regression models. FINDINGS : The cohort included 4064 children from 149 countries. The median age at diagnosis was 23·2 months (IQR 11·0–36·5). Extraocular tumour spread (cT4 of the cTNMH classification) at diagnosis was reported in five (0·8%) of 636 children from high-income countries, 55 (5·4%) of 1027 children from upper-middle-income countries, 342 (19·7%) of 1738 children from lower-middle-income countries, and 196 (42·9%) of 457 children from low-income countries. Enucleation surgery was available for all children and intravenous chemotherapy was available for 4014 (98·8%) of 4064 children. The 3-year survival rate was 99·5% (95% CI 98·8–100·0) for children from high-income countries, 91·2% (89·5–93·0) for children from upper-middle-income countries, 80·3% (78·3–82·3) for children from lower-middle-income countries, and 57·3% (52·1-63·0) for children from low-income countries. On analysis, independent factors for worse survival were residence in low-income countries compared to high-income countries (hazard ratio 16·67; 95% CI 4·76–50·00), cT4 advanced tumour compared to cT1 (8·98; 4·44–18·18), and older age at diagnosis in children up to 3 years (1·38 per year; 1·23–1·56). For children aged 3–7 years, the mortality risk decreased slightly (p=0·0104 for the change in slope). INTERPRETATION : This study, estimated to include approximately half of all new retinoblastoma cases worldwide in 2017, shows profound inequity in survival of children depending on the national income level of their country of residence. In high-income countries, death from retinoblastoma is rare, whereas in low-income countries estimated 3-year survival is just over 50%. Although essential treatments are available in nearly all countries, early diagnosis and treatment in low-income countries are key to improving survival outcomes.The Queen Elizabeth Diamond Jubilee Trust and the Wellcome Trust.https://www.thelancet.com/journals/langlo/homeam2023Paediatrics and Child Healt

Nose-to Brain Direct Delivery of Nanodrug Formulations in Treatment of Neurological Disorders: A Review Study

Global prevalence of neurological disorders such as Parkinson's disease, Alzheimer's disease, epilepsy, and multiple sclerosis is steadily increasing, but, there is still no effective delivery system to deliver therapeutic amounts of drug into the central nervous system (CNS). The blood-brain barrier ​​is the major component to control the entrance of drugs into the brain. Recent studies introduced intranasal drug delivery as a suitable method of drug delivery for bypassing blood-brain barrier and treatment of neurological diseases. The nasal route has been repeatedly examined in several preclinical models to investigate the delivery of drug to the brain via nanoparticles. Among various carriers utilized for drug delivery via nasal route, chitosan is widely used due to being effective in modulating drug charge. Key features of drug delivery systems through nasal route include easy drug delivery, higher stability in nasal cavity, increased penetration ability of drugs through nasal epithelium, and decreased drug metabolism. The present review investigated novel nano-formulations for drug delivery via nose to brain in treatment of major neurological disorders. In preclinical studies, intransaal nanoparticle-based drug delivery systems are found to be more promising, effective, and targeted. However, more preclinical studies are needed to confirm their non-toxicity and beneficial effects

Frequencies of two CYP2C19 defective alleles (CYP2C19*2, and *3) among Iranian population in Mazandaran Province

Background: Cytochrome P450 2C19 (CYP2C19) is a polymorphically expressed enzyme that shows marked interindividual and interethnic variation. CYP2C19*2 and CYP2C19*3 are the most frequently identified defective alleles in Orientals and Caucasian poor metabolizers (PM). The aim of this study was to investigate the frequencies of CYP2C19*1, CYP2C19*2 and CYP2C19*3 alleles and CYP2C19 genotypes in the Mazandarani ethnic group among Iranian Population.  Materials and Methods: The study was conducted in 103 unrelated healthy volunteers. DNA was extracted from leucocytes and analyzed by the PCR-RFLP protocol. The PCR product was digested with restriction enzymes (SmaI and BamH1) and then separated electrophoretically using polyacrylamide gel.. Results: Of the alleles tested, CYP2C19*1, and CYP2C19*2, but not CYP2C19*3, were detected. The frequencies for CYP2C19 alleles *1, *2, and *3 were 91%, 9.0%, and 0.0%, respectively. The frequencies of CYP2C19 genotypes *1/*1, *1/*2, *1/*3, *2/*2, *2/*3 and *3/*3 were 84%, 14%, 0.0%, 2.0%, and 0.0%, respectively. Conclusion: The result of the present study showed that the two inactive alleles of CYP2C19 accounted for 9.0% of CYP2C19 alleles in our sample versus 8.8 - 40.1% reported in other populations. The frequencies of the studied alleles resulted significant differences between our sample and African and Eastern Asian populations

Effect of Standoff Distance and Explosive Material Thickness on Properties of Explosively Welded Copper and 304 Stainless Steel

In this research, the effect of standoff distance and explosive material thickness on metallurgical features of explosive welding connection of copper to 304 stainless steel has been investigated. Experimental analysis were performed using optical microscopy, scanning electron microscopy, microhardness test and tensile shear strength test. The results indicated that due to severe plastic deformation in welding, both grain elongation and refinement occurred near the connection. Also, increasing of welding parameters led to an increase in the locally melted zones. The results showed that chemical composition of the melted zone consisted of elements of both flyer and base plates. By decreasing the explosive material thickness and standoff distance, the hardness of copper interface zone decreased from 103.4 HV to 99.8 HV. Moreover, increasing the temperature in stainless steel connection led to decreased hardness. As such, the maximum tensile shear strength of 244 MPa was observed&nbsp;&nbsp;in the sample with 79 mm explosive thickness and 3 mm standoff and the minimum tensile shear strength of about 208 MPa in the sample with 46 mm explosive thickness and 3 mm standoff. By decreasing explosive thickness and standoff, the bond strength decreased, too. &nbsp

The Role of Radiofrequency Hyperthermia in The Radiosensitization of A Human Prostate Cancer Cell Line

Objective This study evaluated enhanced induced DNA damages and apoptosis of a spheroid culture of DU145 prostate cancer cells treated by a combination of radiofrequency hyperthermia (RF HT) with radiation treatment (RT) from an external radiotherapy machine compared to RT alone. Materials and Methods In this experimental study, DU145 cells were cultured as spheroids until they reached 300 µm in diameter. We exposed these cultures to either: RF HT for 90 minutes at 43˚C originated from a Celsius TCS system, RF HT followed by RT at doses of 2 Gy or 4 Gy (15 MV energy) with 15-minute interval, or RT alone at the above mentioned doses. The trypan blue exclusion assay, alkaline comet assay, and annexin V/PI flow cytometry were performed to measure cell viability, the amount of DNA damage in an individual cell as the tail moment, and percentage of induced cell apoptosis in response to treatments explained. Results We calculated the thermal enhancement factor (TEF) for the combined treatment regime. RF HT followed by the 4 Gy dose of RT resulted in minimum viability (85.33 ± 1.30%), the highest tail moment (1.98 ± 0.18), and highest percentage of apoptotic cells (64.48 ± 3.40%) compared to the other treatments. The results of the TEF assay were 2.54 from the comet assay and 2.33 according to flow cytometry. Conclusion The present data suggest that combined treatment of mega voltage X-rays and RF HT can result in significant radiosensitization of prostate cancer cells