Miracle-dz/UniFAR-FTUs huggingface dataset:
Cannabidiol Treatment in a Murine Model of Systemic Lupus Erythematosus Accelerates Proteinuria Development.

Background: Cannabidiol is a non-psychotropic component of cannabis sativa. Known to induce an immunomodulatory effect, cannabidiol’s therapeutic properties have been explored in a number of autoimmune diseases. Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by its varied manifestation and systemic involvement. Objectives: To evaluate the effect of cannabidiol on disease progression in a murine model of SLE. Methods: NZBxW/F1 mice were treated with either cannabidiol or vehicle by subcutaneous injections. Disease progression was estimated by measurements of proteinuria, histological evaluation of renal disease, levels of anti-dsDNA antibodies, and survival analysis. Results: Mice treated with cannabidiol exhibited rapid progression of glomerular disease with significantly increased proteinuria compared to the control group. Survival analysis revealed a trend (P = 0.058) toward decreased survival among mice treated with cannabidiol. No statistical difference was observed in levels of anti-dsDNA antibodies. Conclusions: Cannabidiol accelerated disease progression in a murine model of SLE. Caution is advised in cannabinoid treatment for SLE patients until further data are collected. IMAJ 2018; 20: 741–745 cannabidiol, cannabinoids, cannabis, NZBxW/F1, systemic lupus erythematosus (SLE), Cannabidiol Treatment in a Murine Model of Systemic Lupus Erythematosus Accelerates Proteinuria Development
Impact of high‐ versus low‐risk genotype on sinonasal radiographic disease in cystic fibrosis

Understanding of how specific mutations impact the cystic fibrosis transmembrane conductance regulator (CFTR) protein has given rise to the classification of CF patients into low‐risk and high‐risk genotypes. Few prior studies have investigated differences in sinonasal disease between low‐risk and high‐risk CF genotypes. This multi‐institutional review aimed to evaluate radiographic sinus disease severity based on genotype.
Breast cancer‐linked lncRNA u‐Eleanor is upregulated in breast of healthy women with lack or short duration of breastfeeding

Recently, it has been revealed that estrogen‐related reproductive factors are linked with some early gene expression lesions associated with malignancy in clinically healthy breasts. Accordingly, the aim of the current study was to evaluate the association of expression levels of estrogen‐related long noncoding RNAs (lncRNAs) upstream Eleanor (u‐Eleanor) and HOX antisense intergenic RNA (HOTAIR) with the different patterns of reproductive factors in breast tissue of healthy women. The subjects of this study were 98 cancer‐free women who had undergone cosmetic mammoplasty. The expression levels of u‐Eleanor and HOTAIR were measured using quantitative real‐time polymerase chain reaction. The results of the current study showed that the women without a history of breastfeeding had a high‐level expression of u‐Eleanor compared with the women with a breastfeeding duration greater than 6 to 24 months (P = 0.03) as well as the women with a breastfeeding duration of more than 24 months (P = 0.005). Furthermore, a higher expression of u‐Eleanor was found in the women with a short breastfeeding duration for 1 to 6 months than that in the women with a breastfeeding duration of greater than 24 months (P = 0.02). In the same way, the results of correlation test (r = −0.258; P = 0.036) and multivariate regression model (β = −0.321; P = 0.023) are indicative of a significant relationship of elevated expression of u‐Eleanor with decreasing breastfeeding duration in the women. These findings could be important to identify the molecular mechanisms behind the relationship between a lack or short duration of the breastfeeding and the risk of breast cancer, which has previously been reported by epidemiological studies.
“Hard to reach, but not out of reach”: Barriers and facilitators to recruiting Black African and Black Caribbean men with prostate cancer and their partners into qualitative research

