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Background: Sirolimus (SIR) is a macrocyclic lactone antibiotic and used therapeutically as a potent immunosuppressant for prophylaxis of kidney transplant rejection. The development of an oral dosage form is challenging because of very poor aqueous solubility (2.6µg/ml). The oral bioavailability of SIR is only 15-20 % and is affected by food and other drugs. The main reasons for low bioavailability are intestinal degradation by enzymes especially by cytochrome P4503A4, efflux by P-glycoprotein and hepatic first-pass metabolism., Objective: The main objective was to prepare a mouth dissolving film dosage form of amorphous SIR to improve dissolution., Methods: Crystalline SIR was transformed to its form amorphous by milling for 2 h at room temperature. Thermogravimetric analysis (TGA), differential scanning calorimetry (DSC) and powder x-ray diffraction (PXRD) were used for characterisation. The stability of amorphous SIR was studied at 4°C and 40°C/75% RH. Amorphous SIR was formulated as oral films by melt extrusion with polyvinylpyrrolidone- vinyl acetate (PVP-VA), Soluplus® and hydroxypropyl cellulose (HPC) as carriers. The films were characterized for drug content, physical state, dissolution profile and stability at 4°C and 40°C/75% RH., Results: The PRXD and DSC confirmed the conversion of crystalline SIR to amorphous form by milling. The solubility of amorphous SIR was several folds higher than its crystalline form, but amorphous SIR was highly unstable at all tested temperatures (4° and 40°C). The extruded films exhibited higher dissolution and stability compared to milled SIR powder alone, but the process of extrusion had some detrimental effect on the chemical stability of amorphous SIR., Conclusion: The film formulations showed a significant improvement in the storage stability of the amorphous form of SIR and the solubility advantage of the amorphous form was evident in the dissolution testing. The oral films can potentially improve the bioavailability of SIR by absorption through the buccal mucosa., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Computed radiography (CR), digital radiography (DR) and biplanar radiography (EOS™ imaging system) are common imaging tools for radiographic evaluation of adolescent idiopathic scoliosis (AIS). The effect of imaging methods in relation to later-on Cobb angle measurements on radiographs is not yet quantified. The study aimed to examine the compatibility between CR, DR and EOS for scoliotic quantification by evaluating the reliability, agreement of different imaging methods, and assessing the prediction performance for EOS measurement from that of CR and DR., Method: A flexible spine phantom was used to simulate 32 different scoliotic curves ranging from 10° to 60°. Each curvature was imaged using DR, CR and EOS systems accordingly. Each of the six observers independently measured Cobb angle twice on each image at a two-week interval. Intraclass correlation coefficient (model 2 and 3), Bland-Altman plot and linear regression analysis were completed to evaluate the reliability, agreement, and the prediction of Cobb angle measurement, respectively., Results: Reliability analysis showed excellent intra-observer reliability (Intraclass correlation coefficient >0.9) for each observer and good inter-observer reliability (Intraclass correlation coefficient = 0.84 for EOS; 0.739 for CR; 0.877 for DR) for each method. Bland-Altman plots demonstrated good agreement between imaging methods without fixed or proportional bias. Excellent coefficient of determination was achieved, with 0.980 for CR versus EOS measurements, and 0.973 for DR versus EOS measurements., Conclusions: Radiographs produced by all of the three methods can provide reliable and accurate Cobb angle measurements for scoliosis assessments. None of the methods systemically underestimates or overestimates the Cobb angle measurement. Additionally, all of the evaluated methods are satisfactory in obtaining images for Cobb angle measurement in AIS. However, the 3D post-processing techniques offered by EOS should also be taken into consideration as it takes a vital role in treatment and monitoring of 3D deformity in the case of scoliosis., The Translational Potential of This Article: In view of the limited availability of biplanar radiography (EOS™ imaging system), computed radiography and digital radiography are demonstrated to be reliable alternatives in scoliosis monitoring as evident in the reliability, agreement and prediction of Cobb angle measurement.

A critical challenge in producing an antibody-based assay with the highest reproducibility and sensitivity is the strategy to immobilize antibodies to solid phase. To date, numerous methods of antibody immobilization were reported but each was subjected to its advantages and limitations. The current study proposes a new potential antibody binding protein, the human neonatal fragment crystallizable (Fc) receptor. This protein has shown its high affinity to the Fc of antibody either in vivo or in vitro. Human neonatal Fc receptor is a heterodimer constructed by p51 α-heavy chain and β2-microglobulin light chain; however, the binding sites toward the antibody are located in the p51 α-heavy chain. Hence, vector cloning and recombinant protein expression were carried out to express the p51 α-heavy chain of the human neonatal Fc receptor (hFcRn-α). The recombinant protein expressed, hFcRn-α, was adopted to pin rabbit IgG against hepatitis B virus surface antigen to a solid phase. A sandwich enzyme-linked immunosorbent assay was further developed to evaluate the efficiency of hFcRn-α-directed immobilization in antigen detection. The result was compared with the conventional physical adsorption method. The findings demonstrated that human neonatal Fc receptor was efficient in pinning antibodies and generating higher signals compared with the physical adsorption of antibody., (© 2017 International Union of Biochemistry and Molecular Biology, Inc.)

Aim: To investigate the enhancement of anticancer activity of thymoquinone (TQ) by the use of nanostructured lipid carrier (NLC) in 4T1 tumor-bearing female BALB/c mice., Material & Methods: TQ was incorporated into NLC (TQNLC) by using high pressure homogenization. TQNLC and TQ were orally administered to the mice., Results & Conclusion: TQNLC and TQ are potential chemotherapeutic drugs as they exhibited anticancer activity. The use of NLC as a carrier has enhanced the therapeutic property of TQ by increasing the survival rate of mice. The antimetastasis effect of TQNLC and TQ to the lungs was evidence by downregulation of MMP-2. TQNLC and TQ induced apoptosis via modulation of Bcl-2 and caspase-8 in the intrinsic apoptotic pathway.

Cardiovascular disease (CVD) has been the main cause of mortality and an important cause of morbidity in Malaysia for several years. To reduce global cardiovascular (CV) risk in the population, primary preventive strategies need to be implemented. Hypercholesterolaemia is one of the major risk factors for CVD. This paper is an expert review on the management of hypercholesterolemia focusing on high and very high risk individuals. In low and Intermediate risk individuals, therapeutic lifestyle changes (TLC) and a healthy lifestyle alone may suffice. In high and very high risk individuals, drug therapy in conjunction with TLC are necessary to achieve the target LDL-C levels which have been shown to slow down progression and sometimes even result in regression of atherosclerotic plaques. Statins are first-line drugs because they have been shown in numerous randomized controlled trials to be effective in reducing CV events and to be safe. In some high risk individuals, despite maximally tolerated statin therapy, target Low Density Lipoprotein Cholesterol (LDL-C) levels are not achieved. These include those with familial hypercholesterolaemia and statin intolerance. This paper discusses non-statin therapies, such as ezetimibe and the newer Proprotein convertase subtilisin/kexin type 9 Inhibitors (PCSK9-i).

