Chitinase-functionalized UiO-66 framework nanoparticles active against multidrug-resistant Candida Auris.

Candida auris (C. auris) is a yeast that has caused several outbreaks in the last decade. Cell wall chitin plays a primary role in the antifungal resistance of C. auris. Herein, we investigated the potential of chitinase immobilized with UiO-66 to act as a potent antifungal agent against C. auris. Chitinase was produced from Talaromyces varians SSW3 in a yield of 8.97 U/g dry substrate (ds). The yield was statistically enhanced to 120.41 U/g ds by using Plackett-Burman and Box-Behnken design. We synthesized a UiO-66 framework that was characterized by SEM, TEM, XRD, FTIR, a particle size analyzer, and a zeta sizer. The produced framework had a size of 70.42 ± 8.43 nm with a uniform cubic shape and smooth surface. The produced chitinase was immobilized on UiO-66 with an immobilization yield of 65% achieved after a 6 h loading period. The immobilization of UiO-66 increased the enzyme activity and stability, as indicated by the obtained Kd and T1/2 values. Furthermore, the hydrolytic activity of chitinase was enhanced after immobilization on UiO-66, with an increase in the Vmax and a decrease in the Km of 2- and 38-fold, respectively. Interestingly, the antifungal activity of the produced chitinase was boosted against C. auris by loading the enzyme on UiO-66, with an MIC50 of 0.89 ± 0.056 U/mL, compared to 5.582 ± 0.57 U/mL for the free enzyme. This study offers a novel promising alternative approach to combat the new emerging pathogen C. auris.

'It's Just Not Working', a Qualitative Exploration of the Weight-Related Healthcare Experiences of Individuals of Arab Heritage With Higher Weight in Australia.

INTRODUCTION: Culturally and linguistically diverse population groups disproportionately experience higher weight and other non-weight-related discrimination in healthcare settings outside of their ancestral country. Little is known about the experiences of individuals with Arab heritage. This study aimed to qualitatively explore the intersectional weight-related healthcare experiences of individuals of Arab heritage with higher weight in Australia. METHODS: A general inductive enquiry approach was used. Purposive, convenience and snowball sampling was used to recruit individuals of Arab heritage residing in Australia. Individuals were invited to participate in an online semistructured interview. Interviews were recorded, transcribed and thematically analysed. RESULTS: Fifteen participants took part in the study. Of these participants, 93% were female (n = 14), 80% were aged between 18 and 44 years (n = 12), 73% were university educated (n = 11), 53% were born outside of Australia (n = 8) and all were Muslim (n = 15). Four main themes were identified: (1) appearance-based judgement, (2) generalised advice and assumptions, (3) cultural responsiveness and (4) healthcare system constraints. CONCLUSION: Individuals of Arab heritage with higher weight in Australia, namely, females, often perceive their healthcare experiences as dismissive of their cultural and religious needs and driven by causality assumptions around weight. It is crucial that care delivered encompasses cultural humility, is weight-inclusive and acknowledges systemic constraints. Cultural safety training benchmarks, healthcare management reform and weight-inclusive healthcare approaches are recommended to assist healthcare providers in delivering effective, holistic and culturally safe care. PATIENT OR PUBLIC CONTRIBUTION: Insights gained from conversations with Arab heritage community members with lived experiences regarding weight-related healthcare encounters informed the study design and approach.

Asthmatic children and MDI verbal inhalation technique counseling.

OBJECTIVES: The present work aimed to study the role of metered-dose inhalers (MDI) verbal counseling on asthmatic children patients inhalation technique and their pulmonary functions. METHODS: In this study many children younger than 18 years old with asthma were collected from University hospital outpatient clinics throughout two years period Their MDI inhalation technique was checked and the number of MDI inhalation technique mistakes were detected and corrected at the first visit and every month for two more visits (three visits). Their peak expiratory flow (PEF) and forced expiratory volume in 1 s (FEV1) as a percentage of the forced vital capacity (FVC) were checked at every visit. RESULTS: 81 asthmatic subjects (54 female) younger than 18 years old were collected with a mean (SD) age 14.4 (1.8) years old. Most of the patients' owned MDI contained salbutamol, however, some patients were using Beclometasone MDI or Beclometasone and salbutamol combination MDI. The mean number of correct steps performed was significantly increased (p < 0.05) as the number of visits increased. "Place the MDI mouthpiece between the teeth and seal with lips" and "To maintain slow inhalation rate until lungs are full" were the least steps correctly performed by the asthmatics children studied. There was a significant increase (p < 0.05) in the pulmonary function test scores at the third visit. CONCLUSIONS: MDI's verbal counseling should be repeated and checked at every opportunity, especially with children, to improve and maintain the recommended MDI inhalation technique. That could be a tool to possibly improve patients' pulmonary functions.

