[Perspective on transition from pediatric to adult health care for patients with neurological disease: current situation and issues].

An improvement in efficacy treatment and development of the social support system has led to many patients with neurological disease being able to reach adulthood. Therefore health care for life from pediatrics to adulthood has become necessary. The Special Committee for Measures Against Transition from Pediatric to Adult Health Care of the Japanese Society of Neurology officially started to examine the current situation and issues of transition from pediatric to adult health care in July 2020. Pediatric neurologists and adult neurologists have an awareness of this issue of constructing a better transition from pediatric to adult health care. However, there are some tasks that need to be resolved in the medical system. We intend to improve the understanding of transition and assessment of medical service fees for transition in cooperation with the Japanese Society of Neurology and the Japanese Society of Child Neurology.

Effect of a Nitrite/Nitrate-Based Accelerator on the Strength Development and Hydrate Formation in Cold-Weather Cementitious Materials.

Recently, there has been increased use of calcium-nitrite and calcium-nitrate as the main components of chloride- and alkali-free anti-freezing agents to promote concrete hydration in cold weather concreting. As the amount of nitrite/nitrate-based accelerators increases, the hydration of tricalcium aluminate (C3A phase) and tricalcium silicate (C3S phase) in cement is accelerated, thereby improving the early strength of cement and effectively preventing initial frost damage. Nitrite/nitrate-based accelerators are used in larger amounts than usual in low temperature areas below -10 °C. However, the correlation between the hydration process and strength development in concrete containing considerable nitrite/nitrate-based accelerators remains to be clearly identified. In this study, the hydrate composition (via X-ray diffraction and nuclear magnetic resonance), pore structures (via mercury intrusion porosimetry), and crystal form (via scanning electron microscopy) were determined, and investigations were performed to elucidate the effect of nitrite/nitrate-based accelerators on the initial strength development and hydrate formation of cement. Nitrite/nitrate-AFm (aluminate-ferret-monosulfate; AFm) was produced in addition to ettringite at the initial stage of hydration of cement by adding a nitrite/nitrate-based accelerator. The amount of the hydrates was attributed to an increase in the absolute amounts of NO2- and NO3- ions reacting with Al2O3 in the tricalcium aluminate (C3A phase). Further, by effectively filling the pores, it greatly contributed to the enhancement of the strength of the hardened cement product, and the degree of the contribution tended to increase with the amount of addition. On the other hand, in addition to the occurrence of cracks due to the release of a large amount of heat of hydration, the amount of expansion and contraction may increase, and it is considered necessary to adjust the amount used for each concrete work.

Evaluation of Mechanical and Shrinkage Behavior of Lowered Temperatures Cementitious Mortars Mixed with Nitrite-Nitrate Based Accelerator.

Recently, calcium nitrite (Ca(NO2)2) and calcium nitrate (Ca(NO3)2) have been increasingly used as the main components of salt- and alkali-free anti-freezing agents, for promoting concrete hydration in cold-weather concreting. With an increase in the amount of nitrite-based accelerator, the hydration of C3A, C3S, and ßC2S in the cement is accelerated, thereby improving its early strength and effectively preventing the initial frost damage. Meanwhile, with an increase in the amount of nitrite-based accelerator, the expansion and shrinkage of the concrete-and, therefore, the crack occurrence-are expected to increase. In this study, various experiments were conducted on shrinkage, crack initiation, and the development of mortar containing a considerable amount of a nitrite-based accelerator. The result confirmed that, as the amount of nitrite-based accelerator was increased, the shrinkage was increased, and cracking in early age was more likely to occur, compared to the cases without the addition of this accelerator.

Physicochemical Study on the Strength Development Characteristics of Cold Weather Concrete Using a Nitrite-Nitrate Based Accelerator.

