Miracle-dz/UniFAR-FTUs huggingface dataset:
Placental passage of olomoucine II, but not purvalanol A, is affected by p-glycoprotein (ABCB1), breast cancer resistance protein (ABCG2) and multidrug resistance-associated proteins (ABCCs)

Abstract 1. Purine cyclin-dependent kinase inhibitors have recently been recognised as promising candidates for the treatment of various cancers. While pharmacodynamic properties of these compounds are relatively well understood, their pharmacokinetics including possible interactions with placental transport systems have not been characterised to date. 2. In this study, we investigated transplacental passage of olomoucine II and purvalanol A in rat focusing on possible role of p-glycoprotein (ABCB1), breast cancer resistance protein (ABCG2) and/or multidrug resistance-associated proteins (ABCCs). Employing the in situ method of dually perfused rat term placenta, we demonstrate transplacental passage of both olomoucine II and purvalanol A against the concentration gradient in foetus-to-mother direction. Using several ATP-binding cassette (ABC) drug transporter inhibitors, we confirm the participation of ABCB1, ABCG2 and ABCCs transporters in the placental passage of olomoucine II, but not purvalanol A. 3. Transplacental passage of olomoucine II and purvalanol A from mother to foetus is significantly reduced by active transporters, restricting thereby foetal exposure and providing protection against harmful effects of these xenobiotics. Importantly, we demonstrate that in spite of their considerable structural similarity, the two molecules utilise distinct placental transport systems. These facts should be kept in mind when introducing these prospective anticancer candidates and/or their analogues into the clinical area.
Impact of KRAS and TP53 Co-Mutations on Outcomes After First-Line Systemic Therapy Among Patients With STK11-Mutated Advanced Non-Small-Cell Lung Cancer.

PURPOSE The STK11 gene encodes a serine/threonine protein kinase that regulates cell polarity and functions as a tumor suppressor. Patients with non-small-cell lung cancer (NSCLC) and STK11 mutations often have other co-mutations. We evaluated the impact of KRAS and TP53 co-mutations on outcomes after first-line systemic therapy for patients with metastatic or recurrent NSCLC that harbors STK11 mutations. METHODS We conducted a retrospective review of patients with metastatic NSCLC and STK11 mutations treated at the University of Pennsylvania. STK11 mutations were identified through next-generation sequencing (NGS) in tissue or plasma. Cox proportional hazard models were used to determine the relationship between STK11 co-mutations and survival outcomes. The Kaplan-Meier method was used to estimate overall survival (OS) and progression-free survival (PFS). RESULTS From February 2013 to December 2016, samples from 1,385 patients with NSCLC were analyzed by NGS; of these, 77 patients (6%) harbored an STK11 mutation (n = 56, tissue; n = 21, plasma). Of the 62 patients included, 18 had an STK11 mutation alone, 19 had STK11/KRAS, 18 had STK11/TP53, and seven had STK11/KRAS/TP53. Patients with STK11/KRAS co-mutations had a worse median PFS (2.4 months) compared with STK11 alone (5.1 months; log-rank P = .048), STK11/TP53 (4.3 months; log-rank P = .043), and STK11/KRAS/ TP53 (13 months; log-rank P = .03). Patients with STK11/KRAS co-mutation experienced shorter median OS (7.1 months) compared with STK11 alone (16.1 months; log-rank P < .001), STK11/TP53 (28.3 months; log-rank P < .001), and STK11/KRAS/TP53 (22 months; log-rank P = .025). CONCLUSION Among patients with advanced NSCLC and STK11 mutations treated with first-line systemic therapy, co-mutation with KRAS was associated with significantly worse PFS and OS. By contrast, co-mutation of STK11 with TP53 conferred a better prognosis.
Bacterial Profile and Their Antimicrobial Susceptibility Patterns of Computer Keyboards and Mice at Gondar University Hospital, Northwest Ethiopia

