Failure of desensitization with Pfizer-BioNTech COVID-19 vaccine in two asthmatic patients.

Summary: Since December 2020, in various countries of the world, many cases of severe allergic reactions after administration of PfizerBioNTech COVID-19 vaccine, were reported. A great concern has arisen among the doctors who administer the vaccine and the allergic patients who undergo vaccinations. In Italy guidelines were published in order to stratify the risk in the allergic population. In mRNA vaccines, the component currently suspected of causing allergic reactions is the polyethylene glycol excipient (PEG or macrogol). In patients who have shown an immediate allergic reaction to vaccine and who are negative to skin tests for PEG, desensitization with the same vaccine is proposed. In this paper we describe two cases of asthma after the first COVID vaccine administration in which desensitization has failed.

A linear viscoelasticity for decadal to centennial time scale mantle deformation.

The extended Burgers material (EBM) model provides a linear viscoelastic theory for interpreting a variety of rock deformation phenomena in geophysics, playing an increasingly important role in parameterizing laboratory data, providing seismic wave velocity and attenuation interpretations, and in analyses of solid planetary tidal dispersion and quality factor Q. At the heart of the EBM approach is the assumption of a distribution of relaxation spectra tied to rock grain boundary and interior granular mobility. Furthermore, the model incorporates an asymptotic long-term limiting behavior that is Maxwellian. Here we use the extensively developed linear theory of viscoelasticity to isolate those parameters of EBM that apply to both post-seismic relaxation processes involving flow of olivine rich upper mantle material and to studies of tides, where periods of forcing range from 12 h to 18.6 years. The isolated EBM parameters should also apply to theoretical and geodetic studies of glacial isostatic adjustment, especially when the initiation of continuous cryospheric surface unloading dates to the 20th or 21st century. Using analytical Laplace transformed solutions of Boussinesq's half-space load problem, we show that the effects of EBM transient rheology may have substantial influence on geodetic interpretations of unloading induced crustal motions even on time scales that are sub-decadal.

North Atlantic climate far more predictable than models imply.

Quantifying signals and uncertainties in climate models is essential for the detection, attribution, prediction and projection of climate change1-3. Although inter-model agreement is high for large-scale temperature signals, dynamical changes in atmospheric circulation are very uncertain4. This leads to low confidence in regional projections, especially for precipitation, over the coming decades5,6. The chaotic nature of the climate system7-9 may also mean that signal uncertainties are largely irreducible. However, climate projections are difficult to verify until further observations become available. Here we assess retrospective climate model predictions of the past six decades and show that decadal variations in North Atlantic winter climate are highly predictable, despite a lack of agreement between individual model simulations and the poor predictive ability of raw model outputs. Crucially, current models underestimate the predictable signal (the predictable fraction of the total variability) of the North Atlantic Oscillation (the leading mode of variability in North Atlantic atmospheric circulation) by an order of magnitude. Consequently, compared to perfect models, 100 times as many ensemble members are needed in current models to extract this signal, and its effects on the climate are underestimated relative to other factors. To address these limitations, we implement a two-stage post-processing technique. We first adjust the variance of the ensemble-mean North Atlantic Oscillation forecast to match the observed variance of the predictable signal. We then select and use only the ensemble members with a North Atlantic Oscillation sufficiently close to the variance-adjusted ensemble-mean forecast North Atlantic Oscillation. This approach greatly improves decadal predictions of winter climate for Europe and eastern North America. Predictions of Atlantic multidecadal variability are also improved, suggesting that the North Atlantic Oscillation is not driven solely by Atlantic multidecadal variability. Our results highlight the need to understand why the signal-to-noise ratio is too small in current climate models10, and the extent to which correcting this model error would reduce uncertainties in regional climate change projections on timescales beyond a decade.

Reference parameters of peripheral immune cell populations in broiler chickens using a large database.

1. Peripheral blood immune evaluation of broilers by flow cytometry is commonly used in avian research. However, indicative immune parameters in healthy animals have not yet been determined. In this trial, confidence intervals were determined for several circulating immune cell subsets.2. The intervals were determined from over 1,000 healthy broilers from commercial lines. To verify the usefulness of the data, they were compared to animals under salmonellosis or mycotoxin challenges.3. Confidence intervals were determined for several immune cells in the peripheral blood of broilers. The importance of some immune cells in discriminating diseased from healthy controls was demonstrated.4. This work initiated the construction of reference values for cellular parameters in broilers as a tool for the avian immunology community. Accordingly, the entire dataset of healthy animals was made available for use with other analyses and for improvement by others.