There has recently been an increased use of anti-freezing agents that are primarily composed of salt- and alkali-free calcium nitrite (Ca(NO2)2) and calcium nitrate (Ca(NO3)2) to promote the hydration reaction of concrete in cold weather concreting. Nitrite-nitrate based accelerators accelerate the hydration of C3A and C3S in cement more quickly when their quantities are increased, thereby boosting the concrete's early strength and effectively preventing early frost damage. However, the connection between the hydrate formation behavior and the strength development characteristic over time has yet to be clearly identified. Therefore, in this study, a wide range of physicochemical reviews were carried out to clarify the relationship between the hydrate formation behavior and the strength development characteristics, both at an early age and at later ages, which results from the addition of nitrite-nitrate based accelerators to concrete in varying amounts. These accelerators also act as anti-freezing agents. The results show that an increased quantity of nitrite-nitrate based accelerators caused an increase in the early strength of the concrete. This was due to the formation of nitrite and nitrate hydrates in large amounts, in addition to ettringite containing SO42, which is generated during the hydration reaction of normal Portland cement at an early age. On the other hand, at later ages, there was a rise in nitrite and nitrate hydrates with needle crystal structures exhibiting brittle fracture behavior. A decrease in C-S-H gel and Ca(OH)2 hydrates, deemed to have caused a decline in strength on Day 3 and thereafter, was also observed.

An investigation of factors related to the use of respite care services for children with severe motor and intellectual disabilities (SMID) living at home in Japan.

Limited time away from the child is cited as the main factor that increases the burden for the primary caregiver of severely disabled children. The aim of this study was to quantitatively elucidate the factors related to the desire to use social services and the actual use of respite care services by the primary caregivers of severely disabled children in Japan. In this study, we investigated the use of respite care services in accordance with the primary caregivers' wishes by examining inhibiting or promoting factors associated with respite care service use only among those who wished to use social services. A total of 169 Japanese mothers participated and answered the questionnaires. We conducted a logistic regression analysis and a multiple regression analysis to investigate the factors related to respite care service use. The most important factors affecting a primary caregiver's desire to use social services were the belief that the child would enjoy using social services and the family's approval of the social service use. The most important factors affecting respite care service use were the family's approval of the use and a large care burden on the primary caregiver. Respite care services should be sought out before the care burden becomes too great to enable the primary caregiver to more easily contribute to the continuation of home care. A background of mother-child separation anxiety disrupted the use of respite care. However, believing that the child enjoys using social services may reduce primary caregivers' psychological resistance to being separated from their child, which is supported by tradition. Thus, it is also important for respite care service providers to provide information about the children to their primary caregivers and families while they are using respite care services.

[Treatment for self-injurious behavior in mentally handicapped populations--a report from our practice].

OBJECTIVE: Self-injurious behavior (SIB) is a common problem in individuals with intellectual disabilities, yet its clinical management remains to be established. We aimed to clarify the background factors and profiles of SIB in mentally and physically handicapped subjects and subsequently examined the efficacy of treatments attempted in our practice in order to achieve a better understanding of SIB and appro- priate interventions in these populations. METHODS: We surveyed 92 mentally handicapped subjects with SIB (including 25 females and 67 males, most of whom also had physical disabilities) as outpatients or inpatients of our institution using a retrospective questionnaire com- pleted by the corresponding doctors. RESULTS: Regarding psychobehavioral complications, impulsive mood swings (such as sudden rage) were more frequent than other behaviors. As to probable triggers of SIB, the patient's physical condition (17 cases) and noise or the temperature of the surrounding environment (38 cases) were identified. A total of 81 of 92 patients were given a prescription for SIB. Risperidone was the most commonly prescribed drug (75 cases), found to be effective in 38 (50.6%) cases, whereas phenothiazine antipsychotics were often more effective in patients with profound SIB. SSRIs (selective serotonin reuptake inhibitors) were applied in 20 cases, being effective in only five (25%) patients and discontinued in 11 (55%) patients due to the onset of several side effects, including overexcitement. As an additional agent for mood control, the antiepileptic topiramate was effective in 10 (76.9%) of 13 cases. Aside from medication, equipment for elbow extension was beneficial in some of the patients with profound SIB. CONCLUSIONS: Pharmacological intervention is sometimes beneficial, albeit only partly. Clinicians must therefore also consider triggers and factors in the surrounding environment for the development of SIB in mentally handicapped individuals.

A survey of subcutaneous blood flow in patients with SMID and subcutaneous ceftazidime administration using mentholated warm compresses in healthy subjects.