Access and recruitment barriers may have contributed to the underrepresentation of Black African/Caribbean men and their partners in current psychosocial research related to prostate cancer survivors. Whilst some studies have explored recruitment barriers and facilitators from participants' perspectives, little is known from researchers' point of view. This paper aimed to address this gap in the literature. Recruitment strategies included the following: cancer support groups, researchers' networks, media advertisement, religious organisations, National Health Service hospitals and snowball sampling. Thirty-six eligible participants (men = 25, partners = 11) were recruited into the study. Recruitment barriers comprised of gate-keeping and advertisement issues and the stigma associated with prostate cancer disclosure. Facilitators which aided recruitment included collaborating with National Health Service hospitals, snowball sampling, flexible data collection, building rapport with participants to gain their trust and researcher's attributes. Findings highlight that "hard to reach" Black African/Caribbean populations may be more accessible if researchers adopt flexible but strategic and culturally sensitive recruitment approaches. Such approaches should consider perceptions of stigma associated with prostate cancer within these communities and the influence gatekeepers can have in controlling access to potential participants. Increased engagement with healthcare professionals and gatekeepers could facilitate better access to Black African/Caribbean populations so that their voices can be heard and their specific needs addressed within the healthcare agenda.
Bone Immune Response to Materials, Part I: Titanium, PEEK and Copper in Comparison to Sham at 10 Days in Rabbit Tibia

Bone anchored biomaterials have become an indispensable solution for the restoration of lost dental elements and for skeletal joint replacements. However, a thorough understanding is still lacking in terms of the biological mechanisms leading to osseointegration and its contrast, unwanted peri-implant bone loss. We have previously hypothesized on the participation of immune mechanisms in such processes, and later demonstrated enhanced bone immune activation up to 4 weeks around titanium implants. The current experimental study explored and compared in a rabbit tibia model after 10 days of healing time, the bone inflammation/immunological reaction at mRNA level towards titanium, polyether ether ketone (PEEK) and copper compared to a Sham control. Samples from the test and control sites were, after a healing period, processed for gene expression analysis (polymerase chain reaction, (qPCR)) and decalcified histology tissue analysis. All materials displayed immune activation and suppression of bone resorption, when compared to sham. The M1 (inflammatory)/M2 (reparative) -macrophage phenotype balance was correlated to the proximity and volume of bone growth at the implant vicinity, with titanium demonstrating a M2-phenotype at 10 days, whereas copper and PEEK were still dealing with a mixed M1- and M2-phenotype environment. Titanium was the only material showing adequate bone growth and proximity inside the implant threads. There was a consistent upregulation of (T-cell surface glycoprotein CD4) CD4 and downregulation of (T-cell transmembrane glycoprotein CD8) CD8, indicating a CD4-lymphocyte phenotype driven reaction around all materials at 10 days.
Volumetric 18F‐FDG‐PET parameters as predictors of locoregional failure in low‐risk HPV‐related oropharyngeal cancer after definitive chemoradiation therapy

We sought to investigate the prognostic value of volumetric positron emission tomography (PET) parameters in patients with human papillomavirus (HPV)‐related oropharyngeal squamous cell carcinoma (OPSCC) and a ≤10 pack‐year smoking history treated with chemoradiation.
More Natural Does Not Equal More Normal: Lesbian, Gay, and Bisexual People’s Views About Different Pathways to Parenthood

Heterosexual reproduction is often seen as normal and natural, with the two descriptors commonly understood as mutually reinforcing. I argue that, despite their apparent similarity, the meanings of “normal” and “natural” are distinct in important ways—a distinction that questions the positioning of lesbian motherhood and gay fatherhood as inferior. Through an analysis of lesbian, gay, and bisexual people’s ethical judgments about different ways of creating families, I show that pathways to parenthood that make a family appear “more normal” rely on means of reproduction that seem, in fact, “less natural. ” Conversely, reproductive possibilities seen as “more organic” create families that depart more substantially from the cultural norm of the nuclear family. As a result of this tension, different pathways to parenthood can be justified as being “in children’s best interests. ” However, while this children-centered justification can be flexibly applied, it also has contradictory meanings.
Positioning High-Throughput CETSA in Early Drug Discovery through Screening against B-Raf and PARP1