In order to improve the aqueous solubility and dissolution of Tacrolimus (TAC), amorphous solid dispersions of TAC were prepared by hot melt extrusion with three hydrophilic polymers, Polyvinylpyrrolidone vinyl acetate (PVP VA64), Soluplus ® and Hydroxypropyl Cellulose (HPC), at a drug loading of 10% w / w . Molecular modeling was used to determine the miscibility of the drug with the carrier polymers by calculating the Hansen Solubility Parameters. Powder X-ray diffraction and differential scanning calorimetry (DSC) studies of powdered solid dispersions revealed the conversion of crystalline TAC to amorphous form. Fourier transform Infrared (FTIR) spectroscopy results indicated formation of hydrogen bond between TAC and polymers leading to stabilization of TAC in amorphous form. The extrudates were found to be stable under accelerated storage conditions for 3 months with no re-crystallization, indicating that hot melt extrusion is suitable for producing stable amorphous solid dispersions of TAC in PVP VA64, Soluplus ® and HPC. Stable solid dispersions of amorphous TAC exhibited higher dissolution rate, with the solid dispersions releasing more than 80% drug in 15 min compared to the crystalline drug giving 5% drug release in two hours. These stable solid dispersions were incorporated into orally-disintegrating tablets in which the solid dispersion retained its solubility, dissolution and stability advantage., Competing Interests: The authors report no conflict of interest.

The purpose of the study was to test the efficacy of neoadjuvant palbociclib therapy and to evaluate its impact on cell cycle arrest and changes in EndoPredict (EP) scores before and after treatment. Postmenopausal women with histologically proven ER+ve, HER2-ve invasive breast cancer, 2 cm or greater, were enrolled in an open-label, single-arm study. Twenty eligible patients were given letrozole 2.5 mg per day together with palbociclib 125 mg per day for 3 out of 4 weeks in repeated cycles for 16 weeks (4 cycles) before surgery. The primary end points were clinical response rates (cRR) and preoperative endocrine prognostic index (PEPI). The secondary end points were pathologic response and gene expression testing with EP test on collected tumor samples. The following results were obtained. 17 patients showed a clinical response of 50% or more, including 8 complete responses and 9 partial responses. There was significant reduction in area ( P  < 0.0001) and volume ( P  = 0.017) of the cancer. Pathologic complete response (pCR) was achieved in one patient; all cancers were downgraded after treatment. Ki67 ( P  = 0.044) and EP scores ( P  < 0.0001) were significantly reduced after treatment. Analysis of the relative gene expression levels showed that all proliferative genes, IL6ST and RBBP8 were decreased after palbociclib treatment. 6 patients with intermediate and three patients with high PEPI risk scores were found to have low EPclin scores. All patients with high PEPI relapse risk score had high EPclin score. In conclusion, effective clinical response was demonstrated by neoadjuvant letrozole in combination with palbociclib. Compared with PEPI, EPclin might be a better parameter to estimate prognosis after neoadjuvant therapy., (© 2018 The authors.)

Biopharmaceutical properties of poorly water-soluble antimalarial drug, Artemisinin (ART), were improved by formulating amorphous solid dispersions with transglycosylated food additives (Hsp-G and Stevia-G) via co-spray drying. Both the formulated ART/Hsp-G and ART/Stevia-G showed superior dissolution properties with a burst release of more than 95% of drug within 5 min, whereas untreated ART dissolved only 4% in 5min. The supersaturation solubility of the formulated ART was enhanced by 2-fold as compared with untreated counterpart. The storage stability tests indicated that these formulations chemically stable at room temperature and under low humidity (<18% RH) conditions. However, high humidity (75% RH) induced re-crystallization and caused changes in the physical appearance of the solid dispersions. In addition, both the food additives and ART formulated samples showed low cytotoxicity to Caco-2 cell line suggesting their good biocompatibility. Thus, the formation of solid dispersions of ART with transglycosylated food additives is a potentially safe and effective approach to enhance the bioavailability of poorly water-soluble ART., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The influence of mesoporous silica nanoparticles (MSNs) loaded with antibiotics on the mechanical properties of functional poly(methyl methacrylate)-(PMMA) based bone cements is investigated. The incorporation of MSNs to the bone cements (8.15wt%) shows no detrimental effects on the biomechanical properties of the freshly solidified bone cements. Importantly, there are no significant changes in the compression strength and bending modulus up to 6 months of aging in PBS buffer solution. The preserved mechanical properties of MSN-functionalized bone cements is attributed to the unchanged microstructures of the cements, as more than 96% of MSNs remains in the bone cement matrix to support the cement structures after 6 months of aging. In addition, the MSN-functionalized bone cements are able to increase the drug release of gentamicin (GTMC) significantly as compared with commercially available antibiotic-loaded bone cements. It can be attributed to the loaded nano-sized MSNs with uniform pore channels which build up an effective nano-network path enable the diffusion and extended release of GTMC. The combination of excellent mechanical properties and sustainable drug delivery efficiency demonstrates the potential applicability of MSN-functionalized PMMA bone cements for orthopedic surgery to prevent post-surgery infection., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background & Aims: The epidemiology of Helicobacter pylori infection has changed with improvements in sanitation and methods of eradication. We performed a systematic review and meta-analysis to evaluate changes in the global prevalence of H pylori infection., Methods: We performed a systematic search of the MEDLINE and EMBASE databases for studies of the prevalence of H pylori infection published from January 1, 1970 through January 1, 2016. We analyzed data based on United Nations geoscheme regions and individual countries. We used a random effects model to calculate pooled prevalence estimates with 95% confidence intervals (CIs), weighted by study size. We extrapolated 2015 prevalence estimates to obtain the estimated number of individuals with H pylori infection., Results: Among 14,006 reports screened, we identified 263 full-text articles on the prevalence of H pylori infection; 184 were included in the final analysis, comprising data from 62 countries. Africa had the highest pooled prevalence of H pylori infection (70.1%; 95% CI, 62.6-77.7), whereas Oceania had the lowest prevalence (24.4%; 95% CI, 18.5-30.4). Among individual countries, the prevalence of H pylori infection varied from as low as 18.9% in Switzerland (95% CI, 13.1-24.7) to 87.7% in Nigeria (95% CI, 83.1-92.2). Based on regional prevalence estimates, there were approximately 4.4 billion individuals with H pylori infection worldwide in 2015., Conclusions: In a systematic review and meta-analysis to assess the prevalence of H pylori infection worldwide, we observed large amounts of variation among regions-more than half the world's population is infected. These data can be used in development of customized strategies for the global eradication., (Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.)

