•SCA patients have inflammatory mediator’s levels higher than in healthy controls.•RBC from SCA patients induce TLR and NLRP3 inflammasome expression.•HU does not prevent NLRP3 inflammasome- and ...TLR-dependent inflammation.•TLR and NLRP3 pathways may be key inducers for inflammation in SCA.
This study tested the hypothesis that sickle red blood cell (SS-RBC) induce Toll-like receptors (TLR) and Nod-like receptor family, pyrin domain containing 3 (NLRP3)- inflammasome expression in peripheral blood mononuclear cells (PBMC). TLR and NLRP3 inflammasome could contribute to the maintenance of the inflammatory status in sickle cell anemia (SCA) patients, since SS-RBC act as danger signals activating these pathways. In this study, first, we evaluated TLR (2, 4, 5 and 9), NLRP3, Caspase-1, interleukin (IL)-1β and IL-18 expression in PBMC freshly isolated from SCA patients (SS-PBMC) in comparison with PBMC from healthy individuals (AA-PBMC). In the second moment, we investigated whether SS-RBC could interfere with the expression of these molecules in PBMC from healthy donor, in the absence or presence of hydroxyurea (HU) in vitro. TLRs and NLRP3 inflammasome expression were investigated by qPCR. IL-1β, Leukotriene-B4 (LTB4) and nitrite production were measured in PBMC (from healthy donor) culture supernatants. TLR2, TLR4, TLR5, NLRP3 and IL-1β were highly expressed in SS-PBMC when compared to AA-PBMC. Additionally, SS-RBC induced TLR9, NLRP3, Caspase-1, IL-1β and IL-18 expression and induced IL-1β, LTB4 and nitrite production in PBMC cultures. HU did not prevent TLR and NLRP3 inflammasome expression, but increased TLR2 and IL-18 expression and reduced nitrite production. In conclusion, our data suggest that TLR and inflammasome complexes may be key inducers of inflammation in SCA patients, probably through SS-RBC; also, HU does not prevent NLRP3 inflammasome- and TLR-dependent inflammation, indicating the need to develop new therapeutic strategies to SCA patients that act with different mechanisms of those observed for HU.
The duration of pregnancy is influenced by fetal and maternal genetic and non-genetic factors. Here we report a fetal genome-wide association meta-analysis of gestational duration, and early preterm, ...preterm, and postterm birth in 84,689 infants. One locus on chromosome 2q13 is associated with gestational duration; the association is replicated in 9,291 additional infants (combined P = 3.96 × 10
). Analysis of 15,588 mother-child pairs shows that the association is driven by fetal rather than maternal genotype. Functional experiments show that the lead SNP, rs7594852, alters the binding of the HIC1 transcriptional repressor. Genes at the locus include several interleukin 1 family members with roles in pro-inflammatory pathways that are central to the process of parturition. Further understanding of the underlying mechanisms will be of great public health importance, since giving birth either before or after the window of term gestation is associated with increased morbidity and mortality.
The Gastropoda is one of the best studied classes of marine invertebrates. Yet, most species have been delimited based on morphology only. The application of DNA barcodes has shown to be greatly ...useful to help delimiting species. Therefore, sequences of the cytochrome c oxidase I gene from 108 specimens of 34 morpho-species were used to investigate the molecular diversity within the gastropods from the Portuguese coast. To the above dataset, we added available COI-5P sequences of taxonomically close species, in a total of 58 morpho-species examined. There was a good match between ours and sequences from independent studies, in public repositories. We found 32 concordant (91.4%) out of the 35 Barcode Index Numbers (BINs) generated from our sequences. The application of a ranking system to the barcodes yield over 70% with top taxonomic congruence, while 14.2% of the species barcodes had insufficient data. In the majority of the cases, there was a good concordance between morphological identification and DNA barcodes. Nonetheless, the discordance between morphological and molecular data is a reminder that even the comparatively well-known European marine gastropods can benefit from being probed using the DNA barcode approach. Discordant cases should be reviewed with more integrative studies.
