Fluorescence-based nano-oxygen particles for spatiometric monitoring of cell physiological conditions

Closed-loop artificial pancreas systems have recently been proposed as a solution for treating stage I diabetes by reproducing the function of the pancreas. However, there are many unresolved issues associated with their development, including monitoring and controlling oxygen, immune responses and the optimization of glucose. All of which need to be monitored and controlled to produce an efficient and viable artificial organ, that can become integrated in the patient and maintain homeostasis. This research focused on monitoring oxygen concentration, specifically achieving this kinetically as the oxygen gradient in an artificial pancreas made of alginate spheres containing islet cells. Functional Nanoparticle (NP) for measuring the oxygen gradient in different hydrogel cellular environments using fluorescence-based (F) microscopy were developed and tested. By ester bond, a linker Pluronic F127 was conjugated with a carboxylic acid modified polystyrene Nanoparticle (510 nm). A hydrophilic/ hydrophobic interaction between the commercially available oxygen sensitive fluorophore with F127 results in Fluorescence-based Nano oxygen particle (FNOP). The in-house synthesized FNOP was calibrated inside electro sprayed alginate filled hydrogels and demonstrated a good broad Dynamic Range (2.73-22.23) mg/L as well as a Resolution of -0.01 mg/L with an accuracy of ± 4%. The calibrated FNOP was utilised for continuous measuring of oxygen concentration gradient for cell lines RIN-m5F / HeLa for more than five days in alginate hydrogel spheres in vitro

A Multicriteria Decision Analysis Comparing Pharmacotherapy for Chronic Neuropathic Pain, Including Cannabinoids and Cannabis-Based Medical Products

BACKGROUND: Pharmacological management of chronic neuropathic pain (CNP) still represents a major clinical challenge. Collective harnessing of both the scientific evidence base and clinical experience (of clinicians and patients) can play a key role in informing treatment pathways and contribute to the debate on specific treatments (e.g., cannabinoids). A group of expert clinicians (pain specialists and psychiatrists), scientists, and patient representatives convened to assess the relative benefit–safety balance of 12 pharmacological treatments, including orally administered cannabinoids/cannabis-based medicinal products, for the treatment of CNP in adults. METHODS: A decision conference provided the process of creating a multicriteria decision analysis (MCDA) model, in which the group collectively scored the drugs on 17 effect criteria relevant to benefits and safety and then weighted the criteria for their clinical relevance. FINDINGS: Cannabis-based medicinal products consisting of tetrahydrocannabinol/cannabidiol (THC/CBD), in a 1:1 ratio, achieved the highest overall score, 79 (out of 100), followed by CBD dominant at 75, then THC dominant at 72. Duloxetine and the gabapentinoids scored in the 60s, amitriptyline, tramadol, and ibuprofen in the 50s, methadone and oxycodone in the 40s, and morphine and fentanyl in the 30s. Sensitivity analyses showed that even if the pain reduction and quality-of-life scores for THC/CBD and THC are halved, their benefit–safety balances remain better than those of the noncannabinoid drugs. INTERPRETATION: The benefit–safety profiles for cannabinoids were higher than for other commonly used medications for CNP largely because they contribute more to quality of life and have a more favorable side effect profile. The results also reflect the shortcomings of alternative pharmacological treatments with respect to safety and mitigation of neuropathic pain symptoms. Further high-quality clinical trials and systematic comprehensive capture of clinical experience with cannabinoids is warranted. These results demonstrate once again the complexity and multimodal mechanisms underlying the clinical experience and impact of chronic pain

Combination CTLA-4 Blockade and 4-1BB Activation Enhances Tumor Rejection by Increasing T-Cell Infiltration, Proliferation, and Cytokine Production

BACKGROUND: The co-inhibitory receptor Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4) attenuates immune responses and prevent autoimmunity, however, tumors exploit this pathway to evade the host T-cell response. The T-cell co-stimulatory receptor 4-1BB is transiently upregulated on T-cells following activation and increases their proliferation and inflammatory cytokine production when engaged. Antibodies which block CTLA-4 or which activate 4-1BB can promote the rejection of some murine tumors, but fail to cure poorly immunogenic tumors like B16 melanoma as single agents.METHODOLOGY/PRINCIPAL FINDINGS: We find that combining ?CTLA-4 and ?4-1BB antibodies in the context of a Flt3-ligand, but not a GM-CSF, based B16 melanoma vaccine promoted synergistic levels of tumor rejection. 4-1BB activation elicited strong infiltration of CD8+ T-cells into the tumor and drove the proliferation of these cells, while CTLA-4 blockade did the same for CD4+ effector T-cells. Anti-4-1BB also depressed regulatory T-cell infiltration of tumors. 4-1BB activation strongly stimulated inflammatory cytokine production in the vaccine and tumor draining lymph nodes and in the tumor itself. The addition of CTLA-4 blockade further increased IFN-? production from CD4+ effector T-cells in the vaccine draining node and the tumor. Anti 4-1BB treatment, with or without CTLA-4 blockade, induced approximately 75% of CD8+ and 45% of CD4+ effector T-cells in the tumor to express the killer cell lectin-like receptor G1 (KLRG1). Tumors treated with combination antibody therapy showed 1.7-fold greater infiltration by these KLRG1+CD4+ effector T-cells than did those treated with ?4-1BB alone.CONCLUSIONS/SIGNIFICANCE: This study shows that combining T-cell co-inhibitory blockade with ?CTLA-4 and active co-stimulation with ?4-1BB promotes rejection of B16 melanoma in the context of a suitable vaccine. In addition, we identify KLRG1 as a useful marker for monitoring the anti-tumor immune response elicited by this therapy. These findings should aid in the design of future trials for the immunotherapy of melanoma

