Enhancement of oral bioavailability via solid lipid nanoparticles of anticancer drug dasatinib - An in vitro cytotoxicity and pharmacokinetic study

Objective: Dasatinib (DST) is a BCS Class II drug having very low solubility and high permeability. Low aqueous solubility and poor dissolution of DST leads to poor bioavailability, Thus, limited aqueous solubility is the bottleneck for the therapeutic outcome of DST. Animal data suggests that the absolute bioavailability of DST is about 14 to 34% due to an extensive first-pass effect. To overcome hepatic first-pass metabolism and to enhance oral bioavailability, lipid–based drug delivery systems like solid lipid nanoparticles can be used.  Methods: Solid lipid nanoparticles (SLNs) are sub-micron colloidal carriers having a size range of 50–1000 nm. These are prepared with physiological lipid and dispersed in water or aqueous surfactant solution. Dasatinib can be conveniently loaded into solid lipid nanoparticles to improve the oral bioavailability by exploiting the intestinal lymphatic transport. An optimal system was evaluated for bioavailability study in rats compared with that of dasatinib suspension. Results: In vitro cytotoxicity study were done by MTT assay method through ATCC cell lines, the percent inhibition was more in SLN when compared with Suspension. The Pharmacokinetics of dasatinib-SLNs after oral administration in male wistar rats was studied. The bioavailability of dasatinib was increased by 2.28 fold when compared with that of a dasatinib suspension. Conclusion: The results are indicative of SLNs as suitable lipid based carrier system for improving the oral bioavailability of dasatinib. &nbsp

Pengukuran Kualitas Jaringan Internet dengan Sinyal 3G Lte pada STMIK Budi Darma Medan dengan Metode Quality Of Service (QoS)

In today\u27s age the internet needs are very important for communicating or looking for information. The longer the development of the internet network is increasingly widespread such as 1G, 2G, 3G and 4G technologies. Long Term Evolution (LTE) is a long-term radio evolution access network issued by the 3rd (Generation Partnership Project). To improve internet network services at STMIK Budidarma, testing and measurement are carried out using the Quality Of Service (QoS) method to determine the quality and power of data transfer. The Quality Of Service (QoS) method found on a TCP / IP network is one that focuses on allocating bandwidth within the internet network that flows fairly and as needed. The QoS method that relies on testing the process of delay time, latency time, packet request time and creating a network topology to reduce the risk that arises

Association of Environment With the Risk of Developing Psychotic Disorders in Rural Populations: Findings from the Social Epidemiology of Psychoses in East Anglia Study.

IMPORTANCE: Social determinants are important risk factors for the development of first-episode psychosis (FEP); their effects in rural areas are largely unknown. OBJECTIVE: To investigate neighborhood-level factors associated with FEP in a large, predominantly rural population-based cohort. DESIGN, SETTING, AND PARTICIPANTS: This study extracted data on referrals for treatment of potential FEP at 6 Early-Intervention Psychosis services from the Social Epidemiology of Psychoses in East Anglia naturalistic cohort study data set, which covered a population of more than 2 million people in a rural area in the East of England for a period of 3.5 years. All individuals aged 16 to 35 years who presented to Early-Intervention Psychosis services and met diagnostic criteria for first episodes of nonaffective psychoses and affective psychoses (International Statistical Classification of Diseases and Related Health Problems, Tenth Revision diagnostic codes F20-33) were included (n = 631). Persons whose disorders had an organic basis (diagnostic codes F06.X) and those meeting the criteria for substance-induced psychosis (diagnostic codes F1X.5) were excluded. We derived 4 neighborhood-level exposures from a routine population data set using exploratory factor analysis (racial/ethnic diversity, deprivation, urbanicity, and social isolation) and investigated intragroup racial/ethnic density and fragmentation. MAIN OUTCOMES AND MEASURES: Multilevel Poisson regression was performed to determine associations between incidence rates and neighborhood-level factors, after adjustment for individual factors. Results were reported as incidence rate ratios (IRRs). RESULTS: The study included 631 participants who met criteria for FEP and whose median age at first contact was 23.8 years (interquartile range, 19.6-27.6 years); 416 of 631 (65.9%) were male. Crude incidence of FEP was calculated as 31.2 per 100 000 person-years (95% CI, 28.9-33.7). Incidence varied significantly between neighborhoods after adjustment for age, sex, race/ethnicity, and socioeconomic status. For nonaffective psychoses, incidence was higher in neighborhoods that were more economically deprived (IRR, 1.13; 95% CI, 1.06-1.20) and socially isolated (IRR, 1.11; 95% CI, 1.04-1.19). It was lower in more racially/ethnically diverse neighborhoods (IRR, 0.94; 95% CI, 0.87-1.00). Higher intragroup racial/ethnic density (IRR, 0.97; 95% CI, 0.94-1.00) and lower intragroup racial/ethnic fragmentation (IRR, 0.98; 95% CI, 0.96-1.00) were associated with a reduced risk of affective psychosis. CONCLUSIONS AND RELEVANCE: Spatial variation in the incidence of nonaffective and affective psychotic disorders exists in rural areas. This suggests that the social environment contributes to psychosis risk across the rural-urban gradient

