Risperidone Pellets, Pycnogenol®, and Glucomannan Gummy Formulation for Managing Weight Gain and ADHD in Autistic Children.

Gummy formulations are defined as gradually or slowly released solid oral dosage forms. Risperidone is an atypical antipsychotic medication used to treat schizophrenia and autism-related irritability. This study presents the development of visually appealing, patient-tailored medicated gummies that act as a novel pharmaceutical form of Risperidone for pediatrics. In this study, two gummy bases were used, one containing Glucomannan and the other containing Gelatin as a gelling agent, where these gummy bases were loaded with coated Risperidone pellets with a controlled release layer. The final products were evaluated for their pH, viscosity, content uniformity, drug content, and dissolution profile. Both formulas showed proper rheology and met content and weight uniformity standards. The release rates for F1 and F2 in the acidic media were 25% and 11%, respectively, after 2 h. At the same time, a full-release profile for Risperidone was noticed in both formulae at pH 6.8 where the release lasts for 24 h. It can be concluded that the chewable semi-solid dosages (gummies) filled with coated pellets are suitable for pediatric patients since pediatrics have drug-related problems which can be solved using high gastro-resistance coated pellets, which also shows a proper release profile for the drug.

In Vivo Evaluation of Chitosan-Titanium Dioxide Nanopowder as Wound Dressing Material.

BACKGROUND: Films used for wound healing have many advantages, but should be flexible, robust, adherable and prevent maceration. Both Chitosan (CS) and Titanium dioxide nanopowder (TiO2 NP) have good properties to accelerate wound healing and can be used in preparing films. OBJECTIVE: CS and TiO2 NP are combined to formulate films for wound healing. The physical, thermal, chemical, and mechanical characteristics of these films are to be assessed. The antibacterial activity of the films and their performance on wounded rats will be explored. METHODS: Films made of CS and TiO2 NP were characterized by FTIR, TGA, DSC, XRD, and SEM. The films' mechanical characteristics and antimicrobial activity were tested. Films with acceptable mechanical properties were evaluated on rats. RESULTS: Generally, CS-TiO2 films had higher weight and thickness but lowered flexibility compared to films prepared using CS only. The chosen film showed excellent folding endurance with weight and thickness of around 21.98 mg and 0.16 mm. The surface pH for CS-TiO2 films was acidic, and for the selected film, it was 5.18. CS-TiO2 film was active against all studied bacteria and significantly higher than CS films. The antimicrobial activity of Gram-negative bacteria (P. aeruginosa and E. coli) was higher than that of Gram-positive bacteria (S. aureus). Finally, adding TiO2 NP to the films accelerated the healing process of the created wounds in a murine model, compared to control and CS-treated groups. CONCLUSION: Films of TiO2 NP and CS have suitable properties to be used in wound healing and can be further used in the future to load drugs.

Short-Term and Long-Term Stability of Medial Olivocochlear Reflex in Adults with Typical Hearing.

This study aimed to assess the stability of Medial Olivocochlear Reflex (MOCR) function in typical hearing adults with the use of Contralateral Suppression (CS) of Distortion Product Otoacoustic Emissions (DPOAEs). This study included fifty-three (90 ears) participants between the ages of 18-30. Participants were divided into 3 groups (Group A-daily stability, Group B-short-term stability, and Group C- long-term stability). For each group, 4 measurements (30 × 4 = 120sessions) were taken. Group A measurements were taken daily, Group B measurements were taken weekly and Group C measurements were taken monthly. DPOAEs and Contralateral Suppression of DPOAEs were measured for each group. Analyses indicated that Medial Olivocochlear Reflex (MOCR) measured through contralateral suppression of DPOAE was unstable. This result indicates a DPOAE-based measure of the MOCR was not repeated across time. A great deal has been learned using CS of DPOAEs to study medial efferent activation, but several unresolved methodological issues that could impact the data to produce poor stability across time. Those methodological issues need to be explored and researched in the future.