Development of Provesicular Nanodelivery System of Curcumin as a Safe and Effective Antiviral Agent: Statistical Optimization, In Vitro Characterization, and Antiviral Effectiveness.

Curcumin is a natural compound that has many medical applications. However, its low solubility and poor stability could impede its clinical applications. The present study aimed to formulate dry proniosomes to overcome these pitfalls and improve the therapeutic efficacy of Curcumin. Curcumin-loaded proniosomes were fabricated by the slurry method according to 32 factorial design using Design-Expert software to demonstrate the impact of different independent variables on entrapment efficiency (EE%) and % drug released after 12 h (Q12h). The optimized formula (F5) was selected according to the desirability criteria. F5 exhibited good flowability and appeared, after reconstitution, as spherical nanovesicles with EE% of 89.94 ± 2.31% and Q12h of 70.89 ± 1.62%. F5 demonstrated higher stability and a significant enhancement of Q12h than the corresponding niosomes. The docking study investigated the ability of Curcumin to bind effectively with the active site of DNA polymerase of Herpes simplex virus (HSV). The antiviral activity and the safety of F5 were significantly higher than Curcumin. F5 improved the safety of Acyclovir (ACV) and reduced its effective dose that produced a 100% reduction of viral plaques. Proniosomes could be promising stable carriers of Curcumin to be used as a safe and efficient antiviral agent.

Epidural levobupivacaine versus a combination of levobupivacaine and dexamethasone in patients receiving epidural analgesia.

BACKGROUND AND AIMS: The use of dexamethasone as an adjuvant to local anesthetic rarely has been described. Some studies have demonstrated the analgesic effect of local spinal and systemic corticosteroids in combination with bupivacaine. It works by decreasing inflammation and blocking transmission of nociceptive C-fibers and by stopping the ectopic discharge of the nerve. The aim of this randomized controlled trial was to compare the efficacy of epidural levobupivacaine alone versus a combination of levobupivacaine with dexamethasone for labor analgesia. MATERIAL AND METHODS: This prospective double-blind trial included the 60 primigravidas during vaginal delivery with a cervical dilatation ≥4 cm and 50% effacement randomly assigned to one of two groups - Group A (n=30): epidural levobupivacaine 0.125% in normal saline in a total volume of 15 mL and Group B (n=30): epidural levobupivacaine 0.125% in normal saline combined with dexamethasone 4 mg in a total volume of 15 mL. At first request of analgesia, 10 mL of 0.125% levobupivacaine was administrated through epidural catheter. Further analgesia was provided with 8 mL of 0.125% levobupivacaine hourly. Primary outcome measure was the duration of epidural analgesia. Secondary outcome measures include pain score by Visual Analog Scale score before the block and 15 min following it, the total amount of levobupivacaine used, Apgar score and umbilical vein blood gas analysis, maternal satisfaction, and side effects recorded. RESULTS AND CONCLUSION: The duration of epidural analgesia was significantly longer (P < 0.05) upon adding dexamethasone to levobupivacaine. Total epidural levobupivacaine consumption was significantly lower (P = 0.05) in Group B. There were no statistical differences between the two groups regarding hemodynamics, pain score, neonatal outcome, and complications. Epidural dexamethasone plus levobupivacaine prolongs the duration of epidural analgesia during management of labor pain with hemodynamic stability and limited maternal and neonatal adverse effects.

Endoscopic Ultrasound-Guided Fine-Needle Biopsy Versus Aspiration for Tissue Sampling Adequacy for Molecular Testing in Pancreatic Ductal Adenocarcinoma.