Outcomes of ceftriaxone compared with cefazolin or nafcillin/oxacillin for outpatient therapy for methicillin-sensitive Staphylococcus aureus bloodstream infections: Results from a large United States claims database

BACKGROUND: Ceftriaxone is a convenient option for methicillin-sensitive METHODS: In this retrospective cohort, a large insurance claims database was queried from 2010 to 2018 for adults with MSSA bloodstream infection (BSI). Patients discharged on OPAT on cefazolin or oxacillin/nafcillin were compared with ceftriaxone with respect to 90-day hospital readmission with the same infection category and 90-day all-cause readmission using logistic regression models. RESULTS: Of 1895 patients with MSSA BSI, 1435 (75.7%) patients received cefazolin, oxacillin, or nafcillin and 460 (24.3%) ceftriaxone. Readmission due to the same infection category occurred in 366 (19.3%), and all-cause readmission occurred in 535 (28.3%) within 90 days. Risk factors significantly associated with readmission with the same infection category were the oldest sampled age group (61-64 years: adjusted odds ratio [aOR], 1.47 [95% confidence interval {CI}, 1.01-2.14]), intensive care unit stay during index admission (aOR, 2.33 [95% CI, 1.81-3.01]), prosthetic joint infection (aOR, 1.96 [95% CI, 1.18-2.23]), central line-associated BSI (aOR, 1.72 [95% CI, 1.33-2.94]), and endocarditis (aOR, 1.63 [95% CI, 1.18-2.23]). Ceftriaxone was not associated with increased risk of readmission with the same infection category (aOR, 0.89 [95% CI, .67-1.18]), or 90-day all-cause readmission (aOR, 0.86 [95% CI, .66-1.10]) when compared with oxacillin/nafcillin/cefazolin. CONCLUSIONS: In this cohort of MSSA BSI patients discharged on OPAT, there were no differences in outcomes of readmission with the same infection and 90-day all-cause readmission in patients treated with ceftriaxone compared to oxacillin/nafcillin or cefazolin. Patients with complicated BSIs such as endocarditis and epidural abscess were more likely to be prescribed cefazolin or oxacillin/nafcillin

Hydrothermal Synthesis and Characterization of One-dimensional Ceria Nanorod for Chromium Ion Removal from Wastewater

Remediation of wastewater contaminated with Cr(VI) species by ceria particles has received considerable attention in recent years. The main objectives of the present study were to investigate the adsorption of Cr(VI) species on the one-dimensional (1-D) ceria nanorod (CeNR). In where, CeNR has 20–40 nm in diameter and 200–300 nm in length, as confirmed through FE-SEM and TEM images. Higher surface area of CeNR is insisted to the remediation of Cr(VI)-contaminated wastewaters. This work exemplifies the utilization of XAS and BET to reveal the speciation of CeNR for further understands of the very complex adsorption process. It is also very clear that decontamination of Cr species in wastewater via the in-situ remediation with CeNR permeable reactive barriers would be environmentally attractive in the near future. Keywords: Cr(VI)-contaminant, One-dimensional Ceria, Wastewater treatment; XANES/EXAFS

Prevalence, underlying causes, and preventability of sepsis-associated mortality in US acute care hospitals

Importance: Sepsis is present in many hospitalizations that culminate in death. The contribution of sepsis to these deaths, and the extent to which they are preventable, is unknown. Objective: To estimate the prevalence, underlying causes, and preventability of sepsis-associated mortality in acute care hospitals. Design, Setting, and Participants: Cohort study in which a retrospective medical record review was conducted of 568 randomly selected adults admitted to 6 US academic and community hospitals from January 1, 2014, to December 31, 2015, who died in the hospital or were discharged to hospice and not readmitted. Medical records were reviewed from January 1, 2017, to March 31, 2018. Main Outcomes and Measures: Clinicians reviewed cases for sepsis during hospitalization using Sepsis-3 criteria, hospice-qualifying criteria on admission, immediate and underlying causes of death, and suboptimal sepsis-related care such as inappropriate or delayed antibiotics, inadequate source control, or other medical errors. The preventability of each sepsis-associated death was rated on a 6-point Likert scale. Results: The study cohort included 568 patients (289 [50.9%] men; mean [SD] age, 70.5 [16.1] years) who died in the hospital or were discharged to hospice. Sepsis was present in 300 hospitalizations (52.8%; 95% CI, 48.6%-57.0%) and was the immediate cause of death in 198 cases (34.9%; 95% CI, 30.9%-38.9%). The next most common immediate causes of death were progressive cancer (92 [16.2%]) and heart failure (39 [6.9%]). The most common underlying causes of death in patients with sepsis were solid cancer (63 of 300 [21.0%]), chronic heart disease (46 of 300 [15.3%]), hematologic cancer (31 of 300 [10.3%]), dementia (29 of 300 [9.7%]), and chronic lung disease (27 of 300 [9.0%]). Hospice-qualifying conditions were present on admission in 121 of 300 sepsis-associated deaths (40.3%; 95% CI 34.7%-46.1%), most commonly end-stage cancer. Suboptimal care, most commonly delays in antibiotics, was identified in 68 of 300 sepsis-associated deaths (22.7%). However, only 11 sepsis-associated deaths (3.7%) were judged definitely or moderately likely preventable; another 25 sepsis-associated deaths (8.3%) were considered possibly preventable. Conclusions and Relevance: In this cohort from 6 US hospitals, sepsis was the most common immediate cause of death. However, most underlying causes of death were related to severe chronic comorbidities and most sepsis-associated deaths were unlikely to be preventable through better hospital-based care. Further innovations in the prevention and care of underlying conditions may be necessary before a major reduction in sepsis-associated deaths can be achieved

