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Targeted therapy has emerged to be the cornerstone of advanced cancer treatment, allowing for more selectivity and avoiding the common drug toxicity and resistance. Identification of potential targets having vital role in growth and survival of cancer cells got much easier with the aid of the recent advances in high throughput screening approaches. Various protein kinases came into focus as valuable targets in cancer therapy. Meanwhile, benzimidazole-based scaffolds have gained significant attention as promising protein kinase inhibitors with high potency and varied selectivity. Great diversity of these scaffolds has inspired the medicinal chemists to inspect the effect of structural changes upon inhibitory activity on the molecular level through modeling studies. The present review gathers all the considerable attempts to develop benzimidazole-based compounds; designed as protein kinase inhibitors with anticancer activity since 2015; that target aurora kinase, CDK, CK2, EGFR, FGFR, and VEGFR-2; to allow further development and progression regarding benzimidazoles.

Dry powder inhalers (DPIs) are considered a main drug delivery system through pulmonary route. The main objective of this work is to study the flow of differently shaped microparticles in order to find the optimum shape of drug particles that will demonstrate the best flow to the deep lung. The flowability of particles in air or any fluid depends particularly on the drag force which is defined as the resistance of the fluid molecules to the particle flow. One of the most important parameters that affect the drag force is the particles' shape. Computational simulations using COMSOL Multi Physics 5.2 software were performed for investigating the particles flow in the air pathways of lung, and the drag force was calculated for different particles shapes. This was accomplished by screening a set of 17 possible shapes that are expected to be synthesized easily in the micro-scale. In addition, the macro-scale behavior of the investigated shapes was also simulated so as to compare the behavior of the flowing particles in both cases. A very big difference was found between the behavior of particles' flow in the micro and macro scales, but a similar behavior can be obtained if the flow velocity of the microparticles is very high. It was also found that the micro-triangle with aspect ratio 2:1 has the least drag force in both deep and upper lung; so, it should be the shape of choice during the process of particle synthesis for pulmonary drug delivery.

The endocannabinoid system plays a pivotal role, whether it is promoting or dampening hepatic fibrosis. This study investigated the role of Cannabinoid receptor 2 (CB

Carbetapentane citrate, a non-opioid centrally-acting antitussive drug, is a common treatment for cough associated with other diseases such as common cold and respiratory tract infections. Its mode of action is very close to that of atropine; since it acts at the level of the peripheral parasympathetic nerve endings. The drug reaches its maximum plasma concentration (C

This study is aimed at assessing the antihyperglycemic, antihyperlipidemic, and antioxidant effects of Citrus reticulata (C. reticulata) fruit peel hydroethanolic extract and two flavonoids, hesperidin and quercetin, in nicotinamide (NA)/streptozotocin- (STZ-) induced type 2 diabetic rats. In addition, GC-MS and HPLC-MS analyses of the extract were performed and the results indicated the presence of multiple flavonoids including hesperidin, quercetin, naringin, and polymethoxylated flavones (nobiletin and tangeretin). To achieve the aim of the study, diabetic rats with NA/STZ-induced T2DM were orally treated with C. reticulata fruit peel hydroethanolic extract, hesperidin, and quercetin at a dose of 100 mg/kg b.w./day for four weeks. The treatments with C. reticulata fruit peel extract, hesperidin, and quercetin significantly ameliorated the impaired oral glucose tolerance; the elevated serum fructosamine level; the diminished serum insulin and C-peptide levels; the altered HOMA-IR, HOMA-IS, and HOMA-β cell function; the decreased liver glycogen content; the increased liver glucose-6-phosphatase and glycogen phosphorylase activities; the deleteriously affected serum lipid profile; the elevated serum AST and ALT activities; and the raised serum creatinine and urea levels in the diabetic rats. The treatments also produced remarkable improvement in the antioxidant defense system manifested by a decrease in the elevated liver lipid peroxidation and an increase in the lowered glutathione content and GPx, GST, and SOD activities. Furthermore, the three treatments enhanced the mRNA expression of GLUT-4 and the insulin receptor β-subunit, but only quercetin produced a significant increase in the expression of adiponectin in adipose tissue of diabetic rats. In conclusion, C. reticulata fruit peel hydroethanolic extract, hesperidin, and quercetin have potent antidiabetic effects which may be mediated through their insulinotropic effects and insulin-sensitizing actions. In addition, the alleviation of the antioxidant defense system by the extract, hesperidin, and naringin may have an important action to enhance the antidiabetic actions and to improve liver and kidney functions in NA/STZ-induced diabetic rats.

