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Lebanon and Bosnia and Herzegovina share many commonalities involving sectarian and inter-ethnic strife, power-sharing agreement and the multitude of former and current paramilitary and revolutionary organizations. In the greater political view, the roles of paramilitary organizations are often controversial and problematic; however, during the times of civil-emergency, they often fill the niche of the missing first-responders. In Lebanon, a fragmented country, mired in an economic turmoil with occasional outbursts of sectarian violence, the emergency response and assistance are severely curtailed, which was evident in the sluggish response to the Beirut Port Explosion. In Bosnia and Herzegovina, a country mired in the continuous power-struggle among the nationalistic parties, the emergency response is inefficient and fragmented. This paper examines the unique role of former revolutionary organizations in Beirut which have taken the form of de-facto civic organizations and formed the backbone of emergency response, clean-up, and aid distribution. The study outlines several examples where the former revolutionary organizations mobilized and utilized their command authority, hierarchy, and community roles to provide an effective and sustainable emergency response. In Bosnia, the study outlines the cases of community-based organization under the vestiges of the old general communal self-protection. The results indicate that the lessons-learned from the years of civil-strife in Lebanon and vestiges of communal-defence in Bosnia have contributed to the relief distribution, cooperation across the sectarian/ethnic lines and coordination with external NGOs and state actors. Given the magnitude of the recent events (explosions and natural disasters), the role of civic organizations and their strategic approach to emergency response is instrumental to limiting further loss of life and deterioration of the overall security situation.

Western Balkans are entering into the seventh active year of mass-migration crisis with mixed results on the ability to direct, manage, house, register, assist and repatriate certain migrants or groups of migrants. This study collated available information from various process stakeholders and analysed strengths-weaknesses-opportunities-threats (SWOT) in the approaches to migrant crisis in North Macedonia, Albania, Kosovo*, Serbia, Montenegro and Bosnia-Herzegovina. The main goal of the study was to investigate if the opportunities were seized / missed in improving cooperation, communication, interoperability among the stakeholders to make the flow of migration more humane, manageable, transparent (accountable) and effective in the field. Given security considerations and challenges of the migration flow as well as its subsidiary elements involving human smuggling / human trafficking and movement of problematic personnel, the analysis highlights some of the novel operative and technical solutions that can be fielded to improve identification, registration and additional screening or removal as required. Particularly important elements are the advances in digital data capture, biometrics, correlation, language recognition and information sharing among the varying levels of stakeholders. The analysis also identified significant opportunities in improving communication and data sharing among the principal countries of the migration route (North Macedonia – Serbia – Bosnia and Herzegovina), which could be beneficial in enhancing other security-related issues among the Western Balkan countries. The main challenge encountered is the lack of communications and reporting protocols as well as lack of documentation standards suitable for data entry, storage, indexing and searching. The analysis concludes that implementation of standardized, technical solutions may resolve some of the identified communications, mistrust or data sharing issues described in the SWOT analyses.

Aim This study was focused on the isolation and characterization of mesenchymal stem cells (MSCs) from human dental pulp (DPSC). Methods The study was performed in the Department for Oral and Cranio-Maxillo- Facial Surgey Hamad Medical Corporation, Doha, Qatar and Weill Cornell Medical Colleague Doha, Qatar, in period 2010-2011. Dental pulp was extracted from premolars and third molars of 19 healthy patients. The pulp was digested in a solution of 3 mg/mL collagenase type I and 4 mg/mL dispase for 1 hour at 37C. After filtration, cells were cultured in Dulbecco’s Modified Eagle Medium (DMEM Low Glucoses) with 20% Fetal Bovine Serum (FBS), 2mM L-glutamine and antibiotics (100 U/mL penicillin, 100 ug/mL streptomycin) at 37 °C under 5% CO2. Cultures were treated with osteoinductive medium for differentiation MSC in to the osteoblast cell line. Staining with Alizarin red were used for the detection of the osteoblast production and calcification new formed tissue. Results On the total of three out of 19 patients it was possible to isolate DPMSCs after 2 to 3 weeks: in one patient it was not possible to expand MSCs because of infection, and in other two patients positive Alizarin red staining reaction showed osteogenic differentiation capability and strong mineralization in vitro. Conclusion The main advantage of using DPSC is absence of morbidity. MSCs could be isolated noninvasively from teeth, routinely extracted in the clinic and discarded as medical waste. Standardization of clinical and laboratory protocols for DPMSCs isolation and team work coordination could lead to significantly improved result.

Multiple studies have examined the age of onset of major depression, indicating it is most frequent in adolescence and young adulthood. In this context, the offspring of depressed parents have a 2 to 4 time increased risk for depression compared with children of non-depressed parents.Treatment for depression in adolescents can be divided into psychosocial, psychopharmacologic, somatic and combined psychosocial-psychopharmacologic, psychosocial-psychosomatic and psychopharmacologic-psychosomatic.Depression in the children and adolescent population has been an area of research for over 20 years. Among novel therapeutic strategies, transcranial magnetic stimulation (TMS) has demonstrated the most favorable side effect profile. Until this time there are no published suicide attempts associated with this treatment and it may offer an option that is not associated with stigma of electroconvulsive therapy (ECT) or medications. Further research may provide more access to this therapy and hope to children, adolescents with depression and their families.

The great diffusion of the surgical techniques in jaws surgery and the progress of the radiological imagining procedures expressed many interest in clinical anatomy of the mental foramen (MF). The study goal was to determine the precise location of the MF and the surrounding anatomical landmarks. Measurements of the MF position relative to the surgical landmarks and related posterior teeth were made on 20 dry mandibles with complete dentition and intact alveolar bridge obtained from the Institute of Anatomy, School of Medicine, University in Sarajevo. The measurements were made by anthropometric methods on the booth sides of the mandible, and compared with measurement made on the orthopantomogram radiographs of the same mandibles. The most common position of the MF was in line with the longitudinal axis of the second premolar. In the vertical plane on the skulls the MF lays in the midpoint of the distance between the lower border of the mandible and the alveolar margin, however on the orthopantomogram MF appeared slightly bellow the midpoint. In the horizontal plane it lays approximately one third of the distance between the mandibular symphysis and the posterior border of the ramus of the mandible measurement from A-P projection and one quarter of that distance measurement from the profile projection. There were no significant differences between distances MF from posterior border of the ramus of the mandible measurement from A-P and profile projection and the one obtained on orthopantomogram and their ratio is constant value determine das 1,065. The MF was on average 25 mm lateral to the mandibular skeletal midline and symmetrical, and symmetry was preserved on the orthopantomogram. The measurement showed significant differences in distances of M from superior border mandible measurement on dry mandible and orthopantomogram radiographs while distance bellow the MF was not significantly different. The constant values of MF distance to the posterior border of the ramus of the mandible measured as 1,065 and the distance to the medial skeletal line of 2,11 made it possible to also determine average angle of 43 degrees stream of the cor-pus of the mandible behind MF. These values in combination with ratios of MF to the different anatomic landmarks designated as relative horizontal and relative vertical position, would be of importance not only from anatomical but also from practical point of view for estimation of alveolar bridge resorption and preoperative analysis in orthognat postresection or implant surgery in the mandible.

