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Background: Intestinal coccidiosis is a debilitating disease in poultry and livestock, leading to economic impact worldwide. Coccidiosis is prevented and treated in broilers by the inclusion of anticoccidials in feed. Toltrazuril is administered in potable water to treat coccidiosis., Objective: Three robust analytical methods for the quantitation of toltrazuril in pure and pharmaceutical formulations are developed. Furthermore, ecological metrics, either penalization- or color-code-based techniques, are applied for the appraisal of assays., Methods: First, second-derivative (Δλ; 5 nm) spectrophotometric method is used. Toltrazuril is measured from peak to peak at 244-260 nm within a linearity range of 5-25 μg/mL. The second method is an HPTLC analysis performed on an aluminum sheet of silica gel using ethyl acetate-methanol-ammonium chloride buffer-water (8:1:0.5:0.5, by volume respectively) as the elution phase. Toltrazuril, at a retardation factor of 0.66 ± 0.01, is linearly determined in the range of 1-9 μg/spot at 243 nm. The third method is reversed-phase HPLC with diode array detection, using an Agilent C18 column (5 μm, 4.6 × 150 mm) in isocratic elution mode at 1 mL/min flow rate with a mobile phase of acetonitrile and water in a ratio of 80:20 (v/v). Toltrazuril elutes at a retention time of 2.58 ± 0.1 min and is linearly determined at 243 nm in the range of 0.25-25 μg/mL., Results: Calculated 2D-values and peak areas are highly correlated to their corresponding drug concentrations at coefficients: r > 0.999. All methods were International Council of Harmonization (ICH) validated and applied to the dosage form with satisfactory % recoveries (97-103%). Statistical comparisons versus reported one using t-test and F-test disclose insignificant variation. In examining greenness and whiteness norms, the proposed methods were evaluated and ranked alongside four different reported methods., Conclusions: The proposed methods are green, accurate, and can be applied in routine QC for the determination of toltrazuril in pharmaceutical formulations., Highlights: Intestinal coccidiosis substantially affects the chicken intestinal tract leading to reduced growth. Toltrazuril is used for the treatment and prevention of intestinal coccidiosis. Three robust, accurate, and precise analytical methods are developed for toltrazuril determination in pure and pharmaceutical formulations. All proposed methods were ecologically assessed and compared with published ones., (© The Author(s) 2024. Published by Oxford University Press on behalf of AOAC INTERNATIONAL. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: An eConsult is a growing teledermatology tool that has the potential to address health disparities. Trends in teledermatology usage are still being defined in the context of the pandemic, postpandemic recovery, and a growing nonphysician primary care provider population. Objective: The aim was to understand teledermatology utilization trends for asynchronous dermatology eConsults in the geographically expansive state of Texas. Methods: This multicenter retrospective study examined the eConsult tool within a large, nonprofit health system, comparing characteristics of 893 eConsult visits with 27,189 in-person dermatology encounters from January 2022 to March 2023. Results: When comparing the demographics of patients seen through eConsult versus traditional in-person visits, eConsults demonstrated a significantly higher prevalence of pediatric (22.5% vs. 7.6%, p < 0.001), Hispanic/Latino (20.5% vs. 10.4%, p < 0.001), African American (12.5% vs. 6.9%, p < 0.001), Asian (4.6% vs. 2.1%, p < 0.001), and American Indian (1.0% vs. 0.5%, p  = 0.049) patients compared with in-person visits. eConsult users came from areas with a lower percentage of bachelor's degree holders, reduced average household income, and an increased proportion of Medicaid and Tricare users. Physicians (MD/DO) submitted more eConsult cases than nonphysician providers (NPPs), with comparable diagnostic agreement with teledermatologists and similar recommendation rates for in-person dermatology visits. Conclusions: While the limitation of this study was that it was a descriptive data analysis in a single health care system with limited generalizability, eConsults hold promise to broaden dermatologic access for underserved groups, especially children, individuals from underrepresented backgrounds, and Medicaid and Tricare members. While no significant diagnostic or referral differences were seen for eConsults initiated by primary care physician and NPPs, these changing trends should continue to be examined.

