Miracle-dz/UniFAR-FTUs huggingface dataset:
Emerging drugs for bronchiectasis

Introduction: The global burden of disease due to bronchiectasis is high, disproportionately impacting developing countries and disadvantaged populations. Bronchiectasis, the destruction and dilation of airways, is due to a variety of causes and is characterized by a self-perpetuating cycle of airway inflammation, infection and obstruction that results in substantial morbidity and mortality. Although many therapies have been tested that address each of these three components, as well as the diseases that both cause and result from bronchiectasis, there have been few randomized, placebo-controlled trials. Areas covered: In this review, current knowledge of the clinical features, pathophysiology and epidemiology of bronchiectasis among both adults and children is summarized. We discuss the quality and extent of evidence supporting current treatment strategies, focusing on therapies for which the strongest evidence of efficacy exists. We then identify key goals for future research on the causes and treatments of a variety of types of bronchiectasis. Expert opinion: Significant advances in the prevention and treatment of bronchiectasis will require substantially improved understanding of the pathogenesis of this orphan disease. A concerted, global effort to coordinate studies of both the pathophysiology and potential treatments of bronchiectasis, in its many forms, could lead to substantial improvements in outcomes.
VEGF, M-CSF and CA 15-3 as a new tumor marker panel in breast malignancies: a multivariate analysis with ROC curve

Abstract The plasma levels of Vascular endothelial growth factor, macrophage-colony stimulating factor (M-CSF) and CA15-3 in breast cancer patients (BC) were investigated and compared with control groups: benign breast tumor patients and the healthy subjects. Cytokine levels were determined by the use of enzyme-linked immunosorbent assay, CA 15-3 - by chemiluminescent microparticle immunoassay method. Our results have demonstrated significant differences in the concentration of cytokines and CA 15-3 between the groups of BC patients and two control groups. Cytokines have demonstrated equal to CA 15-3 or even higher values of the diagnostic sensitivity (SE), the predictive values of positive and negative test results (PV-PR, PV-NR), and the area under the ROC curve (AUC) in the studied groups. The combined use of tested parameters resulted in the increase of the SE, PV-PR and AUC. These findings suggest the usefulness of both cytokines in the diagnosis of BC, but only M-CSF in discrimination between cancer and non-carcinoma lesions, especially in combination with CA 15-3.
Antisense oligonucleotides directed against insulin-like growth factor-II messenger ribonucleic acids delay the progress of rat hepatocarcinogenesis

Background: Hepatocellular carcinoma (HCC) is a multistep complex process, caused by many of genetic alteration. Insulin-like growth factors and their receptor have been widely implicated to HCC. Insulin-like growth factor-II (IGF-II) is a mitogenic polypeptide, found in various fetal and neonatal tissues of humans and rats and expresses in HCC. Here we investigated anticancer potential of phosphorothioate antisense oligonucleotides (ASOs) against three coding exons (exon-1/exon-2/exon-3) of IGF-II messenger ribonucleic acid in rat hepatocarcinogenesis model. Materials and Methods: During diethylnitrosamine and 2-acetylaminofluorene induced hepatocarcinogenesis, rats were treated with ASOs. Various biochemical and histological studies were conducted. Results: About 40% of carcinogen treated rats, which received two oligomers (against exon-1 or-3) did not show any hepatic lesion, hyperplastic nodule or tumor and remaining 60% of those rats showed lesion incidence and had about 59% and 55% reductions in the numbers of hepatic altered foci, respectively. Reductions in the total lesion-area when compared with carcinogen control rats were 64% and 53%, respectively for the animals treated with carcinogen and received the ASOs against exon-1/-3. Fluorescein isothiocyanate-labeled ASO reached in the hepatocytes in 2 h. No predominant IGF-II overexpression was observed in case of rats treated with the two ASOs. Treatment of the antisense IGF-II oligomers in carcinogen treated rats show better hepatocellular integrity along with several preneoplastic/neoplastic marker isoenzyme/enzyme modulations. Conclusions: Two of the three antisense oligomer-types effectively controlled IGF-II overexpression, causing the delay of the development and/or progress of hepatic cancer in rats.
Comparative metabolism of benzo[a]pyrene by human keratinocytes infected with high-risk human papillomavirus types 16 and 18 as episomal or integrated genomes

