The carbonyl nucleobase adduct MAde is a potent antigen for adaptive polyclonal MR1-restricted T cells.

The major histocompatibility complex (MHC) class I-related molecule MHC-class-I-related protein 1 (MR1) presents metabolites to distinct MR1-restricted T cell subsets, including mucosal-associated invariant T (MAIT) and MR1T cells. However, self-reactive MR1T cells and the nature of recognized antigens remain underexplored. Here, we report a cell endogenous carbonyl adduct of adenine (8-(9H-purin-6-yl)-2-oxa-8-azabicyclo[3.

Nucleobase adducts bind MR1 and stimulate MR1-restricted T cells.

MR1T cells are a recently found class of T cells that recognize antigens presented by the major histocompatibility complex-I-related molecule MR1 in the absence of microbial infection. The nature of the self-antigens that stimulate MR1T cells remains unclear, hampering our understanding of their physiological role and therapeutic potential. By combining genetic, pharmacological, and biochemical approaches, we found that carbonyl stress and changes in nucleobase metabolism in target cells promote MR1T cell activation.

Evolution of Fetal Growth in Symptomatic Sars-Cov-2 Pregnancies.

Introduction: SARS-CoV-2 is a viral disease with potentially devastating effects. Observational studies of pregnant women infected with SARS-CoV-2 report an increased risk for FGR. This study utilizes data from a prospective SARS-CoV-2 registry in pregnancy, investigating the progression of fetuses to fetal growth restriction (FGR) at birth following maternal SARS-CoV-2 and evaluating the hypothesis of whether the percentage of SGA at birth is increased after maternal SARS-CoV-2 taking into account the time interval between infection and birth.

Evaluation of UGT1A1 and CYP3A Genotyping and Single-Point Irinotecan and Metabolite Concentrations as Predictors of the Occurrence of Adverse Events in Cancer Treatment.

Purpose: The variability on irinotecan (IRI) pharmacokinetics and toxicity has been attributed mostly to genetic variations in the UGT1A1 gene, responsible for conjugation of the active metabolite SN-38. Also, CYP3A mediates the formation of inactive oxidative metabolites of IRI. The association between the occurrence of severe adverse events, pharmacokinetics parameters, and UGT1A1 and CYP3A4 predicted phenotypes was evaluated, as the evaluation of [SN-38]/IRI dose ratio as predictor of severe adverse events.

Local Tumor Infiltration and Locoregional Recurrence in Desmoplastic Cutaneous Squamous Cell Carcinoma.

Background: Perusal of the literature of cutaneous squamous cell carcinoma (SCC) reveals that the role of the desmoplastic subtype is indistinct. Data on local infiltration and recurrence are inconsistent dependent on surgical technique, histological method, and investigated collective.

Objective: The aim of the study was to analyze local infiltration and locoregional recurrence of the desmoplastic subtype under a uniform procedure.

Sensitive determination of 11-nor-9-carboxy-Δ9-tetrahydrocannabinol and complementary cannabinoids in hair using alkaline digestion and mixed-mode solid phase extraction followed by liquid-chromatography-tandem mass spectrometry.

Hair drug testing can be used for the evaluation of cannabis use with a large detection window, and is required for professional driving license granting in Brazil. A positive hair result for cannabis use requires quantification of the metabolite THC-COOH above the cutoff value of 0.2 ng/g.

Simple determination of valproic acid serum concentrations using BioSPME followed by gas chromatography-mass spectrometric analysis.

Valproic acid (VA) is a drug widely used on the treatment of epilepsy and bipolar affective disorders, with stablished therapeutic concentration ranges in serum. The measurement of VA serum concentrations using chromatographic methods requires a sample preparation step. In this context, this study aims to describe the development and validation of an assay for VA measurement in serum using a new microextraction strategy, known as BioSPME, followed by GC-MS analysis.

Responses of the Hybrid between Sphagneticola trilobata and Sphagneticola calendulacea to Low Temperature and Weak Light Characteristic in South China.

Hybridization between exotic and native species is of great interest to evolutionary biologists and ecologists because it usually shows a quick evolution of species and invasiveness. It has been reported that such hybridization frequently increases the adaptation and aggressiveness of the new hybrids. A hybrid between invasive Sphagneticola trilobata and its native congener S.

Blunted endocrine and cardiovascular reactivity in young healthy women reporting a history of childhood adversity.

Background: Chronic or prolonged stress exposure in childhood can alter structural and functional brain development, leading to mental and physical illness and alterations of psychobiological stress systems in adulthood. Recently, attenuation in stress reactivity of the hypothalamic-pituitary-adrenal (HPA) axis and cardiovascular system have been related to the number of adverse childhood experiences (ACEs). We set out to investigate the association of ACE duration and age of ACE occurrence on stress reactivity.

Using ecological memory as an indicator to monitor the ecological restoration of four forest plantations in subtropical China.

A large area of plantations has been established worldwide and especially in China. Evaluating the restoration status of these plantations is essential for their long-term management. Based on our previous work, we used an ecological memory (EM) approach to evaluate four 26-year-old plantations that represent four common kinds of plantations in subtropical China, i.

Retrocyte Display® technology: generation and screening of a high diversity cellular antibody library.

