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The article discusses the prevalence of food allergies and accidental allergic reactions in children, highlighting the need for tailored strategies based on age and severity. A multicenter survey involving caregivers of children with food allergies explored factors contributing to accidental exposure, such as age, food allergens, and pre-hospital responses. Findings suggest the importance of enhanced awareness, parental supervision, and patient education to prevent severe reactions and improve pre-hospital medication management, especially in children aged 4-6 years. The study emphasizes the necessity of age-appropriate education and guidance for children with food allergies to mitigate risks of accidental exposure. [Extracted from the article]

Background: Functional gastrointestinal disorders (FGIDs), including functional dyspepsia (FD) and irritable bowel syndrome (IBS), are characterized by chronic and recurrent gastrointestinal symptoms. Clinically, FD and IBS often resemble gastrointestinal dysmotility caused by autoimmune autonomic neuropathy. We examined the seropositive frequency of autoantibodies against ganglionic nicotinic acetylcholine receptors (gnAChRs) in patients presenting with FGIDs. Objective: To elucidate the seropositivity of gnAChR antibodies and the clinical features of seropositive FD and IBS. Materials and Methods: We measured autoantibodies against the gnAChR α3 and β4subunits using luciferase immunoprecipitation systems. Serum samples from patients with any autonomic symptoms were obtained from hospitals in Japan between January 2012 and August 2018 (1787 serum samples of 1381 patients). We selected FD and IBS patients and compared the clinical characteristics and prevalence of autonomic symptoms between those with seropositive and seronegative IBS and FD. Results: Nine IBS and two FD cases (one comorbid case with IBS) were found. We found four patients (36.4%) in whom gnAChR antibodies were positive in these eleven patients. Sicca symptoms were observed in three of four cases (75%) of seropositive FGID compared with zero of seven cases (0%) of seronegative FGID. Conclusions: We found patients with gnAChR antibodies in FD and IBS patients. These data will be valuable for elucidating the pathophysiology of these FGIDs and developing new treatment strategies. [ABSTRACT FROM AUTHOR]

Recent studies have shown an association between excessive smartphone use and health problems. Along with such mounting concerns, health risk information on excessive smartphone use has been presented through various media. Such information is usually aimed at making smartphone users understand the associated health risks, thereby preventing excessive use or reducing current use. However, according to self-affirmation theory, such information may pose a threat to heavy smartphone users because it implies that they are engaging in maladaptive behavior. Therefore, to defend themselves, they may not accept the information and may not be highly motivated to reduce their usage. According to self-affirmation theory, such maladaptive defensive responses can be reduced through the affirmation of important values. We examined whether self-affirmation prior to reading health risk information increased heavy users' motivation to reduce smartphone usage. Participants (142 undergraduate students aged 18–22 years) reported their mean daily smartphone use. They then completed a writing task that affirmed/did not affirm an important personal value. Next, they read an article on the health risks of smartphone overuse and reported their motivation to reduce smartphone use. As a result, when heavy users did not self-affirm, they were significantly less motivated to reduce use than light users. However, when heavy users self-affirmed, their motivation was significantly higher than when they did not self-affirm. This effect of self-affirmation was not shown in light users. These results suggest that health risk information combined with self-affirmation is effective in reducing smartphone usage by heavy users. [ABSTRACT FROM AUTHOR]

Background: Autoimmune autonomic ganglionopathy (AAG) is characterized by serum autoantibodies against the ganglionic acetylcholine receptor (gAChR). Immunomodulatory treatments may alleviate AAG symptoms, but the most appropriate treatment strategy is unclear. Objective: This study aimed to confirm the effectiveness of treatments, particularly immunotherapy, in patients with seropositive AAG in Japan, as well as to determine the most effective treatment and the best assessment method for clinical response to treatment. Methods: We collected data from a previous cohort study of patients with seropositive AAG. The clinical autonomic and extra-autonomic symptoms were objectively counted and subjectively assessed using the modified Composite Autonomic Symptom Score. Post-treatment changes in the gAChR antibody level were evaluated. Results: Thirty-one patients received immunotherapy. Among them, 19 patients received intravenous methylprednisolone; 27, intravenous immunoglobulin; 3, plasma exchange; 18, oral steroids; 2, tacrolimus; 1, cyclosporine; and 1, mycophenolate mofetil. Patients who received immunotherapy showed improvements in the total number of symptoms (from 6.2 ± 2.0 to 5.1 ± 2.0) and modified Composite Autonomic Symptom Score (from 37.4 ± 15.3 to 26.6 ± 12.8). Orthostatic intolerance, sicca, and gastrointestinal symptoms were ameliorated by immunotherapy. Immunotherapy decreased the antibody levels (gAChRα3 antibodies, from 2.2 ± 0.4 to 1.9 ± 0.4, p = 0.08; gAChRβ4 antibodies, from 1.6 ± 0.1 to 1.0 ± 0.2, p = 0.002), but antibody levels increased in 10 patients despite immunotherapy. The rate of improvement in the total number of symptoms was higher in patients with combined therapy than in patients with non-combined therapy (70.7% vs 28.6%). Conclusions: The scores in many items on the rating scale decreased after immunotherapy in patients with seropositive AAG, particularly in the combined immunotherapy group. However, more accurate assessment scales for clinical symptoms and multicenter randomized, placebo-controlled prospective studies are warranted to establish future treatment strategies. [ABSTRACT FROM AUTHOR]