Background: Infection with human papillomavirus (HPV) is a critical factor in the development of cervical cancer. Smoking is an additional risk factor. Tobacco smoke carcinogens, such as benzo[a]pyrene (B[a]P), and their cytochrome P450-related metabolites are present in significantly higher levels in the cervical mucus of women smokers than in nonsmokers. We determined the metabolism and P450 expression of B[a]P-treated human keratinocytes infected with HPV-16 or -18. Materials and Methods: Monolayer cultures of uninfected primary human foreskin keratinocytes, human vaginal and cervical keratinocytes carrying episomal genomes of HPV-16 and -18, respectively, and invasive cervical carcinoma cell lines carrying either HPV-16 or -18 genomes integrated into the host DNA, were incubated with 0.1 μM [3H]B[a]P. The resulting oxidative metabolites were analyzed and quantified by radioflow high-performance liquid chromatography. Additionally, all cell lines were incubated with unlabeled 0.1 μM B[a]P for Western blot analysis of cytochrome P450 1A1 and 1B1. Results: Significant enhancement in levels of both detoxification and activation metabolites was found in incubations with all types of HPV-infected cells compared with control incubations (P < 0.05). The highest capacity to metabolize B[a]P was observed with cells containing integrated HPV-18 genomes. Induction of cytochrome 1B1 was observed in HPV-16 and -18 integrated, and in HPV-16 episomal cell types. Conclusions: Both viral genotype and genomic status in the host cell affect B[a]P metabolism and cytochrome P450 1B1 expression. An increase of DNA-damaging metabolites might result from exposure of HPV-infected women to cigarette smoke carcinogens.
Prolonged sulforaphane treatment does not enhance tumorigenesis in oncogenic K-ras and xenograft mouse models of lung cancer

Background: Sulforaphane (SFN), an activator of nuclear factor erythroid-2 related factor 2 (Nrf2), is a promising chemopreventive agent which is undergoing clinical trial for several diseases. Studies have indicated that there is gain of Nrf2 function in lung cancer and other solid tumors because of mutations in the inhibitor Kelch-like ECH-associated protein 1 (Keap1). More recently, several oncogenes have been shown to activate Nrf2 signaling as the main prosurvival pathway mediating ROS detoxification, senescence evasion, and neoplastic transformation. Thus, it is important to determine if there is any risk of enhanced lung tumorigenesis associated with prolonged administration of SFN using mouse models of cancer. Materials and Methods: We evaluated the effect of prolonged SFN treatment on oncogenic K-ras (K-rasLSL-G12D)-driven lung tumorigenesis. One week post mutant-K-ras expression, mice were treated with SFN (0.5 mg, 5 d/wk) for 3 months by means of a nebulizer. Fourteen weeks after mutant K-ras expression (K-rasLSL-G12D), mice were sacrificed, and lung sections were screened for neoplastic foci. Expression of Nrf2-dependent genes was measured using real time RT-PCR. We also determined the effect of prolonged SFN treatment on the growth of preclinical xenograft models using human A549 (with mutant K-ras and Keap1 allele) and H1975 [with mutant epidermal growth factor receptor (EGFR) allele] nonsmall cell lung cancer cells. Results: Systemic SFN administration did not promote the growth of K-rasLSL-G12D-induced lung tumors and had no significant effect on the growth of A549 and H1975 established tumor xenografts in nude mice. Interestingly, localized delivery of SFN significantly attenuated the growth of A549 tumors in nude mice, suggesting an Nrf2-independent antitumorigenic activity of SFN. Conclusions: Our results demonstrate that prolonged SFN treatment does not promote lung tumorigenesis in various mouse models of lung cancer.
Community knowledge and attitude to pulmonary tuberculosis in rural Edo state, Nigeria.