Myofibroma (MF) is a benign neoplasm derived from myofibroblasts. While they are infrequent, these tumors are predominantly found in the pediatric group and seldom manifest as intraosseous mandibular tumors. Herein, we present a 9-year-old female with a radiolucent lesion in the left mandible associated with malposed left lower canine and 1st premolar teeth. Clinical examination revealed a slightly tender 5×4 cm firm mass resulting in an expansion of the buccal and lingual aspects of the mandible in the canine and first premolar region. An incisional biopsy revealed a benign tumor consisting of spindle cells organized in fascicles, alongside dispersed thin-walled blood vessels. Tumor cells tested positive for α-smooth muscle actin (SMA) and vimentin. Given these findings, a diagnosis of MF was established. To the best of our knowledge, only 45 cases of solitary MF of the mandible have been reported in the pediatric age group in the literature. We describe one additional case and provide a review of the literature., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Lazim et al.)

Background Central giant cell granuloma (CGCG) presents as a locally invasive, intraosseous lesion characterized by the accumulation of multinucleated giant cells amidst a matrix of hemorrhage and reactive fibrous tissue that infiltrates bone trabeculae. This idiopathic non-neoplastic proliferative lesion primarily affects the mandible, typically presenting as either unilocular or multilocular radiolucencies on X-rays. Although trauma or intraosseous hemorrhages are potential triggers, the precise histogenesis and etiology remain unclear. CGCG predominantly occurs in children and young adults, with a slight female predilection. Methods and materials A retrospective analysis of 21 cases of CGCG diagnosed at the Oral Pathology/Pathology department of Temple University Hospital between 2015 and 2022 was conducted. Each case was evaluated based on various parameters, including age, gender, presenting symptoms, radiographic findings, clinical differential diagnosis, and histological confirmation. The primary radiographic technique employed for diagnosis was X-ray imaging of the mandible and maxilla. The histological examination involved cutting paraffin-embedded tissue into 5-micrometer-thick sections, which were then stained using routine hematoxylin and eosin (H&E) stain. Notably, no specialized histochemical or immunohistochemical stains were utilized in the evaluation process. Results In our study, we reviewed 21 cases; 9 were male, 11 were female, and one had no available gender data. The age range was 15-76 years, with a mean of 50 years. The mandible was the most commonly affected location (17 cases; 81%) while the maxilla was less commonly involved (4 cases; 19%). Many CGCG lesions were asymptomatic (13 cases; 62%); eight cases (38%) were symptomatic, with pain and fullness of the affected dental region being the main manifestations. In a few cases, conditions such as brown tumor (severe hyperparathyroidism) and odontogenic neoplasms, such as ameloblastoma, were suspected clinically and radiographically. The diagnosis of CGCG with associated acute and chronic inflammation was confirmed in all the cases. Histological evaluation of routinely stained slides was the main diagnostic tool utilized. No special stains or molecular studies were required to establish the final diagnosis. Conclusions Our investigation has determined that CGCG exhibits a non-neoplastic nature, displaying a spectrum of behaviors ranging from non-aggressive to aggressive tendencies. While CGCG is predominantly observed in the mandible, rare instances of involvement in the maxilla have also been documented. Importantly, no confirmed association with neoplastic lesions was identified during our analysis. The clinical course of CGCG tends to be indolent, with some cases presenting in association with impacted teeth. It's noteworthy that CGCG can present features mimicking neoplastic conditions, such as ameloblastoma, or localized lesions linked to systemic disorders such as hyperparathyroidism (brown tumor)., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Temple University's Human Research Protection Program (HRPP) issued approval 28418. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Lazim et al.)

The presence of antibiotics in water systems had raised a concern about their potential harm to the aquatic environment and human health as well as the possible development of antibiotic resistance. Herein, this study investigates the power of adsorption using graphene-polypyrrole (GRP-PPY) nanoparticles as a promising approach for the removal of Moxifloxacin HCl (MXF) as a model antibiotic drug. GRP-PPY nanoparticles synthesis was performed with a simple and profitable method, leading to the formation of high surface area particles with excellent adsorption properties. Characterization was assessed with various techniques, including Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), X-ray diffraction (XRD) and Brunauer-Emmett-Teller (BET). Box-Behnken experimental design was developed to optimize the adsorption process. Critical parameters such as initial antibiotic concentration, nanoparticle concentration, and pH were investigated. The Freundlich isotherm model provided a good fit to the experimental data, indicating multilayer adsorption of MXF onto the GRP-PPY-NP. As a result, a high adsorption capacity of MXF (92%) was obtained in an optimum condition of preparing 30 μg/mL of the drug to be adsorbed by 1 mg/mL of GRP-PPY-NP in pH 9 within 1 h in a room temperature. Moreover, the regeneration and reusability of GRP-PPY-NP were investigated. They could be effectively regenerated for 3 cycles using appropriate desorption agents without significant loss in adsorption capacity. Overall, this study highlights the power of GRP-PPY-NP as a highly efficient adsorbent for the removal of MXF from wastewater as it is the first time to use this NP for a pharmaceutical product which shows the study's novelty, and the findings provide valuable insights into the development of sustainable and effective wastewater treatment technologies for combating antibiotic contamination in aquatic environments., (© 2024. The Author(s).)

Google Trends has been extensively used in different sectors from finance to tourism, the economy, fashion, the fun industry, the oil trade, and healthcare. This scoping review aims to summarize the role of Google Trends as a monitoring and a predicting tool in the COVID-19 pandemic. Inclusion criteria for this scoping review were original English-language peer-reviewed research articles on the COVID-19 pandemic conducted in 2020 using Google Trends as a search tool. Articles that were in a language other than English, were only in abstract form, or did not discuss the role of Google Trends during the COVID-19 pandemic were excluded. According to these criteria, a total of 81 studies were included to cover the period of the first year after the emergence of the crisis. Google Trends can potentially help health authorities to plan and control pandemics earlier and to decrease the risk of infection among people., (© The Author(s) 2023. Published by Oxford University Press on behalf of Postgraduate Medical Journal. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Eco-friendly stannic oxide nanoparticles functionalized with gallic acid (SnO 2 /GA NP) were synthesized and employed as a novel photocatalyst for the degradation of citalopram, a commonly prescribed antidepressant drug. SnO 2 /GA NP were characterized using high-resolution transmission electron microscopy, Fourier transform infrared spectroscopy, Brunauer-Emmett-Teller measurements and X-ray diffraction. A validated RP-HPLC assay was developed to monitor citalopram concentration in the presence of its degradation products. Full factorial design (2 4 ) was conducted to investigate the effect of irradiation time, pH, SnO 2 /GA NP loading and initial citalopram concentration on the efficiency of the photodegradation process. Citalopram initial concentration was found to be the most significant parameter followed by irradiation time and pH, respectively. At optimum conditions, 88.43 ± 0.7% degradation of citalopram (25.00 µg/mL) was obtained in 1 h using UV light (1.01 mW/cm 2 ). Citalopram kinetics of degradation followed pseudo-first order rate with K obs and t 0.5 of - 0.037 min -1 and 18.73 min, respectively. The optimized protocol was successfully applied for treatment of water samples collected during different cleaning validation cycles of citalopram production lines. The reusability of SnO 2 /GA NP was studied for 3 cycles without significant loss in activity. This approach would provide a green and economic alternative for pharmaceutical wastewater treatment of organic pollutants., (© 2022. The Author(s).)

