The effect of functional exercise along with online nutritional education on inflammatory biomarkers in children with autism spectrum disorder during COVID-19 pandemic: a randomized clinical trial

Background and Objectives: Autism spectrum disorder (ASD) is a neuro-developmental disorder which is mostly caused by deficits in social interactions. Lack of physical activity and poor nutritional habits are common problems in these patients which may be exaggerated by the Covid-19 pandemic. The study aims to assess the effect of functional training along with online nutrition education on inflammatory biomarkers in children with ASD. Subjects and Methods: In this randomized controlled clinical trial, 80 children with ASD (age=9.73+or-1.29 years, weight=49.94+or-2.08 kg, height=146.08+or-40 cm, body mass index=24.71 +or-1.48 kg/m2) were randomly divided into four groups of training, education, training+ education, and control. The interventions lasted for 8 weeks. The inflammatory biomarkers including white blood cell (WBC) count, C-reactive protein (CRP) level, neutrophil count, eosinophil count, and basophil count were assessed (using blood samples collected from antecubital vein) before and after the interventions. Results: There was no significant difference between the groups before the interventions (P>0.05). After the intervention, the results showed a significant decrease in WBC (P<0.001), CRP (P=0.001), neutrophils (sig.=0.009), and eosinophil (P=0.003) in all groups. Basophil count decreased in all groups (P=0.01) except in the education group. Conclusion: Functional training and online nutrition education are beneficial interventions for management of inflammatory biomarkers in children with ASD which can be used during the Covid-19 pandemic.

Translating the biology of ß common receptor-engaging cytokines into clinical medicine.

The family of cytokines that comprises IL-3, IL-5, and GM-CSF was discovered over 30 years ago, and their biological activities and resulting impact in clinical medicine has continued to expand ever since. Originally identified as bone marrow growth factors capable of acting on hemopoietic progenitor cells to induce their proliferation and differentiation into mature blood cells, these cytokines are also recognized as key mediators of inflammation and the pathobiology of diverse immunologic diseases. This increased understanding of the functional repertoire of IL-3, IL-5, and GM-CSF has led to an explosion of interest in modulating their functions for clinical management. Key to the successful clinical translation of this knowledge is the recognition that these cytokines act by engaging distinct dimeric receptors and that they share a common signaling subunit called ß-common or ßc. The structural determination of how IL-3, IL-5, and GM-CSF interact with their receptors and linking this to their differential biological functions on effector cells has unveiled new paradigms of cell signaling. This knowledge has paved the way for novel mAbs and other molecules as selective or pan inhibitors for use in different clinical settings.

Evaluation of Inosine-Acedoben-Dimepranol as an immunomodulator in broiler chicks vaccinated with Infectious bronchitis virus vaccine

Protecting livestock against diseases by enhancing its immunity is essential and required in poultry industry. Therefore, the aim of the present study was to evaluate the possible immunoenhancing effects of Inosine-Acedoben-Dimepranol (IAD) in broiler chicks. A total of 150 chicks were used in the present study, divided into 6 groups (25 for each) and subjected to different treatments. It has been found that IAD significantly (P 0.05) increased total leukocytic count, with increased granulocyte (neutrophils, eosinophils, basophils), lymphocyte and monocyte counts compared to control chicks. IAD significantly (P 0.05) increased total protein as a result of increased globulins in plasma when compared with those of control. IAD has been found to significantly (P 0.05) increase immune response of IB vaccine in IAD + IB vaccine-treated groups compared to control measured by ELISA. IAD exhibited antiviral effect indicated by increased survival percent of chicks challenged with virulent IB virus with survival 100% in the groups received IAD large dose plus vaccine. Data of the present study may indicate that supplying chicks with IAD in drinking water is a good recommendation in poultry industry based on its immune enhancing properties.

