The historical transformation of individual concepts into populational ones: an explanatory shift in the gestation of the modern synthesis.

In this paper, I will conduct three interrelated analyses. First, I will develop an analysis of various concepts in the history of biology that used to refer to individual-level phenomena but were then reinterpreted by the Modern Synthesis in terms of populations. Second, a similar situation can be found in contemporary evolutionary theory. While different approaches reflect on the causal role of developing organisms in evolution, proponents of the Modern Synthesis refrain from any substantial change by reinterpreting and explaining individual-level phenomena from a population perspective. Finally, I will approach these historical and contemporary debates by arguing for the statistical reading of natural selection, which holds that explanations by natural selection are statistical. My main conclusion is that the historical conceptual reinterpretations belong to a new explanatory strategy developed by the Modern Synthesis based on population thinking. Adopting the statistical point of view has three advantages for the issues discussed in this paper. First, understanding historical conceptual change as part of an explanatory shift fits with the emergence of population biology as a discipline that employs statistical methods. Second, concerning current debates in evolutionary biology, the statisticalist reading can validate the goal of both sides of the dispute. It ascribes an invaluable role to the population statistical explanation of the MS and also commends the study of developmental and organismal causes of adaptive evolution. Finally, the division of explanatory roles in evolutionary biology, embarrassed by statisticalism, can be related to the different interpretations that important biological concepts have undergone throughout history and contemporary biology, i.e., that the division of explanatory roles allows for a division of conceptual interpretations.

Component-resolved diagnosis in childhood and prediction of asthma in early adolescence: A birth cohort study.

INTRODUCTION: Component-resolved diagnosis (CRD) has been decisive in exploring the mechanisms of IgE sensitization, but the predictive ability to detect asthma has not been addressed. We aim to develop and evaluate the performance of a personalized predictive algorithm for asthma that integrates information on allergic sensitization using CRD. METHODS: One thousand one hundred one twenty-five children from the Generation XXI birth cohort were randomly selected to perform a screening test for allergic sensitization and a subsample was characterized using CRD against 112 allergen components. Allergen components were analyzed using volcano plots and partial least squares (PLS) analysis. Logistic regression was performed to assess the associations between the obtained latent components (LC) and allergic outcomes (asthma, rhinitis, eczema) including other potential predictors used in previous asthma risk scores. The accuracy of the model in predicting asthma was assessed using Receiver Operating Characteristic (ROC) curve statistics. RESULTS: In the PLS, the first LC was positively associated with asthma, rhinitis, and eczema. This LC was mainly driven by positive weights for Der p 1/2/23, Der f 1/2, and Fel d 1. The main components in the second LC were pollen and food allergens. History of early wheezing and parental allergy were included in the predictive model and the area under the curve improved to 0.82. CONCLUSIONS: This is the first approach to improve the clinical applicability of CRD by combining CRD and clinical data to predict asthma at 13 years. Sensitization to distinct allergen molecules seems relevant to improve the accuracy of asthma prediction models.

Exhaled breath condensate pH determinants in school-aged children: A population-based study.

BACKGROUND: Exhaled breath condensate (EBC) pH is a promising biomarker of airway inflammation. Lack of method standardization and interstudy variability precludes its use in clinical practice. While endogenous determinants have been described, underlying mechanisms for variability are mostly unknown. Thus, we aimed to assess the association between asthma and EBC pH in children, while studying potential environmental factors for interstudy variability. METHODS: A cross-sectional analysis of exhaled breath condensates from 613 children, aged 7-12 years, was conducted. Assessments included lung function and airway reversibility, exhaled nitric oxide, allergic sensitization, and body mass index (BMI). Indoor air quality (IAQ) was assessed in children's classrooms during 5 school days. Post-deaeration EBC pH showed a bimodal distribution, and the sample was split into acidic and alkaline groups. Regression models were constructed to assess the effects of asthma and asthma adjusted to IAQ parameters on EBC pH. RESULTS: Following adjustment to gender and BMI, asthma was significantly associated with a lower EBC pH in the acidic group. The effect of asthma on EBC pH was independent of IAQ, in both groups. In the acidic group, EBC pH was significantly affected by temperature [ß = -0.09 (-0.15, -0.02)] and PM 2.5 concentration [ß = -0.16 (-0.32, -0.01)], and in the alkaline group by relative humidity [ß = 0.07 (0.02, 0.13)] and concentration of endotoxins [ß = -0.06 (-0.1, -0.01)]. CONCLUSION: Our study shows that in addition to individual determinants such as asthma, environmental factors may influence and should be taken into consideration when interpreting EBC pH level in children.

