The impact of exposure to desert dust on infants' symptoms and countermeasures to reduce the effects.

BACKGROUND: The association between particulate matter (PM), including desert dust, and allergic symptoms has not been well studied. We examined whether PM exacerbated nose/eye/respiratory symptoms in infants, with a focus on the desert dust element, and assessed possible countermeasures. METHODS: We conducted a panel study of 1492 infants from October 2014 to July 2016 in 3 regions in Japan as an adjunct study of the Japan Environment and Children's Study. Infants' daily symptom scores and behaviors were acquired by web-based questionnaires sent to mothers, who answered within a day using mobile phones. Odds ratios (OR) for symptom development per increased fine PM or desert dust exposure were estimated. Regular use of medications and behaviors on the day of exposure were investigated as possible effect modifiers. RESULTS: Infants developed nose/eye/respiratory symptoms significantly more often in accordance with fine particulate levels (adjusted OR per 10 µg/m3 increase: 1.04, 95% confidence interval [CI]: 1.01-1.07). A model including both fine particulates and desert dust showed reduced OR for fine particulates and robust OR for desert dust (adjusted OR per 0.1/km increase: 1.16, 95% CI: 1.09-1.23). An increased OR was observed both in infants who had previously wheezed and in those who had never wheezed. Receiving information on the particulate forecast, reducing time outdoors, closing windows, and regular use of leukotriene receptor antagonists were significant effect modifiers. CONCLUSIONS: Transborder desert dust arrival increased the risk of nose/eye/respiratory symptoms development in infants. Regular use of leukotriene receptor antagonists and other countermeasures reduced the risk.

Association between vitamin D deficiency and allergic symptom in pregnant women.

BACKGROUND: Vitamin D has been reported to affect both innate, and acquired immunity with immune cells such as dendritic cells having the vitamin D receptors. The co-occurrence of the high prevalence of allergic diseases and vitamin D deficiency globally documented in recent decades, has prompted a hypothesis on whether there is a reasonable association between them. OBJECTIVE: To investigate the association between serum vitamin D deficiency and allergic symptoms. METHODS: Historical cohort. On a cohort study for the association between desert dust exposure and allergic symptoms in 3,327 pregnant women during spring and fall in 2011-2013 in Japan conducted as an adjunct study to the Japan Environment and Children's Study, we promptly acquired subjects' daily allergic symptom scores by sending a web-based questionnaire to each participant on some days. Of the 29,434 answers provided by 3,327 participating pregnant women, we extracted 13,356 answers from 1,475 pregnant women that were answered within a 3-month period after blood samplings. And we measured 25(OH)D levels on those samples to investigate the association between their vitamin D deficiency (serum 25(OH)D < 20ng/mL) and the occurrence of any allergic symptom (allergic symptom score> 0) within 3 months. RESULTS: Serum 25(OH)D was less than 20ng/mL in 1,233 of 1,745 samples (70.7%). The adjusted odds ratio (aOR) for occurrence of any allergic symptom in deficient cases compared with non-deficient cases was 1.33 (95% CI: 1.07-1.64, p = 0.01). Further, vitamin D deficiency significantly enhanced the risk increase at desert dust events and at pollen exposure (p-values for interaction <0.1). CONCLUSION: We confirmed the association between serum vitamin D deficiency and allergic symptoms in Japanese pregnant women.

High frequency of vitamin D deficiency in current pregnant Japanese women associated with UV avoidance and hypo-vitamin D diet.

BACKGROUND: As a consequence of indoor occupations and reduced exposure to sunlight, concerns have been raised that vitamin D deficiency is widespread in developed countries. Vitamin D is known to be associated with increased risks of morbidity and mortality in various diseases. OBJECTIVE: To investigate the serum vitamin D status and its relation with life-style factors in pregnant Japanese women. METHODS: Among a cohort for 3,327 pregnant women who participated in an the adjunct study of the Japan Environment and Children's Study during 2011-2013, in which data were obtained on various life-style factors, including both dietary intake of vitamin D and frequency of UV exposure, this study consisted of 1,592 pregnant women, from whom 2,030 serum samples were drawn in Jan, Apr, Jul, and Oct, and the association between serum 25(OH)D level and life-style factors were analyzed using linear mixed models. RESULTS: Serum 25(OH)D levels were less than 20ng/mL in 1,486 of 2,030 samples (73.2%). There was an obvious seasonal change, with serum 25(OH)D levels of less than 20 ng/mL in 89.8% and 47.8% of samples in spring (April) and autumn (October), respectively. Both the frequency spent under sunlight and dietary intake of vitamin D were significantly associated with serum 25(OH)D level. An increase in sunlight exposure of more than 15 min for 1 to 2 days per week in non-winter, or dietary intake of 2 µg/day of vitamin D resulted in an elevation of 1 ng/mL in serum 25(OH)D levels. CONCLUSION: These findings indicate that vitamin D deficiency is very severe in Japanese pregnant women, especially those rarely exposed to sunlight. The benefits of UV rays should also be informed of when its risk is alerted, and clinicians should propose the adequate UV exposure level.

