Promoter Deletion Leading to Allele Specific Expression in a Genetically Unsolved Case of Primary Ciliary Dyskinesia.

Variation in the non-coding genome represents an understudied mechanism of disease and it remains challenging to predict if single nucleotide variants, small insertions and deletions, or structural variants in non-coding genomic regions will be detrimental. Our approach using complementary RNA-seq and targeted long-read DNA sequencing can prioritize identification of non-coding variants that lead to disease via alteration of gene splicing or expression. We have identified a patient with primary ciliary dyskinesia with a pathogenic coding variant on one allele of the SPAG1 gene, while the second allele appears normal by whole exome sequencing despite an autosomal recessive inheritance pattern. RNA sequencing revealed reduced SPAG1 transcript levels and exclusive allele specific expression of the known pathogenic allele, suggesting the presence of a non-coding variant on the second allele that impacts transcription. Targeted long-read DNA sequencing identified a heterozygous 3 kilobase deletion of the 5' untranslated region of SPAG1, overlapping the promoter and first non-coding exon. This non-coding deletion was missed by whole exome sequencing and gene-specific deletion/duplication analysis, highlighting the importance of investigating the non-coding genome in patients with "missing" disease-causing variation. This paradigm demonstrates the utility of both RNA and long-read DNA sequencing in identifying pathogenic non-coding variants in patients with unexplained genetic disease.

Lack variation of low slow-wave activity over time in the frontal region in NREM sleep may be associated with dyskinesia in Parkinson's disease.

OBJECTIVE: Levodopa-induced dyskinesia (DYS) adversely affects the quality of life of Parkinson's disease (PD) patients. However, few studies have focused on the relationship between DYS and sleep and electroencephalography (EEG). Our study aimed to establish the objective physiological indicators assessed by polysomnography (PSG) that are associated with DYS in PD patients. METHODS: We enrolled 122 patients with PD, divided into two groups: PD with DYS (n = 27) and PD without DYS group (non-DYS, n = 95). The demographics and clinical characteristics and sleep assessment in the two groups were collected. More importantly, overnight six-channel PSG parameters were compared in the two groups. We also compared different bands and brain regions of average power spectral density within each group. RESULTS: Compared with the non-DYS group, the DYS group tended to have a significantly higher percentage of nonrapid eye movement sleep (NREM). Gender, levodopa equivalent daily dose (LEDD), rapid eye movement (REM) sleep (min), and the NREM percentage were positively correlated with the occurrence of DYS. After adjusting for gender, disease duration, LEDD, taking amantadine or not, and Montreal Cognitive Assessment (MoCA), NREM%, N3%, and REM (min), the percentage of NREM sleep (p = 0.035), female (p = 0.002), and LEDD (p = 0.005), and REM sleep time (min) (p = 0.012) were still associated with DYS. There was no significant difference in whole-night different bands of average power spectral density between two groups. There was no significant difference in normalized average power spectral density of slow wave activity (SWA) (0.5-2 Hz, 0.5-4 Hz, and 2-4 Hz) of early and late NREM sleep in the DYS group. Dynamic normalized average power spectral density of SWA of low-frequency (0.5-2 Hz) reduction in the frontal region (p = 0.013) was associated with DYS in logistic regression after adjusting for confounding factors. CONCLUSION: PD patients with DYS have substantial sleep structure variations. Higher NREM percentage and less REM percentage were observed in PD patients with DYS. Dynamic normalized average power spectral density of low-frequency (0.5-2 Hz) SWA reduction in the frontal area could be a new electrophysiological marker of DYS in PD.

Case Report: Primary ciliary dyskinesia due to CCNO mutations: a Chinese pediatric case series and literature review.

