A Comparison Study between Traditional and Deep-Reinforcement-Learning-Based Algorithms for Indoor Autonomous Navigation in Dynamic Scenarios.

At the beginning of a project or research that involves the issue of autonomous navigation of mobile robots, a decision must be made about working with traditional control algorithms or algorithms based on artificial intelligence. This decision is not usually easy, as the computational capacity of the robot, the availability of information through its sensory systems and the characteristics of the environment must be taken into consideration. For this reason, this work focuses on a review of different autonomous-navigation algorithms applied to mobile robots, from which the most suitable ones have been identified for the cases in which the robot must navigate in dynamic environments. Based on the identified algorithms, a comparison of these traditional and DRL-based algorithms was made, using a robotic platform to evaluate their performance, identify their advantages and disadvantages and provide a recommendation for their use, according to the development requirements of the robot. The algorithms selected were DWA, TEB, CADRL and SAC, and the results show that-according to the application and the robot's characteristics-it is recommended to use each of them, based on different conditions.

Unanswered questions on the use of biologics in pediatric asthma.

The emergence of biologic therapies for the management of asthma has been a revolutionary change in our capacity to manage this disease. Since the launch of omalizumab, several other biologics have been marketed or are close to being marketed, suggesting that a plethora of monoclonal antibodies can be expected in the coming years. This will facilitate the transition to the paradigm of personalized medicine, but on the other hand will decisively further complicate the choice of the most appropriate treatment, in the absence of reliable enough biological markers. For these reasons, along with the relatively short time of use with these treatments, there are recurrently arising questions for which there are not even moderately documented answers, and for which the only solution must be based, with all reservations, on the combination of indirect evidence and expertise. In this paper, we attempt to address such questions, providing relevant commentaries and considering the whole width of the evidence base.

The use of systemic corticosteroids in asthma management in Latin American countries.

The stepwise treatment approach recommended by the Global Initiative for Asthma (GINA) includes systemic corticosteroids (SCS) suggested as a final step if asthma is severe and/or difficult to treat. Yet, despite the effectiveness of SCS, they are also associated with potentially irreversible adverse outcomes such as type 2 diabetes, adrenal suppression, and cardiovascular disease. Based on recent data indicating that the risk of developing these conditions can increase after as few as 4 short-term (burst) courses of SCS, even patients with mild asthma who receive SCS occasionally for exacerbations are also at risk of these events. As a result, recent updates by GINA and the Latin American Thoracic Society recommend decreasing SCS use by optimizing administration of non-SCS therapies and/or increasing the use of alternatives, such as biologic agents. Recent and ongoing studies characterizing treatment patterns among patients with asthma have revealed alarming trends suggesting the widespread overuse of SCS around the world. In Latin America, asthma prevalence is approximately 17%, and data suggest that the majority of patients have uncontrolled disease. In this review, we summarize currently available data on asthma treatment patterns in Latin America, which indicate that SCS are prescribed to 20-40% of patients with asthma considered to be well controlled and over 50% of patients with uncontrolled disease. We also offer potential strategies to help reduce SCS use for asthma in everyday clinical practice.

Utility of biomarkers in the diagnosis and monitoring of asthmatic children.

Asthma imposes a heavy morbidity burden during childhood; it affects over 10% of children in Europe and North America and it is estimated to exceed 400 million people worldwide by the year 2025. In clinical practice, diagnosis of asthma in children is mostly based on clinical criteria; nevertheless, assessment of both physiological and pathological processes through biomarkers, support asthma diagnosis, aid monitoring, and further lead to better treatment outcomes and reduced morbidity. Recently, identification and validation of biomarkers in pediatric asthma has emerged as a top priority across leading experts, researchers, and clinicians. Moreover, the implementation of non-invasive biomarkers for the assessment and monitoring of paediatric patients with asthma, has been prioritized; however, only a proportion of them are currently included in the clinical practise. Although, the use of non-invasive biomarkers is highly supported in recent asthma guidelines for documenting diagnosis and supporting monitoring of asthmatic patients, data on the Pediatric population are limited. In the present report, the Pediatric Asthma Committee of the World Allergy Organization (WAO), aims to summarize and discuss available data for the implementation of non-invasive biomarkers in the diagnosis and monitoring in children with asthma. Information on the most studied biomarkers, including spirometry, oscillometry, markers of allergic sensitization, fractional exhaled nitric oxide, and the most recent exhaled breath markers and "omic" approaches, will be reviewed. Practical limitations and considerations based on both experts' opinion and critical review of the literature, on the utility of all "well-known" and newly introduced non-invasive biomarkers will be presented. A critical commentary on biomarkers' use in diagnosing and monitoring asthma during the COVID-19 pandemic, cost and availability of biomarkers in different settings and in developing countries, the differences on the biomarkers use between Primary Practitioners, Pediatricians, and Specialists and their role on the longitudinal aspect of asthma is provided.