HAZ, a novel peptide with broad-spectrum antibacterial activity.

Objective: The growing microbial resistance to antibiotics is a global public concern, which creates serious needs for newer antimicrobial agents. Antimicrobial peptides (AMPs) are increasingly exploited in drug development as therapeutic candidates. Here, we aimed to design and characterize a novel peptide with broad spectrum antimicrobial activity. Methods: Hybridization and sequence modification approaches were used to design the novel peptide, named HAZ, aiming at optimizing the physicochemical parameters involved in antimicrobial activity. Peptide activities were assessed alone or combined with different selected antibiotics against various sensitive and drug-resistant bacterial strains. In addition, the hemolysis and the cytotoxic activities of HAZ peptide were evaluated on human red blood cells and epithelial adenocarcinoma cells (A549), respectively. Results: HAZ peptide was sequentially modified to result in favored physicochemical parameters (helicity 95.24 %, hydrophobic ratio 47 %, and net charge of 8 + ). Functional assessment of HAZ revealed significant antimicrobial activity, with MIC values of 15 - 20 µM against tested bacterial strains. It also exhibited biofilm eradication activity at slightly higher concentrations. HAZ-antibiotics combinations exhibited a synergistic action mode that led to dramatic decrease in the MIC values for both HAZ peptide and the antibiotic. Such efficacy was accompanied with minimal hemolytic toxicity on human erythrocytes. Importantly, HAZ displayed promising anticancer activity against human lung cancer cells. Conclusion: Rationally-designed antimicrobial peptides offer promising alternatives to the current antibiotics for management of infectious diseases. HAZ peptide is a broad-spectrum AMP, and a promising candidate for antimicrobial and anticancer drug development.

Polymeric Nanoparticles for Inhaled Vaccines.

Many recent studies focus on the pulmonary delivery of vaccines as it is needle-free, safe, and effective. Inhaled vaccines enhance systemic and mucosal immunization but still faces many limitations that can be resolved using polymeric nanoparticles (PNPs). This review focuses on the use of properties of PNPs, specifically chitosan and PLGA to be used in the delivery of vaccines by inhalation. It also aims to highlight that PNPs have adjuvant properties by themselves that induce cellular and humeral immunogenicity. Further, different factors influence the behavior of PNP in vivo such as size, morphology, and charge are discussed. Finally, some of the primary challenges facing PNPs are reviewed including formulation instability, reproducibility, device-related factors, patient-related factors, and industrial-level scale-up. Herein, the most important variables of PNPs that shall be defined in any PNPs to be used for pulmonary delivery are defined. Further, this study focuses on the most popular polymers used for this purpose.

An Update on Laboratory-Based Diagnostic Biomarkers for Multiple Sclerosis and Beyond.

BACKGROUND: Multiple sclerosis (MS) is an immune-mediated central nervous system (CNS) inflammatory demyelinating disease in which analysis of clinical presentation, imaging studies, and laboratory tests aid in diagnosis. CONTENT: This review discusses laboratory tests ordered to rule out and rule in MS, such as the traditional measurement of cerebrospinal fluid (CSF) IgG index and oligoclonal bands. Biomarkers discovered in the past 2 decades, such as aquaporin-4 (AQP4) antibodies and myelin oligodendrocyte glycoprotein (MOG) antibodies, have been incorporated into clinical practice in the diagnosis of disorders referred to as MS mimics. The importance of test selection, assay methodology, optimal sample for testing, and diagnostic utility of these biomarkers is reviewed. Other laboratory testing that can aid in the differentiation between MS and these biomarker-defined CNS demyelinating diseases is described. There is a focus on emerging biomarkers such as the use of kappa immunoglobulin free light chain concentration in CSF and kappa CSF index measurement as an alternative to oligoclonal bands which has a potential for an improvement in laboratory workflows. Finally, the role of biomarkers of disease activity and prognosis are discussed, including neurofilament light chain, glial fibrillary acidic protein, and myelin basic protein. Future perspectives with improved laboratory testing tools and discovery of additional biomarkers are provided. SUMMARY: Laboratory testing for demyelinating disorders using CSF and serum are routine practices that can benefit from an update, as novel biomarker-defined entities have reduced the potential for MS misdiagnosis, and CSF/serum biomarkers reinstated in the diagnostic criteria of MS.