The objective of this study is to enhance the dissolution rate, supersaturation and physicochemical stability of combination of two poorly water-soluble anti-malarial drugs, artemisinin (ART) and mefloquine (MFQ), by encapsulating them inside mesoporous silica (SBA-15) via co-spray drying. Characteristic studies such as powder X-ray diffraction (PXRD), transmission electron microscopy (TEM) and scanning electron microscope (SEM) clearly indicate the amorphization of the crystalline drugs. ART/MQF/SBA-15 formulations show a superior dissolution enhancement with a burst release of more than 95% of drugs within 30min. In addition, the combination formulation exhibits a stable supersaturation enhancement by 2-fold higher than that of the untreated crystalline counterparts. ART/MQF/SBA-15 samples possess excellent physicochemical stability under 2 different moderate storage conditions for 6 months. The amorphization of ART and MFQ via nano-confinement using mesoporous SBA-15 is a potentially promising approach to enhance the solubility of poorly water-soluble anti-malarial drugs that co-formulated into a single dosage form., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Hand hygiene at key moments during patient care is considered an important infection prevention and control measure to reduce healthcare-associated infections. While there is extensive research in Western settings, there is little in the United Arab Emirates where particular cultural and religious customs are thought to influence hand hygiene behaviour., Aim: To examine the hand hygiene knowledge and beliefs of health professionals at a tertiary care hospital in the United Arab Emirates., Methods: A mixed methods design employed a survey followed by focus groups with nurses and doctors., Findings: A total of 109 participants (13.6%) completed the survey: 96 nurses (88%) and 13 doctors (12%). Doctors' hand hygiene knowledge was slightly higher than that of nurses (78.5% versus 73.5%). There was no significant difference in scores on the hand hygiene beliefs scale between nurses (M = 103.06; SD = 8.0) and doctors (M = 99.00; SD = 10.53; t (80) = 1.55; p = 0.13, two-tailed). Seven categories emerged following transcript analysis., Discussion: Hand hygiene knowledge scores suggest further hand hygiene education is required, especially on alcohol-based hand rub use. Addressing doctors' beliefs is particularly important given the leadership roles that doctors play in healthcare settings., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Quercetin is well known for its beneficial health effects on the human body. However, the slow dissolution rate leading to poor bioavailability constitutes a barrier to being further developed for nutritional products. In this work, quercetin was co-precipitated with dietary fibers into a fast-dissolving nanoformulation via antisolvent precipitation, followed by spray drying. With the help of cellulose fiber, resistant starch or resistant maltodextrin, a high dissolution rate and good storage stability was achieved for quercetin nanoformulations. In addition, nanoformulations exhibited higher level of antioxidant activities in contrast to raw quercetin. The developed quercetin/dietary fiber nanoformulations could be used as supplements or functional ingredients for food development., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Besides its poor dissolution rate, the bitterness of quercetin also poses a challenge for further development. Using carnauba wax, shellac or zein as the shell-forming excipient, this work aimed to microencapsulate quercetin by hot-melt extrusion for taste-masking. In comparison with non-encapsulated quercetin, the microencapsulated powders exhibited significantly reduced dissolution in the simulated salivary pH 6.8 medium indicative of their potentially good taste-masking efficiency in the order of zein > carnauba wax > shellac. In vitro bitterness analysis by electronic tongue confirmed the good taste-masking efficiency of the microencapsulated powders. In vitro digestion results showed that carnauba wax and shellac-microencapsulated powders presented comparable dissolution rate with the pure quercetin in pH 1.0 (gastric) and 6.8 (intestine) medium; while zein-microencapsulated powders exhibited a remarkably slower dissolution rate. Crystallinity of quercetin was slightly reduced after microencapsulation while its chemical structure remained unchanged. Hot-melt extrusion microencapsulation could thus be an attractive technique to produce taste-masked bioactive powders.

The use of sunlight to drive organic reactions constitutes a green and sustainable strategy for organic synthesis. Herein, we discovered that the earth-abundant aluminum oxide (Al 2 O 3 ) though paradigmatically known to be an insulator could induce an immense increase in the selective photo-oxidation of different benzyl alcohols in the presence of a large variety of dyes and O 2 . This unique phenomenon is based on the surface complexation of benzyl alcohol (BnOH) with the Brønsted base sites on Al 2 O 3 , which reduces its oxidation potential and causes an upshift in its HOMO for electron abstraction by the dye. The surface complexation of O 2 with Al 2 O 3 also activates the adsorbed O 2 for receiving electrons from the photoexcited dyes. This discovery brings forth a new understanding on utilizing surface complexation mechanisms between the reactants and earth abundant materials to effectively achieve a wider range of photoredox reactions.

Nellix Endovascular Aneurysm Sealing (EVAS) system is a new concept and technology of abdominal aortic aneurysm (AAA) repair. Elective EVAS using Nellix device was performed for a 83-year-old man with AAA. 2-month post-EVAS CTA surveillance demonstrated mild enlargement of aneurysmal sac and separation of the EndoBags, but without detectable endoleak. The patient developed sudden AAA rupture with retroperitoneal hematoma at about 4 months after EVAS. We postulated that early enlargement of aneurysmal sac and separation of EndoBags of Nellix devices after EVAS, even without detectable endoleak, might indicate significant aneurysmal wall weakening with increased risk of later AAA rupture. To the best of the authors' knowledge, this was the first reported case of aortic rupture after EVAS without detectable endoleak during and after the procedure.

Neonatal Fc-receptor (FcRn) with its affinity to immunoglobulin G (IgG) has been the subject of many pharmacokinetic studies in the past century. This protein is well known for its unique feature in maintaining the circulating IgG from degradation in blood plasma. FcRn is formed by non-covalent association between the α-chain with the β-2-microglobulin (β2m). Many studies have been conducted to produce FcRn in the laboratory, mainly using mammalian tissue culture as host for recombinant protein expression. In this study, we demonstrate a novel strategy to express the α-chain of FcRn using Escherichia coli as the expression host. The expression vector that carries the cDNA of the α-chain was transformed into expression host, Rosetta-gami 2 strain for inducible expression. The bacterial culture was grown in a modified growth medium which constitutes of terrific broth, sodium chloride (NaCl), glucose and betaine. A brief heat shock at 45 °C was carried out after induction, before the temperature for expression was reduced to 22 °C and grown for 16 h. The soluble form of the α-chain of FcRn expressed was tested in the ELISA and dot blot immunoassay to confirm its native functionality. The results implied that the α-chain of FcRn expressed using this method is functional and retains its pH-dependent affinity to IgG. Our study significantly suggests that the activity of human FcRn remain active and functional in the absence of β2m., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Ultrafine palladium nanoparticles (Pd NPs) with 8 and 3 nm sizes were effectively fabricated in triazine functionalized porous organic polymer (POP) TRIA that was developed by nonaqueous polymerization of 2,4,6-triallyoxy-1,3,5-triazine. The Pd NPs encapsulated POP (Pd-POP) was fully characterized using several techniques. Further studies revealed an excellent capability of Pd-POP for catalytic transfer hydrogenation of alkenes at room temperature with superior catalytic performance and high selectivity of desired products. Highly flammable H2 gas balloon at high pressure and temperature used in conventional hydrogenation reactions was not needed in the present synthetic system. Catalytic activity is strongly dependent on the size of encapsulated Pd NPs in the POP. The Pd-POP catalyst with Pd NPs of 8 nm in diameter exhibited higher catalytic activity for alkene hydrogenation as compared with the Pd-POP catalyst encapsulating 3 nm Pd NPs. Computational studies were undertaken to gain insights into different catalytic activities of these two Pd-POP catalysts. High reusability and stability as well as no Pd leaching of these Pd-POP catalysts make them highly applicable for hydrogenation reactions at room temperature.

Unlabelled: The increasing prevalence of breast augmentation presents new challenges in breast imaging interpretation. Magnetic resonance imaging (MRI) is recognized as the gold standard for the evaluation of augmented breasts. This article reviews the MRI features of different breast augmentation techniques, their associated complications, and the role of MRI in the assessment of concurrent breast abnormalities., Teaching Points: • MRI has the highest sensitivity and specificity for implant rupture detection. • MRI is able to discriminate the nature of implanted prosthesis or injected materials. • Sensitivity of cancer detection by MRI is not reduced through implants.

