Measurement of the Positive Muon Anomalous Magnetic Moment to 0.20 ppm.

We present a new measurement of the positive muon magnetic anomaly, a_{µ}≡(g_{µ}-2)/2, from the Fermilab Muon g-2 Experiment using data collected in 2019 and 2020. We have analyzed more than 4 times the number of positrons from muon decay than in our previous result from 2018 data. The systematic error is reduced by more than a factor of 2 due to better running conditions, a more stable beam, and improved knowledge of the magnetic field weighted by the muon distribution, ω[over ˜]_{p}^{'}, and of the anomalous precession frequency corrected for beam dynamics effects, ω_{a}. From the ratio ω_{a}/ω[over ˜]_{p}^{'}, together with precisely determined external parameters, we determine a_{µ}=116 592 057(25)×10^{-11} (0.21 ppm). Combining this result with our previous result from the 2018 data, we obtain a_{µ}(FNAL)=116 592 055(24)×10^{-11} (0.20 ppm). The new experimental world average is a_{µ}(exp)=116 592 059(22)×10^{-11} (0.19 ppm), which represents a factor of 2 improvement in precision.

Management of systemic prostate cancer: current algorithm from castration sensitive to castration resistant setting.

In recent years, the advanced knowledge of clinical, biological and molecular features of prostate cancer have led to the introduction of new drugs and have allowed the relocation of old drugs in different settings. In this way, the new concepts of systemic disease arise: high risk or high volume vs. low risk and low volume disease castration sensitive prostate cancer (CSPC), diversifying the use of previously approved drugs (CRPC) and opening new scenarios for sequence therapy. The aim of this review is to integrate new developments into the medical management of systemic prostate cancer.

Properties of Daily Helium Fluxes.

We present the precision measurement of 2824 daily helium fluxes in cosmic rays from May 20, 2011 to October 29, 2019 in the rigidity interval from 1.71 to 100 GV based on 7.6×10^{8} helium nuclei collected with the Alpha Magnetic Spectrometer (AMS) aboard the International Space Station. The helium flux and the helium to proton flux ratio exhibit variations on multiple timescales. In nearly all the time intervals from 2014 to 2018, we observed recurrent helium flux variations with a period of 27 days. Shorter periods of 9 days and 13.5 days are observed in 2016. The strength of all three periodicities changes with time and rigidity. In the entire time period, we found that below ∼7 GV the helium flux exhibits larger time variations than the proton flux, and above ∼7 GV the helium to proton flux ratio is time independent. Remarkably, below 2.4 GV a hysteresis between the helium to proton flux ratio and the helium flux was observed at greater than the 7σ level. This shows that at low rigidity the modulation of the helium to proton flux ratio is different before and after the solar maximum in 2014.

FTO rs9939609 influence on adipose tissue localization in the Italian population.

OBJECTIVE: Among the genes involved in obesity, the Fat mass and obesity-associated gene (FTO) is certainly one of the most known and the relation between FTO rs9939609 and BMI is highly discussed; nevertheless, data about its influence on body composition are limited. MATERIALS AND METHODS: We carried out a study on a sample of 1066 Italian subjects, whose body composition and FTO rs9939609 were analyzed. RESULTS: We found significant relations between FTO with arm (p=0.01), abdomen (p=0.00), and trunk circumferences (p=0.00), BMI (p=0.01), FM% (p=0.00), and android FM% (p=0.01), whereas no relations were found between FTO and both gynoid fat and lean mass. CONCLUSIONS: To conclude, the relation between FTO and BMI is confirmed and is related specifically with android FM%. These results indicated that FTO rs9939609 may be a genetic etiological factor for obesity. Indeed, the specificity for the android FM% would indicate FTO as an etiological factor in the development of cardiovascular diseases.

Preferential flow modelling of chlorpyrifos leaching in two arid soils of irrigated agricultural production areas in Argentine Patagonia.

An analysis was made of the transport and fate of the organophosphate pesticide chlorpyrifos in productive soils from the Alto Valle of the Río Negro in Argentine Patagonia. The climate of the region is arid, so traditional fruit production is under flood irrigation. The soils in the floodplain are predominantly Aridisols with textures ranging from sandy loam to clay loam. The calibration was performed with water table data and chlorpyrifos concentration in the soil horizons. Field experiments made with Brilliant Blue FCF at the profile scale enabled the parametrisation of the dual-permeability model MACRO. The model calibration was evaluated by a comparison of observed and simulated data and statistics. The simulation of the groundwater table depth was satisfactory and the chlorpyrifos leaching revealed a different pattern in the two soil types studied. The sandy loam texture soil produced more percolation of irrigation water, but the clay loam soil produced greater leaching of chlorpyrifos under similar application conditions, presumably due to preferential flow under non-equilibrium conditions. Productive management alternatives to reduce leaching into the underlying unconfined aquifer were simulated. Among these, the incorporation of organic matter was the best alternative.

