The axolotl genome and the evolution of key tissue formation regulators.

Salamanders serve as important tetrapod models for developmental, regeneration and evolutionary studies. An extensive molecular toolkit makes the Mexican axolotl (Ambystoma mexicanum) a key representative salamander for molecular investigations. Here we report the sequencing and assembly of the 32-gigabase-pair axolotl genome using an approach that combined long-read sequencing, optical mapping and development of a new genome assembler (MARVEL). We observed a size expansion of introns and intergenic regions, largely attributable to multiplication of long terminal repeat retroelements. We provide evidence that intron size in developmental genes is under constraint and that species-restricted genes may contribute to limb regeneration. The axolotl genome assembly does not contain the essential developmental gene Pax3. However, mutation of the axolotl Pax3 paralogue Pax7 resulted in an axolotl phenotype that was similar to those seen in Pax3-/- and Pax7-/- mutant mice. The axolotl genome provides a rich biological resource for developmental and evolutionary studies.

Author Correction: The axolotl genome and the evolution of key tissue formation regulators.

In the originally published version of this Article, the sequenced axolotl strain (the homozygous white mutant) was denoted as 'D/D' rather than 'd/d' in Fig. 1a and the accompanying legend, the main text and the Methods section. The original Article has been corrected online.

Cutaneous Manifestations Related to COVID-19 Immune Dysregulation in the Pediatric Age Group.

PURPOSE OF REVIEW: At the juncture of the COVID-19 pandemic, the world is currently in an early phase of collecting clinical data and reports of its skin manifestations, and its pathophysiology is still highly conjectural. We reviewed cutaneous manifestations associated with COVID-19 in the pediatric age group. RECENT FINDINGS: Children infected by SARS-CoV-2 usually develop milder respiratory symptoms, but cutaneous manifestations seem a little more prevalent than in adults. These skin features of infection by the coronavirus can be similar to those produced by other common viruses, but there are also reports of cases with more heterogeneous clinical pictures, which have made their classification difficult. To date, the more frequently reported skin variants featured in pediatric cases are purpuric (pseudo-chilblain, necrotic-acral ischemia, hemorrhagic macules, and/or cutaneous necrosis), morbilliform/maculopapular, erythema multiforme, urticarial, vesicular, Kawasaki-like, and miscellaneous (highly variable in both frequency and severity). Their pathophysiological mechanism is still elusive and is likely to be the result of the complex involvement of one or more mechanisms, like direct virus-induced skin damage, vasculitis-like reactions, and/or indirect injury as a consequence of a systemic inflammatory reaction. In this review, we presented and discussed clinical cases as examples of different cutaneous responses reported in some children with SARS-CoV-2 infection, differential diagnosis considerations, and a preliminary conceptual approach to some of their probable associated pathologic mechanisms.

Coronavirus disease 2019, allergic diseases, and allergen immunotherapy: Possible favorable mechanisms of interaction.

Background: Both, allergen immunotherapy (AIT) and SARS-COV-2 infection cause a set of immunologic changes that respectively vary during the course of the treatment or the disease. Objective: To review immune changes brought along by each of these entities and how they might interrelate. Methods: We start presenting a brief review of the structure of the new coronavirus and how it alters the functioning of the human immune system. Subsequently, we describe the immune changes induced by AIT and how these changes could be favorable or unfavorable in the allergic patient infected with SARS-CoV-2 at a particular point of time during the evolving infection. Results: We describe how a healthy immune response against SARS-CoV-2 develops, versus an immune response that is initially suppressed by the virus, but ultimately overactivated, leading to an excessive production of cytokines (cytokine-storm-like). These changes are then linked to the clinical manifestations and outcomes of the patient. Reviewing the immune changes secondary to AIT, it becomes clear how AIT is capable of restoring a healthy innate immunity. Investigators have previously shown that the frequency of respiratory infections is reduced in allergic patients treated with AIT. On the other hand it also increases immunoregulation. Conclusion: As there are many variables involved, it is hard to predict how AIT could influence the allergic patient's reaction to a SARS-CoV-2 infection. In any case, AIT is likely to be beneficial for the patient with allergic rhinitis and/or allergic asthma in the context of the SARS-CoV-2 pandemic as controlling allergic diseases leads to a reduced need for contact with healthcare professionals. The authors remind the reader that everything in this article is still theoretical, since at the moment, there are no published clinical trials on the outcome of COVID-19 in allergic patients under AIT.