This paper presents a novel potentiometric approach for the determination of palonosetron HCl using two sensors; ionophore-free and ionophore-doped ones. The two sensors successfully determined the cited drug in the range of 1 × 10 -5 -1 × 10 -2  M with respective Nernstian slopes of 54.9 ± 0.25 and 59.3 ± 0.16 mV/decade. Incorporating calix[8]arene as an ionophore resulted in a lower detection limit (LOD = 3.1 × 10 -6  M) and enhanced selectivity when compared to the ionophore-free sensor (LOD = 7.9 × 10 -6  M). This modification was also associated with faster response for the ionophore-doped sensor (response time = 20 s) compared to the ionophore-free one (response time = 30 s). The two sensors showed a stable response over a pH range of 3.0-8.0. They successfully determined palonosetron HCl in presence of its oxidative degradation products. They were also used for direct determination of the drug in commercially available parenteral solution without any interference from other dosage forms' additives., (© 2022. The Author(s).)

Objectives. Nearly 60 million people suffer from computer vision syndrome (CVS) globally, resulting in reduced work productivity. This study aimed to determine the prevalence of CVS, describe the working conditions, visualize ergonomic factors and determine preventive measures application among university staff members. Methods . A cross-sectional study was conducted with university medical staff members using a semi-structured questionnaire that included a validated CVS questionnaire. Results. CVS prevalence was 81.2%. Dryness, headache, feeling that sight is worsening and difficulty in focusing on near vision were the most experienced symptoms. Prevalence of CVS was significantly higher among females (52.3%), those having a higher mean work duration (21.65 ± 7.55 years), those who frequently use a smartphone (84.9%) and those spending most of their screen time during both day and night (87.1%). Visual ergonomics and preventive measures application, such as correct screen level, regular cleaning of the screen, appropriate illumination and use of eye drops, were significantly associated with negative CVS. Conclusions. These results raised attention to the essential need for visual assessment of university staff members for early and proper diagnosis of CVS to minimize its impact on working performance. Accordingly, it is recommended to organize university-based awareness programs regarding CVS for working personnel.

Aims: Due to the continuous changes in modern lifestyle and the need to explore the effect of these changes on the risk of developing cancer, ongoing research on the epidemiology and characteristics of cancer patients is requested. This study explored the epidemiology of cancer, its characteristics, treatment patterns, and risk factors in the southern region of Saudi Arabia., Methods: A retrospective cross-sectional study was conducted using cancer patients' medical records at Asir Central Hospital in the southern region of Saudi Arabia. Active patients' records were extracted between January 2013 and December 2019., Results: A total of 2038 patients were identified during the study period, with a mean age of 60.9 (SD: 19.0) years. The patients had survived with their cancer for a median duration of 4 years (IQR: 2-6). Around 4.6% of the patients required ICU admission with a median period of 9 days (IQR: 5-14.75). The death rate during the study period was 10.9%. Around 20.8% of the cases were metastatic, of which 77.8% were at stage four of metastasis, and 19.7% of the patients were receiving chemotherapy for their disease. The most common types of cancer were malignant neoplasms of digestive organs, comprising 40.8% of the sample. Older age (60 years and above) and using specific chronic disease medications were predictors associated with a higher risk of death due to cancer ( p < 0.05). Smoking history, using specific chronic disease medications, and having previous surgery were predictors associated with a higher risk of ICU admission ( p < 0.05)., Conclusion: Breast, colon, and liver cancers were the most prevalent in the southern region of Saudi Arabia. Several modifiable cancer risk factors were identified. The results of this study should support decision-makers in the initiation of programs for key modifiable risk factors that enhance lifestyle changes and reduce cancer risks.

Zamzam water is the most frequently used drinking water by millions of people in Saudi Arabia. It is carried all the time by millions of pilgrims to their home countries as gifts to close and near relatives and friends. Safety of constituents of Zamzam water is a vital health topic. British Broadcasting Corporation (BBC) raised many health concerns regarding the high serum arsenic and nitrate contents in Zamzam water that may cause cancer. It is role of scientific research to present scientific facts to relieve such concerns. Arsenic is a carcinogen while nitrate causes methemogloinemia that affect oxygen carriage by haemoglobin. An ethical committee approval was obtained. Eighteen white albino mice (40-45 g) were used in this study. Three experimental groups were allocated (six mice per group): tap water group, distilled water group and Zamzam water group. Our data revealed that Zamzam water exerts tissue-protective effects that contradict malignancy. Our data proved that Zamzam water is pathogen-free causing no bacterial growth on CLED agar colonies. Zamzam water consumption for three consecutive months in mice was quite safe for the general health and significantly decreased serum uric acid ( p < 0.05) (possibly due to Zamzam-induced urine alkalinisation facilitating uric acid excretion). Regular Zamzam water consumption significantly decreased serum cholesterol ( p < 0.05) and serum triglycerides ( p < 0.05). Hypolipidemic effects of Zamzam water may be due to its high mineral content facilitating increased lipids metabolism. Our data confirmed safety of prolonged use of Zamzam water comparable to other drinking water types regarding the metabolic and synthetic functions of the liver. Nitrates in Zamzam water are thought to be an original constituent that may be useful (exerting vasodilation, antithrombotic, and immunoregulatory effects) and not harmless. This may occur due to high Zamzam content of calcium, magnesium and selenium. Histologically, our data confirmed that Zamzam water was quite safe to renal parenchyma and comparable to other types of drinking water. In conclusion, health concerns raised by BBC regarding Zamzam water safety were a good chance for fruitful scientific research investigations that confirmed safety and beneficial effects of Zamzam water for human health., Competing Interests: None., (AJBR Copyright © 2020.)

A sensitive micellar electrokinetic chromatography method is presented to simultaneously quantify ofloxacin, gatifloxacin, dexamethasone sodium phosphate and prednisolone acetate. The method has the advantages of being rapid, accurate, reproducible, ecologically acceptable and sensitive. The electrophoretic separation utilized 20 mm borate buffer as background electrolyte with pH 10.0 ± 0.1 and 50 mm sodium dodecyl sulfate as a micelle forming molecule. A capillary tube (50 μm i.d., 33 cm) of fused silica was used and on-column diode array detection at 243 nm for dexamethasone sodium phosphate and prednisolone acetate, and 290 nm for ofloxacin and gatifloxacin. Various factors were optimized such as the background electrolyte (type, concentration and pH), addition of sodium dodecyl sulfate and its concentration, detection wavelength, applied voltage and injection parameters. The studied drugs were efficiently separated in 6.2 min, at 20 kV with high resolution. The greenness of the method was estimated using an eco-scale tool and the presented method was found to have excellent green characteristics. The method was validated in conformance with International Conference on Harmonization guidelines, with acceptable accuracy, precision and selectivity. The suggested method can be employed for the economic analysis of the four drugs in dissimilar binary combinations of eye drops saving solvents and chemicals., (© 2020 John Wiley & Sons, Ltd.)