BACKGROUND AND AIMS: There is limited literature on sample adequacy for molecular testing in pancreatic ductal adenocarcinoma obtained via endoscopic ultrasound (EUS) fine-needle aspiration (FNA) versus EUS fine-needle biopsy (FNB). We aimed to compare these two modalities regarding sample adequacy for molecular and genomic sequencing. METHODS: We reviewed all patients with pancreatic ductal adenocarcinoma who underwent EUS at Saint Luke's Hospital from 2018 to 2021. The patients were categorized based on the method of EUS tissue acquisition, specifically FNA or FNB. A comprehensive evaluation was conducted for all cases by cytotechnologists. RESULTS: Out of 132 patients who underwent EUS-guided biopsies, 76 opted for FNA, 48 opted for FNB, and 8 opted for a combination of both. The average number of passes required for FNB and FNA was 2.58 ± 1.06 and 2.49 ± 1.07, respectively (p = 0.704), indicating no significant difference. Interestingly, 71.4% (35) of FNB-obtained samples were deemed adequate for molecular testing, surpassing the 32.1% (26) adequacy observed with FNA (p < 0.001). Additionally, 46.4% (26) of FNB-obtained samples were considered adequate for genomic testing, a notable improvement over the 23.8% (20) adequacy observed with FNA (p = 0.005). CONCLUSION: Although the number of passes required for cytologic diagnosis did not differ significantly between EUS-FNB and EUS-FNA, the former demonstrated superiority in obtaining samples adequate for molecular testing. Tumor surface area and cellularity were crucial parameters in determining sample adequacy for molecular testing, irrespective of the chosen tissue acquisition modality.

Accuracy of energy and nutrient intake estimation versus observed intake using 4 technology-assisted dietary assessment methods: a randomized crossover feeding study.

BACKGROUND: Technology-assisted 24-h dietary recalls (24HRs) have been widely adopted in population nutrition surveillance. Evaluations of 24HRs inform improvements, but direct comparisons of 24HR methods for accuracy in reference to a measure of true intake are rarely undertaken in a single study population. OBJECTIVES: To compare the accuracy of energy and nutrient intake estimation of 4 technology-assisted dietary assessment methods relative to true intake across breakfast, lunch, and dinner. METHODS: In a controlled feeding study with a crossover design, 152 participants [55% women; mean age 32 y, standard deviation (SD) 11; mean body mass index 26 kg/m2, SD 5] were randomized to 1 of 3 separate feeding days to consume breakfast, lunch, and dinner, with unobtrusive weighing of foods and beverages consumed. Participants undertook a 24HR the following day [Automated Self-Administered Dietary Assessment Tool-Australia (ASA24); Intake24-Australia; mobile Food Record-Trained Analyst (mFR-TA); or Image-Assisted Interviewer-Administered 24-hour recall (IA-24HR)]. When assigned to IA-24HR, participants referred to images captured of their meals using the mobile Food Record (mFR) app. True and estimated energy and nutrient intakes were compared, and differences among methods were assessed using linear mixed models. RESULTS: The mean difference between true and estimated energy intake as a percentage of true intake was 5.4% (95% CI: 0.6, 10.2%) using ASA24, 1.7% (95% CI: -2.9, 6.3%) using Intake24, 1.3% (95% CI: -1.1, 3.8%) using mFR-TA, and 15.0% (95% CI: 11.6, 18.3%) using IA-24HR. The variances of estimated and true energy intakes were statistically significantly different for all methods (P < 0.01) except Intake24 (P = 0.1). Differential accuracy in nutrient estimation was present among the methods. CONCLUSIONS: Under controlled conditions, Intake24, ASA24, and mFR-TA estimated average energy and nutrient intakes with reasonable validity, but intake distributions were estimated accurately by Intake24 only (energy and protein). This study may inform considerations regarding instruments of choice in future population surveillance. This trial was registered at Australian New Zealand Clinical Trials Registry as ACTRN12621000209897.

Impact of educational programme on patient's health outcomes following open heart surgeries.