A relatively unexplored method to enhance the sensory and nutritional properties of chocolate is to use plant polyphenols. In this study, a low cost agricultural waste product - mangosteen (Garcinia mangostana Linn.) pericarp - was added as powder in graded amounts (1%, 2% and 3%w/w) to dark and compound chocolates during the mixing stage and evaluated. The particle size distributions of the chocolates were mostly within 30 μm and the chocolates displayed a homogeneous morphology. The polyphenols (procyanidins and xanthones) in mangosteen pericarp powder were also stable to simulated chocolate processing. The 3% pericarp powder concentration significantly expanded the bioactive profile and total phenolic content (13% in dark chocolates and 50% in compound chocolates) compared to their plain counterparts without affecting sensory qualities. Such low cost plant polyphenols could enhance the bioactive and flavor profile of chocolates, especially in low cocoa content compound chocolates., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Respiratory lung infections due to multidrug-resistant (MDR) superbugs are on a global upsurge and have very grim clinical outcomes. Their MDR profile makes therapeutic options extremely limited. Although a highly toxic antibiotic, colistin, is favored today as a "last-line" therapeutic against these hard-to-treat MDR pathogens, it is fast losing its effectiveness. This work therefore seeks to identify and tailor-make useful combination regimens (that are potentially rotatable and synergistic) as attractive alternative strategies to address the rising rates of drug resistance. Three potentially rotatable ternary dry powder inhaler constructs (each involving colistin and 2 other different-classed antibiotics chosen from rifampicin, meropenem, and tigecycline) were identified (with distinct complementary killing mechanisms), coformulated via spray drying, evaluated on their aerosol performance using a Next-Generation Impactor and tested for their efficacies against a number of MDR pathogens. The powder particles were of respirable size (d50, 3.1 ± 0.3 μm-3.4 ± 0.1 μm) and predominantly crumpled in morphology. When dispersed via a model dry powder inhaler (Aerolizer(®)) at 60 L/min, the powders showed concomitant in vitro deposition with fine particle fractions of ∼53%-70%. All formulations were successfully tested in the laboratory to be highly effective against the MDR pathogens. In addition, a favorable synergistic interaction was detected across all 3 formulations when tested against MDR Pseudomonas aeruginosa., (Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

Inflammatory bowel disease (IBD) has become more common in Asia over the past few decades. The rate of increase in prevalence of the disease varies greatly in Asia, with several countries in East Asia experiencing a more than doubled increase in IBD prevalence over the past decade. Historically, ulcerative colitis (UC) is more common than Crohn's disease (CD) in Asia. However, a reverse trend is beginning to appear in more developed countries in Asia such as Japan, Korea, and Hong Kong. While Asian IBD patients share many similarities with their Western counterparts, there are important differences with significant clinical implications. In Asia, there are more men with CD, more ileo-colonic involvement in CD, less familial aggregation, fewer extra-intestinal manifestations and worse clinical outcomes for older-onset patients with UC. These differences are likely related to the different genetic makeup and environmental exposures in different regions. Evaluation of the differences and rates in epidemiologic trends may help researchers and clinicians estimate disease burden and understand the reasons behind these differences, which may hold the key to unravel the etiology of IBD.

Unlabelled: Endothelial progenitor cells (EPCs) are currently being studied as candidate cell sources for revascularization strategies. Significant advances have been made in understanding the biology of EPCs, and preclinical studies have demonstrated the vasculogenic, angiogenic, and beneficial paracrine effects of transplanted EPCs in the treatment of ischemic diseases. Despite these promising results, widespread clinical acceptance of EPCs for clinical therapies remains hampered by several challenges. The present study provides a concise summary of the different EPC populations being studied for ischemic therapies and their known roles in the healing of ischemic tissues. The challenges and issues surrounding the use of EPCs and the current strategies being developed to improve the harvest efficiency and functionality of EPCs for application in regenerative medicine are discussed., Significance: Endothelial progenitor cells (EPCs) have immense clinical value for cardiovascular therapies. The present study provides a concise description of the EPC subpopulations being evaluated for clinical applications. The current major lines of investigation involving preclinical and clinical evaluations of EPCs are discussed, and significant gaps limiting the translation of EPCs are highlighted. The present report could be useful for clinicians and clinical researchers with interests in ischemic therapy and for basic scientists working in the related fields of tissue engineering and regenerative medicine., (©AlphaMed Press.)

To improve antibiotic properties, poly(methyl methacrylate) (PMMA)-based bone cements are formulated with antibiotic and nanostructured materials, such as hydroxyapatite (HAP) nanorods, carbon nanotubes (CNT) and mesoporous silica nanoparticles (MSN) as drug carriers. For nonporous HAP nanorods, the release of gentamicin (GTMC) is not obviously improved when the content of HAP is below 10%; while the high content of HAP shows detrimental to mechanical properties although the release of GTMC can be substantially increased. As a comparison, low content of hollow nanostructured CNT and MSN can enhance drug delivery efficiency. The presence of 5.3% of CNT in formulation can facilitate the release of more than 75% of GTMC in 80 days, however, its mechanical strength is seriously impaired. Among nanostructured drug carriers, antibiotic/MSN formulation can effectively improve drug delivery and exhibit well preserved mechanical properties. The hollow nanostructured materials are believed to build up nano-networks for antibiotic to diffuse from the bone cement matrix to surface and achieve sustained drug release. Based on MSN drug carrier in formulated bone cement, a binary delivery system is also investigated to release GTMC together with other antibiotics., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Encapsulation of drugs in mesoporous silica using co-spray drying process has been recently explored as potential industrial method. However, the impact of spray drying on manufacturability, physiochemical stability and bioavailability in relation to conventional drug load processes are yet to be fully investigated. Using a 2(3) factorial design, this study aims to investigate the effect of drug-loading process (co-spray drying and solvent impregnation), mesoporous silica pore size (SBA-15, 6.5 nm and MCM-41, 2.5 nm) and percentage drug load (30% w/w and 50% w/w) on material properties, crystallinity, physicochemical stability, release profiles and bioavailability of fenofibrate (FEN) loaded into mesoporous silica. From the scanning electronic microscopy (SEM) images, powder X-ray diffraction and Differential scanning calorimetry measurements, it is indicated that the co-spray drying process was able to load up to 50% (w/w) FEN in amorphous form onto the mesoporous silica as compared to the 30% (w/w) for solvent impregnation. The in vitro dissolution rate of the co-spray dried formulations was also significantly (p = 0.044) better than solvent impregnated formulations at the same drug loading. Six-month accelerated stability test at 40 °C/75 RH in open dish indicated excellent physical and chemical stability of formulations prepared by both methods. The amorphous state of FEN and the enhanced dissolution profiles were well preserved, and very low levels of degradation were detected after storage. The dog data for the three selected co-spray-dried formulations revealed multiple fold increment in FEN bioavailability compared to the reference crystalline FEN. These results validate the viability of co-spray-dried mesoporous silica formulations with high amorphous drug load as potential drug delivery systems for poorly water soluble drugs.