A middle aged woman with isolated ACTH deficiency associated with transient growth hormone deficiency.

Isolated ACTH deficiency (IAD) is a rare entity characterized by secondary adrenal insufficiency with low levels of serum cortisol, decreased production of ACTH, adequate secretion of other pituitary hormones and normal pituitary structure on radioimaging. The prevalence of IAD as a cause of secondary adrenal insufficiency has not been determined. Impairment of growth hormone (GH) secretion has been noted in 20 to 30% of patients with IAD which is normalized after glucocorticoid replacement. We report the case of a 50 years-old female with symptoms and laboratory results suggestive of adrenal insufficiency. Insulin tolerance test confirmed ACTH and growth hormone deficiency. The rest of the anterior pituitary hormones were normal. A pituitary MRI was unremarkable. Glucocorticoid replacement therapy started and eight months afterwards glucagon stimulation test revealed persistent ACTH deficiency but nor- mal growth hormone secretion. IAD can present with nonspecific symptoms and could be potentially fatal in an acute stressful period. Prompt recognition is essential to decrease morbidity and mortality.

Circulating levels of miR-150 are associated with poorer outcomes of A/H1N1 infection.

BACKGROUND: Overproduction of pro-inflammatory cytokines and chemokines is frequently associated with severe clinical manifestations in patients infected with influenza A/H1N1 virus. Micro-RNAs (miRNAs) are highly conserved small non-coding RNA molecules that post-transcriptionally regulate gene expression and are potential biomarkers and therapeutic targets in different inflammatory conditions. METHODS: We studied the circulating and miRNA profiles in critically ill A/H1N1 patients, A/H1N1 patients with milder disease, asymptomatic housemates and healthy controls. Cytokine, chemokine and growth factors that were potential targets of differentially expressed miRNAs were assessed. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment and interactome analysis of these miRNAs were also performed. RESULTS: Critically ill patients exhibited a significant over-expression of circulating miR-150 (p<0.005) when compared to patients with milder disease. miR-29c, miR-145 and miR-22 were differentially expressed in patients with severe A/H1N1 disease whereas miR-210, miR-126 and miR-222 were downregulated in individuals exposed to the A/H1N1 virus. Significant correlations (p<0.05) between circulating levels of miR-150 with IL-1ra, IL-2, IL-6, CXCL8, IFN-γ, CXCL10 and G-CSF were detected, particularly in critically ill patients. CONCLUSION: The up-regulation of miR-150 is associated with poorer outcomes of A/H1N1 infection. The differential expression of miRNAs related with immune processes in severe A/H1N1 disease supports the potential role of these miRNAs as biomarkers of disease progression.

Multiple Skeletal Deformities in a Middle-Aged Man.

A 54-year-old man was seen in our endocrinology clinic with evidence of a limited range of motion in his left foot. He had a history of diabetes mellitus type 2 and atrial fibrillation. His family history included evidence of skeletal deformities in some of his relatives. This could imply the potential existence of a hereditary condition. It is worth noting that spontaneous mutations have been reported in some cases. A pertinent physical examination revealed a surgical scar on the patient's left knee, a hallux valgus deformity on his left foot with compromised joint function, and painless bony prominences on that same foot. The skeletal survey findings were consistent with multiple hereditary exostoses. Multiple osteochondromatosis (MO) is a rare genetic disorder associated with serious complications that may significantly affect the health related quality of life of anyone having the disorder. To prevent further complications, these patients require long-term follow-up with regular clinical and radiological examinations.

Do We Need Hormonal Screening In Patients With Subcentimeter Pituitary Microadenomas?