The Pattern of Thyroid Malignancy and Its Associated Characteristics Among United Arab Emirates Population With More Focus on Patients in the Bethesda III Category.

INTRODUCTION: Thyroid cancer is the most prevalent endocrine cancer worldwide. It is the second most common type of cancer among United Arab Emirates (UAE) women and ranks as the sixth most common type of cancer overall among the UAE population. There are limited studies in the UAE related to thyroid malignancy. This study aimed to determine the pattern of thyroid malignancy among the UAE population and its associated characteristics, with more emphasis on patients categorized as Bethesda III by cytopathology, and furthermore, to determine the significance of advanced diagnostic methods in the assessment of thyroid nodules. METHODS: A retrospective review of the electronic medical charts of adult patients (age 18 and above) who were diagnosed with a thyroid nodule by ultrasound during the years 2019 and 2020. It is a comparative study of different variables associated with thyroid nodules and thyroid malignancy. RESULTS: A total of 1072 patients were diagnosed with thyroid nodules upon initial ultrasound. We had 174 patients diagnosed with thyroid malignancy, constituting 16% (95% CI 0.14-0.19) of the total study population. 78% of the thyroid malignancy patients were women as compared to men, and this difference was statistically significant (p=0.042). Non-UAE nationals comprised 61% of the population diagnosed with thyroid malignancy (95% CI 1.37-2.68). Malignancy was found to be more common in patients with multinodular goiter, in the 30 to 39-year age group, and in patients with high ultrasound and Bethesda grades. From the total study population, 140 patients had cytology reports in the Bethesda III category. Thyroid malignancy was found in 30 patients with Bethesda III, and this comprised 17% of the total population who were diagnosed with thyroid malignancy. CONCLUSION: Despite being a single-center study, it highlights the percentage of thyroid malignancy and its associated factors among the UAE population. Thyroid ultrasound grading and Bethesda classification guide physicians in risk stratification, but it remains challenging in patients who fall into the Bethesda III category. Intervention versus regular follow-up should not depend on a single value but on the overall clinical picture and the use of advanced diagnostic methods.

Preparation and Characterization of Docetaxel-PLGA Nanoparticles Coated with Folic Acid-chitosan Conjugate for Cancer Treatment.

The conjugation of chitosan (CS) and folic acid (FA) was prepared and used to coat PLGA nanoparticles (NPs) that are loaded with Docetaxel (DTX) to target cancer cells that have lower pH and overexpression of folate receptors in comparison to normal cells. Three formulations had been prepared to reach the highest loading capacity (LC%) and encapsulation efficiency (EE%) and to study the effect of the amount of FA-CS on the drug release. The sizes, charges, homogeneity, surface morphology, LC% and EE% of the NPs were determined. The NPs were characterized using FTIR and XRD. In vitro release profiles of DTX from PLGA NPs, at pH 5.5 and 7.4 were determined. Finally, in vitro cytotoxicity assay on three cancer cell lines (RPMI 2650, Calu-3, and A549) was studied. The sizes of the three formulations ranged between 250.3±1.7 and 356.3±17.7. All prepared formulations showed acceptable monodispersity with highly positive charges. The EE% was above 85% and the LC% ranged between 6-35%. The in vitro release of DTX show an inverse relation to the amounts of FA-CS used and the pH of the dissolution medium. Coated PLGA NPs showed a significant difference in RPMI 2650, Calu-3, and A549 cell viability in comparison to free DTX. The NPs components were safe and non-toxic to human cells. In conclusion, coating PLGA NPs with FA-CS may be used as a good carrier for chemotherapeutic agents that selectively target carcinogenic tissues.