Oral mite anaphylaxis is a new syndrome characterized by severe allergic symptoms occurring immediately after eating foods made with mite-contaminated wheat flour. This syndrome, which is more ...prevalent in tropical environments, is triggered more often by pancakes, and for that reason, it has been designated “the pancake syndrome.” Because cooked foods are able to induce the symptoms, it has been suggested that thermoresistant allergens are involved in its pathogenesis. A variety of this syndrome can occur during physical exercise (dust mite ingestion–associated exercise-induced anaphylaxis).
Objectives were to investigate progesterone concentrations and fertility comparing 2 different intervals from PGF2α treatment and induced ovulation in an estrogen-based ovulation synchronization ...protocol for timed artificial insemination (TAI) or timed embryo transfer (TET) in lactating dairy cows. A total of 1,058 lactating Holstein cows primiparous (n=371) and multiparous (n=687), yielding 34.1±0.33 kg of milk/d at various days in milk were randomly assigned to receive treatment with PGF2α on either d 7 or 8 of the following protocol: d 0: 2mg of estradiol benzoate + controlled internal drug release device; d 8: controlled internal drug release device removal + 1.0mg of estradiol cypionate; d 10: TAI or d 17: TET. Only cows with a corpus luteum at d 17 received an embryo and all cows received GnRH at TET. Pregnancy diagnoses were performed by detection (transrectal ultrasonography) of an embryo on d 28 or a fetus on d 60. Fertility pregnancy per artificial insemination (P/AI) or pregnancy per embryo transfer (P/ET) was affected by breeding technique (AI vs. ET) and time of PGF2α treatment (d 7 vs. 8) at the 28-d pregnancy diagnosis for TAI 32.9% (238) vs. 20.6% (168) and TET cows 47% (243) vs. 40.7% (244) and at the 60-d pregnancy diagnosis for TAI 30% (238) vs. 19.2% (168) and TET cows 37.9% (243) vs. 33.5% (244). The progesterone (P4) concentration at d 10 altered fertility in TAI cows, with higher P/AI in cows with P4 concentration <0.1 ng/mL compared with cows with P4 concentration ≥0.1 ng/mL, and in ET cows, with higher P/ET in cows with P4 concentration <0.22 ng/mL compared with cows with P4 concentration ≥0.22 ng/mL. Prostaglandin F2α treatment at d 7 increased the percentage of cows with P4 <0.1 ng/mL on d 10 39.4 (85) vs. 23.2 (54). Reducing the period between PGF2α and TAI from 72 to 48h in dairy cows resulted in a clear reduction in fertility in cows bred by TAI and a subtle negative effect in cows that received TET. The earlier PGF2α treatment benefits are most likely mediated through gamete transport, fertilization, or early embryo development and a more subtle effect of earlier PGF2α treatment that may be mediated through changes in the uterine or hormonal environment that manifests itself after ET on d 7.
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•A simple pathway for preparation of all- nanocellulose foams was developed.•CNFs dispersions are a mixture of clusters and networks of entangled nanofibers.•Electrostatic ...complexation leads to obtaining stiffer and wet-resilient foams.
Supramolecular assembly of biobased components in water is a promising strategy to construct advanced materials. Herein, electrostatic complexation was used to prepare wet-resilient foams with improved mechanical property. Small-angle X-ray scattering and cryo-transmission electron microscopy experiments showed that suspensions with oppositely charged cellulose nanofibers are a mixture of clusters and networks of entangled fibers. The balance between these structures governs the colloidal stability and the rheological behavior of CNFs in water. Foams prepared from suspensions exhibited maximum compressive modulus at the mass composition of 1:1 (ca 0.12 MPa), suggesting that meaningful attractive interactions happen at this point and act as stiffening structure in the material. Besides the electrostatic attraction, hydrogen bonds and hydrophobic contacts may also occur within the clustering, improving the water stability of cationic foams. These results may provide a basis for the development of robust all- cellulose materials prepared in water, with nontoxic chemicals.