A novel strategy has been adopted for the construction of a copolymer of benzene-benzylamine-1 (BBA-1), which is a porous organic polymer (POP) with a high BET surface area, through Friedel-Crafts alkylation of benzylamine and benzene by using formaldehyde dimethyl acetal as a cross-linker and anhydrous FeCl3 as a promoter. Ruthenium nanoparticles (Ru NPs) were successfully distributed in the interior cavities of polymers through NaBH4, ethylene glycol, and hydrothermal reduction routes, which delivered Ru-A, Ru-B, and Ru-C materials, respectively, and avoided aggregation of metal NPs. Homogeneous dispersion, the nanoconfinement effect of the polymer, and the oxidation state of Ru NPs were verified by employing TEM, energy-dispersive X-ray spectroscopy mapping, cross polarization magic-angle spinning (13)C NMR spectroscopy, and X-ray photoelectron spectroscopy analytical tools. These three new Ru-based POP materials exhibited excellent catalytic performance in the hydrogenation of nitroarenes at RT (with a reaction time of only ≈ 30 min), with high conversion, selectivity, stability, and recyclability for several catalytic cycles, compared with other traditional materials, such as Ru@C, Ru@SiO2, and Ru@TiO2, but no clear agglomeration or loss of catalytic activity was observed. The high catalytic performance of the ruthenium-based POP materials is due to the synergetic effect of nanoconfinement and electron donation offered by the 3D POP network. DFT calculations showed that hydrogenation of nitrobenzene over the Ru (0001) catalyst surface through a direct reaction pathway is more favorable than that through an indirect reaction pathway., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Selective C-C bond cleavage under ambient conditions is a challenging chemical transformation that can be a valuable tool for organic syntheses and macromolecular disassembly. Herein, we show that base metal vanadium photocatalysts can harvest visible light to effect the chemoselective C-C bond cleavage of lignin model compounds under ambient conditions. Lignin, a major aromatic constituent of non-food biomass, is an inexpensive, accessible source of fine chemical feedstocks such as phenols and aryl ethers. However, existing lignin degradation technologies are harsh and indiscriminately degrade valuable functional groups to produce intractable mixtures. The selective, photocatalytic depolymerization of lignin remains underexplored. In the course of our studies on lignin model compounds, we have uncovered a new C-C activation reaction that takes place under exceptionally mild conditions with high conversions. We present our fundamental studies on representative lignin model compounds, with the aim of expanding and generalizing the substrate scope in the future. Visible light is employed in the presence of earth-abundant vanadium oxo catalysts under ambient conditions. Selective C-C bond cleavage leads to valuable and functionally rich fine chemicals such as substituted aryl aldehydes and formates. Isotope labeling experiments, product analyses, and intermediate radical trapping, together with density functional theory studies, suggest a unique pathway that involves a photogenerated T 1 state during the C-C bond cleavage reactions. Our study demonstrates a sustainable approach to harvest sunlight for an unusual, selective bond activation, which can potentially be applied in organic transformations and biomass valorization.

The chemisorption of pyrimidine and s-triazine, two aromatic molecules with N atoms in the aromatic ring, is studied by first principles calculations to examine not only the chemisorption energy, but also the reaction barriers and the cooperative effects. Among the reaction paths at low coverage, the formation of a cross-bridge structure with two N-Si dative bonds is almost barrierless and should be dominant at low temperature. At higher coverage and low temperature, these cross-row structures should produce an ordered zig-zag pattern, even though it is not the energetically most stable arrangement. Upon heating, the zig-zag pattern could be transformed into lines along dimer rows. These two molecules also provide structural motifs that could facilitate the formation of ordered adsorption structures on Si(100). By symmetry, the complexity of tight-bridge structures could be greatly reduced, while the X-C-X motif, with X being an electronegative atom, could provide the building blocks for cross-row bridges.

Mafraq Hospital performs an average of 10,000 surgeries every year. The impact of having high volume high risk surgical procedures calls for the need to ensure safe surgery and a prevention of surgical site infection (SSI). SSI represents a significant portion of healthcare-associated infections (HAIs). The impact on morbidity, mortality, and cost of care has resulted in identifying the need to reduce SSI as a top priority to prevent healthcare associated infections. The good news is that the majority of SSIs are preventable. Mafraq Hospital performs a range of surgical procedures that covers 14 surgical specialties. The infection prevention and control team performs surveillance for SSI for all patients who undergo operative procedure included in Centers for Disease Control and Prevention (CDC) National Healthcare Safety Network (NHSN) Operative Procedure Category (40 surgical procedures). Out of the 40 CDC NHSN listed, 33 operative procedures were performed at Mafraq Hospital, of which 17 were reported with SSI for 2013 and 2014. Surgical site infection has implicated an increase average length of stay from seven to 10 additional postoperative hospital days and additional costs of AED 10,000 to AED 100,000/SSI depending on procedure and pathogen. A multidisciplinary team was formed to develop and implement measures to reduce/eliminate surgical site infection, as well as evaluate and monitor compliance. Hence a group of multidisciplinary teams were initiated to analyse the results, find out the gaps, and implement a quality improvement project to correct the deficits. Recommendations for appropriate improvement measures were formed on evidence-based international guidelines from the Institute for Healthcare Improvement (IHI) and CDC. Evidence based practice supports that many of the causes of surgical site infection can be prevented with proper medical attention and care.

Airway mucus hypersecretion is a common clinical feature of many severe respiratory diseases, and when complicated by a recalcitrant bacterial infection, the whole treatment regimen thereby becomes more challenging and protracted. The accumulation of thickened mucus secretions in the lower airways provides a nutrient-rich breeding ground for bacteria that promotes their growth and limits the ease of effective eradication. Unfortunately, no direct-inhaled dry powder formulation to treat these respiratory mucoid infections more effectively is available commercially. This work therefore seeks to develop a highly-efficacious ternary dry powder inhaler (DPI) formulation (ciprofloxacin hydrochloride (CIP), gatifloxacin hydrochloride (GAT) and ambroxol hydrochloride (AMB)) capable of delivering a novel multi-pronged attack (synergy, quorum quenching and mucociliary clearance) on Pseudomonas aeruginosa, a common respiratory bacteria found in mucoid infections. The powders were prepared via spray drying, evaluated on their aerosol performance via a multi-stage liquid impinger (MSLI) and tested for their efficacies in bacteria-spiked artificial sputum medium (ASM). The optimized particles were of respirable-size (d50 of ∼1.61±0.03μm) and slightly corrugated. When dispersed via an Aerolizer® inhaler at 60L/min, the powder showed concomitant in vitro deposition, minimal capsule, device and throat retention, and highly promising and uniform fine particle fractions (of the loaded dose) of ∼64-69%, which was a vast improvement over the singly-delivered actives. Favourably, when tested on bacteria-spiked ASM, the optimized ternary formulation (with AMB) was more effective at killing bacteria (i.e. faster rate of killing) than just the synergistic antibiotics alone (binary formulation; without AMB). In conclusion, a ternary antibiotic-(non-antibiotic) DPI formulation involving a unique multi-pronged attack mechanism was successfully pioneered and optimized for mucoid infections., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Composites of a Ni-doped metal organic framework (MOF) with reduced graphene oxide (rGO) are synthesized in bulk (gram scale) quantities. The composites are composed of rGO sheets, which avoid restacking from the physical presence of MOF crystals. At larger concentration of rGO, the MOF crystals are distributed on the overlapping and continuous rGO sheets. Ni in Ni-doped MOF is found to engage in a two-electron, reversible, efficient, redox reaction shuttling between Ni and Ni(OH)2 in aqueous potassium hydroxide (KOH) electrolyte. The reaction is rather unique as Ni-based supercapacitors use a one-electron transfer Faradaic redox reaction between Ni(OH)2 and NiO(OH). Employing electrochemical impedance spectroscopy, we determined the charge transfer resistance to be 184 mΩ for MOF, 74 mΩ for a Ni-doped MOF and 6 mΩ for a rGO-Ni-doped MOF composite, but these modifications do not affect the mass transfer resistance. This novel redox reaction in conjunction with the lowered charge transfer resistance from the introduction of rGO underpins the synergy that dramatically increases the capacitance to 758 F/g in the rGO-Ni-doped MOF composite, when the parent MOF could store only 100 F/g and a physical composite of rGO and Ni-doped MOF could algebraically achieve about 240 F/g. A generic approach of doping MOFs with a redox active metal and forming a composite with rGO transforms an electro-inactive MOF to high capacity energy storage material with energy density of 37.8 Wh/kg at a power density of 227 W/kg. These results can promote the development of high-performance energy storage materials from the wide family of MOFs available.