Background: The microorganisms can found in every environment and pathogenic bacteria pose serious health problems. Computer keyboards and mice have been documented as an environmental object or fomites serving as sources of microorganisms particularly in the hospital setting. According to some reports, due to the application of the computer in the hospital environment, cross contamination of microorganism from healthcare provider to the patient is common. Objective: the aim of this study was to assess bacterial isolates and their drug susceptibility patterns from computer keyboards and mouse from Gondar University Hospital, Northwest Ethiopia. Methodology: A cross sectional study was conducted in Gondar University Hospital from April 30 to June 30/ 2013. Samples were collected from computers located in Gondar University Hospital by using sterile cotton swaps. Then the collected samples were inoculated on BAP, CAP and MAC media. The bacterial isolates were examined and identified by colonial morphology, Gram reaction and biochemical characteristics. Antibiotic susceptibility test was done by disc diffusion method. Data analysis was done by using SPSS version 20 and P - values less than 0.05 were considered statistically significant. Result: Growth was seen in all samples. From the total bacterial isolates, 208 (60.5%) were Gram positive bacteria and 136 (39.5%) were Gram negative bacteria. The isolates included Coagulase negative staphylococcus (CoNs), Bacillus spp. and Staphylococcus aureus. Providential spp. , Citrobacter spp. Enterobacter spp, E.coli, Acenitobacter spp, Seratia spp P. aeruginosa, and Proteus spp. It is very dreadful to observe that some of these bacteria are highly resistant to the commonly used antibiotics. Moreover, multidrug resistance was observed. Conclusion: Isolation of bacteria from "high-touch" surfaces such as computer keyboardsa and mice is indicative of the need for awareness on cleaning of such surfaces or disinfection and adequate hand hygiene. These bacteria identified have pathogenic potential and hence their presence on computer surfaces may be additional reservoirs for the transmission of microorganisms and become vectors for cross-transmission of bacterial infections in the hospitals/health care setting and its surroundings.
Self Nano Emulsifying Drug Delivery Systems for Oral Delivery of Hydrophobic Drugs

Self-emulsifying drug delivery systems (SNEDDS) are highly in quest due to their innumerable benefits like better portability, improved stability and higher drug loading, coupled with ease and economy of their production. SNEDDS are used to improve the solubility of high lipophilic drugs. SNEDDS are improving the oral bioavailability of limited water-soluble drug compounds. These SNEDDS are isotrophic mixtures of oil, surfactant, co-surfactant and drug that form oil in water emulsion in aqueous environment under gentle agitation. This paper presents an overview of the design, preparation and characterization, effects on the bioavailability of various drugs and various literature reports on diverse types of self-emulsifying formulations.
Expression of gastrin‐releasing peptide is increased by prolonged stretch of human myometrium, and antagonists of its receptor inhibit contractility

• Increased uterine stretch appears to increase the risk of preterm labour, but the mechanism by which this might occur is unknown. • Gastrin‐releasing peptide (GRP) mRNA levels are increased by stretch of myometrial explants and incubation of stretched explants in GRP antagonists can decrease their contractility. • GRP may be a target for novel therapies to decrease the risk of preterm labour in women with multiple pregnancies.
Animal Models of Colorectal Cancer in Chemoprevention and Therapeutics Development

Considering the complexity of genetic and epigenetic events that occurs during colorectal carcinogenesis and the uncertainty in relying solely on extrapolation from cell culture models, it is essential to use animal models relevant to the molecular characteristics of colorectal cancer (CRC). Requirements for a mouse model of CRC are that the model has relevance to the molecular pathways involved in human CRC, that there are correlates with factors that affect the frequency of the disease in human populations, and that the chemopreventive/therapeutic agent-induced signal is sufficient to carry out the project with an affordable and statistically significant number of mice. In this chapter we will discuss how animal models have not only advanced our understanding of CRC initiation and progression but have also greatly facilitated the development of newer chemopreventive and therapeutic strategies to reduce mortality and incidence.
The Clinical Potential of Estrogen for the Prevention of Osteoarthritis: What is Known and What Needs to be Done?