LIM-kinase 1 (LIMK-1), a serine/threonine kinase containing LIM and PDZ domains, plays a role in Rac-mediated actin cytoskeletal reorganization. There is a potential connection between Rac, LIMK-1, cofilin and actin-filament dynamics. Rac prompts the kinase activity of LIMK-1, which in turn leads to phosphorylation and inactivation of cofilin. It probably also prompts a fall in the rate of actin depolymerization. LIMK-1 activity may be localized to confined regions within the cell by the binding of LIMK-1 to F-actin.

Objective: Patients with acquired autonomic dysfunction may have antibodies specific to the ganglionic nicotinic acetylcholine receptor (gAChR). However, the clinical features of children and adolescents with acquired autonomic dysfunction (AAD) remain unclear. This study aimed to determine the clinical features of pediatric patients with acquired autonomic dysfunction. Methods: This study retrospectively examined a series of patients of AAD with serum gAChR antibodies who were referred to our laboratory for antibody testing between January 2012 and April 2019. The study included 200 patients (<20 years, 20 cases; ≥20 years, 175 cases) with clinical features of AAD. Results: Upon comparing pediatric and adult patients, we found that antecedent infection and autonomic symptoms at onset with gastrointestinal symptoms occurred more frequently in children with AAD. We confirmed that four children (20.0%) met the diagnostic criteria for postural orthostatic tachycardia syndrome (POTS). A significantly higher number of children than adults had POTS (P = 0.002). In addition, upper GI dysfunction was more prevalent in children than in adults (P = 0.042). In particular, nausea and vomiting occurred in 60.0% of children with AAD and in 21.1% of adults (P < 0.001). The frequency of paralytic ileus was significantly higher in children with AAD (20.0%) relative to adults (6.3%) (P = 0.030). Regarding extra‐autonomic manifestations, encephalopathy was more frequent in children (15.0%) than in adults (1.1%) (P < 0.001). Interpretation: Pediatric AAD patients have their own clinical characteristics, and these features may be unique to children and adolescents. [ABSTRACT FROM AUTHOR]

Background: The existence of several autoantibodies suggests an autoimmune basis for gastrointestinal (GI) dysmotility. Whether GI motility disorders are features of autoimmune autonomic ganglionopathy (AAG) or are related to circulating anti-ganglionic acetylcholine receptor (gAChR) antibodies (Abs) is not known. The aim of this study was to determine the associations between autonomic dysfunction, anti-gAChR Abs, and clinical features in patients with GI motility disorders including achalasia and chronic intestinal pseudo-obstruction (CIPO).Methods: First study: retrospective cohort study and laboratory investigation. Samples from 123 patients with seropositive AAG were obtained between 2012 and 2017. Second study: prospective study. Samples from 28 patients with achalasia and 14 patients with CIPO were obtained between 2014 and 2016, and 2013 and 2017, respectively. In the first study, we analyzed clinical profiles of seropositive AAG patients. In the second study, we compared clinical profiles, autonomic symptoms, and results of antibody screening between seropositive, seronegative achalasia, and CIPO groups.Results: In the first study, we identified 10 patients (8.1%) who presented with achalasia, or gastroparesis, or paralytic ileus. In the second study, we detected anti-gAChR Abs in 21.4% of the achalasia patients, and in 50.0% of the CIPO patients. Although patients with achalasia and CIPO demonstrated widespread autonomic dysfunction, bladder dysfunction was observed in the seropositive patients with CIPO as a prominent clinical characteristic of dysautonomia.Conclusions: These results demonstrate a significant prevalence of anti-gAChR antibodies in patients with achalasia and CIPO. Anti-gAChR Abs might mediate autonomic dysfunction, contributing to autoimmune mechanisms underlying these GI motility disorders. [ABSTRACT FROM AUTHOR]