Pulmonary arterial hypertension (PAH) is a chronic ailment of the lungs, exhibiting elevated arterial pressure and vascular resistance; with a mean arterial pressure above 25 mmHg at rest and above 30 mmHg during exercise. It is associated with poor prognosis, and its prevalence is estimated to be 15 cases per one million. The current treatment options for PAH are discussed with the prostanoid class of drugs being the most effective. The latter drugs act by dilating systemic and pulmonary arterial vascular beds and, with sustained long-term usage, altering pulmonary remodelling. They are administered as IV infusions or inhalation solutions. Despite their clinical effectiveness, prostanoids have short half-lives requiring frequent administration of 6-9 times daily and thus suffer from poor compliance. Controlled release inhalation delivery systems for treatment of PAH, ranging from liposomes, biodegradable nano- and microparticles, formation of co-precipitates and complexation with cyclodextrins, are explored. Arising from these formulation strategies, we developed novel polymeric microspheres for inhalation to reduce dosing frequency and improve medication compliance. These microspheres are designed with release modifiers, to reside in the lung which is the site of drug action for a longer duration so as to release the drug slowly and consistently over a prolonged period. This could lead to the development of the first commercially available controlled release inhalation product.

Dissolution of poorly water-soluble drug, Artemisinin (ART), was enhanced by encapsulating the drug particles inside pore channels of ordered mesoporous silica, SBA-15, via co-spray drying. The drug release profiles of ART were investigated by using flow-through cell (USP IV) and in vitro dissolution tester (USP II). The co-spray-dried ART/SBA-15 samples demonstrated significantly improved dissolution rates and supersaturation compared to the untreated ART. The low cytotoxicity effect of ART and SBA-15 on Caco-2 cells after 24 h incubation demonstrated the biocompatibility of ART/SBA-15. Finally, the storage stability of the samples was investigated for 6 months under five different storage conditions. Overall, the solid dispersions exhibited excellent physical stability; however, their chemical stability was affected by humidity regardless of storage temperatures. The formulation of solid dispersions of ART/SBA-15 is potentially safe and an effective approach to enhance the solubility of poorly water-soluble ART.

Thymoquinone (TQ) has been shown to exhibit antitumor properties. Thymoquinone-loaded nanostructured lipid carrier (TQ-NLC) was developed to improve the bioavailability and cytotoxicity of TQ. This study was conducted to determine the cytotoxic effects of TQ-NLC on breast cancer (MDA-MB-231 and MCF-7) and cervical cancer cell lines (HeLa and SiHa). TQ-NLC was prepared by applying the hot high pressure homogenization technique. The mean particle size of TQ-NLC was 35.66 ± 0.1235 nm with a narrow polydispersity index (PDI) lower than 0.25. The zeta potential of TQ-NLC was greater than -30 mV. Polysorbate 80 helps to increase the stability of TQ-NLC. Differential scanning calorimetry showed that TQ-NLC has a melting point of 56.73°C, which is lower than that of the bulk material. The encapsulation efficiency of TQ in TQ-NLC was 97.63 ± 0.1798% as determined by HPLC analysis. TQ-NLC exhibited antiproliferative activity towards all the cell lines in a dose-dependent manner which was most cytotoxic towards MDA-MB-231 cells. Cell shrinkage was noted following treatment of MDA-MB-231 cells with TQ-NLC with an increase of apoptotic cell population (P < 0.05). TQ-NLC also induced cell cycle arrest. TQ-NLC was most cytotoxic towards MDA-MB-231 cells. It induced apoptosis and cell cycle arrest in the cells.

Background: Surgical site infection rates are of great interest to patients, surgeons, hospitals and third-party payers. While previous studies have reported hospital-acquired infection rates that are nonspecific to all surgical services, there remain no overall reported infection rates focusing specifically on plastic surgery in the literature., Objective: To estimate the reported surgical site infection rate in plastic surgery procedures over a 10-year period at an academic hospital in Canada., Methods: A review was conducted on reported plastic surgery surgical site infection rates from 2003 to 2013, based on procedures performed in the main operating room. For comparison, prospective infection surveillance data over an eight-year period (2005 to 2013) for nonplastic surgery procedures were reviewed to estimate the overall operative surgical site infection rates., Results: A total of 12,183 plastic surgery operations were performed from 2003 to 2013, with 96 surgical site infections reported, corresponding to a net operative infection rate of 0.79%. There was a 0.49% surgeon-reported infection rate for implant-based procedures. For non-plastic surgery procedures, surgical site infection rates ranged from 0.04% for cataract surgery to 13.36% for high-risk abdominal hysterectomies., Discussion: The plastic surgery infection rate at the study institution was found to be <1%. This rate was equal to, or somewhat less than, surgical site infection rates. However, these results do not report patterns of infection rates germane to procedures, season, age groups or sex. To provide more in-depth knowledge of this topic, multicentre studies should be conducted.

Traditional environmental cleaning monitoring through visual assessment can identify gross lapses in practice. However, in recent years the limitations underlying this need for ongoing compliance with cleaning and disinfection policies in the patient's immediate surroundings have become widely recognised. The value of objectively monitoring and improving environmental cleaning and disinfection in healthcare settings is becoming increasingly identified as a crucial element of strategies to mitigate the transmission of healthcare-associated infections. Mafraq Hospital has adopted a new method using an invisible fluorescent marker system to target on surfaces in patient's immediate surroundings. Evaluation of at least 30 surfaces and objects in patient rooms revealed that only 11% of targets had been cleaned. Simulation training, educational interventions, empowerment, change involvement and acknowledgment were executed, leading to a sustained improvement of 77% in both quarter 2 and 3 of 2013 in cleaning and disinfecting of all surfaces and objects.

Utilization of sugars (e.g. lactose, sucrose) as matrix formers for spray drying of drug nanosuspensions is associated with two drawbacks: (1) sugars are incapable of preventing agglomeration of drug nanoparticles (NPs) in the suspension state; and (2) the spray-dried sugars are usually amorphous and hygroscopic. This work aimed to apply a clay, montmorillonite (MMT) as an alternative matrix former for spray drying of drug nanosuspensions with fenofibrate (feno) as a model compound. Drug nanosuspensions were synthesized by liquid antisolvent precipitation with different amount of MMT followed by spray drying. It is found that MMT is able to reduce the agglomeration of drug nanoparticles in the suspension state, as observed from the gradual alleviation of the clogging with the increased clay during the spray drying. The spray-dried feno NPs/MMT powders exhibited a much lower moisture sorption than spray-dried feno NPs/lactose powders as evidenced by the dynamic vapor sorption (DVS) analysis. The dissolution within 5 min for the spray-dried feno NPs/MMT powders at drug:MMT weight ratio of 1:3 was 81.4 ± 1.8% and the total dissolution within 60 min was 93.4 ± 0.9%. Our results demonstrate that MMT is a useful matrix former for preservation of the high dissolution rate of nanosized drug particles after drying., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Despite advances in vaccination and antimicrobial therapy, community-acquired pneumonia (CAP) remains as a leading cause of morbidity and mortality worldwide. As the severity of CAP has been linked to the extent of inflammation in the body, adjunctive therapeutic measures aimed at modulating the immune response have therefore become increasingly attractive in recent years. In particular, for CAP patients with underlying medical conditions such as chronic obstructive pulmonary disease (COPD), a steroid-antibiotic combination will no doubt be a useful and timely therapeutic intervention. Unfortunately, no combined steroid-antibiotic dry powder formulation is available commercially or has been reported in the academic literature. The aim of this work was hence to develop a novel steroid-antibiotic dry powder inhaler formulation [ciprofloxacin hydrochloride (CIP) and beclomethasone dipropionate (BP)] for inhaled anti-infective therapy. The spray-dried powder was of respirable size (d50 of ∼2.3 μm), partially crystalline and had BP preferentially deposited on the particle surface. Favorably, when formulated as a binary mix, both CIP and BP showed much higher drug release and fine particle fractions (of the loaded dose) over their singly delivered counterparts, and had robust activity against the respiratory tract infection-causing bacteria Klebsiella pneumoniae, Pseudomonas aeruginosa, and Staphylococcus aureus., (© 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.)