Osteoarthritis (OA) remains a major epidemiological problem worldwide. The lack of established chondroprotective agents limits the clinical management of this disease to relief of symptoms, such as pain and joint stiffness. The marked increase in the prevalence and incidence of OA among women after the menopause draws attention to the possible contribution of estrogen deficiency to acceleration of cartilage degradation. Hormone replacement therapy (HRT) seems to counter the adverse influence of ovariectomy on the progression of joint lesions in various animal models, including nonhuman primates. Although decreases in the risk of OA associated with long-term HRT were repeatedly observed in large-scale epidemiological studies, the chondroprotective potential of this therapeutic option has received modest recognition among healthcare professionals. The overall diversity of results hampering our ability to draw conclusions at the present time arises from the diversity of methodological approaches and selected outcome measures of OA. Randomized clinical trials using state-of-the-art methodology, such as high-resolution magnetic resonance imaging that allows direct visualization and morphometric characterization of articular cartilage and biochemical markers of cartilage turnover that can provide early indication of therapeutic effects, are awaited to obtain evidence-based answers to the utility of estrogen in the prevention of OA.
Clinical Profile of a Patient With Cleft Lip/Palate With Secondary Skeletal Deformities

provide better results until reaching 150 cm. In 150 cm distance, all pixel-counting measurements achieved by performing the aforementioned divisions are equal resulting as 1.0 which means that the face is displayed in the photograph with its true proportions without any distortion (Table 1 and Fig. 2). In conclusion, facial photographs should be taken from a distance of 150 cm (1.5 m) by zooming in until the patient’s face and neck to the level of the clavicle fits exactly into the frame to achieve natural facial photographs with minimal distortion when using compact cameras. Gökhan Temiz, MD Hakan Şirinoğlu, MD Murat Sarici, MD Nebil Yeşiloğlu, MD Dr. Lütfi Kırdar Kartal Training and Research Hospital Department of Plastic Reconstructive and Aesthetic Surgery Kartal, Istanbul drhakansirinoglu@gmail.com
Analysis of quality of life and influencing factors in 197 Chinese patients with port-wine stains

Abstract Port-wine stains (PWS) are congenital capillary malformations, usually occurring on the face, neck, and other exposed parts of the skin, that have serious psychological and social impact on the patient. Most researchers focus on the treatment of PWS, but the quality of life (QoL) of PWS patients is seldom researched. The objective of this study is to evaluate the QoL of patients with PWS on exposed parts and explore the factors influencing the QoL of PWS patients. The QoL of 197 cases with PWS on exposed parts were prospectively studied using the Dermatology Life Quality Index questionnaire (DLQI), and the factors influencing the patients’ QoL were analyzed by single-factor analysis and multiple-factor logistic regression analysis. The reliability and validity of the QoL of PWS patients were then assessed by DLQI. A total of 197 valid questionnaires were collected. The DLQI scores in PWS cases ranged from 2 to 16, with 2 to 5 in 52.29% (103/197), 6 to 10 in 42.13% (83/197), and 11 to 20 in 5.58% (11/197). The main score elements of the DLQI focused on symptoms and feelings, daily activities, and social entertainment. Single-factor analysis and multiple-factor logistic regression analysis showed that the main influencing factors were female sex, skin hypertrophy, and lesion area >30 cm2. The inter-item correlation averaged 47.46% and the Cronbach &agr; was 0.740, indicating high internal consistency. Correlation of the 6 dimensions of the DLQI questionnaires with the total scores showed that the Spearman correlation coefficient r ranged from 0.550 to 0.782 (P < .001), with symptoms and feelings having a correlation coefficient of 0.782 and a high correlation with total scores. This study shows that PWS has mild to moderate influence on the QoL of most patients, mainly on daily activities, social entertainment, and feelings.
Adult Stem Cell Niches — Stem Cells in the Female Reproductive System