Construction and characterization of a recombinant vaccine encoding the nucleocapsid protein gene of avian infectious bronchitis virus / Construção e caracterização de uma vacina recombinante codificando o gene da proteina do nucleocapsideo do virus da bronquite infecciosa das galinhas

A vacinação é a forma mais utilizada para prevenir a bronquite infecciosa causada pelo vírus da bronquite infecciosa das galinhas (IBV). Contudo, as vacinas convencionais são incapazes de diferenciar aves infectadas de vacinadas. No presente trabalho foi construído, caracterizado, e avaliado como candidato vacinal, um adenovírus recombinante expressando o gene N do IBV. O gene N foi clonado em um adenovírus humano tipo 5 defectivo e transfectado para as células HEK-293A para gerar rAd5_N. Após o vetor ser obtido como esperado e a confirmação da expressão da proteína N em HEK-293ª, foi realizada inoculação pela via oculo-nasal na dose de 10 7 TCID 50 /0,1mL para imunização de galinhas livres de patógenos específicos (SPF). A resposta imunológica do Ad5_N e a proteção contra o desafio ao IBV foram avaliadas e comparadas com uma vacina viva comercial. Não foram detectados anticorpos anti-IBV em aves vacinadas com o Ad5_N. A vacina comercial induziu anticorpos detectáveis a partir do 7º dia pós-vacinal. Em aves vacinadas com o Ad5_N não houve aumento na expressão de IFNγ. Neste estudo, o rAd5_N obtido não conferiu proteção contra desafio com IBV-M41. Os resultados indicam a necessidade de avaliar adenovírus recombinantes expressando outros genes do IBV.(AU)

Slowdown in Antarctic mass loss from solid Earth and sea-level feedbacks.

Geodetic investigations of crustal motions in the Amundsen Sea sector of West Antarctica and models of ice-sheet evolution in the past 10,000 years have recently highlighted the stabilizing role of solid-Earth uplift on polar ice sheets. One critical aspect, however, that has not been assessed is the impact of short-wavelength uplift generated by the solid-Earth response to unloading over short time scales close to ice-sheet grounding lines (areas where the ice becomes afloat). Here, we present a new global simulation of Antarctic evolution at high spatiotemporal resolution that captures all solid Earth processes that affect ice sheets and show a projected negative feedback in grounding line migration of 38% for Thwaites Glacier 350 years in the future, or 26.8% reduction in corresponding sea-level contribution.

Basal Tryptase Levels Can Predict Clinical Severity in Hymenoptera Venom Anaphylaxis and Ischemic Cardiovascular Disorders

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Ethical considerations of mobile phone use by patients in KwaZulu-Natal: Obstacles for mHealth?

BACKGROUND: mHealth has the potential to facilitate telemedicine services, particularly in the developing world. Concern has been expressed about the confidentiality of health information that is relayed by mobile phone. AIM: We examined the habits and practices of mobile phone use by patients in KwaZulu-Natal, South Africa. METHODS: We conducted a descriptive survey of two patient populations: 137 urban patients attending private practitioners and 139 patients in remote rural areas attending outpatient departments in Government-funded hospitals. The questionnaire covered several domains: demographics, mobile phone use, privacy and confidentiality and future use for health-related matters. RESULTS: Two hundred and seventy-six patients completed the questionnaire. We found that a third of our participants shared their mobile phone with others, 24% lent their phone to others and more than half received health-related messages for other people. Mobile phone theft was common, as was number changing. Thirty-eight percent of the people were not able to afford airtime for more than a week in the past year and 22% of rural patients were unable to keep their phone charged. Mobile phone signal coverage was significantly worse in the rural areas than in urban areas. CONCLUSION: This study highlights the legal and ethical ramifications that these practices and findings will have on mHealth programmes in our setting. Healthcare providers and regulators will need to consider how patients use and manage their mobile phones when developing services and regulations.

Direct magnetocaloric characterization and simulation of thermomagnetic cycles.

An experimental setup for the direct measurement of the magnetocaloric effect capable of simulating high frequency magnetothermal cycles on laboratory-scale samples is described. The study of the magnetocaloric properties of working materials under operative conditions is fundamental for the development of innovative devices. Frequency and time dependent characterization can provide essential information on intrinsic features such as magnetic field induced fatigue in materials undergoing first order magnetic phase transitions. A full characterization of the adiabatic temperature change performed for a sample of Gadolinium across its Curie transition shows the good agreement between our results and literature data and in-field differential scanning calorimetry.