Sequence Skill Acquisition and Off-Line Learning in Normal Aging

It is well known that certain cognitive abilities decline with age. The ability to form certain new declarative memories, particularly memories for facts and events, has been widely shown to decline with advancing age. In contrast, the effects of aging on the ability to form new procedural memories such as skills are less well known, though it appears that older adults are able to acquire some new procedural skills over practice. The current study examines the effects of normal aging on procedural memory more closely by comparing the effects of aging on the encoding or acquisition stage of procedural learning versus its effects on the consolidation, or between-session stage of procedural learning. Twelve older and 14 young participants completed a sequence-learning task (the Serial Reaction Time Task) over a practice session and at a re-test session 24 hours later. Older participants actually demonstrated more sequence skill during acquisition than the young. However, older participants failed to show skill improvement at re-test as the young participants did. Age thus appears to have a differential effect upon procedural learning stages such that older adults' skill acquisition remains relatively intact, in some cases even superior, compared to that of young adults, while their skill consolidation may be poorer than that of young adults. Although the effect of normal aging on procedural consolidation remains unclear, aging may actually enhance skill acquisition on some procedural tasks

The textual characteristics of traditional and Open Access scientific journals are similar

<p>Abstract</p> <p>Background</p> <p>Recent years have seen an increased amount of natural language processing (NLP) work on full text biomedical journal publications. Much of this work is done with Open Access journal articles. Such work assumes that Open Access articles are representative of biomedical publications in general and that methods developed for analysis of Open Access full text publications will generalize to the biomedical literature as a whole. If this assumption is wrong, the cost to the community will be large, including not just wasted resources, but also flawed science. This paper examines that assumption.</p> <p>Results</p> <p>We collected two sets of documents, one consisting only of Open Access publications and the other consisting only of traditional journal publications. We examined them for differences in surface linguistic structures that have obvious consequences for the ease or difficulty of natural language processing and for differences in semantic content as reflected in lexical items. Regarding surface linguistic structures, we examined the incidence of conjunctions, negation, passives, and pronominal anaphora, and found that the two collections did not differ. We also examined the distribution of sentence lengths and found that both collections were characterized by the same mode. Regarding lexical items, we found that the Kullback-Leibler divergence between the two collections was low, and was lower than the divergence between either collection and a reference corpus. Where small differences did exist, log likelihood analysis showed that they were primarily in the area of formatting and in specific named entities.</p> <p>Conclusion</p> <p>We did not find structural or semantic differences between the Open Access and traditional journal collections.</p

Exploring the effects of telehealth on medical human resources supply: a qualitative case study in remote regions

BACKGROUND: The availability of medical human resource supply is a growing concern for rural and remote communities in many countries. In the last decade, various telehealth experiences in Canada have highlighted the potential impact of this technology on professional practice. The purpose of this study was to explore physicians' and managers' perceptions regarding the potential of telehealth to support recruitment and retention of physicians in remote and rural regions. METHODS: A case study in Eastern Quebec was performed to explore this complex phenomenon. The analytical framework was based on two literature reviews and a Delphi study. Data were collected from semi-structured interviews with 41 physicians and 22 managers. Transcripts were produced and interview content was coded independently by two judges and validated by an expert panel. RESULTS: Interviews have highlighted the potential impact of telehealth on several factors influencing the recruitment and retention of physicians in rural and remote regions. The potential effects of telehealth on physicians' choice of practice location could be seen at the professional, organizational, educational and individual levels. For instance, telehealth could improve work satisfaction by allowing a regional on-call duty system and a better follow-up of patients. However, there are also certain limits related to telehealth, such as the fear that it would eventually replace all continuing medical education activities and onsite specialists in remoteregions. CONCLUSION: Telehealth is likely to have an impact on several factors related to medical workforce supply in remote and rural regions. However, the expected benefits will materialize if and only if this technology is properly integrated into organizations as a support to professional practice

Enhancing the reporting of implementation research

In the 10 years since the inception of Implementation Science, we have witnessed a continued rise in the number of submissions received, reflecting the continued global interest in methods to enhance the uptake of research findings into healthcare practice and policy. We receive over 750 submissions annually, and there is now a large gap between what is submitted and what gets published. In this editorial, we restate the journal scope and current boundaries. We also identify some specific reporting issues that if addressed will help enhance the scientific reporting quality and transparency of the manuscripts we receive. We hope that this editorial acts as a further guide to researchers seeking to publish their work in Implementation Science