The female genital tract is a complex and physiologically dynamic system of organs which undergo continuous and profound changes during the reproductive years. Each of its components – ovaries, fallopian tubes and uterus has unique and indispensable roles in reproduction. Each month, under stimulation from the pituitary gland, the ovaries produce and release a mature oocyte, which moves into the neighboring fallopian tube. Concep‐ tion takes place in the lumen of the tube and the mucosal epithelium lining plays a critical part in the transport of the gametes and the successful transfer of the zygote to the uterus, where it implants 6-12 days after fertilization. Considering the importance of successful reproduction for species survival, there is strong evolutionary pressure to make the process robust and to respond quickly to any cellular damage with effective repair mechanisms. Also, the inner layer of the uterus, the endometrium, is subjected to monthly shedding and regeneration in order to sustain a suitable environment for implantation of a potential embryo. Similar to other tissues like intestine and hair, which continue to undergo rapid cellular turnover throughout adult life, there is an increasing number of studies describ‐ ing the existence of adult stem cells in the genital tract that ensure tissue renewal through‐ out life.
Interactive Effects of Networked Publics and Social Media on Transforming the Public Sphere: A Survey of Iran's Leaderless 'Social Media Revolution'

It has been argued that hierarchical 'command and control' leadership is required to coordinate massive and rapid military or disaster response. Against this, the concept of leaderless 'social media revolution' refers to the wide-spread use of Web 2.0 social media by ordinary citizens to transform the public sphere and engage in collective political action, including coordinating massive and rapid protests against government. However, conceptual and empirical research efforts remain scarce to date. This research draws on the emergent perspective on causal agency in effecting change in social systems to examine our research proposition that the interactive effects of networked publics and social media would transform the public sphere for conversation when democracy is much desired by the citizens. We then discuss our online survey results and key findings of Iranian Face book users' views and experiences before, during, and after the 2009 Presidential election and in the aftermath of citizen protests.
Drugs for neglected diseases: a failure of the market and a public health failure?

Infectious diseases cause the suffering of hundreds of millions of people, especially in tropical and subtropical areas. Effective, affordable and easy‐to‐use medicines to fight these diseases are nearly absent. Although science and technology are sufficiently advanced to provide the necessary medicines, very few new drugs are being developed. However, drug discovery is not the major bottleneck. Today’s R&D‐based pharmaceutical industry is reluctant to invest in the development of drugs to treat the major diseases of the poor, because return on investment cannot be guaranteed. With national and international politics supporting a free market‐based world order, financial opportunities rather than global health needs guide the direction of new drug development. Can we accept that the dearth of effective drugs for diseases that mainly affect the poor is simply the sad but inevitable consequence of a global market economy? Or is it a massive public health failure, and a failure to direct economic development for the benefit of society? An urgent reorientation of priorities in drug development and health policy is needed. The pharmaceutical industry must contribute to this effort, but national and international policies need to direct the global economy to address the true health needs of society. This requires political will, a strong commitment to prioritize health considerations over economic interests, and the enforcement of regulations and other mechanisms to stimulate essential drug development. New and creative strategies involving both the public and the private sector are needed to ensure that affordable medicines for today’s neglected diseases are developed. Priority action areas include advocating an essential medicines R&D agenda, capacity‐building in and technology transfer to developing countries, elaborating an adapted legal and regulatory framework, prioritizing funding for essential drug development and securing availability, accessibility, distribution and rational use of these drugs.
Absorption and Distribution Patterns of RF Fields

Over the past five to ten years, magnetic resonance imaging (MRI) has become an important tool for medical diagnostic applications. There are several aspects of the intense magnetic fields that require close scrutiny from the point of view of patient safety. These include larger static magnetic fields, large spatial gradients of the magnetic fields, rapidly switched magnetic fields, and higher and higher frequency RF magnetic fields. In this report, we will examine the absorption and distribution patterns of radio-frequency (RF) magnetic fields, which in emerging techniques may be of frequencies as high as 200 MHz. Highly simplified homogeneous spherical, cylindrical, and disk models have in the past been used to obtain power depositions due to RF magnetic fields.12 Because only homogeneous models have been used, these models, naturally, are incapable of providing information on distributions of RF absorption (specific absorption rates or SARs) . For RF dosimetry, we have developed an anatomically based model of the human body‘ and a new numerically efficient method called the impedance method that we and our colleagues have used to obtain S A R distributions for frequencies up to 63 In the impedance method, we represent the body or the parts thereof by a threedimensional network of impedances, each of which represents a certain subregion of the body typically about 1-1.5 cm in length. Durney et al.’ have recently generalized the impedance network formulation using the complete set of Maxwell’s equations, which should therefore be usable at any frequency. This generalization involves inclusion of inductances in addition to the resistance-capacitance equivalent impedances that were used previously.M
The Relationship between Brand Personality and Consumers’ Personality among Students