Sustainable analytical chemistry is gaining great interest in global environmental pollution control. In addition, valsartan (VAS) and sacubitril (SAB) have been recently approved by the FDA as a fixed-dose combination "LCZ696". It showed efficacy and safety enough to extend its application from heart failure to hypertension control. VAS/SAB dual therapy is considered expensive; however, its prescription has increased significantly worldwide. This prescription increased the demand for developing sustainable analytical methods that simultaneously analyze VAS and SAB. Highly sensitive and selective spectrofluorimetric methods have been developed for this purpose. A synchronous spectrofluorimetric technique was applied. In one method, it was followed by spectral derivatization at the first-order level. The signals were recorded at 230 and 211 nm for VAS and SAB, respectively. Synchronous spectrofluorimetry was coupled to a dual-wavelength mathematical approach in the second method. Signals were derived by subtracting synchronous responses at 241 nm, 226 nm, and 239 nm from the response at 208 nm for VAS and SAB, respectively. Method validation was carried out following ICH guidelines. VAS showed linear calibration curves spanning the range of 60-200 and 80-600 ng mL -1 for the derivative and dual wavelength-assisted approaches, respectively. SAB achieved linear responses in the range of 17-190 and 30-350 ng mL -1 for the first and second methods, respectively. The green profile of the proposed methods was confirmed using the analytical eco-scale (AES), green analytical procedure index (GAPI), and analytical greenness metric (AGREE) tools. The proposed hybrid methods proved highly sustainable through the whiteness RGB 12 algorithm evaluation approach. Whiteness was comparatively assessed for the proposed and reported methods based on relative scoring depending on the parameters of each method. Despite this scoring approach being accurate as a relative score for comparative purposes, it gave rise to underestimated absolute scores. Therefore, to obtain a proper conclusion from the comparative whiteness study, all the methods were ranked according to their whiteness score, illustrating the excellent whiteness ranks of the proposed methods. Upon complete comparison with the reported methods, the suggested ones showed several advantages concerning analytical performance and the greenness level. The proven affordability and simplicity encourage their wide industrial application in developing countries., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Background: The global financial market is still highly threatened by bovine fasciolosis, a parasitic infection that targets cattle, mainly in tropical regions. Binary combination of ivermectin (IVER) and clorsulon (CLO), in challenging concentration ratios, is typically indicated for treatment and control of fasciolosis., Objective: The present study aims at smart simultaneous spectrophotometric assay of both compounds at their high ratio in marketed formulation and synthetic mixtures, without any prior separation. Furthermore, their greenness profile was evaluated and compared with previous reported assay methods, including the official one., Methods: Mathematical-based proposed methods are the dual-wavelength, induced dual-wavelength, and first derivative ratio methods. Each is developed, optimized, and applied to determine simultaneously IVER and CLO at linear ranges of 1-30 and 5-40 μg/mL, respectively. They have been validated according to ICH guidelines. Statistical Student t-tests and F-tests compared the proposed methods with a USP chromatographic technique. Ecological appraisal is accomplished using three independent metrics: Analytical Eco-Scale (AES), Green Analytical Procedure Index (GAPI), and Analytical GREEnness Metric Approach (AGREE)., Results: Satisfactory recoveries, ICH compliance, and adherence of proposed methods to the ecological safety margin are achieved., Conclusions: Developed methods are eco-friendly and cost-effective and can accomplish a routine quantitative quality control for concurrent determination of both drugs., Highlights: Veterinary antimicrobials need analytical quality control using safer and green methodologies. Data manipulated spectral analyses of IVER and CLO, in a ratio of 1:10% (v/v), are developed and optimized. AES, GAPI, and AGREE approaches illustrate the high green compliance in respect to assays reported in the literature. Furthermore, the United States Pharmacopeia (USP) assay for IVER and CLO in injectable dosage form depends on analysis of each drug separately in the presence of the other drug, but it cannot determine both drugs simultaneously., (© The Author(s) 2023. Published by Oxford University Press on behalf of AOAC INTERNATIONAL. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Hepatocellular Carcinoma (HCC) is a malignancy with increasing incidence and morbidity. For patients with a poor prognosis, engagement with advanced care planning and end-of life (EOL) services (I.e., palliative care, hospice) can address physical, financial, and social complications of a terminal diagnosis. Minimal data exist on the demographics of the patients being referred to and enrolling in EOL services for HCC., Aims: We aim to report the relationship between demographics and EOL service referral., Methods: Retrospective review of a prospectively maintained high-volume liver center registry of patients diagnosed with HCC from 2004 to 2022. EOL services eligible patients were defined as BCLC stage C or D, evidence of metastases, and/or transplant ineligible., Results: Black patients were more likely to be referred than white patients (OR 1.47 (1.03, 2.11)). Once referred, patients were significantly more likely to be enrolled if they had insurance coverage, though no other factors in models were significant. There were no significant differences in survival among those referred who did or did not enroll, after controlling for other factors., Conclusion: Black patients were more likely to be referred compared to white patients and patients who were insured were more likely to be enrolled. Whether this is indicative of black patients being appropriately referred at a higher rate, being offered EOL care instead of aggressive treatment, or other unknown factors warrants further study., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The primary objectives of green chemistry are the reduction of generation and use of hazardous substances. In healthcare, the most active areas of research in green chemistry are medication manufacturing and analysis. Analysts take serious steps for converting traditional analytical methods to eco-friendly ones that minimize the negative effects of solvents and chemicals on the environment and improve the healthcare. In the proposed work, two analytical methods are presented for the quantification of Finasteride (FIN) and Tadalafil (TAD) simultaneously in newly launched FDA-approved dosage form without prior separation. The first method is derivative spectrophotometry, which is based on measuring the amplitudes of first derivative spectrophotometric peaks of FIN and TAD in ethanolic solution at 221 nm and 293 nm, respectively. On the other hand, measuring the peak-to-peak amplitudes of second derivative spectrum of TAD solution at 291-299 nm was also performed. Regression equations show good linearity for FIN and TAD in the ranges of 10-60 μg mL -1 and 5-50 μg mL -1 , respectively. The second method is the RP-HPLC method, where the chromatographic separation was achieved using the XBridgeTM C18 (150 × 4.6 mm, 5 μm) column. The eluent was the mixture of acetonitrile:phosphate buffer with triethylamine, 1% (v/v) adjusted to pH = 7 in the ratio of 50 : 50 (by volume). The flow rate was 1.0 mL min -1 with DAD-detection at 225 nm. This analytical procedure was linear over the ranges of 10-60 μg mL -1 and 2.5-40 μg mL -1 for FIN and TAD, respectively. The presented methods were validated (regarding ICH guidelines) and statistically compared by applying the t -test and F -test with the reported method. The greenness appraisal was performed using three different tools. The proposed validated methods were found to be green, sensitive, selective, and can be successfully used for quality control test., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Background: Carbon dots, CDs, have excellent photoluminescence properties, good biocompatibility, low toxicity and good light stability. The optical, magnetic and electronic properties of CDs make them a hugely relevant tool to be used in pharmaceutical analysis, bioimaging, drug delivery, and other fields. The fluorescence of carbon nanodots makes it suitable for assay of some nitrogenous compounds of high pharmaceutical interest. In this work, we develop simple, fast and green spectrophotometric methods for quantification of Azithromycin and Rasagiline mesilate using synthesized fluorescent CDs from garlic peels., Results: The spectrometric methods depend on stoichiometric reactions of both drugs with fluorescent CDs. Carbon dots exhibit a declared absorption peak λ max at 238 nm and potent fluorimetric emission at λ em 528 nm, upon excitation at λ ex 376 nm. Drugs' concentrations in ppm are efficiently calculated using Stern-Volmer Equation. Decrease in fluorescence (Δ F  =  F o  -  F ) and the F -ratio values are linearly correlated to molar concentration of each quencher (drug). A significant linear diminish in the dots' measured absorbance and fluorimetric emission values was observed. Validation of all the developed methods was according to the ICH guidelines., Conclusions: In a new way, this work successfully indicates, spectrometric methods for rapid detection of two non-fluorophoric nitrogenous compounds using potent carbon nanodots. Consequently, these green developed methods offer several benefits as simplicity, ease of quantification, accuracy and precision that encourage the application of the developed methods in routine analysis of Azithromycin and Rasagiline mesilate in quality control laboratories as analytical tool., Supplementary Information: The online version contains supplementary material available at 10.1186/s43088-023-00346-z., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s) 2023.)

Background and Objectives : Mortality and illness due to COVID-19 have been linked to a condition known as cytokine release syndrome (CRS) that is characterized by excessive production of inflammatory cytokines, particularly interleukin-6 (IL-6). Tocilizumab (TCZ), a recent IL-6 antagonist, has been redeployed as adjunctive treatment for CRS remission in COVID-19 patients. This study aimed to determine the efficacy of Tocilizumab on patients' survival and the length of stay in hospitalized COVID-19 patients admitted to the intensive care unit. Methods : Between January 2021 and June 2021, a multicenter retrospective cohort study was carried out in six tertiary care hospitals in Egypt's governorate of Giza. Based on the use of TCZ during ICU stay, eligible patients were divided into two groups (control vs. TCZ). In-hospital mortality was the main outcome. Results : A total of 740 patient data records were included in the analysis, where 630 patients followed the routine COVID-19 protocol, while 110 patients received TCZ, need to different respiratory support after hospitalization, and inflammatory mediators such as C-reactive protein (CRP), ferritin, and Lactate dehydrogenase (LDH) showed a statistically significant difference between the TCZ group and the control group. Regarding the primary outcome (discharged alive or death) and neither the secondary outcome (length of hospital stay), there is no statistically significant difference between patients treated with TCZ and the control group. Conclusions : Our cohort of patients with moderate to severe COVID-19 did not assert a reduction in the risk of mortality or the length of stay (LOS) after TCZ administration.

Background: E-cadherin is a classic cadherin that mediates keratinocyte adhesion., Aims: To assess the tissue expression of E-cadherin and its proteolytic serum fragment (soluble E-cadherin) in pemphigus vulgaris (PV) before and after clinical remission compared with controls., Patients: Thirty-seven PV patients and thirty controls were enrolled. Pemphigus disease area index (PDAI) was calculated for patients at baseline and after remission. Punch biopsy specimens were taken from patients before, and after remission, and from controls for assessment of tissue E-cadherin by immunofluorescence. Similarly, serum samples were collected for assessment of serum soluble E-cadherin by ELISA., Results: Presence, intensity, and mean intensity of tissue E-cadherin were significantly reduced in PV patients before treatment compared with controls (p < 0.001). Detected E-cadherin showed mainly a basal and suprabasal distribution with cell surface and a cytoplasmic expression. Serum E-cadherin was significantly higher in patients before treatment compared with controls (p = 0.006). With remission, tissue E-cadherin presence, intensity, mean intensity, and serum E-cadherin showed statistically significant improvement (p = 0.003, <0.001, <0.001, and 0.003 respectively). Tissue E-cadherin presence and serum E-cadherin level reached values equivalent to the controls (p = 0.49 and 0.44, respectively)., Conclusions: Disruption of tissue E-cadherin and upregulation of serum soluble E-cadherin can contribute to the pathogenesis of PV. Clinical remission of PV is associated with normalization of tissue and serum E-cadherin., (© 2022 Wiley Periodicals LLC.)

A simple, sensitive and rapid RP-HPLC method is presented, for the first time, for the simultaneous determination of moxifloxacin hydrochloride and metronidazole in different biological fluids including saliva and plasma without any matrix interference. The separation was performed using ACN and phosphate buffer (30 : 70% v/v) as the mobile phase on a Zorbax Eclipse Plus-C18 column attached to a guard column. The method was validated according to the FDA guidelines for bioanalytical method validation and was successfully applied for simultaneous determination of the studied drugs in saliva and plasma samples. The good precision and selectivity of the developed method allow it to be used for routine therapeutic drug monitoring of such drugs and it presents a simple and sensitive analytical tool for performing versatile pharmacokinetics and bioavailability studies. A DAD detector is valuable to determine each drug at its maximum wavelength to ensure high sensitivity. Determination of such a combination in saliva introduces a quick and non-invasive alternative to blood analysis., Competing Interests: There are no conflicts of interest to declare., (This journal is © The Royal Society of Chemistry.)