BACKGROUND: Postcardiac surgery, numerous factors have been shown to predict postoperative harm of QoL, such as age, female sex, history of hypertension, chronic obstructive pulmonary disease, education level, marital status, and also psychological factors such as the presence of mood disorders. So, the essential key to self-management is behavioural change, which is necessary to improve the quality of life of patients and Health outcomes. AIM: The aim of this study is to evaluate the impact of the education programme on patients' health outcomes following open heart surgeries. PATIENTS AND METHODS: Quasi-experimental research design carried out in intensive care for open heart surgery in Suez Canal university hospitals at Ismailia Governate on all available both sex patients performing open heart surgery for 6-month period (60) using the following four tools: the first tool for patient's risk stratification model Euro Scale sheet; the second tool New York Heart Association scale for assessing functional abilities; the third tool for health outcomes sheet for assessing patient's quality of life and health status; and the fourth tool for assessing Hospital Anxiety and Depression Scale. RESULTS: There was no significant difference found in the patient's vital signs before and after the educational programme. On the other hand, there was no statistically significant difference between overall quality of life and socio-demographic characteristics before and after the educational programme. CONCLUSION: This study concluded that the educational programme has a positive effect on patients' quality of life in patients' educational programme; improve patient's health status as indicated by improved patient outcomes. RELEVANCE TO CLINICAL PRACTICE: The most important finding was the value of the educational training programme to address the needs of open heart surgery patients, indicating that after heart surgery, patient education by training can be helpful in self-care, and nurses can use a programme containing preparatory information to enhance results, alleviate patients problems, and improve the quality of life in patients with CABG.

Rare Case of a Clival Chondroma Resulting in Panhypopituitarism.

Chondromas are rare benign tumors composed of hyaline cartilage that can arise in various locations in the body. Their occurrence in the clivus, leading to panhypopituitarism, is exceptionally rare. This case report describes a 93-year-old female with a known clival chondroma who presented with altered mental status, presumed to be secondary to toxic metabolic encephalopathy due to an infectious cause. Further diagnostic evaluation revealed pituitary hormone levels below the normal range. This case report aims to highlight a unique case of panhypopituitarism attributed to a chondroma in the clivus with tumor extension to the sellar region, emphasizing the diagnostic challenges and treatment options for this unusual pathology.

Multifunctional 99mTc-5-azacitidine Gold Nanoparticles: Formulation, In Vitro Cytotoxicity, Radiosynthesis, and In Vivo Pharmacokinetic Study.

BACKGROUND: 5-azacitidine is a very potent chemotherapeutic agent that suffers from certain disadvantages. OBJECTIVE: This study aims to prepare gold nanoparticles as a new nano-formula of 5-azacitidine that can improve its bioavailability and decrease its side effects. METHODS: 5-azacytidine-loaded GA-AuNPs were prepared and characterized by UV-Vis spectroscopy, infrared (IR), and electronic transmission microscope (TEM). This new platform was characterized in vitro by measuring its zeta potential, particle size, and drug loading efficacy, and the anti-proliferative effect on the MCF-7 cell line was evaluated. In vivo biodistribution studies of 99mTc-5-aza solution and 99mTc-5-aza-gold nano formula were conducted in tumor-bearing mice by different routes of administration (intravenous and intra-tumor). RESULTS: 5-Aza-GA-AuNPs formula was successfully prepared with an optimum particle size of ≈34.66 nm, the zeta potential of -14.4 mV, and high entrapment efficiency. 99mTc-5-Aza-GA-AuNPs were successfully radiosynthesized with a labeling yield of 95.4%. Biodistribution studies showed high selective accumulation in tumor and low uptake in non-target organs in the case of the 5-Aza-GA-AuNPs formula than the 99mTc-5-azacitidine solution. CONCLUSION: 99mTc-5-Aza-GA-AuNPs improved the selectivity and uptake of 5-azacitidine in cancer. Moreover, 99mTc-5-Aza-GA-AuNPs could be used as hopeful theranostic radiopharmaceutical preparation for cancer.

Non-deteriorative eco-friendly water-saving tactic for removal of vegetable matters from wool fleece using xylanase and cellulase.