The role of environmental allergen control in the management of asthma.

Allergen exposure may exacerbate asthma symptoms in sensitized patients. Allergen reduction or avoidance measures have been widely utilized; however, there is ongoing controversy on the effectiveness of specific allergen control measures in the management of children with asthma. Often, allergen avoidance strategies are not recommended by guidelines because they can be complex or burdensome, although individual patients may benefit. Here we explore the potential for intervention against exposure to the major allergens implicated in asthma (ie, house dust mites, indoor molds, rodents, cockroaches, furry pets, and outdoor molds and pollens), and subsequent effects on asthma symptoms. We critically assess the available evidence regarding the clinical benefits of specific environmental control measures for each allergen. Finally, we underscore the need for standardized and multifaceted approaches in research and real-life settings, which would result in the identification of more personalized and beneficial prevention strategies.

Physician's experience on managing asthma in adolescents: results of the International AMADO (Asthma Management in ADOlescents) survey.

BACKGROUND: Worldwide prevalence of asthma seems to be increasing in adolescents, but limited data is available regarding the management of asthma in this age group. OBJECTIVE: Therefore, we conducted an international survey focused on physicians who manage asthma in order to understand how Asthma Management in ADOlescents (AMADO) is currently performed. METHODS: The AMADO survey is a web-based global survey of physician's attitudes towards the management of asthma in adolescents, circulated for 17 weeks. The survey had an anonymous and voluntary standard. The questionnaire consisted in 27 questions covering the training background of respondents, difficulties in diagnosis, and in management of asthma in adolescents. RESULTS: Two hundred forty-four responses were received from 46 countries, from all continents. Most (65%) of participants indicated allergy as being their main specialty. The majority of participants (62%) had more than 5 years of clinical practice, but 62% have no formal training in management of adolescents with asthma. Most of participants (96%) indicated having at least one case of asthma in adolescents per month. 60% of respondents mentioned that the asthmatic adolescents only had the consultation due to the family imposition. All respondents mentioned having difficulties in the management of asthma in adolescents due to patient poor adherence. Overall, 44% of participants have no specific health care resources for adolescents in their departments. Main suggestions from the participants were: optimization of time and personalized communication to these cohort, and standardization of multidisciplinary actions to improve adherence to asthma control treatment. CONCLUSION: Management of asthma in adolescents is still a challenge in clinical practice. The results from this survey helped us to identify the key issues to improve clinical outcomes in the future. This survey is the first step of the international AMADO initiative, which intends to optimize diagnosis and control of asthma and prevent avoidable deaths.

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.

Childhood asthma outcomes during the COVID-19 pandemic: Findings from the PeARL multi-national cohort.

BACKGROUND: The interplay between COVID-19 pandemic and asthma in children is still unclear. We evaluated the impact of COVID-19 pandemic on childhood asthma outcomes. METHODS: The PeARL multinational cohort included 1,054 children with asthma and 505 non-asthmatic children aged between 4 and 18 years from 25 pediatric departments, from 15 countries globally. We compared the frequency of acute respiratory and febrile presentations during the first wave of the COVID-19 pandemic between groups and with data available from the previous year. In children with asthma, we also compared current and historical disease control. RESULTS: During the pandemic, children with asthma experienced fewer upper respiratory tract infections, episodes of pyrexia, emergency visits, hospital admissions, asthma attacks, and hospitalizations due to asthma, in comparison with the preceding year. Sixty-six percent of asthmatic children had improved asthma control while in 33% the improvement exceeded the minimal clinically important difference. Pre-bronchodilatation FEV1 and peak expiratory flow rate were improved during the pandemic. When compared to non-asthmatic controls, children with asthma were not at increased risk of LRTIs, episodes of pyrexia, emergency visits, or hospitalizations during the pandemic. However, an increased risk of URTIs emerged. CONCLUSION: Childhood asthma outcomes, including control, were improved during the first wave of the COVID-19 pandemic, probably because of reduced exposure to asthma triggers and increased treatment adherence. The decreased frequency of acute episodes does not support the notion that childhood asthma may be a risk factor for COVID-19. Furthermore, the potential for improving childhood asthma outcomes through environmental control becomes apparent.