Genomic structure and genetic drift in C57BL/6 congenic metabolic mutant mice.

We used a genome-wide single nucleotide polymorphism (SNP) approach to characterize the genomic structures of four representative C57BL/6 (B6) congenic mutant mouse lines to include the A) long-chain acyl-CoA dehydrogenase (Acadl), B) melanocortin 3 receptor (Mc3r), C) endothelial nitric oxide synthase (Nos3), and D) a replacement of mouse apolipoprotein E (Apoe) by human apolipoprotein E-2 (APOE2). We wanted to evaluate the size and flanking genes of the 129 strain origin mutant allele intervals on the B6 background. Additionally, we wanted to evaluate genetic drift among not only the four mutant lines and their respective B6 origin substrains, but also the drift between two commonly used B6 lines obtained from Jackson Laboratory and Taconic. Overall, we found a range of 129 origin interval sizes in the congenic mutant lines analyzed that ranged from a ~2.8 kb human sequence for APOE2 embedded in a 129S6 interval to the largest being a ~16 Mb fragment containing the targeted Nos3 (eNos) gene. Given the range of 129 strain interval sizes, we found 129 strain flanking genes via annotation in genome data bases ranging from one gene both upstream and downstream of the APOE2 allele to seven genes-upstream and five genes-downstream at the Nos3 locus. Furthermore, we found fourteen SNP differences between the Jackson Laboratory and Taconic B6 mice. These genetic differences were associated with marked adiposity differences between the two B6 substrains. This study demonstrates both the fidelity and the caveats of using congenic gene targeted mouse models and recognizing the importance of selecting the appropriately matched wild-type control mouse line.

Driving magnetostructural transitions in layered intermetallic compounds.

We report the dramatic effect of applied pressure and magnetic field on the layered intermetallic compound Pr(0.5)Y(0.5)Mn(2)Ge(2). In the absence of pressure or magnetic field this compound displays interplanar ferromagnetism at room temperature and undergoes an isostructural first order magnetic transition (FOMT) to an antiferromagnetic state below 158 K, followed by another FOMT at 50 K due to the reemergence of ferromagnetism as praseodymium orders (T(C)(Pr)). The application of a magnetic field drives these two transitions towards each other, whereas the application of pressure drives them apart. Pressure also produces a giant magnetocaloric effect such that a threefold increase of the entropy change associated with the lower FOMT (at T(C)(Pr)) is seen under a pressure of 7.5 kbar. First principles calculations, using density functional theory, show that this remarkable magnetic behavior derives from the strong magnetoelastic coupling of the manganese layers in this compound.

[The mental stress of the accompaniment in Alzheimer's disease]. / Le travail psychique de l'accompagnement dans la maladie d'Alzheimer.

INTRODUCTION: Alzheimer's disease affects patients in time and space and all dimensions of emotional, cognitive and social life. It is, in return, an unprecedented threat for the family, a disaster for each member of the family. Because of the love story, because of the suffering, the disease remains the relationship between patient and caregiver. We try to approach their suffering according to the carer's reports. Our research, conducted with support from France Alzheimer, aims to understand the nuances of the experience of becoming the accompanying person, drawing on some key moments of this accompaniment. METHODOLOGY: It is through an exploratory research that we met eight caregivers of patients with Alzheimer's disease. Among them, seven were the spouses (four of seven patients are men), and one was the daughter of a patient. In a clinical psychological environment, we asked each caregiver the same question: "How would you talk about living or having lived Alzheimer'disease?" Our response will only aim to support words of the participant whenever necessary, but will also propose in difficult and particularly challenging moments, the possibility of sharing to enable the participant to verbalize their emotions. RESULTS: The meeting with some caregivers evidenced the preservation of a particular relationship with the patient, relationship within which the caregiver perceives in return the unspeakable weight of a disease, which works silently. Alzheimer's disease induces psychological modifications and requires great investment by caregivers, which is grafted on an earlier relationship. We should not consider the modifications in a linear relationship patient-caregiver but in a circular relationship, which complicates the relation of the couple and makes it indecisive. The violence of the confrontation with this disease results from multiple factors: social representations, impact of the diagnosis, evolution of the disease, affectivity and permanent interactions, in spite of the non verbal communication of the patient, which associates a love story, behaviour disorders and the impact on the social circle. The family's responses are for example denial, overprotection, mothering and aggressiveness in caregiving in order to maintain the relationship. Becoming a caregiver is difficult because of the limit between professional and caregiver. Accompaniment is not a simple role of watching and caring. Because of the love, because of the strength of the communication which continues even in the absence of words, the investment remains massive and Alzheimer's disease opens a distance where the relationship, if it is perturbed, is none the less reactivated, and makes the accompaniment possible, however painful it may be.