A 54-year-old woman came to our endocrinology clinics presenting with upper and lower extremity paresthesia, salt cravings, episodes of hypotension, fatigue and a long term history of depression. Physical exam was unremarkable. Cervical and brain MRI ordered by her neurologist three years ago revealed sella and pituitary normal in size, stable very small 3 mm pituitary incidentaloma and mild disc bulging. Basal pituitary hormonal screening showed low cortisol and ACTH levels. Insulin Tolerance Test and Glucagon Stimulation Test confirmed secondary ACTH deficiency with concomitant GH deficiency. In spite of medical counseling the patient refused glucocorticoid replacement. Due to the non-specific symptoms of this condition it remains a challenge to be diagnosed by clinicians. In conclusion: Our case shows that hormonal deficiencies may occur in small tumors less than 6 mm.

Multinational experience with hypersensitivity drug reactions in Latin America.

BACKGROUND: Epidemiologic drug allergy data from Latin America are scarce, and there are no studies on specific procedures focusing on this topic in Latin America. OBJECTIVE: To assess the clinical characteristics and management of hypersensitivity drug reactions in different Latin American countries. METHODS: An European Network of Drug Allergy questionnaire survey was implemented in 22 allergy units in 11 Latin American countries to report on consecutive patients who presented with a suspected hypersensitivity drug reaction. Each unit used its own protocols to investigate patients. RESULTS: Included were 868 hypersensitivity drug reactions in 862 patients (71% of adults and elderly patients were women and 51% of children were girls, P = .0001). Children presented with less severe reactions than adults and elderly patients (P < .0001). Urticaria and angioedema accounted for the most frequent clinical presentations (71%), whereas anaphylaxis was present in 27.3% of cases. There were no deaths reported. Nonsteroidal anti-inflammatory drugs (52.3%), ß-lactam antibiotics (13.8%), and other antibiotics (10.1%) were the drugs used most frequently. Skin prick tests (16.7%) and provocation tests (34.2%) were the study procedures most commonly used. A large proportion of patients were treated in the emergency department (62%) with antihistamines (68%) and/or corticosteroids (53%). Only 22.8% of patients presenting with anaphylaxis received epinephrine. CONCLUSION: Nonsteroidal anti-inflammatory drugs and antibiotics were the drugs used in at least 75% of patients. More than half the reactions were treated in the emergency department, whereas epinephrine was administered in fewer than 25% of patients with anaphylaxis. Dissemination of guidelines for anaphylaxis among primary and emergency department physicians should be encouraged.

[Drug allergy: Fundamental aspects in diagnosis and treatment.] / Alergia a medicamentos: aspectos fundamentales en el diagnóstico y tratamiento. Reporte de grupo del Colegio Mexicano de Inmunología Clínica y Alergia.

BACKGROUND: Any substance used as a treatment for any disease can produce harmful or unpleasant events called adverse drug reactions (ADRs). They are due to inherent biological effects of the drug and are caused by immunological and non-immunological mechanisms. OBJECTIVES: To describe the immunological mechanisms of hypersensitivity reactions (HSR) to drugs, their epidemiology, risk factors, classification, clinical manifestations, diagnosis, treatment, and prognosis. METHODS: A review of the most current literature in English and Spanish was carried out, in the main databases, related to the HSR of various drug groups. RESULTS: This study describes the terms used to define ADRs and HSRs, their classification and clinical manifestations, current diagnostic tools, treatment algorithms and prognosis of the most frequently used medications and with the highest prevalence of reported adverse events. CONCLUSION: ADRs are a challenging entity, with a complex pathophysiology that has not been fully understood. Its approach requires a careful consideration since not all drugs have validated tests for their diagnosis nor a specific treatment. When indicating the use of any drug, the severity of the disease, the availability of other treatments and the potential risks of developing future adverse events should always be taken into consideration.

