To assess nurses' compliance with central line associated bloodstream infection (CLABSI) prevention guidelines related to maintenance of the central line and the predictors of compliance. Method: This was an observational study that used a descriptive cross-sectional design. A sample of 171 intensive care unit (ICU) nurses were observed and their compliance was recorded on a structured observational sheet. The study was conducted in the ICUs of 15 hospitals located in 5 cities in Jordan. Data were collected over a 5-month period from March to July 2017. Central lines were all inserted by physicians inside the ICUs.

Due to low Fe bioavailability and low consumption per meal, lentil must be fortified to contribute significant bioavailable Fe in the Bangladeshi diet. Moreover, since red lentil is dehulled prior to consumption, an opportunity exists at this point to fortify lentil with Fe. Thus, in the present study, lentil was Fe-fortified (using a fortificant Fe concentration of 2800 µg g-1) and used in 30 traditional Bangladeshi meals with broad differences in concentrations of iron, phytic acid (PA), and relative Fe bioavailability (RFeB%). Fortification with NaFeEDTA increased the iron concentration in lentil from 60 to 439 µg g-1 and resulted in a 79% increase in the amount of available Fe as estimated by Caco-2 cell ferritin formation. Phytic acid levels were reduced from 6.2 to 4.6 mg g-1 when fortified lentil was added, thereby reducing the PA:Fe molar ratio from 8.8 to 0.9. This effect was presumably due to dephytinization of fortified lentil during the fortification process. A significant (p ≤ 0.01) Pearson correlation was observed between Fe concentration and RFeB% and between RFeB% and PA:Fe molar ratio in meals with fortified lentil, but not for the meal with unfortified lentil. In conclusion, fortified lentil can contribute significant bioavailable Fe to populations at risk of Fe deficiency.

Onion (Allium cepa L.) is widely consumed as food or medicinal plant due to its well-defined health benefits. The antioxidant and antihyperlipidemic effects of onion and its extracts have been reported well. However, very limited information on anti-hyperglycemic effect is available in processed onion extracts. In our previous study, we reported that Amadori rearrangement compounds (ARCs) produced by heat-processing in Korean ginseng can reduce carbohydrate absorption by inhibiting intestinal carbohydrate hydrolyzing enzymes in both in vitro and in vivo animal models. To prove the enhancement of anti-hyperglycemic effect and ARCs content by heat-processing in onion extract, a correlation between the anti-hyperglycemic activity and the total content of ARCs of heat-processed onion extract (ONI) was investigated. ONI has a high content of ARCs and had high rat small intestinal sucrase inhibitory activity (0.34 ± 0.03 mg/mL, IC50) relevant for the potential management of postprandial hyperglycemia. The effect of ONI on the postprandial blood glucose increase was investigated in Sprague Dawley (SD) rats fed on sucrose or starch meals. The maximum blood glucose levels (Cmax) of heat-processed onion extract were significantly decreased by about 8.7% (from 188.60 ± 5.37 to 172.27 ± 3.96, p < 0.001) and 14.2% (from 204.04 ± 8.73 to 175.13 ± 14.09, p < 0.01) in sucrose and starch loading tests, respectively. These results indicate that ARCs in onion extract produced by heat-processing have anti-diabetic effect by suppressing carbohydrate absorption via inhibition of intestinal sucrase, thereby reducing the postprandial increase of blood glucose. Therefore, enhancement of ARCs in onion by heat-processing might be a good strategy for the development of the new product on the management of hyperglycemia.