Human volatilome analysis using eNose to assess uncontrolled asthma in a clinical setting.

BACKGROUND: Analyses of exhaled volatile organic compounds (VOCs) have shown promising results when distinguishing individuals with asthma. Currently, there are no biomarkers for uncontrolled asthma. Therefore, we aimed to assess, in a real-life clinical setting, the ability of the exhaled VOC analysis, using an electronic nose (eNose), to identify individuals with uncontrolled asthma. METHODS: A cross-sectional study was conducted, and breath samples from 199 participants (130 females, aged 6-78, 66% with asthma) were analysed using an eNose. A multivariate unsupervised cluster analysis, using the resistance data from 32 sensors, could distinguish three clusters of VOC patterns in the training and testing groups. Comparisons between the clusters were performed using the one-way ANOVA, Kruskal-Wallis and chi-squared tests. RESULTS: In the training set (n = 121), three different clusters covering asthma, lung function, symptoms in the previous 4 weeks and age were identified. The pairwise comparisons showed significant differences with respect to chest tightness during exercise, dyspnoea and gender. These findings were confirmed in the testing set (n = 78) where the training model identified three clusters. The participants who reported fewer respiratory symptoms (dyspnoea and night-time awakenings) were grouped into one cluster, while the others comprised participants who showed similar poor control over symptoms with the distribution of the individuals with asthma being significantly different between them. CONCLUSIONS: In a clinical setting, the analysis of the exhaled VOC profiles using an eNose could be used as a fast and noninvasive complementary assessment tool for the detection of uncontrolled asthma symptoms.

The oral bacteriomes of patients with allergic rhinitis and asthma differ from that of healthy controls.

Allergic rhinitis and asthma are two of the most common chronic respiratory diseases in developed countries and have become a major public health concern. Substantial evidence has suggested a strong link between respiratory allergy and upper airway dysbacteriosis, but the role of the oral bacteriota is still poorly understood. Here we used 16S rRNA massive parallel sequencing to characterize the oral bacteriome of 344 individuals with allergic rhinitis (AR), allergic rhinitis with asthma (ARAS), asthma (AS) and healthy controls (CT). Four of the most abundant (>2%) phyla (Actinobacteriota, Firmicutes, Fusobacteriota, and Proteobacteria) and 10 of the dominant genera (Actinomyces, Fusobacterium, Gemella, Haemophilus, Leptotrichia, Neisseria, Porphyromonas, Prevotella, Streptococcus, and Veillonella) in the oral cavity differed significantly (p ≤ 0.03) between AR, ARAS or AS and CT groups. The oral bacteriome of ARAS patients showed the highest intra-group diversity, while CT showed the lowest. All alpha-diversity indices of microbial richness and evenness varied significantly (p ≤ 0.022) in ARAS vs. CT and ARAS vs. AR, but they were not significantly different in AR vs. CT. All beta-diversity indices of microbial structure (Unifrac, Bray-Curtis, and Jaccard distances) differed significantly (p ≤ 0.049) between each respiratory disease group and controls. Bacteriomes of AR and ARAS patients showed 15 and 28 upregulated metabolic pathways (PICRUSt2) mainly related to degradation and biosynthesis (p < 0.05). A network analysis (SPIEC-EASI) of AR and ARAS bacteriomes depicted simpler webs of interactions among their members than those observed in the bacteriome of CT, suggesting chronic respiratory allergic diseases may disrupt bacterial connectivity in the oral cavity. This study, therefore, expands our understanding of the relationships between the oral bacteriome and allergy-related conditions. It demonstrates for the first time that the mouth harbors distinct bacteriotas during health and allergic rhinitis (with and without comorbid asthma) and identifies potential taxonomic and functional microbial biomarkers of chronic airway disease.