CSF Kappa Free Light Chains: Cutoff Validation for Diagnosing Multiple Sclerosis.

OBJECTIVE: To determine and validate a cerebrospinal fluid (CSF) κ (KCSF) value statistically comparable to detection of CSF-specific oligoclonal bands (OCB) to support the diagnosis of multiple sclerosis (MS). PATIENTS AND METHODS: A total of 702 retrospective and 657 prospective paired CSF/serum samples from residual waste samples of physician-ordered OCB tests were obtained and tested for KCSF at Mayo Clinic. Charts were reviewed by a neurologist blinded to KCSF results. Specificity and sensitivity for MS diagnosis were evaluated to establish a diagnostic cutoff value for KCSF in the retrospective cohort and then validated in the prospective cohort. RESULTS: Retrospective and prospective subgroups, respectively, included MS (n=85, 70), non-MS (n=615, 585), and undetermined diagnosis (excluded, n=2, 2). The retrospective data established a KCSF cutoff value of 0.1 mg/dL to be comparable to OCB testing. In the retrospective subgroup, KCSF vs OCB sensitivities for diagnosis of MS were 68.2% vs 75.0% (P=.08) and specificities were 86.1% vs 87.6% (P=.27). The KCSF area under the receiver operating characteristic curve was 0.772 (95% CI, 0.720 to 0.824), and for OCB was 0.813 (95% CI, 0.764 to 0.861). The prospective cohort was then used to validate the diagnostic KCSF value of 0.1 mg/dL; KCSF vs OCB sensitivities were 78.6% for both (P>.99) and specificities were 87.1% vs 89.4% (P=.09). CONCLUSION: The KCSF value of 0.1 mg/dL is a valid alternative to OCB testing, offering a standardized quantitative measure, eliminating human error, reducing cost and turnaround time, with no significant difference in sensitivity and specificity. This study provides class I evidence that a KCSF value of 0.1 mg/dL can be used in place of OCB testing to support the diagnosis of MS.

Strabismus Surgery Outcomes and Their Determinants in Patients with Chronic Sixth Nerve Palsy.

PURPOSE: Patients with chronic sixth nerve palsy (CSNP) comprise a heterogeneous population, and the optimal surgical solution remains uncertain. Here, we present the success rate and factors associated with the success of strabismus surgeries for CSNP. METHODS: This was a retrospective cohort study of patients with strabismus due to CSNP operated on between 2015 and 2019 in a tertiary eye hospital in central Saudi Arabia. Surgical success was defined as a horizontal deviation of ≤10 prism diopters (PDs) assessed at least 12 months after surgery. Differences between groups with respect to the primary outcome were assessed. RESULTS: Fifty-five patients were analyzed with a median follow-up of 24 (range 12-48) months. Superior rectus and inferior rectus transposition (34.5%) and medial rectus recession with lateral rectus resection (32.7%) were the main surgeries performed. The overall success rate was 67.3% (95% confidence interval 54.9-79.7). Bilateral CSNP (P = 0.05), a higher preoperative angle of deviation (P = 0.002), or a greater degree of preoperative limitation of abduction (P = 0.012), but not the type of surgery (P = 0.09), were more likely to result in an under-corrected outcome of >10 PD. The preoperative deviation angle showed a trend toward being associated with a poor outcome after surgery (P = 0.06). Six patients with high-angle deviation before surgery required second surgery. CONCLUSION: While the surgical procedure does not impact outcomes, the severity of preoperative horizontal deviation might impact surgical success and the need for reoperation. Patients with severe CSNP should be counseled appropriately about the chances of surgical success and the potential need for further interventions.

The effect of grape seed and green tea extracts on the pharmacokinetics of imatinib and its main metabolite, N-desmethyl imatinib, in rats.

