The multifunctional solute carrier 3A2 (SLC3A2) confers a poor prognosis in the highly proliferative breast cancer subtypes

Background: Breast cancer (BC) is a heterogeneous disease characterised by variant biology, metabolic activity and patient outcome. This study aimed to evaluate the biological and prognostic value of the membrane solute carrier, SLC3A2 in BC with emphasis on the intrinsic molecular subtypes. Methods: SLC3A2 was assessed at the genomic level, using METABRIC data (n=1,980), and proteomic level, using immunohistochemistry on TMA sections constructed from a large well-characterised primary BC cohort (n=2,500). SLC3A2 expression was correlated with clinicopathological parameters, molecular subtypes, and patient outcome. Results: SLC3A2 mRNA and protein expression were strongly correlated with higher tumour grade and poor Nottingham prognostic index (NPI). High expression of SLC3A2 was observed in triple negative (TN), HER2+, and ER+ high proliferation subtypes. SLC3A2 mRNA and protein expression were significantly associated with the expression of c-MYC in all BC subtypes (p<0.001). High expression of SLC3A2 protein was associated with poor patient outcome (p<0.001)), but only in the ER+ high proliferation (p=0.01) and triple negative (p=0.04) subtypes. In multivariate analysis SLC3A2 protein was an independent risk factor for shorter breast cancer specific survival (p<0.001). Conclusions: SLC3A2 appears to play a role in the aggressive BC subtypes driven by MYC and could act as a potential prognostic marker. Functional assessment is necessary to reveal its potential therapeutic value in the different BC subtypes

A systematic review of dietary, nutritional, and physical activity interventions for the prevention of prostate cancer progression and mortality

PURPOSE: Given the long-term, although potentially fatal, nature of prostate cancer, there is increasing observational evidence for the reduction in disease progression and mortality through changes in lifestyle factors. METHODS: We systematically reviewed dietary, nutritional, and physical activity randomized interventions aimed at modifying prostate cancer progression and disease-specific mortality, including a detailed assessment of risk of bias and methodological quality. RESULTS: Forty-four randomized controlled trials of lifestyle interventions, with prostate cancer progression or mortality outcomes, were identified. Substantial heterogeneity of the data prevented a meta-analysis. The included trials involved 3,418 prostate cancer patients, median 64 men per trial, from 13 countries. A trial of a nutritional supplement of pomegranate seed, green tea, broccoli, and turmeric; a trial comparing flaxseed, low-fat diet, flaxseed, and low-fat diet versus usual diet; and a trial supplementing soy, lycopene, selenium, and coenzyme Q10, all demonstrated beneficial effects. These trials were also assessed as having low risk of bias and high methodological quality (as were seven other trials with no evidence of benefit). The remaining trials were either underpowered, at high or unclear risk of bias, inadequately reported, of short duration or measured surrogate outcomes of unproven relationship to mortality or disease progression, which precluded any benefits reported being reliable. CONCLUSION: Large, well-designed randomized trials with clinical endpoints are recommended for lifestyle modification interventions. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10552-015-0659-4) contains supplementary material, which is available to authorized users

Combined search for the quarks of a sequential fourth generation

Results are presented from a search for a fourth generation of quarks produced singly or in pairs in a data set corresponding to an integrated luminosity of 5 inverse femtobarns recorded by the CMS experiment at the LHC in 2011. A novel strategy has been developed for a combined search for quarks of the up and down type in decay channels with at least one isolated muon or electron. Limits on the mass of the fourth-generation quarks and the relevant Cabibbo-Kobayashi-Maskawa matrix elements are derived in the context of a simple extension of the standard model with a sequential fourth generation of fermions. The existence of mass-degenerate fourth-generation quarks with masses below 685 GeV is excluded at 95% confidence level for minimal off-diagonal mixing between the third- and the fourth-generation quarks. With a mass difference of 25 GeV between the quark masses, the obtained limit on the masses of the fourth-generation quarks shifts by about +/- 20 GeV. These results significantly reduce the allowed parameter space for a fourth generation of fermions.Comment: Replaced with published version. Added journal reference and DO

Mechanisms Underlying Interferon-γ-Induced Priming of Microglial Reactive Oxygen Species Production.