Methods to measure cellular target engagement are increasingly being used in early drug discovery. The Cellular Thermal Shift Assay (CETSA) is one such method. CETSA can investigate target engagement by measuring changes in protein thermal stability upon compound binding within the intracellular environment. It can be performed in high-throughput, microplate-based formats to enable broader application to early drug discovery campaigns, though high-throughput forms of CETSA have only been reported for a limited number of targets. CETSA offers the advantage of investigating the target of interest in its physiological environment and native state, but it is not clear yet how well this technology correlates to more established and conventional cellular and biochemical approaches widely used in drug discovery. We report two novel high-throughput CETSA (CETSA HT) assays for B-Raf and PARP1, demonstrating the application of this technology to additional targets. By performing comparative analyses with other assays, we show that CETSA HT correlates well with other screening technologies and can be applied throughout various stages of hit identification and lead optimization. Our results support the use of CETSA HT as a broadly applicable and valuable methodology to help drive drug discovery campaigns to molecules that engage the intended target in cells.
The cascade of social determinants in producing chronic disease in low-income African-American men

ABSTRACT Purpose: There is a dearth of effective, evidence-based programs to reduce chronic disease in low-income African-American men. We report on the results of formative research in the National Institutes of Health (NIH)-funded MOCHA Moving Forward project on factors identified by the participants to drive health disparities. Methods: Based on individual interviews with 42 middle-aged (40–65 years), low-income African-American men, three themes emerged. Results: First, the results indicate a hierarchy in the perceived relative influence of different factors, with poverty and unemployment perceived to have the most powerful affects. Second, results show that factors in different domains do not operate as discrete independent influences, but rather, interact synergistically. Finally, the findings show how perceived social structural constraints have produced deep cynicism about the future, with notably divergent reactions, producing a sense that there is almost nothing an individual can do, or paradoxically, a greater the sense of personal responsibility. Conclusion: The implications of addressing the cascade of social determinants to reduce chronic disease in African-American men are discussed.
Superficial Characteristics of Titanium after Treatment of Chorreated Surface, Passive Acid, and Decontamination with Argon Plasma

(1) Background. Titanium is characterized by its biocompatibility, resistance to maximum stress, and fatigue and non-toxicity. The composition, surface structure, and roughness of titanium have a key and direct influence on the osseointegration processes when it is used in the form of dental implants. The objective of the present study is to characterize, at chemical, superficial, and biological levels, the result of the application of the sandblasted with large-grit and acid-etched (SLA) treatment consisting of coarse-grained and double-passivated acid blasting with subsequent decontamination with argon plasma on the surface of titanium implants type IV. (2) Methods. Four Oxtein® dental implants (Zaragoza, Spain) were investigated with the following coding: Code L63713T (titanium grade IV, 3.75 mm in diameter, and 13 mm in length). The surface of the implants was SLA type obtained from coarse-grained, double passivated acid, and decontaminated with argon plasma. The samples were in their sealed packages and were opened in our laboratory. The X-ray photoelectron spectroscopy (XPS) technique was used to characterize the chemical composition of the surface, and the scanning electronic microscope (SEM) technique was used to perform topographic surface evaluation. Cell cultures were also performed on both surfaces. (3) Results. The superficial chemical analysis of the studied samples presented the following components, approximately, expressed in atomic percentage: O: 39%; Ti: 18%; C: 39%; N: 2%; and Si: 1%. In the same way, the topographic analysis values were obtained in the evaluated roughness parameters: Ra: 1.5 μm ± 0.02%; Rq: 1.31 μm ± 0.33; Rz: 8.98 μm ± 0.73; Rp: 5.12 μm ± 0.48; Rv: 3.76 μm ± 0.51; and Rc: 4.92 μm ± 0.24. At a biological level, the expression of osteocalcin was higher (p < 0.05) on the micro-rough surface compared to that machined at 48 and 96 h of culture. (4) Conclusions. The data obtained in our study indicate that the total carbon content, the relative concentration of titanium, and the roughness of the treatment performed on the implants are in agreement with those found in the literature. Further, the roughness of the treatment performed on the implants throws a spongy, three-dimensional surface suitable for bone growth on it. The biological results found are compatible with the clinical use of the surface tested.
Altered Purinergic Receptor Sensitivity in Type 2 Diabetes-Associated Endothelial Dysfunction and Up4A-Mediated Vascular Contraction

