Account of additional factors for damping torsional oscillations.

Some parameters are influenced by the turbine unit's torsional oscillations. The fundamental comes from damping these oscillations, which are brought on by a departure in the turbine blades' speed from the device's prediction of the steam volume, and attenuation of fluctuations due to the distribution of energy in the turbine's productive components. The usual single-machine infinite bus system is used for the analysis. For various turbine-generator shafts and various generator operating situations, rotating mass mechanical system evaluations for small-signal stability and large disturbance are conducted. It is demonstrated that the shaft's "structural' damping (H) and "steam' damping (Kn) coefficients have a considerable impact on the damping of torsional modes. The goal of this work is to determine the effect of changing the damping factors in the mathematical model of the steam turbine shaft on the system's static stability, as well as the extent to which these variables' limits on damping rotational oscillations on the maximum torsional torques generated in the shaft masses. The mathematical model of the steam turbine shaft with a single machine and transmission line to an infinite bus system was simulated using Dymola software, and the static and dynamic effects of damping factors (H) and (Kn) on system stability were demonstrated. By evaluating the best case for parameters with the least influence on the system's stability, the results were obtained by changing the factors (Kn) from 0.005 to 0.5 and (H) from 0.005 to 0.2 and the extent of its effect on the maximum torque of the steam turbine masses and reducing it by 8.4 %, as well as by reducing the settling time of the system after disturbances occur and reaching to Steady state by about 90 %.

Development of new thiazolidine-2,4-dione hybrids as aldose reductase inhibitors endowed with antihyperglycaemic activity: design, synthesis, biological investigations, and in silico insights.

This research study describes the development of new small molecules based on 2,4-thiazolidinedione (2,4-TZD) and their aldose reductase (AR) inhibitory activities. The synthesis of 17 new derivatives of 2,4-TZDs hybrids was feasible by incorporating two known bioactive scaffolds, benzothiazole heterocycle, and nitro phenacyl moiety. The most active hybrid (8b) was found to inhibit AR in a non-competitive manner (0.16 µM), as confirmed by kinetic studies and molecular docking simulations. Furthermore, the in vivo experiments demonstrated that compound 8b had a significant hypoglycaemic effect in mice with hyperglycaemia induced by streptozotocin. Fifty milligrams per kilogram dose of 8b produced a marked decrease in blood glucose concentration, and a lower dose of 5 mg/kg demonstrated a noticeable antihyperglycaemic effect. These outcomes suggested that compound 8b may be used as a promising therapeutic agent for the treatment of diabetic complications.

New benzothiazole hybrids as potential VEGFR-2 inhibitors: design, synthesis, anticancer evaluation, and in silico study.

A new series of 2-aminobenzothiazole hybrids linked to thiazolidine-2,4-dione 4a-e, 1,3,4-thiadiazole aryl urea 6a-d, and cyanothiouracil moieties 8a-d was synthesised. The in vitro antitumor effect of the new hybrids was assessed against three cancer cell lines, namely, HCT-116, HEPG-2, and MCF-7 using Sorafenib (SOR) as a standard drug. Among the tested compounds, 4a was the most potent showing IC50 of 5.61, 7.92, and 3.84 µM, respectively. Furthermore, compounds 4e and 8a proved to have strong impact on breast cancer cell line with IC50 of 6.11 and 10.86 µM, respectively. The three compounds showed a good safety profile towards normal WI-38 cells. Flow cytometric analysis of the three compounds in MCF-7 cells revealed that compounds 4a and 4c inhibited cell population in the S phase, whereas 8a inhibited the population in the G1/S phase. The most promising compounds were subjected to a VEGFR-2 inhibitory assay where 4a emerged as the best active inhibitor of VEGFR-2 with IC50 91 nM, compared to 53 nM for SOR. In silico analysis showed that the three new hybrids succeeded to link to the active site like the co-crystallized inhibitor SOR.

Design, synthesis, antitumor, and VEGFR-2 inhibition activities of novel 4-anilino-2-vinyl-quinazolines: Molecular modeling studies.