Nasal Bacteriomes of Patients with Asthma and Allergic Rhinitis Show Unique Composition, Structure, Function and Interactions.

Allergic rhinitis and asthma are major public health concerns and economic burdens worldwide. However, little is known about nasal bacteriome dysbiosis during allergic rhinitis, alone or associated with asthma comorbidity. To address this knowledge gap we applied 16S rRNA high-throughput sequencing to 347 nasal samples from participants with asthma (AS = 12), allergic rhinitis (AR = 53), allergic rhinitis with asthma (ARAS = 183) and healthy controls (CT = 99). One to three of the most abundant phyla, and five to seven of the dominant genera differed significantly (p < 0.021) between AS, AR or ARAS and CT groups. All alpha-diversity indices of microbial richness and evenness changed significantly (p < 0.01) between AR or ARAS and CT, while all beta-diversity indices of microbial structure differed significantly (p < 0.011) between each of the respiratory disease groups and controls. Bacteriomes of rhinitic and healthy participants showed 72 differentially expressed (p < 0.05) metabolic pathways each related mainly to degradation and biosynthesis processes. A network analysis of the AR and ARAS bacteriomes depicted more complex webs of interactions among their members than among those of healthy controls. This study demonstrates that the nose harbors distinct bacteriotas during health and respiratory disease and identifies potential taxonomic and functional biomarkers for diagnostics and therapeutics in asthma and rhinitis.

Bone and Cytokine Markers Associated With Bone Disease in Systemic Mastocytosis.

BACKGROUND: Mastocytosis encompasses a heterogeneous group of diseases characterized by tissue accumulation of clonal mast cells, which frequently includes bone involvement. Several cytokines have been shown to play a role in the pathogenesis of bone mass loss in systemic mastocytosis (SM), but their role in SM-associated osteosclerosis remains unknown. OBJECTIVE: To investigate the potential association between cytokine and bone remodeling markers with bone disease in SM, aiming at identifying biomarker profiles associated with bone loss and/or osteosclerosis. METHODS: A total of 120 adult patients with SM, divided into 3 age and sex-matched groups according to their bone status were studied: (1) healthy bone (n = 46), (2) significant bone loss (n = 47), and (3) diffuse bone sclerosis (n = 27). Plasma levels of cytokines and serum baseline tryptase and bone turnover marker levels were measured at diagnosis. RESULTS: Bone loss was associated with significantly higher levels of serum baseline tryptase (P = .01), IFN-γ (P = .05), IL-1ß (P = .05), and IL-6 (P = .05) versus those found in patients with healthy bone. In contrast, patients with diffuse bone sclerosis showed significantly higher levels of serum baseline tryptase (P < .001), C-terminal telopeptide (P < .001), amino-terminal propeptide of type I procollagen (P < .001), osteocalcin (P < .001), bone alkaline phosphatase (P < .001), osteopontin (P < .01), and the C-C Motif Chemokine Ligand 5/RANTES chemokine (P = .01), together with lower IFN-γ (P = .03) and RANK-ligand (P = .04) plasma levels versus healthy bone cases. CONCLUSIONS: SM with bone mass loss is associated with a proinflammatory cytokine profile in plasma, whereas diffuse bone sclerosis shows increased serum/plasma levels of biomarkers related to bone formation and turnover, in association with an immunosuppressive cytokine secretion profile.

Mast Cell Activation Syndromes: Comparison Between Two Scoring Models to Predict for Mast Cell Clonality.

