Investigating the impact of poverty on colonization and infection with drug-resistant organisms in humans: a systematic review

Background Poverty increases the risk of contracting infectious diseases and therefore exposure to antibiotics. Yet there is lacking evidence on the relationship between income and non-income dimensions of poverty and antimicrobial resistance. Investigating such relationship would strengthen antimicrobial stewardship interventions. Methods A systematic review was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed, Ovid, MEDLINE, EMBASE, Scopus, CINAHL, PsychINFO, EBSCO, HMIC, and Web of Science databases were searched in October 2016. Prospective and retrospective studies reporting on income or non-income dimensions of poverty and their influence on colonisation or infection with antimicrobial-resistant organisms were retrieved. Study quality was assessed with the Integrated quality criteria for review of multiple study designs (ICROMS) tool. Results Nineteen articles were reviewed. Crowding and homelessness were associated with antimicrobial resistance in community and hospital patients. In high-income countries, low income was associated with Streptococcus pneumoniae and Acinetobacter baumannii resistance and a seven-fold higher infection rate. In low-income countries the findings on this relation were contradictory. Lack of education was linked to resistant S. pneumoniae and Escherichia coli. Two papers explored the relation between water and sanitation and antimicrobial resistance in low-income settings. Conclusions Despite methodological limitations, the results suggest that addressing social determinants of poverty worldwide remains a crucial yet neglected step towards preventing antimicrobial resistance

Molecular characterization of irinotecan (SN-38) resistant human breast cancer cell lines

Background: Studies in taxane and/or anthracycline refractory metastatic breast cancer (mBC) patients have shown approximately 30% response rates to irinotecan. Hence, a significant number of patients will experience irinotecan-induced side effects without obtaining any benefit. The aim of this study was to lay the groundwork for development of predictive biomarkers for irinotecan treatment in BC. Methods: We established BC cell lines with acquired or de novo resistance to SN-38, by exposing the human BC cell lines MCF-7 and MDA-MB-231 to either stepwise increasing concentrations over 6months or an initial high dose of SN-38 (the active metabolite of irinotecan), respectively. The resistant cell lines were analyzed for cross-resistance to other anti-cancer drugs, global gene expression, growth rates, TOP1 and TOP2A gene copy numbers and protein expression, and inhibition of the breast cancer resistance protein (ABCG2/BCRP) drug efflux pump. Results: We found that the resistant cell lines showed 7-100 fold increased resistance to SN-38 but remained sensitive to docetaxel and the non-camptothecin Top1 inhibitor LMP400. The resistant cell lines were characterized by Top1 down-regulation, changed isoelectric points of Top1 and reduced growth rates. The gene and protein expression of ABCG2/BCRP was up-regulated in the resistant sub-lines and functional assays revealed BCRP as a key mediator of SN-38 resistance. Conclusions: Based on our preclinical results, we suggest analyzing the predictive value of the BCRP in breast cancer patients scheduled for irinotecan treatment. Moreover, LMP400 should be tested in a clinical setting in breast cancer patients with resistance to irinotecan

Distributions of Antibody Titers to Mycoplasma pneumoniae in Korean Children in 2000-2003

The aim of study was to describe Mycoplasma pneumoniae epidemics in a hospital-based population. Special attention was paid to the relationship between antibody titer to M. pneumoniae and sex, age, and atopy. During the eight 6-month periods between January 2000 and December 2003, serum samples were obtained from 1,319 Korean children who presented with respiratory symptoms, and were examined for antibodies to M. pneumoniae using the indirect particle agglutination test. Geometric mean antibody titers peaked in the second half of 2000 and then decreased gradually, a second peak occurred in the second half of 2003. Likewise, the frequency of high antibody titers (≥1:640) also peaked during these two periods. Antibody titers in children aged 0-3 yr were lower than in older children during both peak periods and for 2 yr after the first peak. Sex and atopy had no effect on antibody titers. During the years 2000-2003, geometric mean antibody titers and the frequencies of high antibody titers varied with time. These changes suggest a cyclic pattern of M. pneumoniae infection, with two epidemic peaks separated by 3 yr

