HER2/neu expression status of post BCG recurrent non-muscle-invasive bladder urothelial carcinomas in relation to their primary ones

Background: Transurethral resection (TUR) followed by adjuvant therapy is still the treatment of choice of Non-Muscle-Invasive Bladder Urothelial Carcinoma (NMIBUC). However, recurrence is one of the most troublesome features of these lesions. Early second resection and adjuvant BCG therapy has been shown to improve the outcome. Objective: To evaluate the prognostic value of C-erbB-2 (HER2/neu) expression status in Non-Muscle-Invasive Bladder Urothelial Carcinoma cases, before and after intravesical Bacillus Calmette Guerin (BCG immunotherapy). Materials and methods: HER2/neu expression was studied in 120 (Ta-T1) Non-Muscle-Invasive Urothelial Carcinoma cases. The expression was evaluated and compared to the expression after Bacillus Calmette Guerin (BCG) immunotherapy. Results: HER2/neu expression in low and high grade of the Non- Muscle-Invasive Urothelial Carcinoma was (38%) and (83%) respectively. The difference of the expression rates by tumor grade was statistically significant. In recurring lesions post BCG therapy, C-erbB-2 expression was markedly decreased (31.6%) when compared to its expression before therapy (65%). Conclusions: The HER2/neu expression increased as the tumor grade rose. The reduction in expression following BCG treatment in Non-Invasive transitional cell carcinoma cases could reflect a reduction of the potential malignancy of the tumor

STUDI OPTIMALISASI SIMPANG EMPAT BERSINYAL DI SIMPANG EMPAT AIR HITAM KOTA SAMARINDA

       Volume lalu lintas Kota Samarinda mengalami peningkatan setiap tahunnya yang diakibatkan bertambahnya jumlah kepemilikan kendaraan. Kemacetan pada perempatan Simpang Air Hitam Samarinda merupakan salah satu dampak dari pertumbuhan lalu lintas yang cukup tinggi dan belum berfungsinya system lalu lintas secara baik. Dengan memperhatikan kondisi geometri jalan, volume arus lalulintas, hambatan samping dan lingkungan simpang yang merupakan daerah komersil, maka dicoba untuk diatasi dengan menggunakan manajemen simpang bersinyal. Cara penelitian yang dilakukan adalah dengan melakukan survey di lapangan untuk mendapatkan data primer maupun data sekunder yang kemudian akan diolah dengan menggunakan manajemen simpang. Perencanaan menggunakan acuan Manual Kapasitas Jalan Indonesia (MKJI) 1997 dan menggunakan program Excel 2010 untuk mengolah data lalu lintas. Data lalu lintas diperoleh dari pencacahan jumlah kendaraan di lapangan yang dilakukan selama 3 hari (09, 10, 11 Juli 2013) pada jam-jam sibuk dan disajikan dalam bentuk tabel data kendaraan dan kemudian perilaku lalu lintas simpang dapat dianalisis Dari hasil analisis dapat disimpulkan bahwa persimpangan Simpan Empat Air Hitam Samarinda memiliki nilai Derajat Kejenuhan (DS) = 0.89. Nilai ini telah melewati nilai derajat kejenuhan yang disarankan oleh MKJI 1997 untuk simpang bersinyal yaitu DS ≤ 0,85. Rekayasa geometri yang telah dilakukan sebagai alternatif dapat mengurang derajat kejenuhan yang diinginkan yaitu sesuai dengan yang disarankan olen MKJI 1997

Morphoneotectonics and prospects of oil and gas presence in deserts of Iraq

The article deals with the prospects of Iraq’s oil and gas potential. It should be noted that there has not been much attention payed to the desert regions of Iraq located on the Arabian plate. However, recent studies show prospectivity of the Iraq deserts. As a result of the recent investigation of river valleys in the region, the following main morphotectonic processes were identified: rejuvenation of the river network and emergence of new river basins; division of individual rivers into two or more parts; interception of the river network. As a result of long-term field and cameral geological and geomorphological studies in the area of the Western and Southern deserts, it was possible to reconstruct the existing tectonic activity of the area from the Miocene period to the present day. It is established that the regional Euphrates fault on the territory of Iraq occupies an exceptionally important place, which was previously underestimated. Adjacent echelon faults of the following order formed a system of pre-existent tectonic blocks with different kinematics and morphology. The causes and mechanism of neotectonic Neogene-Quaternary movements of the earth’s surface are established. Thus, separate tectonic blocks are identified, which generally form zonal regions of uplifts or valleys. The areas of elevated blocks (for example, the raising of Al-Najaf Al-Ashraf of the third order) are created by plicative dome structures in the cover near the Euphrates fault, favorable for the accumulation of HC