Over the last nearly three decades in vitro display technologies have played an important role in the discovery and optimization of antibodies and other proteins for therapeutic applications. Here we describe the use of retroviral expression technology for the display of full-length IgG on B lineage cells in vitro with a hallmark of a tight and stable genotype to phenotype coupling. We describe the creation of a high-diversity (>1.

Clinical accuracy of a PLEX-ID flu device for simultaneous detection and identification of influenza viruses A and B.

Respiratory tract infections caused by influenza A and B viruses often present nonspecifically, and a rapid, high-throughput laboratory technique that can identify influenza viruses is clinically and epidemiologically desirable. The PLEX-ID Flu assay (Abbott Molecular Inc., Des Plaines, IL) incorporates multilocus PCR and electrospray ionization-mass spectrometry to detect and differentiate influenza A 2009 H1N1 (H1N1-p), seasonal H1N1 (H1N1-s), influenza A H3N2, and influenza B viruses in nasopharyngeal swab (NPS) specimens.

Randomized, multicenter trial on the effect of radiation therapy on plantar fasciitis (painful heel spur) comparing a standard dose with a very low dose: mature results after 12 months' follow-up.

Purpose: To conduct a randomized trial of radiation therapy for painful heel spur, comparing a standard dose with a very low dose.

Methods And Materials: Sixty-six patients were randomized to receive radiation therapy either with a total dose of 6.0 Gy applied in 6 fractions of 1.

Primary human keratinocytes efficiently induce IL-1-dependent IL-17 in CCR6+ T cells.

Keratinocytes and activated T cells interact in skin inflammation by virtue of chemokines and cytokines. T cell-derived IL-17 has been described to play an important role in the course of psoriatic inflammation. In this study, we addressed how keratinocytes influence the secretion of IL-17 in autologous T cell subsets.

Oral levofloxacin 500 mg once daily in the treatment of chronic bacterial prostatitis.

The aim of this study was to confirm further the efficacy and safety of levofloxacin in patients with chronic bacterial prostatitis (CBP) in Europe. Men with a history of CBP were enrolled in a prospective, multinational (eight countries), open-label study to receive levofloxacin 500 mg once daily per os (p.o.

Impairment of respiratory muscle function in pulmonary hypertension.

It has been suggested that impaired respiratory muscle function occurs in patients with PH (pulmonary hypertension); however, comprehensive investigations of respiratory muscle function, including the application of non-volitional tests, needed to verify impairment of respiratory muscle strength in patients with PH have not yet been performed. In the present study, respiratory muscle function was assessed in 31 patients with PH (20 females and 11 males; mean pulmonary artery pressure, 51+/-20 mmHg; median World Health Organization class 3.0+/-0.

Are fruit colors adapted to consumer vision and birds equally efficient in detecting colorful signals?

Reproduction in plants often requires animal vectors. Fruit and flower colors are traditionally viewed as an adaptation to facilitate detection for pollinators and seed dispersers. This longstanding hypothesis predicts that fruits are easier to detect against their own leaves compared with those of different species.

Characterization of ghrelin receptor activity in a rat pituitary cell line RC-4B/C.

Ghrelin, a 28 amino acid, octanoylated peptide, is an endogenous ligand for the growth hormone secretagogue receptor (GHS-R). In addition to various endocrine functions, including stimulation of GH release, ghrelin has been characterized as an important regulator of energy homeostasis. Ghrelin administration has been shown to increase adiposity in rodents and stimulate food intake in humans.

2,4-diaminopyrimidine derivatives as potent growth hormone secretagogue receptor antagonists.

Ghrelin, a gut-derived orexigenic hormone, is an endogenous ligand of the growth hormone secretagogue receptor (GHS-R). Centrally administered ghrelin has been shown to cause hunger and increase food intake in rodents. Inhibition of ghrelin actions with ghrelin antibody, peptidyl GHS-R antagonists, and antisense oligonucleosides resulted in weight loss and food intake decrease in rodents.

Optimization of 2,4-diaminopyrimidines as GHS-R antagonists: side chain exploration.

The synthesis and structure-activity relationships of the 4- and 6-substituents of 2,4-diaminopyrimidine-based growth hormone secretagogue receptor (GHS-R) antagonists are described. Diaminopyrimidines with 6-norbornenyl (4n) and 6-tetrahydrofuranyl (4p) substitutents were found to exhibit potent GHS-R antagonism and good selectivity (approximately 1000-fold) against dihydrofolate reductase.

Evaluation and validation of a new risk score (CLEOPATRA score) to predict the probability of premature delivery for patients with threatened preterm labor.

Objective: To develop a clinically useful tool to predict the probability of preterm delivery in patients with threatened preterm labor.

Methods: One hundred and seventy patients with preterm labor between 24 and 34 weeks of gestation were included. Preterm delivery < 37 weeks of gestation was the main endpoint of the study.

Optimized Scansystem platelet kit for bacterial detection with enhanced sensitivity: detection within 24 h after spiking.

Background And Objectives: The prevention and detection of bacterial contamination of platelet concentrates remains a major challenge for transfusion medicine. To be suitable for blood-transfusion services, the contamination detection method must be highly sensitive, easy to perform and preferably of low cost. In this spiking study, we evaluated the new optimized Scansystem Platelet Kit detection method for use on apheresis platelets.