Excitotoxicity and oxidative stress play vital roles in the development of neurodegenerative disorders including Alzheimer's disease (AD). In the present study, we investigated the effect of N-((3,4-dihydro-2H-benzo[h]chromen-2-yl)methyl)-4-methoxyaniline (BL-M) on excitotoxic neuronal cell damage in primary cultured rat cortical cells, and compared to that of memantine, a non-competitive N-methyl-d-aspartate (NMDA) receptor antagonist clinically used to treat AD. We found that BL-M inhibited glutamate- or N-methyl-d-aspartate (NMDA)-induced excitotoxic cell damage. The IC50 value of BL-M against NMDA toxicity was comparable to that of memantine. BL-M potently inhibited intracellular reactive oxygen species generated by glutamate or NMDA. Additionally, it inhibited the formation of 1,1-diphenyl-2-picryl-hydrazyl radicals in vitro and lipid peroxidation in rat brain homogenates. In contrast, memantine showed minimal or negligible antioxidant activity. Western blotting and immunocytochemical analyses showed that BL-M, not memantine, increased the ERK1/2 phosphorylation and subsequent phosphorylation of cAMP response element-binding protein (CREB). The inhibition of NMDA toxicity by BL-M was dramatically reversed by U0126, a well-known MEK inhibitor, suggesting that ERK1/2-mediated CREB phosphorylation is required for the neuroprotective action. Collectively, in this study, we demonstrated the neuroprotective effect of a newly synthesized chromene derivative BL-M and its underlying action mechanism(s). In contrast to memantine, BL-M exhibited marked antioxidant activity. Furthermore, it enhanced the ERK-mediated phosphorylation of CREB, which plays a crucial neuroprotective role. Our findings suggest that BL-M may be beneficial for AD and other neurodegenerative disorders associated with excitotoxicity as well as oxidative stress.

We used the Luminex Bead Array Multiplex Immunoassay to measure cytokines, chemokines and growth factors responses to the same antigens used for RD1-based Interferon γ Release Assay (IGRA) test. Seventy-nine individuals, 27 active TB, 32 latent infection subsets, 20 individuals derivative purified protein (PPD) negative (subjects that do not have any indurative cutaneous reaction after 72 hrs of intradermal injection of PPD) and with other pulmonary disease were retrospectively studied. Forty-eight analytes were evaluated by Luminex Assay in plasma obtained from whole blood stimulated cells. The diagnostic accuracies of the markers detected were evaluated by ROC curve analysis and by the combination of multiple biomarkers to improve the potential to discriminate between infection/disease and non infection. Among 48 cytokines, 13 analytes, namely IL-3, IL-12-p40, LIF, IFNα2, IL-2ra, IL-13, b-NGF, SCF, TNF-β, TRAIL, IL-2, IFN-γ, IP-10, and MIG, were significantly higher in the active TB and LTBI groups, compared to NON-TB patients, while MIF was significantly lower in active TB patients compared to NON-TB and LTBI groups. The diagnostic accuracies of the markers detected in the culture supernatants evaluated by ROC curve analysis revealed that 11 analytes (IL2, IP10, IFN-γ, IL13, MIG, SCF, b-NGF, IL12-p40, TRAIL, IL2 Ra, LIF) discriminated between NON-TB and LTBI groups, with AUC for all analytes ≥0.73, while 14 analytes (IL2, IP10, IFN-γ, MIG, SCF, b-NGF, IL12-p40, TRAIL, IL2Ra, MIF, TNF-β, IL3, IFN-α2, LIF) discriminated between NON-TB and active TB groups, with AUC ≥0.78, that is a moderate, value in terms of accuracy of a diagnostic test. Finally, the combinations of seven biomarkers resulted in the accurate prediction of 88.89% of active TB patients, 82.35% of subjects with latent infection and 90% of non-TB patients, respectively. Taken together, our data suggest that combinations of whole blood Mycobacterium tuberculosis (Mtb) antigen dependent cytokines production could be useful as biomarkers to determine tuberculosis disease states when compared to non TB cohort.