BACKGROUND: Imatinib is mainly metabolized by CYP3A4 and to a lesser extent by other isoenzymes, with N-desmethyl imatinib being its major equipotent metabolite. Being a CYP3A4 substrate, imatinib co-administration with CYP3A4 modulators would change its pharmacokinetic profile. The cancer chemoprevention potential and anticancer efficacy of many herbal products such as grape seed (GS) and green tea (GT) extracts had led to an increase in their concomitant use with anticancer agents. GS and GT extracts were demonstrated to be potent inhibitors of CYP3A4. The aim of this study is to investigate the effect of standardized GS and/or GT extracts at two different doses on the pharmacokinetics of imatinib and its metabolite, N-desmethyl imatinib, in SD-rats. METHODS: Standardized GS and/or GT extracts were administered orally once daily for 21 days, at low (l) and high (h) doses, 50 and 100 mg/kg, respectively, before the administration of a single intragastric dose of imatinib. Plasma samples were collected and analyzed for imatinib and N-desmethyl imatinib concentrations using LC-MS/MS method, then their non-compartmental pharmacokinetic parameters were determined. RESULTS: h-GS dose significantly decreased imatinib's Cmax and the [Formula: see text] by 61.1 and 72.2%, respectively. Similar effects on N-desmethyl imatinib's exposure were observed as well, in addition to a significant increase in its clearance by 3.7-fold. l-GT caused a significant decrease in imatinib's Cmax and [Formula: see text] by 53.6 and 63.5%, respectively, with more significant effects on N-desmethyl imatinib's exposure, which exhibited a significant decrease by 79.2 and 81.1%, respectively. h-GT showed similar effects as those of l-GT on the kinetics of imatinib and its metabolite. However, when these extracts were co-administered at low doses, no significant effects were shown on the pharmacokinetics of imatinib and its metabolite. Nevertheless, increasing the dose caused a significant decrease in Cmax of N-desmethyl imatinib by 71.5%. CONCLUSIONS: These results demonstrated that the pharmacokinetics of imatinib and N-desmethyl imatinib had been significantly affected by GS and/or GT extracts, which could be partially explained by the inhibition of CYP3A-mediated metabolism. However, the involvement of other kinetic pathways such as other isoenzymes, efflux and uptake transporters could be involved and should be characterized.

Piperine Alters the Pharmacokinetics and Anticoagulation of Warfarin in Rats.

INTRODUCTION: Piperine, the bioactive compound of black pepper, and warfarin are metabolized by cytochrome P450 enzymes and are both highly plasma protein-bound compounds. In this study, we evaluated the effect of co-administered piperine on the pharmacokinetics and anticoagulation of warfarin in rats. METHODS: We studied four Sprague-Dawley rat groups: a negative control group receiving only oral warfarin, a test group receiving warfarin plus piperine, a positive control group receiving warfarin plus sulfaphenazole (CYP2C inhibitor), and another positive control group receiving warfarin plus ketoconazole (CYP3A inhibitor). We also analyzed plasma concentrations of warfarin and its major metabolite, 7-hydoxywarfarin. Blood clotting time, calculated as international normalized ratio (INR), was also measured. RESULTS: Our results showed that although co-administration of piperine produced a non-significant decrease in warfarin concentrations, it resulted in significantly lower 7-hydroxywarfarin metabolite concentrations. Piperine significantly decreased, by sixfold, AUC0-∞, by eightfold, Cmax, but significantly increased, by fivefold, CL/F and, by sixfold, Vd/F of 7-hydroxywarfarin. The INR values were consistent with the decrease in warfarin concentration in the presence of piperine and showed a significant decrease at 24 h after warfarin dose. CONCLUSION: We conclude that piperine could be a potent inhibitor of cytochrome P450 metabolism of warfarin in vivo and, contrary to the expectation, may reduce the plasma concentration and anticoagulation of warfarin. This interaction could have a clinical significance and should be investigated in patients.