Microglial priming and enhanced reactivity to secondary insults cause substantial neuronal damage and are hallmarks of brain aging, traumatic brain injury and neurodegenerative diseases. It is, thus, of particular interest to identify mechanisms involved in microglial priming. Here, we demonstrate that priming of microglia with interferon-γ (IFN γ) substantially enhanced production of reactive oxygen species (ROS) following stimulation of microglia with ATP. Priming of microglial ROS production was substantially reduced by inhibition of p38 MAPK activity with SB203580, by increases in intracellular glutathione levels with N-Acetyl-L-cysteine, by blockade of NADPH oxidase subunit NOX2 activity with gp91ds-tat or by inhibition of nitric oxide production with L-NAME. Together, our data indicate that priming of microglial ROS production involves reduction of intracellular glutathione levels, upregulation of NADPH oxidase subunit NOX2 and increases in nitric oxide production, and suggest that these simultaneously occurring processes result in enhanced production of neurotoxic peroxynitrite. Furthermore, IFNγ-induced priming of microglial ROS production was reduced upon blockade of Kir2.1 inward rectifier K+ channels with ML133. Inhibitory effects of ML133 on microglial priming were mediated via regulation of intracellular glutathione levels and nitric oxide production. These data suggest that microglial Kir2.1 channels may represent novel therapeutic targets to inhibit excessive ROS production by primed microglia in brain pathology

Materials for Diabetes Therapeutics

This review is focused on the materials and methods used to fabricate closed-loop systems for type 1 diabetes therapy. Herein, we give a brief overview of current methods used for patient care and discuss two types of possible treatments and the materials used for these therapies–(i) artificial pancreases, comprised of insulin producing cells embedded in a polymeric biomaterial, and (ii) totally synthetic pancreases formulated by integrating continuous glucose monitors with controlled insulin release through degradable polymers and glucose-responsive polymer systems. Both the artificial and the completely synthetic pancreas have two major design requirements: the device must be both biocompatible and be permeable to small molecules and proteins, such as insulin. Several polymers and fabrication methods of artificial pancreases are discussed: microencapsulation, conformal coatings, and planar sheets. We also review the two components of a completely synthetic pancreas. Several types of glucose sensing systems (including materials used for electrochemical, optical, and chemical sensing platforms) are discussed, in addition to various polymer-based release systems (including ethylene-vinyl acetate, polyanhydrides, and phenylboronic acid containing hydrogels).Juvenile Diabetes Research Foundation International (17-2007-1063)Leona M. and Harry B. Helmsley Charitable Trust (09PG-T1D027)United States. National Institutes of Health (F32 EB011580-01

Value of hospital antimicrobial stewardship programs [ASPs]:a systematic review

Abstract Background Hospital antimicrobial stewardship programs (ASPs) aim to promote judicious use of antimicrobials to combat antimicrobial resistance. For ASPs to be developed, adopted, and implemented, an economic value assessment is essential. Few studies demonstrate the cost-effectiveness of ASPs. This systematic review aimed to evaluate the economic and clinical impact of ASPs. Methods An update to the Dik et al. systematic review (2000–2014) was conducted on EMBASE and Medline using PRISMA guidelines. The updated search was limited to primary research studies in English (30 September 2014–31 December 2017) that evaluated patient and/or economic outcomes after implementation of hospital ASPs including length of stay (LOS), antimicrobial use, and total (including operational and implementation) costs. Results One hundred forty-six studies meeting inclusion criteria were included. The majority of these studies were conducted within the last 5 years in North America (49%), Europe (25%), and Asia (14%), with few studies conducted in Africa (3%), South America (3%), and Australia (3%). Most studies were conducted in hospitals with 500–1000 beds and evaluated LOS and change in antibiotic expenditure, the majority of which showed a decrease in LOS (85%) and antibiotic expenditure (92%). The mean cost-savings varied by hospital size and region after implementation of ASPs. Average cost savings in US studies were $732 per patient (range:$2.50 to $2640), with similar trends exhibited in European studies. The key driver of cost savings was from reduction in LOS. Savings were higher among hospitals with comprehensive ASPs which included therapy review and antibiotic restrictions. Conclusions Our data indicates that hospital ASPs have significant value with beneficial clinical and economic impacts. More robust published data is required in terms of implementation, LOS, and overall costs so that decision-makers can make a stronger case for investing in ASPs, considering competing priorities. Such data on ASPs in lower- and middle-income countries is limited and requires urgent attention

Occupational Safety Precautions among Nurses at Four Hospitals, Nablus District, Palestine