BACKGROUND A high level of community awareness and positive perception toward pulmonary TB (PTB) and its management is crucial for the success of any control strategy. This study was carried out to assess the knowledge, attitudes, and practice as regard to TB and its treatment. MATERIALS AND METHODS A descriptive cross sectional study involving 193 persons was carried out in a rural community in Ward 5 of Etsako-West local government area of Edo state, selected through a multi-stage sampling process. RESULTS About 86% of respondents had heard of PTB, with a greater proportion being females (55.7%). Mean knowledge score (16.26±5.8) showed that a greater proportion (55.1%) had poor knowledge (range 0-35), with males having better (though not significant) knowledge than females (mean score 17.28±5.9 and 16.94±5.0, respectively, P=0.68). Although attitude toward TB did not influence caring for sick relatives or friends, it impeded social interactions and marriage prospects with infected persons within the community. CONCLUSION Knowledge and attitude toward PTB was generally poor in this rural community. Efforts should be intensified by health authorities in the local government to raise awareness and knowledge of the disease, so as to improve social perception and early recognition of infection.
A qualitative study of causes of prescribing errors among junior medical doctors in a Nigeria in-patient setting.

AIMS The aims of this study were to identify and understand the factors underlying prescribing errors in order to determine how to prevent them. MATERIALS AND METHODS A prospective qualitative study that involved face-to-face interviews and human factor analysis in a Tertiary Referral Hospital in Central Nigeria, from July 2011 to December 2011. Pharmacists in the study hospital prospectively reviewed prescription orders generated by doctors in selected wards (male and female medical, pediatric and the private wing wards) and identified prescribing errors. The 22 prescribers involved in the errors were interviewed, and given questionnaires to discover factors causing the errors. A model of human error theory was used to analyze the responses. RESULTS Responses from the doctors suggest that most errors were made because of slips in attention. Lack of drug knowledge was not the single causative factor in any incident. Risk factors identified included individual, team, environment, and task factors. Junior doctors were affected by the prescribing habits of their seniors. Organizational factors identified included inadequate training/experience, absence of reference materials and absence of self-awareness of errors. Defenses against error such as other clinicians and guidelines were absent or deficient, and supervision was inadequate. CONCLUSIONS To reduce the risk of prescribing errors, a number of strategies addressing individual, task, team, and environmental factors such as training of junior doctors, enforcing good practice in prescription writing, supervision, and reviewing the workload of junior doctors must be established.
Radiolabeling of lipid-based nanoparticles for diagnostics and therapeutic applications: a comparison using different radiometals

Radiolabeling of nanoparticles (NPs) has been performed for a variety of reasons, such as for studying pharmacokinetics, for imaging, or for therapy. Here, we describe the in vitro and in vivo evaluation of DTPA-derivatized lipid-based NP (DTPA-NP) radiolabeled with different radiometals, including 111In and 99mTc, for single-photon emission computed tomography (SPECT), 68Ga for positron emission tomography (PET), and 177Lu for therapeutic applications. PEGylated DTPA-NP with varying DTPA amounts, different composition, and size were radiolabeled with 111In, 177Lu, and 68Ga, using various buffers. 99mTc-labeling was performed directly and by using the carbonyl aquaion, [99mTc(H2O)3(CO)3]+. Stability was tested and biodistribution evaluated. High labeling yields (>90%) were achieved for all radionuclides and different liposomal formulations. Specific activities (SAs) were highest for 111In (>4 MBq/μg liposome), followed by 68Ga and 177Lu; for 99mTc, high labeling yields and SA were only achieved by using [99mTc(H2O)3(CO)3]+. Stability toward DTPA/histidine and in serum was high (>80 % RCP, 24 hours postpreparation). ). Biodistribution in Lewis rats revealed no significant differences between NP in terms of DTPA loading and particle composition; however, different uptake patterns were found between the radionuclides used. We observed lower retention in blood (<3.3 %ID/g) and lower liver uptake (< 2.7 %ID/g) for 99mTc- and 68Ga, compared to 111In-NP (blood, <4 %ID/g; liver, <3.6 %ID/g). Imaging potential was shown by both PET magnetic resonance imaging fusion imaging and SPECT imaging. Overall, our study shows that PEGylated DTPA-NP are suitable for radiolabeling studies with a variety of radiometals, thereby achieving high SA suitable for targeting applications.
Ethanol injection method for hydrophilic and lipophilic drug-loaded liposome preparation

