COVID 19 infection clinical features in pediatric patients in Southwestern Iran: a cross-sectional, multi-center study.

With the SARS-CoV-2 pandemic, the impact of recent coronavirus, especially in children, cannot be ignored. In this study, we evaluated the SARS-CoV-2 infection rates and associated features in children less than 18 years of age in "Fars" and "Kohgiluyeh and Boyer Ahmad", provinces, Iran. 5943 children who were suspected cases to SARS-CoV-2 infection were enrolled in this study. Demographic and clinical data of SARS-CoV-2 patients were collected from 16 February 2020 to 20 June 2021. Underlying conditions were considered in this study as well. Among 5943 patients suspected COVID 19 cases, 13.51% were confirmed by real-time PCR assay. The female/male ratio was 1:1.3 with a mean age of 5.71 years. 11.2% of confirmed patients were transferred and admitted in Pediatric ICU. COVID 19 was significantly higher in children with malignancy and diabetes rather than those with other underlying diseases. Children of all ages were susceptible to COVID 19, and there is no significant difference between both sexes. Most of the COVID 19 cases were in 10-18 years old group. Among a number of children with different underlying diseases, children with malignancy had the highest rate of SARS-CoV-2 infection, followed by those with diabetes.

Frailty assessment using a novel approach based on combined motor and cardiac functions: a pilot study.

BACKGROUND: Previous research showed association between frailty and an impaired autonomic nervous system; however, the direct effect of frailty on heart rate (HR) behavior during physical activity is unclear. The purpose of the current study was to determine the association between HR increase and decrease with frailty during a localized upper-extremity function (UEF) task to establish a multimodal frailty test. METHODS: Older adults aged 65 or older were recruited and performed the UEF task of rapid elbow flexion for 20 s with the right arm. Wearable gyroscopes were used to measure forearm and upper-arm motion, and electrocardiography were recorded using leads on the left chest. Using this setup, HR dynamics were measured, including time to peak HR, recovery time, percentage increase in HR during UEF, and percentage decrease in HR during recovery after UEF. RESULTS: Fifty-six eligible participants were recruited, including 12 non-frail (age = 76.92 ± 7.32 years), and 40 pre-frail (age = 80.53 ± 8.12 years), and four frail individuals (age = 88.25 ± 4.43 years). Analysis of variance models showed that the percentage increase in HR during UEF and percentage decrease in HR during recovery were both 47% smaller in pre-frail/frail older adults compared to non-frails (p < 0.01, effect size = 0.70 and 0.62 for increase and decrease percentages). Using logistic models with both UEF kinematics and HR parameters as independent variables, frailty was predicted with a sensitivity of 0.82 and specificity of 0.83. CONCLUSION: Current findings showed evidence of strong association between HR dynamics and frailty. It is suggested that combining kinematics and HR data in a multimodal model may provide a promising objective tool for frailty assessment.

Frailty Identification Using Heart Rate Dynamics: A Deep Learning Approach.

Previous research showed that frailty can influence autonomic nervous system and consequently heart rate response to physical activities, which can ultimately influence the homeostatic state among older adults. While most studies have focused on resting state heart rate characteristics or heart rate monitoring without controlling for physical activities, the objective of the current study was to classify pre-frail/frail vs non-frail older adults using heart rate response to physical activity (heart rate dynamics). Eighty-eight older adults (≥65 years) were recruited and stratified into frailty groups based on the five-component Fried frailty phenotype. Groups consisted of 27 non-frail (age = 78.80±7.23) and 61 pre-frail/frail (age = 80.63±8.07) individuals. Participants performed a normal speed walking as the physical task, while heart rate was measured using a wearable electrocardiogram recorder. After creating heart rate time series, a long short-term memory model was used to classify participants into frailty groups. In 5-fold cross validation evaluation, the long short-term memory model could classify the two above-mentioned frailty classes with a sensitivity, specificity, F1-score, and accuracy of 83.0%, 80.0%, 87.0%, and 82.0%, respectively. These findings showed that heart rate dynamics classification using long short-term memory without any feature engineering may provide an accurate and objective marker for frailty screening.

Multitarget Drug Design, Molecular Docking and PLIF Studies of Novel Tacrine-Coumarin Hybrids for the Treatment of Alzheimer's Disease.

Alzheimer's disease (AD) as a complicated and progressive neurodegenerative disorder is the most common form of dementia and memory loss. On account of the multifactorial etiology of AD, the multi-target-directed ligand (MTDL) approach is a promising method in searching new drug candidates for this disease. Here, in this paper more than 500 tacrine-coumarin hybrids have been designed and drug-likeness, molecular docking and descriptor analysis of them were performed to find out a drug candidate with less toxicity and better binding affinity than tacrine. The docking analysis was carried out using human acetylcholineesterase (1ACJ), human butyrylcholineesterase (4BDS) and ß-secretase (BACE1) (1W51) enzymes using AutoDock 4.2 and Vina. The promising results were obtained on the types of interactions. Based on docking on three targets and PLIF studies, the compounds that have better results were introduced as good candidates for synthesis. The validity of docking protocols was verified using a set of known active ligands and decoys on these targets.

Preparation, characterization and immunological evaluation of alginate nanoparticles loaded with whole inactivated influenza virus: Dry powder formulation for nasal immunization in rabbits.

It has become important to explore more efficient and feasible influenza vaccines, since epidemics of influenza virus cause hundreds of thousands of deaths all around the world. Improving immunogenicity of parentral influenza vaccines has given rise to mucosal delivery routes. In this study, alginate nanoparticles (NPs) were efficiently synthetized by ionic gelation method and influenza virus and CpG ODN or Quillaja Saponin (QS) adjuvants were actively incorporated into alginate NPs. The prepared particles were evaluated for both humoral and cellular immune responses in rabbits' nostrils. The vaccination started with a prime dose and followed by three boosters (two intranasal (IN) on days 45 and 60 and the last dose, intramuscular (IM) on day 75). HAI titer had increased in all the samples; although, only in the group received WV + CPG suspension reached to the protective HAI titer. All the immunized rabbits elicited significantly high sIgA levels on day 75, compared to the negative and the IM groups. At the end of the study, IN administration of CpG ODN adjuvant with virus antigen induced higher IgG level than the groups vaccinated with alginate NPs with or without CpG ODN (P < 0.001). As for the cellular immunity, CpG ODN was capable of inducing significant levels of IL-4 and TNF-α, either through inoculation along with the virus suspension or as incorporated in alginate NPs. According to the obtained data, CpG ODN adjuvant showed higher immunogenic potential as part of a vaccine delivery system than QS. Moreover, applying alginate polymer as a nasal delivery system carrier was not deemed immunogenic against influenza whole virus.

Immunization Against Cutaneous Leishmaniasis by Alginate Microspheres Loaded With Autoclaved Leishmania Major (ALM) and Quillaja Saponins.

Leishmania antigens are weak immunogens and need to be potentiated by various adjuvants and delivery systems. Alginate microspheres as antigen delivery system and Quillaja saponins (QS) as immunoadjuvant have been used to enhance the immune response against Autoclaved Leishmania major (ALM). Microspheres were prepared by an emulsification technique and characterized for size, encapsulation efficiency and release profile of encapsulates. BALB/c mice were immunized three times in 3-weeks intervals using ALM plus QS loaded microspheres [(ALM+QS)ALG], ALM encapsulated with alginate microspheres [(ALM)ALG], (ALM)ALG + QS, ALM + QS, ALM alone or PBS. The intensity of infection induced by L. major challenge was assessed by measuring size of footpad swelling. The strongest protection, showed by significantly (P < 0.05) smaller footpad, were observed in mice immunized with (ALM)ALG+QS. The (ALM+QS)ALG, ALM and PBS groups showed the least protection and highest swelling, while the (ALM)ALG and ALM+QS showed an intermediate protection with no significant difference. The mice immunized with (ALM+QS)ALG showed the highest IgG2a/IgG1 ratio (P<0.05). The highest IFN-γ and IL-4 production was seen in ALM+QS (P<0.01). It is concluded that QS adjuvant has a mixed Th1/Th2 effect and has increased both humoral and cellular immune responses.