Occupational hazards, exposure to blood and body fluids (BBF) accidents and safety precautions constitute an important public health issue. We assessed the prevalence and determinants of exposure to occupational hazards among nurses, and their knowledge of occupational safety precautions. In a cross-sectional study, we surveyed 332 nurses working in 4 hospitals, Nablus, West Bank, Palestine, by a questionnaire. Bivariate analysis tested the associations between ever exposure and the high likelihood of BBF exposure and the independent socio-demographic and occupational variables. Binary logistic regression analysis was used to assess the associations between the same two exposures and selected independent variables (those significant in the bivariate analysis). Prevalence of ever exposure to BBF was 51.7%, and was associated with working in private and charitable hospitals (OR 2.62, 2.68, respectively), having 4–6 family members (OR 0.52) and “nursing” being as one's top career choice at university (OR 0.48). The prevalence of high likelihood of BBF exposure was 62.2%, and was associated with working in charitable and private hospitals (OR 7.81, 2.43, respectively) and “nursing” being as one's top career choice (OR 0.57). Regarding knowledge, most respondents believed it is necessary to enact laws and regulations regarding occupational safety precautions, reported the use of sharps containers, immediate disinfection after an accident, reporting an accident, and using personal protective equipment. Nurses had adequate knowledge of the risks of their hospital work. Nevertheless, they exhibited high prevalence of exposure to BBF accidents. Future studies are needed to re-evaluate existing occupational safety guidelines in hospitals, establish monitoring and evaluation protocols for health care workers' adherence to the guidelines, and institute well-defined policies for reporting occupational injury incidents so these can be handled appropriately

Search for Pair Production of Third-Generation Leptoquarks and Top Squarks in pp Collisions at √s=7 TeV

Results are presented from a search for the pair production of third-generation scalar and vector leptoquarks, as well as for top squarks in R-parity-violating supersymmetric models. In either scenario, the new, heavy particle decays into a τ lepton and a b quark. The search is based on a data sample of pp collisions at √s=7  TeV, which is collected by the CMS detector at the LHC and corresponds to an integrated luminosity of 4.8  fb[superscript -1]. The number of observed events is found to be in agreement with the standard model prediction, and exclusion limits on mass parameters are obtained at the 95% confidence level. Vector leptoquarks with masses below 760 GeV are excluded and, if the branching fraction of the scalar leptoquark decay to a τ lepton and a b quark is assumed to be unity, third-generation scalar leptoquarks with masses below 525 GeV are ruled out. Top squarks with masses below 453 GeV are excluded for a typical benchmark scenario, and limits on the coupling between the top squark, τ lepton, and b quark, λ333′ are obtained. These results are the most stringent for these scenarios to date

Impact of Protracted War Crisis on Dental Students: A Comparative Multicountry Cross-sectional Study

BACKGROUND: The impact of conflict and war crisis on dental students is poorly understood. Given the prolonged conflicts and political instability in the Arabic-speaking countries, it is crucial to investigate the effect of these conditions on dental students. This study aimed to assess the impact of protracted war on dental students by comparing the personal, university, and wider context challenges they face across war-affected and unaffected countries. METHODS: A cross-sectional study was conducted including a convenience sample of dental students from 13 universities in 12 Arabic-speaking countries. Respondents were those at entry and exit points of their undergraduate dental training. A self-administered paper questionnaire collected anonymized data on sociodemographics, and personal, university, and wider context challenges that students were facing. Multivariable Poisson regression analyses were carried out. RESULTS: The overall response rate was 64.8%. The mean age was 21.2 (standard deviation = 2.1) years, with 68% of participants being female. After adjusting for age and sex, dental students in Arabic-speaking countries affected by protracted war crisis were significantly more likely to report wider context challenges compared to their counterparts in unaffected countries (n = 2448; beta = 1.12; 95% confidence interval: 1.10-1.13; P < 0.001). DISCUSSION: Dental students in Arabic-speaking countries affected by protracted war crisis were more likely to suffer from wider context challenges such as difficulties in attendance due to the deterioration of security and lack of flexibility of teaching time to accommodate the different circumstances induced by the war crisis. Supporting dental students in areas affected by protracted war crises is needed and may include developing online dental education programs

Graphene-Based Nanocomposites for Energy Storage

Since the first report of using micromechanical cleavage method to produce graphene sheets in 2004, graphene/graphene-based nanocomposites have attracted wide attention both for fundamental aspects as well as applications in advanced energy storage and conversion systems. In comparison to other materials, graphene-based nanostructured materials have unique 2D structure, high electronic mobility, exceptional electronic and thermal conductivities, excellent optical transmittance, good mechanical strength, and ultrahigh surface area. Therefore, they are considered as attractive materials for hydrogen (H2) storage and high-performance electrochemical energy storage devices, such as supercapacitors, rechargeable lithium (Li)-ion batteries, Li–sulfur batteries, Li–air batteries, sodium (Na)-ion batteries, Na–air batteries, zinc (Zn)–air batteries, and vanadium redox flow batteries (VRFB), etc., as they can improve the efficiency, capacity, gravimetric energy/power densities, and cycle life of these energy storage devices. In this article, recent progress reported on the synthesis and fabrication of graphene nanocomposite materials for applications in these aforementioned various energy storage systems is reviewed. Importantly, the prospects and future challenges in both scalable manufacturing and more energy storage-related applications are discussed