Enhanced solubility and functionality of valrubicin (AD-32) against cancer cells upon encapsulation into biocompatible nanoparticles

Among numerous drug-delivery approaches, reconstituted high-density lipoprotein (rHDL) nanocarriers have proven particularly applicable for delivering highly hydrophobic drugs. In this study, we have investigated the enhancement of the therapeutic impact of valrubicin (AD-32), an antineoplastic agent that has been limited to intravesicular application against bladder cancer, despite the encouraging original preclinical data. Earlier studies validated the superior therapeutic efficacy of AD-32 over doxorubicin. In the present study, rHDL/AD-32 nanoparticles were formulated and characterized with regard to encapsulation efficiency, physicochemical properties, selective toxicity, and receptor-mediated uptake. The half maximal inhibitory concentration values (IC50) for rHDL/AD-32 nanoparticles were 1.8 and 2.6 times lower than the free AD-32 for prostate (PC-3) and ovarian (SKOV-3) cancer cell lines, respectively, whereas nonmalignant cell lines demonstrated 5 and 1.48 times higher IC50 doses with rHDL/AD-32 formulations. The data obtained demonstrated effective receptor- mediated uptake of AD-32 from the rHDL nanocarriers by PC-3 and SKOV-3 cancer cells via a targeted drug-delivery process. The rHDL/AD-32 formulation was stable for 6 months when stored at 4°C or at −20°C, as 92% of the AD-32 was retained in the nanoparticles. The findings from this study show that the rHDL/AD-32 formulation can overcome the solubility barriers of AD-32 and thus serve as an effective systemically administered chemotherapeutic agent

The role of cholesterol metabolism and cholesterol transport in carcinogenesis: a review of scientific findings, relevant to future cancer therapeutics

While the unique metabolic activities of malignant tissues as potential targets for cancer therapeutics has been the subject of several recent reviews, the role of cholesterol metabolism in this context is yet to be fully explored. Cholesterol is an essential component of mammalian cell membranes as well as a precursor of bile acids and steroid hormones. The hypothesis that cancer cells need excess cholesterol and intermediates of the cholesterol biosynthesis pathway to maintain a high level of proliferation is well accepted, however the mechanisms by which malignant cells and tissues reprogram cholesterol synthesis, uptake and efflux are yet to be fully elucidated as potential therapeutic targets. High and low density plasma lipoproteins are the likely major suppliers of cholesterol to cancer cells and tumors, potentially via receptor mediated mechanisms. This review is primarily focused on the role(s) of lipoproteins in carcinogenesis, and their future roles as drug delivery vehicles for targeted cancer chemotherapy

The downside of tobacco control? Smoking and self-stigma: a systematic review

Objective Little is known about the consequences of tobacco smoking stigma on smokers and how smokers may internalize smoking-related stigma. This review summarizes existing literature on tobacco smoking self-stigma, investigating to what extent smokers are aware of negative stereotypes, agree with them and apply them to themselves. Methods We carried out a systematic search of Pubmed/Web of Science/PsycInfo databases for articles related to smoking self-stigma through June 2013. Reference lists and citations of included studies were also checked and experts were contacted. After screening articles for inclusion/exclusion criteria we performed a quality assessment and summarized findings according to the stages of self-stigma as conceptualized in Corrigan's progressive model of self-stigma (aware, agree, apply and harm). Initial searches yielded 570 articles. Results Thirty of these articles (18 qualitative and 12 quantitative studies) met criteria for our review. Awareness of smoking stigma was virtually universal across studies. Coping strategies for smoking stigma and the degree to which individuals who smoke internalized this stigma varied both within and across studies. There was considerable variation in positive, negative, and non-significant consequences associated with smoking self-stigma. Limited evidence was found for subgroup differences in smoking-related stigma. Conclusion While there is some evidence that smoking self-stigma leads to reductions in smoking, this review also identified significant negative consequences of smoking self-stigma. Future research should assess the factors related to differences in how individuals respond to smoking stigma. Public health strategies which limit the stigmatization of smokers may be warranted

Supplementary information for: "Dissociative electron attachment and electronic excitation in Fe(CO)(5)"