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.

CME suggestions for pediatricians, allergists, and dermatologists, directed by an online survey on urticaria knowledge.

BACKGROUND: The Mexican Guidelines for the diagnosis and treatment of urticaria have been published. Just before their launch, physicians' knowledge was explored relating to key issues of the guidelines. OBJECTIVE: The aim of this study was to investigate the opinion of medical specialists concerning urticaria management. METHODS: A SurveyMonkey® survey was sent out to board-certified physicians of three medical specialties treating urticaria. Replies were analyzed per specialty against the evidence-based recommendations. RESULTS: Sixty-five allergists (ALLERG), 24 dermatologists (DERM), and 120 pediatricians (PED) sent their replies. As for diagnosis: ALERG 42% and PED 76% believe cutaneous mastocytosis, urticarial vasculitis, and hereditary angioedema are forms of urticaria, versus DERM 29% (P < 0.005). Most of the specialties find that the clinical history and physical examination are enough to diagnose acute urticaria, except DERM 45% (P < 0.01). DERM 45% believe laboratory-tests are necessary, as opposed to <15% ALLERG-PED (P < 0.005). However, PED 69% did not know that the most frequent cause of acute urticaria in children is infections, versus ALLERG-DERM 30% (P < 0.005). Many erroneously do laboratory testing in physical urticaria and ALLERG 51%, DERM 59%, and PED 37% do extensive laboratory testing in chronic spontaneous urticaria (CSU); many more PED 59% take Immunoglobulin G (IgG) against foods (P < 0.005). More than half of non-allergists do not know about autologous serum testing nor autoimmunity (P < 0.05). As for treatment, there were a few major gaps: when CSU was controlled, >75% prescribed antihistamines pro re nata, and >85% gave first-generation antiH1 for insomnia. Finally, >40% of DERM did not know that cyclosporine A, omalizumab, or other immunosuppressants could be used in recalcitrant cases. CONCLUSION: Specialty-specific continuous medical education might enhance urticaria management.

CME suggestions for pediatricians, allergists, and dermatologists, directed by an online survey on urticaria knowledge

BACKGROUND: The Mexican Guidelines for the diagnosis and treatment of urticaria have been published. Just before their launch, physicians' knowledge was explored relating to key issues of the guidelines. OBJECTIVE: The aim of this study was to investigate the opinion of medical specialists concern­ing urticaria management. METHODS: A SurveyMonkey(R) survey was sent out to board-certified physicians of three medical specialties treating urticaria. Replies were analyzed per specialty against the evidence-based recommendations. RESULTS: Sixty-five allergists (ALLERG), 24 dermatologists (DERM), and 120 pediatricians (PED) sent their replies. As for diagnosis: ALERG 42% and PED 76% believe cutaneous mastocyto­sis, urticarial vasculitis, and hereditary angioedema are forms of urticaria, versus DERM 29% (P < 0.005). Most of the specialties find that the clinical history and physical examination are enough to diagnose acute urticaria, except DERM 45% (P < 0.01). DERM 45% believe laborato­ry-tests are necessary, as opposed to <15% ALLERG-PED (P < 0.005). However, PED 69% did not know that the most frequent cause of acute urticaria in children is infections, versus ALLERG- DERM 30% (P < 0.005). Many erroneously do laboratory testing in physical urticaria and ALLERG 51%, DERM 59%, and PED 37% do extensive laboratory testing in chronic spontaneous urticaria (CSU); many more PED 59% take Immunoglobulin G (IgG) against foods (P < 0.005). More than half of non-allergists do not know about autologous serum testing nor autoimmunity (P < 0.05). As for treatment, there were a few major gaps: when CSU was controlled, >75% prescribed antihistamines pro re nata, and > 85% gave first-generation antiH1 for insomnia. Finally, > 40% of DERM did not know that cyclosporine A, omalizumab, or other immunosuppressants could be used in recalcitrant cases. CONCLUSION: Specialty-specific continuous medical education might enhance urticaria management

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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.