In this article, a hydrophobic (beclomethasone dipropionate; BDP) and a hydrophilic (cytarabine; Ara-C) drugs have been encapsulated in liposomes in order to be administered via the pulmonary route. For this aim, a liposome preparation method, which is easy to scale up, the ethanol injection method, has been selected. The effects of critical process and formulation parameters have been investigated. The drug-loaded liposomes were prepared and characterized in terms of size, zeta potential, encapsulation efficiency, release study, cell uptake, and aerodynamic behavior. Small multilamellar vesicles, with sizes ranging from about 80 to 170 nm, were successfully obtained. Results indicated a significant influence of phospholipid and cholesterol amounts on liposome size and encapsulation efficiency. The higher encapsulation efficiencies were about 100% for the hydrophobic drug (BDP) and about 16% for the hydrophilic one (Ara-C). The in vitro release study showed a prolonged release profile for BDP, in contrast with Ara-C, which was released more rapidly. The cell-uptake test revealed that fluorescent liposomes have been well internalized into the cytoplasm of SW-1573 human lung carcinoma cells, confirming the possibility to use liposomes for lung cell targeting. Nebulized Ara-C and BDP liposomes presented aerodynamic diameters compatible with deep lung deposition. In conclusion, the elaborated liposomes seem to be promising carriers for both Ara-C and BDP pulmonary delivery.
Development and characterization of effective topical liposomal system for localized treatment of cutaneous candidiasis

The localized delivery of fluconazole (FLZ) by conventional therapy is a major impediment in achieving its therapeutic efficacy against skin infections, such as cutaneous candidiasis. Therefore, the present study was aimed to develop FLZ-loaded vesicular construct(s), such as liposomes and niosomes, incorporated into carbopol gel (1%; w/w) for sustained, localized application. The liposomes and niosomes were prepared by the lipid/nonionic surfactant-based dry-film hydration method and were characterized for different parameters. In addition, antifungal activity was carried out on experimentally induced cutaneous candidiasis in immunosuppressed albino rats. The results showed that the size of liposomes and niosomes was found to be 0.348 ± 0.054 and 0.326 ± 0.033 μm with encapsulation efficiency of 31.8 ± 1.36 and 27.6 ± 1.08%, respectively. The skin-retention studies of FLZ from in vitro and in vivo experiments showed significantly higher accumulation of drug in the case of liposomal gel. The in vivo localization studies in viable skin showed that liposomal gel could produce 14.2-fold higher drug accumulation, compared with plain gel, while it was 3.3-fold more in the case of an equivalent-dose application in the form of niosomal gel. The antifungal study also confirmed the maximum therapeutic efficacy of liposomal gel, as the lowest number of cfu/mL was recorded following liposomal FLZ application. The studies signify the potential of liposomal gel for topical delivery of FLZ with increased accumulation of drug in various strata of skin vis-a-vis through sustained release of drug could maintain the localized effect, resulting in an effective treatment of a life-threatening cutaneous fungal infection.
Manufacture of liposomes by isopropanol injection: characterization of the method

Unilamellar liposomes are conventionally prepared by rapid injection of an ethanolic solution of lipids into an aqueous medium. The aim of the present study was to control, more efficiently, vesicle diameter by using an alternative solvent. The results show that isopropanol injection is a good alternative to ethanol injection for the manufacture of liposomes. Particle size can be controlled by the variation of process parameters, such as stirring speed of the aqueous phase and injection flow rate of lipid-isopropanol solution. Diameter of vesicles obtained by this method is less affected by the nature of phospholipid, as well as lipid concentration, than in the ethanol-injection process. In addition, the vesicles are generally smaller (approximately 40–210 nm). Accurate characterization of the particles, by fluorescence, 31P-NMR, and cryo–transmission electron microscopy, showed that particles are formed of a single lipid bilayer around an aqueous cavity. We thus provide the scientific community with a fully characterized alternative method to produce unilamellar vesicles.
Ultradeformable liposomes with terpenes for delivery of hydrophilic compound