Geometry of Fe(CO)5 (xyz coordinates); Excited states: Spin and dipole allowed transitions; Spin allowed, dipole forbidden transitions; Singlet-triplet transitions.The supplementary information for: Allan, M., Lacko, M., Papp, P., Matejcik, S., Zlatar, M., Fabrikant, I. I., Kocisek, J.,& Fedor, J. (2018). Dissociative electron attachment and electronic excitation in Fe(CO)(5). Physical Chemistry Chemical Physics, Royal Soc Chemistry, Cambridge., 20(17), 11692-11701. [https://doi.org/10.1039/c8cp01387j]The published version of the article: [https://cer.ihtm.bg.ac.rs/handle/123456789/2312]The peer-reviewed version of the article: [http://cer.ihtm.bg.ac.rs/handle/123456789/2659

The mechanisms and processes of connection: developing a causal chain model capturing impacts of receiving recorded mental health recovery narratives.

BACKGROUND: Mental health recovery narratives are a core component of recovery-oriented interventions such as peer support and anti-stigma campaigns. A substantial number of recorded recovery narratives are now publicly available online in different modalities and in published books. Whilst the benefits of telling one's story have been investigated, much less is known about how recorded narratives of differing modalities impact on recipients. A previous qualitative study identified connection to the narrator and/or to events in the narrative to be a core mechanism of change. The factors that influence how individuals connect with a recorded narrative are unknown. The aim of the current study was to characterise the immediate effects of receiving recovery narratives presented in a range of modalities (text, video and audio), by establishing the mechanisms of connection and the processes by which connection leads to outcomes. METHOD: A study involving 40 mental health service users in England was conducted. Participants were presented with up to 10 randomly-selected recovery narratives and were interviewed on the immediate impact of each narrative. Thematic analysis was used to identify the mechanisms of connection and how connection leads to outcome. RESULTS: Receiving a recovery narrative led participants to reflect upon their own experiences or those of others, which then led to connection through three mechanisms: comparing oneself with the narrative and narrator; learning about other's experiences; and experiencing empathy. These mechanisms led to outcomes through three processes: the identification of change (through attending to narrative structure); the interpretation of change (through attending to narrative content); and the internalisation of interpretations. CONCLUSIONS: This is the first study to identify mechanisms and processes of connection with recorded recovery narratives. The empirically-based causal chain model developed in this study describes the immediate effects on recipients. This model can inform selection of narratives for use in interventions, and be used to support peer support workers in recounting their own recovery narratives in ways which are maximally beneficial to others

Socio-economic and racial/ethnic disparities in the nutritional quality of packaged food purchases in the USA, 2008-2018

Objective: To determine whether disparities exist in the nutritional quality of packaged foods and beverage purchases by household income, education and race/ethnicity and if they changed over time. Design: We used Nielsen Homescan, a nationally representative household panel, from 2008 to 2018 (n = 672 821 household-year observations). Multivariate, multilevel regressions were used to model the association between sociodemographic groups and a set of nutritional outcomes of public health interest, including nutrients of concern (sugar, saturated fat and Na) and calories from specific food groups (fruits, non-starchy vegetables, processed meats, sugar-sweetened beverages and junk foods). Setting: Household panel survey. Participants: Approximately 60 000 households each year from the USA. Results: Disparities were found by income and education for most outcomes and widened for purchases of fruits, vegetables and the percentage of calories from sugar between 2008 and 2018. The magnitude of disparities was largest by education. Disparities between Black and White households include the consumption of processed meats and the percentage of calories from sugar, while no disparities were found between White and Hispanic households. Disparities have been largely persistent, as any significant changes over time have been substantively small. Conclusions: Policies to improve the healthfulness of packaged foods must be expanded beyond SSB taxes, and future research should focus on what mediates the relationship between education and diet so as not to exacerbate disparities

Service user and caregiver involvement in mental health system strengthening in low- and middle-income countries: a cross-country qualitative study