Effect of desert dust exposure on allergic symptoms: A natural experiment in Japan.

BACKGROUND: Desert dust originating from arid and semiarid areas is transported to widespread regions, including Japan. Desert dust particles exert adjuvant effects in animals. OBJECTIVE: To examine whether desert dust enhances allergic symptoms in real-life settings and to explore its effect modifiers. METHODS: We conducted an observational study of 3,327 pregnant women during spring and fall in October 2011 to May 2013 in 3 regions in Japan as an adjunct study of the Japan Environment & Children's Study. We acquired participants' daily symptom scores by sending a questionnaire to their mobile phones on high desert-dust days (>0.07/km) and on some randomly selected other days (control days) for each participant. RESULTS: Pregnant women had an increased risk of allergic symptoms on high desert-dust days (adjusted odds ratio [OR], 1.10; 95% CI, 1.04-1.18). The increased OR was mostly driven by those who showed positive IgE to Japanese cedar pollen when pollen simultaneously dispersed (adjusted OR, 1.25; 95% CI, 1.13-1.38), whereas no clear risk increase was observed in the absence of pollen or for participants with negative IgE to Japanese cedar pollen. The risk elevation was observed from low levels of desert dust in a dose-dependent manner even on control days. CONCLUSION: Ambient desert dust level was associated with an increased risk of allergic symptoms in pollen-sensitized pregnant women when pollen was present in the air. The risk increase was dose dependent and was observed from low levels of desert dust. These results support a hypothesis that ambient desert dust particles exert adjuvant effects in human in real-life settings. TRIAL REGISTRATION: clinicaltrials.gov Identifier: UMIN000010826.

Birth cohort study on the effects of desert dust exposure on children's health: protocol of an adjunct study of the Japan Environment & Children's Study.

INTRODUCTION: Desert dust is estimated to constitute about 35% of aerosol in the troposphere. Desertification, climatic variability and global warming all can contribute to increased dust formation. This study aims to examine possible health effects of desert dust exposure on pregnant women and their children. The purpose of this report was to present the study protocol. METHODS AND ANALYSIS: This 4-year birth cohort study began in 2011 as an adjunct study of the Japan Environment & Children's Study (JECS) involving three regions: Kyoto, Toyama and Tottori. The JECS participants of the three regions above who also agreed to participate in this adjunct study were enrolled prior to delivery. Light Detecting and Ranging (LIDAR) with a polarisation analyser, which can distinguish mineral dust particles from other particles, is used for exposure measurements. Outcomes are allergic symptoms for mothers and development of asthma and other allergic or respiratory diseases for their children. Data are acquired in a timely manner by connecting local LIDAR equipment to an online questionnaire system. Participants answer the online questionnaire using mobile phones or personal computers. ETHICS AND DISSEMINATION: The study protocol was approved by the ethics committees of Kyoto University, University of Toyama and Tottori University. All participants provided written informed consent. The results of this study will be published in peer-reviewed journals and disseminated to the scientific community and general public. TRIAL REGISTRATION NUMBER: UMIN000010826.

Zonisamide Induces Crystalluria without Urinary pH Changes in Children and Young Adults.

Purpose. Adjunctive zonisamide therapy was demonstrated to be beneficial for multiple-disabled patients with refractory childhood-onset epilepsy. Zonisamide is well tolerated, but urolithiasis and calcium sludge in the bladder were sometimes described in patients treated with antiepileptic drug polytherapy including zonisamide. In previous studies, alkaline urine and crystalluria were shown to be risk factors for urolithiasis. Therefore, the effects of zonisamide addition and withdrawal on the urinary pH and crystalluria were investigated in patients treated with antiepileptic drug polytherapy to clarify the cause of urolithiasis induced by zonisamide. Methods. The urinary pH and the degree of crystalluria were retrospectively studied in epilepsy patients one month after the addition or withdrawal of zonisamide as part of their antiepileptic drug treatment regimen over the previous three years. Results. A total of 27 zonisamide-on patients and 16 zonisamide-off patients were enrolled in the study. The urinary pH did not change after the addition or withdrawal of zonisamide. However, the degree of crystalluria significantly increased after the addition (P < 0.001) of zonisamide and decreased after its withdrawal (P < 0.01). Conclusions. Zonisamide induces crystalluria without alkalinization of the urine. Crystalluria should be carefully monitored in patients treated with zonisamide to prevent urolithiasis.