Objective: To determine whether the apparent excess incidence of pneumothorax and pneumomediastinum in patients with coronavirus disease 2019 (COVID-19) is explained adequately by iatrogenic causes vs reflecting sequelae of severe acute respiratory syndrome coronavirus 2 infection., Patients and Methods: We retrospectively reviewed patients within our health care system from March 15, 2020, through May 31, 2020, who had a diagnosis of pneumothorax or pneumomediastinum during hospitalization for confirmed COVID-19 infection with attention to timing of pneumothorax and pneumomediastinum; presence, laterality, and placement, or attempts at central lines; and presence of mechanical ventilation before the event., Results: We report clinical data and outcomes from 9 hospitalized patients with COVID-19 who developed pneumothorax and/or pneumomediastinum among more than 1200 hospitalized patients admitted within our hospital system early in the pandemic. Many events were inexplicable by iatrogenic needle injury, including 1 spontaneous case without central line access or mechanical ventilation. One occurred before central line placement, 2 in patients with only a peripherally inserted central line, and 1 contralateral to a classic central line. Three of these 9 patients died of complications of COVID-19 during their hospital stay., Conclusion: With COVID-19 affecting the peripheral lung pneumocytes, patients are vulnerable to develop pneumothorax or pneumomediastinum irrespective of their central line access site. We hypothesize that COVID-19 hyperinflammation, coupled with the viral tropism that includes avid involvement of peripheral lung pneumocytes, induces a predisposition to peripheral bronchoalveolar communication and consequent viral hyperinflammatory-triggered pneumothorax and pneumomediastinum., (© 2021 [Author/Employing Institution].)

A hybrid Spectrofluorimetric method was developed for the simultaneous determination of binary mixtures, without prior separation steps. It coupled synchronous spectrofluorimetry with derivative ratio mathematical treatment. The method was applied successfully to quantify a new model binary mixture consisting of Valsartan (VAL) and Sacubitril (SAC). This mixture was recently approved by FDA as LCZ696. It added a great value in reducing morbidity and mortality in resistant heart failure (HF) patients. First derivative ratio synchronous fluorescence was measured at 258-295 (peak-to-peak) and 204 nm for VAL and SAC, respectively. ICH guidelines were fulfilled for the method validation. VAL and SAC showed linear responses in the range of 60-200 and 20-200 ng mL -1 , respectively. The proposed method was compared, in details, with the reported ones. Its high accuracy, selectivity, simplicity and affordable cost recommend method application in large-scale routine analysis of LCZ696 tablets. Moreover, reliable application of this new integrated spectrofluorimetric method suggests expansion of its application for various therapeutic combinations and different matrices., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The global severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic leading to coronavirus disease 2019 (COVID-19) is straining hospitals. Judicious resource allocation is paramount but difficult due to the unpredictable disease course. Once hospitalized, discerning which patients may progress to critical disease would be valuable for resource planning. Medical records were reviewed for consecutive hospitalized patients with COVID-19 in a large healthcare system in Texas. The main outcome was progression to critical disease within 10 days from admission. Albumin trends from admission to 7 days were analyzed using mixed-effects models, and progression to critical disease was modeled by multivariable logistic regression of laboratory results. Risk models were evaluated in an independent group. Of 153 non-critical patients, 28 (18%) progressed to critical disease. The rate of decrease in mean baseline-corrected ( Δ ) albumin was -0.08 g/dL/day (95% CI -0.11 to -0.04; p<0.001) or four times faster, in those who progressed compared with those who did not progress. A model of Δ albumin combined with lymphocyte percentage predicting progression to critical disease was validated in 60 separate patients (sensitivity, 0.70; specificity, 0.74). ALLY (delta albumin and l y mphocyte percentage) is a simple tool to identify patients with COVID-19 at higher risk of disease progression when: (1) a 0.9 g/dL or greater albumin drop from baseline within 5 days of admission or (2) baseline lymphocyte of ≤10% is observed. The ALLY tool identified >70% of hospitalized cases that progressed to critical COVID-19 disease. We recommend prospectively tracking albumin. This is a globally applicable tool for all healthcare systems., Competing Interests: Competing interests: None declared., (© American Federation for Medical Research 2021. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ.)

As an anticoagulant, Edoxaban (EDX) is a high risk drug that may cause a life-threatening bleeding. Also, it is prescribed as a chronic therapy for atrial fibrillation and venous thromboembolism patients. They are special population that needs appropriate care and optimum dosing of EDX. Hence, its monitoring in the patient plasma is fundamental, especially in emergency and special circumstances. However, such patient mostly receives many drugs of different pharmacological classes, side by side with EDX. This study represents the first attempt to quantify EDX in plasma without interference of the plasma matrix or concomitant medications. An accurate RP-HPLC-DAD method was developed for this purpose. It succeeded to monitor EDX level, selectively, without interference of plasma matrix or 16 of its frequently co-administered drugs. All drugs were extracted from plasma samples by protein precipitation followed by evaporation and concentration. EDX was well resolved from the co-administered drugs on C 8 column using linear gradient elution of methanol and phosphate buffer (pH 4), at a flow rate of 1 mL/min. EDX appeared at retention time 9.6 min and was quantified at its λ max (290 nm). It exhibited a linear response over the concentration range of 0.15-2.2 μg/mL plasma which covers the reported therapeutic concentration. The suggested method fulfilled the US FDA guidelines for bioanalytical method validation. The developed method is fully discussed in comparison with the reported techniques. An in vivo study was performed to ensure applicability of the method on real plasma samples without interference from plasma matrix, co-administered drugs or the expected metabolites. It presented a unique selectivity of the method that guarantees accurate laboratory monitoring of EDX in plasma in almost all combined treatments including such novel oral anticoagulant drug., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Green validated spectrophotometric methods are developed for simultaneous determination of Azithromycin (AZI) and Levofloxacin (LEVO) antibiotic mixture. Determination of AZI presents a real analytical challenge as its structure lacks any chromophore, and hence it cannot be determined by direct spectrophotometry. However, the reaction of AZI with perchloric acid produces a green product that can be accurately determined spectrophotometrically. Thus, the work presented demonstrates simple green and sensitive methods for the simultaneous determination of AZI and LEVO mixture. Method I depends on direct measurement of absorbance of azithromycin and levofloxacin in perchloric acid methanolic solution at 482 nm and 224 nm, respectively. While, Method II depends on measuring the first derivative spectrophotometric peak-to-peak amplitudes of AZI and LEVO in perchloric acid methanolic solution at 475-490 nm and 280-253 nm, respectively. Regression analysis shows good linearity for AZI and LEVO over the concentration ranges of 5-50 and 2.5-20 μg/mL for method I and 5-50 and 5-40 μg/mL for method II for AZI and LEVO, respectively. The proposed methods were validated in compliance with ICH guidelines. The suggested procedures are successfully applied for the assay of AZI and LEVO mixture in bulk powder and laboratory-prepared tablets. Greenness profile of the proposed methods were compared with other published methods through applying the Eco-scale protocol. Assessment results demonstrated that the proposed methods are greener than other reported methods. Moreover, upon comparison with other methods, the proposed methods showed better or comparable sensitivity in addition to being selective and rapid with no requirement for laborious extraction techniques. These advantages encourage the application of the proposed methods in routine analysis of AZI and LEVO in quality control laboratories as green and simple analytical tool., (© 2020 Published by Elsevier Ltd.)