The aphid genus Myzaphis van der Goot, 1913 from the tribe Macrosiphini is revised to include eight species. Apterous and alate viviparous females, known fundatrices and known sexual morphs (oviparous females and males) of Myzaphis bucktoni, M. juchnevitschae, M. rosarum, M. tianshanica and M. turanica are re-described and illustrated. Lectotype and paralectotypes of Myzaphis bucktoni and M. turanica are designated. The status of M. komatsubarae nomen dubium is discussed. Myzaphis avariolosa is regarded as a species belonging to the genus Ericaphis. Three new species: M. oezdemirae Kanturski & Barjadze sp. nov., M. tuatayae Kanturski & Barjadze sp. nov. from Turkey and M. rezwanii Kanturski & Barjadze sp. nov. from Iran are described and illustrated. Myzaphis bucktoni is recorded from Portugal for the first time. Diagnosis of the genus Myzaphis van der Goot, 1913 is redefined and a new genus Richardsaphis Kanturski & Barjadze gen. nov. is erected with the type species R. canadensis (Richards) comb. nov. Richardsaphis is for the first time recorded from the USA and hitherto unknown oviparous female and alate male are described and illustrated. Original keys to species of the genus Myzaphis and aphid genera of the tribe Macrosiphini with 2-2-2 first tarsal chaetotaxy are also provided.

Understanding the relationship between external stimuli and the spiking activity of cortical populations is a central problem in neuroscience. Dense recurrent connectivity in local cortical circuits can lead to counterintuitive response properties, raising the question of whether there are simple arithmetical rules for relating circuits' connectivity structure to their response properties. One such arithmetic is provided by the mean field theory of balanced networks, which is derived in a limit where excitatory and inhibitory synaptic currents precisely balance on average. However, balanced network theory is not applicable to some biologically relevant connectivity structures. We show that cortical circuits with such structure are susceptible to an amplification mechanism arising when excitatory-inhibitory balance is broken at the level of local subpopulations, but maintained at a global level. This amplification, which can be quantified by a linear correction to the classical mean field theory of balanced networks, explains several response properties observed in cortical recordings and provides fundamental insights into the relationship between connectivity structure and neural responses in cortical circuits.

Circulating tumor DNA (ctDNA) analysis is being incorporated into cancer care; notably in profiling patients to guide treatment decisions. Responses to targeted therapies have been observed in patients with actionable mutations detected in plasma DNA at variant allele fractions (VAFs) below 0.5%. Highly sensitive methods are therefore required for optimal clinical use. To enable objective assessment of assay performance, detailed analytical validation is required. We developed the InVisionFirst™ assay, an assay based on enhanced tagged amplicon sequencing (eTAm-Seq™) technology to profile 36 genes commonly mutated in non-small cell lung cancer (NSCLC) and other cancer types for actionable genomic alterations in cell-free DNA. The assay has been developed to detect point mutations, indels, amplifications and gene fusions that commonly occur in NSCLC. For analytical validation, two 10mL blood tubes were collected from NSCLC patients and healthy volunteer donors. In addition, contrived samples were used to represent a wide spectrum of genetic aberrations and VAFs. Samples were analyzed by multiple operators, at different times and using different reagent Lots. Results were compared with digital PCR (dPCR). The InVisionFirst assay demonstrated an excellent limit of detection, with 99.48% sensitivity for SNVs present at VAF range 0.25%-0.33%, 92.46% sensitivity for indels at 0.25% VAF and a high rate of detection at lower frequencies while retaining high specificity (99.9997% per base). The assay also detected ALK and ROS1 gene fusions, and DNA amplifications in ERBB2, FGFR1, MET and EGFR with high sensitivity and specificity. Comparison between the InVisionFirst assay and dPCR in a series of cancer patients showed high concordance. This analytical validation demonstrated that the InVisionFirst assay is highly sensitive, specific and robust, and meets analytical requirements for clinical applications.