ANTECEDENTES: Cualquier sustancia prescrita en el tratamiento de algún padecimiento es capaz de producir eventos dañinos o desagradables, y se denominan reacciones adversas a medicamentos. Estas reacciones se originan por mecanismos inmunológicos y no inmunológicos. OBJECTIVOS: Describir los mecanismos inmunológicos de las reacciones de hipersensibilidad a medicamentos, epidemiologia, factores de riesgo, clasificación, manifestaciones clínicas, diagnóstico, tratamiento y pronóstico. MÉTODOS: Se revisó la bibliografía actualizada, en inglés y español, asociada con reacciones de hipersensibilidad a medicamentos en las principales bases de datos. RESULTADOS: Se describen los términos para definir las reacciones adversas y de hipersensibilidad a medicamentos, su clasificación y manifestaciones clínicas, métodos diagnósticos actuales y en estudio, algoritmos de tratamiento y pronóstico de los medicamentos más frecuentemente prescritos y con mayor prevalencia de eventos adversos reportados. CONCLUSIÓN: Las reacciones adversas a medicamentos representan un reto, con una fisiopatología compleja y no del todo comprendida. Su abordaje requiere un enfoque cuidadoso, porque no todos los fármacos cuentan con pruebas validadas para establecer el diagnóstico y tratamiento específico. Antes de indicar cualquier medicamento debe considerarse la gravedad de la enfermedad, disponibilidad de otros tratamientos y riesgos potenciales de sufrir eventos adversos.

Measuring Psychological Flexibility: The Cultural Adaptation and Psychometric Properties of the AAQ for Substance Abuse among Spanish Speaking Population in Correctional and Community settings.

Evaluating psychological flexibility is key in determining the mechanism of action of an ACT intervention. This study aims to evaluate the psychometric properties of the Spanish version of the Acceptance and Action Questionnaire - Substance Abuse (AAQ-SA), a measure of psychological flexibility, among 402 adults with Substance Use Disorders (SUDs) in Puerto Rico recruited from either a prison population or community treatment settings. To evaluate the factor structure of the AAQ-SA, we conducted confirmatory factor analyses with the two-factor structure proposed by the original authors and the three-factor structure found in a Mexican sample. We found the two-factor structure to be a better fit of the data from our sample. After implementing modifications to the model, the two-factor structure demonstrated adequate model fit indices. To gather evidence of convergent validity, we evaluated correlations between scores of the AAQ-SA and those of depression, self-efficacy, and self-stigma measures. The current study suggests that the AAQ-SA is a promising measure of psychological flexibility for the present target populations. Further research is needed to examine the psychometric properties of scores of the AAQ-SA, including discriminant validity.

European and Mexican vs US diagnostic extracts of Bermuda grass and cat in skin testing.

BACKGROUND: Laboratory testing of various diagnostic extracts has shown lower potencies for several European and Mexican extracts relative to the US Food and Drug Administration (FDA) reference (10,000 BAU/mL). Quantitative skin prick testing (QSPT) with Dermatophagoides pteronyssinus extracts have previously shown a similar picture. OBJECTIVE: To compare European and Mexican Bermuda grass (BG) and cat diagnostic extracts against an FDA-validated extract using QSPT. METHODS: Six diagnostic BG and cat extracts (1 reference FDA extract, 3 European extracts, 1 imported nonstandardized extract from the United States, and 1 Mexican extract) were tested with quadruplicate QSPT, as a concentrate and as 2 serial 2-fold dilutions, in cat and BG allergic individuals. RESULTS: BG showed good dose response in wheal size for the concentrate (1:2-1:4 dilutions; steep part of the curve). Cat showed poorer dose response. The Wilcoxon test for linked random samples was used to investigate whether the distribution of the reference differed from each of the test extracts to a statistically significant degree (2-sided asymptotic significance, α = .05). All BG and 2 cat extracts were statistically less potent than the 10,000 BAU/mL US reference. European BG extracts were 7,700, 4,100, and 1,600 BAU/mL, and cat extracts were 12,500, 4,400, and 5,100 BAU/mL. CONCLUSIONS: The potency of some diagnostic extracts of BG and cat used in Europe, Mexico, and the United States differs, with the US extracts being generally more potent. On the basis of provocation tests, optimal diagnostic concentrations should be determined. Similar comparisons using other manufacturers and therapeutic extracts might be interesting.

The genome of Bacillus coahuilensis reveals adaptations essential for survival in the relic of an ancient marine environment.