Primary ciliary dyskinesia (PCD) is a hereditary disorder characterized by defects in cilia that impair mucociliary clearance. This study focuses on PCD caused by mutations in the Cyclin O (CCNO) gene and reports on three cases involving Chinese children. Case 1 was an 8-year-and-3-month-old boy who presented with respiratory distress after birth and later developed a recurrent productive cough and purulent nasal discharge. He was initially diagnosed with diffuse panbronchiolitis (DPB) due to the presence of diffuse micronodules in lung CT scans. Case 2 was the younger sister of case 1. She also presented with respiratory distress after birth, with a chest radiograph revealing atelectasis. She required oxygen supplementation until the age of 2 months. Case 3 was a 4-year-and-4-month-old girl with a history of neonatal pneumonia, persistent pulmonary atelectasis, and recurrent lower respiratory tract infections. Her chest radiograph also showed diffuse micronodules. In all three cases, the final diagnosis of PCD was confirmed by genetic testing. Cases 1 and 2 exhibited homozygous c.248_252dup TGCCC (p.G85Cfs*11) mutations in the CCNO gene, while case 3 harbored a homozygous c.258_262dup GGCCC (p.Q88Rfs*8) mutation. A literature review indicated that the common clinical features of CCNO-PCD include neonatal respiratory distress (40/49, 81.6%), chronic cough (31/33, 93.9%), rhinosinusitis (30/35, 85.7%), bronchiectasis (26/35, 74.3%), and low nasal nitric oxide (nNO, 40/43, 93.0%). Notably, situs inversus has not been reported. In CCNO-PCD patients, cilia may appear structurally normal but were severely reduced in number or entirely absent. Lung CT scans in these patients may exhibit diffuse micronodules and "tree-in-bud" signs, which can lead to a clinical misdiagnosis of DPB. nNO screening combined with genetic testing is an optimized diagnostic strategy. Treatment options include the use of anti-infective and anti-inflammatory agent, along with daily airway clearance. This study underscores the importance of genetic testing in neonates and children with suspected PCD or those clinically diagnosed with DPB to enable an early diagnosis and prompt intervention, thereby enhancing the prognosis for these patients.

Heterozygous KCNJ10 Variants Affecting Kir4.1 Channel Cause Paroxysmal Kinesigenic Dyskinesia.

BACKGROUND: More than 60% of paroxysmal kinesigenic dyskinesia (PKD) cases are of uncertain variants. OBJECTIVE: The aim was to elucidate novel genetic contribution to PKD. METHODS: A total of 476 probands with uncertain genetic causes were enrolled for whole-exome sequencing. A method of case-control analysis was applied to identify the candidate genes. Whole-cell patch-clamp recording was applied to verify the electrophysiological impact of the identified variants. A mouse model with cerebellar heterozygous knockout of the candidate gene was developed via adeno-associated virus injection, and dystonia-like phenotype inducement and rotarod tests were performed. In vivo multiunit electrical recording was applied to investigate the change in neural excitability in knockout mice. RESULTS: Heterozygous variants of potassium inwardly rectifying channel subfamily J member 10 (KCNJ10) clustered in PKD patients were compared with those in the control groups. Fifteen variants were detected in 16 of 522 probands (frequency = 3.07%). Patients with KCNJ10 variants tended to have a milder manifestation compared to those with PRRT2 (proline-rich transmembrane protein 2) variants. KCNJ10 variants partially altered the transmembrane location of inwardly rectifying potassium channel 4.1 (Kir4.1). The Kcnj10 expression is consistent with the natural course of PKD. Variants resulted in different degrees of reduction in cell Kir4.1 currents, and mice with heterozygous conditional knockout of Kcnj10 in the cerebellum presented dystonic posture, together with poor motor coordination and motor learning ability in rotarod tests. The firing rate of deep cerebellar nuclei was significantly elevated in Kcnj10-cKO mice. CONCLUSION: We identified heterozygous variants of KCNJ10 in PKD. Impaired function of Kir4.1 might lead to abnormal neuronal excitability, which attributed to PKD. © 2024 International Parkinson and Movement Disorder Society.

Biliary Dyskinesia and Hyperkinesis.

Biliary dyskinesia refers to a group of functional and motility disorders of the biliary system in patients presenting with typical biliary pain, but without any visible structural abnormalities on standard imaging. The Rome IV Criteria establishes diagnostic criteria for functional gallbladder disorder (gallbladder dyskinesia and biliary hyperkinesia), functional biliary sphincter of Oddi disorder (biliary dyskinesia), and pancreatic sphincter of Oddi disorder. Many diagnostic adjuncts such as hepatobiliary scintigraphy and sphincter of Oddi manometry exist, although these results are supportive and not necessarily diagnostic for biliary dyskinesia. Surgical intervention is most successful when selecting for patients with typical biliary pain.

[Radiology of bronchiectasis]. / Radiologie von Bronchiektasen.