Primary toxicity targets of alcohol and its metabolites in the pancreas are cellular energetics and endoplasmic reticulum (ER). Therefore, the role of AMP-Activated Protein Kinase (AMPKα) in amelioration of ethanol (EtOH)-induced pancreatic acinar cell injury including ER/oxidative stress, inflammatory responses, the formation of fatty acid ethyl esters (FAEEs) and mitochondrial bioenergetics were determined in human pancreatic acinar cells (hPACs) and AR42J cells incubated with/without AMPKα activator [5-aminoimidazole-4-carboxamide ribonucleotide (AICAR)]. EtOH treated hPACs showed concentration and time-dependent increases for FAEEs and inactivation of AMPKα, along with the upregulation of ACC1 and FAS (key lipogenic proteins) and downregulation of CPT1A (involved β-oxidation of fatty acids). These cells also showed significant ER stress as evidenced by the increased expression for GRP78, IRE1α, and PERK/CHOP arm of unfolded protein response promoting apoptosis and activating p-JNK1/2 and p-ERK1/2 with increased secretion of cytokines. AR42J cells treated with EtOH showed increased oxidative stress, impaired mitochondrial biogenesis, and decreased ATP production rate. However, AMPKα activation by AICAR attenuated EtOH-induced ER/oxidative stress, lipogenesis, and inflammatory responses as well as the formation of FAEEs and restored mitochondrial function in hPACs as well as AR42J cells. Therefore, it is likely that EtOH-induced inactivation of AMPKα plays a crucial role in acinar cell injury leading to pancreatitis. Findings from this study also suggest that EtOH-induced inactivation of AMPKα is closely related to ER/oxidative stress and synthesis of FAEEs, as activation of AMPKα by AICAR attenuates formation of FAEEs, ER/oxidative stress and lipogenesis, and improves inflammatory responses and mitochondrial bioenergetics., (Copyright © 2020 Elsevier Inc. All rights reserved.)

In the pharmaceutical industry, finding cost-effective and real-time analyzers that provide valid data is a good aim. The purpose of this work was to propose a link between the pharmaceutical industry and the recent innovations in solid-contact ion-selective electrodes (SC-ISEs) for the utilization of these electrodes as real-time analyzers to evaluate the concentration of tetrahydrozoline HCl in different matrices. The backbone of these new potentiometric sensors is the conjunction of calix[6]arene and (2-hydroxypropyl)-β-cyclodextrin as molecular recognition elements and a network of multi-walled carbon nanotubes as a solid transducer material between an ionophore-doped PVC membrane and microfabricated Cu electrodes. The proposed sensors were optimized to determine tetrahydrozoline, and their performances were assessed according to the IUPAC recommendations. The proposed solid-contact sensors were compared with liquid contact sensors, and the former sensors were found to be better than the latter sensors in terms of durability, handling, and easier adaptation to industry with comparable sensitivity. The measurements were implemented using phosphate buffer (pH: 6). The best obtained linearity range was 1 × 10-2 to 1 × 10-7 M, and the best LOD was 1 × 10-8 M. The sensors with the best performance were successfully applied to determine tetrahydrozoline in a pharmaceutical eye preparation and rabbit tears. The obtained results were statistically compared to those obtained by the official method of analysis, and no significant difference was obtained. The eco-score of the method was assessed using the eco-scale tool and also compared with that of the official method. The proposed approach was validated according to the International Council for Harmonisation (ICH) guidelines.

The growing technology of stationary phase chemistry has a great impact on the chromatographic system performance and analysis economics. In this context, a simple rapid reversed phase high-performance liquid chromatography method development is presented for the analysis of gatifloxacin (GFN) and dexamethasone sodium phosphate (DSP) in their ophthalmic formulation. A two-step optimization approach has been conducted using optimum chromatographic conditions as well as proper selection of stationary phase. The chromatographic separation was carried out using sodium phosphate buffer pH 3.0 ± 0.1 and acetonitrile 72:28 v/v, respectively, with flow rate 1 mL min-1 and simultaneous detection at 243 nm. Three different column technologies were investigated at the optimum set of the chromatographic conditions: Xbridge® bridged ethylene hybrid silica, Kinetex™ Core-Shell and the Onyx™ Monolithic stationary phase. The monolithic column has shown better chromatographic separation, based on system suitability testing as well as shorter analysis time and sensitivity. The proposed method was validated according to International Conference on Harmonization guidelines. The linearity was achieved for GFN and DSP in the range 0.58-120 μg mL-1 and 0.50-120 μg mL-1, respectively, with acceptable accuracy, precision and selectivity., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Reasons for formulation instability were investigated either encountered during production or analytical processes of azilsartan medoxomil (AZM)/chlorthalidone hydrochloride (CLT) tablets. Through the identification of the most feasible degradation pathways, several strategies were proposed to enhance the stability of AZM/CLT formulation. Furthermore, a robust HPLC-UV method was developed and validated for the determination of AZM, CLT in the presence of their possible degradation products. For chromatographic method development, typical quality by design (QbD) approach was implemented. In order to optimize fourteen chromatographic responses, we have used a central composite design with four factors (pH, temperature, flow rate, and acetonitrile %). However, the developed method provides a design space, but optimum parameters were Inertsil C8 column (150 x 4.6 mm, 5 μm), mobile phase composed of 0.025 M phosphate buffer pH 2.7 and acetonitrile (52.5: 47.5%), with flow rate of 1.5 mL.min -1 and detection wavelength 225 nm at 33 °C. The method was then validated according to ICH guidelines and applied to quantitate AZM and CLT in the pharmaceutical formulation. To the best of our knowledge, this manuscript is the first attempt to discuss such instability issues, to propose strategies that enhance the stability of AZM/CLT tablet formulation, to develop robust stability-indicating method taking into consideration the realistic degradation products in addition to minor ones., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Nadifloxacin, mometasone furoate and miconazole nitrate are formulated together as a topical antifungal dosage form. In this work, a reversed-phase ultra-performance liquid chromatographic method coupled with a diode array detector (RP-UPLC-DAD) was developed and validated to determine nadifloxacin, mometasone furoate and miconazole nitrate simultaneously in their bulk powder, in pharmaceutical preparation and in spiked human plasma samples. Separation was achieved on an ACQUITY UPLC C18 column of 2.2 μm particle size (2.1 × 100 mm) via isocratic elution using a mobile phase consisting of methanol, acetonitrile and water with ratio (50:20:30; v/v/v) and 0.1 g ammonium acetate, then pH was adjusted to (7.00) using acetic acid, flow rate 0.6 mL/min, temperature 30°C and UV detection at 220 nm. The method is linear in a range from 5 to 400 μg/mL for both nadifloxacin and miconazole nitrate and from 20 to 500 μg/mL for mometasone furoate. The method was validated according to the ICH guidelines then applied successfully to determine the mentioned drugs in their pharmaceutical preparation and spiked human plasma samples. For plasma samples, the results showed that the method can determine nadifloxacin, mometasone furoate and miconazole nitrate in human plasma samples with high accuracy and precision., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Inclusion complexes of β-cyclodextrin with Estradiol valerate (EST) or Norethisterone acetate (NOR) have been utilized for synchronous fluorescence spectrofluorimetry. β-cyclodextrin improves fluorescence intensity as well as water solubility of the studied drugs. Samples in aqueous medium adjusted with ammonia were used in synchronous fluorescence to resolve the overlapped emission spectra. The effects of β-cyclodextrin concentration and Δ λ have been optimized for sensitive and selective analysis of EST and NOR binary mixture. Synchronous fluorescence intensity of the two drugs is measured at Δ λ of 70 nm. EST and NOR can be simultaneously determined at 230 nm and 270 nm, respectively. Calibration curves were linear over the ranges of 0.5-6.0 μg mL -1 and 0.2-2.0 μg mL -1 for EST and NOR, respectively. Official guidelines were followed to estimate the validation parameters of the proposed method. The detection limits were 0.08 μg mL -1 for EST and 0.007 μg mL -1 for NOR. The proposed method was successfully used for the analysis of EST and NOR in their commercial preparations and the obtained results revealed statistical agreement with those obtained by application of the reported method for both drugs. The proposed method is compared favorably to previously published method in terms of simplicity and hazardous solvent consumption., (Copyright © 2019. Published by Elsevier B.V.)