The aim of this work is to build a Computational fluid dynamics (CFD) model to study the flowability of fungal spores and pollen grains to predict their ability to flow to the deep lung in order to relate this to the potentiality of allergies, and predict the possibility of using spores/pollen grains-mimicking microparticles for pulmonary drug delivery. The CFD model was designed using COMSOL Multiphysics to calculate the drag forces exerted on the pollens and spores by the air in the upper and lower lung bronchioles. Experimental verification was conducted by comparing the aerosolization of Aspergillus spores and spherical microparticles, as a control shape, using Next Generation Impactor as a lung-simulation device. The CFD model showed that the drag force exerted on the spores and pollen grains can affect their pathogenicity. In addition, the shapes of some spores (e.g. Alternaria, Drechslera and Aspergillus) or pollens (e.g. Quercus and Eucalyptus) have low drag and can be used for drug delivery to the deep lung. The experimental results coincided with the CFD model and showed that the shape of Aspergillus spores can reach the deep lung with about 1.6-fold higher dose than the spherical shape. The obtained results indicate that shapes of some spores and pollen grains are drag-minimizing allowing them to spread and to be inhaled to the deep lung; so they can be used for the development of dry powder inhaler formulations.

Descriptions of the mosquitoes of the Republic of the Sudan are mostly limited to works published more than 60 years ago. Khartoum State in central Sudan, which encompasses the capital city, has experienced many outbreaks of diseases caused by mosquito-borne pathogens, including Rift Valley fever. In this paper we focus on the composition of Aedes mosquitoes in high-risk areas in and around major agricultural projects. This is based on longitudinal surveillance of adults and larvae during the hot dry and rainy seasons in 2013. A total of 630 adult female mosquitoes were collected. Anopheles mosquitoes were the most abundant (n = 456, 72.4), followed by Culex (n = 96, 15.2) and Aedes (n = 78, 12.4). Only three Aedes species were identified: Aedes caballus (n = 38, 48.7 of the Aedes), Aedes vexans arabiensis (n = 30, 38.5) and Aedes caspius (n = 10, 12.8). A total of 42,549 larvae were collected. Aedes larvae were the most abundant (n = 30,936, 72.7), followed by Culex (n = 9656, 22.7) and Anopheles (n = 1957, 4.6). The Aedes larvae included Ae. caspius (n = 21,957, 71.0 of the Aedes), Ae. vexans arabiensis (n = 5577, 18.0), Aedes quasiunivittatus (n = 107, 0.3), Aedes dentatus (Theobald) (n = 204, 0.7) and 3091 unidentifiable larvae (10.0), denoted as Forms X, Y and Z. We discuss the bionomics of the four identified species of Aedes and provide updated keys for the identification of the mosquito genera and the larvae and adults of the Aedes species recorded from the Republic of the Sudan. © 2017 Informa UK Limited, trading as Taylor Francis Group.

Zinc alloys are used in very wide industrial applications due to their excellent physical and mechanical properties. To improve the corrosion resistance, anodizing process is used. Anodizing of Zinc Alloy ZA12 is investigated in 1 M H2SO4 solution for 10, 20 30,40 and 50 mins at a constant voltage of 5V. Atomic force microscope (AFM) used to study the surface roughness of the anodic film. The results show that the surface roughness of anodic film is primarily depending on the anodizing time and coating average thickness. Furthermore, the microhardness also increases with the anodizing time. The corrosion performances in sea water of both anodized and non-anodized zinc specimens are acquired by potentiostatic polarization. Corrosion current density (iCorr) and corrosion potential (ECorr) are obtained from potentiostatic polarization studies. The studies show that the corrosion current density and corrosion rate were reduced with increasing the anodizing time which enlarges anodic film average thickness. The results of corrosion rates indicate an enhancement in corrosion resistance of anodized Zinc Alloy ZA12 in the sea water. Contact angle test measurements for ZnO layer formation on zinc alloy AZ12 were detected which indicate that the contact angle of un-anodized film seems to be elevated than that of anodized film after sealing the anodic film.

