Dual Drug-Loaded Coaxial Nanofiber Dressings for the Treatment of Diabetic Foot Ulcer

Dunia A Alzahrani,1 Khulud A Alsulami,1 Fatemah M Alsulaihem,1 Abrar A Bakr,1 Rayan Y Booq,2 Ahmed J Alfahad,3 Alhassan H Aodah,1 Samar A Alsudir,4 Amany A Fathaddin,5,6 Essam J Alyamani,2 Aliyah A Almomen,7 Essam A Tawfik1 1Advanced Diagnostics and Therapeutics Technologies Institute, Health Sector, King Abdulaziz City for Science and Technology (KACST), Riyadh, 11442, Saudi Arabia; 2Wellness and Preventative Medicine Institute, Health Sector, King Abdulaziz City for Science and Technology (KACST), Riyadh, 11442, Saudi Arabia; 3Waste Management and Recycling Technologies Institute, Sustainability and Environment Sector, King Abdulaziz City for Science and Technology (KACST), Riyadh, 11442, Saudi Arabia; 4Bioengineering Institute, Health Sector, King Abdulaziz City for Science and Technology (KACST), Riyadh, 11442, Saudi Arabia; 5Department of Pathology, College of Medicine, King Saud University, Riyadh, 12372, Saudi Arabia; 6King Saud University Medical City, Riyadh, 12372, Saudi Arabia; 7Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh, 11451, Saudi ArabiaCorrespondence: Essam A Tawfik, Email [email protected]: Diabetes mellitus is frequently associated with foot ulcers, which pose significant health risks and complications. Impaired wound healing in diabetic patients is attributed to multiple factors, including hyperglycemia, neuropathy, chronic inflammation, oxidative damage, and decreased vascularization.Rationale: To address these challenges, this project aims to develop bioactive, fast-dissolving nanofiber dressings composed of polyvinylpyrrolidone loaded with a combination of an antibiotic (moxifloxacin or fusidic acid) and anti-inflammatory drug (pirfenidone) using electrospinning technique to prevent the bacterial growth, reduce inflammation, and expedite wound healing in diabetic wounds.Results: The fabricated drug-loaded fibers exhibited diameters of 443 ± 67 nm for moxifloxacin/pirfenidone nanofibers and 488 ± 92 nm for fusidic acid/pirfenidone nanofibers. The encapsulation efficiency, drug loading and drug release studies for the moxifloxacin/pirfenidone nanofibers were found to be 70 ± 3% and 20 ± 1 μg/mg, respectively, for moxifloxacin, and 96 ± 6% and 28 ± 2 μg/mg, respectively, for pirfenidone, with a complete release of both drugs within 24 hours, whereas the fusidic acid/pirfenidone nanofibers were found to be 95 ± 6% and 28 ± 2 μg/mg, respectively, for fusidic acid and 102 ± 5% and 30 ± 2 μg/mg, respectively, for pirfenidone, with a release rate of 66% for fusidic acid and 80%, for pirfenidone after 24 hours. The efficacy of the prepared nanofiber formulations in accelerating wound healing was evaluated using an induced diabetic rat model. All tested formulations showed an earlier complete closure of the wound compared to the controls, which was also supported by the histopathological assessment. Notably, the combination of fusidic acid and pirfenidone nanofibers demonstrated wound healing acceleration on day 8, earlier than all tested groups.Conclusion: These findings highlight the potential of the drug-loaded nanofibrous system as a promising medicated wound dressing for diabetic foot applications.Keywords: diabetes mellitus, diabetic foot ulcers, nanofibers, electrospinning, drug delivery, wound healing, moxifloxacin, fusidic acid, pirfenidon

Meningococcal, influenza virus, and hepatitis B virus vaccination coverage level among health care workers in Hajj

Abstract Background The objective of this study was to assess the compliance of health care workers (HCWs) employed in Hajj in receiving the meningococcal, influenza, and hepatitis B vaccines. Methods A cross-sectional survey of doctors and nurses working in all Mena and Arafat hospitals and primary health care centers who attended Hajj-medicine training programs immediately before the beginning of Hajj of the lunar Islamic year 1423 (2003) using self-administered structured questionnaire which included demographic data and data on vaccination history. Results A total of 392 HCWs were studied including 215 (54.8%) nurses and 177 (45.2%) doctors. One hundred and sixty four (41.8%) HCWs were from Makkah and the rest were recruited from other regions in Saudi Arabia. Three hundred and twenty three (82.4%) HCWs received the quadrivalent (ACYW135) meningococcal meningitis vaccine with 271 (83.9%) HCWs receiving it at least 2 weeks before coming to Hajj, whereas the remaining 52 (16.1%) HCWs received it within Conclusion The meningococcal and hepatitis B vaccination coverage level among HCWs in Hajj was suboptimal and the influenza vaccination level was notably low. Strategies to improve vaccination coverage among HCWs should be adopted by all health care facilities in Saudi Arabia.</p