Introduction: Autoimmune autonomic ganglionopathy (AAG) is an acquired immune-mediated disorder that leads to autonomic failure. The disorder is associated with autoantibodies to the ganglionic nicotinic acetylcholine receptor (gAChR). We subsequently reported that AAG is associated with an overrepresentation of psychiatric symptoms, sensory disturbance, autoimmune diseases, and endocrine disorders. Area covered: The aim of this review was to describe AAG and highlight its pivotal pathophysiological aspects, clinical features, laboratory examinations, and therapeutic options. Expert commentary: AAG is a complex neuroimmunological disease, these days considered as an autonomic failure with extra-autonomic manifestations (and various limited forms). Further comprehension of the pathophysiology of this disease is required, especially the mechanisms of the extra-autonomic manifestations should be elucidated. There is the possibility that the co-presence of antibodies that were directed against the other subunits in both the central and peripheral nAChRs in the serum of the AAG patients. Some patients improve with immunotherapies such as IVIg and/or corticosteroid and/or plasma exchange. 123I-MIBG myocardial scintigraphy may be a useful tool to monitor the therapeutic effects of immunotherapies. [ABSTRACT FROM AUTHOR]

Abstract: The aim of this study was to evaluate the association between postural orthostatic tachycardia syndrome (POTS) and circulating antiganglionic acetylcholine receptor (gAChR) antibodies. We reviewed clinical assessments of Japanese patients with POTS, and determined the presence of gAChR antibodies in serum samples from those patients. Luciferase immunoprecipitation systems detected anti‐gAChRα3 and β4 antibodies in the sera from POTS (29%). Antecedent infections were frequently reported in patients in POTS patients. Moreover, autoimmune markers and comorbid autoimmune diseases were also frequent in seropositive POTS patients. Anti‐gAChR antibodies were detectable in significant number of patients with POTS, and POTS entailed the element of autoimmune basis. [ABSTRACT FROM AUTHOR]

The patient is an 80‐year‐old man. At the age of 76, he presented with acute onset of severe orthostatic hypotension and diarrhea. Anti‐ganglionic acetylcholine receptor (anti‐gAChR) antibodies were positive, and prednisolone was effective. He was diagnosed with autoimmune autonomic ganglionopathy (AAG) based on acute onset autonomic dysfunction, positive anti‐gAChR antibodies, and efficacy of prednisolone. After the event of AAG, he gradually developed Parkinson's disease (PD). Parkinsonism is described as a complication of AAG in the previous literature. Anti‐gAChR antibodies might inhibit dopamine neurotransmission and be associated with the development of PD. [ABSTRACT FROM AUTHOR]

Background/Aims: Anti-ganglionic nicotinic acetylcholine receptor (gAChR) antibodies are observed in autoimmune diseases, as well as in patients with autoimmune autonomic ganglionopathy. However, the genetic background of anti-gAChR antibodies is unclear. Here, we investigated HLA alleles in autoimmune hepatitis (AIH) patients with or without anti-gAChR antibodies. Methodology/Principal Findings: Genomic DNA from 260 patients with type-1 autoimmune hepatitis (AIH) were genotyped for HLA-A, B, DRB1, and DQB1 loci. Anti-gAChR antibodies in the sera form AIH patients were measured using the luciferase immunoprecipitation system, and examined allelic association in patients with or without anti-gAChR antibodies. Methodology/ Methods: We detected anti-α3 or -β4 gAChR antibodies in 11.5% (30/260) of patients with AIH. Among AIH patients there was no significant association between HLA-A, B DQB1 alleles and the positivity for anti-gAChR antibodies. Whereas the HLA-DRB1*0403 allele showed a significantly increased frequency in AIH patients with anti-gAChR antibodies compared with those without anti-gAChR antibodies. Conclusions/Significance: The frequency of the HLA-DRB1*0403 allele differed among Japanese patients with AIH according to the presence or absence of anti-gAChR antibodies. Our findings suggest that particular HLA class II molecules might control the development of anti-gAChR antibodies in the autoimmune response to gAChR. [ABSTRACT FROM AUTHOR]