Radioimmunotherapy is increasingly used alone and in combination with standard chemotherapy as a preparative conditioning tool for patients with variety of hematological malignancies before allogeneic and autologous stem cell transplantation. This approach, if optimized, has the potential to close the gap between the benefit and toxicity of conditioning regimens. This article is intended to provide a summary of the basic elements of this approach as well as a concise and up-to-date scoping review of the studies that evaluated the safety and efficacy of integrating radioimmunotherapy in the conditioning regimens.

Allogeneic hematopoietic cell transplantation (HCT) is an increasingly used curative modality for hematological malignancies and other benign conditions. Attempts to reduce the morbidity/mortality and improve survival in patients undergoing HCT are crucial. The ability to diagnose acute graft versus host disease (aGvHD) in a timely manner, or even predict aGvHD prior to clinical manifestations, along with the accurate stratification of these patients are critical steps to improve the treatment and outcomes of these patients. Many novel biomarkers that may help in achieving these goals have been studied recently. This overview is intended to assist clinicians and investigators by providing a comprehensive review and analytical interpretation of the current knowledge concerning GvHD and biomarkers likely to prove useful in diagnosis and risk-stratification of this condition, along with the difficulties that hamper this approach.

Leukostasis is a poorly understood and life-threatening complication of acute hyperleukocytic leukemia. The incidence of hyperleukocytosis and leukostasis differs among various subtypes of leukemias. While the pathophysiology of leukostasis is not fully understood, recent research has elucidated many novel pathways that may have therapeutic implications in the future. Respiratory and neurological compromise represents the classical clinical manifestations of leukostasis. If it is not diagnosed and treated rapidly, the one-week mortality rate is approximately 40%. Targeted induction chemotherapy is an important component of the successful treatment of leukostasis, although other modalities of cytoreduction are being used and investigated. Copyright © 2016 John Wiley & Sons, Ltd.

Background In solid tumours, antibiotic use during immune checkpoint inhibitor (ICI) treatment is associated with shorter survival. Following allogeneic haematopoietic cell transplantation (allo-HCT), antibiotic-induced gut microbiome alterations are associated with risk of relapse and mortality. These findings suggest that the gut microbiota can modulate antitumour immune response across tumour types, though it is not clear if the impact on outcomes is specific to immune therapy. An important limitation of previous studies is that the analysis combined all antibiotic exposures irrespective of the antibiotic spectrum of activity. Whether antibiotic exposure during induction chemotherapy in acute myeloid leukaemia (AML) affects risk of relapse is also unknown.Patients and methods We performed a single-centred retrospective analysis of antibiotic exposures in metastatic/advanced non-small cell lung cancer (NSCLC) and renal cell cancer (RCC) receiving ICI and newly diagnosed AML patients receiving induction chemotherapy achieving a complete remission 1. Antibiotic use within 4 weeks before and 6 weeks after the ICI initiation were included. In AML patients, antibiotic exposures between days 1 and 28 of induction were collected. Antibiotics were a priori stratified based on spectrum of activity. Primary outcomes of interest were progression-free survival (PFS), overall survival (OS) in NSCLC and RCC and relapse-free survival (RFS) in AML.Results 140 patients with NSCLC, 55 with RCC and 143 with AML were included. In multivariable analysis, PFS and OS were shorter in NSCLC patients who received broad-spectrum anti-anaerobes (PFS, HR=3.2, 95% CI 1.6 to 6.2, p