Background: Vitamin D deficiency associated with dyslipidemia can contribute towards cardiovascular diseases. Previous studies have found that Saudi Arabia has a high burden of vitamin D deficiency and cardiovascular disease risk factors. We aimed to explore the relationship between vitamin D deficiency and dyslipidemia, including total cholesterol, low-density lipids, high-density lipids (HDL), and triglycerides (TG) in apparently healthy Saudi male and female participants aged 30-75 years., Methods: A cross-sectional study was conducted on 1717 apparently healthy Saudi participants from 18 primary health care centers in Riyadh. Data collectors conducted the interviews, took anthropometric measurements, and collected the blood samples. Serum 25-hydroxyvitamin vitamin D (25(OH)D) levels were measured using an electrochemiluminescence assay method. Lipid panel was measured by a fully automated analyzer using enzymatic methods., Results: Multivariable logistic regression analysis revealed that the adjusted odds ratio (OR A ) of low level of HDL cholesterol in association with 25(OH)D deficiency was 2.1 times higher in males (OR A = 2.1; 95% CI = 1.1, 3.9) and 1.3 times higher in females (OR A = 1.3; 95% CI = 0.9, 1.9). A significant excess odds ratio of high levels of TG in association with 25(OH) D deficiency was observed in females (OR A = 3.0; 95% CI = 1.1, 7.9) but not in males., Conclusion: Vitamin D deficiency is highly prevalent in Saudi Arabia. Low levels of HDL cholesterol in men and high TG levels in women are associated with vitamin D deficiency. The results emphasize the importance of treating vitamin D deficiency in the general population.

Background/objectives: Psoriasis is one of the immune-mediated inflammatory diseases where CD4+ T lymphocytes, mainly Th1 cells, and B lymphocytes contribute in their pathogenesis through a pro-inflammatory effect, production of antibodies, activation of T cells and cytokine synthesis. B and T lymphocyte attenuator (BTLA) is a co-inhibitory molecule expressed on T and B lymphocytes as well as other immune cells, and it is necessary to inhibit homoeostatic expansion and activation of lymph node and skin-resident γδ T cells. BTLA expression is regulated by RORγt and IL-7. The study aimed at adding more insight on the role played by co-inhibitory molecule BTLA in psoriasis vulgaris and its inter-relation with RORγt and IL-7 to establish a basis for novel treatment strategies., Methods: This case-control study included 25 patients and 25 controls examined for gene expression of BTLA, RORγt and IL-7., Results: B and T lymphocyte attenuator was significantly lower in psoriasis patients, whereas both RORγt and IL-7 were higher in comparison with controls. A significant positive correlation between disease severity (PASI) and both RORγt and IL-7 as well as between RORγt and IL-7 was found. A significant negative correlation between BTLA and both RORγt and IL-7 was found. Neither the age nor the duration of disease had any correlation with BTLA, RORγt or IL-7. BTLA had no correlation with PASI. Regarding the control group, a significant negative correlation between RORγt and IL-7 was found., Conclusion: B and T lymphocyte attenuator, RORγt and IL-7 play an important role in psoriasis., (© 2019 The Australasian College of Dermatologists.)

Background: MERS-CoV emerged as a zoonotic disease in Saudi Arabia with 1437 cases as of July 2016. This study aimed at describing the epidemiology of MERS-CoV infection, clinical aspects of the disease and the determinants of survival., Methods: The medical records of Prince Mohamed Bin Abdulaziz Hospital were reviewed between April 2014 and December 2015 to identify admission and discharge with MERS-CoV. Patient's characteristics, epidemiologic and clinical data and laboratory results were extracted and described. Logistic regression analyses were used to model the determinants of the survival of these patients. Significance of the results were judged at the 5% level., Results: 249 confirmed cases were admitted mostly in August (20.48%) and September (14.86%) of the year 2015. A third (39.36%) reported contact with an index case, developed the disease after 6.2days and continued to shed the virus for 13.17days on average. The case fatality rate was 20.08%. Independent predictors of being discharged alive among confirmed cases were younger age (OR A =0.953), breathing ambient air (OR A =8.981), not being transferred to the ICU (OR A =24.240) and not receiving renal replacement therapy (OR A =8.342). These variables explain 63.9% of the variability of patients' status at discharge., Conclusion: MERS-CoV spread from human-to-human as community acquired and nosocomial infection. The study identified high risk patients in need for special medical attention in order to improve patients' outcome., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

High performance liquid chromatographic (HPLC) method with a pre-column derivatization based on Hantzsch condensation reaction was applied for simultaneous determination of alendronate sodium (ALN) and its main related impurity, 4-Aminobutanoic acid (ABA) at its pharmacopeial limit. The separation of colored condensation products of ALN and ABA were achieved on Agilent Zobrax Eclipse SB-C18 analytical column (250 × 4.6 mm, 5 μm) using a mobile phase composed of acetonitrile-0.1 M acetate buffer, pH 5.0 (15:85, v/v). The flow rate was 1 mL min -1 . The detection was carried out at 340 nm using photo-diode array detector. Peak areas were used for the linear regression line in the range of 10-500 and 0.2-40 μg mL -1 for ALN and ABA, respectively. Different conditions for the optimization of the derivatization reactions as well as for the HPLC measurement were studied. The proposed method was validated for linearity, precision, accuracy, specificity and robustness. This method was used to check the purity of ALN in the presence of ABA (related impurity) at the pharmacopeial limit (0.5%). For comparison purpose, another method was proposed which involves synchronous fluorescence measurement after ALN reaction with fluorescamine. In this method, the third derivative synchronous spectra were estimated as peak to peak measurement from 339 to 370 nm for ALN determination with LOD and LOQ of 24 and 73 ng mL -1 , respectively, showing very high sensitivity. Both methods have been applied for determination of the alendronate sodium (ALN) in bulk and pharmaceutical preparations without interference of additives in tablets or oral solution., (Copyright © 2018. Published by Elsevier Taiwan LLC.)

Background: The quality of life (QoL) of children with attention-deficit/hyperactivity disorder (ADHD) has not been addressed in Saudi Arabia despite the considerable attention it has on account of its prevalence, duration of illness, and sociopsychological effects. The aim of this study was to report on the QoL of children with ADHD and test the concord between children's and parents' reports., Materials and Methods: Using the generic PedsQL™ (version 4.0) from both children's and parents' perspectives, a cross-sectional study of 112 children was conducted on children aged 5-18 years with an established diagnosis of ADHD attending child psychiatry clinics of three referral hospitals in Riyadh between December 2015 and May 2016., Results: A total of 112 children with an established diagnosis of ADHD were recruited from the Child Psychiatry Clinic of Al Amal Mental Health Complex (41.1%), Prince Sultan Military Medical City (PSMMC), (33%), and King Khalid University Hospital (KKUH), (25.9%). The majority were boys (74.1%) and Saudi nationals (93.8%). The mean age of children with ADHD was 10.45 ± 3.06 years (Range 5 - 18 years). One-fourth of the mothers of children with ADHD had completed high school and 41.1% had a diploma, university, or postgraduate degree. One-third of the fathers of these children had completed high school (34%) and 38.4% had a diploma, university, or postgraduate degree. The intra-class correlation coefficients between the scores of children and parents were good for physical functioning, fair for social functioning, but moderate for school, emotional, and psychosocial functioning. Children rated themselves significantly better than their parents for emotional, social, school, and psychosocial functioning. The standardized response means indicated a small difference for social functioning and medium differences for the other three domains. The only significant discrepancy was observed in social functioning in relation to the child's age., Conclusion: Parents mirrored adequately the observable physical component of the QoL of their children. The QoL report of children with ADHD with respect to communications and intellectual abilities should be taken into account whenever possible and their parents' report also should be sought to provide a more comprehensive view of the child's status., Competing Interests: There are no conflicts of interest.