OBJECTIVES: To investigate subcutaneous blood flow rate (SBFR) in healthy volunteers and patients with severe motor and intellectual disabilities (SMID), and evaluate the effect of mentholated warm compresses (MWCs) on SBFR and subcutaneous ceftazidime absorption in healthy volunteers. METHODS: SBFR at the forearm, chest and abdomen were evaluated in Japanese healthy volunteers and in adults with SMID. The effects of MWCs on blood flow rate and ceftazidime pharmacokinetics were evaluated in healthy volunteers. RESULTS: SBFR was significantly lower in the forearms of female patients with SMID (n = 11) than in the forearms of healthy females (n = 6); it was not significantly lower in the abdomen or chest. There were no significant differences between male patients (n = 18) or controls (n = 12) in SBFR at any site. MWC application increased SBFR 1.3- to 2.0-fold compared with baseline in healthy controls (n = 6). MWC application increased ceftazidime maximum blood concentration, SBFR and time above mutant prevention concentration in a single healthy subject. CONCLUSIONS: Abdominal SBFR in patients with SMID did not differ from that of healthy subjects. MWC application increases SBFR and subcutaneous drug absorption rate in healthy humans.

Absorption Kinetics of Subcutaneously Administered Ceftazidime in Hypoperfused Guinea Pigs.

BACKGROUND: Pneumonia is the most common cause of death in patients with severe motor and intellectual disabilities (SMID), and intravenous ceftazidime (CAZ) is a widely used treatment for such infections. However, intravenous administration in patients with SMID may be difficult because of insufficient vascular development. OBJECTIVES: The aim of our study was to determine the feasibility of subcutaneous drug administration by mentholated warm compresses (WMCs) as an alternative delivery method for ceftazidime in patients with SMID. METHODS: CAZ was subcutaneously administered to the abdominal region of naphazoline-treated hypoperfused guinea pigs, which were used as a hemodynamic model of patients with SMID. MWCs or warm compresses (WCs) were applied to the injection site to increase blood flow. We calculated the cumulative CAZ absorption over time by using the deconvolution method. RESULTS: Application of MWCs or WCs increased blood flow at the administration site and increased CAZ plasma levels. Application of MWCs or WCs after subcutaneous CAZ injection led to higher CAZ plasma levels than the mutant prevention concentration for a longer period than was observed for CAZ administration without the application of MWCs or WCs. CONCLUSIONS: The application of MWCs or WCs enhanced subcutaneous CAZ absorption by increasing blood flow. MWCs and WCs are considered to be safe and routine methods to induce defecation after surgery on the digestive system; thus, the combination of these methods and subcutaneous CAZ administration is a potential method for treating pneumonia in patients with SMID.

Clinical, biochemical and molecular analysis of 13 Japanese patients with ß-ureidopropionase deficiency demonstrates high prevalence of the c.977G > A (p.R326Q) mutation [corrected].

ß-ureidopropionase (ßUP) deficiency is an autosomal recessive disease characterized by N-carbamyl-ß-amino aciduria. To date, only 16 genetically confirmed patients with ßUP deficiency have been reported. Here, we report on the clinical, biochemical and molecular findings of 13 Japanese ßUP deficient patients. In this group of patients, three novel missense mutations (p.G31S, p.E271K, and p.I286T) and a recently described mutation (p.R326Q) were identified. The p.R326Q mutation was detected in all 13 patients with eight patients being homozygous for this mutation. Screening for the p.R326Q mutation in 110 Japanese individuals showed an allele frequency of 0.9 %. Transient expression of mutant ßUP enzymes in HEK293 cells showed that the p.E271K and p.R326Q mutations cause profound decreases in activity (≤ 1.3 %). Conversely, ßUP enzymes containing the p.G31S and p.I286T mutations possess residual activities of 50 and 70 %, respectively, suggesting we cannot exclude the presence of additional mutations in the non-coding region of the UPB1 gene. Analysis of a human ßUP homology model revealed that the effects of the mutations (p.G31S, p.E271K, and p.R326Q) on enzyme activity are most likely linked to improper oligomer assembly. Highly variable phenotypes ranging from neurological involvement (including convulsions and autism) to asymptomatic, were observed in diagnosed patients. High prevalence of p.R326Q in the normal Japanese population indicates that ßUP deficiency is not as rare as generally considered and screening for ßUP deficiency should be included in diagnosis of patients with unexplained neurological abnormalities.

