DAB2IP associates with hereditary angioedema: Insights into the role of VEGF signaling in HAE pathophysiology.

BACKGROUND: In the recent years, there was an important improvement in the understanding of the pathogenesis of hereditary angioedema (HAE). Notwithstanding, in a large portion of patients with unknown mutation (HAE-UNK) the genetic cause remains to be identified. OBJECTIVES: To identify new genetic targets associated with HAE, a large Argentine family with HAE-UNK spanning 3 generations was studied. METHODS: Whole exome sequencing was performed on affected family members to identify potential genetic variants associated with HAE-UNK. In silico analyses and experimental studies were applied to assess the role of the identified gene variant. RESULTS: A missense variant (p.D239N) in DAB2IP was identified. The variant occurred in the C2-domain, the region interacting with vascular endothelial growth factor receptor 2 (VEGFR2). It was found to be rare, and predicted to have a detrimental effect on the functionality of DAB2IP. Protein structure modeling predicted changes in the mutant p.D239N protein structure, impacting protein stability. The p.D239N variant affected the subcellular localization of VEGFR2. Cells transfected with the DAB2IP-239N transcript exhibited an intracellular distribution, and VEGFR2 remained associated with the cell membrane. The altered localization pattern indicated reduced colocalization of the mutant protein with VEGFR2, suggesting a diminished ability of VEGFR2 binding. CONCLUSIONS: The study identified a novel missense variant (p.D239N) in DAB2IP in a family with HAE-UNK and highlighted the role of dysregulated VEGF-mediated signaling in altered endothelial permeability. DAB2IP loss-of-function pathogenic variants lead to the impairment of the endothelial VEGF/VEGFR2 ligand system and represent a new pathophysiologic cause of HAE-UNK.

Novel systematic processing of cardiac magnetic resonance imaging identifies target regions associated with infarct-related ventricular tachycardia.

AIMS: There is lack of agreement on late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) imaging processing for guiding ventricular tachycardia (VT) ablation. We aim at developing and validating a systematic processing approach on LGE-CMR images to identify VT corridors that contain critical VT isthmus sites. METHODS AND RESULTS: This is a translational study including 18 pigs with established myocardial infarction and inducible VT undergoing in vivo characterization of the anatomical and functional myocardial substrate associated with VT maintenance. Clinical validation was conducted in a multicentre series of 33 patients with ischaemic cardiomyopathy undergoing VT ablation. Three-dimensional LGE-CMR images were processed using systematic scanning of 15 signal intensity (SI) cut-off ranges to obtain surface visualization of all potential VT corridors. Analysis and comparisons of imaging and electrophysiological data were performed in individuals with full electrophysiological characterization of the isthmus sites of at least one VT morphology. In both the experimental pig model and patients undergoing VT ablation, all the electrophysiologically defined isthmus sites (n = 11 and n = 19, respectively) showed overlapping regions with CMR-based potential VT corridors. Such imaging-based VT corridors were less specific than electrophysiologically guided ablation lesions at critical isthmus sites. However, an optimized strategy using the 7 most relevant SI cut-off ranges among patients showed an increase in specificity compared to using 15 SI cut-off ranges (70 vs. 62%, respectively), without diminishing the capability to detect VT isthmus sites (sensitivity 100%). CONCLUSION: Systematic imaging processing of LGE-CMR sequences using several SI cut-off ranges may improve and standardize procedure planning to identify VT isthmus sites.

Systemic inflammation and cortical neurochemistry in never-medicated first episode-psychosis individuals.