Objectives: The objectives of this study were to determine the rate of mobile phones use while driving by the students of King Saud University, Riyadh, Saudi Arabia, their perception of the risks, and contribution to collisions., Materials and Methods: A cross-sectional study was conducted in May 2014 targeting 986 male students of King Saud University, Riyadh, Saudi Arabia. A questionnaire was used to obtain data on possessing a driving license, years of driving experience, driving hours, and collision or near misses in the 6 months preceding the study. Eight statements were used to assess the behavior and perceptions related to the use of mobile phones while driving. Data were analyzed using the Chi-square statistic, odds ratio, and the 95% confidence interval., Results: Almost half of the participants (45.3%) had driving experience of 4-6 years and 18.3% of them did not possess a driving license. Collision in the preceding 6 months was reported by 44.6% of participants, and 37.9% of them attributed these collisions to mobile phones. Variable proportions reported that they always texted (53.3%) or talked on a handheld (66.2%) or hands-free (26.1%) phones while driving. A higher proportion conceded that there were hazards in texting (77.0%) and speaking on handheld mobile phones (83.9%) rather than hands-free (35.9%) while driving. The risk increased significantly from 2.052 among participants who reported that they drove daily for 1-2 h to 3.165 of those who reported that they drove for more than 6 h. No significant risk was observed in relation to participants' perceptions, age, driving experience, and possession of a driving license., Conclusions: There was a risk of collision with the use of handheld and hands-free mobile phones. As hands-free mobile phones are no safer, national legislation should consider restricting their use by drivers and implementing legislations to reinforce safety on the roads. An objective assessment of the contribution of mobile phones to road traffic injuries is recommended., Competing Interests: There are no conflicts of interest.

Around 15-30% of AIDS patients fail to recover their CD4(+) T cell levels following combined antiretroviral therapy despite successful inhibition of HIV-1 replication. The exact reasons for this immune recovery failure are not completely understood. HLA alleles are among the candidate that may explain this failure. A total of 65 adult AIDS patients, with viral load of <50 copies per ml were investigated. Viral load and CD4 T cells counts were performed following standard techniques. HLA genotyping was performed using PCR-SSP technique. The Statistical Package for Social Sciences (SPSS version 19) was used for data processing and analysis. A significantly higher proportion of poor immune responders were carrying HLA-A68 (4.8% compared to 25.0%, P=0.025) and HLA-B15 (2.4% compared to 20.8%, P=0.023). The etiological fraction (Efe%) among carriers of HLA-A68 was 57.89% (95% CI=26.79, 75.79) and was 61.35% (95% CI=35.33, 76.91) among carriers of HLA-B15., (Copyright © 2016 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.)

In the present study, we evaluated the effect of deleting Twist1 on keratinocyte proliferation and on skin tumor development using the two-stage chemical carcinogenesis model. BK5.Cre × Twist1(flox/flox) mice, which have a keratinocyte-specific Twist1 knockout (Twist1 KO), developed significantly reduced numbers of papilloma (70% reduction) and squamous cell carcinoma (75% reduction) as well as delayed tumor latency compared to wild-type (WT) mice. Interestingly, knockdown of Twist1 in primary keratinocytes impeded cell cycle progression at the G1/S transition that coincided with reduced levels of the cell cycle proteins c-Myc, Cyclin E1, and E2F1 and increased levels of p53 and p21. Furthermore, ChIP analyses revealed that Twist1 bound to the promoter regions of Cyclin E1, E2F1, and c-Myc at the canonical E-box binding motif suggesting a direct transcriptional regulation. Further analyses of Twist1 KO mice revealed a significant reduction in the number of label-retaining cells as well as the number of α6-integrin(+) /CD34(+) cells in the hair follicles of untreated mice compared to WT mice. These mice also exhibited significantly reduced epidermal proliferation in response to TPA treatment that again correlated with reduced levels of cell cycle regulators and increased levels of p53 and p21. Finally, Twist1 deficiency in keratinocytes led to an upregulation of p53 via its stabilization and nuclear localization, which is responsible for the increased expression of p21 in these cells. Collectively, these findings indicate that Twist1 has a novel role in epithelial carcinogenesis by regulating proliferation of keratinocytes, including keratinocyte stem cells during tumor promotion., (© 2015 Wiley Periodicals, Inc.)

Plant endo-β-1,4-glucanases (EGases) include cell wall-modifying enzymes that are involved in nematode-induced growth of syncytia (feeding structures) in nematode-infected roots. EGases in the α- and β-subfamilies contain signal peptides and are secreted, whereas those in the γ-subfamily have a membrane-anchoring domain and are not secreted. The Arabidopsis α-EGase At1g48930, designated as AtCel6, is known to be down-regulated by beet cyst nematode (Heterodera schachtii) in Arabidopsis roots, whereas another α-EGase, AtCel2, is up-regulated. Here, we report that the ectopic expression of AtCel6 in soybean roots reduces susceptibility to both soybean cyst nematode (SCN; Heterodera glycines) and root knot nematode (Meloidogyne incognita). Suppression of GmCel7, the soybean homologue of AtCel2, in soybean roots also reduces the susceptibility to SCN. In contrast, in studies on two γ-EGases, both ectopic expression of AtKOR2 in soybean roots and suppression of the soybean homologue of AtKOR3 had no significant effect on SCN parasitism. Our results suggest that secreted α-EGases are likely to be more useful than membrane-bound γ-EGases in the development of an SCN-resistant soybean through gene manipulation. Furthermore, this study provides evidence that Arabidopsis shares molecular events of cyst nematode parasitism with soybean, and confirms the suitability of the Arabidopsis-H. schachtii interaction as a model for the soybean-H. glycines pathosystem., (© 2014 BSPP AND JOHN WILEY & SONS LTD.)

Routine HIV testing of all pregnant women in Oman has been introduced without prior knowledge of women's attitudes towards testing or their behaviour in the event of a positive test. This study recruited 1000 Omani pregnant women from antenatal clinics to explore their knowledge of HIV/AIDS, attitudes towards HIV testing and intended behaviours in the event of a positive test. Mother-to-child transmission was recognized by 86.6% of the women but only 21.0% knew that it was preventable and a few acknowledged the important role of antiviral drugs. Half of the women (51.9%) reported having been tested for HIV and 75.8% agreed about routine HIV testing for all pregnant women. A higher level of knowledge was significantly associated with a favourable intended behaviour related to voluntary testing, disclosure and seeking professional assistance in the event of a positive HIV test. The results are discussed in relation to opt-in and opt-out approaches to voluntary testing during pregnancy.

Two simple methods have been developed and validated for the simultaneous determination of rosiglitazone maleate (ROS) and metformin hydrochloride (MET) in synthetic mixtures and coated tablets in a ratio of 1:250 (ROS:MET). The first method was a spectrophotometric one. The minor component, ROS was determined by measuring the values of absorbance at λmax 312 nm and the D1 amplitudes at 331 nm where MET shows no absorption contribution. However, absorbance interferences from tablet excipients were successfully corrected by D1 at 331 nm zero-crossing technique. Study of spectral interference from tablet excipients was included in the text. Standard curves for Amax and D1 methods were in the concentration range 20.0-80.0 μg mL(-1). The major component, MET was determined both in binary mixtures and tablets by measuring its Amax at 236 nm. Extensive dilution eliminated any absorption contribution from the coexisting ROS or tablet matrix. Standard curves showed linearity in the concentration range 4.0-12.8 μg mL(-1). The second method was based on high performance thin layer chromatography (HPTLC) separation of the two drugs followed by densitometric measurements of their spots at 230 nm. The separation was carried out on Merck HPTLC aluminium sheets of silica gel 60 F254 using methanol:water:NH4Cl 1% w/v (5:4:1 v/v/v) as the mobile phase. Linear calibration graphs of peak area values were obtained versus concentrations in the range of 0.4-2.0 μg band(-1) and 20.0-100.0 μg band(-1) for ROS and MET, respectively. According to International Conference on Harmonisation (ICH) guidelines, different validation parameters were verified for the two methods and presented.

