Pharmacological activation of BK channels protects against LPS-induced pneumonia.

Bacterial pneumonia causes 1.4 million deaths annually worldwide. Besides antibiotics, current treatments are mostly supportive, and no other targeted therapies exist that improve patient outcomes.

Evaluation of a Multiplex Electrochemiluminescence Assay for Detection of Anti-Pneumococcal Antibodies in the Diagnosis of Selective Polysaccharide Antibody Deficiency.

Streptococcus pneumoniae can be responsible for severe infections, especially in patients with primary antibody deficiencies like selective anti-polysaccharide antibodies deficiency (SPAD). The reference method recommaned by the World Health Organization for assessment of anti-pneumococcal capsular polysaccharides (PCPs) IgG antibodies is a standardized serotype-specific ELISA (WHO-SSA), but this manual method is time-consuming and limit the number of evaluated PCPs. We aim to evaluate the performance values of a multiplex assay based on electrochemiluminescence (ECL-plex).

Discovering leaf and stripe rust resistance in soft red winter wheat through genome-wide association studies.

Leaf rust (LR) and stripe rust (YR), which are caused by Puccinia triticina and Puccinia striiformis, respectively, are among the most devastating wheat rusts worldwide. These diseases can be managed by using genetically resistant cultivars, an economical and environmentally safer alternative to fungicides. Over 100 and 80 Lr and Yr resistance genes have been discovered, respectively; however, rust pathogens are overcoming introduced resistance genes in the southeastern United States.

Diagnosis, Characteristics, and Outcome of Selective Anti-polysaccharide Antibody Deficiencies In A Retrospective Cohort of 55 Adult Patients.

Selective anti-polysaccharide antibody deficiency (SPAD) predisposes to encapsulated bacterial infections. The diagnosis is challenging, and literature reports are scarce in adult patients, we therefore aim to describe the demographics, infectious complications, therapeutic strategies, and outcome of adult patients. We conducted a multicenter observational study involving 55 adult patients with SPAD.

A new species of the genus (Gastropoda, Stylommatophora, Xanthonychidae) from Sierra de Penjamo, Guanajuato, Mexico.

Background: Mexican terrestrial malacofauna is highly diverse, but poorly studied. The genus includes near to 60 species, most with insular distributions on single mountains from South Texas (USA) to entral Mexico.

New Information: sp.

A Genome-Wide Association Study Approach to Identify Novel Major-Effect Quantitative Trait Loci for End-Use Quality Traits in Soft Red Winter Wheat.

Wheat is used for making many food products due to its diverse quality profile among different wheat classes. Since laboratory analysis of these end-use quality traits is costly and time-consuming, genetic dissection of the traits is preferential. This study used a genome-wide association study (GWAS) of ten end-use quality traits, including kernel protein, flour protein, flour yield, softness equivalence, solvent's retention capacity, cookie diameter, and top-grain, in soft red winter wheat (SRWW) adapted to US southeast.

Y SIR-Spheres Activity Measurement with New SIROS D-Vial Delivery Kit.

A new Y SIR-Spheres delivery kit (SIROS D-vial and shield) has been introduced with a different physical form from the legacy V-Vial kit. Here, we establish the dose calibrator settings and exposure-rate-to-activity conversion factor to assay Y SIR-Spheres activity in the new SIROS kit. Eight D-vials with initial Y activities from 1.

Quantitative evaluation of Y-PET/CT and Y-SPECT/CT-based dosimetry following Yttrium-90 radioembolization.

Background: Following yttrium-90 radioembolization (Y-RE), Y-PET/CT and Y-SPECT/CT imaging provide the means to calculate the voxelized absorbed dose distribution. Given the widespread use of the two imaging modalities and lack of well-established standardized dosimetry protocols for Y-RE, there is a clinical need to systematically investigate and evaluate differences in the performance of voxel-based dosimetry between Y-PET/CT and Y-SPECT/CT.

Purpose: To quantitatively analyze and compare Y-PET/CT and Y-SPECT/CT-based dosimetry following Y-RE.

A comparison of methods for in vivo activity and absorbed dose quantification with PET/CT following yttrium-90 radioembolization.

Background: Yttrium-90 (Y) positron emission tomography (PET)/computed tomography (CT) imaging is increasingly being used to perform tumor (T) and normal liver (NL) voxel dosimetry after Y-radioembolization (Y-RE). Yet, the accuracy of in vivo Y-PET/CT imaging, subject to motion blur and co-registration inaccuracies, and Y-PET/CT dose quantification, subject to availability of different voxel dosimetry algorithms, are not well understood.