Bronchiectasis is an irreversible bronchial dilatation. It is chronically progressive through a vicious circle of secretion retention, infection, inflammation and structural damage. The underlying causes are diverse and the severity of the disease is variable, which makes both the diagnostics and treatment challenging. Computed tomography (CT) is the gold standard in the diagnosis of bronchiectasis and can be helpful in clarifying the etiology. The type of bronchiectasis, the distribution of the bronchiectasis within the lungs and associated findings are particularly relevant. Imaging is also important in monitoring the progression of bronchiectasis. In the usual report of the findings this is carried out visually and descriptively, while semiquantitative scores and computer-aided quantitative analysis of the respiratory tract enable a more precise assessment and are used in particular for clinical studies.

Successful Electroconvulsive Therapy for Tardive Dyskinesia and Tardive Dystonia Refractory to Valbenazine Treatment: A Case Report and Narrative Literature Review.

Tardive dyskinesia and dystonia are intractable extrapyramidal symptoms caused by the blockade of dopamine receptors by antipsychotic drugs. In addition to the reduction or discontinuation of the causative drug, valbenazine for tardive dyskinesia and botulinum toxin for tardive dystonia have been reported to be effective. However, their efficacy has not been fully demonstrated. In this study, we report the case of a female patient with bipolar disorder, valbenazine-resistant tardive dystonia, and tardive dyskinesia who achieved improvement in extrapyramidal symptoms with electroconvulsive therapy. Additionally, we conducted a narrative literature review on the safety and efficacy of electroconvulsive therapy for tardive dyskinesia and dystonia.

Internal carotid artery dissection in a patient with Parkinson's disease after COVID-19 infection.

Background: Internal carotid artery (ICA) dissection is a relatively rare cause of acute ischemic stroke. Stretching and compression of ICA due to sudden acceleration, deceleration, and rotational forces are risk factors for ICA dissection. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is believed to trigger an inflammatory response that exacerbates endothelial dysfunction and leads to arterial dissection. Although levodopa-induced cervical dyskinesia in Parkinson's disease often manifests as choreiform movement, dissection has not been reported in such patients. Case presentation: A 51-year-old man with Parkinson's disease (PD) presented with gradually worsening neck pain and transient aphasia 1 week after mild coronavirus disease 2019 (COVID-19) infection. The patient already had neck pain due to cervical spondylosis and presented with levodopa-induced cervical dyskinesia. Magnetic resonance imaging revealed acute ischemic stroke in the left parietal lobe and an intramural hematoma with an area of stenosis in the left ICA. The patient was diagnosed with left ICA dissection. Conclusions: COVID-19 infection can cause vessel wall vulnerability. Although patients with PD often have neck pain, ICA dissection should be considered a differential diagnosis if the patient has a recent history of COVID-19.

Unraveling the membrane topology of TMEM151A: a step towards understanding its cellular role.

Transmembrane protein 151A (TMEM151A) has been identified as a causative gene for paroxysmal kinesigenic dyskinesia, though its molecular function remains almost completely unknown. Understanding the membrane topology of transmembrane proteins is crucial for elucidating their functions and possible interacting partners. In this study, we utilized molecular dynamics simulations, immunocytochemistry, and electron microscopy to define the topology of TMEM151A. Our results validate a starting AlphaFold model of TMEM151A and reveal that it comprises a transmembrane domain with two membrane-spanning alpha helices connected by a short extracellular loop and an intramembrane helix-hinge-helix structure. Notably, most of the protein is oriented towards the intracellular side of the membranes with a large cytosolic domain featuring a combination of alpha-helix and beta-sheet structures, as well as the protein N- and C-termini. These insights into TMEM151A's topology and orientation of its domains with respect of the cell membranes provide essential information for future functional studies and represent a first fundamental step for understanding its role in the pathogenesis of paroxysmal kinesigenic dyskinesia.

Genetic Variants Supporting the Diagnosis of Primary Ciliary Dyskinesia in Japan.

