The amygdala is composed of multiple nuclei with unique functions and connections in the limbic system and to the rest of the brain. However, standard in vivo neuroimaging tools to automatically ...delineate the amygdala into its multiple nuclei are still rare. By scanning postmortem specimens at high resolution (100–150µm) at 7T field strength (n = 10), we were able to visualize and label nine amygdala nuclei (anterior amygdaloid, cortico-amygdaloid transition area; basal, lateral, accessory basal, central, cortical medial, paralaminar nuclei). We created an atlas from these labels using a recently developed atlas building algorithm based on Bayesian inference. This atlas, which will be released as part of FreeSurfer, can be used to automatically segment nine amygdala nuclei from a standard resolution structural MR image. We applied this atlas to two publicly available datasets (ADNI and ABIDE) with standard resolution T1 data, used individual volumetric data of the amygdala nuclei as the measure and found that our atlas i) discriminates between Alzheimer's disease participants and age-matched control participants with 84% accuracy (AUC=0.915), and ii) discriminates between individuals with autism and age-, sex- and IQ-matched neurotypically developed control participants with 59.5% accuracy (AUC=0.59). For both datasets, the new ex vivo atlas significantly outperformed (all p < .05) estimations of the whole amygdala derived from the segmentation in FreeSurfer 5.1 (ADNI: 75%, ABIDE: 54% accuracy), as well as classification based on whole amygdala volume (using the sum of all amygdala nuclei volumes; ADNI: 81%, ABIDE: 55% accuracy). This new atlas and the segmentation tools that utilize it will provide neuroimaging researchers with the ability to explore the function and connectivity of the human amygdala nuclei with unprecedented detail in healthy adults as well as those with neurodevelopmental and neurodegenerative disorders.
•We visualized 9 nuclei boundaries (anterior amygdaloid area, cortico-amygdaloid transition area; basal, lateral, accessory basal, central, cortical medial, paralaminar nuclei) using ultra-high-resolution ex vivo imaging.•Nuclei were consistent across cases and raters.•We built a segmentation atlas of the amygdala nuclei, which will be distributed with FreeSurfer.•Atlas was applied to 2 datasets and showed higher discriminability of Alzheimer's & autism than previously possible.•The atlas will provide neuroimaging researchers with the ability to test nucleus function with greater spatial specificity.
•We studied the relationship between free-range pigs’ tail and their behaviour.•Tails were held in full curl (30%), half curl (30%) or actively hanging (35%)•A full curl tail occurred most during ...locomotion.•During behaviours regarded as positive, the tail was most in an active hanging pose.•A distinction between subtle tail postures is recommended for behaviour studies.
The tail of pigs has been suggested as a welfare indicator as it can provide insight into a pig’s behavioural and emotional states. Tail posture and motion have so far mainly been studied in the context of tail biting behaviour. The aim of this study was to investigate the relationship between pigs’ natural behaviour and their tail posture and tail motion. This was studied in a free-range farm in which tail biting is absent. In total 214 pigs of different age categories were observed individually (sows, gilts, boars, and 6-month old pigs) or by group (6-month and 1-year old pigs) for their tail posture, tail motion and behaviour, using live observations and videos obtained by drone. Results showed that a fully curled tail occurred most during locomotion (P < 0.001); and an actively hanging tail occurred more during foraging (P < 0.001), excavation (P = 0.006), feeding (P = 0.017), receipt of agonistic behaviour (P = 0.036), and non-agonistic social interactions (P = 0.046). A fully curled tail (P < 0.001) and a half curled tail (P < 0.005) occurred least in the group of sows. Tail motion was infrequent (6.7% of observations), and involved mainly loosely wagging, which occurred more during locomotion (P = 0.006) and non-agonistic social interactions (P = 0.006). A higher temperature-humidity index increased the probability of half curled tails (P < 0.001) and loose wagging (P < 0.001), while reducing the probability of active (P < 0.001) and passive hanging tails (P = 0.013). These results provide insight into tail posture and tail motion in pigs under semi-natural conditions, showing especially that hanging tails are not primarily associated with tail biting, and that the use of tail postures for welfare assessment should be in consideration with the context in which the animals are kept.