Purinergic signaling may be altered in diabetes accounting for endothelial dysfunction. Uridine adenosine tetraphosphate (Up4A), a novel dinucleotide substance, regulates vascular function via both purinergic P1 and P2 receptors (PR). Up4A enhances vascular contraction in isolated arteries of diabetic rats likely through P2R. However, the precise involvement of PRs in endothelial dysfunction and the vasoconstrictor response to Up4A in diabetes has not been fully elucidated. We tested whether inhibition of PRs improved endothelial function and attenuated Up4A-mediated vascular contraction using both aortas and mesenteric arteries of type 2 diabetic (T2D) Goto Kakizaki (GK) rats vs. control Wistar (WT) rats. Endothelium-dependent (EDR) but not endothelium-independent relaxation was significantly impaired in both aortas and mesenteric arteries from GK vs. WT rats. Non-selective inhibition of P1R or P2R significantly improved EDR in aortas but not mesenteric arteries from GK rats. Inhibition of A1R, P2X7R, or P2Y6R significantly improved EDR in aortas. Vasoconstrictor response to Up4A was enhanced in aortas but not mesenteric arteries of GK vs. WT rats via involvement of A1R and P2X7R but not P2Y6R. Depletion of major endothelial component nitric oxide enhanced Up4A-induced aortic contraction to a similar extent between WT and GK rats. No significant differences in protein levels of A1R, P2X7R, and P2Y6R in aortas from GK and WT rats were observed. These data suggest that altered PR sensitivity accounts for endothelial dysfunction in aortas in diabetes. Modulating PRs may represent a potential therapy for improving endothelial function.
Healthcare Resource Use, Cost, and Sick Leave Following Kidney Transplantation in Sweden: A Population-Based, 5-Year, Retrospective Study of Outcomes: COIN

Background Improved understanding of the impact of kidney transplantation on healthcare resource use/costs and loss of productivity could aid decision making about funding allocation and resources needed for the treatment of chronic kidney disease in stage 5. Material/Methods This was a retrospective study utilizing data from Swedish national health registers of patients undergoing kidney transplantation. Primary outcomes were renal disease-related healthcare resource utilization and costs during the 5 years after transplantation. Secondary outcomes included total costs and loss of productivity. Regression analysis identified factors that influenced resource use, costs, and loss of productivity. Results During the first year after transplantation, patients (N=3120) spent a mean of 25.7 days in hospital and made 21.6 outpatient visits; mean renal disease-related total cost was €66,014. During the next 4 years, resource use was approximately 70% (outpatient) to 80% (inpatient) lower, and costs were 75% lower. Before transplantation, 62.8% were on long-term sick leave, compared with 47.4% 2 years later. Higher resource use and costs were associated with age <10 years, female sex, graft from a deceased donor, prior hemodialysis, receipt of a previous transplant, and presence of comorbidities. Higher levels of sick leave were associated with female sex, history of hemodialysis, and type 1 diabetes. Overall 5-year graft survival was 86.7% (95% CI 85.3–88.2%). Conclusions After the first year following transplantation, resource use and related costs decreased, remaining stable for the next 4 years. Demographic and clinical factors, including age <10 years, female sex, and type 1 diabetes were associated with higher costs and resource use.
Bedaquiline and delamanid in the treatment of multidrug‐resistant tuberculosis: Promising but challenging