The effect of cannabidiol on the pharmacokinetics of carbamazepine in rats.

Carbamazepine (CBZ) is mainly metabolized by CYP3A4 into carbamazepine-10,11-epoxide (CBZE). Cannabidiol (CBD) is a potent inhibitor of the CYP3A family. The aim of this study is to determine the effect of acute and chronic administration of CBD on the pharmacokinetics of CBZ and CBZE. Male SD rats were assigned into four acute and four chronic groups: control (CBZ only), positive control (ketoconazole), low-dose cannabidiol (l-CBD), and high-dose cannabidiol (h-CBD). Acute CBD groups were administered a single dose of CBD, while chronic CBD groups were given multiple doses of CBD for 14 days (q.d.) before CBZ administration. Plasma samples had been collected and analyzed for CBZ and CBZE, then their noncompartmental pharmacokinetic parameters before and after CBD administration were determined. The co-administration of a single l-CBD has significantly increased CBZ's [Formula: see text] by 53.1%. Furthermore, CBZE kinetics showed a significant decrease in Cmax by 31.8%. Acute h-CBD caused similar effects on CBZ's [Formula: see text] with 40.4% significant decrease in CBZE's Cmax, when compared to the control. Chronic h-CBD caused a significant decrease in CBZ's Cmax and [Formula: see text] by 75.3% and 65.7%, respectively. Besides, [Formula: see text] and Cmax of CBZE significantly decreased by 75.3% and 78.3%, respectively. These results demonstrated that the pharmacokinetics of CBZ and CBZE had been significantly affected by CBD. When CBD has been administered as a single dose, the effect is believed to be mainly caused by the inhibition of CBZ metabolism through CYP3A. The effect of chronic administration of CBD probably includes kinetic pathways other than the inhibition of CYP3A-dependent pathways. Graphical abstract.

Simultaneous determination of warfarin and 7-hydroxywarfarin in rat plasma by HPLC-FLD.

In this study, high-performance liquid chromatography with fluorescence detection (HPLC-FLD) has been used for the first time, for direct determination of warfarin and its major metabolite, 7-hydroxywarfarin, in rat plasma. The simple and sensitive method was developed using Fortis® reversed-phase diphenyl column (150 × 4.6 mm, 3 µm) and a mobile phase composed of phosphate buffer (25 mmol L-1)/methanol/acetonitrile (70:20:10, V/V/V), adjusted to pH 7.4, at a flow rate of 0.8 mL min-1. The diphenyl chemistry of the stationary phase provided a unique selectivity for separating the structurally related aromatic analytes, warfarin and 7-hydroxywarfarin, allowing their successful quantification in the complex plasma matrix. The method was linear over the range 0.01-25 µg mL-1, for warfarin and 7-hydroxywarfarin, and was found to be accurate, precise and selective in accordance with US FDA guidance for bioanalytical method validation. The method was sensitive enough to quantify 0.01 µg mL-1 of warfarin and 7-hydroxywarfarin (LLOQ) using only 100 µL of plasma. The applicability of this method was demonstrated by analyzing samples obtained from rats after oral administration of a single warfarin dose, and studying warfarin and 7-hydroxywarfarin pharmacokinetics.

Gold nanoparticles and angiogenesis: molecular mechanisms and biomedical applications.

Angiogenesis is the formation of new blood vessels from pre-existing vessels. It is a highly regulated process as determined by the interplay between pro-angiogenic and anti-angiogenic factors. Under certain conditions the balance between angiogenesis stimulators and inhibitors is altered, which results in a shift from physiological to pathological angiogenesis. Therefore, the goal of therapeutic targeting of angiogenic process is to normalize vasculature in target tissues by enhancing angiogenesis in disease conditions of reduced vascularity and blood flow, such as tissue ischemia, or alternatively to inhibit excessive and abnormal angiogenesis in disorders like cancer. Gold nanoparticles (AuNPs) are special particles that are generated by nanotechnology and composed of an inorganic core containing gold which is encircled by an organic monolayer. The ability of AuNPs to alter vasculature has captured recent attention in medical literature as potential therapeutic agents for the management of pathologic angiogenesis. This review provides an overview of the effects of AuNPs on angiogenesis and the molecular mechanisms and biomedical applications associated with their effects. In addition, the main synthesis methods, physical properties, uptake mechanisms, and toxicity of AuNPs are briefly summarized.