Biomimetic magnetic nanoparticles (BMNPs) mediated by MamC have proven to be photothermal agents able to allow an optimized cytotoxicity against tumoral cells when used simultaneously as drug ...nanotransporters and as hyperthermia agents. However, it remains unclear whether BMNPs need to be internalized by the cells and/or if there is a threshold for internal Fe concentration for the photothermal therapy to be effective. In this study, three different situations for photothermal treatments have been simulated to disentangle the effect of BMNPs cell uptake on cell viability after photothermal treatments. Human hepatoblastoma (HepG2) cell line was treated with suspensions of BMNPs, and protocols were developed to have only intracellular BMNPs, only extracellular BMNPs or both, followed by photothermal exposure of the treated cell cultures. Our data demonstrate that: (1) Although the heating efficiency of the photothermal agent is not altered by its location (intra/extracellular), the intracellular location of BMNPs is crucial to ensure the cytotoxic effect of photothermal treatments, especially at low Fe concentration. In fact, the concentration of BMNPs needed to reach the same cytotoxic effect following upon laser irradiation of 0.2 W/cm2 is three times larger if BMNPs are located extracellularly compared to that needed if BMNPs are located intracellularly; (2) For a given location of the BMNPs, cell death increases with BMNPs (or Fe) concentration. When BMNPs are located intracellularly, there is a threshold for Fe concentration (∼ 0.5 mM at laser power intensities of 0.1 W/cm2) needed to affect cell viability following upon cell exposure to photothermia. (3) Bulk temperature rise is not the only factor accounting for cell death. Actually, temperature increases inside the cells cause more damage to cell structures and trigger cell death more efficiently than an increase in the temperature outside the cell.
Abstract Aim To identify new biomarkers to detect untreated and treated periodontitis in gingival crevicular fluid (GCF) using sequential window acquisition of all theoretical mass spectra ...(SWATH‐MS). Materials and Methods GCF samples were collected from 44 periodontally healthy subjects and 40 with periodontitis (Stages III–IV). In the latter, 25 improved clinically 2 months after treatment. Samples were analysed using SWATH‐MS, and proteins were identified by the UniProt human‐specific database. The diagnostic capability of the proteins was determined with generalized additive models to distinguish the three clinical conditions. Results In the untreated periodontitis vs. periodontal health modelling, five proteins showed excellent or good bias‐corrected (bc)‐sensitivity/bc‐specificity values of >80%. These were GAPDH, ZG16B, carbonic anhydrase 1, plasma protease inhibitor C1 and haemoglobin subunit beta. GAPDH with MMP‐9, MMP‐8, zinc‐α‐2‐glycoprotein and neutrophil gelatinase‐associated lipocalin and ZG16B with cornulin provided increased bc‐sensitivity/bc‐specificity of >95%. For distinguishing treated periodontitis vs. periodontal health, most of these proteins and their combinations revealed a predictive ability similar to previous modelling. No model obtained relevant results to differentiate between periodontitis conditions. Conclusions New single and dual GCF protein biomarkers showed outstanding results in discriminating untreated and treated periodontitis from periodontal health. Periodontitis conditions were indistinguishable. Future research must validate these findings.
The influence of magnetic interactions in assemblies formed by either aggregated or disaggregated uniform γ-Fe2O3 particles are investigated as a function of particle size, concentration, and applied ...field. Hyperthermia and magnetization measurements are performed in the liquid phase of colloids consisting of 8 and 13 nm uniform γ-Fe2O3 particles dispersed in water and hexane. Although hexane allows obtaining the disagglomerated particle system, aggregation is observed in the case of water colloids. The zero field cooled (ZFC) curves show a discontinuity in the magnetization values associated with the melting points of water and hexane. Additionally, for 13 nm γ-Fe2O3 dispersed in hexane, a second magnetization jump is observed that depends on particle concentration and shifts toward lower temperature by increasing applied field. This second jump is related to the strength of the magnetic interactions as it is only present in disagglomerated particle systems with the largest size, i.e., is not observed for 8 nm superparamagnetic particles, and surface effects can be discarded. The specific absorption rate (SAR) decreases with increasing concentration only for the hexane colloid, whereas for aqueous colloids, the SAR is almost independent of particle concentration. Our results suggest that, as a consequence of the magnetic interactions, the dipolar field acting on large particles increases with concentration, leading to a decrease of the SAR.
Summary
Background
Cutaneous reactions after severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) vaccines are poorly characterized.
Objective
To describe and classify cutaneous reactions ...after SARS‐CoV‐2 vaccination.