The antitumor activity of newly synthesized 4-anilino-2-vinylquinazolines 8a-r was measured comparable to sorafenib as a standard drug. The 2-vinylquinazolines 8a-r were evaluated for their in vitro antitumor activity. The most active antitumor agents were subjected to in vitro VEGFR-2 inhibition and apoptotic inducing assay. Compounds 8 h, 8 l, and 8r showed potential antitumor activities with IC50 values of 4.92-14.37 µM relative to the reference drug, sorafenib (IC50 values of 5.47-9.18 µM). Compound 8 h possessed potential VEGFR-2 inhibitory activity (IC50 = 60.27 nM) compared to standard drug sorafenib (IC50 = 55.43 nM), whereas compound 8 l showed moderate inhibitory activity (IC50 = 93.50 nM). The most active compound, 8 h, exhibited total apoptosis with 36.24% on MCF-7 cells, more than the apoptotic effect provoked by sorafenib (32.46%) and the cell cycle arrested at a G1/S phase. Compound 8 h, a potent VEGFR-2 inhibitor, was docked into the VEGFR-2 binding pocket, where this compound showed binding interaction similar to co-crystallized inhibitor sorafenib.

A calcineurin-Hoxb13 axis regulates growth mode of mammalian cardiomyocytes.

A major factor in the progression to heart failure in humans is the inability of the adult heart to repair itself after injury. We recently demonstrated that the early postnatal mammalian heart is capable of regeneration following injury through proliferation of preexisting cardiomyocytes1,2 and that Meis1, a three amino acid loop extension (TALE) family homeodomain transcription factor, translocates to cardiomyocyte nuclei shortly after birth and mediates postnatal cell cycle arrest3. Here we report that Hoxb13 acts as a cofactor of Meis1 in postnatal cardiomyocytes. Cardiomyocyte-specific deletion of Hoxb13 can extend the postnatal window of cardiomyocyte proliferation and reactivate the cardiomyocyte cell cycle in the adult heart. Moreover, adult Meis1-Hoxb13 double-knockout hearts display widespread cardiomyocyte mitosis, sarcomere disassembly and improved left ventricular systolic function following myocardial infarction, as demonstrated by echocardiography and magnetic resonance imaging. Chromatin immunoprecipitation with sequencing demonstrates that Meis1 and Hoxb13 act cooperatively to regulate cardiomyocyte maturation and cell cycle. Finally, we show that the calcium-activated protein phosphatase calcineurin dephosphorylates Hoxb13 at serine-204, resulting in its nuclear localization and cell cycle arrest. These results demonstrate that Meis1 and Hoxb13 act cooperatively to regulate cardiomyocyte maturation and proliferation and provide mechanistic insights into the link between hyperplastic and hypertrophic growth of cardiomyocytes.

Quinazoline Based HSP90 Inhibitors: Synthesis, Modeling Study and ADME Calculations Towards Breast Cancer Targeting.

A new 2-thioquinazolinones series was designed and synthesized as HSP90 inhibitors based on the structure of hit compound VII obtained by virtual screening approach. Their in vitro anti-proliferative activity was evaluated against three human cancer cell lines rich in HSP90 namely; colorectal carcinoma (HCT-116), and cervical carcinoma (Hela), breast carcinoma (MCF-7). Compounds 5a, 5d, 5e and 9h showed a significant broad spectrum anti-proliferative activity against all tested cell lines. They were characterized by potent effect against breast cancer in particular with IC50 of 11.73, 8.56, 7.35 and 9.48 µM, respectively against Doxorubicin (IC50 4.17 µM). HSP90 ATPase activity inhibition assay were conducted where compound 5d exhibited the best IC50 with 1.58 µM compared to Tanespimycin (IC50 = 2.17 µM). Compounds 5a and 9h showed higher IC50 values of 3.21 and 3.41 µM, respectively. The effects of 5a, 5d and 9h on Her2 (a client proteins of HSP90) and HSP70 were evaluated in MCF-7 cells. All tested compounds were found to reduce Her2 protein expression levels and induce Hsp70 protein expression levels significantly, emphasizing that antibreast cancer effect is a consequence of HSP90 chaperone inhibition. Cell cycle analysis of MCF-7 cells treated with 5d showed cell cycle arrest at G2/M phase 38.89% and pro-apoptotic activity as indicated by annexin V-FITC staining by 22.42%. Molecular docking studies suggested mode of interaction to HSP90 via hydrogen bonding. ADME properties prediction of the active compounds suggested that they could be used as orally absorbed anticancer drug candidates.