Psychological morbidity as a moderator of intention to quit smoking : a study of smokers and former smokers

Objective: To analyze psychological morbidity as a moderator of the relationship between smoking representations and quality of life in smokers and former smokers, as well as to determine which psychological variables discriminate between smokers with and without the intention to quit smoking. Methods: This was a quantitative, correlational cross-sectional study involving a convenience sample of 224 smokers and 169 former smokers. Results: In smokers and former smokers, psychological morbidity had a moderating effect on the relationship between mental/physical quality of life and smoking representations (cognitive representations, emotional representations, and comprehensibility). Smokers with the intention to quit smoking more often presented with low comprehensibility, threatening emotional representations, behavioral beliefs, and perceived behavioral control, as well as with normative/control beliefs, than did those without the intention to quit. Conclusions: The results of this study underscore the importance of the moderating effect exerted by psychological morbidity, as well as that of sociocognitive variables, among smokers who have the intention to quit smoking.ResumoObjetivo: Analisar a morbidade psicológica como um moderador na relação entre as representações do tabaco e a qualidade de vida em fumantes e ex-fumantes, assim como conhecer as variáveis psicológicas que discriminam os fumantes com e sem intenção para deixar de fumar. Métodos: Estudo quantitativo, correlacional e transversal com uma amostra de conveniência constituída por 224 fumantes e 169 ex-fumantes. Resultados: Verificou-se um efeito moderador da morbidade psicológica na relação entre a qualidade de vida (física e mental) e as representações do tabaco (representações cognitivas e emocionais e compreensão) nos fumantes e nos ex-fumantes. Os fumantes com intenção para deixar de fumar apresentavam menor compreensão, representações emocionais mais ameaçadoras, mais crenças de comportamento, maior controle comportamental percebido e mais crenças normativas/controle do que aqueles sem essa intenção. Conclusões: Os resultados deste estudo enfatizam a importância da morbidade psicológica como moderadora, bem como das variáveis sociocognitivas, junto dos fumantes que querem deixar de fumar

Phase I Randomised Clinical Trial of an HIV-1CN54, Clade C, Trimeric Envelope Vaccine Candidate Delivered Vaginally

We conducted a phase 1 double-blind randomised controlled trial (RCT) of a HIV-1 envelope protein (CN54 gp140) candidate vaccine delivered vaginally to assess immunogenicity and safety. It was hypothesised that repeated delivery of gp140 may facilitate antigen uptake and presentation at this mucosal surface. Twenty two healthy female volunteers aged 18–45 years were entered into the trial, the first receiving open-label active product. Subsequently, 16 women were randomised to receive 9 doses of 100 µg of gp140 in 3 ml of a Carbopol 974P based gel, 5 were randomised to placebo solution in the same gel, delivered vaginally via an applicator. Participants delivered the vaccine three times a week over three weeks during one menstrual cycle, and were followed up for two further months. There were no serious adverse events, and the vaccine was well tolerated. No sustained systemic or local IgG, IgA, or T cell responses to the gp140 were detected following vaginal immunisations. Repeated vaginal immunisation with a HIV-1 envelope protein alone formulated in Carbopol gel was safe, but did not induce local or systemic immune responses in healthy women

The effects of alcohol consumption, psychological distress and smoking status on emergency department presentations in New South Wales, Australia

BACKGROUND: Despite clear links between risky alcohol consumption, mental health problems and smoking with increased morbidity and mortality, there is inconclusive evidence about how these risk factors combine and if they are associated with increased attendance at emergency departments. This paper examines the population-level associations and interactions between alcohol consumption, psychological distress and smoking status with having presented to an emergency department in the last 12 months. METHODS: This study uses data from a representative sample of 34,974 participants aged 16 years and over from the New South Wales Population Health Survey, administered between 2002 and 2004. Statistical analysis included univariate statistics, cross-tabulations, and the estimation of prevalence rate ratios using Cox's proportional hazard regression model. RESULTS: Results show that high-risk alcohol consumption, high psychological distress and current smoking were all significantly and independently associated with a greater likelihood of presenting to an emergency department in the last year. Presenting to an emergency department was found to be three times more likely for women aged 30 to 59 years with all three risk factors and ten times more likely for women aged 60 years or more who reported high risk alcohol consumption and high psychological distress than women of these age groups without these risk factors. For persons aged 16 to 29 years, having high-risk alcohol consumption and being a current smoker doubles the risk of presenting to an emergency department. CONCLUSION: The combination of being a high-risk consumer of alcohol, having high psychological distress, and being a current smoker are associated with increased presentations to emergency departments, independent of age and sex. Further research is needed to enhance recognition of and intervention for these symptoms in an emergency department setting in order to improve patient health and reduce future re-presentations to emergency departments