Alu RNA accumulation induces epithelial-to-mesenchymal transition by modulating miR-566 and is associated with cancer progression.

Alu sequences are the most abundant short interspersed repeated elements in the human genome. Here we show that in a cell culture model of colorectal cancer (CRC) progression, we observe accumulation of Alu RNA that is associated with reduced DICER1 levels. Alu RNA induces epithelial-to-mesenchymal transition (EMT) by acting as a molecular sponge of miR-566. Moreover, Alu RNA accumulates as consequence of DICER1 deficit in colorectal, ovarian, renal and breast cancer cell lines. Interestingly, Alu RNA knockdown prevents DICER1 depletion-induced EMT despite global microRNA (miRNA) downregulation. Alu RNA expression is also induced by transforming growth factor-ß1, a major driver of EMT. Corroborating this data, we found that non-coding Alu RNA significantly correlates with tumor progression in human CRC patients. Together, these findings reveal an unexpected DICER1-dependent, miRNA-independent role of Alu RNA in cancer progression that could bring mobile element transcripts in the fields of cancer therapeutic and prognosis.

Training of Spanish allergology residents in pediatric allergology: a survey of the current situation

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A comparison of the nutritional status between adult celiac patients on a long-term, strictly gluten-free diet and healthy subjects.

BACKGROUND/OBJECTIVES: There are conflicting data on the effect of a gluten-free diet (GFD) on the nutritional status of celiac patients. In the present study, we evaluated, in adult celiac patients, the influence of a long-term, strictly GFD on their nutritional status and compared it with matched healthy volunteers. SUBJECTS/METHODS: Our study included 39 celiac patients and 39 healthy volunteers. The body mass index (BMI) of patients and controls was evaluated at enrollment, while the patients' BMI before the GFD was retrieved from clinical records. In addition, at enrollment, in both groups, we compared BMI, fat mass (FM), bone mineral density (BMD), as well as their dietary intake, recorded on a 7-day diary. RESULTS: At the time of diagnosis, the majority of celiac patients (82.0%) had a normal BMI or were overweight, while 10.3% were malnourished. After the GFD, patients with a normal BMI showed a significant weight increase (P=0.002), but none of them switched in the overweight or obese category. Two (50%) of the four malnourished patients achieved a normal BMI. Controls and patients on a GFD had a similar BMI, FM, BMD and total calorie intake, but the amount of lipids and fiber intake was significantly different in the two groups (P=0.003 and P<0.0001, respectively). CONCLUSIONS: Our study demonstrates that a GFD is able to improve the nutritional status of celiac patients without inducing overweight or obesity. Our findings are related to a celiac population adopting a GFD based on a Mediterranean-type diet.

Position document: IgE-mediated cow's milk allergy

The present document offers an update on the recommendations for managing patients with cow's milk allergy - a disorder that manifests in the first year of life, with an estimated prevalence of 1.6-3% in this paediatric age group. The main causal allergens are the caseins and proteins in lactoserum (beta-lactoglobulin, alpha-lactoalbumin), and the clinical manifestations are highly variable in terms of their presentation and severity. Most allergic reactions affect the skin, followed by the gastrointestinal and respiratory systems, and severe anaphylaxis may occur. The diagnosis of cow's milk allergy is based on the existence of a suggestive clinical history, a positive allergy study and the subsequent application of controlled exposure testing, which constitutes the gold standard for confirming the diagnosis. The most efficient treatment for cow's milk allergy is an elimination diet and the use of adequate substitution formulas. The elimination diet must include milk from other mammals (e.g., sheep, goat, etc.) due to the risk of cross-reactivity with the proteins of cow's milk. Most infants with IgE-mediated cow's milk allergy become tolerant in the first few years of life. In those cases where cow's milk allergy persists, novel treatment options may include oral immunotherapy, although most authors do not currently recommend this technique in routine clinical practice. Enough evidence is not there to confirm the efficacy of elimination diets in the mother and infant for preventing the appearance of cow's milk allergy. Likewise, no benefits have been observed with prebiotic and probiotic dietetic supplements in infants for preventing food allergy

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Targeted Mutagenesis, Precise Gene Editing, and Site-Specific Gene Insertion in Maize Using Cas9 and Guide RNA.