The aims of this paper are to: (i) explore the experiences of involvement of mental health service users, their caregivers, mental health centre heads and policy makers in mental health system strengthening in three low- and middle-income countries (LMICs) (Ethiopia, Nepal and Nigeria); (ii) analyse the potential benefits and barriers of such involvement; and (iii) identify strategies required to achieve greater service user and caregiver participation. A cross-country qualitative study was conducted, interviewing 83 stakeholders of mental health services. Our analysis showed that service user and caregiver involvement in the health system strengthening process was an alien concept for most participants. They reported very limited access to direct participation. Stigma and poverty were described as the main barriers for involvement. Several strategies were identified by participants to overcome existing hurdles to facilitate service user and caregiver involvement in the mental health system strengthening process, such as support to access treatment, mental health promotion and empowerment of service users. This study suggests that capacity building for service users, and strengthening of user groups would equip them to contribute meaningfully to policy development from informed perspectives. Involvement of service users and their caregivers in mental health decision-making is still in its infancy in LMICs. Effective strategies are required to overcome existing barriers, for example making funding more widely available for Ph.D. studies in participatory research with service users and caregivers to develop, implement and evaluate approaches to involvement that are locally and culturally acceptable in LMICs

Coping with stigma and discrimination: evidence from mental health service users in England

Mental health stigma and discrimination are significant problems. Common coping orientations include: concealing mental health problems, challenging others and educating others. We describe the use of common stigma coping orientations and explain variations within a sample of English mental health service users. Cross-sectional survey data were collected as part of the Viewpoint survey of mental health service users’ experiences of discrimination (n = 3005). Linear regression analyses were carried out to identify factors associated with the three stigma coping orientations. The most common coping orientation was to conceal mental health problems (73%), which was strongly associated with anticipated discrimination. Only 51% ever challenged others because of discriminating behaviour, this being related to experienced discrimination, but also to higher confidence to tackle stigma. Although stigma coping orientations vary by context, individuals often choose to conceal problems, which is associated with greater anticipated and experienced discrimination and less confidence to challenge stigma. The direction of this association requires further investigation

Empowering SMEs to make better decisions with Business Intelligence: A Case Study

With the advance of Business Information Systems (BIS), irrespective of the size, companies have adopted an approach to electronic data collection and management for two decades. The advancement in technology means they have in their possessions large volumes of historical data. Large organizations have cached on this and use a range of tools and techniques to leverage the usefulness of this information to make more informed business decisions. For most small and medium- sized enterprises (SMEs), however, such data typically sits in an archive without being utilized. While SMEs appreciate the need for utilizing historical data to make more informed business decisions, they often lack the technical knowhow and funding to embrace an effective BI solution. In this paper, drawing from our experience in implementing a BI solution for a UK SME we discuss some potential tools and strategies that could help SMEs overcome these challenges so as to reap the benefits of adopting an effective BI solution

About the Problem of Differentiation Between the Oaks Quercus pubescens Willd. and Quercus virgiliana. (Ten.) Ten.

U radu su prikazane razlike između srodnih maljavodlakavih hrastova Quercus pubescens i Q. virgiliana. Isto tako prikazana je njihova približna rasprostranjenost u Hrvatskoj, te mogućnost njihova razlikovanja na terenu. Istaknute su i poteškoće u uspješnom određivanju i prepoznavanju navedenih hrastova.In the work the morphological differences between the related downy hairy oaks Quercus pubescens and Q. virgiliana are analyzed. They occupy large areas especially in the Adriatic littoral of the Republic of Croatia, but they develop sporadically in its hinterland, too. The said oaks can be differentiated from each other by the morphology of their leaf, cupule and bark, by the arrangement of flowers on a short fruit shoot as well as by the appearance of their cupule. Q. pubescens has a leaf with 4–6 pairs of lateral lobes, and the petiole is 1–2 cm, maximum 3 cm, long. Its bark at the trunk base is shallowly longitudinally furrowed. All female flowers of the short, fruit shoot are sitting, placed terminally. All ripe acorns are sitting, placed terminally. The cupule covered with small, triangular scales arranged like tiles on a roof is smooth in appearance. Q. virgiliana has a leaf with 3–4 (-5) pairs of lateral lobes, and the petiole is more than 3 cm long. Its bark at the trunk base is deeply furrowed, on the cross cut like a cogwheel. The female flowers are arranged on a more or less long rachis, not longer than 10 cm, in the form of an ear, and the ears can be arranged both terminally and laterally in leaf axils. In the ear there are often clusters of several flowers. One or several ripe acorns are on a more or less long stalk, usually 1–2 cm long. At the top or sidewise on the cupule the remnant of the rachis can often be noticed in the form of a curved, dry extension. The cupule scales are verrucously swollen or protuberated, making the entire cupule verrucously wrinkled. In case of any deviation from the above parameters, as a rule the hybrids are involved