BACKGROUND: The Red Española de Mastocitosis (Spanish Network on Mastocytosis) score (REMAs) and the National Institutes of Health idiopathic clonal anaphylaxis score (NICAS) were developed for more efficient screening of mast cell (MC) clonality in MC activation syndromes. In a limited idiopathic anaphylaxis case series, the NICAS showed higher accuracy compared with the REMAs. OBJECTIVE: To compare the performance of the REMAs against the NICAS in the diagnosis of MC clonality. METHODS: We compared the diagnostic value of the REMAs against the NICAS in 182 patients (63% men, median age 56 years) who presented with anaphylaxis triggered by Hymenoptera venom allergy (45%), drugs (15%), food (11%), idiopathic anaphylaxis (20%), and mixed causes (10%). KIT mutation was assessed in parallel in whole blood and bone marrow (BM) and, when negative, in highly purified BM MC. TPSAB1 was genotyped in a subset of 71 patients. RESULTS: We found higher accuracy and rates of correctly classified patients for the REMAs (82% and 84%) compared with the NICAS (75% and 75%; P = .02 and P = .03, respectively), particularly among men (P = .05), patients with systemic mastocytosis (P = .05), those presenting anaphylaxis owing to any cause featuring urticaria (P = .04), cardiovascular symptoms (P = .02), and/or presyncope (P = .02) and those with a blood-negative/BM-positive KIT mutational profile (P = .002), but not hereditary α-tryptasemia-associated genotypes. Combined assessment of the REMAs and KITD816V in blood yielded an overall improved classification efficiency of 86% versus 84% for REMAs. CONCLUSIONS: The combined use of the REMAs and blood detection of KITD816V is recommended, but more sensitive blood-based molecular assays to detect KITD816V are needed.

Anisakis Allergy: Raising Awareness.

INTRODUCTION: Ingestion of Anisakis is a common cause of allergic reactions to seafood in countries in which undercooked/raw seafood is part of gastronomic traditions. Despite current trends for the ingestion of raw/marinated/undercooked fish, the prevalence rate of anisakiasis and allergy to Anisakis is still considered to be low in Portugal. We aimed to review the current pathogenic mechanisms, the clinical and diagnostic approach of Anisakis allergy, and Anisakis-related eviction measures, while raising awareness to this problem. MATERIAL AND METHODS: Literature search in the MEDLINE and Scopus databases, regarding Anisakis allergy. CONCLUSION: Assessment of sensitization to Anisakis should be included in the workup study of urticaria/angioedema and anaphylaxis, as there is a rise in consumption of raw and undercooked fish. Ingestion of previously frozen and properly cooked fish appears to be safe for most patients who are allergic to Anisakis.

Introdução: A ingestão de Anisakis é uma causa frequente de alergia a pescado, em países onde o hábito de ingerir estes alimentos crus/pouco cozinhados faz parte das tradições gastronómicas. Apesar do aumento na frequência de ingestão de peixe cru/marinado/pouco cozinhado que se verifica em Portugal, a prevalência de anisaquíase e alergia ao Anisakis continua a ser considerada como sendo baixa. O nosso objectivo foi rever os mecanismos fisiopatológicos da alergia a Anisakis, a abordagem clínica e diagnóstica, e as medidas de evicção de Anisakis. Em simultâneo, pretendemos consciencializar para este problema de saúde crescente. Material e Métodos: Foi efetuada uma pesquisa e revisão bibliográfica nas bases de dados MEDLINE e Scopus, sobre alergia ao Anisakis e anisaquíase. Conclusão: A avaliação da sensibilização ao Anisakis deve ser incluída no estudo inicial da urticária/angioedema e anafilaxia, dado que o consumo de peixe cru e malcozinhado está a aumentar. A ingestão de peixe previamente congelado e sujeito a uma cocção correta parece ser segura para a grande maioria dos doentes alérgicos ao Anisakis.

Cystic lymphangioma of the pancreatic head treated by enucleation: Case report and literature review.

INTRODUCTION: The widespread use of imaging methods has led to an increased identification of asymptomatic Pancreatic Cystic Lymphangiomas (PCL), a rare entity for which available information is very limited. PRESENTATION OF CASE: We present the case of an asymptomatic 61-year-old male, submitted to elective enucleation of a pancreatic head PCL at our institution. After four years of follow-up the patient is doing well and has no clinical or imaging signs of recurrence. DISCUSSION: Though rare, PCL should be included in the differential diagnosis of pancreatic cystic neoplasms. All efforts should be made to ascertain a preoperative diagnosis, as expectant follow-up could be a reasonable approach in asymptomatic patients and/or poor surgical candidates. In the face of an uncertain diagnosis, complete surgical excision may be the treatment of choice. CONCLUSION: The medical community worldwide should be encouraged to report all cases of PCL, as to increment the overall knowledge about this lesion.

Supply of Antioxidants vs. Recruit Firefighters' Cellular Immune Status: A Randomized Double-Blinded Placebo-Controlled Parallel-Group Trial.