Targeted mutagenesis, editing of endogenous maize (Zea mays) genes, and site-specific insertion of a trait gene using clustered regularly interspaced short palindromic repeats (CRISPR)-associated (Cas)-guide RNA technology are reported in maize. DNA vectors expressing maize codon-optimized Streptococcus pyogenes Cas9 endonuclease and single guide RNAs were cointroduced with or without DNA repair templates into maize immature embryos by biolistic transformation targeting five different genomic regions: upstream of the liguleless1 (LIG1) gene, male fertility genes (Ms26 and Ms45), and acetolactate synthase (ALS) genes (ALS1 and ALS2). Mutations were subsequently identified at all sites targeted, and plants containing biallelic multiplex mutations at LIG1, Ms26, and Ms45 were recovered. Biolistic delivery of guide RNAs (as RNA molecules) directly into immature embryo cells containing preintegrated Cas9 also resulted in targeted mutations. Editing the ALS2 gene using either single-stranded oligonucleotides or double-stranded DNA vectors as repair templates yielded chlorsulfuron-resistant plants. Double-strand breaks generated by RNA-guided Cas9 endonuclease also stimulated insertion of a trait gene at a site near LIG1 by homology-directed repair. Progeny showed expected Mendelian segregation of mutations, edits, and targeted gene insertions. The examples reported in this study demonstrate the utility of Cas9-guide RNA technology as a plant genome editing tool to enhance plant breeding and crop research needed to meet growing agriculture demands of the future.

Cas9-Guide RNA Directed Genome Editing in Soybean.

Recently discovered bacteria and archaea adaptive immune system consisting of clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated (Cas) endonuclease has been explored in targeted genome editing in different species. Streptococcus pyogenes Cas9-guide RNA (gRNA) was successfully applied to generate targeted mutagenesis, gene integration, and gene editing in soybean (Glycine max). Two genomic sites, DD20 and DD43 on chromosome 4, were mutagenized with frequencies of 59% and 76%, respectively. Sequencing randomly selected transgenic events confirmed that the genome modifications were specific to the Cas9-gRNA cleavage sites and consisted of small deletions or insertions. Targeted gene integrations through homology-directed recombination were detected by border-specific polymerase chain reaction analysis for both sites at callus stage, and one DD43 homology-directed recombination event was transmitted to T1 generation. T1 progenies of the integration event segregated according to Mendelian laws and clean homozygous T1 plants with the donor gene precisely inserted at the DD43 target site were obtained. The Cas9-gRNA system was also successfully applied to make a directed P178S mutation of acetolactate synthase1 gene through in planta gene editing.

Analysis of profitability in the diagnosis of allergy to beta-lactam antibiotics

Drug allergy is the third most common reason for allergy consultations. There is a tendency to call any adverse drug reaction (ADR) allergic, even without confirmatory allergy study. OBJECTIVES: (1) Evaluate time of resolution allergy to beta-lactam's study in a sample of 100 patients. (2) Analyse cost-effectiveness of current diagnostic study (skin tests, specific IgE and drug provocation test (DPT)). (3) Describe type and frequency of ADRs in adult/paediatric patients. (4) Compare cost of complete study with DPT. (5) Assess the need to restructure current study methodology according to results obtained. The study is part of a strategic plan of the allergy department (2005-2010). Patients with suspected allergy to beta-lactams were included. Procedures performed: medical history, specific IgE, skin tests and DPT. Cost/patient analysis. Cost of protocol analysis for current diagnostic/direct DPT. RESULTS: 100 patients were studied, 52 females/48 males; 43 children/57 adults. Symptoms: 89 cutaneous, 4 anaphylaxis, 3 vasovagal reactions, 6 non-specific symptoms and 4 not recalled. Allergy was confirmed in six patients (only one child). Complete-study cost: 149.3 Euros/patient. DPT-study cost: 97.19 Euros/patient (34.9% less). Resolution time 9-13 months, absenteeism 28.04%. CONCLUSIONS: In the series studied, diagnosis of allergy to beta-lactams was confirmed in 6% of patients (2.3% of paediatric patients). After analysing results and cost of the study we believe that we should propose a specific diagnostic algorithm in those paediatric patients without suspected IgE-mediated ADR, and for those patients direct DPT should be conducted. This will reduce cost/patient (−34.9%), time of resolution and absenteeism

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Intention to prescribe self-injectable epinephrine: are there differences depending on who assesses the patient post-reaction?