The carbonization of wool fleece (WF) is conducted to remove the adhered vegetable matter (VM) from contaminated WF using sulfuric acid, followed by drying and backing. This process has a deteriorative effect on WF and requires a tremendous quantity of water for rinsing WF after carbonization to remove any H2SO4 residuals. Herein, we propose an alternative eco-friendly water-saving process for the removal of VM from WF using enzymes. Cellulase-containing xylanase from the fungus Aspergillus terreus, and cellulase-free xylanase from the fungus Aspergillus flavus AW1 were used to remove the VM from WF. The effect of some process parameters on the amount of the removed VM was assessed. Alkali solubility as well as sulfur and cystine content were used to follow the alteration in the chemistry of the bio-treated WF. The fiber morphology was examined using scanning electron microscopy. The dyeability of the treated WF towards acid, reactive, and basic dyes was monitored. The results revealed that the removal of the VM from WF by applying the examined enzymes was effective and could be an appropriate, non-destructive, eco-friendly water-saving substitute to the conventional carbonization procedures. By virtue of enzyme specificity, the proposed process removed the VM without deteriorating the fiber.

Selective Androgen Receptor Modulators (SARMs)-Induced Liver Injury: A Case Report and Review of Literature.

Drug-induced liver injury (DILI) is one of the leading causes of death from acute liver failure (ALF) in the United States, accounting for approximately 13% of ALF cases in the United States. Selective androgen receptor modulators (SARMs) were first developed to increase muscle mass while avoiding the side effects of conventional androgenic steroids. Although not Food and Drug Administration (FDA) approved, they are widely available online and are consumed to enhance athletic performance. We report a 22-year-old, previously healthy male, who presented with a two-week history of worsening jaundice, nausea, fatigue, pruritus, dark urine, and light stools. He reported taking the SARM, RAD-140, for 16 weeks. Examination showed scleral icterus. The liver panel showed alkaline phosphatase (ALP) 5.3 µkat/L, alanine transaminase (ALT) 1.66 µkat/L, aspartate transaminase (AST) 1.18 µkat/L, direct bilirubin 294 µmol/L, total bilirubin 427.5 µmol/L, and international normalized ratio (INR) 0.9. Viral hepatitis and autoimmune panel were unremarkable. Alpha-1 antitrypsin and ceruloplasmin levels were within normal limits. Bile sludge was seen on ultrasound. Magnetic resonance cholangiopancreatography (MRCP) abdomen showed segmental narrowing of the intrahepatic ducts. Endoscopic retrograde cholangiopancreatography (ERCP) was unremarkable. Liver biopsy showed mixed portal hepatitis, cholestasis, and biliary reactive changes with ceroid-loaded macrophages; a picture consistent with DILI. The patient was treated supportively and discharged with scheduled hepatology follow-up. At the one-month follow-up, his total bilirubin had fallen from a peak of 530 mol/L to 188 mol/L. The diagnosis of DILI can be made based on the timing of exposure and the exclusion of other etiologies. Liver enzymes normalized three to 12 months after product discontinuation. We hope this report will remind primary care physicians of the potential hepatotoxic side effects of muscle-building compounds and encourage them to report suspected DILI to the FDA using the MedWatch system.

Novel nasal niosomes loaded with lacosamide and coated with chitosan: A possible pathway to target the brain to control partial-onset seizures.

This work aimed to develop and produce lacosamide-loaded niosomes coated with chitosan (LCA-CTS-NSM) using a thin-film hydration method and the Box-Behnken design. The effect of three independent factors (Span 60 amount, chitosan concentration, and cholesterol amount) on vesicle size, entrapment efficiency, zeta potential, and cumulative release (8 h) was studied. The optimal formulation of LCA-CTS-NSM was chosen from the design space and assessed for morphology, in vitro release, nasal diffusion, stability, tolerability, and in vivo biodistribution for brain targeting after intranasal delivery. The vesicle size, entrapment, surface charge, and in vitro release of the optimal formula were found to be 194.3 nm, 58.3%, +35.6 mV, and 81.3%, respectively. Besides, it exhibits sustained release behavior, enhanced nasal diffusion, and improved physical stability. Histopathological testing revealed no evidence of toxicity or structural damage to the nasal mucosa. It demonstrated significantly more brain distribution than the drug solution. Overall, the data is encouraging since it points to the potential for non-invasive intranasal administration of LCA as an alternative to oral or parenteral routes.

Quality by design approach for development and validation of a RP-HPLC method for simultaneous estimation of xipamide and valsartan in human plasma.