The Cuatro Ciénegas Basin (CCB) in the central part of the Chihuahan desert (Coahuila, Mexico) hosts a wide diversity of microorganisms contained within springs thought to be geomorphological relics of an ancient sea. A major question remaining to be answered is whether bacteria from CCB are ancient marine bacteria that adapted to an oligotrophic system poor in NaCl, rich in sulfates, and with extremely low phosphorus levels (<0.3 microM). Here, we report the complete genome sequence of Bacillus coahuilensis, a sporulating bacterium isolated from the water column of a desiccation lagoon in CCB. At 3.35 Megabases this is the smallest genome sequenced to date of a Bacillus species and provides insights into the origin, evolution, and adaptation of B. coahuilensis to the CCB environment. We propose that the size and complexity of the B. coahuilensis genome reflects the adaptation of an ancient marine bacterium to a novel environment, providing support to a "marine isolation origin hypothesis" that is consistent with the geology of CCB. This genomic adaptation includes the acquisition through horizontal gene transfer of genes involved in phosphorous utilization efficiency and adaptation to high-light environments. The B. coahuilensis genome sequence also revealed important ecological features of the bacterial community in CCB and offers opportunities for a unique glimpse of a microbe-dominated world last seen in the Precambrian.

[Psychometric Properties of the Scale of Negative Attitudes Towards Trans People in Healthcare Providers in Puerto Rico]. / Propiedades psicométricas de la Escala de Actitudes Negativas hacia Personas Trans en proveedores de salud en Puerto Rico.

The ignorance towards the Trans people can cause healthcare providers to assume negative attitudes towards this population. It is relevant to understand with more amplitude the manifestations of stigma towards the Trans population using instruments whose psychometry is adequate. The main objective of the present study was to evaluate the reliability of the Scale of Negative Attitudes towards Trans People (EANT, in Spanish) and its factorial structure in healthcare providers in Puerto Rico. As a secondary objective, differences in attitudes towards Trans people between physical healthcare providers and mental healthcare providers were evaluated. The sample consisted of 67 healthcare providers recruited according to their availability. A point-biserial correlation, a Cronbach's alpha analysis, a Confirmatory Factor Analysis (CFA), and the non-parametric Mann-Whitney test were carried out to examine our objectives. The results confirmed that the EANT has a one-dimensional structure. The Cronbach's alpha internal consistency index of the scale was .75. No significant differences were found in attitudes towards Trans people between physical healthcare providers and mental healthcare providers. Finally, a discussion of the research findings is presented, as well as its limitations and contributions.

Leachate treatment: comparison of a bio-coagulant (Opuntia ficus mucilage) and conventional coagulants using multi-criteria decision analysis.

The main aim of this research was to compare a bio-coagulant, organic coagulant, and a conventional coagulant applied to the treatment of leachates. Coagulant options were Stage 1 FeCl3, Stage 2 Polyamine, and Stage 3 Opuntia ficus mucilage (OFM). Optimal conditions for maximum chemical oxygen demand (COD) removal were determined by experimental data and Response Surface Methodology. The application of Multiple Criteria Decision Analysis using Multi-Criteria Matrix (MCM) was explored by evaluating the Coagulation-Flocculation processes. Maximum COD removal (%) and the best MCM scores (on a scale from 0 to 100) were: Stage 1: 69.2±0.9 and 48.50, Stage 2: 37.8±1.1 and 79.0, and Stage 3: 71.1±1.7, and 81.5. Maximum COD removal using FeCl3 and OFM was not statistically different (p 0.15 < 0.05). OFM extraction process was evaluated (yield 0.70 ± 1.17%, carbohydrate content 32.6 ± 1.18%). MCM allows the evaluation of additional technical aspects, besides oxygen COD removal, as well as economic aspects, permitting a more comprehensive analysis. Significant COD removals indicate that the use of OFM as a coagulant in the treatment of stabilized leachate was effective. Opuntia ficus cladodes, a residue, were used to treat another residue (leachates).

Atmospheric pollen count in Monterrey, Mexico.

