Preparation and in vivo Assessment of Nystatin-Loaded Solid Lipid Nanoparticles for Topical Delivery against Cutaneous Candidiasis

Solid lipid nanoparticles (SLNs) have gained great attention for the topical treatment of skin associated fungal infection as they facilitate the skin penetration of loaded drugs. Our work deals with the preparation of nystatin loaded solid lipid nanoparticles (NystSLNs) using the hot homogenization and ultrasonication method. The prepared NystSLNs were characterized in terms of entrapment efficiency, particle size, zeta potential, transmission electron microscopy, differential scanning calorimetry, rheological behavior and in vitro drug release. A stability study for 6 months was performed. A microbiological study was conducted in male rats infected with Candida albicans, by counting the colonies and examining the histopathological changes induced on the skin of infected rats. The results showed that SLNs dispersions are spherical in shape with particle size ranging from 83.26±11.33 to 955.04±1.09 nm. The entrapment efficiencies are ranging from 19.73±1.21 to 72.46±0.66% with zeta potential ranging from -18.9 to -38.8 mV and shear-thinning rheological Behavior. The stability studies done for 6 months showed that nystatin (Nyst) is a good candidate for topical SLN formulations. A least number of colony forming unit/ ml (cfu/ml) was recorded for the selected NystSLN compared to the drug solution and the commercial Nystatin® cream present in the market. It can be fulfilled from this work that SLNs provide a good skin targeting effect and may represent promising carrier for topical delivery of Nyst offering the sustained release and maintaining the localized effect, resulting in an effective treatment of cutaneous fungal infection

The prognostic significance of minimal residual disease in adult Egyptian patients with precursor acute lymphoblastic leukemia

AbstractBackgroundMinimal residual disease (MRD) studies in adult acute lymphoblastic leukemia (ALL) give highly significant prognostic information superior to other standard criteria as age, gender and total leucocytic count (TLC) in distinguishing patients at high and low risk of relapse.ObjectivesWe aimed to determine the value of MRD monitoring by flowcytometry (FCM) in predicting outcome in adult Precursor ALL patients.Patients and methodsBone marrow (BM) samples were analyzed by 4-color FCM collected at diagnosis and after induction therapy (MRD1) to correlate MRD positivity with disease free survival (DFS) and overall survival (OS).ResultsStudy included 57 adult ALL patients (44 males and 13 females) with a median age of 22years (18–49). DFS showed no significant difference with age, gender and initial TLC (p=0.838, 0.888 and 0.743, respectively). Cumulative DFS at 2years was 34% for B-lineage ALL (n: 35) and 57% for T-lineage ALL (n: 18) (p=0.057). Cumulative DFS at 2years was 7% for MRD1 positive (high risk, HR) versus 57% for MRD1 negative patients (Low risk, LR) (p<0.001). Cumulative DFS at 2years was 29% for HR patients (n: 26) versus 55% for LR (n: 27) according to GMALL classification (p=0.064). Cumulative OS did not differ according to age, gender and TLC (p=0.526, 0.594 and 0.513, respectively). Cumulative OS at 2years was 36% for B ALL (n: 39) versus 77% for TALL (n: 18) (p=0.016) and was 49% for Philadelphia chromosome (Ph) negative patients versus 0% for Ph-positive patients (p<0.001). Regarding MRD1, OS at 2years was 18% for MRD1 HR (n: 17) versus 65% for MRD1 LR (n: 38) (p<0.001). OS was 35% for high-risk patients (n: 30) and 62% for low-risk patients (n: 27) classified according to GMALL risk stratification (p=0.017).ConclusionMRD by FCM is a strong independent predictor of outcome in terms of DFS and OS and is a powerful informative parameter in guiding individual treatment in ALL patients

Characteristic maps for the Brauer algebra

The classical characteristic map associates symmetric functions to characters of the symmetric groups. There are two natural analogues of this map involving the Brauer algebra. The first of them relies on the action of the orthogonal or symplectic group on a space of tensors, while the second is provided by the action of this group on the symmetric algebra of the corresponding Lie algebra. We consider the second characteristic map both in the orthogonal and symplectic case, and calculate the images of central idempotents of the Brauer algebra in terms of the Schur polynomials. The calculation is based on the Okounkov--Olshanski binomial formula for the classical Lie groups. We also reproduce the hook dimension formulas for representations of the classical groups by deriving them from the properties of the primitive idempotents of the symmetric group and the Brauer algebra.Comment: 23 pages, minor changes made, a reference adde