Studies of cellular and cytokine profiles have contributed to the inflammation hypothesis of schizophrenia; however, precise markers of inflammatory dysfunction remain elusive. A number of proton magnetic resonance spectroscopy (1H-MRS) studies in patients with first-episode psychosis (FEP) have shown higher brain levels of metabolites such as glutamate, myo-inositol (mI) and choline-containing compounds (tCho), suggesting neuroinflammation. Here, we present peripheral inflammatory profiles in antipsychotic-naive FEP patients and age-and-sex matched healthy controls, as well as cortical glutamate, mI and tCho levels using 1H-MRS. Inflammatory profiles were analyzed using cytokine production by peripheral blood mononuclear cells, that were either spontaneous or stimulated, in 48 FEP patients and 23 controls. 1H-MRS of the medial prefrontal cortex was obtained in 29 FEP patients and 18 controls. Finally, 16 FEP patients were rescanned after 4 weeks of treatment (open-label) with Risperidone. FEP patients showed a higher proportion of proinflammatory Th1/Th17 subset, and an increased spontaneous production of Interleukin (IL)-6, IL-2 and IL-4 compared with the control group. Results obtained from 1H-MRS showed no significant difference in either glutamate, mI or tCho between FEP and control groups. At baseline, CD8% showed a negative correlation with glutamate in FEP patients; after 4 weeks of risperidone treatment, the FEP group exhibited a decrease in glutamate levels which positively correlated with CD4 + T cells. Nevertheless, these correlations did not survive correction for multiple comparisons. FEP patients show evidence of immune dysregulation, affecting both the innate and adaptive immune response, with a predominantly Th2 signature. These findings, along with the changes produced by antipsychotic treatment, could be associated with both systemic and central inflammatory processes in schizophrenia.

Measurement of Cutting Temperature in Interrupted Machining Using Optical Spectrometry.

This research presents an experimental study focused on measuring temperature at the tool flank during the up-milling process at high cutting speed. The proposed system deals with emissivity compensation through a two-photodetector system and during calibration. A ratio pyrometer composed of two photodetectors and a multimode fiber-optic coupler is employed to capture the radiation emitted by the cutting insert. The pyrometer is calibrated using an innovative calibration system that addresses theoretical discrepancies arising from various factors affecting the measurement of cutting temperature. This calibration system replicates the milling process to generate a calibration curve. Experimentally, AISI 4140 steel is machined with coated tungsten carbide inserts, using cutting speeds of 300 and 400 m/min, and feed rates of 0.08 and 0.16 mm/tooth. The results reveal a maximum recorded cutting temperature of 518 °C and a minimum of 304 °C. The cutting temperature tends to increase with higher cutting speeds and feed rates, with cutting speed being the more influential factor in this increase. Both the pyrometer calibration and experimental outcomes yield satisfactory results. Finally, the results showed that the process and the device prove to be a convenient, effective, and precise method of measuring cutting temperature in machine processes.

Mycofumigation of postharvest blueberries with volatile compounds from Trichoderma atroviride IC-11 is a promising tool to control rots caused by Botrytis cinerea.

Botrytis cinerea, the causal agent of the gray mold, is a filamentous fungus that infects blueberries and can cause important production losses in postharvest storage. Considering that the use of synthetic fungicides is not allowed on blueberries in postharvest conditions, alternative and natural strategies are needed to control gray mold. The objective of this work was to evaluate the capability of volatile organic compounds (VOCs) produced by Trichoderma atroviride IC-11 to control B. cinerea growth in blueberries after harvest. These VOCs inhibited almost completely B. cinerea growth in vitro. The most abundant volatile compound was 6-pentyl-α-pyrone (6PP). In vitro assays with pure 6PP confirmed its antifungal activity. The incidence of gray mold was evaluated in blueberries inoculated with B. cinerea and exposed to volatiles of T. atroviride IC-11. Gray mold incidence among those stored in air at 20 °C for 14 days was 100%, while the incidence among the volatile-treated fruit was 17%. Gray mold incidence among those stored in air at 4 °C for 31 days was 82%, while the incidence among the volatile-treated fruit was 11%. T. atroviride IC-11 VOCs inhibited mycelial growth and conidia germination of B. cinerea. The binding of VOCs to the surface of hyphae caused their vacuolation and deterioration. Selective cytotoxicity of 6PP on B. cinerea was observed but not on human intestinal cells at specific concentrations that controlled gray mold. The postharvest mycofumigation of blueberries with T. atroviride IC-11 VOCs is a promising approach to protect these fruits from gray mold.

Low-Density Granulocytes and Neutrophil Extracellular Traps as Biomarkers of Disease Activity in Adult Inflammatory Myopathies.