There are few reports of pollen count and identification in Mexico; therefore, it is important to generate more information on the subject. This study was designed to describe the prevalence of pollen in the city of Monterrey, Mexico, during the year 2004. Atmospheric pollen was collected with a Hirst air sampler, with an airflow of 10 L/minute during 2004. Pollen was identified with light microscopy; the average monthly pollen count as well as total was calculated from January 2004 to January 2005. The months with the highest concentration of pollen were February and March (289 and 142 grains/m(3) per day, respectively), and July and November had the lowest concentration (20 and 11 grains/m(3) per day, respectively). Most of the pollen recollected corresponded to tree pollen (72%). Fraxinus spp had the highest concentration during the year (19 grains/m(3) per day; 27.5% of the total concentration of pollen). Tree pollen predominated from January through March; with Fraxinus spp, Morus spp, Celtis spp, Cupressus spp, and Pinus spp as the most important. Weed pollen predominated in May, June, and December and the most frequently identified, were Amaranthaceae/Chenopodiaceae, Ambrosia spp, and Parietaria spp. The highest concentration of grass pollen was reported during the months of May, June, September, October, and December with Gramineae/Poaceae predominating. Tree pollen was the most abundant during the year, with the ash tree having the highest concentration. Weed and grass pollen were perennial with peaks during the year.

"Effect of valerenic acid on neuroinflammation in a MPTP-induced mouse model of Parkinson's disease".

Parkinson´s disease is the most important neuromotor pathology due to the prominent loss of dopaminergic neurons in the substantia nigra pars compacta. There is an inherent deficiency of dopamine in Parkinson´s disease, which is aggravated when neuroinflammatory processes are present. Several biomolecules are interesting candidates for the regulation of inflammation and possible neuroprotection, such as valerenic acid, one of the main components of Valeriana officinalis. A 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP)-induced mouse model of Parkinson's disease was developed to evaluate the motor effects of valerenic acid. The evaluation was carried out with four tests (an invert screen test for muscle strength, cross beam test, open field mobility test and lifting on hind legs test). Subsequently, the neuroinflammatory process was evaluated through ELISA of pro-inflammatory cytokines (IL-1ß, IL-6, TNF-α and IFN-γ). The decreases in the inflammatory and neurodegenerative processes were evaluated by Western blot and immunohistochemistry analyses of the tissues, which included an evaluation of the tyrosine hydroxylase and GFAP proteins. Finally, the predicted mechanism of action of valerenic acid was supported by molecular docking calculations with the 5-HT5A receptor. The results indicate that the use of valerenic acid as a co-treatment decreases the neuroinflammation in Parkinson's disease induced by MPTP and provides evidence of a decrease in the evaluated pro-inflammatory cytokines and in the amount of GFAP in the mesencephalic area. Valerenic acid prevents neuroinflammation in a Parkinson's disease mouse model, which might reflect the neuroprotection of dopaminergic neurons with the recovery of motor ability.

Chronic urticaria and thyroid pathology.

Urticaria is defined as the sudden appearance of erythematous, itchy wheals of variable size, with or without angioedema (AE) (swelling of the deeper layers of the skin). Its classification depends on time course of symptoms and the presence of eliciting factors. When it lasts less than 6 weeks it is classified as acute urticaria (AU), and if the symptoms persist for more than 6 weeks, it is classified as chronic urticaria (CU). Current International Guidelines also classify CU as chronic spontaneous urticaria (CSU) and inducible urticarial, according to the absence or presence of environmental triggering factors. CSU is defined as urticaria and/or angioedema in which there is no evidence of a specific eliciting factor. CSU is associated with autoimmunity in 30-45% of the cases, sharing some immunological mechanisms with other autoimmune diseases, and is associated with autoimmune thyroid disease (ATD) in about 4.3%-57.4% patients. Several studies suggest that adequate therapy with anti-thyroid drugs or levothyroxine in early stages of ATD and CSU, may help to remit the latter; but there is still a lack of double-blind, placebo-controlled studies that support this hypothesis in patients without abnormal thyroid hormone levels. The objective of this review is to describe the pathophysiology of chronic spontaneous urticaria and its association with autoimmune thyroid disease.