Synthetic approaches, anticancer potential, HSP90 inhibition, multitarget evaluation, molecular modeling and apoptosis mechanistic study of thioquinazolinone skeleton: Promising antibreast cancer agent.

New series of compounds bearing 2-thioquinazolinone scaffold were designed, synthesized as HSP90 inhibitors. Anti-proliferative activity of the synthesized compounds was evaluated against HCT-116, Hela and MCF-7 cell lines and compound 5k was found to be the most active member of the entire study with IC50 of 4.47, 7.55 and 4.04 µM, respectively, compared to DOX (IC50 of 5.23, 5.57 and 4.17 µM, respectively). Most of the tested compounds revealed lower cytotoxicity against normal fibroblast cells WI-38. Compounds 5b, 5k and 8a showed potent HSP90 inhibitory activities with IC50 values in nanomolar range; 71.32, 25.07 and 56.78 nm, respectively, against Tanespimycin (IC50 of 86.45 nm). Their HSP90 inhibitory activities were confirmed by their down regulation of HSP90 client protein Her2 and up regulation of chaperone HSP70 levels. Compound 5k had shown potent multi-target inhibitory activities against EGFR, VEGFR-2 and Topoisomerase-2 with IC50 values in nanomolar range; 38.5, 126.95 and 25.85 nm, respectively. Compound 5k was further evaluated for cell cycle distribution and apoptosis induction on MCF-7 cells using flow cytometry. Compound 5k arrested the cell cycle on MCF-7 at a G2/M phase by 35.06% and induced apoptosis by 19.82%. Mechanistic evaluation of apoptosis induction was studied by following ways triggering mitochondrial apoptotic pathway through inducing ROS accumulation, increasing Bax/Bcl-2 ratio and activation of caspases 6, 7 and 9. Comparative molecular modeling study was performed between active and inactive HSP90 inhibitors. Docking studies into the active site of HSP90 N-terminal domain showed good agreement with the obtained biological results. ADMET analysis and parameters of Lipinski's rule of five were calculated where compound 5k had reasonable drug-likeness with acceptable physicochemical properties so it could be used as promising orally absorbed antibreast targeted therapy.

[Multidisciplinary approach to oral rehabilitation in wounded fighters].

Maxillofacial injuries during military service and in operations in particular, often involve soft and hard tissues, including fractures of bone and teeth. This kind of injury demands a multidisciplinary approach including specialists in oral and maxillofacial surgery periodontists, endodontics, orthodontics and prosthodontics. A comprehensive therapy is achieved by a complete cooperation between the disciplines for a long-term. We present a case report of a complex oral rehabilitation of a fighter wounded in "Zuk Eitan" operation, as an example of the multidisciplinary approach in our department.

Histological and immunohistochemical effects of Curcuma longa on activation of rat hepatic stellate cells after cadmium induced hepatotoxicity.

The liver is a target for toxic chemicals such as cadmium (Cd). When the liver is damaged, hepatic stellate cells (HSC) are activated and transformed into myofibroblast-like cells, which are responsible for liver fibrosis. Curcuma longa has been reported to exert a hepato-protective effect under various pathological conditions. We investigated the effects of C. longa administration on HSC activation in response to Cd induced hepatotoxicity. Forty adult male albino rats were divided into: group 1 (control), group 2 (Cd treated), group 3 (C. longa treated) and group 4 (Cd and C. longa treated). After 6 weeks, liver specimens were prepared for light and electron microscopy examination of histological changes and immunohistochemical localization of alpha smooth muscle actin (αSMA) as a specific marker for activated HSC. Activated HSC with a positive αSMA immune reaction were not detected in groups 1 and 3. Large numbers of activated HSC with αSMA immune reactions were observed in group 2 in addition to Cd induced hepatotoxic changes including excess collagen deposition in thickened portal triads, interlobular septa with hepatic lobulation, inflammatory cell infiltration, a significant increase in Kupffer cells and degenerated hepatocytes. In group 4, we observed a significant decrease in HSC that expressed αSMA with amelioration of the hepatotoxic changes. C. longa administration decreased HSC activation and ameliorated hepatotoxic changes caused by Cd in adult rats.