Fatigue in children with cancer at the end of life.

CONTEXT: Fatigue is a prevalent source of suffering in children with advanced cancer; yet, little is known about it. OBJECTIVES: This study aimed to describe fatigue experienced by children with advanced cancer and to identify the factors associated with suffering from fatigue and its treatment. METHODS: A retrospective cross-sectional study of 141 parents of children who died of cancer (response rate: 64%) was conducted in two tertiary-level U.S. pediatric hospitals. RESULTS: By parent report, 96% of children experienced fatigue in the last month of life. Nearly 50% experienced significant suffering from fatigue; this was associated with suffering from pain, dyspnea, anorexia, nausea/vomiting, diarrhea, anxiety, sadness, or fear (P<0.05), and with side effects from pain or dyspnea treatment (P<0.05). In multivariate analysis of symptom-related factors, suffering from nausea/vomiting (odds ratio [OR]=3.93, 95% confidence interval [CI]=1.23-12.61, P=0.02); anorexia (OR=7.52, 95% CI=1.87-30.25, P=0.005); and fear (OR=5.13, 95% CI=2.03-12.96, P ≤ 0.001) remained independently associated with fatigue. Children suffering from fatigue had primary oncologists with fewer years' experience than children who did not suffer from fatigue (mean=7.7 years, standard deviation [SD]=4.9 vs. mean of 9.9 years, SD=6.0, P=0.02). Among children with fatigue, 17 of 129 (13%) received fatigue-directed treatment, which was successful in 3 of 12 (25%). Children experiencing side effects from dyspnea or pain treatment were more likely to be treated for fatigue (relative risk=1.25, 95% CI=1.06-1.47, P=0.009). CONCLUSION: Fatigue is a common source of suffering in children with cancer at the end of life. Palliation of this symptom is rarely successful. Increased attention to factors associated with fatigue and effective interventions to ameliorate fatigue are needed.

Impaired glucose tolerance and predisposition to the fasted state in liver glycogen synthase knock-out mice.

Conversion to glycogen is a major fate of ingested glucose in the body. A rate-limiting enzyme in the synthesis of glycogen is glycogen synthase encoded by two genes, GYS1, expressed in muscle and other tissues, and GYS2, primarily expressed in liver (liver glycogen synthase). Defects in GYS2 cause the inherited monogenic disease glycogen storage disease 0. We have generated mice with a liver-specific disruption of the Gys2 gene (liver glycogen synthase knock-out (LGSKO) mice), using Lox-P/Cre technology. Conditional mice carrying floxed Gys2 were crossed with mice expressing Cre recombinase under the albumin promoter. The resulting LGSKO mice are viable, develop liver glycogen synthase deficiency, and have a 95% reduction in fed liver glycogen content. They have mild hypoglycemia but dispose glucose less well in a glucose tolerance test. Fed, LGSKO mice also have a reduced capacity for exhaustive exercise compared with mice carrying floxed alleles, but the difference disappears after an overnight fast. Upon fasting, LGSKO mice reach within 4 h decreased blood glucose levels attained by control floxed mice only after 24 h of food deprivation. The LGSKO mice maintain this low blood glucose for at least 24 h. Basal gluconeogenesis is increased in LGSKO mice, and insulin suppression of endogenous glucose production is impaired as assessed by euglycemic-hyperinsulinemic clamp. This observation correlates with an increase in the liver gluconeogenic enzyme phosphoenolpyruvate carboxykinase expression and activity. This mouse model mimics the pathophysiology of glycogen storage disease 0 patients and highlights the importance of liver glycogen stores in whole body glucose homeostasis.

Understanding the inverse magnetocaloric effect in antiferro- and ferrimagnetic arrangements.

The inverse magnetocaloric effect occurs when a magnetic material cools down under applied magnetic field in an adiabatic process. Although the existence of the inverse magnetocaloric effect was recently reported experimentally, a theoretical microscopic description is almost nonexistent. In this paper we theoretically describe the inverse magnetocaloric effect in antiferro- and ferrimagnetic systems. The inverse magnetocaloric effects were systematically investigated as a function of the model parameters. The influence of the Néel and the compensation temperature on the magnetocaloric effect is also analyzed using a microscopic model.