Ethanol (EtOH) metabolism itself can be a predisposing factor for initiation of alcoholic liver disease (ALD). Therefore, a dose dependent study to evaluate liver injury was conducted in hepatic alcohol dehydrogenase (ADH) deficient (ADH - ) and ADH normal (ADH + ) deer mice fed 1%, 2% or 3.5% EtOH in the liquid diet daily for 2 months. Blood alcohol concentration (BAC), liver injury marker (alanine amino transferase (ALT)), hepatic lipids and cytochrome P450 2E1 (CYP2E1) activity were measured. Liver histology, endoplasmic reticulum (ER) stress, AMP-activated protein kinase (AMPK) signaling and cell death proteins were evaluated. Significantly increased BAC, plasma ALT, hepatic lipids and steatosis were found only in ADH - deer mice fed 3.5% EtOH. Further, a significant ER stress and increased un-spliced X-box binding protein 1 were evident only in ADH - deer mice fed 3.5% EtOH. Both strains fed 3.5% EtOH showed deactivation of AMPK, but increased acetyl Co-A carboxylase 1 and decreased carnitine palmitoyltransferase 1A favoring lipogenesis were found only in ADH - deer mice fed 3.5% EtOH. Therefore, irrespective of CYP2E1 overexpression; EtOH dose and hepatic ADH deficiency contribute to EtOH-induced steatosis and liver injury, suggesting a linkage between ER stress, dysregulated hepatic lipid metabolism and AMPK signaling.

Ponatinib (Iclusig®) is a multi-targeted tyrosine kinase inhibitor (TKIs). It is active against T315I and other BCR-ABL mutants. Investigation of in vivo metabolism of ponatinib was done using Sprague Dawley rats by giving one oral dose of PNT (4.7 mg/kg) to each rat and urine samples were gathered at several time intervals from dosing. Filteration of urine samples was done through 0.45 μm syringe filters. Phase separation using ACN was applied for extraction of ponatinib related metabolites. Characterization and identification of one in vivo phase II metabolite and thirteen in vivo phase I of PNT were done using LC-MS/MS. Phase I metabolic reactions were reduction, N-demethylation, hydroxylation, N-oxidation, oxidation and amide hydrolysis. Phase II metabolic reaction was glucuronidation of hydroxyl benzyl metabolites of ponatinib. The major in vivo metabolic reactions were α hydroxylation and α oxidation at piperazine ring. Literature review revealed no articles that have been published on in vivo metabolism of ponatinib in Sprague Dawley rats or ponatinib in vivo phase I and phase II metabolites structural characterization and identification., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Vandetanib (Caprelsa tablets, VNT) is an orally inhibitor of vascular endothelial growth factor receptor 2. The current research reports the characterization and identification of in vitro, in vivo and reactive intermediates of VNT. In vitro metabolites of VNT were performed by incubation with rat liver microsomes (RLMs). Extraction of vandetanib and its in vitro metabolites from the incubation mixtures were done by protein precipitation. In vivo metabolism was done by giving one oral dose of vandetanib (30.8 mg/kg) to Sprague Dawley rats in metabolic cages by using oral gavage. Urine was gathered then filtered at certain time intervals (0, 6, 12, 18, 24, 48, 72, 96 and 120 h) from vandetanib dosing. A similar volume of ACN was added to each collected urine sample. Both layers (organic and aqueous) were injected into liquid chromatography electro spray ionization tandem mass spectrometry (LC-ESI-MS/MS) to detect in vivo vandetanib metabolites. N-methyl piperidine ring of vandetanib is considered a cyclic tertiary amine that undergoes metabolism forming iminium intermediates that are very reactive toward nucleophilic macromolecules. Incubation of vandetanib with RLMs in the presence of 1.0 mM KCN was made to check reactive metabolites as it is usually responsible for noticeable idiosyncratic toxicities including phototoxicity and QT interval prolongation. Four in vivo phase I, one in vivo phase II metabolites, six in vitro phase I metabolites and four cyano conjugates of vandetanib were detected by LC-MS/MS. In vitro and in vivo phase I metabolic reactions were N-oxide formation, N-demethylation, α-carbonyl formation and α-hydroxylation. In vivo phase II metabolic reaction was direct conjugation of vandetanib with glucuronic acid. All metabolic reactions occurred in N-methyl piperidine of vandetanib which causes toxicity and instability of vandetanib.

Foretinib (GSK1363089) is a multiple receptor tyrosine kinases inhibitor. In this study, a reliable, fast liquid chromatography-tandem mass spectrometric method was described for assaying foretinib in plasma, urine, and rat liver microsome samples. Simple extraction procedure by protein preciptation with acetonitrile was implemented for foretinib and brigatinib (internal standard) analysis. Chromatographic resolution of analytes was achieved on C 18 column with the help of isocratic mobile phase. The binary mobile phase consisted of 60% ammonium formate (10 mM, pH 4.2) and 40% acetonitrile at a flow rate of 0.25 mL/min. Run time was 3 min, and both foretinib and brigatinib were eluted within 0.74 and 1.95 min; they were detected in positive ion mode utilizing multiple reactions monitoring mode. Linearity of the proposed method ranged from 5 to 500 ng/mL (r 2  ≥ 0.9993) in the human plasma. Lower limit of quantification and detection were 6.0 and 1.8 ng/mL, respectively. Intraday and interday precision and accuracy were 0.16 to 1.67 % and -2.39 to -0.52 %. In vitro half-life and intrinsic clearance were 24.93 min and 6.56 mL/min/kg, respectively. Literature review showed that no previous studies have been proposed for the analytical quantification of foretinib in human plasma or its metabolic stability. The established method was also applied to estimate the rate of foretinib excretion in rat urine. The developed method can be used for foretinib pharmacokinetic applications.

Masitinib (MST) is an orally administered drug that targets mast cells and macrophages, important cells for immunity, by inhibiting a limited number of tyrosine kinases. It is currently registered in Europe and USA for the treatment of mast cell tumors in dogs. AB Science announced that the European Medicines Agency has accepted a conditional marketing authorization application for MST to treat amyotrophic lateral sclerosis. In our work, we focused on studying in vivo metabolism of MST in Sprague-Dawley rats. Single oral dose of MST (33 mg kg -1 ) was given to Sprague-Dawley rats (kept in metabolic cages) using oral gavage. Urine was collected and filtered at 0, 6, 12, 18, 24, 48, 72 and 96 h from MST dosing. An equal amount of ACN was added to urine samples. Both organic and aqueous layers were injected into liquid chromatography-tandem mass spectrometry (LC-MS/MS) to detect in vivo phase I and phase II MST metabolites. The current work reports the identification and characterization of twenty in vivo phase I and four in vivo phase II metabolites of MST by LC-MS/MS. Phase I metabolic pathways were reduction, demethylation, hydroxylation, oxidative deamination, oxidation and N-oxide formation. Phase II metabolic pathways were the direct conjugation of MST, N-demethyl metabolites and oxidative metabolites with glucuronic acid. Part of MST dose was excreted unchanged in urine. The literature review showed no previous articles have been made on in vivo metabolism of MST or detailed structural identification of the formed in vivo phase I and phase II metabolites.