BACKGROUND/OBJECTIVE: Biomarkers for disease activity and damage accrual in idiopathic inflammatory myopathies (IIMs) are currently lacking. The purpose of this cross-sectional study is to analyze the relationship among low-density granulocytes (LDGs), neutrophil extracellular traps (NETs), and clinical and immunological features of patients with IIM. METHODS: We assessed disease activity, damage accrual, amount of LDGs, NETs, expression of LL-37, and serum cytokines in 65 adult patients with IIM. Differences between groups and correlations were assessed by Kruskal-Wallis, Mann-Whitney U, and Spearman ρ tests. The association between LDGs, NETs, disease activity, calcinosis, and cutaneous ulcers was assessed by logistic regression. To address the capacity of LDGs and NETs to diagnose disease activity, we used receiving operating characteristic curves. RESULTS: Low-density granulocytes were higher in patients with active disease, ulcers, calcinosis, and anti-MDA5 antibodies, which correlated with serum levels of IL-17A and IL-18. Neutrophil extracellular traps were higher in patients with calcinosis, elevated titers of antinuclear antibodies, and positive anti-PM/Scl75 tests. The combination of a high proportion of both total LDGs and NETs was associated with the presence of calcinosis and cutaneous ulcers. LL-37 was higher in NETs originating from LDGs. Normal-density neutrophils were elevated in patients with active dermatomyositis. CONCLUSIONS: Low-density granulocytes and NETs containing LL-37 are increased in patients with IIM and active disease, and correlate with proinflammatory cytokines. Both total and CD10+ LDGs are potential biomarkers for disease activity and, in combination with NETs, have the potential to detect patients who are at risk for cutaneous ulcers and calcinosis.

Lactobacillus gasseri liver abscess and bacteremia: a case report.

BACKGROUND: Lactobacillus is a genus of Gram-positive non-spore-forming rods usually found in the microbiota of the oral cavity, gastrointestinal tract, and female genitourinary tract. Also, they are commonly used in the food industry as supplements and probiotics. Lactobacilli are normally considered non-pathogenic to the human body, however, under certain circumstances such as immunosuppression, they can cause severe infections, with only a few cases of bacteremia, infective endocarditis, pneumonia, meningitis, and intra-abdominal infections reported. Among these presentations, a pyogenic liver abscess is rather rare. CASE PRESENTATION: We describe the case of a 59-year-old man with a history of diabetes mellitus and multiple abdominal surgeries with the latest being in 2014 presenting with bacteremia and multiple large pyogenic liver abscesses due to Lactobacillus gasseri, which did not appear to be related to the use of probiotics or immunosuppression. CONCLUSIONS: Given the high prevalence of diabetes mellitus and the increased use of probiotics, it is expected that in the future we will see an increase in infections caused by Lactobacilli. Medical management with antibiotics and percutaneous drainage were successful strategies for the treatment of this unusual case of pyogenic liver abscesses and bacteremia caused by Lactobacillus gasseri.

Sensor Information Sharing Using a Producer-Consumer Algorithm on Small Vehicles.

There are several tools, frameworks, and algorithms to solve information sharing from multiple tasks and robots. Some applications such as ROS, Kafka, and MAVLink cover most problems when using operating systems. However, they cannot be used for particular problems that demand optimization of resources. Therefore, the objective was to design a solution to fit the resources of small vehicles. The methodology consisted of defining the group of vehicles with low performance or are not compatible with high-level known applications; design a reduced, modular, and compatible architecture; design a producer-consumer algorithm that adjusts to the simultaneous localization and communication of multiple vehicles with UWB sensors; validate the operation with an interception task. The results showed the feasibility of performing architecture for embedded systems compatible with other applications managing information through the proposed algorithm allowed to complete the interception task between two vehicles. Another result was to determine the system's efficiency by scaling the memory size and comparing its performance. The work's contributions show the areas of opportunity to develop architectures focusing on the optimization of robot resources and complement existing ones.

TLR expression in peripheral monocyte subsets of patients with idiopathic inflammatory myopathies: association with clinical and immunological features.