Development of global cortical networks in early infancy.

Human cognition and behaviors are subserved by global networks of neural mechanisms. Although the organization of the brain is a subject of interest, the process of development of global cortical networks in early infancy has not yet been clarified. In the present study, we explored developmental changes in these networks from several days to 6 months after birth by examining spontaneous fluctuations in brain activity, using multichannel near-infrared spectroscopy. We set up 94 measurement channels over the frontal, temporal, parietal, and occipital regions of the infant brain. The obtained signals showed complex time-series properties, which were characterized as 1/f fluctuations. To reveal the functional connectivity of the cortical networks, we calculated the temporal correlations of continuous signals between all the pairs of measurement channels. We found that the cortical network organization showed regional dependency and dynamic changes in the course of development. In the temporal, parietal, and occipital regions, connectivity increased between homologous regions in the two hemispheres and within hemispheres; in the frontal regions, it decreased progressively. Frontoposterior connectivity changed to a "U-shaped" pattern within 6 months: it decreases from the neonatal period to the age of 3 months and increases from the age of 3 months to the age of 6 months. We applied cluster analyses to the correlation coefficients and showed that the bilateral organization of the networks begins to emerge during the first 3 months of life. Our findings suggest that these developing networks, which form multiple clusters, are precursors of the functional cerebral architecture.

A qualitative motion analysis study of voluntary hand movement induced by music in patients with Rett syndrome.

Patients with Rett syndrome are known to respond well to music irrespective of their physical and verbal disabilities. Therefore, the relationship between auditory rhythm and their behavior was investigated employing a two-dimensional motion analysis system. Ten female patients aged from three to 17 years were included. When music with a simple regular rhythm started, body rocking appeared automatically in a back and forth direction in all four patients who showed the same rocking motion as their stereotyped movement. Through this body rocking, voluntary movement of the hand increased gradually, and finally became sufficient to beat a tambourine. However, the induction of body rocking by music was not observed in the other six patients who did not show stereotyped body rocking in a back and forth direction. When the music stopped suddenly, voluntary movement of the hand disappeared. When the music changed from a simple regular rhythm to a continuous tone without an auditory rhythm, the periodic movement of both the hand and body prolonged. Auditory rhythm shows a close relationship with body movement and facilitates synchronized body movement. This mechanism was demonstrated to be preserved in some patients with Rett syndrome, and stimulation with music could be utilized for their rehabilitation.

Effect of antiepileptic drug polytherapy on urinary pH in children and young adults.

OBJECTS: The relationship between antiepileptic drugs (AEDs) polytherapy and urinary pH was studied to demonstrate the effect and difference of AED polytherapy compared to monotherapy. MATERIALS AND METHODS: A total of 271 urine samples from patients receiving AED polytherapy aged from 7 months to 35 years were enrolled. Two AEDs were co-administered to 215 patients, three AEDs to 45 patients, four AEDs to ten patients, and five AEDs to one patient. RESULTS: The distribution of urinary pH shifted to the alkaline range with increasing numbers of co-administered AEDs (p < 0.0001). The distribution of urinary pH shifted to the alkaline side with AED polytherapy that included valproate (p < 0.05) or acetazolamide (p < 0.03). The distribution of urinary pH did not change with or without zonisamide, carbamazepine, phenobarbital, phenytoin, or clonazepam. CONCLUSIONS: Urinary pH should be monitored in patients receiving AED polytherapy, particularly those receiving valproate, acetazolamide, or various AEDs in combination.

Neonatal oral imitation in patients with severe brain damage.

BACKGROUND: Neonates reproduce facial movements in response to an adult model just after birth. This neonatal oral imitation usually disappears at about 2- to 3-months of age following the development of cortical control. There is controversy relating to the nature and neural basis of such neonatal imitation. To address this issue, we studied the relationship between oral imitation, primitive reflexes, and residual voluntary movement in patients with severe brain damage. METHODS: Six male and six female patients with cerebral palsy, from 4 to 39 years, were included in this study. Oral imitation was examined when they were awake and looked at the experimenter. Patients were evaluated as performing oral imitation when they opened their mouth repeatedly without visual feedback regarding their own behavior in response to the experimenter's oral movement. Tongue or lip protrusion was not examined because none of patients were able to do those behaviors due to their physical disability. Rooting and sucking reflexes were also investigated as representatives of primitive reflexes. RESULTS: Six patients (50%) performed oral imitation. Mouth opening was not observed repeatedly in response to other facial expression without opening the mouth such as surprise or smile, excluding the possibility of nonspecific oral reaction. They exhibited little voluntary movement of their extremities. Half of them also manifested at least one primitive reflex. No patients exhibiting residual voluntary movements of their extremities performed oral imitation or primitive reflexes. CONCLUSIONS: Oral imitation reappears in a similar way to primitive reflexes in patients showing severely impaired cortical function and little voluntary movement of their extremities due to severe brain damage, suggesting that neonatal oral imitation is mainly controlled by the subcortical brain region.