Impact of COVID-19 on Pediatric Asthma: Practice Adjustments and Disease Burden.

BACKGROUND: It is unclear whether asthma may affect susceptibility or severity of coronavirus disease 2019 (COVID-19) in children and how pediatric asthma services worldwide have responded to the pandemic. OBJECTIVE: To describe the impact of the COVID-19 pandemic on pediatric asthma services and on disease burden in their patients. METHODS: An online survey was sent to members of the Pediatric Asthma in Real Life think tank and the World Allergy Organization Pediatric Asthma Committee. It included questions on service provision, disease burden, and the clinical course of confirmed cases of COVID-19 infection among children with asthma. RESULTS: Ninety-one respondents, caring for an estimated population of more than 133,000 children with asthma, completed the survey. COVID-19 significantly impacted pediatric asthma services: 39% ceased physical appointments, 47% stopped accepting new patients, and 75% limited patients' visits. Consultations were almost halved to a median of 20 (interquartile range, 10-25) patients per week. Virtual clinics and helplines were launched in most centers. Better than expected disease control was reported in 20% (10%-40%) of patients, whereas control was negatively affected in only 10% (7.5%-12.5%). Adherence also appeared to increase. Only 15 confirmed cases of COVID-19 were reported among the population; the estimated incidence is not apparently different from the reports of general pediatric cohorts. CONCLUSIONS: Children with asthma do not appear to be disproportionately affected by COVID-19. Outcomes may even have improved, possibly through increased adherence and/or reduced exposures. Clinical services have rapidly responded to the pandemic by limiting and replacing physical appointments with virtual encounters.

Challenges and choices in the pharmacological treatment of non-severe pediatric asthma: A commentary for the practicing physician.

In recent years, asthma research has focused intensely on the severe part of the disease spectrum, leading to new treatments, mostly therapeutic monoclonal antibodies. However, severe asthma accounts for not more than 2% of asthma in the pediatric population. Therefore, non-severe asthma remains a major health problem in children, not only for patients and parents but also for healthcare professionals such as general practitioners, pediatricians and allergists who take care of these patients. It is thus essential to identify and put in context novel concepts, applicable to the treatment of these patients. Recent evidence suggests benefits from using anti-inflammatory treatment even for the mildest cases, for whom until now only symptomatic bronchodilation was recommended. Likewise, "reliever" medication may be better combined with an inhaled corticosteroid (ICS). Among "new" treatments (for children), ICS formulation in ultrafine particles has showed promise and tiotropium is gaining access to the pediatric population. Maintenance and reliever therapy (MART) is an option for moderate disease. Most importantly, personalized response to medications appears to be considerable, therefore, it may need to be taken into account. Overall, these new options provide opportunities for multiple new management strategies. The deployment of such strategies in different populations remains to be evaluated.

Influence of pH on the formation of a polyelectrolyte complex by dissipative particle dynamics simulation: From an extended to a compact shape.

This work aims to investigate the influence of pH on the mechanism of assembly of macromolecules. We studied the effect of the pH on the interaction of two polyelectrolytes of opposed charge, having the same size, by means of dissipative particle dynamics method. The system consisted of a strong cationic and a weak anionic polyelectrolyte in an aqueous solution containing monovalent counterions. The analysis was made by varying the pH of the solution, which modifies the charge fraction of the weak anionic polyelectrolyte with a dissociation acid constant pKa of 5.5, while the polycation is fully charged in all the pH range used, characteristic of a strong polyelectrolyte. In order to describe the influence of pH on the complexation process, we have analyzed the pair radial distribution functions polyanion-counterion, polycation-counterion, and polyanion-polycation. The complex conformation was studied by means of the radius of gyration and the end-to-end distance of both chains as the pH varied from 1 to 14. A relevant finding obtained here was the relationship between the radial distribution functions and the counterion release from the polyelectrolytes, which leads to a reduction in the size of the complex when pH increased. Surprisingly, a transition from an extended to a compact polyelectrolyte complex was obtained when the pH reached the dissociation acid constant pKa of the weak polyelectrolyte. This systematic study can help to understand a large number of more realistic problems in biological systems such as protein complex, chromatin phase transition, or in complex systems applied in biomedical science.