Mechanism of drug resistance in HIV-1 protease subtype C in the presence of Atazanavir

AIDS is one of the deadliest diseases in the history of humankind caused by HIV. Despite the technological development, curtailing the viral infection inside human host still remains a challenge. Therapies such as HAART uses a combination of drugs to inhibit the viral activity. One of the important targets includes HIV protease and inhibiting its activity will minimize the production of mature structural proteins. However, the genetic diversity and the occurrence of drug resistant mutations adds complexity to effective drug design. In this study, we aimed at understanding the drug binding mechanism of one such subtype, namely subtype C and its insertion variant L38HL. We performed multiple molecular dynamics simulations along with binding free energy analysis of wild-type and L38HL bound to Atazanavir (ATV). From the analysis, we revealed that the insertion alters the hydrogen bond and hydrophobic interaction networks. The alterations in the interaction networks increase flexibility at the hinge-fulcrum interface. Further, the effects of these changes affect flap tip curling. Moreover, the changes in the hinge-fulcrum-cantilever interface alters the concerted motion of the functional regions leading to change in the direction of flap movement thus causing a subtle change in the active site volume. Additionally, formation of intramolecular hydrogen bonds in the ATV docked to L38HL restricted the movement of R1 and R2 groups thereby altering the interactions. Overall, the changes in the flexibility of flap together with the changes in the active site volume and compactness of the ligand provide insights for increased binding affinity of ATV with L38HL

Understanding Drug Resistance of Wild-Type and L38HL Insertion Mutant of HIV-1 C Protease to Saquinavir

Acquired immunodeficiency syndrome (AIDS) is one of the most challenging infectious diseases to treat on a global scale. Understanding the mechanisms underlying the development of drug resistance is necessary for novel therapeutics. HIV subtype C is known to harbor mutations at critical positions of HIV aspartic protease compared to HIV subtype B, which affects the binding affinity. Recently, a novel double-insertion mutation at codon 38 (L38HL) was characterized in HIV subtype C protease, whose effects on the interaction with protease inhibitors are hitherto unknown. In this study, the potential of L38HL double-insertion in HIV subtype C protease to induce a drug resistance phenotype towards the protease inhibitor, Saquinavir (SQV), was probed using various computational techniques, such as molecular dynamics simulations, binding free energy calculations, local conformational changes and principal component analysis. The results indicate that the L38HL mutation exhibits an increase in flexibility at the hinge and flap regions with a decrease in the binding affinity of SQV in comparison with wild-type HIV protease C. Further, we observed a wide opening at the binding site in the L38HL variant due to an alteration in flap dynamics, leading to a decrease in interactions with the binding site of the mutant protease. It is supported by an altered direction of motion of flap residues in the L38HL variant compared with the wild-type. These results provide deep insights into understanding the potential drug resistance phenotype in infected individuals

Clinico-Pathological Features and Immunohistochemical Comparison of p16, p53, and Ki-67 Expression in Muscle-Invasive and Non-Muscle-Invasive Conventional Urothelial Bladder Carcinoma

Introduction: The identification of bladder detrusor muscle invasion in urothelial cancer is essential for prognosis and management. We studied the clinical, histological, and immunohistochemical expression of p16, p53, and Ki-67 in urothelial detrusor muscle-invasive bladder cancer (MIBC) and urothelial non-detrusor muscle-invasive bladder cancer (NMIBC) in Egyptian patients. Methods: Sixty-two bladder urothelial cancer cases obtained through TURBT were included and divided into two groups: (MIBC, stage T2) and NMIBC (T1). Tissue blocks were recut and re-examined microscopically; then, the immunostaining of p16, p53, and Ki-67 was performed to compare both groups and evaluate the 13% cut-off for Ki-67, 20% for p53, and p16 intensity in various conditions aided by telepathology technology. Results and conclusion: Hematuria was the main clinical first presentation, with no significant difference between either group. The mean age was 61.6 years, with male predominance (52 males and 10 females). The absence of papillary histological pattern was associated with a higher stage, including detrusor muscle invasion (p = 0.000). The overall average percent of p53 immunostaining was 12.9%, revealing no significant difference between MIBC and NMIBC when a cut-off of 20% was implicated. The Ki-67 expression was correlated with higher grade and muscle invasion; however, no association was found with the other two markers’ expression. The negative immunostaining of p16 was associated with low grade and NMIBC in the case of the preservation of the papillary pattern. We recommend further studies on the cut-off of widely used markers and more immunohistochemical and genetic studies on the p16(INK4A), taking into consideration the histological pattern of conventional carcinomas