Epidemiological and clinical characteristics of 140 patients with Delta COVID-19 in Gansu Province

OBJECTIVE: To analyze the differences of clinical characteristics, laboratory tests and imaging examinations in patients with Novel Coronavirus(SARS-COV-2)Delta variant infection in Gansu province, so as to provide reference for the prevention and treatment of SARS-COV-2. METHODS: The medical records, laboratory tests and imaging studies of 140 patients with SARS-COV-2 Delta variant infection admitted to Yantan Branch and Zhangye Second Hospital of Lanzhou Second People's Hospital from Oct. to Dec. 2021 in Gansu province were retrospectively analyzed. RESULTS: Among the 140 infected patients, 65 were males and 75 were females. The oldest was 87 years old, and the youngest was 1 year and 8 months, with an average age of(42.65+or-20.87) years old. Twenty percent of confirmed patients had fever. The mean duration of positive nucleic acid was 19.74 days. There were significant differences in the expression levels of serum amyloid A(SAA), interleukin-6(IL-6), C-reactive protein(CRP), basophil granulocytes(BAS) and lymphocyte(LYM) in patients with different types. Pulmonary lesions were found in 101 patients(72.14%) by imaging, and the proportion of abnormal lung imaging in mild, ordinary and severe patients accounted for 55.81%, 73.13% and 100% respectively. CONCLUSION: The majority of patients with COVID-19 Delta infection in Gansu province were mild and ordinary type. There were fewer fever patients. The main clinical manifestations were cough, expectoration and pharyngeal discomfort. Severe and critically ill patients are older and have more underlying diseases.

Role of Basophils in a Broad Spectrum of Disorders.

Basophils are the rarest granulocytes and have long been overlooked in immunological research due to their rarity and similarities with tissue-resident mast cells. In the last two decades, non-redundant functions of basophils have been clarified or implicated in a broad spectrum of immune responses, particularly by virtue of the development of novel analytical tools for basophils. Basophils infiltrate inflamed tissues of patients with various disorders, even though they circulate in the bloodstream under homeostatic conditions. Depletion of basophils results in the amelioration or exaggeration of inflammation, depending on models of disease, indicating basophils can play either beneficial or deleterious roles in a context-dependent manner. In this review, we summarize the recent findings of basophil pathophysiology under various conditions in mice and humans, including allergy, autoimmunity, tumors, tissue repair, fibrosis, and COVID-19. Further mechanistic studies on basophil biology could lead to the identification of novel biomarkers or therapeutic targets in a broad range of diseases.

IFN-γ Induces PD-L1 Expression in Primed Human Basophils.

Programmed death-ligand 1 (PD-L1) plays a key role in maintaining immune tolerance and also in immune evasion of cancers and pathogens. Though the identity of stimuli that induce PD-L1 in various human innate cells and their function are relatively well studied, data on the basophils remain scarce. In this study, we have identified one of the factors, such as IFN-γ, that induces PD-L1 expression in human basophils. Interestingly, we found that basophil priming by IL-3 is indispensable for IFN-γ-induced PD-L1 expression in human basophils. However, priming by other cytokines including granulocyte-macrophage colony-stimulating factor (GM-CSF) and thymic stromal lymphopoietin (TSLP) was dispensable. Analyses of a published microarray data set on IL-3-treated basophils indicated that IL-3 enhances IFNGR2, one of the chains of the IFNGR heterodimer complex, and CD274, thus providing a mechanistic insight into the role of IL-3 priming in IFN-γ-induced PD-L1 expression in human basophils.

SARS-CoV-2 Induces Cytokine Responses in Human Basophils.

Basophils play a key role in the orientation of immune responses. Though the interaction of SARS-CoV-2 with various immune cells has been relatively well studied, the response of basophils to this pandemic virus is not characterized yet. In this study, we report that SARS-CoV-2 induces cytokine responses and in particular IL-13, in both resting and IL-3 primed basophils. The response was prominent under IL-3 primed condition. However, either SARS-CoV-2 or SARS-CoV-2-infected epithelial cells did not alter the expression of surface markers associated with the activation of basophils, such as CD69, CD13 and/or degranulation marker CD107a. We also validate that human basophils are not permissive to SARS-CoV-2 replication. Though increased expression of immune checkpoint molecule PD-L1 has been reported on the basophils from COVID-19 patients, we observed that SARS-CoV-2 does not induce PD-L1 on the basophils. Our data suggest that basophil cytokine responses to SARS-CoV-2 might help in reducing the inflammation and also to promote antibody responses to the virus.