Methods
A nationwide Spanish cross‐sectional study was conducted. We included patients with cutaneous reactions within 21 days of any dose of the approved vaccines at the time of the study. After a face‐to‐face visit with a dermatologist, information on cutaneous reactions was collected via an online professional survey and clinical photographs were sent by email. Investigators searched for consensus on clinical patterns and classification.
Results
From 16 February to 15 May 2021, we collected 405 reactions after vaccination with the BNT162b2 (Pfizer‐BioNTech; 40·2%), mRNA‐1273 (Moderna; 36·3%) and AZD1222 (AstraZeneca; 23·5%) vaccines. Mean patient age was 50·7 years and 80·2% were female. Cutaneous reactions were classified as injection site (‘COVID arm’, 32·1%), urticaria (14·6%), morbilliform (8·9%), papulovesicular (6·4%), pityriasis rosea‐like (4·9%) and purpuric (4%) reactions. Varicella zoster and herpes simplex virus reactivations accounted for 13·8% of reactions. The COVID arm was almost exclusive to women (95·4%). The most reported reactions in each vaccine group were COVID arm (mRNA‐1273, Moderna, 61·9%), varicella zoster virus reactivation (BNT162b2, Pfizer‐BioNTech, 17·2%) and urticaria (AZD1222, AstraZeneca, 21·1%). Most reactions to the mRNA‐1273 (Moderna) vaccine were described in women (90·5%). Eighty reactions (21%) were classified as severe/very severe and 81% required treatment.
Conclusions
Cutaneous reactions after SARS‐CoV‐2 vaccination are heterogeneous. Most are mild‐to‐moderate and self‐limiting, although severe/very severe reactions are reported. Knowledge of these reactions during mass vaccination may help healthcare professionals and reassure patients.
What is already known about this topic?
In clinical trials, COVID‐19 vaccines were associated with cutaneous adverse events, especially local injection site reactions.
Previous descriptions of cutaneous reactions beyond the injection site were case reports or mostly reported by non‐dermatologists and lacked clinical images.
What does this study add?
We describe and classify a large, representative sample of patients with unexplained skin manifestations after COVID‐19 vaccination, using consensus to define associated morphological patterns.
We describe six morphological reaction patterns and herpesvirus reactivations, and their association with demographic factors and the medical record, and provide illustrations to allow for easy recognition.
Linked Comment: V. Bataille and S. Puig. Br J Dermatol 2022; 186:15.
Plain language summary available online
Identification of the potential habitat of European anchovy (Engraulis encrasicolus) at different life stages in relation to environmental conditions is an interesting subject from both ecological ...and management points of view. For this purpose, acoustic data from different seasons and different parts of the Mediterranean Sea along with satellite environmental and bathymetry data were modelled using generalized additive models. Similarly, egg distribution data from summer ichthyoplankton surveys were used to model potential spawning habitat. Selected models were used to produce maps presenting the probability of anchovy presence (adults, juveniles and eggs) in the entire Mediterranean basin, as a measure of habitat adequacy. Bottom depth and sea surface chlorophyll concentration were the variables found important in all models. Potential anchovy habitats were located over the continental shelf for all life stages examined. An expansion of the potential habitat from the peak spawning (early summer) to the late spawning season (early autumn) was observed. However, the most suitable areas for the presence of anchovy spawners seem to maintain the same size between seasons. Potential juvenile habitats were associated with highly productive inshore waters, being less extended and closer to coast during winter than late autumn. Potential spawning habitat in June and July based on ichthyoplankton surveys overlapped but were wider in extent compared with adult potential habitat from acoustics in the same season. Similarities and dissimilarities between the anchovy habitats as well as comparisons with sardine habitats in the oligotrophic Mediterranean Sea and other ecosystems with higher productivity are discussed.
The aims of this study were to determine the prevalence of fatigue in patients with inflammatory bowel disease IBD, to identify the factors associated with fatigue and its severity, to assess the ...impact of fatigue on quality of life QoL, and to evaluate the relationship between fatigue and sleep disorders.
This was a prospective multicentre study conducted at 22 Spanish centres. Consecutive patients followed at IBD Units were included. Fatigue was evaluated with the Fatigue Severity Scale FSS and the Fatigue Impact Scale FIS. Quality of life and sleep quality were assessed using the IBD Questionnaire-Short Form IBDQ-9 and the Pittsburgh Sleep Quality Index PSQI, respectively.