Purpose: The purpose of this study was to investigate the accuracy of Y-PET/CT-based activity estimates following Y-RE and characterize differences between Y-PET/CT-based voxel dosimetry algorithms.

Two-pore potassium channel TREK-1 (K2P2.1) regulates NLRP3 inflammasome activity in macrophages.

Because of the importance of potassium efflux in inflammasome activation, we investigated the role of the two-pore potassium (K2P) channel TREK-1 in macrophage inflammasome activity. Using primary alveolar macrophages (AMs) and bone marrow-derived macrophages (BMDMs) from wild-type (wt) and mice, we measured responses to inflammasome priming [using lipopolysaccharide (LPS)] and activation (LPS + ATP). We measured IL-1β, caspase-1, and NLRP3 via ELISA and Western blot.

Quantitative Trait Locus Analysis of Hessian Fly Resistance in Soft Red Winter Wheat.

The Hessian fly (HF) is an invasive insect that has caused millions of dollars in yield losses to southeastern US wheat farms. Genetic resistance is the most sustainable solution to control HF. However, emerging biotypes are quickly overcoming resistance genes in the southeast; therefore, identifying novel sources of resistance is critical.

Single-Compartment Dose Prescriptions for Ablative Y-Radioembolization Segmentectomy.

Background: Yttrium-90 (Y) radioembolization is increasingly being utilized with curative intent. While single-compartment doses with respect to the perfused volume for the complete pathologic necrosis (CPN) of tumors have been reported, the actual doses delivered to the tumor and at-risk margins that leads to CPN have hitherto not been estimated. We present an ablative dosimetry model that calculates the dose distribution for tumors and at-risk margins based on numerical mm-scale dose modeling and the available clinical CPN evidence and report on the necessary dose metrics needed to achieve CPN following Y-radioembolization.

Predicting the net administered activity in Y-radioembolization patients from post-procedure Y-SPECT/CT.

Background: The calculation of the net administered activity (A ) in patients undergoing Y-radioembolization is essential for dosimetry and radiation safety, yet current methods for measuring residual Y activity are often associated with high uncertainty. Therefore, an accurate, robust, and clinically viable method for the determination of A across approved Y microsphere devices is desirable.

Purpose: We report on a novel method to determine A by leveraging the quantitative capabilities of SPECT/CT to measure Y-emission in vivo from patients following Y-radioembolization with glass or resin microspheres.

Hemolysis is associated with altered heparan sulfate of the endothelial glycocalyx and with local complement activation in thrombotic microangiopathies.

The complement system plays a key role in the pathophysiology of kidney thrombotic microangiopathies (TMA), as illustrated by atypical hemolytic uremic syndrome. But complement abnormalities are not the only drivers of TMA lesions. Among other potential pathophysiological actors, we hypothesized that alteration of heparan sulfate (HS) in the endothelial glycocalyx could be important.

Activation of Endothelial Large Conductance Potassium Channels Protects against TNF-α-Induced Inflammation.

Elevated TNF-α levels in serum and broncho-alveolar lavage fluid of acute lung injury patients correlate with mortality rates. We hypothesized that pharmacological plasma membrane potential (Em) hyperpolarization protects against TNF-α-induced CCL-2 and IL-6 secretion from human pulmonary endothelial cells through inhibition of inflammatory Ca-dependent MAPK pathways. Since the role of Ca influx in TNF-α-mediated inflammation remains poorly understood, we explored the role of L-type voltage-gated Ca (Ca) channels in TNF-α-induced CCL-2 and IL-6 secretion from human pulmonary endothelial cells.

Protection from acute lung injury by a peptide designed to inhibit the voltage-gated proton channel.

There are no targeted medical therapies for Acute Lung Injury (ALI) or its most severe form acute respiratory distress syndrome (ARDS). Infections are the most common cause of ALI/ARDS and these disorders present clinically with alveolar inflammation and barrier dysfunction due to the influx of neutrophils and inflammatory mediator secretion. We designed the C6 peptide to inhibit voltage-gated proton channels (Hv1) and demonstrated that it suppressed the release of reactive oxygen species (ROS) and proteases from neutrophils .

Monte Carlo-derived Tc uptake quantification with commercial planar MBI: Tumor and breast activity concentrations.

Background: Current molecular breast imaging (MBI) images are limited to qualitative evaluation, not absolute measurement, of Tc uptake in benign and malignant breast tissues.