Basophils and Mast Cells in COVID-19 Pathogenesis.

Basophils and mast cells are among the principal inducers of Th2 responses and have a crucial role in allergic and anti-parasitic protective immunity. Basophils can function as antigen-presenting cells that bind antigens on their surface and boost humoral immune responses, inducing Th2 cell differentiation. Their depletion results in lower humoral memory activation and greater infection susceptibility. Basophils seem to have an active role upon immune response to SARS-CoV-2. In fact, a coordinate adaptive immune response to SARS-CoV-2 is magnified by basophils. It has been observed that basophil amount is lower during acute disease with respect to the recovery phase and that the grade of this depletion is an important determinant of the antibody response to the virus. Moreover, mast cells, present in a great quantity in the nasal epithelial and lung cells, participate in the first immune response to SARS-CoV-2. Their activation results in a hyperinflammatory syndrome through the release of inflammatory molecules, participating to the "cytokine storm" and, in a longer period, inducing pulmonary fibrosis. The literature data suggest that basophil counts may be a useful prognostic tool for COVID-19, since their reduction is associated with a worse prognosis. Mast cells, on the other hand, represent a possible therapeutic target for reducing the airway inflammation characteristic of the hyperacute phase of the disease.

Ruling Out Coronavirus Disease 2019 in Patients with Pneumonia: The Role of Blood Cell Count and Lung Ultrasound.

Coronavirus disease 2019 (COVID-19) is characterized by a distinctive blood leucocyte pattern and B-lines on lung ultrasound (LUS) as marker of alveolar-interstitial syndrome. We aimed to evaluate the accuracy of blood leucocyte count alone or in combination with LUS for COVID-19 diagnosis. We retrospectively enrolled consecutive patients diagnosed with community acquired pneumonia (CAP) at hospital admission to derive and validate cutoff values for blood cell count that could be predictive of COVID-19 before confirmation by the nucleic acid amplification test (NAAT). Cutoff values, generated and confirmed in inception (41/115, positive/negative patients) and validation (100/180, positive/negative patients) cohorts, were ≤17 and ≤10 cells/mm3 for basophils and eosinophils, respectively. Basophils and/or eosinophils below cutoff were associated with sensitivity of 98% (95%CI, 94-100) and negative likelihood ratio of 0.04 (95%CI, 0.01-0.11). In a subgroup of 265 subjects, the sensitivity of B-line on LUS was 15% lower (p < 0.001) than that of basophils and/or eosinophils below cutoff. The combination of B-lines with basophils and eosinophils below cutoff was associated with a moderate increase of the positive likelihood ratio: 5.0 (95%CI, 3.2-7.7). In conclusion, basophil and eosinophil counts above the generated cutoff virtually rule out COVID-19 in patients with CAP. Our findings can help optimize patient triage pending the NAAT results.

White Blood Cells and Severe COVID-19: A Mendelian Randomization Study.

Increasing evidence shows that white blood cells are associated with the risk of coronavirus disease 2019 (COVID-19), but the direction and causality of this association are not clear. To evaluate the causal associations between various white blood cell traits and the COVID-19 susceptibility and severity, we conducted two-sample bidirectional Mendelian Randomization (MR) analyses with summary statistics from the largest and most recent genome-wide association studies. Our MR results indicated causal protective effects of higher basophil count, basophil percentage of white blood cells, and myeloid white blood cell count on severe COVID-19, with odds ratios (OR) per standard deviation increment of 0.75 (95% CI: 0.60-0.95), 0.70 (95% CI: 0.54-0.92), and 0.85 (95% CI: 0.73-0.98), respectively. Neither COVID-19 severity nor susceptibility was associated with white blood cell traits in our reverse MR results. Genetically predicted high basophil count, basophil percentage of white blood cells, and myeloid white blood cell count are associated with a lower risk of developing severe COVID-19. Individuals with a lower genetic capacity for basophils are likely at risk, while enhancing the production of basophils may be an effective therapeutic strategy.