Major intrinsic proteins (MIP) are characterized by a transmembrane pore-type architecture that facilitates transport across biomembranes of water and a variety of low molecular weight solutes. They are found in all parts of life, with remarkable protein diversity. Very little is known about MIP from fungi. And yet, it can legitimately be stated that MIP are pivotal molecular components in the privileged relationships fungi enjoy with plants or soil fauna in various environments. To date, MIP have never been studied in a mycoparasitism situation. In this study, the diversity, expression and functional prediction of MIP from the genus Trichoderma were investigated. Trichoderma spp. genomes have at least seven aquaporin genes. Based on a phylogenetic analysis of the translated sequences, members were assigned to the AQP, AQGP and XIP subfamilies. In in vitro and in planta assays with T. harzianum strain Ths97, expression analyses showed that four genes were constitutively expressed. In a mycoparasitic context with Fusarium solani, the causative agent of fusarium dieback on olive tree roots, these genes were up-regulated. This response is of particular interest in analyzing the MIP promoter cis-regulatory motifs, most of which are involved in various carbon and nitrogen metabolisms. Structural analyses provide new insights into the possible role of structural checkpoints by which these members transport water, H2O2, glycerol and, more generally, linear polyols across the membranes. Taken together, these results provide the first evidence that MIP may play a key role in Trichoderma mycoparasitism lifestyle.

In this paper we report the development of a cost-effective, modular, open source, and fully automated slide-scanning microscope, composed entirely of easily available off-the-shelf parts, and capable of bright field and fluorescence modes. The automated X-Y stage is composed of two low-cost micrometer stages coupled to stepper motors operated in open-loop mode. The microscope is composed of a low-cost CMOS sensor and low-cost board lenses placed in a 4f configuration. The system has approximately 1 micron resolution, limited by the f/# of available board lenses. The microscope is compact, measuring just 25×25×30 cm, and has an absolute positioning accuracy of ±1 μm in the X and Y directions. A Z-stage enables autofocusing and imaging over large fields of view even on non-planar samples, and custom software enables automatic determination of sample boundaries and image mosaicking. We demonstrate the utility of our device through imaging of fluorescent- and transmission-dye stained blood and fecal smears containing human and animal parasites, as well as several prepared tissue samples. These results demonstrate image quality comparable to high-end commercial microscopes at a cost of less than US$400 for a bright-field system, with an extra US$100 needed for the fluorescence module.

The DE-PLAN-CAT project (Diabetes in Europe-Prevention using lifestyle, physical activity and nutritional intervention-Catalonia) has shown that an intensive lifestyle intervention is feasible in the primary care setting and substantially reduces the incidence of diabetes among high-risk Mediterranean participants. The DP-TRANSFERS project (Diabetes Prevention-Transferring findings from European research to society) is a large-scale national programme aimed at implementing this intervention in primary care centres whenever feasible.

Reprogramming somatic cells to a pluripotent cell state (induced Pluripotent Stem (iPS) cells) requires reprogramming of metabolism to support cell proliferation and pluripotency, most notably changes in carbohydrate turnover that reflect a shift from oxidative to glycolytic metabolism. Some aspects of iPS cell metabolism differ from embryonic stem (ES) cells, which may reflect a parental cell memory, or be a consequence of the reprogramming process. In this study, we compared the metabolism of 3 human iPS cell lines to assess the fidelity of metabolic reprogramming. When challenged with reduced oxygen concentration, ES cells have been shown to modulate carbohydrate use in a predictably way. In the same model, 2 of 3 iPS cell lines failed to regulate carbohydrate metabolism. Oxygen is a well-characterized regulator of cell function and embryo viability, and an inability of iPS cells to modulate metabolism in response to oxygen may indicate poor metabolic fidelity. As metabolism is linked to the regulation of the epigenome, assessment of metabolic responses of iPS cells to physiological stimuli during characterization is warranted to ensure complete cell reprogramming and as a measure of cell quality.

The HIV care cascade has improved in Latin America over the last decade. However, the influence of alcohol and noninjected drug use (NIDU) on cascade outcomes is mostly unknown. This study estimated the association of alcohol and NIDU with retention in care, loss to follow up (LTFU), and virologic failure (VF).