Primary ciliary dyskinesia (PCD; OMIM 244400) is a rare genetic disorder affecting motile cilia and is characterized by impaired mucociliary clearance in the airway epithelium that leads to chronic oto-sinopulmonary manifestations. To date, over 50 PCD-causing genes have been identified, with these genes and their variants varying globally across populations. We performed targeted resequencing of 42 PCD-causative genes in 150 Japanese patients suspected of having PCD and identified pathogenic or likely pathogenic variants in 51 patients. Among these, 24 patients exhibited a homozygous deletion of DRC1 exons 1-4, the most common cause of PCD in Japan. The allele frequency of this deletion was estimated at 0.0034 (95% CI: 0.0025-0.0044), based on bioinformatic analysis of 7906 whole-genome sequences from the general Japanese population. Additionally, RNA sequencing of nasal samples supplemented in silico variant predictions, aiding in the identification of causative variants. Considering potential ethnic differences, it is essential to accumulate global data on these variants and their functional impacts.

Impact of local anesthesia on ciliary dyskinesia diagnosis by digital high-speed videomicroscopy.

This prospective study investigates the impact of local anesthesia on ciliary function in nasal epithelium. The primary objective was to assess whether lidocaine 2% and naphazoline 0.5% nasal spray alter ciliary beat frequency and pattern in subjects undergoing nasal brushing, aiming to enhance primary ciliary dyskinesia (PCD) diagnosis. HYPOTHESIS: It was hypothesized that local anesthesia administration would not significantly affect ciliary function in nasal epithelium. STUDY DESIGN: A prospective, simple-blind randomized study was conducted between 2020 and 2023. The study employed digital high-speed videomicroscopy to analyze ciliary beat frequency and pattern. PATIENT/SUBJECT SELECTION: A cohort of 38 participants was recruited, consisting of 25 healthy volunteers and 13 referred individuals (including seven diagnosed with PCD). Selection criteria ensured the absence of chronic respiratory diseases, recent respiratory tract infections, or regular use of nasal medications. METHODOLOGY: Participants underwent nasal brushing with administration of lidocaine and naphazoline nasal spray in one nostril and saline in the contralateral nostril. Ciliary beat frequency and pattern were measured using digital high-speed video microscopy. RESULTS: Nasal spray administration did not significantly alter ciliary beat frequency or pattern compared to saline (p = 0.841 and p = 0.125, respectively). Subgroup analysis revealed consistent results across healthy volunteers, referred patients, and PCD patients. CONCLUSION: Local anesthesia with lidocaine and naphazoline spray did not affect ciliary function outcomes. These findings support the safe use of these agents in clinical practice for PCD diagnostic procedures. Further research with larger cohorts is warranted for validation.

Evidence for secondary ciliary dyskinesia in patients with cystic fibrosis.

BACKGROUND: Mucociliary clearance (MCC) impairment can be due to mucus abnormalities or to a ciliary dysfunction, which can be innate, or secondary to infection and/or inflammation. In cystic fibrosis (CF), it is well documented that MCC is impaired due to mucus abnormalities, but little is known concerning ciliary beating. This study aimed to confirm that ciliary dyskinesia is present in CF, and if this might be innate or secondary to the chronic infection and/or inflammation. METHODS: Ciliated epithelial samples were obtained by nasal brushing from 51 CF patients, and from 30 healthy subjects. Ciliary beating was evaluated using digital high-speed videomicroscopy at 37 °C, allowing to evaluate ciliary beat frequency (CBF) and the percentage of abnormal beat pattern (CBP); this was repeated after air-liquid interface (ALI) cell culture. RESULTS: Ciliary dyskinesia was higher in CF patients than in healthy subjects, with a lower CBF and a higher percentage of abnormal CBP. Ciliary dyskinesia, already present in childhood, normalized after ALI cell culture. A chronic airway colonization did not worsen ciliary dyskinesia. CONCLUSIONS: We showed that, in CF, a ciliary dyskinesia, present from childhood, might contribute to the impaired MCC. Our results also found that the abnormal ciliary beating was not associated with a chronic infection, and resolved after ALI cell culture, suggesting that ciliary dyskinesia in CF is not innate, and might be secondary to chronic inflammation.

Effect of 5-alpha reductase inhibitors in animal models of Parkinson's disease.