Autoimmune autonomic ganglionopathy (AAG) is a rare acquired channelopathy that is characterized by pandysautonomia, in which autoantibodies to ganglionic nicotinic acetylcholine receptors (gAChR) may play a central role. Radioimmunoprecipitation (RIP) assays have been used for the sensitive detection of autoantibodies to gAChR in the serum of patients with AAG. Here, we developed luciferase immunoprecipitation systems (LIPS) to diagnose AAG based on IgGs to both the α3 and β4 gAChR subunits in patient serum. We reviewed the serological and clinical data of 50 Japanese patients who were diagnosed with AAG. With the LIPS testing, we detected anti-α3 and -β4 gAChR antibodies in 48% (24/50) of the patients. A gradual mode of onset was more common in the seropositive group than in the seronegative group. Patients with AAG frequently have orthostatic hypotension and upper and lower gastrointestinal tract symptoms, with or without anti-gAChR. The occurrence of autonomic symptoms was not significantly different between the seropositive and seronegative group, with the exception of achalasia in three patients from the seropositive group. In addition, we found a significant overrepresentation of autoimmune diseases in the seropositive group and endocrinological abnormalities as an occasional complication of AAG. Our results demonstrated that the LIPS assay was a useful novel tool for detecting autoantibodies against gAChR in patients with AAG. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To evaluate parents’ knowledge regarding foreign body aspiration (FBA) and determine the factors that are associated with lack of knowledge. Methods: An 8-item questionnaire regarding knowledge of FBA was developed and distributed at regular check-ups for children younger than 24 months old. Results: Out of the 1766 questionnaires distributed, 1603 were recovered and most of them (1539) were answered by mothers. After omitting 49 questionnaires with incomplete data, 1490 questionnaires answered by mothers were analyzed. Only 4.3% [95% CI 3.3–5.3] of mothers did not recognize a small toy as a cause of FBA, while 20.2% [95% CI 18.2–22.2] did not know that peanuts and other nuts can be causes of FBA, and 48.1% [95% CI 45.5–50.6] did not know that they should not give peanuts to a child younger than 3 years old. Regarding clinical signs, 27.7% [95% CI 25.4–30.0] and 41.8% [95% CI 39.3–44.3] of mothers did not know that sudden choking and sudden coughing were symptoms suggesting FBA, respectively. Being a mother with a child younger than 12 months old and being a mother with a first child were independent risk factors for lack of knowledge about FBA, regardless of the age of the mother. Conclusions: A substantial number of mothers lack knowledge regarding FBA. To prevent FBA and to make timely diagnoses, parents, especially mothers with children younger than 12 months old and mothers with a first child should be given adequate information. [Copyright &y& Elsevier]

BACKGROUND: A relevant relationship exists between the upper and lower airway, indicating the concept of a unified airway. This study aimed to evaluate whether rhinitis has an association with asthma in children. METHODS: A cross-sectional nationwide survey was performed among children 6-7, 13-14, and 16-17 years old, using the International Study of Asthma and Allergies in Children (ISAAC) questionnaire in Japan. According to the responses to the ISAAC core questions, a child who had experienced nasal symptoms in the past 12 months in the absence of a cold was defined as having current rhinitis. RESULTS: After excluding 11,475 children because of incomplete data, 136,506 children were analyzed. Even after adjusting for demographics, sex, and obesity, children with current rhinitis were more likely to have asthma (adjusted odds ratio [OR], 3.10 [95% CI, 2.92-3.30] in children aged 6-7 years; OR, 3.76 [95% CI, 3.45-4.10] in children aged 13-14 years; and OR, 3.59 [95% CI, 3.33-3.88] in children aged 16-17 years). Children whose daily activities were more impaired by rhinitis symptoms had a significantly higher prevalence of severe asthma. The adjusted ORs for severe asthma among asthmatic children whose daily activities were severely impaired by rhinitis symptoms were 3.66 (95% CI, 2.29-5.85) in children aged 6-7 years, 2.55 (95% CI, 1.64-3.96) in children aged 13-14 years, and 1.87 (95% CI, 1.24-2.82) in children aged 16-17 years compared with asthmatic children whose daily activities were not impaired at all. CONCLUSION: There was a close association between rhinitis and asthma in young children to adolescents. Asthma should be examined in children with rhinitis symptoms. [ABSTRACT FROM AUTHOR]

Congenital myasthenic syndromes (CMSs) are a heterogeneous group of genetic disorders affecting neuromuscular transmission. The agrin/muscle-specific kinase (MuSK) pathway is critical for proper development and maintenance of the neuromuscular junction (NMJ). We report here an Iranian patient in whom CMS was diagnosed since he presented with congenital and fluctuating bilateral symmetric ptosis, upward gaze palsy and slowly progressive muscle weakness leading to loss of ambulation. Genetic analysis of the patient revealed a homozygous missense mutation c.2503A>G in the coding sequence of MUSK leading to the p.Met835Val substitution. The mutation was inherited from the two parents who were heterozygous according to the notion of consanguinity. Immunocytochemical and electron microscopy studies of biopsied deltoid muscle showed dramatic changes in pre- and post-synaptic elements of the NMJs. These changes induced a process of denervation/reinnervation in native NMJs and the formation, by an adaptive mechanism, of newly formed and ectopic NMJs. Aberrant axonal outgrowth, decreased nerve terminal ramification and nodal axonal sprouting were also noted. In vivo electroporation of the mutated MuSK in a mouse model showed disorganized NMJs and aberrant axonal growth reproducing a phenotype similar to that observed in the patient's biopsy specimen. In vitro experiments showed that the mutation alters agrin-dependent acetylcholine receptor aggregation, causes a constitutive activation of MuSK and a decrease in its agrin- and Dok-7-dependent phosphorylation. [ABSTRACT FROM AUTHOR]