INTRODUCTION: Anaphylaxis is the most severe of all allergic reactions and can even prove fatal. There is limited evidence of a difference in prescribing patterns for self-injectable epinephrine (SIE) between general paediatricians and paediatricians with greater knowledge of allergology. OBJECTIVES: Assess knowledge about prescribing SIE of a sample of primary care/hospital paediatricians and paediatricians with specialised knowledge of allergology through a questionnaire asking them about clinical cases of anaphylaxis in their daily paediatric practice. MATERIALS AND METHODS: Participants were primary care and hospital paediatricians practicing in different regions of the province of Barcelona and paediatricians with specialised knowledge in the field of allergology from Spain. RESULTS: A total of 183 paediatricians responded. Of that 59.6% were paediatricians with specialised knowledge of allergology. General paediatricians in most cases correctly prescribed SIE device (more than 70% answered correctly in five of the eight clinical cases). In the case of drug anaphylaxis, which is an avoidable allergen for which SIE is not indicated, 67.5% of general paediatricians would prescribe it. In the case of exercise-induced anaphylaxis there were also differences in the prescription of epinephrine by general paediatricians, with only 40% prescribing it. CONCLUSIONS: In this study the percentage of SIE prescriptions would be higher than expected by general paediatricians, with no differences in the cases proposed between them and the paediatricians with better knowledge of allergology. Despite these results, it is important to insist on conducting education programmes and disseminating them to facilitate physicians' recognition and treatment of anaphylactic reactions

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Position document: IgE-mediated cow's milk allergy.

The present document offers an update on the recommendations for managing patients with cow's milk allergy - a disorder that manifests in the first year of life, with an estimated prevalence of 1.6-3% in this paediatric age group. The main causal allergens are the caseins and proteins in lactoserum (beta-lactoglobulin, alpha-lactoalbumin), and the clinical manifestations are highly variable in terms of their presentation and severity. Most allergic reactions affect the skin, followed by the gastrointestinal and respiratory systems, and severe anaphylaxis may occur. The diagnosis of cow's milk allergy is based on the existence of a suggestive clinical history, a positive allergy study and the subsequent application of controlled exposure testing, which constitutes the gold standard for confirming the diagnosis. The most efficient treatment for cow's milk allergy is an elimination diet and the use of adequate substitution formulas. The elimination diet must include milk from other mammals (e.g., sheep, goat, etc.) due to the risk of cross-reactivity with the proteins of cow's milk. Most infants with IgE-mediated cow's milk allergy become tolerant in the first few years of life. In those cases where cow's milk allergy persists, novel treatment options may include oral immunotherapy, although most authors do not currently recommend this technique in routine clinical practice. Enough evidence is not there to confirm the efficacy of elimination diets in the mother and infant for preventing the appearance of cow's milk allergy. Likewise, no benefits have been observed with prebiotic and probiotic dietetic supplements in infants for preventing food allergy.

Allergy medical care network: a new model of care for specialties

In 2005 the Althaia Foundation Allergy Department performed its daily activity in the Hospital Sant Joan de Deu of Manresa. Given the increasing demand for allergy care, the department's performance was analysed and a strategic plan (SP) for 2005---2010 was designed. The main objective of the study was to assess the impact of the application of the SP on the department's operations and organisational level in terms of profitability, productivity and quality of care. MATERIAL AND METHODS: Descriptive, retrospective study which evaluated the operation of the allergy department. The baseline situation was analysed and the SP was designed. Indicators were set to perform a comparative analysis after application of the SP. RESULTS: The indicators showed an increase in medical care activity (first visits, 34%; successive visits, 29%; day hospital treatments, 51%), high rates of resolution, reduced waiting lists. Economic analysis indicated an increase in direct costs justified by increased activity and territory attended. Cost optimisation was explained by improved patient accessibility, minimised absenteeism in the workplace and improved cost per visit. CONCLUSIONS: After application of the SP a networking system was established for the allergy speciality that has expanded the territory for which it provides care, increased total activity and the ability to resolve patients, optimised human resources, improved quality of care and streamlined medical cost

No disponible

Intention to prescribe self-injectable epinephrine: Are there differences depending on who assesses the patient post-reaction?