A total of 544 consecutive adult IBD patients were included 50% women, mean age 44 years, 61% Crohn's disease. The prevalence of fatigue was 41% (95% confidence interval CI = 37-45%). The variables associated with an increased risk of fatigue were: anxiety OR = 2.5, 95% CI = 1.6-3.7, depression OR = 2.4, 95% CI = 1.4-3.8, presence of extraintestinal manifestations EIMs OR = 1.7, 95% CI = 1.1-2.6, and treatment with systemic steroids OR = 2.8, 95% CI = 1.4-5.7. The presence of EIMs regression coefficient, RC = 8.2, 95% CI = 2.3-14.2, anxiety RC = 25.8, 95% CI = 20.0-31.5, depression RC = 30.6, 95% CI = 24.3-37.0, and sleep disturbances RC = 15.0, 95% CI = 9.3-20.8 were associated with severity of fatigue. Patients with fatigue had a significantly decreased IBDQ-9 score p < 0.001.
The prevalence of fatigue in IBD patients is remarkably high and has a negative impact on QoL. Therapy with systemic steroids is associated with an increased risk of fatigue. The severity of fatigue is associated with anxiety, depression, sleep disorders, and the presence of EIMs. Fatigue was not associated with anaemia, disease activity or anti-TNF therapy.
A classical methodology to design free‐base meso‐tetra‐(1‐pyrenyl)porphyrin (H2TPyrP) and their corresponding metalloporphyrins containing Zn(II), Cu(II), Ni(II), Co(III), and Mn(III) was described. ...These porphyrins were characterized in terms of structure, photophysical, and interactions profile with calf‐thymus deoxyribonucleic acid (CT‐DNA) and bovine serum albumin (BSA). H2TPyrP exhibited five characteristic bands in the visible wavelength: Soret (432 nm) and Q‐bands (520–650 nm range), while the metalloporphyrins showed some spectrum shifts according to the nature of the ion, which were also explored by time‐dependent density functional theory (TD‐DFT) calculations. The fluorescence and singlet oxygen quantum yield (Φfl, ΦΔ, respectively) decreased with the presence of metal species in the porphyrin core. The porphyrins interact spontaneously via a ground‐state association in the minor groove of CT‐DNA following the increasing order of binding: CuTPyrP<H2TPyrP<CoTPyrP<MnTPyrP<NiTPyrP<ZnTPyrP, while for BSA the suitable complex geometry for Co(III) and Mn(III) complexes increased the binding capacity.
Meso‐tetra‐(1‐pyrenyl)porphyrin containing Zn(II), Cu(II), Ni(II), Co(III), and Mn(III) were synthesized in good yield (45–90 %). The effects of ion nature on the photophysics and interaction with biomacromolecules were evaluated by the combination of experimental assays and theoretical calculations. The fluorescence and singlet oxygen quantum yield decreased as the biomacromolecule interactions increased with the presence of metal species in the porphyrin core.
The limited use of palladium‐103 and ‐109 radionuclides for molecular radiotherapy is surely due to the lack of appropriate ligands capable of fulfilling all criteria required for application in ...nuclear medicine. Furthermore, the thermodynamic properties of these complexes in solution remain difficult to establish. The challenge is compounded when considering that radiolabeling of compounds for translation to clinical trials requires fast complexation. Thus, the coordination of Pd(II) and 103/109Pd‐nuclides is a huge challenge in terms of molecular design and physicochemical characterization. Herein, we report a comprehensive study highlighting TE1PA, a monopicolinate cyclam – already established in nuclear imaging with 64Cu‐PET (positron emission tomography) imaging tracers – as a highly relevant chelator for natural Pd and subsequently 109Pd‐nuclide. The structural, thermodynamic, kinetic and radiolabeling studies of Pd(II) with TE1PA, as well as the comparison of this complex with three structurally related derivatives, support palladium‐TE1PA radiopharmaceuticals as leading candidates for targeted nuclear medicine.
Radiopharmaceuticals: Since the macrocyclic gold standards used in nuclear medicine are not suitable to Pd(II) coordination, its radioisotopes remain understated for radiopharmaceutical applications. The monopicolinate cyclam TE1PA presented here is a highly relevant chelator for natural and radioactive Pd, opening avenues to enrich the current palette of radiopharmaceuticals for targeted radiotherapy.
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