Improving treatment outcomes in multidrug‐resistant tuberculosis (MDR‐TB) is partly hampered by inadequate effective antitubercular agents. Development of bedaquiline and delamanid has potentially changed the treatment landscape for MDR‐TB. This review provides an update on the progress of these novel antitubercular agents. We review published studies aimed at evaluating clinical efficacy and effectiveness of bedaquiline and delamanid. Five prospective clinical studies and seven retrospective studies on bedaquiline showed that patients treated with a bedaquiline‐containing regimen had a high culture conversion rate ranging from 65 to 100% and a satisfactory treatment outcome. The combined use with linezolid might add to the effectiveness of bedaquiline. Controversies about bedaquiline resistance are discussed. Three clinical trials have reported outcomes on delamanid and showed that introducing delamanid to a background regimen improved culture conversion rate at 2 months from 29.6% to more than 40%. A higher favorable treatment rate was also observed among patients who received delamanid for more than 6 months, but about a quarter of patients defaulted in the control group. Seven retrospective studies were summarized and found a treatment benefit as well. More reliable evidence from randomized clinical trials reporting on the treatment outcomes is needed urgently to support a strong recommendation for the use of delamanid. Advances in the combined use of bedaquiline and delamanid are also reviewed, and the combination may be well tolerated but requires electrocardiograph monitoring.
Treating osteosarcoma with CAR T cells

Novel therapies to treat patients with solid cancers that have developed resistance to chemotherapy represent unmet needs of considerable dimensions. In the present review, we will address the attempts to develop chimeric antigen receptor (CAR) targeted immunotherapy against osteosarcoma (OS). This aggressive cancer displays its peak incidence in children and young adults. The main cause of patient death is lung metastases with a 5‐year survival as low as 5%‐10% in the primary metastatic setting and 30% in the relapse situation, respectively. Effective adjuvant combination chemotherapy introduced more than 40 years ago improved the survival rates from below 20% to around 60% in patients; however, since then, no major breakthroughs have been made. The use of immune checkpoint inhibitors has been disappointing in OS, while other types of immunotherapies such as CAR T cells remain largely unexplored. Indeed, for CAR T‐cell therapy to be efficacious, two main criteria need to be fulfilled: (a) CAR T cells should target an epitope selectively expressed on the cell surface of OS in order to prevent toxicities in normal tissues and (b) the target should also be widely expressed on OS metastases. These challenges have already been undertaken in OS and illustrate the difficulties in developing tomorrow's CAR‐T treatment in a solid tumour. We will discuss the experiences with CAR‐T therapy development and efficacy to combat the clinical challenges in OS.
Communications Skills in the Pharmacy Profession: A Cross Sectional Survey of UK Registered Pharmacists and Pharmacy Educators

Objectives: To determine UK pharmacists’ experiences of their current communication skills and undergraduate training and to identify communication skills training and teaching at UK schools of pharmacy. Methods: Two surveys were developed. The first survey was sent to UK practicing pharmacists examining their current communication skills and interest in behavioural counselling techniques such as Motivational Interviewing (MI). A second survey was sent to all UK Schools of Pharmacy investigating communication skills training and teaching. Results: In the first survey pharmacists reported low satisfaction with their undergraduate communication skills training. A convenience sample of 109 UK pharmacists responded to the first survey. Forty-four per cent (n = 48) of the respondents stated that they continued their professional development in communication skills after an undergraduate degree. Seventy (65.4%) were not familiar with behavioural counselling techniques such as MI. The most common patient consultation delivered by pharmacists was around adherence to medicine 22.4% (n = 50). Pharmacists expressed a need for further training in clinical areas such as mental health 25.7% (n = 80). Results from the second survey to pharmacy schools showed that Schools of Pharmacy response rate was 60% (18/30). All 18 schools stated that they teach health behaviour change consultation skills and this is mostly delivered by a clinical pharmacist. Teaching communication skills was mostly delivered as role play with peers (n = 17). Conclusion: This first national survey of communication skills training in Schools of Pharmacy shows that newer graduates have received more communication training compared to older graduates, however pharmacists’ respondents still felt that they were under prepared for behaviour change patient consultations. MI training would be welcomed by those. Practice Implications: Structured courses in communication skills, including behavioural change techniques, are needed for practicing UK pharmacists.