A new rapid, simple, and sensitive RP-HPLC method was carried out through applying Quality by Design approach for determination of xipamide and valsartan in Human plasma. Fractional factorial design was used for screening of four independent factors: pH, flow rate, detection wavelength, and % of MeOH. Analysis of variance (ANOVA) confirmed that flow rate and % of MeOH were only significant. Chromatographic conditions optimization was carried out through using central composite design. Method analysis was performed using BDS Hypersil C8 column (250 × 4.6 mm, 5 µm) and an isocratic mobile phase of MeOH and 0.05 M KH2PO4 buffer pH 3 (64.5:35.5, v/v) at 1.2 mL/min flow rate with UV detection at 240 nm and 10 µL injection volume. According to FDA guidelines, the method was then validated for the determination of the two drugs clinically in human plasma in respect of future pharmacokinetic and bioequivalence simulation studies. The standard curve was linear in the concentration range of 5-100 µg/mL for both drugs, with a determination coefficient (R2) of 0.999. Also, the average recoveries lied within the range from 99.89 to 100.03%. The proposed method showed good predictability and robustness.

Intranasal Delivery of Granisetron to the Brain via Nanostructured Cubosomes-Based In Situ Gel for Improved Management of Chemotherapy-Induced Emesis.

This research aimed to boost granisetron (GS) delivery to the brain via the intranasal route to better manage chemotherapy-induced emesis. Glycerol monooleate (GMO), Poloxamer 407 (P 407) and Tween 80 (T 80) were used to formulate GS-loaded cubosomes (GS-CBS) utilizing a melt dispersion-emulsification technique. GS-CBS were characterized by testing particle diameter, surface charge and entrapment efficiency. The formulations were optimized using a Box-Behnken statistical design, and the optimum formula (including GMO with a concentration of 4.9%, P 407 with a concentration of 10%, and T 80 with a concentration of 1%) was investigated for morphology, release behavior, ex vivo permeation through the nasal mucosa, and physical stability. Moreover, the optimal formula was incorporated into a thermosensitive gel and subjected to histopathological and in vivo biodistribution experiments. It demonstrated sustained release characteristics, increased ex vivo permeability and improved physical stability. Moreover, the cubosomal in situ gel was safe and biocompatible when applied to the nasal mucosa. Furthermore, compared to a drug solution, the nose-to-brain pathway enhanced bioavailability and brain distribution. Finally, the cubosomal in situ gel may be a potential nanocarrier for GS delivery to the brain through nose-to-brain pathway.

Potential Use of Tailored Citicoline Chitosan-Coated Liposomes for Effective Wound Healing in Diabetic Rat Model.

PURPOSE: This study aimed to formulate citicoline-loaded chitosan-coated liposomes (CT-CS-LPs) for topical administration and evaluated for wound healing in a diabetic animal model. METHODS: CT-LPs were formulated via a thin-film hydration approach and coated with chitosan (CS). Box-Behnken statistical design investigated the effects of lipid amount, chitosan concentration, and cholesterol amount on vesicle diameter, surface charge, and entrapment efficiency. The potential of the optimized CT-CS-LPs gel for wound healing was further evaluated in streptozocin-induced diabetic rats. The different healing stages were evaluated by several techniques, including general and special staining techniques, in addition to antibody immunohistochemistry. RESULTS: The optimized CT-CS-LPs obtained had a mean size of 211.6 nm, a 50.7% entrapment efficiency, and a positive surface charge of 32.1 mV. In addition, the optimized CT-CS-LPs exhibited in vitro sustained release behavior. The in vivo experiments revealed that treatment with the optimized CT-CS-LPs boosts the healing process of the skin wound in diabetic rats by reducing inflammation, accelerating re-epithelization, angiogenesis, fibroblast proliferation, and connective tissue remodeling, leading to rapid wound closure. CONCLUSION: Chitosan-coated liposomes containing citicoline have emerged as a potential approach for promoting the healing process in diabetic rats. However, the therapeutic effectiveness of the suggested approach in diabetic patients needs to be investigated.

An auxin-inducible, GAL4-compatible, gene expression system for Drosophila.