Purpose: This work assesses the accuracy of previously-published and newly-proposed tumor and normal breast tissue Tc uptake MBI measurements using simulations of a commercial dual-headed planar MBI system under typical clinical and acquisition protocols.

Methods: Quantification techniques were tested in over 4000 simulated acquisitions of spherical and ellipsoid tumors with clinically relevant uptake conditions using a validated Monte Carlo application of the GE Discovery NM750b system.

Monte Carlo-derived Tc uptake quantification with commercial planar MBI: Absolute tumor activity.

Background: Molecular breast imaging (MBI) of Tc-sestamibi is an emerging adjunct qualitative tool in the detection and diagnosis of breast cancer.

Purpose: This work outlines the development and performance evaluation of a methodology to absolutely quantify tumor Tc activity uptake using a commercially available dual-headed MBI system by implementing corrections for background, scatter, attenuation, and detector characteristics.

Methods: A validated Monte Carlo application of a commercial MBI system was used to simulate over 7000 unique acquisitions of spherical and ellipsoidal tumors in breast tissue.

Activation of TREK-1 () potassium channels protects against influenza A-induced lung injury.

Influenza-A virus (IAV) infects yearly an estimated one billion people worldwide, resulting in 300,000-650,000 deaths. Preventive vaccination programs and antiviral medications represent the mainstay of therapy, but with unacceptably high morbidity and mortality rates, new targeted therapeutic approaches are urgently needed. Since inflammatory processes are commonly associated with measurable changes in the cell membrane potential (Em), we investigated whether Em hyperpolarization via TREK-1 () K channel activation can protect against influenza-A virus (IAV)-induced pneumonia.

High Frequency of Specific Polysaccharide Antibody Deficiency in Adults With Unexplained, Recurrent and/or Severe Infections With Encapsulated Bacteria.

Background: Primary immunodeficiencies (PIDs) in adults are mainly revealed by recurrent and/or severe bacterial infections. The objective of this study was to evaluate a systematic research strategy of PIDs in adults with unexplained bacterial infections, with a special focus on specific polysaccharide antibody deficiency (SPAD).

Methods: In this prospective multicenter study, inclusion criteria were recurrent benign upper and lower respiratory tract infections (RTIs) for at least two years (group 1), at least one upper or lower RTI requiring hospitalization (group 2), and/or at least one invasive infection documented with encapsulated bacteria (group 3).

Evaluation of Arterial and Venous Allografts in Subinguinal Bypasses.

Background: Autologous saphenous vein is the preferred conduit for below-the-knee bypasses in patients with critical limb-threatening ischemia. Alternative graft must be considered for patients without (autologous saphenous vein). The aim of this article is to evaluate the mid-term performance of arterial allograft (AA) and venous allograft (VA) used as alternative conduits.

Factors modulating Tc-MAA planar lung dosimetry for Y radioembolization.

Purpose: To investigate the accuracy and biases of predicted lung shunt fraction (LSF) and lung dose (LD) calculations via Tc-macro-aggregated albumin ( Tc-MAA) planar imaging for treatment planning of Y-microsphere radioembolization.

Methods And Materials: LSFs in 52 planning and LDs in 44 treatment procedures were retrospectively calculated, in consecutive radioembolization patients over a 2 year interval, using Tc-MAA planar and SPECT/CT imaging. For each procedure, multiple planar LSFs and LDs were calculated using different: (1) contours, (2) views, (3) liver Tc-MAA shine-through compensations, and (4) lung mass estimations.

Organ-level internal dosimetry for intra-hepatic-arterial administration of Tc-macroaggregated albumin.

Purpose: There are no published data on organ doses following intra-hepatic-arterial administration of Tc-macroaggregated-albumin (IHA Tc-MAA) routinely used in Y-radioembolization treatment planning to assess intra- and extra-hepatic depositions and calculate lung-shunt-fraction (LSF). We propose a method to model the organ doses following IHA Tc-MAA that incorporates three in vivo constituent biodistributions, the Tc-MAA that escape the liver due to LSF, and the Tc-MAA dissociation fraction (DF).

Methods: The potential in vivo biodistributions for IHA Tc-MAA are: Liver-Only MAA with all activity sequestered in the liver (LSF = 0&DF = 0), Intravenous MAA with all activity transferred intravenously as Tc-MAA (LSF = 1&DF = 0), and Intravenous Pertechnetate with all activity is transferred intravenously as Tc-pertechnetate (LSF = 0&DF = 1).