Effect of antiepileptic drug monotherapy on urinary pH in children and young adults.

OBJECTS: Since alkaline urine is a risk factor for urolithiasis, the relationship between antiepileptic drugs and urinary pH was retrospectively studied in epilepsy patients treated with antiepileptic drug monotherapy for more than 1 month. METHODS: A total of 913 urinary samples from antiepileptic drug-treated patients were compared with 780 age-matched control samples, and with 112 samples from epilepsy patients who had not been treated with antiepileptic drugs. The antiepileptic drugs administered were carbamazepine, valproate, phenobarbital, zonisamide, sulthiame, and phenytoin. CONCLUSIONS: The proportion of the acid urine in the valproate-treated patients was lower than that in controls. The proportion of the alkaline urine in the valproate-treated patients was higher than that in controls. This effect was independent of age, sex, and the serum valproate concentration. There was no significant difference in urinary pH among the epilepsy patients treated with other antiepileptic drugs, the epilepsy patients who had not been treated with antiepileptic drugs, and the controls.

Effect of antiepileptic drug polytherapy on crystalluria.

Urolithiasis is a rare side effect of antiepileptic drugs. To clarify the risk factors for urolithiasis induced by antiepileptic drugs, the effect of antiepileptic drug monotherapy on crystalluria was studied, and zonisamide or sulthiame therapy and alkaline urine were demonstrated to be risk factors. In the next investigation, the effect of antiepileptic drug polytherapy on crystalluria was retrospectively studied in epilepsy patients treated for more than 1 month during the last 7 years. A total of 278 urine specimens from epilepsy patients aged between 7 months and 36 years were enrolled in this study. The mean age was 12.3 years. There were 109 samples from females and 169 from males. Antiepileptic drugs administered in this study were valproate (174 urinary samples), zonisamide (139), carbamazepine (138), phenobarbital (65), phenytoin (52), acetazolamide (17), clonazepam (15), sulthiame (6), ethosuximide (6), nitrazepam (4), and clobazam (4). Epilepsy patients treated with antiepileptic drug polytherapy were frequently found to have crystalluria in patients demonstrating alkaline urine and taking acetazolamide, zonisamide (particularly with high serum levels), or many antiepileptic drugs in combination. Regular urinalysis seems to be necessary in these patients, and the evaluation for urolithiasis should be performed if persistent crystalluria is demonstrated.

Carbamazepine-induced IgG1 and IgG2 deficiency associated with B cell maturation defect.

This paper presents the first case of asymptomatic IgG1 and IgG2 deficiency induced by carbamazepine (CBZ). The patient has remained asymptomatic since CBZ was started because IgM reduced only transiently, IgA decreased but remained within the normal range, and the specific antibodies to organisms having capsular polysaccharide antigens were not defective in this case. Analysis of membrane surface immunoglobulin (sIg) on B lymphocytes indicated that the maturation of B cells was defective from sIgM+ cells to sIgG+ cells. There have been no previous reports of IgG deficiency induced by CBZ due to this mechanism. Immunoglobulins should be carefully examined in patients treated with CBZ, particularly after its initiation.

Frequent seizures with elevated interleukin-6 at the eruptive stage of exanthema subitum.

A 15-month-old girl developed frequent seizures at the eruptive stage of exanthema subitum. The eruption persisted for 2 weeks. Serum immunoglobulin G antibody to human herpes virus type 6 (HHV-6) increased markedly. Interleukin-6 was elevated whereas HHV-6 deoxyribonucleic acid was not detected in cerebrospinal fluid. These findings suggest that immune-mediated reactions after HHV-6 infection rather than direct action of active HHV-6 are responsible for frequent seizures in this case.

Juvenile dermatomyositis associated with subclinical hypothyroidism due to auto-immune thyroiditis.

We report a rare association of juvenile dermatomyositis with subclinical hypothyroidism due to auto-immune thyroiditis. Although the patient had no symptoms of hypothyroidism, thyroid auto-antibodies remained elevated even after disease remission.

Remission of West syndrome associated with valproate hepatotoxicity.

A 6-month-old girl developed West syndrome and it remitted in association with valproate-induced hepatic dysfunction. Plasma -alanine elevated after valproate hepatotoxicity, which seemed to be a possible cause of remission. The patient has been seizure-free with normal electroencephalogram for 12 months without any anticonvulsants. Her developmental milestones were within normal limits at the age of 18 months.