INTRODUCTION: Anaphylaxis is the most severe of all allergic reactions and can even prove fatal. There is limited evidence of a difference in prescribing patterns for self-injectable epinephrine (SIE) between general paediatricians and paediatricians with greater knowledge of allergology. OBJECTIVES: Assess knowledge about prescribing SIE of a sample of primary care/hospital paediatricians and paediatricians with specialised knowledge of allergology through a questionnaire asking them about clinical cases of anaphylaxis in their daily paediatric practice. MATERIALS AND METHODS: Participants were primary care and hospital paediatricians practicing in different regions of the province of Barcelona and paediatricians with specialised knowledge in the field of allergology from Spain. RESULTS: A total of 183 paediatricians responded. Of that 59.6% were paediatricians with specialised knowledge of allergology. General paediatricians in most cases correctly prescribed SIE device (more than 70% answered correctly in five of the eight clinical cases). In the case of drug anaphylaxis, which is an avoidable allergen for which SIE is not indicated, 67.5% of general paediatricians would prescribe it. In the case of exercise-induced anaphylaxis there were also differences in the prescription of epinephrine by general paediatricians, with only 40% prescribing it. CONCLUSIONS: In this study the percentage of SIE prescriptions would be higher than expected by general paediatricians, with no differences in the cases proposed between them and the paediatricians with better knowledge of allergology. Despite these results, it is important to insist on conducting education programmes and disseminating them to facilitate physicians' recognition and treatment of anaphylactic reactions.

Allergy medical care network: a new model of care for specialties.

UNLABELLED: In 2005 the Althaia Foundation Allergy Department performed its daily activity in the Hospital Sant Joan de Deu of Manresa. Given the increasing demand for allergy care, the department's performance was analysed and a strategic plan (SP) for 2005-2010 was designed. The main objective of the study was to assess the impact of the application of the SP on the department's operations and organisational level in terms of profitability, productivity and quality of care. MATERIAL AND METHODS: Descriptive, retrospective study which evaluated the operation of the allergy department. The baseline situation was analysed and the SP was designed. Indicators were set to perform a comparative analysis after application of the SP. RESULTS: The indicators showed an increase in medical care activity (first visits, 34%; successive visits, 29%; day hospital treatments, 51%), high rates of resolution, reduced waiting lists. Economic analysis indicated an increase in direct costs justified by increased activity and territory attended. Cost optimisation was explained by improved patient accessibility, minimised absenteeism in the workplace and improved cost per visit. CONCLUSIONS: After application of the SP a networking system was established for the allergy speciality that has expanded the territory for which it provides care, increased total activity and the ability to resolve patients, optimised human resources, improved quality of care and streamlined medical costs.

Analysis of profitability in the diagnosis of allergy to beta-lactam antibiotics.

UNLABELLED: Drug allergy is the third most common reason for allergy consultations. There is a tendency to call any adverse drug reaction (ADR) allergic, even without confirmatory allergy study. OBJECTIVES: (1) Evaluate time of resolution allergy to beta-lactam's study in a sample of 100 patients. (2) Analyse cost-effectiveness of current diagnostic study (skin tests, specific IgE and drug provocation test (DPT)). (3) Describe type and frequency of ADRs in adult/paediatric patients. (4) Compare cost of complete study with DPT. (5) Assess the need to restructure current study methodology according to results obtained. The study is part of a strategic plan of the allergy department (2005-2010). Patients with suspected allergy to beta-lactams were included. Procedures performed: medical history, specific IgE, skin tests and DPT. Cost/patient analysis. Cost of protocol analysis for current diagnostic/direct DPT. RESULTS: 100 patients were studied, 52 females/48 males; 43 children/57 adults. SYMPTOMS: 89 cutaneous, 4 anaphylaxis, 3 vasovagal reactions, 6 non-specific symptoms and 4 not recalled. Allergy was confirmed in six patients (only one child). Complete-study cost: 149.3 Euros/patient. DPT-study cost: 97.19 Euros/patient (34.9% less). Resolution time 9-13 months, absenteeism 28.04%. CONCLUSIONS: In the series studied, diagnosis of allergy to beta-lactams was confirmed in 6% of patients (2.3% of paediatric patients). After analysing results and cost of the study we believe that we should propose a specific diagnostic algorithm in those paediatric patients without suspected IgE-mediated ADR, and for those patients direct DPT should be conducted. This will reduce cost/patient (-34.9%), time of resolution and absenteeism.