Effects of short deprivation and re-exposure intervals on the ethanol drinking behavior of selectively bred high alcohol-consuming rats.

Alcoholics generally display cycles of excessive ethanol intake, abstinence and relapse behavior. Using an animal model of relapse-like drinking, the alcohol deprivation effect (ADE), our laboratory has shown that repeated 2-week cycles of ethanol deprivation and re-exposure, following an initial 6-week access period, result in a robust ADE by alcohol-preferring (P) and high alcohol-drinking (HAD-1 and HAD-2) rats. These rat lines have been selectively bred to prefer a 10% ethanol solution over water. The present study examined whether P and HAD rats would display an ADE using much shorter ethanol deprivation and re-exposure intervals. Rats were given either continuous or periodic concurrent access to multiple concentrations (10%, 20%, and 30% [vol/vol]) of ethanol. The periodic protocol involved access to ethanol for 12 days followed by four cycles of 4 days of deprivation and 4 days of re-exposure to ethanol access. High-alcohol-drinking rats displayed a robust 24-h ADE upon first re-exposure (HAD-1: approximately 5 vs. 8g/kg/day; HAD-2: approximately 6 vs. 9g/kg/day, baseline vs. re-exposure), whereas P rats ( approximately 7 vs. 8g/kg/day) displayed a modest, nonsignificant, increase in 24-h intake. In a separate group of rats, ethanol intake and blood alcohol concentrations after the first hour of the fourth re-exposure cycle were HAD-1: 2.0g/kg and 97 mg%, HAD-2: 2.3g/kg and 73 mg%, and P: 1.2g/kg and 71 mg%; with all three lines displaying a robust first hour ADE. These findings suggest that (a) an ADE may be observed with short ethanol deprivation and re-exposure intervals in HAD rats, and (b) the genetic make-up of the P and HAD rats influences the expression of this ADE.

Combination of immunohistochemistry and ploidy analysis to assist histopathological diagnosis of molar diseases.

BACKGROUND: Differential diagnosis between hydropic abortion, partial mole and complete mole is still a challenge for pathologists but really important for patient management. MATERIAL AND METHOD: In this study, we have evaluated 111 products of conception from the first trimester. Histological analysis was made according to the main diagnostic histopathological features described in the literature and the cases were categorized in hydropic abortus (HA), partial mole (PM) and complete mole (CM). Immunohistochemistry was performed using monoclonal antibody against p57(kip) protein a putative paternally imprinted inhibitor gene and DNA ploidy was analysed in all cases by image cytometry. RESULTS: All 23 HAs presented a diploid DNA content and were p57(kip2) positive. From the 28 CMs, 12 cases (43%) were diploid and 16 cases (57%) were tetraploid but no expression of p57(kip2) was found with positive internal controls. From the 60 PMs, 58 cases were positive for p57(kip2) expression and 53 cases (88%) were triploid, 6 cases (10%) tetraploid and 1 case (2%) diploid. CONCLUSION: This study on 111 cases of early pregnancies confirms the usefulness of immunohistochemistry and cytometry but demonstrates the importance of the combination of both techniques to assist histology for the best reliable diagnosis.

Modification of nitrogen remobilization, grain fill and leaf senescence in maize (Zea mays) by transposon insertional mutagenesis in a protease gene.

A maize (Zea mays) senescence-associated legumain gene, See2beta, was characterized at the physiological and molecular levels to determine its role in senescence and resource allocation. A reverse-genetics screen of a maize Mutator (Mu) population identified a Mu insertion in See2beta. Maize plants homozygous for the insertion were produced. These See2 mutant and sibling wild-type plants were grown under high or low quantities of nitrogen (N). The early development of both genotypes was similar; however, tassel tip and collar emergence occurred earlier in the mutant. Senescence of the mutant leaves followed a similar pattern to that of wild-type leaves, but at later sampling points mutant plants contained more chlorophyll than wild-type plants and showed a small extension in photosynthetic activity. Total plant weight was higher in the wild-type than in the mutant, and there was a genotype x N interaction. Mutant plants under low N maintained cob weight, in contrast to wild-type plants under the same treatment. It is concluded, on the basis of transposon mutagenesis, that See2beta has an important role in N-use and resource allocation under N-limited conditions, and a minor but significant function in the later stages of senescence.