Enhancing innate immunity against virus in times of COVID-19: Trying to untangle facts from fictions.

INTRODUCTION: In light of the current COVID-19 pandemic, during which the world is confronted with a new, highly contagious virus that suppresses innate immunity as one of its initial virulence mechanisms, thus escaping from first-line human defense mechanisms, enhancing innate immunity seems a good preventive strategy. METHODS: Without the intention to write an official systematic review, but more to give an overview of possible strategies, in this review article we discuss several interventions that might stimulate innate immunity and thus our defense against (viral) respiratory tract infections. Some of these interventions can also stimulate the adaptive T- and B-cell responses, but our main focus is on the innate part of immunity. We divide the reviewed interventions into: 1) lifestyle related (exercise, >7 h sleep, forest walking, meditation/mindfulness, vitamin supplementation); 2) Non-specific immune stimulants (letting fever advance, bacterial vaccines, probiotics, dialyzable leukocyte extract, pidotimod), and 3) specific vaccines with heterologous effect (BCG vaccine, mumps-measles-rubeola vaccine, etc). RESULTS: For each of these interventions we briefly comment on their definition, possible mechanisms and evidence of clinical efficacy or lack of it, especially focusing on respiratory tract infections, viral infections, and eventually a reduced mortality in severe respiratory infections in the intensive care unit. At the end, a summary table demonstrates the best trials supporting (or not) clinical evidence. CONCLUSION: Several interventions have some degree of evidence for enhancing the innate immune response and thus conveying possible benefit, but specific trials in COVID-19 should be conducted to support solid recommendations.

Compromising between European and US allergen immunotherapy schools: Discussions from GUIMIT, the Mexican immunotherapy guidelines.

BACKGROUND: Allergen immunotherapy (AIT) has a longstanding history and still remains the only disease-changing treatment for allergic rhinitis and asthma. Over the years 2 different schools have developed their strategies: the United States (US) and the European. Allergen extracts available in these regions are adapted to local practice. In other parts of the world, extracts from both regions and local ones are commercialized, as in Mexico. Here, local experts developed a national AIT guideline (GUIMIT 2019) searching for compromises between both schools. METHODS: Using ADAPTE methodology for transculturizing guidelines and AGREE-II for evaluating guideline quality, GUIMIT selected 3 high-quality Main Reference Guidelines (MRGs): the European Academy of Allergy, Asthma and Immunology (EAACI) guideines, the S2k guideline of various German-speaking medical societies (2014), and the US Practice Parameters on Allergen Immunotherapy 2011. We formulated clinical questions and based responses on the fused evidence available in the MRGs, combined with local possibilities, patient's preference, and costs. We came across several issues on which the MRGs disagreed. These are presented here along with arguments of GUIMIT members to resolve them. GUIMIT (for a complete English version, Supplementary data) concluded the following. RESULTS: Related to the diagnosis of IgE-mediated respiratory allergy, apart from skin prick testing complementary tests (challenges, in vitro testing and molecular such as species-specific allergens) might be useful in selected cases to inform AIT composition. AIT is indicated in allergic rhinitis and suggested in allergic asthma (once controlled) and IgE-mediated atopic dermatitis. Concerning the correct subcutaneous AIT dose for compounding vials according to the US school: dosing tables and formula are given; up to 4 non-related allergens can be mixed, refraining from mixing high with low protease extracts. When using European extracts: the manufacturer's indications should be followed; in multi-allergic patients 2 simultaneous injections can be given (100% consensus); mixing is discouraged. In Mexico only allergoid tablets are available; based on doses used in all sublingual immunotherapy (SLIT) publications referenced in MRGs, GUIMIT suggests a probable effective dose related to subcutaneous immunotherapy (SCIT) might be: 50-200% of the monthly SCIT dose given daily, maximum mixing 4 allergens. Also, a table with practical suggestions on non-evidence-existing issues, developed with a simplified Delphi method, is added. Finally, dissemination and implementation of guidelines is briefly discussed, explaining how we used online tools for this in Mexico. CONCLUSIONS: Countries where European and American AIT extracts are available should adjust AIT according to which school is followed.