The sudden change phenomenon of quantum discord

Even if the parameters determining a system's state are varied smoothly, the behavior of quantum correlations alike to quantum discord, and of its classical counterparts, can be very peculiar, with the appearance of non-analyticities in its rate of change. Here we review this sudden change phenomenon (SCP) discussing some important points related to it: Its uncovering, interpretations, and experimental verifications, its use in the context of the emergence of the pointer basis in a quantum measurement process, its appearance and universality under Markovian and non-Markovian dynamics, its theoretical and experimental investigation in some other physical scenarios, and the related phenomenon of double sudden change of trace distance discord. Several open questions are identified, and we envisage that in answering them we will gain significant further insight about the relation between the SCP and the symmetry-geometric aspects of the quantum state space.Comment: Lectures on General Quantum Correlations and their Applications, F. F. Fanchini, D. O. Soares Pinto, and G. Adesso (Eds.), Springer (2017), pp 309-33

Endothelial progenitor cells in diabetic retinopathy

Diabetic retinopathy (DR) is a leading cause of visual impairment worldwide. Patients with DR may irreversibly lose sight as a result of the development of diabetic macular oedema (DMO) and/or proliferative diabetic retinopathy (PDR); retinal blood vessel dysfunction and degeneration plays an essential role in their pathogenesis. Although new treatments have been recently introduced for DMO, including intravitreal vascular endothelial growth factor inhibitors (anti-VEGFs) and steroids, a high proportion of patients (~40-50%) do not respond to these therapies. Furthermore, for people with PDR laser photocoagulation remains a mainstay therapy despite this being an inherently destructive procedure. Endothelial progenitor cells (EPCs) are a low-frequency population of circulating cells known to be recruited to sites of vessel damage and tissue ischemia where they promote vascular healing and re-perfusion. A growing body of evidence suggests the number and function of EPCs is altered in patients with varying degrees of diabetes duration, metabolic control and in the presence of absence of DR. While there are no clear-cut outcomes from these clinical studies, there is mounting evidence that some EPC sub-types may be involved in the pathogenesis of DR and may also serve as biomarkers for disease progression and stratification. Moreover, some EPC sub-types have considerable potential as therapeutic modalities for DMO and PDR in the context of cell therapy. This review presents basic clinical concepts of DR and combines this with a general insight on EPCs and how they relate to future directions in understanding and treating this important diabetic complication

Osmotin-loaded magnetic nanoparticles with electromagnetic guidance for the treatment of Alzheimer's disease

Alzheimer's disease (AD) is the most prevalent age-related neurodegenerative disease, pathologically characterized by the accumulation of aggregated amyloid beta (Aβ) in the brain.</p

Enhancing protective microglial activities with a dual function TREM2 antibody to the stalk region

Triggering receptor expressed on myeloid cells 2 (TREM2) is essential for the transition of homeostatic microglia to a disease‐associated microglial state. To enhance TREM2 activity, we sought to selectively increase the full‐length protein on the cell surface via reducing its proteolytic shedding by A Disintegrin And Metalloproteinase (i.e., α‐secretase) 10/17. We screened a panel of monoclonal antibodies against TREM2, with the aim to selectively compete for α‐secretase‐mediated shedding. Monoclonal antibody 4D9, which has a stalk region epitope close to the cleavage site, demonstrated dual mechanisms of action by stabilizing TREM2 on the cell surface and reducing its shedding, and concomitantly activating phospho‐SYK signaling. 4D9 stimulated survival of macrophages and increased microglial uptake of myelin debris and amyloid β‐peptide in vitro. In vivo target engagement was demonstrated in cerebrospinal fluid, where nearly all oluble TREM2 was 4D9‐bound. Moreover, in a mouse model for Alzheimer's disease‐related pathology, 4D9 reduced amyloidogenesis, enhanced microglial TREM2 expression, and reduced a homeostatic marker, suggesting a protective function by driving microglia toward a disease‐associated state

Dual FGF-2 and Intergrin α5β1 Signaling Mediate GRAF-Induced RhoA Inactivation in a Model of Breast Cancer Dormancy