Biochemical conversion of lignocellulosic biomass to liquid fuels requires pretreatment and enzymatic hydrolysis of the biomass to produce fermentable sugars. Degradation products produced during thermochemical pretreatment, however, inhibit the microbes with regard to both ethanol yield and cell growth. In this work, we used synthetic hydrolysates (SynH) to study the inhibition of yeast fermentation by water-soluble components (WSC) isolated from lignin streams obtained after extractive ammonia pretreatment (EA). We found that SynH with 20g/L WSC mimics real hydrolysate in cell growth, sugar consumption and ethanol production. However, a long lag phase was observed in the first 48 h of fermentation of SynH, which is not observed during fermentation with the crude extraction mixture. Ethyl acetate extraction was conducted to separate phenolic compounds from other water-soluble components. These phenolic compounds play a key inhibitory role during ethanol fermentation. The most abundant compounds were identified by Liquid Chromatography followed by Mass Spectrometry (LC-MS) and Gas Chromatography followed by Mass Spectrometry (GC-MS), including coumaroyl amide, feruloyl amide and coumaroyl glycerol. Chemical genomics profiling was employed to fingerprint the gene deletion response of yeast to different groups of inhibitors in WSC and AFEX-Pretreated Corn Stover Hydrolysate (ACSH). The sensitive/resistant genes cluster patterns for different fermentation media revealed their similarities and differences with regard to degradation compounds.

Mulberry (Morus alba L.) is an important economic tree species in many countries. Quantitative real time PCR (qRT-PCR) has become a widely used method for gene expression studies in plants. A suitable reference gene is essential to ensure accurate and reliable results for qRT-PCR analyses. However, no reports describing the selection of reference genes have been published for mulberry. In this work, we evaluated the stability of twenty candidate reference genes in different plant tissues and under different stress conditions by qRT-PCR in mulberry using algorithms in two programs-geNorm and NormFinder. The results revealed that TUB2, UBI4, ACTIN3 and RPL4 were ranked as the most stable reference genes in the samples subsets, whereas EF1α4 and TUB3showed the least stability with both algorithms. To further validate the stability of the reference genes, the expression patterns of six genes of mulberry were analyzed by normalization with the selected reference genes. Our study will benefit future analyses of gene expression in mulberry.

The success of Staphylococcus aureus, as both a human and animal pathogen, stems from its ability to rapidly adapt to a wide spectrum of environmental conditions. Two-component systems (TCSs) play a crucial role in this process. Here, we describe a novel staphylococcal virulence factor, SpdC, an Abi-domain protein, involved in signal sensing and/or transduction. We have uncovered a functional link between the WalKR essential TCS and the SpdC Abi membrane protein. Expression of spdC is positively regulated by the WalKR system and, in turn, SpdC negatively controls WalKR regulon genes, effectively constituting a negative feedback loop. The WalKR system is mainly involved in controlling cell wall metabolism through regulation of autolysin production. We have shown that SpdC inhibits the WalKR-dependent synthesis of four peptidoglycan hydrolases, SceD, SsaA, LytM and AtlA, as well as impacting S. aureus resistance towards lysostaphin and cell wall antibiotics such as oxacillin and tunicamycin. We have also shown that SpdC is required for S. aureus biofilm formation and virulence in a murine septicemia model. Using protein-protein interactions in E. coli as well as subcellular localization in S. aureus, we showed that SpdC and the WalK kinase are both localized at the division septum and that the two proteins interact. In addition to WalK, our results indicate that SpdC also interacts with nine other S. aureus histidine kinases, suggesting that this membrane protein may act as a global regulator of TCS activity. Indeed, using RNA-Seq analysis, we showed that SpdC controls the expression of approximately one hundred genes in S. aureus, many of which belong to TCS regulons.