A Cell-Free Microtiter Plate Screen for Improved [FeFe] Hydrogenases

, a potential renewable fuel. Attempts to exploit these catalysts in engineered systems have been hindered by the biotechnologically inconvenient properties of the natural enzymes, including their extreme oxygen sensitivity. Directed evolution has been used to improve the characteristics of a range of natural catalysts, but has been largely unsuccessful for [FeFe] hydrogenases because of a lack of convenient screening platforms. [FeFe] hydrogenase HydA1 with a specific activity ∼4 times that of the wild-type enzyme. cell extracts, which allows unhindered access to the protein maturation and assay environment

Individual identification via electrocardiogram analysis

Background: During last decade the use of ECG recordings in biometric recognition studies has increased. ECG characteristics made it suitable for subject identification: it is unique, present in all living individuals, and hard to forge. However, in spite of the great number of approaches found in literature, no agreement exists on the most appropriate methodology. This study aimed at providing a survey of the techniques used so far in ECG-based human identification. Specifically, a pattern recognition perspective is here proposed providing a unifying framework to appreciate previous studies and, hopefully, guide future research. Methods: We searched for papers on the subject from the earliest available date using relevant electronic databases (Medline, IEEEXplore, Scopus, and Web of Knowledge). The following terms were used in different combinations: electrocardiogram, ECG, human identification, biometric, authentication and individual variability. The electronic sources were last searched on 1st March 2015. In our selection we included published research on peer-reviewed journals, books chapters and conferences proceedings. The search was performed for English language documents. Results: 100 pertinent papers were found. Number of subjects involved in the journal studies ranges from 10 to 502, age from 16 to 86, male and female subjects are generally present. Number of analysed leads varies as well as the recording conditions. Identification performance differs widely as well as verification rate. Many studies refer to publicly available databases (Physionet ECG databases repository) while others rely on proprietary recordings making difficult them to compare. As a measure of overall accuracy we computed a weighted average of the identification rate and equal error rate in authentication scenarios. Identification rate resulted equal to 94.95 % while the equal error rate equal to 0.92 %. Conclusions: Biometric recognition is a mature field of research. Nevertheless, the use of physiological signals features, such as the ECG traits, needs further improvements. ECG features have the potential to be used in daily activities such as access control and patient handling as well as in wearable electronics applications. However, some barriers still limit its growth. Further analysis should be addressed on the use of single lead recordings and the study of features which are not dependent on the recording sites (e.g. fingers, hand palms). Moreover, it is expected that new techniques will be developed using fiducials and non-fiducial based features in order to catch the best of both approaches. ECG recognition in pathological subjects is also worth of additional investigations

Transcriptional activation of the Axl and PDGFR-α by c-Met through a ras- and Src-independent mechanism in human bladder cancer

<p>Abstract</p> <p>Background</p> <p>A cross-talk between different receptor tyrosine kinases (RTKs) plays an important role in the pathogenesis of human cancers.</p> <p>Methods</p> <p>Both NIH-Met5 and T24-Met3 cell lines harboring an inducible human c-Met gene were established. C-Met-related RTKs were screened by RTK microarray analysis. The cross-talk of RTKs was demonstrated by Western blotting and confirmed by small interfering RNA (siRNA) silencing, followed by elucidation of the underlying mechanism. The impact of this cross-talk on biological function was demonstrated by Trans-well migration assay. Finally, the potential clinical importance was examined in a cohort of 65 cases of locally advanced and metastatic bladder cancer patients.</p> <p>Results</p> <p>A positive association of Axl or platelet-derived growth factor receptor-alpha (PDGFR-α) with c-Met expression was demonstrated at translational level, and confirmed by specific siRNA knock-down. The transactivation of c-Met on Axl or PDGFR-α <it>in vitro </it>was through a <it>ras</it>- and Src-independent activation of mitogen-activated protein kinase/extracellular signal-regulated kinase (MEK/ERK) pathway. In human bladder cancer, co-expression of these RTKs was associated with poor patient survival (<it>p </it>< 0.05), and overexpression of c-Met/Axl/PDGFR-α or c-Met alone showed the most significant correlation with poor survival (<it>p </it>< 0.01).</p> <p>Conclusions</p> <p>In addition to c-Met, the cross-talk with Axl and/or PDGFR-α also contributes to the progression of human bladder cancer. Evaluation of Axl and PDGFR-α expression status may identify a subset of c-Met-positive bladder cancer patients who may require co-targeting therapy.</p