Efficacy and safety of alternating norfloxacin and rifaximin as primary prophylaxis for spontaneous bacterial peritonitis in cirrhotic ascites: a prospective randomized open-label comparative multicenter study.

BACKGROUND AND AIM: Primary prevention of spontaneous bacterial peritonitis (SBP) is an important strategy to reduce morbidity and mortality in cirrhotic patients with ascites. Efficacy and safety of alternating rifaximin and norfloxacin as primary prophylaxis is questionable. METHODS: Three hundred thirty-four cirrhotic patients with high SAAG (≥1.1) ascites, protein level in ascitic fluid less than 1.5 g/dL with advanced liver disease (Child-Pugh score >9 points with serum bilirubin level >3 mg/dL) or renal impairment (serum creatinine level >1.2 mg/dL, blood urea nitrogen level >25 mg/dL, or serum sodium level <130 mEq/L) were included in an open-label, randomized study aimed at comparing alternating use of norfloxacin and rifaximin vs. norfloxacin or rifaximin alone as primary prophylaxis for SBP. Both intention-to-treat and per-protocol efficacy analyses were done after 6 months of treatment by assessment of ascitic fluid neutrophil count. Safety analysis was done for all intention-to-treat populations. RESULTS: Alternating norfloxacin and rifaximin showed superior prophylaxis by intention-to-treat (74.7 vs. 56.4% vs. 68.3%, p < 0.048). Pairwise analysis showed that alternating regimen had lower probability to develop SBP when compared to a norfloxacin-based regimen in intention-to-treat (p = 0.016) and per protocol analysis (p = 0.039). There was no difference among the studied groups regarding the incidence and severity of adverse events reported. CONCLUSIONS: Alternating norfloxacin- and rifaximin-based primary prophylaxis for SBP showed higher efficacy with the same safety profile when compared with monotherapy of norfloxacin.

HIV/AIDS knowledge, attitudes and beliefs among a group of Iraqis.

This study aimed to build a baseline profile of knowledge, attitudes and beliefs of Iraqis toward HIV/AIDS. Questionnaire interviews were conducted in 2006 with 335 people attending HIV testing centres in Baghdad. Most respondents (82.7%) had heard about AIDS, mainly from the mass media (71.0%), and 91.9% knew that AIDS is an infectious disease, most commonly via sexual relationships (74.9%). There was no association between knowledge level and acceptance of caring for an HIV-positive relative or marrying an HIV-positive partner, but there was a significant association between low knowledge level and negative attitudes towards sharing food, sitting on the bus and working at the same place with an HIV-positive individual.

HIV/AIDS knowledge, attitudes and beliefs among a group of Iraqis

This study aimed to build a baseline profile of knowledge, attitudes and beliefs of Iraqis toward HIV/AIDS. Questionnaire interviews were conducted in 2006 with 335 people attending HIV testing centres in Baghdad. Most respondents [82.7%] had heard about AIDS, mainly from the mass media [71.0%], and 91.9% knew that AIDS is an infectious disease, most commonly via sexual relationships [74.9%]. There was no association between knowledge level and acceptance of caring for an HIV-positive relative or marrying an HIV-positive partner, but there was a significant association between low knowledge level and negative attitudes towards sharing food, sitting on the bus and working at the same place with an HIV-positive individual

Osteonecrosis of the jaw induced by orally administered bisphosphonates: incidence, clinical features, predisposing factors and treatment outcome.