Recently, stress myocardial computed tomographic perfusion (CTP) was shown to detect myocardial ischemia. Our main objective was to evaluate the feasibility of dipyridamole stress CTP and compare it ...to single-photon emission computed tomography (SPECT) to detect significant coronary stenosis using invasive conventional coronary angiography (CCA; stenosis >70%) as the reference method. Thirty-six patients (62 ± 8 years old, 20 men) with previous positive results with SPECT (<2 months) as the primary inclusion criterion and suspected coronary artery disease underwent a customized multidetector-row CT protocol with myocardial perfusion evaluation at rest and during stress and coronary CT angiography (CTA). Multidetector-row computed tomography was performed in a 64-slice scanner with dipyridamole stress perfusion acquisition before a second perfusion/CT angiographic acquisition at rest. Independent blinded observers performed analysis of images from CTP, CTA, and CCA. All 36 patients completed the CT protocol with no adverse events (mean radiation dose 14.7 ± 3.0 mSv) and with interpretable scans. CTP results were positive in 27 of 36 patients (75%). From the 9 (25%) disagreements, 6 patients had normal coronary arteries and 2 had no significant stenosis (8 false-positive results with SPECT, 22%). The remaining patient had an occluded artery with collateral flow confirmed by conventional coronary angiogram. Good agreement was demonstrated between CTP and SPECT on a per-patient analysis (kappa 0.53). In 26 patients using CCA as reference, sensitivity, specificity, and positive and negative predictive values were 88.0%, 79.3%, 66.7%, and 93.3% for CTP and 68.8, 76.1%, 66.7%, and 77.8%, for SPECT, respectively (p = NS). In conclusion, dipyridamole CT myocardial perfusion at rest and during stress is feasible and results are similar to single-photon emission CT scintigraphy. The anatomical-perfusion information provided by this combined CT protocol may allow identification of false-positive results by SPECT.
Justice-involved veterans are more likely to experience myriad mental health sequelae. Nonetheless, examination of personality psychopathology among justice-involved veterans remains limited, with ...studies focused on males within correctional settings. We examined Department of Veterans Affairs (VA) electronic medical records for 1,534,108 (12.28% justice-involved) male and 127,230 (8.79% justice-involved) female veterans. Male and female veterans accessing VA justice-related services were both approximately three times more likely to have a personality disorder diagnosis relative to those with no history of using justice-related services. This effect persisted after accounting for VA use (both overall and mental health), age, race, and ethnicity. Augmenting and tailoring VA justice-related services to facilitate access to evidence-based psychotherapy for personality psychopathology may promote optimal recovery and rehabilitation among these veterans.
•Trial-level attentional bias score demonstrated superior split-half reliability.•Temporal stability was significantly high in trial-level bias score.•Traditional mean-level attentional bias score ...demonstrated low reliability.•Evidence on the external validity of both bias scores was limited.
Attentional bias (AB) is an individual difference risk factor that represents the extent to which cigarette cues capture one’s attention. AB is typically indexed by mean bias score (MBS), theoretically assuming that AB is static. However, poor reliability of MBS has threatened valid interpretation of the results on AB. Based on observed trial-by-trial temporal fluctuation and variability of attentional allocation, trial-level bias score (TLBS) has been introduced as an alternative index with evidence of better psychometric properties in various populations, as compared to MBS. However, such evidence is limited among daily smokers. The current study aimed to replicate and extend extant findings in a sample of daily smokers by hypothesizing that TLBS, as compared to MBS, would demonstrate superior reliability and external validity.
Forty-eight daily smokers completed self-reports, ad-libitum smoking, and a dot-probe task three times, which was comprised of 36 pairs of pictorial stimuli of cigarette and neutral cues, yielding 144 total trials.
The TLBS demonstrated superior internal (range intra class correlation ICC = 0.79–0.95) and test-retest reliability (range ICC = 0.64–0.88) compared to MBS (range ICC = 0.31–0.40 and 0.06–0.16, respectively). However, few significant relations between either the MBS or TLBS and measures of biobehavioral and self-report indices of smoking reinforcement were observed.
The current findings demonstrate that TLBS, as compared to MBS, is a more reliable measure of AB among daily smokers, while evidence of its external validity is limited.
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