Parkinson's disease (PD) is characterized by motor symptoms due to loss of brain dopamine and non-motor symptoms, including gastrointestinal disorders. Although there is no cure for PD, symptomatic treatments are available. L-Dopa is the gold standard PD therapy, but most patients develop dyskinesias (LID), which are challenging to manage. Amantadine is recognized as the most effective drug for LID, but its adverse effects limit the use in patients. Here we review how 5α-reductase inhibitors (5ARIs), drugs used to treat benign prostatic hyperplasia and alopecia, exhibit beneficial effects in PD animal models. 5ARIs show neuroprotective properties in brain and gut dopaminergic systems, and reduce dyskinesias in rodent model of PD. Additionally, the 5ARI finasteride dampened dopaminergic-induced drug gambling in PD patients. Neuroprotection and antidyskinetic activities of 5ARIs in animal models of PD suggest their potential repurposing in men with PD to address gut dysfunction, protect brain DA and inhibit dyskinesias.

Impact of 5-Lipoxygenase Deficiency on Dopamine-Mediated Behavioral Responses.

The 5-lipoxygenase/leukotriene system has been implicated in both physiological and pathological states within the central nervous system. Understanding how this system interacts with the dopaminergic system could provide valuable insights into dopamine-related pathologies. This study focused on examining both motor and non-motor dopamine-related responses in 5-lipoxygenase/leukotriene-deficient mice. We used pharmacological agents such as amphetamine, apomorphine, and reserpine to challenge the dopaminergic system, evaluating their effects on prepulse inhibition reaction (PPI), general motor activity, and oral involuntary movements. Additionally, we analyzed striatal glial marker expression (GFAP and Iba-1) in reserpine-treated mice. The 5-lipoxygenase/leukotriene-deficient mice exhibited increased spontaneous locomotor activity, including both horizontal and vertical exploration, along with stereotyped behavior compared to wild-type mice. This hyperactivity was reduced by acute apomorphine treatment. Although basal PPI responses were unchanged, 5-lipoxygenase/leukotriene-deficient mice displayed a significant reduction in susceptibility to amphetamine-induced PPI disruption. Conversely, these mice were more vulnerable to reserpine-induced involuntary movements. There were no significant differences in the basal expression of striatal GFAP and Iba-1 positive cells between 5-lipoxygenase/leukotriene-deficient and wild-type mice. However, reserpine treatment significantly increased GFAP immunoreactivity in wild-type mice, an effect not observed in 5-lipoxygenase-deficient mice. Additionally, the percentage of activated microglia was significantly higher in reserpine-treated wild-type mice, an effect absents in 5-lipoxygenase/leukotriene-deficient mice. Our findings suggest that 5-lipoxygenase/leukotriene deficiency leads to a distinctive dopaminergic phenotype, indicating that leukotrienes may influence the modulation of dopamine-mediated responses.

Effects of Using a Special Weighted Vest on Muscle Activity around the Scapula during Knee Push-Up Plus in Healthy Subjects.

Muscle imbalances in the upper body can lead to ineffective movement patterns and potential injury. The purpose of this study was to investigate the muscle activity, impact, and muscle activation ratio of the serratus anterior (SA), upper trapezius (UT), lower trapezius (LT), and pectoralis major (PM) during the knee push-up plus (KPUP) exercise under various loads. METHOD: Electromyography assessed scapular muscle activity in 32 healthy adults (15 males, 17 females) during three KPUP variations. RESULTS: PM and UT showed no significant activity differences across loads, whereas SA and LT did. SA activity was significantly higher in the weighted KPUP (WKPUP) 3 kg than that in KPUP and WKPUP 1 kg. LT activity was also significantly higher in WKPUP 3 kg compared to KPUP and WKPUP 1 kg, with KPUP showing higher activity than WKPUP 1 kg. PM/SA ratios remained consistent across loads, while UT/LT ratios varied significantly, being notably lower at 3 kg compared to 0 kg and 1 kg. Similarly, UT/SA ratios differed significantly among loads, being notably lower at 3 kg and 1 kg compared to 0 kg. CONCLUSION: WKPUP with 3 kg demonstrated significantly higher SA and LT activity compared to KPUP and WKPUP 1 kg. The lowest UT/LT ratio was observed during the WKPUP 3 kg, suggesting its effectiveness for optimizing muscle activation balance during KPUP exercises. These findings may inform the development of exercise protocols aimed at improving scapular stabilization.

Effectiveness of Vitamin E in Treatment of Antipsychotic-Induced Tardive Dyskinesia and Extrapyramidal Symptoms: A Case Report.