Peroxisome proliferator activated receptor-alpha (PPARα) and Egl nine homolog 3 (EGLN3) play critical roles in facilitating the adaptation to a hypoxic environment. However, the relationship between EGLN3 and PPARα variants and hypoxic adaptation remains poorly understood in Tibetan chickens. To better understand the effects of genetic variation, we sequenced exons of PPARα and EGLN3 in 138 Lowland chickens (LC) from 7 breeds that were located in Emei, Miyi, Shimian, Wanyuan, Pengxian, and Muchuan in the Sichuan province, and Wenchang in the Hainan province (altitudes for these locations are below 1800 meters). Total 166 Tibetan chickens (TC) from 7 subpopulations that were located in Shigatse, Lhoka, Lhasa, Garze, Aba, Diqing and Yushu in the Tibetan area were also sequenced (altitudes greater than 2700 meters). One single-nucleotide polymorphism (rs316017491, C > T) was identified in EGLN3 and was shared by TC and LC with no significant difference for allele frequencies between them (P > 0.05). Six single-nucleotide polymorphisms (SNP1, A29410G; SNP2, rs13886097; SNP3, T29467C; SNP4, rs735915170; SNP5, rs736599044; and SNP6, rs740077421) including one non-synonymous mutation (SNP2, T > C) were identified in PPARα. This is the first report of SNP1 and SNP3. There was a difference between TC and LC for allele frequencies (P <0.01), except for SNP1, SNP4, and SNP5) The fix index statistic test indicated that there was population differentiation between TC and LC for SNP2, SNP3, and SNP6 in PPARα (P < 0.05). Phylogenetic analysis showed that the genetic distance among chickens, finch and great tit were close for both EGLN3 and PPARα. Bioinformatics analysis of PPARα showed that SNP2 leads to an amino acid substitution of Ile for Met, which results in the protein being more likely to be hydrolyzed. Thus, genetic variation in PPARα may play a role in the ability of TC to adapt to a high altitude environment; however we were unable to identify a relationship between polymorphisms in EGLN3 and environmental adaptability.

Cationic liposome-nucleic acid (CL-NA) complexes, which form spontaneously, are a highly modular gene delivery system. These complexes can be sterically stabilized via PEGylation [PEG: poly (ethylene glycol)] into nanoparticles (NPs) and targeted to specific tissues and cell types via the conjugation of an affinity ligand. However, there are currently no guidelines on how to effectively navigate the large space of compositional parameters that modulate the specific and nonspecific binding interactions of peptide-targeted NPs with cells. Such guidelines are desirable to accelerate the optimization of formulations with novel peptides. Using PEG-lipids functionalized with a library of prototypical tumor-homing peptides, we varied the peptide density and other parameters (binding motif, peptide charge, CL/DNA charge ratio) to study their effect on the binding and uptake of the corresponding NPs. We used flow cytometry to quantitatively assess binding as well as internalization of NPs by cultured cancer cells. Surprisingly, full peptide coverage resulted in less binding and internalization than intermediate coverage, with the optimum coverage varying between cell lines. In, addition, our data revealed that great care must be taken to prevent nonspecific electrostatic interactions from interfering with the desired specific binding and internalization. Importantly, such considerations must take into account the charge of the peptide ligand as well as the membrane charge density and the CL/DNA charge ratio. To test our guidelines, we evaluated the in vivo tumor selectivity of selected NP formulations in a mouse model of peritoneally disseminated human gastric cancer. Intraperitoneally administered peptide-tagged CL-DNA NPs showed tumor binding, minimal accumulation in healthy control tissues, and preferential penetration of smaller tumor nodules, a highly clinically relevant target known to drive recurrence of the peritoneal cancer.

To analyze age representation trends over time in antiepileptic drug (AED) trials and to assess trial design elements as possible barriers to enrollment of elderly patients.

Patients attend primary care with many types of problems and to achieve a range of possible outcomes. There is currently a lack of patient-reported outcome measures (PROMs) designed to capture these diverse outcomes. The objective of this systematic review was to identify, describe and appraise generic PROMs suitable for measuring outcomes from primary care.