Untargeted Metabolite Profiling of Cerebrospinal Fluid Uncovers Biomarkers for Severity of Late Infantile Neuronal Ceroid Lipofuscinosis (CLN2, Batten Disease).

Late infantile neuronal ceroid lipofuscinosis (CLN2 disease) is a rare lysosomal storage disorder caused by a monogenetic deficiency of tripeptidyl peptidase-1 (TPP1). Despite knowledge that lipofuscin is the hallmark disease product, the relevant TPP1 substrate and its role in neuronal physiology/pathology is unknown. We hypothesized that untargeted metabolite profiling of cerebrospinal fluid (CSF) could be used as an effective tool to identify disease-associated metabolic disruptions in CLN2 disease, offering the potential to identify biomarkers that inform on disease severity and progression. Accordingly, a mass spectrometry-based untargeted metabolite profiling approach was employed to differentiate CSF from normal vs. CLN2 deficient individuals. Of 1,433 metabolite features surveyed, 29 linearly correlated with currently employed disease severity scores. With tandem mass spectrometry 8 distinct metabolite identities were structurally confirmed based on retention time and fragmentation pattern matches, vs. standards. These putative CLN2 biomarkers include 7 acetylated species - all attenuated in CLN2 compared to controls. Because acetate is the major bioenergetic fuel for support of mitochondrial respiration, deficient acetylated species in CSF suggests a brain energy defect that may drive neurodegeneration. Targeted analysis of these metabolites in CSF of CLN2 patients offers a powerful new approach for monitoring CLN2 disease progression and response to therapy.

Bridging medical simulation with computer science and engineering: A growing field of study.

BACKGROUND: Medical simulation has become an essential educational tool in the curricula of healthcare professionals. A literature review revealed a knowledge gap in healthcare simulation education with respect to the technological expertise required to operate highly sophisticated simulation equipment. With this motivation, a case study was designed to determine if implementing on-site technological expertise allows for the facile navigation of high fidelity manikins. Next, a research study was conducted to evaluate engineering students understanding of simulation, and their interest to attend a program in medical simulation. OBJECTIVES: To determine if on-site technological expertise lifts barriers associated with manikin use and to assess levels of understanding and interest among engineering students following exposure to the technology used in healthcare simulation. DESIGN: A prospective, descriptive study with pre-post surveys. SETTINGS: The Nursing Skills and Simulation Center at a New England University campus. PARTICIPANTS: Engineering students attending 6 different engineering programs (Computer Science, Computer Engineering, Mechanical Engineering, Biomedical Engineering, Electrical Engineering and Technology Management) and having different educational levels (undergraduate and graduate). METHODS: Two assessments were applied to engineering students attending a class on technology used in healthcare simulation. A pre-test measured the understanding and interest of students in the engineering/computer science courses before attending a simulation class. A post-test assessment measured their improvement in understanding and interest to learn more about simulation technologies. RESULTS: Statistical analysis and comparisons of pre-and post-test assessments show a 23% gain in understanding of this field following exposure to the healthcare simulation class. Furthermore, post test results show greater than 67% of those surveyed have an interest in attending a program in healthcare simulation. CONCLUSIONS: The results indicate the collaboration of nursing and engineering has lifted known barriers to simulation education, and reveal engineering students have an interest in the field of medical simulation.