Ultradeformable liposomes containing penetration enhancers were created to deliver NaFl. Vesicles were investigated for their particle size, zeta potential, NaFl entrapment efficiency (%EE), loading efficiency, and in vitro skin penetration. The vesicles obtained were spherical in shape, with a particle size of less than 100 nm and a negative surface charge (–6 to –11 mV). The %EE of NaFl loaded in vesicles ranged from 37 to 48%. Ultradeformable liposomes with monoterpenes (d-limonene, 1,8-cineole and geraniol) significantly improved NaFl penetration through the skin. Confocal laser scanning microscopy analysis confirmed skin-penetration results and was used to evaluate the behavior of hydrophilic compounds penetrating through the skin.
HORMONAL STATUS (ESTROGEN RECEPTORS - PROGESTERONE) AND HER-2 Neu IN VARIOUS CYCLIN D1 EXPRESSIONS IN BREAST CANCER

Breast cancer is the most common malignancy and leading death cause of malignancy in women in the world. Expression of estrogen receptors (ER) and progesterone receptors (PR) has long been used to determine endocrine therapy patients. Family of human epidermal growth factor receptor, namely (HER-2/neu) has been used as markers to predict prognosis and therapy response. But many ductal breast carcinoma patients showed expression of ER, PR, and HER-2 neu negative (triple negative tumors). There should be further research for patients with triple negative tumors, to find prognostic markers and therapies. The purposed of this study was to analyze the relationship between hormonal status and HER-2 expression with cyclin D1expression in breast ductal carcinoma. This study was an observational analytic study, conducted at the Department of Pathology Faculty of Medicine Airlangga University/Dr. Soetomo. Paraffin blocks of 35 patients with invasive ductal breast carcinoma, which has not been treated with anti-cancer drug, in a variety hormonal status and HER-2 neu expression, followed by immunohistochemical examination. The results obtained, 31.4% patients in the age group 50 to 59 years. Cyclin D1 positive expression in 54.3% samples, and positive in 87.5% samples with ER positive and negative in 55.6% samples with negative ER. In positive PR sample, cyclin D1 positive in 72.7% samples, and cyclin D1 negative in 54.2% samples with negative PR. Also showed that cyclin D1 positive in 85.7% samples with HER-2 positive and negative in 66.7% samples with HER-2 negative. In conclusion, there is a positive correlation between expression of ER and HER-2 neu by cyclin D1 expression.
Who are the Homeless? Numbers, Trends and Characteristics of Those Without Homes in Calgary

In 2008, Calgary was the first city in Canada to institute a 10-year plan to end homelessness. The plan was introduced in part due to the steady and rapid growth in homelessness in the city since 1992. Since 2008 growth in the number of homeless people has stopped despite a rapidly growing city. The number of people enumerated as homeless by point-in-time counts has fallen from 304 persons per 100,000 population to 256 persons per 100,000 population in 2014, a drop of more than 15 per cent. Looking beyond simple counts of the number of homeless people, we examine how people who are homeless use emergency shelters. Tracking shelter use over a five year period by nearly 33,000 individuals, we find that, contrary to what might be thought to be true, the great majority (86%) of people who use emergency shelters in Calgary do so very infrequently and for only short periods of time. Visiting shelters less than twice (on average), these “transitional” users stayed in shelters for an average of only 15 days spread during the five years of our study. Another 12% of people used emergency shelters more frequently; an average of 8 times spread over five years. These “episodic” users stayed for a total of 113 days on average. Only a tiny minority, just 1.6% of all shelter users, stayed in shelters for very long periods. These “chronic” users visited shelters an average of three and a half times and stayed a total of 928 days over the five years of our study. Because they stay in shelters for long periods, chronic shelter users occupy one-third of shelter beds. The implication of this is that finding stable, supportive housing for just 1.6% of those experiencing homeless – a total of about 900 individuals in Calgary -- would free-up one-third of beds in emergency shelters. Providing supportive housing for episodic users as well would free-up another one-third of beds and so enable shelter providers to focus on their main function as providers of emergency housing. Moving people from emergency shelters into supportive housing delivers savings in the form of reduced interactions for these people with the criminal justice and healthcare systems; savings that have been shown in other studies to significantly off-set the cost of supportive housing. Planning to end homelessness has always been an ambitious goal. While the homeless serving community has made significant gains in understanding how best to solve the problem, greater effort may be required of local, provincial and federal policy makers to find ways of resolving the issue that is at the heart of Calgary’s homelessness problem; namely, the lack of affordable rental accommodations.