Remote Postischemic Conditioning Promotes Stroke Recovery by Shifting Circulating Monocytes to CCR2+ Proinflammatory Subset.

Brain injury from stroke is typically considered an event exclusive to the CNS, but injury progression and repair processes are profoundly influenced by peripheral immunity. Stroke stimulates an acute inflammatory response that results in a massive infiltration of peripheral immune cells into the ischemic area. While these cells contribute to the development of brain injury, their recruitment has been considered as a key step for tissue repair. The paradoxical role of inflammatory monocytes in stroke raises the possibility that the manipulation of peripheral immune cells before infiltration into the brain could influence stroke outcome. One such manipulation is remote ischemic limb conditioning (RLC), which triggers an endogenous tolerance mechanism. We observed that mice subjected to poststroke RLC shifted circulating monocytes to a CCR2+ proinflammatory monocyte subset and had reduced acute brain injury, swelling, and improved motor/gait function in chronic stroke. The RLC benefits were observed regardless of injury severity, with a greater shift to a CCR2+ subset in severe stroke. Adoptive transfer of CCR2-deficient monocytes abolished RLC-mediated protection. The study demonstrates the importance of RLC-induced shift of monocytes to a CCR2+ proinflammatory subset in attenuating acute injury and promoting functional recovery in chronic stroke. The defined immune-mediated mechanism underlying RLC benefits allows for an evidence-based framework for the development of immune-based therapeutic strategies for stroke patients.SIGNIFICANCE STATEMENT Stroke is the leading cause of physical disability worldwide but has few treatment options for patients. Because remote ischemic limb conditioning (RLC) elicits endogenous tolerance in neither an organ- nor a tissue-specific manner, the immune system has been considered a mediator for an RLC-related benefit. Application of RLC after stroke increased a proinflammatory CCR2+ monocyte subset in the blood and the brain. RLC reduced acute stroke injury and promoted motor/gait function during the recovery phase. The RLC benefits were absent in mice that received CCR2-deficient monocytes. This preclinical study shows the importance of CCR2+ proinflammatory monocytes in RLC benefits in stroke and provides a therapeutic RLC platform as a novel immune strategy to improve outcomes in stroke patients.

Corticosterone-Mediated Body Weight Loss Is an Important Catabolic Process for Poststroke Immunity and Survival.

Background and Purpose- Stroke-induced acute severe body weight (BW) loss is associated with a high rate of mortality during a critical poststroke period. Several interventions to reduce weight loss, however, have not been successful. Currently, the biological significance of this extraordinary catabolic process is not well understood. Spleen-derived monocytes/macrophages (MMs) are the major immune cells recruited to the injured brain. The trafficking of MMs has been shown to be important for tissue repair and recovery. The purpose of the study is to investigate whether the BW reduction is essential for MM-mediated immune response for mice to survive and whether a corticosterone-mediated catabolic event underlies the processes. Methods- C57BL/6 male mice (12-week-old) were subjected to transient middle cerebral artery occlusion. BW, total MMs, and their Ly-6Chigh and Ly-6Clow subsets were determined in the spleen, blood, and the brain in poststroke mice. Poststroke survival rate and MM subsets were determined in mice with adrenalectomy, sham-adrenalectomy, and adrenalectomy mice supplemented with corticosterone. Results- Stroke reduced BW with a maximum reduction at day 3 poststroke (17.2±5.2%). The reduction at day 3 was positively linked to injury severity and selective depletion of MMs, but no other types of immune cells, in the spleen. Notably, the splenic MM depletion was significantly greater in mice with severe BW reduction (≥18% at day 3). In the blood, stroke depleted circulating MMs to a similar degree in animals with moderate and severe BW loss. Ly-6C+ monocyte infiltration in the poststroke brain was greater in mice with severe BW loss. Blocking the catabolic process by adrenalectomy significantly increased poststroke mortality, but the mortality was partially rescued by corticosterone supplement in adrenalectomy mice. Conclusions- Stroke-induced BW loss facilitates MM-mediated immune response, and the adrenal corticosterone-mediated catabolic process is necessary for poststroke survival. Visual Overview- An online visual overview is available for this article.