High Performance Anticorrosive Polyester Coatings on Mild Steel In Mixed Acid Mixtures Environments

Anticorrosive polyester based composite coatings on mild steel applied to mixed acid storage tank containing varying compositions of Sulfuric Acid, Nitric acid provide anticorrosive solutions. These coatings are capable to inhibit the redox reactions. In consideration of above, the purpose of present work is to prevent corrosion on mixed acid storage tank through application of appropriate polyester coatings on their surface and structures that will be used in chemical industries where these acids are being stored. In this project, the surface of mild steel was coated by protective polymer coatings. Lab scale storage tanks of mild steel were coated with anticorrosive (fiber reinforced laminate-vinyl and fiber reinforced laminate palatal p-4). Various coatings compositions were explored based on esters. Electrochemical Impedance Spectroscopy (EIS), Gamry Potentiostat Tafel Scan analyses tools were used and Scanning Electron Microscopy (SEM) was conducted to investigate the surface morphology of these coatings. The applied polymer based composite coatings provided excellent corrosion resistance in both Laminate palatal fiber reinforced (LAM-P/FR) and laminate vinyl fiber reinforced (LAM-V/FR) coatings condition and reduction in corrosion rate. These bespoke coatings can be widely used to protect mild steel structures which are usually acid storage tanks and are used in various chemical industries with acidic environment. The study estimated that 25 to 30% of annual corrosion costs could be saved as well as production increases if these corrosion protection coatings were employed

Predictors of disengagement from Early Intervention in Psychosis services.

BACKGROUND: The effectiveness of Early Intervention in Psychosis (EIP) services for individuals with a first episode of psychosis (FEP) could be thwarted by high rates of early disengagement.AimsTo investigate which factors predict disengagement with EIP services. METHOD: Using data from a naturalistic cohort of 786 EIP clients in East Anglia (UK), we investigated the association between sociodemographic and clinical predictors and disengagement using univariable and multivariable Cox proportional hazards models. RESULTS: Over half (54.3%) of our sample were discharged before receiving 3 years of EIP care, with 92 (11.7%) participants discharged due to disengagement. Milder negative symptoms, more severe hallucinations, not receiving an FEP diagnosis, polysubstance use and being employed were associated with greater disengagement. CONCLUSIONS: Our findings highlight heterogeneous reasons for disengagement with EIP services. For some patients, early disengagement may hinder efforts to sustain positive long-term EIP outcomes. Efforts to identify true FEP cases and target patients with substance use problems and more severe positive symptoms may increase engagement.Declaration of interestNone

Molecular identification and genetic diversity study of the Iraqi truffles

The aim of this study is to investigate the molecular identification of the Iraqi truffles species and a better understanding of genetic diversity in the center of the truffles habitat. Thirty-two samples were collected from the Iraqi desert and local markets. Samples were chosen depending on the morphological diversity of the fruit body and sample collection area. Results of ITS region sequencing for the 32 samples showed two genuses Tirmania and Terfezia are the main dominant, 4 species of Tirmania pinoyi and 28 species of Terfezia claveryi. All species sequences were deposited in NCBI GenBank and all had accessions number. The neighbor-Joining method was used to generate a phylogenic tree to study the genetic diversity of the ITS sequences for the 32 Iraqi truffle samples. Results showed a high genetic diversity for the Iraqi truffles samples. The phylogenic study showed Iraqi truffles clustered with different groups as a clade with the reference sequences from other countries represent three continents Asia, Africa, and Europe. Also, we found in this study a unique cluster group for the Iraqi sequences for T. pinoyi and T. claveryi truffles cluster in one group and do not match with any reference sequences used in this study. This is a piece of strong evidence proofed the Iraqi habitat could be the origin of center diversity for the T. pinoyi and T. claveryi truffles