The ability to control transgene expression, both spatially and temporally, is essential for studying model organisms. In Drosophila, spatial control is primarily provided by the GAL4/UAS system, whilst temporal control relies on a temperature-sensitive GAL80 (which inhibits GAL4) and drug-inducible systems. However, these are not ideal. Shifting temperature can impact on many physiological and behavioural traits, and the current drug-inducible systems are either leaky, toxic, incompatible with existing GAL4-driver lines, or do not generate effective levels of expression. Here, we describe the auxin-inducible gene expression system (AGES). AGES relies on the auxin-dependent degradation of a ubiquitously expressed GAL80, and therefore, is compatible with existing GAL4-driver lines. Water-soluble auxin is added to fly food at a low, non-lethal, concentration, which induces expression comparable to uninhibited GAL4 expression. The system works in both larvae and adults, providing a stringent, non-lethal, cost-effective, and convenient method for temporally controlling GAL4 activity in Drosophila.

Prospective, randomized controlled study to assess the role of dexmedetomidine in patients with supratentorial tumors undergoing craniotomy under general anesthesia.

BACKGROUND: Preliminary data on the perioperative use of dexmedetomidine in patients undergoing craniotomy for brain tumor under general anesthesia indicate that the intraoperative administration of dexmedetomidine is opioid-sparing, results in less need for antihypertensive medication, and may offer greater hemodynamic stability at incision and emergence. Dexmedetomidine, alpha 2 adrenoceptor agonist, is used as adjuvant to anesthetic agents. Relatively recent studies have shown that dexmedetomidine is able to decrease circulating plasma norepinephrine and epinephrine concentration in approximately 50%, decreases brain blood flow by directly acting on post-synaptic alpha 2 receptors, decreases CSF pressure without ischemic suffering and effectively decreases brain metabolism and intracranial pressure and also, able to decrease injury caused by focal ischemia. PURPOSE: This prospective, randomized, double-blind study was designed to assess the perioperative effect of intraoperative infusion of dexmedetomidine in patients with supratentorial tumors undergoing craniotomy under general anesthesia. METHODS: Fourty patients with CT- scanning proof of supratentorial tumors were classified equally into 2 groups (twenty patients in each group). Group A:--Dexmedetomidine was given as a bolus dose of 1 microg/kg in 20 minutes before induction of anesthesia, followed by a maintenance infusion of 0.4 microg/kg/hr. The infusion was discontinued when surgery ended. Group B:--The patients received similar volumes of saline. RESULTS: Heart rate and mean arterial blood pressure, decreased significantly in patients of group A (dexmedetomidine group) compared to group B (placebo group) (p-value < 0.05). There was no significant statistical difference between the two groups regarding the central venous pressure and arterial partial pressure of carbon dioxide (p-value > 0.05). The intraoperative end-tidal sevoflurane (%) in patients of group A was less than in patients of group B (p-value < 0.05). The intracranial pressure decreased in patients of Group A more than group B (p-value < 0.05). The Glasgow coma scale (GCS) improved in patients of group A and deteriorated in patients of Group B with significant statistical difference between the two groups (p-value < 0.05). The total fentanyl requirements from induction to extubation of patients increased in patients of group B more than in patients of group A (p-value < 0.05). The total postoperative patients' requirements for antiemetic drugs within the 2 hours after extubation decreased in patients of group A more than group B (p-value < 0.05). The postoperative duration from the end of surgery to extubation decreased significantly in patients of group A more than group B (p-value < 0.05). The total urine output during the duration from drug administration to extubation of patients increased in patients of group A more than group B (p-value < 0.05). CONCLUSION: Continuous intraoperative infusion of dexmedetomidine during craniotomy for supratentorial tumors under general anesthesia maintained the hemodynamic stability, reduced sevoflurane and fentanyl requirements, decreased intracranial pressure, and improved significantly the outcomes.

Prospective, randomized study to assess the role of dexmedetomidine in patients with supratentorial tumors undergoing craniotomy under general anaesthesia.