Factors associated with the empowerment of Japanese families raising a child with developmental disorders.

We identified factors associated with the empowerment of Japanese families using the Family Empowerment Scale (FES) to contribute to the improvement of empowerment in Japanese families raising a child with developmental disorders (DDs). The study was conducted in 350 caregivers who raised children aged 4-18 years with DDs in urban and suburban districts in Japan. Multiple regression analysis of data collected from 275 respondents revealed that a decrease in family empowerment level correlated with a higher number of siblings reared together, a shorter period since the diagnosis was made, and lower awareness of social support and self-efficacy in caregivers. Medications, possession of an intellectual disability certificate, infrequent hospital visits of the child, disuse of local services by caregivers, and young caregivers also correlated with a lower level of empowerment in the Japanese family.

Empowerment process for families rearing children with developmental disorders in Japan.

The understanding of developmental disorders and the support that is offered to families rearing a child with developmental disorders always have been limited in Japan. To clarify the empowerment process for families rearing a child with developmental disorders, we interviewed 20 mothers of children who lived in the wider Tokyo area, Japan. To analyze the data, we adopted the modified grounded theory approach. The results identified three stages in the empowerment process: confusion over caring for the child, confrontation with the child with the disorder, and expectations of a valuable life for the child. The empowerment process showed step-by-step progress: families that were originally ill-equipped to deal with their child's disorders were able to deal with them in collaboration with professionals through approaching the local administration and were able to shift their stance on child-rearing along with their child's growth. To promote the family empowerment process, cross-jurisdictional and cross-occupational collaboration among local care teams is needed. The members of the teams should understand the experiences and feelings of the families that are rearing children with developmental disorders in the context of the family's empowerment process.

[An estimation chart for the possibility of aspiration in patients with severe motor and intellectual disabilities: its reliability and accuracy].

Although the most common cause of death in patients with severe motor and intellectual disabilities (SMID) is aspiration pneumonia, there are no criteria to detect aspiration. We have been making an evaluation tool to detect aspiration in patients with SMID easily, in cooperation with the project of comprehensive study of disability, social health, and welfare, supported by the Ministry of Health, Labor and Welfare, Japan. Here we studied the reliability and accuracy of the 2001 edition of the "questionnaires for functions of eating and swallowing" and "estimation chart for the possibility of aspiration" in 20 patients with risk of aspiration (13 with cerebral palsy, six with acquired cerebral palsy and one with muscle disease). Family members or nursing staffs taking care of them answered the questionnaires. A pediatrician and an occupational therapist or speech therapist checked the chart. Reliability was checked by the agreement between the estimation of the two professionals, and accuracy was determined by comparing the results of the chart and videofluolography. The results showed good reliability (kappa 0.63) and accuracy (kappa 0.47). Based on these results and additional analysis of the check items, the new edition of the chart was established.

Genomic rearrangements resulting in PLP1 deletion occur by nonhomologous end joining and cause different dysmyelinating phenotypes in males and females.

In the majority of patients with Pelizaeus-Merzbacher disease, duplication of the proteolipid protein gene PLP1 is responsible, whereas deletion of PLP1 is infrequent. Genomic mechanisms for these submicroscopic chromosomal rearrangements remain unknown. We identified three families with PLP1 deletions (including one family described elsewhere) that arose by three distinct processes. In one family, PLP1 deletion resulted from a maternal balanced submicroscopic insertional translocation of the entire PLP1 gene to the telomere of chromosome 19. PLP1 on the 19qtel is probably inactive by virtue of a position effect, because a healthy male sibling carries the same der(19) chromosome along with a normal X chromosome. Genomic mapping of the deleted segments revealed that the deletions are smaller than most of the PLP1 duplications and involve only two other genes. We hypothesize that the deletion is infrequent, because only the smaller deletions can avoid causing either infertility or lethality. Analyses of the DNA sequence flanking the deletion breakpoints revealed Alu-Alu recombination in the family with translocation. In the other two families, no homologous sequence flanking the breakpoints was found, but the distal breakpoints were embedded in novel low-copy repeats, suggesting the potential involvement of genome architecture in stimulating these rearrangements. In one family, junction sequences revealed a complex recombination event. Our data suggest that PLP1 deletions are likely caused by nonhomologous end joining.