Background: Physical exercise can affect the immune system. We studied the effect of antioxidants on hematological and immune biomarkers after heavy training. Methods: 24 well-trained and well-fed male firefighters were randomly divided into supplemented and placebo groups, and tested for immunology-related variables using venous blood samples in the fasting state, pre- (M1) and post- (M2) five weeks of daily micronutrient supplementation (15 mg of beta-carotene, 200 mg of vitamin C, 136 mg of vitamin E, 200 µg of selenium, 15 mg of zinc, 100 mg of magnesium). Total leukocytes and a differential count for five populations were determined using standard procedures (MAXM­Beckman Coulter Diagnostics; Brea, CA, USA). Lymphocyte subsets were determined through immunophenotyping. Results: Although all values were within the normal range for healthy adults and athletes in the supplemented group (SG), mean CD3+CD8+, CD8+ and CD16+CD56+ decreased (p < 0.05; small to moderate effects), while mean CD4+, CD19+ and CD4+/CD8+ increased (p < 0.05; small effects) after five-weeks. Regarding the placebo group (PG), higher total leukocyte count (p < 0.05; trivial effect) and natural killer cells percentage (CD16+CD56+; p < 0.05; moderate effect) were observed when comparing M1 and M2. Conclusions: Antioxidants supplementation did not alter well-fed male firefighters recruit firefighters' immune cell response during the five-week physical training program.

COVID-19 Vaccination Is Safe among Mast Cell Disorder Patients, under Adequate Premedication.

Reported cases of anaphylaxis following COVID-19 vaccination raised concerns about the safety of these vaccines, namely in patients suffering from clonal mast cell (MC) disorders-a heterogenous group of disorders in which patients may be prone to anaphylaxis caused by vaccination. This study aimed to assess the safety of COVID-19 vaccines in patients with clonal MC disorders. We performed an ambidirectional cohort study with 30 clonal MC disorder patients (n = 26 in the prospective arm and n = 4 in the retrospective arm), that were submitted to COVID-19 vaccination. Among these, 11 (37%) were males, and median age at vaccination date was 41 years (range: 5y to 76y). One patient had prior history of anaphylaxis following vaccination. Those in the prospective arm received a premedication protocol including H1- and H2-antihistamines and montelukast, while those in the retrospective arm did not premedicate. Overall, patients received a total of 81 doses, 73 under premedication and 8 without premedication. No MC activation symptoms were reported. COVID-19 vaccination seems to be safe in patients with clonal mast cell disorders, including those with prior anaphylaxis following vaccination. Robust premedication protocols may allow for vaccination in ambulatory settings.

Mastocytosis presenting with mast cell-mediator release-associated symptoms elicited by cyclo oxygenase inhibitors: prevalence, clinical, and laboratory features.

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently avoided in mastocytosis, because of a potential increased risk for drug hypersensitivity reactions (DHRs) due to inhibition of cyclo-oxygenase (COX), subsequent depletion of prostaglandin E2 and release of leukotrienes. OBJECTIVES: Here, we aimed at determining the prevalence of mast cell (MC) mediator release symptoms triggered by NSAIDs in mastocytosis patients and the associated clinical and laboratory features of the disease. METHODS: Medical records from 418 adults to 223 pediatric mastocytosis patients were retrospectively reviewed. Patients were classified according to tolerance patterns to NSAIDs and other COX inhibitors (COXi) and compared for epidemiological, clinical and laboratory findings. RESULTS: Overall, 87% of adults and 91% of pediatric patients tolerated NSAIDs and other COXi. Among adult and pediatric patients presenting DHRs, 5% and 0% reacted to multiple NSAIDs, 4% and 0.7% were single reactors, and 3% and 8% were single reactors with known tolerance to paracetamol but unknown tolerance to other COXi, respectively. Among adults, hypersensitivity to ≥2 drugs was more frequent among females (p = 0.009), patients with prior history of anaphylaxis to triggers other than NSAIDs or other COXi and Hymenoptera venom (p = 0.009), presence of baseline flushing (p = 0.02), baseline serum tryptase ≥48 ng/ml (p = 0.005) and multilineage KIT mutation (p = 0.02). In contrast, tolerance to NSAIDs and other COXi was more frequent among males (p = 0.02), in patients with anaphylaxis caused by Hymenoptera venom (p = 0.02), among individuals who had skin lesions due to mastocytosis (p = 0.01), and in cases that had no baseline pruritus (p = 0.006). Based on these parameters, a score model was designed to stratify mastocytosis patients who have never received NSAIDs or other COXi apart from paracetamol, according to their risk of DHR. CONCLUSIONS: Our results suggest that despite the frequency of MC mediator related symptoms elicited by NSAIDs and other COXi apart from paracetamol is increased among mastocytosis patients versus the general population, it is lower than previously estimated and associated with unique disease features. Patients that tolerated NSAIDs and other COXi following disease onset should keep using them. In turn, adults with unknown tolerance to such drugs and a positive score should be challenged with a preferential/selective COX-2 inhibitor, while the remaining may be challenged with ibuprofen.