BACKGROUND: Monocytes and toll-like receptors (TLR) have been found in the inflammatory infiltrate of muscle biopsies in patients with idiopathic inflammatory myopathies (IIM), suggesting an important role of these cells in the pathogenesis of myositis. The monocyte subsets, their TLR expression in peripheral blood and their relationship with the clinical characteristics of patients with IIM has not been addressed. METHODS: We recruited 45 patients with IIM diagnosis and 15 age and sex-adjusted healthy controls. We assessed the disease activity and damage, performed a nailfold capillaroscopy and registered the cardio-pulmonary parameters from the medical charts. Monocyte subsets, their expression of TLR2 and TLR4 and the serum Th1/Th2/Th17 cytokines levels were evaluated by flow cytometry. We expressed quantitative variables as medians and interquartile ranges (IQR) or minimum and maximum (min-max). Differences between groups were assessed with Mann-Whitney U and the Kruskal-Wallis tests. Correlation between quantitative variables was assessed with Spearman Rho. RESULTS: Twenty-nine patients were women (64.4%) and 32 (71.1%) had dermatomyositis. In comparison to healthy controls, patients with active IIM had a higher percentage of intermediate monocytes and lower amounts of classical monocytes. Patients with IIM had a higher expression of TLR4 in all their monocyte subsets, regardless of disease activity and prednisone treatment. Serum IL-6 correlated with the TLR2 expression in every monocyte subset and the expression of TLR2 in intermediate monocytes was higher among patients with dysphagia. Subjects with nailfold capillaroscopy abnormalities had a higher amount of TLR2+ classical and non-classical monocytes and those with interstitial lung disease (ILD) had a higher percentage of TLR4+ non-classical monocytes. The classical and intermediate monocytes from patients with anti Mi2 antibodies had a higher expression of TLR4. The percentage of intermediate monocytes and the expression of TLR4 in all monocyte subsets showed a good diagnostic capacity in patients with IIM. CONCLUSION: Patients with IIM have a differential pool of monocyte subsets with an enhanced expression of TLR2 and TLR4, which correlates with disease activity and distinctive clinical features including dysphagia, ILD, vasculopathy, and pro-inflammatory cytokines. These immunological features might be useful as a potential diagnostic tool as well as novel disease activity biomarkers in IIM.

Conformational changes in myeloperoxidase induced by ubiquitin and NETs containing free ISG15 from systemic lupus erythematosus patients promote a pro-inflammatory cytokine response in CD4+ T cells.

BACKGROUND: Neutrophil extracellular traps (NETs) from patients with systemic lupus erythematosus (SLE) are characterized by lower ubiquitylation and myeloperoxidase (MPO) as a substrate. The structural and functional effect of such modification and if there are additional post-translational modifications (PTMs) are unknown. METHODS: To assess the expression and functional role of PTMs in NETs of patients with SLE; reactivation, proliferation and cytokine production was evaluated by flow cytometry using co-cultures with dendritic cells (DC) and CD4+ from SLE patients and healthy controls. The impact of ubiquitylation on MPO was assessed by molecular dynamics. The expression of ISG15 in NETs was evaluated by immunofluorescence and Western Blot. RESULTS: Fifteen patients with SLE and ten healthy controls were included. In the co-cultures of CD4+ lymphocytes with DC stimulated with ubiquitylated MPO or recombinant MPO, a higher expression of IFNγ and IL-17A was found in CD4+ from SLE patients (p < 0.05). Furthermore, with DC stimulated with ubiquitylated MPO a trend towards increased expression of CD25 and Ki67 was found in lupus CD4+ lymphocytes, while the opposite was documented in controls (p < 0.05). Through molecular dynamics we found the K129-K488-K505 residues of MPO as susceptible to ubiquitylation. Ubiquitylation affects the hydration status of the HEME group depending on the residue to which it is conjugated. R239 was found near by the HEME group when the ubiquitin was in K488-K505. In addition, we found greater expression of ISG15 in the SLE NETs vs controls (p < 0.05), colocalization with H2B (r = 0.81) only in SLE samples and increased production of IFNγ in PBMCs stimulated with lupus NETs compared to healthy controls NETs. CONCLUSION: The ubiquitylated MPO has a differential effect on the induction of reactivation of CD4+ lymphocytes in patients with SLE, which may be related to structural changes by ubiquitylation at the catalytic site of MPO. Besides a lower ubiquitylation pattern, NETs of patients with SLE are characterized by the expression of ISG15, and the induction of IFNγ by Th1 cells.

Optical Methods Based on Ultraviolet, Visible, and Near-Infrared Spectra to Estimate Fat and Protein in Raw Milk: A Review.

The present manuscript focuses on reviewing the optical techniques proposed to monitor milk quality in dairy farms to increase productivity and reduce costs. As is well known, the quality is linked to the fat and protein concentration; in addition, this issue is crucial to maintaining a healthy herd and preventing illnesses such as mastitis and ketosis. Usually, the quality of the milk is carried out with invasive methods employing chemical reagents that increase the time analysis. As a solution, several spectroscopy optical methods have been proposed, here, the benefits such as non-invasive measurement, online implementation, rapid estimation, and cost-effective execution. The most attractive optical methods to estimate fat and protein in cow's milk are compared and discussed considering their performance. The analysis is divided considering the wavelength operation (ultraviolet, visible, and infrared). Moreover, the weaknesses and strengths of the methods are fully analyzed. Finally, we provide the trends and a recent technique based on spectroscopy in the visible wavelength.