There are numerous cases in which when a particular brand launches a new product, customers or consumers would start to queue days before the launch of the product. Examples of such products are Apple IPhones and Samsung Galaxy among others. This phenomenon is a familiar occurrence in several countries such as New York, Japan and Singapore. Relating to brand personality, it was found to be significantly related to consumers’ personality. Compared to other studies, this study focuses on finding the relationship and effect of brand personality on consumer personality in order to identify the reasons as to why people were attracted to a particular product. The aim of this study was to investigate the correlation between brand personality and consumers’ personality among the undergraduate students in the Faculty of Management at Universiti Teknologi Malaysia. A descriptive-correlation research was conducted using questionnaires such as Aaker’s Brand Personality and big five personality. Based on random sampling, 242 questionnaires were collected from students in Faculty of Management, Universiti Teknologi Malaysia. The data was analyzed using Data Descriptive Statistics, Pearson Correlation, and Multiple Regression. The results indicated that the dimension of brand personality and dimension of consumers’ personality were highly correlated, in which both had high significance. Moreover, the multiple regression showed that brand personality could affect consumers’ personality. The results of this study can prove the relation between brand personality and consumers’ personality. It showed that through the brands that consumers used, the personality of the consumers could be predicted according to the knowledge about brand personality. DOI: 10.5901/mjss.2015. v6n5p175
Quality of life in survivors of prolonged mechanical ventilatory support

ObjectiveTo examine the long-term quality of life (QOL) in a group of patients after prolonged mechanical ventilatory support. DesignProspective cohort study. SettingOutpatient follow-up. PatientsSurvivors of prolonged mechanical ventilatory support who were discharged from a ventilator rehabilitation unit (VRU). InterventionsMeasurement of health-related QOL using the Sickness Impact Profile (SIP). Measurements and Main Results Forty-six patients were contacted approximately 2 yrs after their discharge from the VRU and asked to complete the SIP. Twenty-five patients (age, 59 ± 17 yrs; duration of mechanical ventilatory support, 45 ± 36 days [mean ± sd]) agreed to participate in this study and completed the SIP questionnaire 23 ± 18 months after their discharge from the VRU. Patients’ VRU stay was 29 ± 21 days. Two patients were discharged with nocturnal ventilatory support, and the rest were completely weaned of mechanical ventilatory support before discharge. Fifteen patients (60%) were discharged to home, eight patients (32%) were discharged to a rehabilitation facility, and two patients (8%) were discharged to a skilled-care facility. Most patients had mild dysfunction, and the global SIP score was 12 ± 10, the physical dimension score was 12 ± 12, and the psychosocial dimension score was 9 ± 11 (SIP scores range from 0 to 100, with higher scores indicating worse QOL). Subgroup analysis showed that postoperative patients had lower SIP scores compared with patients with chronic respiratory diseases (global SIP, 7 ± 6 vs. 19 ± 8;p < .05). Moreover, the patients in the postoperative group were older, but had similar SIP scores as patients who had acute lung injury (17 ± 15). Global SIP scores correlated with age (r = −.40;p = .046), but not with duration of mechanical ventilatory support (r = −.23) or VRU admission Acute Physiology and Chronic Health Evaluation II scores (r = −.39;p = .06). ConclusionsIn survivors of prolonged mechanical ventilatory support, using specific selection criteria shows that there is minimal impairment in the QOL at long-term follow-up. Although some patients continue to have moderate to severe limitations, it is the cause of respiratory failure and the underlying disease, rather than duration of ventilatory support, that have a significant impact on QOL.