AlergiaPT: A Portuguese media campaign to inspire people with allergies to make a positive change in their life.

Allergic diseases comprise a significant cause of morbidity worldwide and a substantial burden on the health and medical systems of both developed and emerging economies. Although highly prevalent, relatively severe, and largely impactful on the quality of life of patients, allergic diseases are commonly trivialized. Increasing awareness of the relevance of allergic diseases as a major public health problem might lead to an improved acknowledgment by governments and health authorities. Based on the positive impact that media campaigns might have on health-related behaviors, as well as the large use of social media by different types of users, social media might be used as a powerful tool for spreading awareness and education even more effective than traditional face-to-face communication. Therefore, we aimed to develop a social media-based communication program, the AlergiaPT, reaching all stakeholders, to increase the awareness of allergic diseases tackling the causes, prevention, control, and economic impact. The AlergiaPT will provide user-generated and interactive content toward engagement, include both long-form and short-form video productions toward education, as well as stories and time-sensitive content toward empowerment. It will be targeted to all populations, engaging different stakeholders. Contents will address the 5 campaign goals: i) allergy health is promoted; ii) tolerance is actively reinforced, and avoidance reduced; iii) treatment control and guided self-management of patients of asthma, rhinitis, food allergy, and atopic eczema are strengthened; iv) recognition and treatment of severe allergy and anaphylaxis are improved, and v) indoor air quality is promoted. Engagement on the campaign will be promoted through stepwise educational takeaways meetings using different social media, and targeting all audience groups, by promoting the organization of resources for common goals and the involvement of social media to improve public awareness. The impact of AlergiaPT will be assessed through google analytics.

Enucleation of a giant symptomatic gastric lipoma, a safe surgical approach.

Gastric lipomas are rare, representing 2-3% of all benign tumours of the stomach. Most of these stomach neoplasms are small and detected incidentally during endoscopic or radiology evaluations. Computed tomography is highly specific imaging for lipoma diagnosis. Endoscopy and endoscopic ultrasound are other important diagnostic modalities to confirm the diagnosis. Identifying typical features can avoid biopsy or surgery in asymptomatic patients. In patients with larger lesions, usually more than 2 cm, clinical presentation may encompass haemorrhage, abdominal pain, pyloric obstruction and dyspepsia. As a result of its extreme low incidence, treatment is not standardized, though it is widely accepted that a symptomatic tumour mandates resection. Here, we present the case of a 60-year-old female presenting with abdominal pain and recurrent vomiting due to a giant gastric lipoma (80 × 35 × 35 mm). The patient underwent laparotomy and an enucleation was performed.

Case Report: Mastocytosis: The Long Road to Diagnosis.

Mastocytosis is a heterogeneous group of disorders characterized by expansion and accumulation of clonal mast cells. Patients mainly present with either cutaneous lesions, anaphylaxis, or both. Its low prevalence and unusual features often hinder its diagnosis for several years. We report the case of an 18-year-old male who was referred to our department with a long-standing history of atypical skin lesions, allergic rhinitis, exercise-induced bronchoconstriction and what was believed to be food-related flushing and anaphylaxis, that was later diagnosed with mastocytosis. This case illustrates the need to consider investigating for mastocytosis when recurrent anaphylaxis is present, especially in the presence of atypical skin lesions, even if normal serum basal tryptase levels and allergic sensitization are present.