All Single-Mode-Fiber Supercontinuum Source Setup for Monitoring of Multiple Gases Applications.

In this paper, a gas sensing system based on a conventional absorption technique using a single-mode-fiber supercontinuum source (SMF-SC) is presented. The SC source was implemented by channeling pulses from a microchip laser into a one kilometer long single-mode fiber (SMF), obtaining a flat high-spectrum with a bandwidth of up to 350 nm in the region from 1350 to 1700 nm, and high stability in power and wavelength. The supercontinuum radiation was used for simultaneously sensing water vapor and acetylene gas in the regions from 1350 to 1420 nm and 1510 to 1540 nm, respectively. The experimental results show that the absorption peaks of acetylene have a maximum depth of approximately 30 dB and contain about 60 strong lines in the R and P branches, demonstrating a high sensitivity of the sensing setup to acetylene. Finally, to verify the experimental results, the experimental spectra are compared to simulations obtained from the Hitran database. This shows that the implemented system can be used to develop sensors for applications in broadband absorption spectroscopy and as a low-cost absorption spectrophotometer of multiple gases.

The role of low density granulocytes and NETosis in the pathogenesis of adult-onset Still's Disease.

OBJECTIVES: To analyse the potential contribution of low-density granulocytes (LDGs) and NETosis, as well as the differential protein cargo of neutrophil extracellular traps (NETs), as physiopathogenic mechanisms of adult-onset Still's disease (AOSD). METHODS: We recruited 30 patients with AOSD according to the Yamaguchi diagnostic criteria. LDGs were addressed by multiparametric flow cytometry as those CD14-, CD15+, CD10+ cells in the peripheral blood mononuclear cells fraction. NETs were quantified by ELISA, immunofluorescence and fluorescence spectrometry. The expression of LL-37 and high mobility group box 1 (HMGB-1) in NETs was measured by immunofluorescence and confocal microscopy. Additionally, normal density neutrophils from healthy controls were stimulated with serum from patients with AOSD and NET induction was assessed by immunofluorescence. RESULTS: Patients with active disease as well as those with arthritis, cutaneous manifestations and fever had a higher amount of NETs and LDGs. Serum NETs from AOSD patients correlated with the number of swollen joints (r=0.41, p=0.032), absolute number of monocytes (r=0.529, p=0.005). The spontaneous NETs from patients with cutaneous manifestations and fever had higher cargo of HMGB-1 compared with patients in remission. CONCLUSIONS: LDGs and NETs are increased in patients with active AOSD and correlate with particular clinical features. Patients with cutaneous lesions and fever present a higher cargo of HMGB1 in their spontaneous NETs.

Implications of bipolar voltage mapping and magnetic resonance imaging resolution in biventricular scar characterization after myocardial infarction.

AIMS: We aimed to study the differences in biventricular scar characterization using bipolar voltage mapping compared with state-of-the-art in vivo delayed gadolinium-enhanced cardiac magnetic resonance (LGE-CMR) imaging and ex vivo T1 mapping. METHODS AND RESULTS: Ten pigs with established myocardial infarction (MI) underwent in vivo scar characterization using LGE-CMR imaging and high-density voltage mapping of both ventricles using a 3.5-mm tip catheter. Ex vivo post-contrast T1 mapping provided a high-resolution reference. Voltage maps were registered onto the left and right ventricular (LV and RV) endocardium, and epicardium of CMR-based geometries to compare voltage-derived scars with surface-projected 3D scars. Voltage-derived scar tissue of the LV endocardium and the epicardium resembled surface projections of 3D in vivo and ex vivo CMR-derived scars using 1-mm of surface projection distance. The thinner wall of the RV was especially sensitive to lower resolution in vivo LGE-CMR images, in which differences between normalized low bipolar voltage areas and CMR-derived scar areas did not decrease below a median of 8.84% [interquartile range (IQR) (3.58, 12.70%)]. Overall, voltage-derived scars and surface scar projections from in vivo LGE-CMR sequences showed larger normalized scar areas than high-resolution ex vivo images [12.87% (4.59, 27.15%), 18.51% (11.25, 24.61%), and 9.30% (3.84, 19.59%), respectively], despite having used optimized surface projection distances. Importantly, 43.02% (36.54, 48.72%) of voltage-derived scar areas from the LV endocardium were classified as non-enhanced healthy myocardium using ex vivo CMR imaging. CONCLUSION: In vivo LGE-CMR sequences and high-density voltage mapping using a conventional linear catheter fail to provide accurate characterization of post-MI scar, limiting the specificity of voltage-based strategies and imaging-guided procedures.