UNLABELLED: Osteonecrosis of the jaw (ONJ) is a well-known devastating side effect of bisphosphonate therapy for cancer. Several ONJ cases of patients using oral bisphosphonates have been reported in the literature. The present study analyzed the clinical features, predisposing factors, and treatment outcome of 11 patients with oral bisphosphonates-related ONJ. INTRODUCTION AND HYPOTHESIS: Osteonecrosis of the jaw (ONJ) is a well-known side effect of parenteral bisphosphonates therapy. Although ONJ has been reported in patients using oral bisphosphonates, documentation of this entity is sparse. It was hypothesized that the clinical features, predisposing factors, and treatment outcome of this population are different from those of oncologic patients. METHODS: This retrospective bi-central study involved 98 ONJ patients, 13 of whom were treated with oral bisphosphonates. Two patients were excluded because of previous use of intravenous bisphosphonates. The profiles of 11 patients were analyzed. RESULTS: The mean duration of alendronate use before developing ONJ was 4.1 years. ONJ was triggered by dental surgery in 9 patients and by ill-fitted dentures in 2. Heavy smokers were the most recalcitrant subjects. Among the nine patients with at least 6 months of follow-up, ONJ healed completely in three, partially in four, and not at all in two. CONCLUSIONS: ONJ is a rare devastating side effect of oral bisphosphonates associated with patient morbidity and high financial burden. Clinicians must be aware of this entity and inform patients of the risks of dental surgery. The synergistic effect of smoking in the pathogenesis of ONJ should be further investigated.

Osteomylelitis and necrosis of the jaw in patients treated with bisphosphonates: a comparative study focused on multiple myeloma.

It was reported that multiple myeloma (MM)-patients suffer from a higher incidence of osteomyelitis and necrosis of the jaws than patients treated with bisphosphonates for other reasons. The aim of this study is to report about 57 cases of bisphosphonate-related osteomyelitis and necrosis of the jaws (BON) and to investigate the differences between BON in MM and non-MM patients. Clinical and laboratory data of 57 cases were assessed. The features of BON and clinical-outcome were compared between the two groups. Treatment approach was assessed as a contributing-factor to treatment-outcome. Clinical presentation included exposed bone, pain, swelling and suppuration with little variation between the two groups. Past dento-alveolar surgery was common in both study-groups. Treatment outcome was poor (33% and 25% responded to treatment in MM group and non-MM group, respectively). Treatment modality did not affect the treatment outcome. The clinical presentation described in this case series should alert the physician to the possibility of BON. Although the literature shows a higher incidence of BON in MM patients compared to non-MM patients, our study suggests that the severity of the clinical presentation and the response to treatment are not worse in MM patients compared with non-MM patients. The predisposition of MM patients to BON should be further investigated.

Day care versus in-patient surgery for age-related cataract.

BACKGROUND: Age-related cataract accounts for more than 40% of cases of blindness in the world with the majority of people who are blind from cataract found in the developing world. With the increased number of people with cataract there is an urgent need for cataract surgery to be made available as a day-care procedure. OBJECTIVES: The objective of this review is to provide reliable evidence regarding the safety, feasibility, effectiveness and cost-effectiveness of cataract extraction performed as day-care versus in-patient procedure. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Group trials register) on The Cochrane Library (Issue 4 2002), MEDLINE (1966 to November 2002), EMBASE (1980 to November 2002) and LILACS (November 2002). SELECTION CRITERIA: This review includes randomised controlled trials comparing day-care and in-patient surgery for age-related cataract. The primary outcome was the achievement of a satisfactory visual acuity six weeks after the operation. DATA COLLECTION AND ANALYSIS: Although two trials are included in the review, adequate data were available for only one trial and therefore pooling of data from studies was not attempted. A descriptive summary is presented. MAIN RESULTS: Two trials, involving a total of 1284 people, are included in this review. One trial reported statistically significant differences in early postoperative complication rates in the day-care group, with an increased risk of increased intraocular pressure, which had no clinical relevance to visual outcomes four months postoperatively. The mean change in visual acuity (Snellen lines) of the operated eye four months postoperatively was 4.1 (standard deviation (SD) 2.3) for the day-care group and 4.1 (SD 2.2) for the in-patient group and not statistically significant. The four-month postoperative mean change in quality of life score measured using the VF14 showed minimal differences between the two groups. Costs were 20% more for the in-patient group and this was attributed to higher costs for overnight stay. One study only reported hotel costs for the non-hospitalised participants making aggregation of data on costs impossible. REVIEWER'S CONCLUSIONS: This review provides some evidence that there is a cost saving but no significant difference in outcome or risk of postoperative complications between day-care and in-patient cataract surgery. This is based on one detailed and methodologically sound trial conducted in the developed world. The success, safety and cost-effectiveness of cataract surgery as a day-care procedure appears to be acceptable but additional well-designed trials are required to confirm these perceptions.