Antipsychotic medications, while crucial in managing severe psychiatric disorders such as schizophrenia and bipolar disorder, are frequently associated with extrapyramidal symptoms (EPS) and tardive dyskinesia (TD). TD, characterized by repetitive, involuntary movements, especially of the face and limbs, poses a substantial clinical challenge due to its often irreversible nature. Conventional management strategies, including dose reduction and switching to atypical antipsychotics, frequently offer limited success, prompting exploration of alternative therapies. This case report highlights the effectiveness of vitamin E, a potent antioxidant, in treating a 28-year-old male with severe antipsychotic-induced EPS and TD, unresponsive to traditional therapies. The patient, who had been receiving paliperidone injections as part of his psychotic disorder treatment regimen, developed marked EPS, including muscle rigidity, a parkinsonian gait, significant motor disturbances as well as tardive dyskinesia. Despite discontinuation of paliperidone and initiation of procyclidine, propranolol, clonazepam, and omega-3 supplements, his symptoms persisted. Introduction of oral vitamin E at 400 IU daily led to a dramatic improvement, with an 80% reduction in EPS and TD symptoms within weeks. The patient's Abnormal Involuntary Movement Scale (AIMS) score decreased from 24 to 4, and his overall quality of life improved significantly. Gradual increase of vitamin E dosage to 1200 IU daily, coupled with tapering of other medications, eventually led to complete resolution of symptoms, as evidenced by an AIMS score of 0. The patient maintained symptom-free status during follow-up, with no recurrence of psychotic symptoms. This case underscores the potential role of vitamin E as a viable adjunctive treatment for TD, particularly in patients who do not respond adequately to conventional therapies. While the literature presents mixed evidence regarding vitamin E's effectiveness, this case adds to the growing body of research suggesting its benefits, especially when introduced early in the disease course. Further large-scale studies are warranted to establish the most effective treatment protocols and identify patient populations most likely to benefit from vitamin E therapy.

A case of primary ciliary dyskinesis with DRC1 deletion and literature review: Additional evidence on the founder effect.

BACKGROUND: Primary ciliary dyskinesia (PCD) is a rare genetic disease caused by defects in various genes affecting ciliary function. It is currently unclear why DRC1 gene variants are a relatively frequent cause of disease in Japanese and Korean patients. METHODS: A 12-year-old Japanese girl with bronchiectasis was suspected of PCD and examined using whole-exome sequencing (WES). The breakpoint region was confirmed by Sanger sequencing and evaluation of transposable elements. RESULTS: Whole-exome sequencing revealed a deletion of DRC1 exons 1-4 in the patient, followed by validation with Sanger sequencing. A DRC1 exon 1-4 deletion is recurrently observed in Japanese and Korean patients with PCD. All reported patients carry the same breakpoint region, which shows signs of Alu-mediated recombination. Intriguingly, common haplotypes were observed around the DRC1 gene in Japanese and Korean patients. CONCLUSION: The recurrent DRC1 exon 1-4 deletion is therefore likely to be a founder variant and should be considered a major genetic cause of PCD in Japanese and Korean patients with PCD.

Ciliary Function, Antigen Stasis and Asthma.

The prevalence of asthma exceeds 3% of the population. Asthma is observed to be more common in children following severe viral lower respiratory illnesses that affect ciliary function, but mechanisms linking ciliary function to asthma pathogenesis have been obscure. Recent data regarding primary ciliary dyskinesia (PCD) may help us to understand the association. Here, I will review what is known about the relationship between ciliary function and asthma. PCD is caused by pathologic variants in over 50 different genes that affect the structure and function of motile cilia. At the cellular level, a characteristic feature shared by most PCD patients is that antigens and other particles are not cleared from the epithelial surface. Poor antigen clearance results in pro-oxidant pathway activation and airway epithelial damage and may predispose PCD patients to DUOX1- and IL33-mediated asthma. Secondary ciliary dysfunction, such as that caused by viruses or by smoking, can also contribute to asthma development. Moreover, variants in genes that affect the function of cilia can be associated with poor lung function, even in the absence of PCD, and with increased asthma severity. The role of antigen stasis on the surface of dysfunctional airway cilia in the pathophysiology of asthma is a novel area for research, because specific airway clearance techniques and other therapeutic interventions, such as antioxidants, could be of value in preventing the development of asthma.