A New Method for Total Fat Detection in Raw Milk Based on Dual Low-Coherence Interferometer.

The present work experimentally demonstrates a multimode fiber optic sensing setup for total fat detection in raw milk samples. The optical fiber arrangement incorporates a low-coherence Fabry-Perot cavity operating in dual response. The system provides a phase modulation for a total fat range from 0.97% to 4.36%. Here, the protein remains constant at 3%. The data indicate that maximum sensitivity close to 616 pm/%fat could be achieved at optimal wavelength operation (500 nm). In addition, the system presented a minimal repeatability error measurement of 0.08%, cross-sensitivity between protein and fat of 0.134, and a regression coefficient of r2=0.9763. A thermal analysis was also performed, which indicate the temperature immunity of the system. The proposed method represents a low-cost alternative to detect minimal fat variations in raw cow milk.

Correlation of Vitamin D with Inflammatory Cytokines, Atherosclerotic Parameters, and Lifestyle Factors in the Setting of Heart Failure: A 12-Month Follow-Up Study.

Vitamin D deficiency is highly prevalent worldwide. It has been associated with heart failure (HF) given its immunoregulatory functions. In-vitro and animal models have shown protective roles through mechanisms involving procollagen-1, JNK2, calcineurin/NFAT, NF-κB, MAPK, Th1, Th2, Th17, cytokines, cholesterol-efflux, oxLDL, and GLUT4, among others. A 12-month follow-up in HF patients showed a high prevalence of vitamin D deficiency, with no seasonal variation (64.7-82.4%). A positive correlation between serum 25(OH)D concentration and dietary intake of vitamin D-rich foods was found. A significant inverse correlation with IL-1ß (R = -0.78), TNF-α (R = -0.53), IL-6 (R = -0.42), IL-8 (R = -0.41), IL-17A (R = -0.31), LDL-cholesterol (R = -0.51), Apo-B (R = -0.57), total-cholesterol (R = -0.48), and triglycerides (R = -0.32) was shown. Cluster analysis demonstrated that patients from cluster three, with the lowest 25(OH)D levels, presented the lowermost vitamin D intake, IL-10 (1.0 ± 0.9 pg/mL), and IL-12p70 (0.5 ± 0.4 pg/mL), but the highest TNF-α (9.1 ± 3.5 pg/mL), IL-8 (55.6 ± 117.1 pg/mL), IL-17A (3.5 ± 2.0 pg/mL), total-cholesterol (193.9 ± 61.4 mg/dL), LDL-cholesterol (127.7 ± 58.2 mg/dL), and Apo-B (101.4 ± 33.4 mg/dL) levels, compared with patients from cluster one. Although the role of vitamin D in the pathogenesis of HF in humans is still uncertain, we applied the molecular mechanisms of in-vitro and animal models to explain our findings. Vitamin D deficiency might contribute to inflammation, remodeling, fibrosis, and atherosclerosis in patients with HF.

Investigation of Agonist Recognition and Channel Properties in a Flatworm Glutamate-Gated Chloride Channel.

Glutamate-gated chloride channels (GluCls) are neurotransmitter receptors that mediate crucial inhibitory signaling in invertebrate neuromuscular systems. Their role in invertebrate physiology and their absence from vertebrates make GluCls a prime target for antiparasitic drugs. GluCls from flatworm parasites are substantially different from and are much less understood than those from roundworm and insect parasites, hindering the development of potential therapeutics targeting GluCls in flatworm-related diseases such as schistosomiasis. Here, we sought to dissect the molecular and chemical basis for ligand recognition in the extracellular glutamate binding site of SmGluCl-2 from Schistosoma mansoni, using site-directed mutagenesis, noncanonical amino acid incorporation, and electrophysiological recordings. Our results indicate that aromatic residues in ligand binding loops A, B, and C are important for SmGluCl-2 function. Loop C, which differs in length compared to other pentameric ligand-gated ion channels (pLGICs), contributes to ligand recognition through both an aromatic residue and two vicinal threonine residues. We also show that, in contrast to other pLGICs, the hydrophobic channel gate in SmGluCl-2 extends from the 9' position to the 6' position in the channel-forming M2 helix. The 6' and 9' positions also seem to control sensitivity to the pore blocker picrotoxin.