The objective of this study was to develop and evaluate solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) utilizing sucrose ester as a stabilizer/emulsifier for the controlled release of drug/active. Both SLNs and NLCs were prepared using different sugar esters to screen out the most suitable stabilizer. Clotrimazole was used as a model active/drug. The effect of different formulation variables on the particle size, polydispersity index and drug encapsulation efficiency of SLNs and NLCs was evaluated and compared. SLNs and NLCs were physicochemically characterized and compared using Cryo-SEM, DSC and XRD. Furthermore, a drug release study of SLNs and NLCs was conducted. Finally, physicochemical stability (size, PI, ZP, EE) of the SLNs and NLCs was checked at 25 ± 2 °C and at 2-8 °C. Among the sucrose esters, D-1216 was found to be most suitable for both SLNs and NLCs. Formulation variables exhibited a significant impact on size, PI and EE of the nanoparticles. SLNs with ∼120 nm size, ∼0.23 PI, ∼I26I mV ZP, ∼87% EE and NLCs with ∼160 nm size, 0.15 PI, ∼I26I mV ZP, ∼88% EE were produced. Cryo-SEM revealed spherical particles with a smooth surface but did not exhibit any difference in surface morphology between SLNs and NLCs. DSC and XRD results demonstrated the disappearance of clotrimazole peak(s) in drug-loaded SLNs and NLCs. Faster drug release was observed from SLNs than NLCs. NLCs were found to be more stable than SLNs in terms of size, PI, EE and drug release. The results indicated that both SLNs and NLCs stabilized with sucrose ester D-1216 can be used as controlled release carriers although NLCs have an edge over SLNs.

This study focused on: (i) feasibility of the previously developed sucrose ester stabilized SLNs and NLCs to encapsulate different imidazole antifungal drugs and (ii) preparation and evaluation of topical gel formulations of those SLNs and NLCs. Three imidazole antifungal drugs; clotrimazole, ketoconazole and climbazole were selected for this study. The results suggested that size, size distribution and drug encapsulation efficiency depend on the drug molecule and type of nanoparticles (SLN/NLC). The drug release experiment always showed faster drug release from NLCs than SLNs when the same drug molecule was loaded in both nanoparticles. However, drug release rate from both SLNs and NLCs followed the order of climbazole > ketoconazole > clotrimazole. NLCs demonstrated better physicochemical stability than SLNs in the case of all drugs. The drug release rate from ketoconazole- and clotrimazole-loaded SLNs became faster after three months than a fresh formulation. There was no significant change in drug release rate from climbazole-loaded SLNs and all drug-loaded NLCs. Gel formulations of SLNs and NLCs were prepared using polycarbophil polymer. Continuous flow measurements demonstrated non-Newtonian flow with shear-thinning behavior and thixotropy. Oscillation measurements depicted viscoelasticity of the gel formulations. Similar to nanoparticle dispersion, drug release rate from SLN- and NLC-gel was in the order of climbazole > ketoconazole > clotrimazole. However, significantly slower drug release was noticed from all gel formulations than their nanoparticle counterparts. Unlike nanoparticle dispersions, no significant difference in drug release from gel formulations containing SLNs and NLCs was observed for each drug. This study concludes that gel formulation of imidazole drug-loaded SLNs and NLCs can be used for sustained/prolonged topical delivery of the drugs.

Background: Long-term outcomes of major upper extremity replantations are infrequently reported. It is believed that replantation is indicated for amputations at all levels in children and for all distal amputations in adults. Replantations of arm or proximal forearm amputations in adults are controversial., Objective: To evaluate the results of major upper extremity replantations, defined as those that are transmetacarpal, through the wrist, forearm, elbow or arm., Methods: A review of these types of replantations performed at the authors' institution from 2002 to 2012 was conducted. Patients' strength, range of motion and two-point discrimination were assessed. Patients completed the Disabilities of the Arm, Shoulder and Hand (DASH), the Michigan Hand Questionnaire (MHQ), and the Hospital Anxiety and Depression scale (HADS)., Results: Seventeen patients underwent major upper extremity replantation surgery. The majority (16 of 17 [94%]) of the included patients were male. Of 17 patients, 13 (76.5%) required reoperations. The mean (± SD) DASH score of seven patients who consented to completing all questionnaires was 75.4±14.2 of 100 (range 59.2 to 91.1). On the MHQ, the mean score for affected hand function was 16% compared with 84% in the unaffected hand. Patients generally demonstrated at least mild levels of anxiety and depression on the HADS., Discussion: The results suggest that major upper extremity injuries and replantations have a significant impact on patients' long-term hand function, and produce long-term anxiety and depressive symptoms.

Purpose: The aim of this work was to develop and characterise S-SEDDS containing fenofibrate (FF) for dissolution enhancement., Methods: The self-emulsifying pre-concentrate was prepared by using different proportion of Labrafac WL1349 as oily phase, Cremophor EL as surfactants and Gelucire 44/14 as co-surfactant. The prepared pre-concentrate was solidified with PEG 6000. For comparison, formulations containing TPGS as surfactant and solidifier were prepared and studied., Results: The cremophor/PEG and TPGS based S-SEDDS formulations containing 10 and 15% w/w FF when dispersed in water, formed nanoemulsion with a size range of 150-200 nm. FF was present in the crystalline state in the formulations. The formulations containing 10% w/w FF showed 90-100% dissolution in 60 min whereas the untreated FF showed only 2-4% dissolution., Conclusion: A novel S-SEDDS was developed for FF using cremophor/PEG and TPGS. The dissolution of FF was enhanced by approximately 20-fold in SGF pH 1.2.

Vitamin E, a potent antioxidant consisting of four isomers each (α, β, γ, δ) of tocopherol (T) and tocotrienol (T3), is found naturally in plant oils at different concentrations. In this study, four semi-purified isonitrogenous and isolipidic (10 %) diets containing canola oil, cold-pressed soybean oil, wheat germ oil, or palm fatty acid distillates (PFAD) as the sole vitamin E source were fed to triplicate groups of red hybrid tilapia (Oreochromis sp.) fingerlings (14.82 ± 0.05 g) for 45 days. Vitamin E concentrations and composition were measured in the muscle, liver, skin, and adipose tissue. Deposition of α-T (53.4-93.1 % of total vitamin E) predominated over deposition of other isomers, except in the liver of fish fed the SBO diet, where α-T and γ-T deposition was in the ratio 40:60. T3 deposition (2.6-29.4 %) was only detected in tissues of fish fed the PFAD diet; adipose tissue was the major storage depot. Fish fed the SBO diet contained significantly more (P < 0.05) muscle thiobarbituric acid-reactive substances. Muscle fatty acid composition reflected dietary fatty acid profile. This is the first study to compare the deposition in fish tissues of the naturally occurring vitamin E isomers present in plant oils. The type and concentration of endogenous vitamin E and the fatty acid composition of plant oils can affect the oxidative stability of tilapia tissues.