Background: Extensive studies using the model system Arabidopsis thaliana to elucidate plant defense signaling and pathway networks indicate that salicylic acid (SA) is the key hormone triggering the plant defense response against biotrophic and hemi-biotrophic pathogens, while jasmonic acid (JA) and derivatives are critical to the defense response against necrotrophic pathogens. Several reports demonstrate that SA limits nematode reproduction., Results: Here we translate knowledge gained from studies using Arabidopsis to soybean. The ability of thirty-one Arabidopsis genes encoding important components of SA and JA synthesis and signaling in conferring resistance to soybean cyst nematode (SCN: Heterodera glycines) are investigated. We demonstrate that overexpression of three of thirty-one Arabidoposis genes in transgenic soybean roots of composite plants decreased the number of cysts formed by SCN to less than 50% of those found on control roots, namely AtNPR1(33%), AtTGA2 (38%), and AtPR-5 (38%). Three additional Arabidopsis genes decreased the number of SCN cysts by 40% or more: AtACBP3 (53% of the control value), AtACD2 (55%), and AtCM-3 (57%). Other genes having less or no effect included AtEDS5 (77%), AtNDR1 (82%), AtEDS1 (107%), and AtPR-1 (80%), as compared to control. Overexpression of AtDND1 greatly increased susceptibility as indicated by a large increase in the number of SCN cysts (175% of control)., Conclusions: Knowledge of the pathogen defense system gained from studies of the model system, Arabidopsis, can be directly translated to soybean through direct overexpression of Arabidopsis genes. When the genes, AtNPR1, AtGA2, and AtPR-5, encoding specific components involved in SA regulation, synthesis, and signaling, are overexpressed in soybean roots, resistance to SCN is enhanced. This demonstrates functional compatibility of some Arabidopsis genes with soybean and identifies genes that may be used to engineer resistance to nematodes.

This study determined the rates and correlates of depression among community-dwelling elderly people, based on data from the comprehensive health assessment conducted in Al-Dakhiliyah governorate in Oman in 2008-2010. Data covered sociodemographic characteristics, medical and nutrition status, functional abilities, depression and dementia. The rate of depression was 16.9%, higher among women than men (19.3% versus 14.3%). Depression was independently predicted by the presence of social risk (OR = 3.44), dementia (OR = 3.17), impairment in activities of daily living (OR = 2.19), joint problems (OR = 1.52) and mobility restriction (OR = 1.43). If dementia was excluded from the model, depression was additionally predicted by poor perception of health (OR = 2.09), impairment in instrumental activities of daily living (OR = 1.47) and older ages of 70-< 80 years (OR = 1.63) and ≥ 80 years (OR = 1.75). Although not presenting as a complaint, depression in not uncommon among elderly people.

New hybrid chemometric method has been applied to the emission response data. It deals with convolution of emission data using 8-points sin xi polynomials (discrete Fourier functions) after the derivative treatment of these emission data. This new application was used for the simultaneous determination of Fexofenadine and Montelukast in bulk and pharmaceutical preparation. It was found beneficial in the resolution of partially overlapping emission spectra of this mixture. The application of this chemometric method was found beneficial in eliminating different types of interferences common in spectrofluorimetry such as overlapping emission spectra and self- quenching. Not only this chemometric approache was applied to the emission data but also the obtained data were subjected to non-parametric linear regression analysis (Theil's method). The presented work compares the application of Theil's method in handling the response data, with the least-squares parametric regression method, which is considered the de facto standard method used for regression. So this work combines the advantages of derivative and convolution using discrete Fourier function together with the reliability and efficacy of the non-parametric analysis of data. Theil's method was found to be superior to the method of least squares as it could effectively circumvent any outlier data points.

A cross-sectional survey was conducted in March 2011 to study the patterns and determinants of physical activity among 439 secondary-school students in Muscat governorate based on a self-administered questionnaire. Half of the students (52.9%) were enrolled in physical education classes and 95.9% reported after-school physical activities. The recommended level of physical activity (> or = 1680 MET minutes/week) was met by 23.9% of students, being significantly lower among girls (9.8%) than boys (38.8%). More girls were in the stages of pre-contemplation (5.8%) and contemplation (26.7%) of adopting exercise while more boys were in the action (15.4%) and maintenance stages (36.0%). Girls reported significantly more barriers to exercise, related to lack of energy, interest in other activities, lack of encouragement, worries about looks, and time constraints from academic responsibilities and family obligations. The full model logistic regression revealed that boys, 11th-grade students and attempts to regulate weight significantly predicted physical activity meeting the recommended levels.

This cross-sectional study aimed to assess knowledge of routes of transmission, awareness of MRSA control guidelines and reasons for non-adherence to guidelines among medical staff at Alexandria University hospitals. A random sample of 158 physicians and 47 nurses answered a self-administered questionnaire. Overall awareness of MRSA control guidelines was 67.3%, and nurses were significantly more aware than physicians (91.5% versus 60.1%). The lowest awareness level was among anaesthesiologists; only 54.4% knew the correct transmission routes. Among medical staff overall, 70.0% accepted the necessity of screening measures for high-risk patients and 35.8% of doctors accepted the use of the same pair of gloves when caring for different body sites on an individual patient. Lack of resources was the most common justification for suboptimum adherence. The study showed low awareness levels of MRSA-related guidelines.

Plant parasitic nematodes cause approximately 157 billion US dollars in losses worldwide annually. The soybean cyst nematode (SCN), Heterodera glycines, is responsible for an estimated one billion dollars in losses to the US farmer each year. A promising new approach for control of plant parasitic nematode control is gene silencing. We tested this approach by silencing the SCN gene HgALD, encoding fructose-1,6-diphosphate aldolase. This enzyme is important in the conversion of glucose into energy and may be especially important in actin-based motility during parasite invasion of its host. An RNAi construct targeted to silence HgALD was transformed into soybean roots of composite plants to examine its efficacy to reduce the development of females formed by SCN. The number of mature females on roots transformed with the RNAi construct designed to silence the HgALD gene was reduced by 58%. These results indicate that silencing the aldolase gene of SCN +can greatly decrease the number of female SCN reaching maturity, and it is a promising step towards broadening resistance of plants against plant-parasitic nematodes., (Published by Elsevier Inc.)

During pathogen attack, the host plant induces genes to ward off the pathogen while the pathogen often produces effector proteins to increase susceptibility of the host. Gene expression studies of syncytia formed in soybean root by soybean cyst nematode (Heterodera glycines) identified many genes altered in expression in resistant and susceptible roots. However, it is difficult to assess the role and impact of these genes on resistance using gene expression patterns alone. We selected 100 soybean genes from published microarray studies and individually overexpressed them in soybean roots to determine their impact on cyst nematode development. Nine genes reduced the number of mature females by more than 50 % when overexpressed, including genes encoding ascorbate peroxidase, β-1,4-endoglucanase, short chain dehydrogenase, lipase, DREPP membrane protein, calmodulin, and three proteins of unknown function. One gene encoding a serine hydroxymethyltransferase decreased the number of mature cyst nematode females by 45 % and is located at the Rhg4 locus. Four genes increased the number of mature cyst nematode females by more than 200 %, while thirteen others increased the number of mature cyst nematode females by more than 150 %. Our data support a role for auxin and ethylene in susceptibility of soybean to cyst nematodes. These studies highlight the contrasting gene sets induced by host and nematode during infection and provide new insights into the interactions between host and pathogen at the molecular level. Overexpression of some of these genes result in a greater decrease in the number of cysts formed than recognized soybean cyst nematode resistance loci.

Background: The gene encoding PAD4 (PHYTOALEXIN-DEFICIENT4) is required in Arabidopsis for expression of several genes involved in the defense response to Pseudomonas syringae pv. maculicola. AtPAD4 (Arabidopsis thaliana PAD4) encodes a lipase-like protein that plays a regulatory role mediating salicylic acid signaling., Results: We expressed the gene encoding AtPAD4 in soybean roots of composite plants to test the ability of AtPAD4 to deter plant parasitic nematode development. The transformed roots were challenged with two different plant parasitic nematode genera represented by soybean cyst nematode (SCN; Heterodera glycines) and root-knot nematode (RKN; Meloidogyne incognita). Expression of AtPAD4 in soybean roots decreased the number of mature SCN females 35 days after inoculation by 68 percent. Similarly, soybean roots expressing AtPAD4 exhibited 77 percent fewer galls when challenged with RKN., Conclusions: Our experiments show that AtPAD4 can be used in an economically important crop, soybean, to provide a measure of resistance to two different genera of nematodes.