Resource allocation optimization with multi-trait genomic prediction for bread wheat (Triticum aestivum L.) baking quality.

KEY MESSAGE: Multi-trait genomic prediction models are useful to allocate available resources in breeding programs by targeted phenotyping of correlated traits when predicting expensive and labor-intensive quality parameters. Multi-trait genomic prediction models can be used to predict labor-intensive or expensive correlated traits where phenotyping depth of correlated traits could be larger than phenotyping depth of targeted traits, reducing resources and improving prediction accuracy. This is particularly important in the context of allocating phenotyping resource in plant breeding programs. The objective of this work was to evaluate multi-trait models predictive ability with different depth of phenotypic information from correlated traits. We evaluated 495 wheat advanced breeding lines for eight baking quality traits which were genotyped with genotyping-by-sequencing. Through different approaches for cross-validation, we evaluated the predictive ability of a single-trait model and a multi-trait model. Moreover, we evaluated different sizes of the training population (from 50 to 396 individuals) for the trait of interest, different depth of phenotypic information for correlated traits (50 and 100%) and the number of correlated traits to be used (one to three). There was no loss in the predictive ability by reducing the training population up to a 30% (149 individuals) when using correlated traits. A multi-trait model with one highly correlated trait phenotyped for both the training and testing sets was the best model considering phenotyping resources and the gain in predictive ability. The inclusion of correlated traits in the training and testing lines is a strategic approach to replace phenotyping of labor-intensive and high cost traits in a breeding program.

Discharge destination and readmission rates in older trauma patients.

BACKGROUND: In older trauma patients, the impact of discharge destination on readmission rates is not known. The objective of this study was to evaluate the association between the discharge destination and the 30-day readmission rate in older trauma patients. MATERIALS AND METHODS: A previously validated database of all patients aged 45 years or older undergoing trauma evaluation at our level 1 trauma center between January 1, 2008 and December 31, 2008 was analyzed to retrospectively compare the incidences of 30-day readmission between patients discharged to home, to inpatient rehabilitation facilities, and to other extended care facilities (ECFs). Demographic information including age and gender and potentially confounding factors including injury severity, trauma activation level, comorbidities, medications, and preinjury functional status were included. Univariate analysis was undertaken using chi-square testing. Multiple logistic regression was performed with potential confounding variables to evaluate for independent contribution to readmission risk. RESULTS: A total of 960 patients were evaluated; 81 patients (8.4%) were excluded, leaving 879 patients included in the analysis. Seventy-six patients (8.6%) were readmitted within 30 d of discharge. Overall, 6% of those discharged to home, 13% of those discharged to ECF, and 16% of those discharged to rehabilitation were readmitted (P < 0.01 on univariate analysis). Overall, 866 (98.5%) patients had data recorded for all variables analyzed using multiple logistic regression; among these, only discharge destination was independently associated with the rate of readmission (P < 0.01). CONCLUSIONS: Discharge to ECFs and inpatient rehabilitation facilities appear to be an independent risk factor for hospital readmissions in this population despite controlling for injury severity and comorbidities. Recognition of this risk factor may aid in the disposition planning of these patients and suggests the need for further evaluation of this correlation at other US medical centers.

Magnetic Field Sensing Based on Bi-Tapered Optical Fibers Using Spectral Phase Analysis.

A compact, magnetic field sensor system based on a short, bi-tapered optical fiber (BTOF) span lying on a magnetic tape was designed, fabricated, and characterized. We monitored the transmission spectrum from a broadband light source, which displayed a strong interference signal. After data collection, we applied a phase analysis of the interference optical spectrum. We here report the results on two fabricated, BTOFs with different interference spectrum characteristics; we analyzed the signal based on the interference between a high-order modal component and the core fiber mode. The sensor exhibited a linear response for magnetic field increments, and we achieved a phase sensitivity of around 0.28 rad/mT. The sensing setup presented remote sensing operation and low-cost transducer magnetic material.