Feeding fish a fish oil finishing diet (FOFD) after grow-out on vegetable oil diet is one strategy to restore eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) levels. We investigated restoration of EPA and DHA in rainbow trout fed a FOFD preceded by a grow-out period on 50% or 75% palm fatty acid distillate (PFAD) diets at optimal (15°C) or elevated (20°C) water temperatures. Using the FOFD restored EPA and DHA in fillet and whole carcass of fish previously fed either 50% PFAD diet from 85% to 98% or 75% PFAD from 66% to 93% of values obtained for fish fed FO diet throughout. Water temperature did not influence EPA and DHA restoration. Growing rainbow trout with diets where FO was replaced by either 50% or 75% PFAD followed by a FOFD reduced FO usage by around 30% and 44% at 15°C, respectively, and 32% and 48% at 20°C, respectively., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Dry powder inhalers (DPIs) are used predominantly for the treatment of pulmonary diseases by delivering drugs directly into the lungs. The drug delivery efficiency is typically low and there is significant drug retention inside the DPI. An innovative 'green' initiative aimed at minimizing drug wastage via channeling the residual drug into the useful inhaled therapeutic fraction was pioneered. Drug retention could be minimized via coating the drug capsule and delivery device with pharmaceutically acceptable force-control agents. This coating reduces the adhesion between the drug particles and the internal surfaces of the DPI, which in turn increases the fine particle dose by as much as 300%., (Copyright © 2013 Elsevier B.V. All rights reserved.)

The present study aimed to investigate the potential role of dietary petroselinic acid (PSA) in enhancing the n-3 long-chain polyunsaturated fatty acid (LC-PUFA) content in fish tissues. Three isolipidic casein-based diets were formulated to comprise graded levels of PSA (0, 10, or 20% of total fatty acid) with the incremented inclusion of coriander seed oil. Fish growth and nutrient digestibility were not significantly (P > 0.05) influenced by dietary PSA level. In general, dietary PSA affected the fatty acid composition of tilapia tissues and whole-body, which reflected dietary fatty acid ratios. Dietary PSA significantly (P < 0.05) increased β-oxidation, particularly on α-linolenic acid (18:3n-3) and linoleic acid (18:2n-6). This study provided evidence that PSA, a pseudoproduct mimicking the structure of 18:3n-6, did reduce Δ-6 desaturation on 18:2n-6 but, contrary to popular speculation, did not stimulate more Δ-6 desaturase activity on 18:3n-3. The overall Δ-6 desaturase enzyme activity may be suppressed at high dietary levels of PSA. Nevertheless, the n-3 and n-6 LC-PUFA biosynthesis was not significantly inhibited by dietary PSA, indicating that the bioconversion efficiency is not modulated only by Δ-6 desaturase. The deposition of n-3 LC-PUFA in liver and fillet lipids was higher in fish fed PSA-supplemented diets.

Pulmonary hypertension (PAH) is a condition of the lungs characterised by an elevated arterial pressure and increased vascular resistance. Existing medications have to be administered frequently, resulting in non compliance by patients. Little work has been reported to date where microspheres have been developed to control the release of drug for treatment of pulmonary hypertension. To transcend this drawback, controlled release microspheres were formulated to minimise the number of doses required for treatment of PAH. Nifedipine and polyvinyl alcohol (PVA) were used as the model drug and release modifier respectively. Microspheres were developed by varying the PVA concentration using the spray drying technique. The formulated microspheres were characterised in terms of particle size, morphology, crystallinity, interaction between PVA and nifedipine via Fourier transformed infra-red spectroscopy (FTIR) and differential scanning calorimetry (DSC), in vitro release profile by employing the United States Pharmacopeia Apparatus type II and in vitro aerosolisation profile by using multi-stage liquid impinger (MSLI). The toxicity of PVA on lung epithelial cells was tested using human alveolar basal epithelium A549 cell line. From the data, it was observed that the microspheres were within the inhalable range (1-10 μm) with spherical morphology. The X-ray diffraction demonstrated that the microspheres were amorphous. There was no interaction between PVA and nifedipine during the formation of microspheres as seen by FTIR. The in vitro release profile showed a burst release followed by controlled release. A more prolonged release can be achieved by increasing the PVA:nifedipine ratio. In vitro aerosolisation showed that the Fine Particle Fractionemitted of the microspheres is greater than 20%, which is similar to that of marketed inhalation formulations. PVA was found to have insignificant effect on cell viability after 48 h of exposure to A549 cell line. In conclusion, microspheres of nifedipine and PVA, prepared by spray drying were found to exhibit suitable properties to achieve controlled release by the inhalation route., (Copyright © 2013 Elsevier B.V. All rights reserved.)

The purpose of this study is to synthesize chitosan (CS) nanoparticles (NPs) by ionic gelation with tripolyphosphate (TPP) as crossslinker in static mixers. The proposed static mixing technique showed good control over the ionic gelation process and 152-376 nm CS NPs were achieved in a continuous and scalable mode. Increasing the flow rates of CS:TPP solution streams, decreasing the CS concentration or reducing the CS:TPP solution volume ratio led to the smaller particles. Sylicylic acid (SA) was used as a model drug and successfully loaded into the CS NPs during the fabrication process. Our work demonstrates that ionic gelation-static mixing is a robust platform for continuous and large scale production of CS NPs for drug delivery., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

In combination antimicrobial therapy, the desired outcome is to broaden the antimicrobial spectrum and to achieve a possible synergistic effect. However, adverse antagonistic species may also emerge from such combinations, leading to treatment failure with serious consequences. It is therefore imperative to screen the drug candidates for compatibility and possible antagonistic interactions. The aim of this work was to develop a novel synergistic dry powder inhaler (DPI) formulation for antimicrobial combination therapy via the pulmonary route. Binary (ciprofloxacin hydrochloride and gatifloxacin hydrochloride, SD-CIP/GAT) and ternary (ciprofloxacin hydrochloride, gatifloxacin hydrochloride, and lysozyme, SD-CIP/GAT/LYS) combinations were prepared via spray-drying on a BUCHI® Nano Spray Dryer B-90. The powder morphologies were spherical with a slightly corrugated surface and all within the respirable size range. The powders yielded fine particle fractions (of the loaded dose) of over 40% when dispersed using an Aerolizer® at 60 L/min. Time-kill studies carried out against the respiratory tract infection-causing bacteria Pseudomonas aeruginosa, Staphylococcus aureus, Klebsiella pneumonia, and Acinetobacter baumannii at 1 × the minimum inhibitory concentration (MIC) over 24h revealed no antagonistic behavior for both the binary and ternary combinations. While the interactions were generally found to be indifferent, a favorable synergistic effect was detected in the dual combination (SD-CIP/GAT) when it was tested against P. aeruginosa bacteria., (Copyright © 2012 Elsevier B.V. All rights reserved.)