Background: Interferon gamma release assays (IGRA) is highly specific for Mycobacterium tuberculosis and is the preferred test in BCG-vaccinated individuals. The few studies that have screened health care workers (HCWs) in Saudi Arabia for latent tuberculosis infection (LTBI) using IGRA have varied in agreement with the traditional tuberculin skin test (TST)., Objective: Assess the prevalence of LTBI among HCWs working in the Hajj pilgrimage using IGRA and TST and measuring their agreement., Design: Cross-sectional prospective., Setting: Multiple non-tertiary care hospitals., Patients and Methods: HCWs who worked during the Hajj pilgrimage in Saudi Arabia in December 2015. Data was collected by standarized questionnaire. Samples were drawn and analyzed by standard methods., Main Outcome Measures: The prevalence of LTBI among HCW and the agreement by kappa statistic between QFT-GIT and TST., Sample Size: 520 subjects., Results: Nurses accounted for 30.7% of the sample and physicians, 19.2%. The majority were BCG vaccinated (98.5%). There were a total of 56 positive by QFT-GIT and the LTBI rate was 10.8%. In 50 QFT positive/476 TST negative the LTBI rate was 10.5% in discordant tests, and in 6 QFT positive/44 TST positive it was 13.6% in concordant tests. The overall agreement between both tests was poor-83% and kappa was 0.02. LTBI prevalence was associated with longer employment (13.1 [9.2] years). The QFT-GIT positive test was significantly higher in physicians (P=.02) and in HCWs working in chest hospitals 16/76 (21.05%) (P=.001)., Conclusion: Agreement between the tests was poor. QFT-GIT detected LTBI when TST was negative in HCWs who had a history of close contact with TB patients., Limitations: A second step TST was not feasible within 2-3 weeks., Conflict of Interest: None.

The single most common cause of chronic pancreatitis (CP, a serious inflammatory disease) is chronic alcohol abuse, which impairs hepatic alcohol dehydrogenase (ADH, a major ethanol oxidizing enzyme). Previously, we found ~5 fold greater fatty acid ethyl esters (FAEEs), and injury in the pancreas of hepatic ADH deficient (ADH - ) vs. hepatic normal ADH (ADH + ) deer mice fed 3.5g% ethanol via liquid diet daily for two months. Therefore, progression of ethanol-induced pancreatic injury was determined in ADH - deer mice fed ethanol for four months to delineate the mechanism and metabolic basis of alcoholic chronic pancreatitis (ACP). In addition to a substantially increased blood alcohol concentration and plasma FAEEs, significant degenerative changes, including atrophy and loss of acinar cells in some areas, ultrastructural changes evident by such features as swelling and disintegration of endoplasmic reticulum (ER) cisternae and ER stress were observed in the pancreas of ethanol-fed ADH - deer mice vs. ADH + deer mice. These changes are consistent with noted increases in pancreatic injury markers (plasma lipase, pancreatic trypsinogen activation peptide, FAEE synthase and cathepsin B) in ethanol-fed ADH - deer mice. Most importantly, an increased levels of pancreatic glucose regulated protein (GRP) 78 (a prominent ER stress marker) were found to be closely associated with increased phosphorylated eukaryotic initiation factor (eIF) 2α signaling molecule in PKR-like ER kinase branch of unfolded protein response (UPR) as compared to X box binding protein 1S and activating transcription factor (ATF)6 - 50kDa protein of inositol requiring enzyme 1α and ATF6 branches of UPR, respectively, in ethanol-fed ADH - vs. ADH + deer mice. These results along with findings on plasma FAEEs, and pancreatic histology and injury markers suggest a metabolic basis of ethanol-induced pancreatic injury, and provide new avenues to understand metabolic basis and molecular mechanism of ACP., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Masitinib (MST) is a selective tyrosine kinase inhibitor. Validated liquid chromatography tandem mass spectrometric method (LC-MS/MS) was developed for the quantification of MST in rat liver microsomes (RLMs) matrix. The developed method was applied to metabolic stability and excretion rate studies. Reversed phase liquid chromatography was used for resolution of MST and bosutinib (IS) using C 18 (50 mm × 2.1 mm, 1.8 μm). Binary solvent system consisted of 35% solvent A (0.1% formic acid in H 2 O, pH: 3.2) and 65% solvent B (acetonitrile) used as mobile phase at flow rate of 0.25 mL with a total run time of 5 min. Injection volume was 5 µL. Generation of ions was done in positive ESI source and quantification of MST and IS were done using MRM mode. The developed method showed a linearity in the range of 5-200 ng/mL (r 2  ≥ 0.9992) with LOQ and LOD of 0.25 and 0.76 ng/mL in RLMs. The intra- and inter-day precision and accuracy ranged from 0.95 to 1.49 and - 5.22 to 1.13%, respectively in RLMs. Rate of disappearance of MST during incubation with RLMs was almost linear allover incubation time. In vitro t 1/2 was 50.38 min and CL in was 3.11 ± 0.2. The developed method was applied also to measure the rate of masitinib excretion in rat urine. The method can used for further pharmacokinetic studies of MST.

Background: Chronic alcohol abuse, a major risk factor for such diseases as hepatitis and cirrhosis, impairs hepatic alcohol dehydrogenase (ADH; key ethanol [EtOH]-metabolizing enzyme). Therefore, differentially altered hepatic and plasma proteomes were identified in chronic EtOH feeding model of hepatic ADH-deficient (ADH - ) deer mice to understand the metabolic basis of alcoholic liver disease (ALD)., Methods: ADH - deer mice were fed 3.5 g% EtOH via Lieber-DeCarli liquid diet daily for 3 months and histology of the liver assessed. Liver and plasma proteins were separated by 2-dimensional gel electrophoresis. The proteins differentially expressed were identified by matrix-assisted laser desorption ionization-time of flight mass spectrometry., Results: Histology of the liver showed panlobular steatosis and infiltration of T lymphocytes. Using the criteria of ≥1.5 for fold change (p-value ≤0.05) with expectation value (E ≤10 -3 ) and protein score (≥64), 18 proteins in the livers and 5 in the plasma of EtOH-fed mice were differentially expressed and identified. Prolyl 4-hydroxylase, cytochrome b-5, endo A cytokeratin, ATP synthase, heat-shock 70 kD proteins, enoyl CoA hydratase, stress-70 protein, peroxiredoxin 1, and ornithine carbamoyl transferase were up-regulated in the livers. However, carbonic anhydrase 3, mitochondrial ATP synthase, aldolase 2, actin γ, laminin receptor, and carbamoyl phosphate synthase were down-regulated. Contrary to the increased expression of creatine kinase M-type, a decreased expression of serine protease inhibitor A3A precursor, sulfated glycoprotein-2 (clusterin), and apolipoprotein E isoforms were found in the plasma of EtOH group., Conclusions: Chronic EtOH feeding in ADH - deer mice causes steatosis and infiltration of T lymphocytes in the livers along with increased expression of proteins involved in endoplasmic reticulum (ER) stress, fibrosis, fatty acid β oxidation and biogenesis, and decreased expression of proteins involved in ATP synthesis, carbohydrate metabolism, in cell regulation and architecture. Reduced expression of various carrier proteins as found in the plasma of EtOH group has a biomarker potential., (Copyright © 2017 by the Research Society on Alcoholism.)

Objectives: The aim of this study was to identify differentially expressed proteins in the pancreatic tissue of hepatic alcohol dehydrogenase-deficient deer mice fed ethanol to understand metabolic basis and mechanism of alcoholic chronic pancreatitis., Methods: Mice were fed liquid diet containing 3.5 g% ethanol daily for 3 months, and differentially expressed pancreatic proteins were identified by protein separation using 2-dimensional gel electrophoresis and identification by mass spectrometry., Results: Nineteen differentially expressed proteins were identified by applying criteria established for protein identification in proteomics. An increased abundance was found for ribosome-binding protein 1, 60S ribosomal protein L31-like isoform 1, histone 4, calcium, and adenosine triphosphate (ATP) binding proteins and the proteins involved in antiapoptotic processes and endoplasmic reticulum function, stress, and/or homeostasis. Low abundance was found for endoA cytokeratin, 40S ribosomal protein SA, amylase 2b isoform precursor, serum albumin, and ATP synthase subunit β and the proteins involved in cell motility, structure, and conformation., Conclusions: Chronic ethanol feeding in alcohol dehydrogenase-deficient deer mice differentially expresses pancreatic functional and structural proteins, which can be used to develop biomarker(s) of alcoholic chronic pancreatitis, particularly amylase 2b precursor, and 60 kDa heat shock protein and those involved in ATP synthesis and blood osmotic pressure.

Vandetanib (VNT) is a new oral tyrosine kinase inhibitor that acts mainly by inhibiting vascular endothelial growth factor receptor (VEGFR). Fast, specific, sensitive and validated LC-MS/MS was established for the determination of VNT in two various matrices including rat liver microsomes (RLMs) and human plasma. This method was applied in metabolic stability investigation of VNT. Resolution of two analytes was performed using C18 column and isocratic mobile phase composed of binary system of 10 mM ammonium formate (pH 4.1) and acetonitrile in a ratio of 1:1. The flow rate was set at 0.25 mL/min and total run time was 4 min with injection volume of 5 µL. Ions were generated by ESI source and analyzed by multiple reaction monitoring mode (basis for quantification) in the Agilent 6410 QqQ analyzer. The linearity of the established method ranged from 5 to 500 ng/mL (r 2  ≥ 0.9996) in human plasma and RLMs. LOQ and LOD were 2.48 and 7.52 ng/mL, and 2.14 and 6.49 in human plasma and RLMs matrices. The intra-day and inter-day precision and accuracy were 0.66-2.66% and 95.05-99.17% in human plasma matrix while in RLMs matrix, ranged from 0.97 to 3.08% and 95.8 to 100.09%, respectively. In vitro half-life was 39.85 min and intrinsic clearance was 3.92 ± 0.28 mL/min/kg.

Context: - Facebook (Menlo Park, California) is one of many online sites that provide potential educational tools for pathologists. We have each founded Facebook groups dedicated to anatomic pathology, in which members can share cases, ask questions, and contribute to discussions., Objectives: - To report our experiences in founding and maintaining these Facebook groups and to characterize the contributed content., Design: - We circulated a survey among the group founders, then compiled and analyzed the responses., Results: - The groups varied in membership and in the quality of member contribution. Most posts were of pathology cases, although other topics (such as research articles) were also shared. All groups remained active and received posts from users all over the world, although all groups had many noncontributing members and received unwanted messages (which were screened and removed). Most founders were glad they had founded the groups because they provided an opportunity to both teach and learn., Conclusions: - Each analyzed Facebook group had a different character, and some downsides exist, but the groups all provided a no-cost way for pathologists and others across the world to interact online with many colleagues.

In the current work, a rapid, specific, sensitive and validated liquid chromatography tandem mass-spectrometric method was developed for the quantification of ponatinib (PNT) in human plasma and rat liver microsomes (RLMs) with its application to metabolic stability. Chromatographic separation of PNT and vandetanib (IS) were accomplished on Agilent eclipse plus C18 analytical column (50 mm × 2.1 mm, 1.8 μm particle size) maintained at 21±2°C. Flow rate was 0.25 mLmin-1 with run time of 4 min. Mobile phase consisted of solvent A (10 mM ammonium formate, pH adjusted to 4.1 with formic acid) and solvent B (acetonitrile). Ions were generated by electrospray (ESI) and multiple reaction monitoring (MRM) was used as basis for quantification. The results revealed a linear calibration curve in the range of 5-400 ngmL-1 (r2 ≥ 0.9998) with lower limit of quantification (LOQ) and lower limit of detection (LOD) of 4.66 and 1.53 ngmL-1 in plasma, 4.19 and 1.38 ngmL-1 in RLMs. The intra- and inter-day precision and accuracy in plasma ranged from1.06 to 2.54% and -1.48 to -0.17, respectively. Whereas in RLMs ranged from 0.97 to 2.31% and -1.65 to -0.3%. The developed procedure was applied for quantification of PNT in human plasma and RLMs for study metabolic stability of PNT. PNT disappeared rapidly in the 1st 10 minutes of RLM incubation and the disappearance plateaued out for the rest of the incubation. In vitro half-life (t1/2) was 6.26 min and intrinsic clearance (CLin) was 15.182± 0.477., Competing Interests: The authors have declared that no competing interests exist.

Spectral resolution of cefquinome sulfate (CFQ) in the presence of its degradation products was studied. Three selective, accurate and rapid spectrophotometric methods were performed for the determination of CFQ in the presence of either its hydrolytic, oxidative or photo-degradation products. The proposed ratio difference, derivative ratio and mean centering are ratio manipulating spectrophotometric methods that were satisfactorily applied for selective determination of CFQ within linear range of 5.0-40.0 μg mL(-1). Concentration Residuals Augmented Classical Least Squares was applied and evaluated for the determination of the cited drug in the presence of its all degradation products. Traditional Partial Least Squares regression was also applied and benchmarked against the proposed advanced multivariate calibration. Experimentally designed 25 synthetic mixtures of three factors at five levels were used to calibrate and validate the multivariate models. Advanced chemometrics succeeded in quantitative and qualitative analyses of CFQ along with its hydrolytic, oxidative and photo-degradation products. The proposed methods were applied successfully for different pharmaceutical formulations analyses. These developed methods were simple and cost-effective compared with the manufacturer's RP-HPLC method., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Two novel cefquinome sulfate (CFQ)-selective electrodes were performed with dibutyl sebacate as a plasticizer using a polymeric matrix of polyvinyl chloride. Sensor 1 was prepared using sodium tetraphenylborate as a cation exchanger without incorporation of ionophore, whereas 2-hydroxy propyl β-cyclodextrin was used as ionophore in sensor 2. A stable, reliable, and linear response was obtained in concentration ranges 3.2 × 10(-5) to 1 × 10(-2) mol/L and 1 × 10(-5) to 1 × 10(-2) mol/L for sensors 1 and 2, respectively. Both sensors could be sufficiently applied for quantitative determination of CFQ in the presence of degradation products either in bulk powder or in pharmaceutical formulations. Sensor 2 provided better selectivity and sensitivity, wider linearity range, and higher performance. Therefore it was used successfully for accurate determination of CFQ in biological fluids such as spiked plasma and milk samples. Furthermore, an online kinetic study was applied to the CFQ alkaline degradation process to estimate the reaction rate and half-life with feasible real-time monitoring. The developed sensors were found to be fast, accurate, sensitive, and precise compared with the manufacturer's reversed-phase chromatographic method.

Background: Surgery is the corner stone for the management of rectal cancer. The purpose of this study was to demonstrate the optimal time of surgical resection after the completion of neoadjuvant chemo-radiotherapy (CRT) in treatment of locally advanced rectal cancer., Materials and Methods: This study compared 2 groups of patients with locally advanced rectal cancer, treated with neoadjuvant CRT followed by surgical resection either 6-8 weeks or 9-14 weeks after the completion of chemo-radiotherapy. The impact of delaying surgery was tested in comparison to early surgical resection after completion of chemo-radiotherapy., Results: The total significant response rate that could result in functional preservation was estimated to be 3.85% in group I and 15.4% in group II. Some 9.62% of our patients had residual malignant cells at one cm surgical margin. All those patients with positive margins at one cm were in group I (19.23%). There was less operative time in group II, but the difference between both groups was statistically insignificant (P=0.845). The difference between both groups regarding operative blood loss and intra operative blood transfusion was significantly less in group II (P=0.044). There was no statistically significant difference between both groups regarding the intra operative complications (P=0.609). The current study showed significantly less post-operative hospital stay period, and less post-operative wound infection in group II (P=0.012 and 0.017). The current study showed more tumor regression and necrosis in group II with a highly significant main effect of time F=61.7 (P<0.001). Pathological TN stage indicated better pathological tumor response in group II (P=0.04). The current study showed recurrence free survival for all cases at 18 months of 84.2%. In group I, survival rate at the same duration was 73.8%, however none of group II cases had local recurrence (censored) (P=0.031). Disease free survival (DFS) during the same duration (18 months) was 69.4 % for patients in group I and 82.3% for group II (P=0.429)., Conclusions: Surgical resection delay up to 9-14 weeks after chemo-radiation was associated with better outcome and better recurrence free survival.

Two novel simple, specific, accurate and precise spectrophotometric methods manipulating ratio spectra are developed and validated for simultaneous determination of Esomeprazole magnesium trihydrate (ESO) and Naproxen (NAP) namely; absorbance subtraction and ratio difference. The results were compared to that of the conventional spectrophotometric methods namely; dual wavelength and isoabsorptive point coupled with first derivative of ratio spectra and derivative ratio. The suggested methods were validated in compliance with the ICH guidelines and were successfully applied for determination of ESO and NAP in their laboratory prepared mixtures and pharmaceutical preparation. No preliminary separation steps are required for the proposed spectrophotometeric procedures. The statistical comparison showed that there is no significant difference between the proposed methods and the reported method with respect to both accuracy and precision., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background and Objectives: Second-hand smoke (SHS) is an important public health problem worldwide. The study aimed to estimate the prevalence of SHS exposure and its associated risk factors among intermediate and secondary school students., Methods: A cross-sectional study was conducted in 2013 among 3400 students from 34 intermediate and secondary schools in Madinah City, Saudi Arabia. Data about sociodemographic and smoking-related factors and SHS exposure were collected using a self-administered questionnaire., Results: Of the 3210 students analyzed, the prevalence of SHS exposure was 32.7% 49.3%, and 25% inside, outside, and both inside and outside the home, respectively. The highest risk of SHS exposure was associated with the adolescent's smoking status, parental smoking, close friends smoking, and family structure. The risk was markedly increased in association with parental smoking for exposure inside the home (OR = 6.49; 95% CI = 5.44-7.73) and with close friends smoking for exposure outside the home (OR = 4.16; 95% CI = 3.54-4.77). The risk of SHS, however, was lower among adolescents having knowledge about smoking and highly educated parents., Conclusion: The study revealed a considerably high prevalence of SHS both inside and outside the home among adolescents. Knowledge and beliefs about SHS exposure are the main preventable approach.

Background: BRCA1 promoter methylation has been detected in DNA from peripheral blood cells of both breast cancer patients and cancer-free females. However, the pathological significance of this epigenetic change in white blood cells (WBC) remains an open question. In this study, we hypothesized that if constitutional BRCA1 methylation reflects an elevated risk for developing breast cancer (BC), WBC that harbor methylated BRCA1 in both cancer-free females and BC patients should exhibit similar molecular changes., Methods: BRCA1 promoter methylation was examined by methylation-specific PCR in WBC from 155 breast cancer patients and 143 cancer-free females. The Human Breast Cancer EpiTect Methyl II Signature PCR Array and The Human Breast Cancer RT2 Profiler™ PCR Array were used to study the methylation status and the expression profile of several breast cancer-related genes, respectively. In addition, we used label-free MS-based technique to study protein expression in plasma., Results: We have shown that 14.2% of BC patients and 9.1% of cancer-free females (carriers) harbored methylated BRCA1 promoter in their WBC. Interestingly, 66.7% of patients harbored methylated BRCA1 promoter in both WBC and tumors. Importantly, we have shown the presence of epigenetic changes in 9 other BC-related genes in WBC of both patients and carriers. Additionally, BRCA1 and 15 other important cancer -related genes were found to be differentially expressed in WBC from patients and carriers as compared to controls. Furthermore, we have shown that the carriers exhibited a unique plasma protein pattern different from those of BC patients and controls, with 10 proteins similarly differentially expressed in patients and carriers as compared to controls., Conclusions: The present results suggest the presence of a strong link between aberrant methylation of the BRCA1 promoter in WBC and breast cancer -related molecular changes, which indicate the potential predisposition of the carriers for developing breast cancer. This informs the potential use of the aberrant methylation of BRCA1 promoter in WBC as a powerful non-invasive molecular marker for detecting predisposed individuals at a very early age.

Background: Breast cancer (BC) is the most common malignancy and the leading cause of cancer-related death amongst women worldwide. The risk factors of this disease are numerous, and their prevalence varies between racial and ethnic groups as well as geographical regions. Therefore, we sought to delineate the association of socio-demographic, reproductive and life-style related risk factors with breast cancer in the Arab population., Methods: Unmatched case-control study was conducted in the kingdom of Saudi Arabia using 534 cases of histologically confirmed breast cancer and 638 controls. Controls were randomly selected from primary health care visits and were free of breast cancer. Unconditional logistic regression analysis was performed to estimate odds ratios (ORs) and to examine the predictive effect of each factor on risk for BC. All study participants were interviewed by trained interviewers at hospital (cases) or at primary health care centers (controls)., Results: A total of 1172 women were eligible for this study, of which 281 (24.0%) were aged ≤35 years, 22.9% illiterate, 43.6% employed, 89.5% married, and 38.1% were obese. Grade III tumors constituted 38.4% of cases. Tumor stage I was 7.5%; II, 50.7%; II, 30.9%; IV, 11.1%. We have shown strong association between breast cancer among Arab females and obesity (OR =2.29, 95% CI 1.68-3.13), positive family history of breast cancer (OR =2.31, 95% CI 1.60 - 3.32), the use of hormonal replacement therapy (OR =2.25, 95% CI 1.65 - 3.08), post-menopause (OR =1.72, 95% CI 1.25 - 2.38), lack of education (OR =9.09, 95% CI 5.88 - 14.29), and never breastfeed (OR =1.89, 95% CI 1.19 - 2.94)., Conclusion: These results indicate the presence of classical risk factors established in the western countries, and also some specific ones, which may result from genetic and/or environmental factors. Thereby, these findings will be of great value to establish adequate evidence-based awareness and preventative measures in the Arab world.