Two stability-indicating chromatographic methods are described for simultaneous determination of amiloride hydrochloride (AMI), atenolol (ATE), and chlorthalidone (CHL) in combined dosage forms. The first method was based on HPTLC separation of the three drugs followed by densitometric measurements of their bands at 274 nm. The separation was carried out on Merck HPTLC silica gel 60F254 aluminum sheets using chloroform-methanol-ammonia 27%, w/w (9 + 2 + 0.3, v/v/v) mobile phase. Analysis data was used for the linear regression graph in the range of 0.1-0.5, 0.8-5.0, and 0.3-1.5 microg/band for AMI, ATE, and CHL, respectively. The second method was based on an RP-HPLC separation of the cited drugs performed on an RP stainless steel C18 analytical column (250 x 4.6 mm id) with a gradient elution system of methanol and 0.05 M aqueous phosphate buffer adjusted to pH 4 as the mobile phase, at the flow rate of 1.0 mL/min. Quantitation was achieved with photodiode array detection at 275 nm for AMI and 225 nm for ATE and CHL. The calibration graphs for each drug were rectilinear in the range of 2-50, 25-150, and 2-100 microg/mL for AMI, ATE, and CHL, respectively. The proposed chromatographic methods were successfully applied for determination of the investigated drugs in pharmaceutical preparations. Both methods were validated in compliance with International Conference on Harmonization guidelines in terms of linearity, accuracy, precision, robustness, LOD, and LOQ.

Transcriptional mapping experiments of the major soybean cyst nematode resistance locus, rhg1, identified expression of the vesicular transport machinery component, α soluble NSF attachment protein (α-SNAP), occurring during defense. Sequencing the α-SNAP coding regions from the resistant genotypes G. max ([Peking/PI 548402]) and G. max ([PI 437654]) revealed they are identical, but differ from the susceptible G. max ([Williams 82/PI 518671]) by the presence of several single nucleotide polymorphisms. Using G. max ([Williams 82/PI 518671]) as a reference, a G → T(2,822) transversion in the genomic DNA sequence at a functional splice site of the α-SNAP([Peking/PI 548402]) allele produced an additional 17 nucleotides of mRNA sequence that contains an in-frame stop codon caused by a downstream G → A(2,832) transition. The G. max ([Peking/PI 548402]) genotype has cell wall appositions (CWAs), structures identified as forming as part of a defense response by the activity of the vesicular transport machinery. In contrast, the 17 nt α-SNAP([Peking/PI 548402]) mRNA motif is not found in G. max ([PI 88788]) that exhibits defense to H. glycines, but lack CWAs. The α-SNAP([PI 88788]) promoter contains sequence elements that are nearly identical to the α-SNAP([Peking/PI 548402]) allele, but differs from the G. max ([Williams 82/PI 518671]) ortholog. Overexpressing the α-SNAP([Peking/PI 548402]) allele in the susceptible G. max ([Williams 82/PI 518671]) genotype suppressed H. glycines infection. The experiments indicate a role for the vesicular transport machinery during infection of soybean by the soybean cyst nematode. However, increased GmEREBP1, PR1, PR2, PR5 gene activity but suppressed PR3 expression accompanied the overexpression of the α-SNAP([Peking/PI 548402]) allele prior to infection.

An efficient chromatographic method for the simultaneous determination of triamterene (TRI) and xipamide (XIP) in urine samples, based on high performance liquid chromatography with photodiode array detector (HPLC-DAD) has been developed. The HPLC separation was performed on a RP stainless-steel C-18 analytical column (250 mm × 4.6 mm, 5 μm) with a gradient elution system of 0.05 M phosphate buffer adjusted to pH 4.0 and methanol as the mobile phase. The method was used to determine the urinary excretion profile and to calculate different urinary pharmacokinetic parameters following oral dose of their combination compared with single oral doses of each drug and hence comparing their bioavailability. Quantitation was performed using chlorthalidone as internal standard. The calibration graphs of each drug were rectilinear in the range of 0.2-40 μg/mL urine for TRI and 0.2-15 μg/mL urine for XIP. An HPLC-DAD method was also successfully developed for the simultaneous determination of the investigated drugs in pharmaceutical preparations. The methods were validated in terms of linearity, accuracy, precision, selectivity, limits of detection and quantitation and other aspects of analytical validation., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Two simple and sensitive kinetic spectrophotometric methods for the determination of sucralose are described. The first method is based upon a kinetic investigation of the oxidation reaction of the drug with alkaline potassium permanganate at room temperature for a fixed time of 30 min. The absorbance of the green coloured manganate ions produced was measured at 610 nm. The second method is based on the reaction of sucralose with cerium (IV) ammonium sulfate in the presence of perchloric acid with the subsequent measurement of the excess unreacted cerium (IV) ammonium sulfate at 320 nm at a fixed time of 30 min in a thermostated water bath at 60 ± 1 °C. This principle is adopted to develop a kinetic method for sucralose determination. The absorbance concentration plots in both methods were rectilinear over the range 4-16 and 10-30 µg ml(-1) , for the first and second methods, respectively. The different experimental parameters affecting the development and stability of the colours were carefully studied and optimized. The determination of sucralose by rate constant method, fixed concentration method, and fixed-time method was also feasible with calibration equations obtained but the latter method was found to be more applicable. The two methods have been applied successfully to commercial tablets., (Copyright © 2010 John Wiley & Sons, Ltd.)

Two spectrophotometric methods are presented for the simultaneous determination of ezetimibe/simvastatin and ezetimibe/atorvastatin binary mixtures in combined pharmaceutical dosage forms without prior separation. The first is the derivative ratio method where the amplitudes of the first derivative of the ratio spectra ((1) DD) at 299.5 and 242.5 nm were found to be linear with ezetimibe and simvastatin concentrations in the ranges 0.5-20 µgml(-1) and 1-40 µgml(-1) , respectively, whereas the amplitudes of the first derivative of the ratio spectra ((1) DD) at 289.5 and 288 nm were selected to determine ezetimibe and atorvastatin in the concentration ranges 5-50 µgml(-1) and 1-40 µgml(-1) , respectively. The second is the H-point standard additions method; absorbances at the two pairs of wavelengths, 228 and 242 nm or 238 and 248 nm, were monitored while adding standard solutions of ezetimibe or simvastatin, respectively. For the analysis of ezetimibe/atorvastatin mixture, absorbance values at 226 and 248 nm or 212 and 272 nm were monitored while adding standard solutions of ezetimibe or atorvastatin, respectively. Moreover, differential spectrophotometry was applied for the determination of ezetimibe in the two mixtures without any interference from the co-existing drug. This was performed by measurement of the difference absorptivities (ΔA) of ezetimibe in 0.07 M 30% methanolic NaOH relative to that of an equimolar solution in 0.07 M 30% methanolic HCl at 246 nm. The described methods are simple, rapid, precise and accurate for the determination of these combinations in synthetic mixtures and dosage forms., (Copyright © 2010 John Wiley & Sons, Ltd.)

The synthesis of some new 3-substituted quinazolin-4(3H)-ones and 3,4-dihydro-quinazolin-2(1H)-one derivatives and their biological evaluation as antitumor agents using the National Cancer Institute (NCI), disease oriented antitumor screening protocol are investigated. Compounds 2-[2-(4-chlorophenyl)-2-oxo-ethylthio]-3-(4-methoxyphenyl)quinazolin-4(3H)-one (3b), and 3-(4-chlorophenyl)-2-[2-(4-methoxyphenyl)-2-oxo-ethylthio]quinazolin-4(3H)-one (3d), are broad-spectrum antitumors showing effectiveness toward numerous cell lines that belong to different tumor subpanels, Compounds 3b, 3d are the most active members in this study. Those two quinazoline analogues could be considered as useful templates for future development to obtain more potent antitumor agent(s)., (Copyright © 2010 Elsevier Masson SAS. All rights reserved.)