Decitabine has been explored as a reduced‐intensity therapy for older or unfit patients with acute myeloid leukemia (AML). To better understand the risk of infections during decitabine treatment, we retrospectively examined the culture results from each infection‐related serious adverse event that occurred among 85 AML and myelodysplastic syndromes (MDS) patients treated in a prospective clinical study using 10‐day cycles of decitabine at Washington University School of Medicine. Culture results were available for 163 infection‐related complications that occurred in 70 patients: 90 (55.2%) events were culture‐negative, 32 (19.6%) were gram‐positive bacteria, 20 (12.3%) were gram‐negative bacteria, 12 (7.4%) were mixed, 6 (3.7%) were viral, 2 (1.2%) were fungal, and 1 (0.6%) was mycobacterial. Infection‐related mortality occurred in 3/24 (13%) of gram‐negative events, and 0/51 gram‐positive events. On average, nearly one third of patients experienced an infection‐related complication with each cycle, and the incidence did not decrease during later cycles. In summary, in patients receiving 10‐day decitabine, infectious complications are common and may occur during any cycle of therapy. Although febrile events are commonly culture‐negative, gram‐positive infections are the most frequent source of culture‐positive infections, but gram‐negative infections represent a significant risk of mortality in AML and MDS patients treated with decitabine.

Emphysematous cholecystitis is an uncommon and dangerous complication of acute cholecystitis. Common risk factors for this disease include male gender, old age, presence of diabetes mellitus and cholelithiasis. The disease is best treated with emergent surgery and parenteral antibiotics. We present the case of an 85-year-old nursing home resident who presented to our institution with a 3-day history of gradually worsening abdominal discomfort.

Leukostasis is a poorly understood and life-threatening complication of acute hyperleukocytic leukemia. The incidence of hyperleukocytosis and leukostasis differs among various subtypes of leukemias. While the pathophysiology of leukostasis is not fully understood, recent research has elucidated many novel pathways that may have therapeutic implications in the future. Respiratory and neurological compromise represents the classical clinical manifestations of leukostasis. If it is not diagnosed and treated rapidly, the one-week mortality rate is approximately 40%. Targeted induction chemotherapy is an important component of the successful treatment of leukostasis, although other modalities of cytoreduction are being used and investigated. Copyright © 2016 John WileySons, Ltd.

Propofol infusion syndrome is a rare but extremely dangerous complication of propofol administration. Certain risk factors for the development of propofol infusion syndrome are described, such as appropriate propofol doses and durations of administration, carbohydrate depletion, severe illness, and concomitant administration of catecholamines and glucocorticosteroids. The pathophysiology of this condition includes impairment of mitochondrial beta-oxidation of fatty acids, disruption of the electron transport chain, and blockage of beta-adrenoreceptors and cardiac calcium channels. The disease commonly presents as an otherwise unexplained high anion gap metabolic acidosis, rhabdomyolysis, hyperkalemia, acute kidney injury, elevated liver enzymes, and cardiac dysfunction. Management of overt propofol infusion syndrome requires immediate discontinuation of propofol infusion and supportive management, including hemodialysis, hemodynamic support, and extracorporeal membrane oxygenation in refractory cases. However, we must emphasize that given the high mortality of propofol infusion syndrome, the best management is prevention. Clinicians should consider alternative sedative regimes to prolonged propofol infusions and remain within recommended maximal dose limits.

We observed a case of Hand-Foot Syndrome (HFS) in a patient treated with decitabine. HFS has not previously been associated with decitabine, although it has been observed following treatment with the structurally similar pyrimidine analogue cytarabine.

Tumor lysis syndrome is an oncometabolic emergency resulting from rapid cell death. Tumor lysis syndrome can occur as a consequence of tumor targeted therapy or spontaneously. Clinicians should stratify every hospitalized cancer patient and especially those receiving chemotherapy for the risk of tumor lysis syndrome. Several aspects of prevention include adequate hydration, use of uric acid lowering therapies, use of phosphate binders and minimization of potassium intake. Patients at high risk for the development of tumor lysis syndrome should be monitored in the intensive care unit. Established tumor lysis syndrome should be treated in the intensive care unit by aggressive hydration, possible use of loop diuretics, possible use of phosphate binders, use of uric acid lowering agents and dialysis in refractory cases.