Vicious walkers, friendly walkers and Young tableaux II: With a wall

We derive new results for the number of star and watermelon configurations of vicious walkers in the presence of an impenetrable wall by showing that these follow from standard results in the theory of Young tableaux, and combinatorial descriptions of symmetric functions. For the problem of $n$-friendly walkers, we derive exact asymptotics for the number of stars and watermelons both in the absence of a wall and in the presence of a wall.Comment: 35 pages, AmS-LaTeX; Definitions of n-friendly walkers clarified; the statement of Theorem 4 and its proof were correcte

Coral spawning in the Gulf of Oman and relationship to latitudinal variation in spawning season in the northwest Indian Ocean

Despite a wealth of information on sexual reproduction in scleractinian corals, there are regional gaps in reproductive records. In the Gulf of the Oman in the Arabian Sea, reproductive timing was assessed in four common species of broadcast spawning corals using field surveys of gamete maturity and aquarium observations of spawning activity. The appearance of mature gametes within the same month for Acropora downingi, A. hemprichii, Cyphastrea microphthalma and Platygyra daedalea (≥ 75% of colonies, n = 848) indicated a synchronous and multi-specific spawning season. Based on gamete disappearance and direct observations, spawning predominantly occurred during April in 2013 (75- 100% of colonies) and May in 2014 (77-94% of colonies). The difference in spawning months between survey years was most likely explained by sea temperature and the timing of lunar cycles during late-stage gametogenesis. These reproductive records are consistent with a latitudinal gradient in peak broadcast spawning activity at reefs in the northwestern Indian Ocean which occurs early in the year at low latitudes (January to March) and progressively later in the year at mid (March to May) and high (June to September) latitudes

Identification of priorities for improvement of medication safety in primary care: a PRIORITIZE study

Background Medication error is a frequent, harmful and costly patient safety incident. Research to date has mostly focused on medication errors in hospitals. In this study, we aimed to identify the main causes of, and solutions to, medication error in primary care. Methods We used a novel priority-setting method for identifying and ranking patient safety problems and solutions called PRIORITIZE. We invited 500 North West London primary care clinicians to complete an open-ended questionnaire to identify three main problems and solutions relating to medication error in primary care. 113 clinicians submitted responses, which we thematically synthesized into a composite list of 48 distinct problems and 45 solutions. A group of 57 clinicians randomly selected from the initial cohort scored these and an overall ranking was derived. The agreement between the clinicians’ scores was presented using the average expert agreement (AEA). The study was conducted between September 2013 and November 2014. Results The top three problems were incomplete reconciliation of medication during patient ‘hand-overs’, inadequate patient education about their medication use and poor discharge summaries. The highest ranked solutions included development of a standardized discharge summary template, reduction of unnecessary prescribing, and minimisation of polypharmacy. Overall, better communication between the healthcare provider and patient, quality assurance approaches during medication prescribing and monitoring, and patient education on how to use their medication were considered the top priorities. The highest ranked suggestions received the strongest agreement among the clinicians, i.e. the highest AEA score. Conclusions Clinicians identified a range of suggestions for better medication management, quality assurance procedures and patient education. According to clinicians, medication errors can be largely prevented with feasible and affordable interventions. PRIORITIZE is a new, convenient, systematic, and replicable method, and merits further exploration with a view to becoming a part of a routine preventative patient safety monitoring mechanism

Valsartan Improves Adipose Tissue Function in Humans with Impaired Glucose Metabolism: A Randomized Placebo-Controlled Double-Blind Trial