Interactions with the bone marrow stroma regulate dormancy and survival of breast cancer micrometastases. In an in vitro model of dormancy in the bone marrow, we previously demonstrated that estrogen-dependent breast cancer cells are partially re-differentiated by FGF-2, re-express integrin α5β1 lost with malignant transformation and acquire an activated PI3K/Akt pathway. Ligation of integrin α5β1 by fibronectin and activation of the PI3K pathway both contribute to survival of these dormant cells. Here, we investigated mechanisms responsible for the dormant phenotype. Experiments demonstrate that integrin α5β1 controls de novo cytoskeletal rearrangements, cell spreading, focal adhesion kinase rearrangement to the cell perimeter and recruitment of a RhoA GAP known as GRAF. This results in the inactivation of RhoA, an effect which is necessary for the stabilization of cortical actin. Experiments also demonstrate that activation of the PI3K pathway by FGF-2 is independent of integrin α5β1 and is also required for cortical actin reorganization, GRAF membrane relocalization and RhoA inactivation. These data suggest that GRAF-mediated RhoA inactivation and consequent phenotypic changes of dormancy depend on dual signaling by FGF-2-initiated PI3K activation and through ligation of integrin α5β1 by fibronectin

Field and Laboratory Responses of Male Leaf Roller Moths, Choristoneura rosaceana and Pandemis pyrusana, to Pheromone Concentrations in an Attracticide Paste Formulation

Male leafroller moths, Choristoneura rosaceana (Harris) (Lepidoptera: Tortricidae) and Pandemis pyrusana (Kearfott), were evaluated for responses to a paste formulation loaded with a range of concentrations of the two species' pheromone blends and evaluated in a laboratory wind tunnel and in the field. Response criteria were flight, flight towards the pheromone source, and contact with the pheromone source for the wind tunnel assays, and capture of moths in traps for the field tests. In the wind tunnel and field, responses of males of both species to the paste generally increased as the pheromone concentration in the paste was increased. There was little response by either species to paste with less than 0.16% pheromone. The relationship between pheromone concentration and response for P. pyrusana was linear and for C. rosaceana was sinusoidal over the range of pheromone concentrations tested. These patterns were seen both in the wind tunnel and in the field. Initial release rates from the paste of (Z)-11-tetradecenyl acetate, the main component of the pheromone blends of both species was 3.6–3.8 ng/h. Inhibitory thresholds for responses were not reached for either species, using pheromone concentrations as high as 16%, in either the wind tunnel or the field. For both species, response of males to rubber septa with one mg pheromone loads was similar to the response to the paste with pheromone at concentrations greater than 3–4%. For C. rosaceana, rates of contact with the paste in the wind tunnel were statistically similar to rates of contact in response to conspecific females, with paste pheromone concentrations above 1.6%. Response rates for males of P. pyrusana were significantly lower to the paste than to conspecific females at all paste pheromone concentrations tested. Overall, the optimum pheromone concentration in the paste for moth attraction to contact was 3.2 % for C. rosaceana and 8% for P. pyrusana

Current CONtrolled Transmit And Receive Coil Elements (C2ONTAR) for Parallel Acquisition and Parallel Excitation Techniques at High-Field MRI

A novel intrinsically decoupled transmit and receive radio-frequency coil element is presented for applications in parallel imaging and parallel excitation techniques in high-field magnetic resonance imaging. Decoupling is achieved by a twofold strategy: during transmission elements are driven by current sources, while during signal reception resonant elements are switched to a high input impedance preamplifier. To avoid B0 distortions by magnetic impurities or DC currents a resonant transmission line is used to relocate electronic components from the vicinity of the imaged object. The performance of a four-element array for 3 T magnetic resonance tomograph is analyzed by means of simulation, measurements of electromagnetic fields and bench experiments. The feasibility of parallel acquisition and parallel excitation is demonstrated and compared to that of a conventional power source-driven array of equivalent geometry. Due to their intrinsic decoupling the current-controlled elements are ideal basic building blocks for multi-element transmit and receive arrays of flexible geometry