[GUIMIT 2019, Mexican Guideline on Immunotherapy. Guideline on the diagnosis of IgE-mediated allergic disease and immunotherapy following the ADAPTE approach]. / GUIMIT 2019, Guía Mexicana de Inmunoterapia. Guía de diagnóstico de alergia mediada por IgE e inmunoterapia aplicando el método ADAPTE.

BACKGROUND: In Mexico, allergen immunotherapy (AIT) and immunotherapy with hymenoptera venom (VIT) is traditionally practiced combining aspects of the European and American school. In addition, both types of extracts (European and American) are commercially available in Mexico. Moreover, for an adequate AIT/VIT a timely diagnosis is crucial. Therefore, there is a need for a widely accepted, up-to-date national immunotherapy guideline that covers diagnostic issues, indications, dosage, mechanisms, adverse effects and future expectations of AIT (GUIMIT 2019). METHOD: With nationwide groups of allergists participating, including delegates from postgraduate training-programs in Allergy/Immunology-forming, the guideline document was developed according to the ADAPTE methodology: the immunotherapy guidelines from European Academy of Allergy and Clinical Immunology, German Society for Allergology and Clinical Immunology, The American Academy of Allergy, Asthma and Immunology and American College of Allergy, Asthma, and Immunology were selected as mother guidelines, as they received the highest AGREE-II score among international guidelines available; their evidence conforms the scientific basis for this document. RESULTS: GUIMIT emanates strong or weak (suggestions) recommendations about practical issues directly related to in vivo or in vitro diagnosis of IgE mediated allergic diseases and the preparation and application of AIT/VIT and its adverse effects. GUIMIT finishes with a perspective on AIT modalities for the future. All the statements were discussed and voted on until > 80 % consensus was reached. CONCLUSIONS: A wide and diverse group of AIT/VIT experts issued transculturized, evidence-based recommendations and reached consensus that might improve and standardize AIT practice in Mexico.

Antecedentes: En México, la inmunoterapia con alérgenos (ITA) y con veneno de himenópteros (VIT) se practica tradicionalmente combinando criterios de las escuelas europea y estadounidense; los dos tipos de extractos están comercialmente disponibles en México. Para una ITA adecuada es crucial un diagnóstico oportuno. Objetivo: Presentar GUIMIT 2019, Guía Mexicana de Inmunoterapia 2019, de base amplia, actualizada, que abarca temas de diagnóstico, indicaciones, dosificación, mecanismos, efectos adversos de la ITA y expectativas con esta modalidad de tratamiento. Método: Con la participación de múltiples grupos mexicanos de alergólogos, que incluían los centros formadores universitarios en alergia e inmunología, se desarrolló el documento de la guía según la metodología ADAPTE. Las guías de inmunoterapia de la European Academy of Allergy and Clinical Immunology, The American Academy of Allergy, Asthma and Immunology, German Society for Allergology and Clinical Immunology y del American College of Allergy, Asthma, and Immunology se seleccionaron como guías fuente, ya que recibieron la puntuación AGREE-II más alta entre las guías internacionales disponibles; su evidencia conforma la base científica de GUIMIT 2019. Resultados: En GUIMIT 2019 se emiten recomendaciones fuertes o débiles (sugerencias) acerca de temas directamente relacionados con el diagnóstico in vivo o in vitro de las enfermedades alérgicas mediadas por IgE, la preparación y aplicación de ITA o VIT y sus efectos adversos; se incluye la revisión de las modalidades de ITA para el futuro. Todos los argumentos que se exponen fueron discutidos y votados con > 80 % de aprobación. Conclusión: Un grupo amplio y diverso de expertos en ITA y VIT emitió recomendaciones transculturizadas basadas en evidencia, que alcanzaron consenso; con ellas se pretende mejorar y homologar la práctica de la inmunoterapia en México.