<div><h3>Background</h3><p>Blockade of the renin-angiotensin system (RAS) reduces the incidence of type 2 diabetes mellitus. In rodents, it has been demonstrated that RAS blockade improved adipose tissue (AT) function and glucose homeostasis. However, the effects of long-term RAS blockade on AT function have not been investigated in humans. Therefore, we examined whether 26-wks treatment with the angiotensin II type 1 receptor blocker valsartan affects AT function in humans with impaired glucose metabolism (IGM).</p> <h3>Methodology/Principal Findings</h3><p>We performed a randomized, double-blind, placebo-controlled parallel-group study, in which 38 subjects with IGM were treated with valsartan (VAL, 320 mg/d) or placebo (PLB) for 26 weeks. Before and after treatment, an abdominal subcutaneous AT biopsy was collected for measurement of adipocyte size and AT gene/protein expression of angiogenesis/capillarization, adipogenesis, lipolytic and inflammatory cell markers. Furthermore, we evaluated fasting and postprandial AT blood flow (ATBF) (¹³³Xe wash-out), systemic inflammation and insulin sensitivity (hyperinsulinemic-euglycemic clamp). VAL treatment markedly reduced adipocyte size (<em>P</em><0.001), with a shift toward a higher proportion of small adipocytes. In addition, fasting (<em>P</em> = 0.043) and postprandial ATBF (<em>P</em> = 0.049) were increased, whereas gene expression of angiogenesis/capillarization, adipogenesis and macrophage infiltration markers in AT was significantly decreased after VAL compared with PLB treatment. Interestingly, the change in adipocyte size was associated with alterations in insulin sensitivity and reduced AT gene expression of macrophage infiltration markers. VAL did not alter plasma monocyte-chemoattractant protein (MCP)-1, TNF-α, adiponectin and leptin concentrations.</p> <h3>Conclusions/Significance</h3><p>26-wks VAL treatment markedly reduced abdominal subcutaneous adipocyte size and AT macrophage infiltration markers, and increased ATBF in IGM subjects. The VAL-induced decrease in adipocyte size was associated with reduced expression of macrophage infiltration markers in AT. Our findings suggest that interventions targeting the RAS may improve AT function, thereby contributing to a reduced risk of developing cardiovascular disease and type 2 diabetes.</p> <h3>Trial Registration</h3><p>Trialregister.nl NTR721 (ISRCTN Registry: ISRCTN<a href="http://www.controlled-trials.com/isrctn/pf/42786336">42786336</a>)</p> </div

Under- treatment and under diagnosis of hypertension: a serious problem in the United Arab Emirates

BACKGROUND: Hypertension, notably untreated or uncontrolled, is a major risk factor for cardiovascular diseases (CVD) morbidity and mortality. In countries in transition, little is known about the epidemiology of hypertension, and its biochemical correlates. This study was carried out in Al Ain, United Arab Emirates, to characterize self-reported (SR) normotensives and hypertensives in terms of actual hypertension status, demographic variables, CVD risk factors, treatment, and sequalae. METHODS: A sample, stratified by SR hypertensive status, of 349 SR hypertensives (Mean age ± SD; 50.8 ± 9.2 yrs; Male: 226) and 640 SR normotensives (42.9 ± 9.3 yrs, Male: 444) among nationals and expatriates was used. Hypertensives and normotensive subjects were recruited from various outpatient clinics and government organizations in Al-Ain city, United Arab Emirates (UAE) respectively. Anthropometric and demographic variables were measured by conventional methods. RESULTS: Both under-diagnosis of hypertension (33%) and under-treatment (76%) were common. Characteristics of undiagnosed hypertensives were intermediate between normotensives and SR hypertensives. Under-diagnosis of hypertension was more common among foreigners than among nationals. Risk factors for CVD were more prevalent among SR hypertensives. Obesity, lack of exercise and smoking were found as major risk factors for CVD among hypertensives in this population. CONCLUSION: Hypertension, even severe, is commonly under-diagnosed and under-treated in the UAE. Preventive strategies, better diagnosis and proper treatment compliance should be emphasized to reduce incidence of CVD in this population

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

Background Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide.Methods A multimethods analysis was performed as part of the GlobalSurg 3 study-a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital.Findings Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3.85 [95% CI 2.58-5.75]; p&lt;0.0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63.0% vs 82.7%; OR 0.35 [0.23-0.53]; p&lt;0.0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer.Interpretation Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised