Fall risk classification with posturographic parameters in community-dwelling older adults: a machine learning and explainable artificial intelligence approach.

BACKGROUND: Computerized posturography obtained in standing conditions has been applied to classify fall risk for older adults or disease groups. Combining machine learning (ML) approaches is superior to traditional regression analysis for its ability to handle complex data regarding its characteristics of being high-dimensional, non-linear, and highly correlated. The study goal was to use ML algorithms to classify fall risks in community-dwelling older adults with the aid of an explainable artificial intelligence (XAI) approach to increase interpretability. METHODS: A total of 215 participants were included for analysis. The input information included personal metrics and posturographic parameters obtained from a tracker-based posturography of four standing postures. Two classification criteria were used: with a previous history of falls and the timed-up-and-go (TUG) test. We used three meta-heuristic methods for feature selection to handle the large numbers of parameters and improve efficacy, and the SHapley Additive exPlanations (SHAP) method was used to display the weights of the selected features on the model. RESULTS: The results showed that posturographic parameters could classify the participants with TUG scores higher or lower than 10 s but were less effective in classifying fall risk according to previous fall history. Feature selections improved the accuracy with the TUG as the classification label, and the Slime Mould Algorithm had the best performance (accuracy: 0.72 to 0.77, area under the curve: 0.80 to 0.90). In contrast, feature selection did not improve the model performance significantly with the previous fall history as a classification label. The SHAP values also helped to display the importance of different features in the model. CONCLUSION: Posturographic parameters in standing can be used to classify fall risks with high accuracy based on the TUG scores in community-dwelling older adults. Using feature selection improves the model's performance. The results highlight the potential utility of ML algorithms and XAI to provide guidance for developing more robust and accurate fall classification models. Trial registration Not applicable.

The Interaction Between Prenatal Exposure to Home Renovation and Reactive Oxygen Species Genes in Cord Blood IgE Response is Modified by Maternal Atopy

PURPOSE: Although home renovation exposure during childhood has been identified as a risk factor for the development of allergy, there is limited information on the association between prenatal exposure to home renovation and cord blood (CB) IgE response. The aims of this study were to identify the effect of prenatal exposure to home renovation on CB IgE levels, and to investigate whether this exposure interacts with neonatal genes and whether the effect can be modified by maternal atopy. METHODS: This study included 1,002 mother-neonate pairs from the COhort for Childhood Origin of Asthma and allergic diseases (COCOA). Prenatal environmental factors were collected using a questionnaire. The levels of CB IgE were measured by the ImmunoCAP system, and DNA was extracted from CB. RESULTS: Exposure to home renovation during the prenatal period was associated with significantly higher levels of CB IgE only in neonates from atopic mothers, and the effect of renovation exposure on CB IgE levels persisted from 31 months before birth. Furthermore, prenatal exposure to home renovation increased the risk of CB IgE response interacting with polymorphisms of NRF2 and GSTP1 genes only in neonates from atopic mothers. CONCLUSIONS: Maternal atopy modified the effect of prenatal exposure to home renovation on CB serum IgE response as well as the interaction between the exposure and neonatal genes involved in the oxidative stress pathway. These findings suggest that the genetically susceptible offspring of atopic mothers may be more vulnerable to the effect of prenatal exposure to home renovation on the development of allergy.

Interactions Between Innate Immunity Genes and Early-Life Risk Factors in Allergic Rhinitis

PURPOSE: Allergic rhinitis (AR) is a common chronic disease. Many factors could affect the development of AR. We investigated early-life factors, such as delivery mode, feeding method, and use of antibiotics during infancy, which could affect the development of AR. In addition, how interactions between these factors and innate gene polymorphisms influence the development of AR was investigated. METHODS: A cross-sectional study of 1,828 children aged 9-12 years was conducted. Three early-life factors and AR were assessed by a questionnaire. Skin prick tests were done. Polymorphisms of TLR4 (rs1927911) and CD14 (rs2569190) were genotyped. RESULTS: Use of antibiotics during infancy increased the risk of AR (aOR [95% CI] 1.511 [1.222-2.037]) and atopic AR (aOR [95% CI], 1.565 [1.078-2.272]). There were synergistic interactions between caesarean delivery, formula feeding, and use of antibiotics in the rate of atopic AR (aOR [95% CI], 3.038 [1.256-7.347]). Additional analyses revealed that the risk for the development of AR or atopic AR subjects with the TLR4 CC genotype were highest when all the 3 early-life factors were present (aOR [95% CI], 5.127 [1.265-20.780] for AR; 6.078 [1.499-24.649] for atopic AR). In addition, the risk for the development of AR or atopic AR in subjects with the CD14 TT genotype were highest when all the 3 early-life factors were present (aOR [95% CI], 5.960 [1.421-15.002] for AR; 6.714 [1.440-31.312] for atopic AR). CONCLUSIONS: Delivery mode, feeding method, and use of antibiotics during infancy appeared to have synergistic interactions in the development of AR. Gene-environment interactions between polymorphism of innate genes and early- life risk factors might affect the development of AR.

Prenatal Particulate Matter/Tobacco Smoke Increases Infants' Respiratory Infections: COCOA Study

PURPOSE: To investigate whether prenatal exposure to indoor fine particulate matter (PM2.5) and environmental tobacco smoke (ETS) affects susceptibility to respiratory tract infections (RTIs) in infancy, to compare their effects between prenatal and postnatal exposure, and to determine whether genetic factors modify these environmental effects. METHODS: The study population consisted of 307 birth cohort infants. A diagnosis of RTIs was based on parental report of a physician's diagnosis. Indoor PM2.5 and ETS levels were measured during pregnancy and infancy. TaqMan was used for genotyping of nuclear factor erythroid 2-related factor (Nrf2) (rs6726395), glutathione-S-transferase-pi (GSTP) 1 (rs1695), and glutathione-S-transferase-mu (GSTM) 1. Microarrays were used for genome-wide methylation analysis. RESULTS: Prenatal exposure to indoor PM2.5 increased the susceptibility of lower RTIs (LRTIs) in infancy (adjusted odds ratio [aOR]=2.11). In terms of combined exposure to both indoor PM2.5 and ETS, prenatal exposure to both pollutants increased susceptibility to LRTIs (aOR=6.56); however, this association was not found for postnatal exposure. The Nrf2 GG (aOR=23.69), GSTM1 null (aOR=8.18), and GSTP1 AG or GG (aOR=7.37) genotypes increased the combined LRTIs-promoting effects of prenatal exposure to the 2 indoor pollutants. Such effects of prenatal indoor PM2.5 and ETS exposure were not found for upper RTIs. CONCLUSIONS: Prenatal exposure to both indoor PM2.5 and ETS may increase susceptibility to LRTIs. This effect can be modified by polymorphisms in reactive oxygen species-related genes.

Association Between Antibiotic Exposure, Bronchiolitis, and TLR4 (rs1927911) Polymorphisms in Childhood Asthma

PURPOSE: The complex interplay between environmental and genetic factors plays an important role in the development of asthma. Several studies have yielded conflicting results regarding the 2 asthma-related risk factors: antibiotic usage during infancy and/or a history of bronchiolitis during early life and the development of asthma. In addition to these risk factors, we also explored the effects of Toll-like receptor 4 (TLR4) polymorphism on the development of childhood asthma. METHODS: This cross-sectional study involved 7,389 middle school students who were from 8 areas of Seoul, Korea, and completed the International Study of Asthma and Allergies in Childhood questionnaire. The TLR4 polymorphism rs1927911 was genotyped in 1,395 middle school students from two areas using the TaqMan assay. RESULTS: Bronchiolitis in the first 2 years of life, antibiotic exposure during the first year of life, and parental history of asthma were independent risk factors for the development of asthma. When combined, antibiotic use and a history of bronchiolitis increased the risk of asthma (adjusted odds ratio [aOR]: 4.64, 95% confidence interval [CI]: 3.09-6.97, P value for interaction=0.02). In subjects with CC genotype of TLR4, antibiotic exposure and a history of bronchiolitis during infancy, the risk of asthma was increased, compared to subjects without these risk factors (aOR: 5.72, 95% CI: 1.74-18.87). CONCLUSIONS: Early-life antibiotic exposures and a history of bronchiolitis are risk factors for asthma in young adolescents. Polymorphisms of TLR4 modified the influence of these environmental factors. Reducing antibiotic exposure and preventing bronchiolitis during infancy may prevent the development of asthma, especially in genetically susceptible subjects.

Association between Recent Acetaminophen Use and Asthma: Modification by Polymorphism at TLR4

The risk of asthma has been increasing in parallel with use of acetaminophen, which is a potential source of oxidative stress. Toll-like receptor 4 (TLR4) plays a critical role not only in innate immunity, but also in mediating reactive oxygen species induced inflammation. Therefore, we investigated associations between acetaminophen usage and TLR4 polymorphism on asthma and bronchial hyperresponsiveness (BHR). The number of 2,428 elementary school children in Seoul and Jeongeup cities was recruited. Subjects who used acetaminophen with a family history of asthma had an increased risk of both asthma diagnosis ever and current asthma. Individuals with CT+TT genotypes at the TLR4 polymorphism, in combination with acetaminophen usage, also demonstrated an increased risk of asthma diagnosis ever (aOR, 2.08; 95% confidence interval [CI], 1.10-3.92). Family history of asthma and acetaminophen usage were risk factors for BHR. Although TLR4 was not an independent risk factor for BHR, individuals with CT+TT genotypes at the TLR4 polymorphism had an increased risk of BHR when combined with acetaminophen usage (aOR, 1.74; 95% CI, 1.03-2.94). In conclusion, acetaminophen usage may be associated with asthma and BHR in genetically susceptible subjects. This effect may be modified by polymorphism at TLR4.

Bacillus Calmette-Guerin Suppresses Asthmatic Responses via CD4+CD25+ Regulatory T Cells and Dendritic Cells

PURPOSE: Bacillus Calmette-Guerin (BCG) is known to suppress the asthmatic responses in a murine model of asthma and to induce dendritic cells (DCs) maturation. Mature DCs play a crucial role in the differentiation of regulatory T cells (Tregs), which are known to regulate allergic inflammatory responses. To investigate whether BCG regulates Tregs in a DCs-mediated manner, we analyzed in a murine model of asthma. METHODS: BALB/c mice were injected intraperitoneally with BCG or intravenously with BCG-stimulated DCs and then sensitized and challenged with ovalbumin (OVA). Mice were analysed for bronchial hyperresponsiveness (BHR), the influx of inflammatory cells in the bronchoalveolar lavage (BAL) fluid, and histopathological changes in the lung. To identify the mechanisms, IgE, IgG1 and IgG2a in the serum were analysed and the CD25+ Tregs in the mice were depleted with anti-CD25 monoclonal antibody (mAb). RESULTS: BCG and the transfer of BCG-stimulated DCs both suppressed all aspects of the asthmatic responses, namely, BHR, the production of total IgE and OVA-specific IgE and IgGs, and pulmonary eosinophilic inflammation. Anti-CD25mAb treatment reversed these effects. CONCLUSIONS: BCG can attenuate the allergic inflammation in a mouse model of asthma by a Tregs-related mechanism that is mediated by DCs.

A Novel Synthetic Mycolic Acid Inhibits Bronchial Hyperresponsiveness and Allergic Inflammation in a Mouse Model of Asthma

PURPOSE: Recognition of microbes is important to trigger the innate immune system. Mycolic acid (MA) is a component of the cell walls of mycobacteria such as Mycobacterium bovis Bacillus Calmette-Guerin. MA has immunogenic properties, which may modulate the innate and adaptive immune response. This study aimed to investigate whether a novel synthetic MA (sMA) inhibits allergic inflammatory responses in a mouse model of asthma. METHODS: BALB/c mice were injected intraperitoneally with sMA followed by sensitization and challenge with ovalbumin (OVA). Mice were examined for bronchial hyperresponsiveness (BHR), the influx of inflammatory cells into the lung tissues, histopathological changes in the lungs and CD4+CD25+Foxp3+ T cells in the spleen, and examined the response after the depleting regulatory T cells (Tregs) with an anti-CD25mAb. RESULTS: Treatment of mice with sMA suppressed the asthmatic response, including BHR, bronchoalveolar inflammation, and pulmonary eosinophilic inflammation. Anti-CD25mAb treatment abrogated the suppressive effects of sMA in this mouse model of asthma and totally depleted CD4+CD25+Foxp3+ T cells in the spleen. CONCLUSIONS: sMA attenuated allergic inflammation in a mouse model of asthma, which might be related with CD4+CD25+Foxp3+ T cell.

Gene-environment interaction between Toll-like receptor 4 and mold exposure in the development of atopic dermatitis in preschool children

PURPOSE: Genetic factors and environmental exposures are recognized as important risk factors for atopic dermatitis (AD) in children. Inflammatory responses by molds can be mediated via Toll-like receptor 4 (TLR4). The aims of this study were to investigate mold as risk factor of AD and gene-environment interaction on AD in preschool children. METHODS: We undertook a cross-sectional survey with 986 preschool children. We investigated five mold exposure measures (dampness stain, dampness damage, visible mold, mold odor, and house repair). The TLR4 polymorphism (rs1927911) was genotyped by TaqMan assay. RESULTS: The prevalence of AD was as follows: AD diagnosis by questionnaire, 35.1%; current AD (lifetime diagnosis together with symptoms in the last 12 months), 21.5%. When children with parental history of AD were exposed to mold odor during infancy and house repair during the last 12 months, the risk for current AD (adjusted odds ratio [aOR], 6.826; 95% confidence interval [CI], 2.511 to 18.554 vs. aOR, 6.143; 95% CI, 2.348 to 16.074) was further increased than only with parental history of AD. In children with the CC genotype of TLR4 polymorphism, the risk of AD was increased by mold exposure. CONCLUSION: This investigation identified that mold exposure is potential risk factor for AD in preschool children. Parental history of AD and mold exposure during infancy and the last 12 months had synergistic effect on high prevalence of AD. We identified that mold exposure and TLR4 polymorphism have an effect on the development of atopic dermatitis.

Mutations in the Filaggrin are Predisposing Factor in Korean Children With Atopic Dermatitis

PURPOSE: Filaggrin (FLG) is a key protein that facilitates the terminal differentiation of the epidermis and the formation of the skin barrier. Recent studies showed that atopic dermatitis (AD) associates closely with loss-of-function mutations in the FLG gene. Asian and European populations differ in the frequencies of FLG mutations. Several FLG mutations, including 3321delA, E2422X, K4671X, S2554X, and R501X, occur frequently in Chinese and Japanese populations. The association between three FLG null mutations and AD in Korean children was investigated. METHODS: The FLG mutations in 1,430 children (aged 0-18 years) with AD and 862 control subjects were genotyped by using the TaqMan assay. RESULTS: The FLG null mutation E2422X was not detected in any patients with AD or control subjects. The R501X null mutation was detected in only one child with AD (0.1%). Children with AD had the 3321delA deletion significantly more frequently (2.4%) than the control subjects (0.0%, P<0.001). Children with AD also had a significantly higher combined allele frequency of the three FLG null mutations (2.6%) than the controls (0.0%, P<0.001). The 3321delA null mutation did not associate significantly with AD severity (P=0.842). When the patients with AD were divided into allergic AD and non-allergic AD patient groups, these two groups did not differ in terms of the frequency of 3321delA. CONCLUSIONS: The Korean children had a lower frequency of FLG mutations than European populations. FLG null mutations may be associated with the development of AD in Korean children.

Acute Human Immunodeficiency Virus Syndrome Presenting with Hemophagocytic Lymphohistiocytosis

Hemophagocytic lymphohistiocytosis (HLH) has been described in patients with advanced stages of human immunodeficiency virus (HIV) infection, but rarely occurs during the seroconversion stage of acute HIV infection. We report a case of acute HIV syndrome that presented with virus-associated HLH. The patient recovered spontaneously without any immunomodulating therapy. This case suggests that acute HIV infection should be included in the differential diagnosis of HLH and indicates that HLH associated with acute HIV infection can have a favorable outcome.

A case of fever of unknown origin after removal of hypothalamic tumor / 대한내과학회지

The preoptic area and anterior hypothalamus plays a pivotal role in body temperature regulation, and damage in this region causes hyperthermia. This hyperthermia is particularly troublesome because of the possibility that it may reflect an occult infectious process. We report a case of fever of unknown origin in a patient after removal of neoplasm involving the hypothalamus. A 29-year old man underwent craniotomy and removal of hypothalamic choroid meningioma. Seventy days after the removal of his tumor, his body temperature began to rise. But, there was no evidence of infection, inflammatory disease, metabolic disease, drug fever and recurred tumor. Repeated administration of antipyretic agent did not reduce body temperature. So, we considered that the elevated temperature had a central basis. The patient was treated with chlorpromazine in an attempt to lower his temperature. This drug reduced successfully his body temperature.

Recently Occurring Adult Tetanus in Korea: Emphasis on Immunization and Awareness of Tetanus

Since a nationwide childhood vaccination with tetanus toxoid, tetanus has become a rare disease in Korea. However, we recently experienced 17 cases of adult tetanus in a university hospital during a 21-month period. Seventy percent of the patients were female, and the mean age was 63 yr (range, 29-87). The majority (88.2%) of the patients did not get primary vaccinations for tetanus and decennial tetanus-diph-theria toxoid booster. Most patients (88.2%), who sustained acute injury, did not seek medical care for their wounds or did not receive the prophylaxis for tetanus. Tetanus was found most frequently among farmers. Tetanus was diagnosed initially only in 53% of patients. The case-fatality ratio was 23.5%. These cases show that recently occurring tetanus in Korea is a disease, affecting the elderly and the female who may have a lower immunity against tetanus, and the farmers who are likely to be exposed to Clostridium tetani. In addition, diagnosis of tetanus is often delayed in area where cases are seen infrequently. Therefore, improved education among patients and physicians, emphasis of anti-tetanus immunization and awareness of tetanus respectively, may be essential for the prevention of disease and the reduction of its mortality.

A Case of Mesenteric Lymphadenitis Due to Mycobacterium avium Complex Infection in the Acquired Immunodeficiency Syndrome Patient / 감염

Mycobacterium avium complex (MAC) refers to infections caused by one of two nontuberculous mycobacterial species, either M. avium or M. intracellulare and the risk of MAC in patients with human immunodeficiency virus (HIV) infection increases as the CD4+ T cell number declines below 50 cells/mm3. In these patients, fever, night sweats, abdominal pain, weight loss and multiple large retroperitoneal and mesenteric lymph nodes should suggest the diagnosis of MAC infection as well as other known causes of lymphadenitis, including lymphoma, Kaposi's sarcoma, dis-seminated histoplasmosis, cryptococcosis and intraabdominal M. tuberculosis. We report an autopsy case of 55 years-old man with HIV-infection who was diagnosed mesenteric lymphadenitis due to MAC infection as a cause of fever of unknown origin during treatment of the primary central nervous system malignant B-cell lymphoma.

A Case of Toxoplasmic Encephalitis in an Advanced AIDS Patient / 감염

Toxoplasmic encephalitis (TE) is the most common cause of opportunistic central nervous system infection in advanced acquired immunodeficiency syndrome (AIDS) patients. The incidence of TE has fallen markedly after the availability of highly active antiretroviral therapy and cotrimoxazole chemoprophylaxis. TE linked to AIDS is a rare entity in Korea, but we must consider TE in the differential diagnosis of the opportunistic infections in AIDS patients. We report a case of toxoplasmic encephalitis in an advanced AIDS patient presenting as progressive right facial palsy.