BACKGROUND: Preliminary data on the perioperative use of dexmedetomidine in patients undergoing craniotomy for brain tumor under general anaesthesia indicate that the intraoperative administration of dexmedetomidine is opioid-sparing, results in less need for antihypertensive medication, and may offer greater hemodynamic stability at incision and emergence. Dexmedetomidine, alpha 2 adrenoceptor agonist used as adjuvant to anaesthetic agents. Relatively recent studies have shown that dexmedetomidine is able to decrease circulating plasma norepinephrine and epinephrine concentration in approximately 50%, decreases brain blood flow by directly acting on post-synaptic alpha 2 receptors, decreases CSF pressure without ischemic suffering and effectively decrease brain metabolism and intracranial pressure and also, able to decrease injury caused by focal ischemia. PURPOSE: This prospective, randomized, double-blind study was designed to assess the perioperative effect of intraoperative infusion of dexmedetomidine in patients with supratentorial tumors undergoing craniotomy under general anaesthesia. METHODS: Forty patients with CT- scanning proof of supratentorial tumors. The patients were classified equally into 2 groups (twenty patients in each group). Group A:--The dexmedetomidine was given as a bolus dose of 1 microg/kg in 20 minutes before induction of anaesthesia, followed by a maintenance infusion of 0.4 microg/kg/hr. The infusion was discontinued when surgery ended. Group B:--The patients received similar volumes of saline. RESULTS: The heart rate and mean arterial blood pressure, decreased in patients of group A (dexmedetomidine group) more than group B (placebo group) with significant statistical difference between the two groups (P-value <0.05). No significant statistical difference between the two groups regarding the central venous pressure and arterial partial pressure of Carbon Dioxide (P-value >0.05). The intraoperative end-tidal sevoflurane (%) in patients of group A less than in patients of group B (P-value <0.05).The intracranial pressure decreased in patients of Group A more than group B (P-value <0.05). The Glasgow coma scale (GCS) improved in patients of group A and deteriorated in patients of Group B with significant statistical difference between the two groups (P-value <0.05). The total fentanyl requirements from induction to extubation of patients increased in patients of group B more than in patients of group A (P-value <0.05). The total postoperative patients' requirements for antiemetic drugs within the 2 hours after extubation decreased in patients of group A more than group B (P-value <0.05). The postoperative duration from the end of surgery to extubation decreased significantly in patients of group A more than group B (P-value <0.05). The total urine output during the duration from drug administration to extubation of patients increased in patients of group A more than group B (P-value <0.05). CONCLUSIONS: Continuous intraoperative infusion of dexmedetomidine during craniotomy for supratentorial tumors under general anaesthesia maintained the haemodynamic stability, reduced sevoflurane and fentanyl requirements, decreased intracranial pressure, and improved significantly the outcomes.

Response Surface Optimization of Ultra-Elastic Nanovesicles Loaded with Deflazacort Tailored for Transdermal Delivery: Accentuated Bioavailability and Anti-Inflammatory Efficacy.

PURPOSE: The aim of the present study was to develop deflazacort (DFZ) ultra-elastic nanovesicles (UENVs) loaded gel for topical administration to evade gastrointestinal adverse impacts accompanying DFZ oral therapy. METHODS: UENVs were elaborated according to D-optimal mixture design employing different edge activators as Span-60, Tween-85 and sodium cholate which were incorporated into the nanovesicles to improve the deformability of vesicles bilayer. DFZ-UENVs were formulated by thin-film hydration technique followed by characterization for different parameters including entrapment efficiency (%EE), particle size, in vitro release and ex vivo permeation studies. The composition of the optimized DFZ-UENV formulation was found to be DFZ (10 mg), Span-60 (30 mg), Tween-85 (30 mg), sodium cholate (3.93 mg), L-α phosphatidylcholine (60 mg) and cholesterol (30 mg). The optimum formulation was incorporated into hydrogel base then characterized in terms of physical parameters, in vitro drug release, ex vivo permeation study and pharmacodynamics evaluation. Finally, pharmacokinetic study in rabbits was performed via transdermal application of UENVs gel in comparison to oral drug. RESULTS: The optimum UENVs formulation exhibited %EE of 74.77±1.33, vesicle diameter of 219.64±2.52 nm, 68.88±1.64% of DFZ released after 12 h and zeta potential of -55.57±1.04 mV. The current work divulged successful augmentation of the bioavailability of DFZ optimum formulation by about 1.37-fold and drug release retardation compared to oral drug tablets besides significant depression of edema, cellular inflammation and capillary congestion in carrageenan-induced rat paw edema model. CONCLUSION: The transdermal DFZ-UENVs can achieve boosted bioavailability and may be suggested as an auspicious non-invasive alternative platform for oral route.