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

Pooled analysis of WHO Surgical Safety Checklist use and mortality after emergency laparotomy

Background The World Health Organization (WHO) Surgical Safety Checklist has fostered safe practice for 10 years, yet its place in emergency surgery has not been assessed on a global scale. The aim of this study was to evaluate reported checklist use in emergency settings and examine the relationship with perioperative mortality in patients who had emergency laparotomy. Methods In two multinational cohort studies, adults undergoing emergency laparotomy were compared with those having elective gastrointestinal surgery. Relationships between reported checklist use and mortality were determined using multivariable logistic regression and bootstrapped simulation. Results Of 12 296 patients included from 76 countries, 4843 underwent emergency laparotomy. After adjusting for patient and disease factors, checklist use before emergency laparotomy was more common in countries with a high Human Development Index (HDI) (2455 of 2741, 89.6 per cent) compared with that in countries with a middle (753 of 1242, 60.6 per cent; odds ratio (OR) 0.17, 95 per cent c.i. 0.14 to 0.21, P <0001) or low (363 of 860, 422 per cent; OR 008, 007 to 010, P <0.001) HDI. Checklist use was less common in elective surgery than for emergency laparotomy in high-HDI countries (risk difference -94 (95 per cent c.i. -11.9 to -6.9) per cent; P <0001), but the relationship was reversed in low-HDI countries (+121 (+7.0 to +173) per cent; P <0001). In multivariable models, checklist use was associated with a lower 30-day perioperative mortality (OR 0.60, 0.50 to 073; P <0.001). The greatest absolute benefit was seen for emergency surgery in low- and middle-HDI countries. Conclusion Checklist use in emergency laparotomy was associated with a significantly lower perioperative mortality rate. Checklist use in low-HDI countries was half that in high-HDI countries.Peer reviewe

Global variation in anastomosis and end colostomy formation following left-sided colorectal resection

Background End colostomy rates following colorectal resection vary across institutions in high-income settings, being influenced by patient, disease, surgeon and system factors. This study aimed to assess global variation in end colostomy rates after left-sided colorectal resection. Methods This study comprised an analysis of GlobalSurg-1 and -2 international, prospective, observational cohort studies (2014, 2016), including consecutive adult patients undergoing elective or emergency left-sided colorectal resection within discrete 2-week windows. Countries were grouped into high-, middle- and low-income tertiles according to the United Nations Human Development Index (HDI). Factors associated with colostomy formation versus primary anastomosis were explored using a multilevel, multivariable logistic regression model. Results In total, 1635 patients from 242 hospitals in 57 countries undergoing left-sided colorectal resection were included: 113 (6·9 per cent) from low-HDI, 254 (15·5 per cent) from middle-HDI and 1268 (77·6 per cent) from high-HDI countries. There was a higher proportion of patients with perforated disease (57·5, 40·9 and 35·4 per cent; P < 0·001) and subsequent use of end colostomy (52·2, 24·8 and 18·9 per cent; P < 0·001) in low- compared with middle- and high-HDI settings. The association with colostomy use in low-HDI settings persisted (odds ratio (OR) 3·20, 95 per cent c.i. 1·35 to 7·57; P = 0·008) after risk adjustment for malignant disease (OR 2·34, 1·65 to 3·32; P < 0·001), emergency surgery (OR 4·08, 2·73 to 6·10; P < 0·001), time to operation at least 48 h (OR 1·99, 1·28 to 3·09; P = 0·002) and disease perforation (OR 4·00, 2·81 to 5·69; P < 0·001). Conclusion Global differences existed in the proportion of patients receiving end stomas after left-sided colorectal resection based on income, which went beyond case mix alone

Naphthaquinones of Alkanna orientalis (L.) Boiss

The roots of Alkanna orientalis (L.) Boiss yielded &#945;- methyl-n-butyl alkannin (compound 1) and alkannin acetate (compound 2). The compounds were identified by UV, MS, 1H NMR and 13C NMR. Quantitative determination of &#945;- methyl-n-butyl alkannin and alkannin acetate in Alkanna orientalis (L) Boiss roots was established by TLC densitometry. Keywords: Alkanna orientalis; naphthaquinones; NMR; &#945;- methyl-n-butyl alkannin; alkannin acetate; TLC densitometry The African Journal of Traditional, Complementary and Alternative Medicines Vol. 4 (1) 2007: pp. 55-5