Spiramycin (SPY) is a medium-spectrum antibiotic with high effectiveness against Gram-positive bacteria. The voltammetric behaviour of spiramycin was studied using differential pulse polarography (DPP) and square wave polarography (SWP). The drug in Britton-Robinson buffer (pH 11.5) is reduced at - 1.45 V, giving rise to a well-defined cathodic peak using hanging mercury drop electrode (HMDE) versus Ag/AgCl electrode. This peak is attributed to the reduction of the aldehyde group. The results proved that the reduction of SPY is an irreversible diffusion-controlled process. The diffusion current-concentration relationship was shown to be rectilinear over the range of 20-80 and 0.8-80 µg ml(-1) using DPP and SWP modes, respectively, with detection limit of 8.5 µg ml(-1) (1.01 × 10(-5) M) and 0.46 µg ml(-1) (5.46 × 10(-7) M) for DPP and SWP modes, respectively. A mechanism is postulated for the reduction of SPY. The proposed techniques were successfully applied to the determination of the studied compound either in pure form or in its formulation., (Copyright © 2010 John Wiley & Sons, Ltd.)

Background and Objectives: Oman provides comprehensive care for the detection and management of diabetes during pregnancy with the goal of reducing or eliminating adverse outcomes for mothers and newborns. We assessed the outcome of pregnancies complicated with diabetes as compared to healthy controls., Subjects and Methods: A 1-year retrospective review of registry records was conducted on pregnant women with gestational diabetes mellitus (GDM) and pre-gestational diabetes mellitus (PGDM). Of the 5394 women registered, 225 had GDM and 56 had PGDM. Fourteen cases of GDM and 2 cases of PGDM were excluded. For each patient recruited, the next healthy control of the same age and parity was selected., Results: Nearly 80% of diabetic women achieved good glycemic control (hemoglobin A1c <7%). Adjusted for hypertension and body mass index, the risk of macrosomia was three times higher among women with GDM (OR=3.03, 95% CI=1.36-6.75) and up to seven times higher among those with PGDM (OR=7.20, 95% CI=2.30-22.61). A significantly higher risk of cesarean delivery was observed among women with GDM (OR=2.70, 95% CI=1.17-4.03) and PGDM (OR=4.39, 95% CI=1.68-11.49). Admission to the special care baby unit was higher among infants born to mothers with PGDM (OR=5.70, 95% CI=2.40-13.51) and GDM (OR=2.85, 95% CI=1.68-4.83)., Conclusion: The findings indicate that many of the unfavorable pregnancy outcomes of diabetes for women and infants have not been brought under control despite the comprehensive care provided. Further studies are recommended to evaluate the system of care provided to pregnant women and to identify gaps in achieving the goals of the St. Vincent Declaration.

Between March and August 2008 we undertook 2 cross-sectional surveys among 1375 residents of 3 randomly selected villages in the district of Gebiley in the North-West Zone, Somalia. We investigated for the presence of malaria infection and the period prevalence of self-reported fever 14 days prior to both surveys. All blood samples examined were negative for both species of Plasmodium. The period prevalence of 14-day fevers was 4.8% in March and 0.6% in August; the majority of fevers (84.4%) were associated with other symptoms including cough, running nose and sore throat; 48/64 cases had resolved by the day of interview (mean duration 5.4 days). Only 18 (37.5%) fever cases were managed at a formal health care facility: 7 within 24 hours and 10 within 24-72 hours of onset. None of the fevers were investigated for malaria; they were treated with antibiotics, antipyretics and vitamins.

Areas in which malaria is not highly endemic are suitable for malaria elimination, but assessing transmission is difficult because of lack of sensitivity of commonly used methods. We evaluated serologic markers for detecting variation in malaria exposure in Somalia. Plasmodium falciparum or P. vivax was not detected by microscopy in cross-sectional surveys of samples from persons during the dry (0/1,178) and wet (0/1,128) seasons. Antibody responses against P. falciparum or P. vivax were detected in 17.9% (179/1,001) and 19.3% (202/1,044) of persons tested. Reactivity against P. falciparum was significantly different between 3 villages (p<0.001); clusters of seroreactivity were present. Distance to the nearest seasonal river was negatively associated with P. falciparum (p = 0.028) and P. vivax seroreactivity (p = 0.016). Serologic markers are a promising tool for detecting spatial variation in malaria exposure and evaluating malaria control efforts in areas where transmission has decreased to levels below the detection limit of microscopy.

A sensitive first derivative spectrofluorimetric method ((1)D-spectrofluorimetry) was developed for the determination of mirtazapine. Calibration graph for mirtazapine determination was established using the first derivative amplitudes of the mirtazapine emission spectrum (λ ex = 314 nm) in 0.1 M sulphuric acid measured at 375-435 nm from peak to peak, as the analytical signals. Moreover, the ratio of (1)D-spectrophotometric peak amplitudes at these wavelengths was calculated and used for the detection of the presence of interferences. Linearity range was found to be between 1 and 40 ng ml(-1) with correlation coefficient (r) = 0.9999. The limit of quantitation (LOQ) was 1.0 ng ml(-1) and the limit of detection (LOD) was 0.2 ng ml(-1). The proposed method was validated according to ICH; and it has been applied for the drug determination in human plasma without prior extraction and in tablets. The proposed method's accuracy, reproducibility, selectivity and simplicity suggest its application in quality control analysis of the drug.

Objective: Child maltreatment is a problem that has longer recognition in the northern hemisphere and in high-income countries. Recent work has highlighted the nearly universal nature of the problem in other countries but demonstrated the lack of comparability of studies because of the variations in definitions and measures used. The International Society for the Prevention of Child Abuse and Neglect has developed instrumentation that may be used with cross-cultural and cross-national benchmarking by local investigators. DESIGN AND SAMPLING: The instrument design began with a team of expert in Brisbane in 2004. A large bank of questions were subjected to two rounds of Delphi review to develop the fielded version of the instrument. Convenience samples included approximately 120 parent respondents with children under the age of 18 in each of six countries (697 total)., Results: This paper presents an instrument that measures parental behaviors directed at children and reports data from pilot work in 6 countries and 7 languages. Patterns of response revealed few missing values and distributions of responses that generally were similar in the six countries. Subscales performed well in terms of internal consistency with Cronbach's alpha in very good range (0.77-0.88) with the exception of the neglect and sex abuse subscales. Results varied by child age and gender in expected directions but with large variations among the samples. About 15% of children were shaken, 24% hit on the buttocks with an object, and 37% were spanked. Reports of choking and smothering were made by 2% of parents., Conclusion: These pilot data demonstrate that the instrument is well tolerated and captures variations in, and potentially harmful forms of child discipline., Practice Implications: The ISPCAN Child Abuse Screening Tool - Parent Version (ICAST-P) has been developed as a survey instrument to be administered to parents for the assessment of child maltreatment in a multi-national and multi-cultural context. It was developed with broad input from international experts and subjected to Dephi review, translation, and pilot testing in six countries. The results of the Delphi study and pilot testing are presented. This study demonstrates that a single instrument can be used in a broad range of cultures and languages with low rates of missing data and moderate to high internal consistency.

An efficient multiresidue method for the simultaneous determination of metronidazole (MET) and spiramycin (SPY) in tilapia fish muscle, based on high performance liquid chromatography with UV detection (HPLC-UV), has been developed. The drugs were extracted with 0.2% orthophosphoric acid-methanol (6:4), and the extracts were cleaned up on a solid phase extraction cartridge, C18 Sep-Pak light column. The LC separation was performed on a RP stainless-steel C-18 analytical column (150 mm x 4.6 mm, 5 microm) with a gradient elution system of 0.05 M phosphate buffer adjusted to pH 2.4-acetonitrile as the mobile phase at the flow rate of 1.0 ml min(-1). A wavelength programming was applied for the UV detection of the analytes. The method not only enabled the determination of the parent drugs, MET and SPY, but also permitted the determination of their metabolites, hydroxymetronidazole (HMET) and neospiramycin (NSPY). The calibration graphs for each drug were rectilinear in the range of 0.005-1.000 microg g(-1) for MET and HMET and 0.025-1.000 microg g(-1) for SPY and NSPY. With this method, the cited drugs with their metabolites were determined in fortified fish muscle tissues at levels of 0.025, 0.1 and 1.0 microg g(-1) with good accuracy and precision. LOD and LOQ obtained for each drug were as follows: 0.002 and 0.005 microg g(-1) for MET and HMET and 0.005 and 0.025 microg g(-1) for SPY and NSPY. Utilization of the method to successfully analyze tilapia fish muscle samples incurred with MET and SPY was described.