Pramlintide, an antidiabetic, is antineoplastic in colorectal cancer and synergizes with conventional chemotherapy.

BACKGROUND: Approximately 90% of patients with metastatic colorectal cancer fail therapy mainly due to resistance. Taking advantage of currently approved agents for treatment of disease conditions other than cancer for the identification of new adjuvant anticancer therapies is highly encouraged. Pramlintide is a parenteral antidiabetic agent that is currently approved for treatment of types 1 and 2 diabetes mellitus. OBJECTIVES: To address the antineoplastic potential of pramlintide in colorectal cancer and to evaluate the ability of pramlintide to enhance the cytotoxicity of 5-fluorouracil, oxaliplatin, and irinotecan against colorectal cancer cell lines expressing wild-type and mutant p53. MATERIALS AND METHODS: The antiproliferative effect of pramlintide alone or in combination with 5-fluorouracil, oxaliplatin, or irinotecan in HCT-116 and HT-29 colorectal cancer cell lines was investigated using MTT cell proliferation assay. IC50 values were calculated using Compusyn software 1.0. Synergy values (R) were calculated using the ratio of IC50 of each primary drug alone divided by combination IC50s. For each two pairs of experiments, Student's t-test was used for analysis. For combination studies, one-way analysis of variance and Tukey post hoc testing was performed using R 3.3.2 software. A p-value of <0.05 was considered significant. RESULTS: Pramlintide inhibited the growth of HCT-116 and HT-29 in a dose-dependent manner, with higher efficacy against the latter (IC50s; 48.67 and 9.10 µg/mL, respectively; p-value =0.013). Moreover, the addition of 5, 10, and 20 µg/mL of pramlintide to HCT-116 and HT-29 with 5-fluorouracil, oxaliplatin, or irinotecan induced the antiproliferative effect synergistically (R>1.6, p-value <0.05). CONCLUSION: Pramlintide enhances the cytotoxicity of conventional chemotherapy against colorectal cancer cell lines harboring wild-type or mutant p53. Thus, pramlintide is a promising potential adjuvant chemotherapy in colorectal cancer.

In vitro lung epithelial cell transport and anti-interleukin-8 releasing activity of liposomal ciprofloxacin.

As a promising long-acting inhaled formulation, liposomal ciprofloxacin (Lipo-CPFX) was characterized in the in vitro human lung epithelial Calu-3 cell monolayer system, compared to ciprofloxacin in solution (CPFX). Its modulated absorptive transport and uptake, and sustained inhibitory activity against induced pro-inflammatory interleukin-8 (IL-8) release were examined. The absorptive transport and uptake kinetics for Lipo-CPFX and CPFX were determined at 0.1-50 mg/ml in the Transwell system. The Lipo-CPFX transport was then challenged for mechanistic exploration via cell energy depletion, a reduced temperature, endocytosis and/or lipid fusion inhibition, and addition of excess non-loaded liposomes. The inhibitory activities of Lipo-CPFX and CPFX against lipopolysaccharide (LPS)-induced IL-8 release were assessed in a co-incubation or pre-incubation mode. In the tight Calu-3 cell monolayers, Lipo-CPFX yielded 15-times slower ciprofloxacin flux of absorptive transport and 5-times lower cellular drug uptake than CPFX. Its transport appeared to be transcellular; kinetically linear, proportional to encapsulated ciprofloxacin concentration; and consistent with the cell energy-independent lipid bilayer fusion mechanism. Lipo-CPFX was equipotent to CPFX in the anti-IL-8 releasing activity upon 24 h co-incubation with LPS. Additionally, Lipo-CPFX, but not CPFX, retained the anti-IL-8 releasing activity even 24 h after pre-incubation. In conclusion, Lipo-CPFX enabled slower absorptive lung epithelial cell transport and uptake of ciprofloxacin, apparently via the lipid bilayer fusion mechanism, and the sustained inhibitory activity against LPS-induced IL-8 release, compared to CPFX.