The mucosal adjuvant potential of cross-linked dextran microspheres as dry powder.

OBJECTIVES: The immunoadjuvant potential of cross-linked dextran microspheres (CDM) as absorption enhancer and Quillaja saponins (QS) as immunomodulator adjuvant was evaluated. MATERIALS AND METHODS: CDM loaded or tetanus-mixed toxoid (TT) or Quillaja saponin (QS) were nasally administered to rabbits in dry powder form, three times in 2 weeks interval and serum IgG and nasal lavage sIgA titers were determined by ELISA. RESULTS: The highest serum IgG titer was induced by parenteral immunization through alum adsorbed TT (P< 0.001). Among nasally immunized groups, the highest serum IgG titer was induced by (TT+QS)CDM (P< 0.01). Mixing of CDM with TT+QS powders (CDM+TT+QS), could not induce the high serum IgG titers as (TT+QS)CDM (P< 0.01). CDM loaded with TT+QS induced higher IgG titers than CDM loaded with TT alone (P< 0.01). No significant difference was observed in nasal lavage sIgA titers of various groups. CONCLUSION: CDM microspheres loaded with TT+QS significantly increased serum anti-TT IgG titers, but mixing of CDM with TT+QS powder could not increase IgG titers. Both QS and CDM adjuvant could not significantly increase the lavage anti-TT IgA titers.

Alginate microspheres encapsulated with autoclaved Leishmania major (ALM) and CpG-ODN induced partial protection and enhanced immune response against murine model of leishmaniasis.

A suitable adjuvant and delivery system are needed to enhance efficacy of vaccines against leishmaniasis. In this study, alginate microspheres as an antigen delivery system and CpG-ODN as an immunoadjuvant were used to enhance immune response and induce protection against an experimental autoclaved Leishmania major (ALM) vaccine. Alginate microspheres were prepared by an emulsification technique and the characteristics of the preparation such as size, encapsulation efficiency and release profile of encapsulates were studied. Mean diameter of microspheres was determined using SEM (Scanning Electron Microscopy) and particle size analyzer. The encapsulation efficiency was determined using Lowry protein assay method. The integrity of ALM antigens was assessed using SDS-PAGE. Mean diameter of microspheres was 1.8±1.0µm. BALB/c mice were immunized three times in 3-weeks intervals with ALM+CpG-ODN loaded microspheres [(ALM+CpG)(ALG)], ALM encapsulated alginate microspheres [(ALM)(ALG)], (ALM)(ALG)+CpG, ALM+CpG, ALM alone or PBS. The intensity of infection induced by L. major challenge was assessed by measuring size of footpad swelling. The strongest protection was observed in group of mice immunized with (ALM+CpG)(ALG). The groups of mice received (ALM+CpG)(ALG), (ALM)(ALG)+CpG, (ALM)(ALG) and ALM+CpG were also showed a significantly (P<0.05) smaller footpad swelling compared with the group that received either ALM alone or PBS. The mice immunized with (ALM+CpG)(ALG) or ALM+CpG showed the significantly (P<0.05) highest IgG2a/IgG1 ratio. The IFN-γ level was significantly (P<0.0001) highest in group of mice immunized with either (ALM)(ALG)+CpG or ALM+CpG. It is concluded that alginate microspheres and CpG-ODN adjuvant when are used simultaneously induced protection and enhanced immune response against ALM antigen.