Language and sensory characteristics are reflected in voice-evoked responses in low birth weight children.

BACKGROUND: Children born with very low birth weight (VLBW) are at higher risk for cognitive impairment, including language deficits and sensorimotor difficulties. Voice-evoked response (P1m), which has been suggested as a language development biomarker in young children, remains unexplored for its efficacy in VLBW children. Furthermore, the relation between P1m and sensory difficulties in VLBW children remains unclear. METHODS: 40 children with VLBW were recruited at 5-to-6 years old (26 male, 14 female, mean age of months ± SD, 80.0 ± 4.9). We measured their voice-evoked brain response using child-customized magnetoencephalography (MEG) and examined the relation between P1m and language conceptual inference ability and sensory characteristics. RESULTS: The final sample comprised 36 children (23 boys, 13 girls; ages 61-86 months; gestational ages 24-36 weeks). As a result of multiple regression analysis, voice-evoked P1m in the left hemisphere was correlated significantly with language ability (ß = 0.414 P = 0.015) and sensory hypersensitivity (ß = 0.471 P = 0.005). CONCLUSION: Our findings indicate that the relation between P1m and language conceptual inference ability observed in term children in earlier studies is replicated in VLBW children, and suggests P1m intensity as a biomarker of sensory sensitivity characteristics. IMPACT: We investigated brain functions related to language development and sensory problems in very low birth-weight children. In very low birth weight children at early school age, brain responses to human voices are associated with language conceptual inference ability and sensory hypersensitivity. These findings promote a physiological understanding of both language development and sensory characteristics in very low birth weight children.

Correlation between umbilical cord hemoglobin and rate of jaundice requiring phototherapy in healthy newborns.

BACKGROUND: Delay of umbilical cord clamping by at least 1 min is recommended for newborns not requiring resuscitation in the International Liaison Committee On Resuscitation-Consensus on Science with Treatment Recommendations (ILCOR-CoSTR) 2010 guidelines. The delay in clamping improves iron status through early infancy but may increase the likelihood of jaundice requiring phototherapy. The present study investigated the relationship between umbilical cord hemoglobin and the rate of jaundice requiring phototherapy in healthy Japanese newborns. METHODS: Cord hemoglobin was measured in healthy newborns and the rate of infants receiving phototherapy for jaundice and other data were obtained from medical records. RESULTS: Jaundice requiring phototherapy mostly occurred in association with high cord blood hemoglobin, which is increased by delayed cord clamping. CONCLUSIONS: Higher cord hemoglobin may increase neonatal jaundice in newborns in Japan, therefore the present results support the Japan Resuscitation Council guideline 2010, which does not recommend delay of umbilical cord clamping by at least 1 min, in contrast to the ILCOR guidelines.

Association Between History of Psychiatric Disorder and Degree of Physical Injury Among Suicide Attempters: Secondary Data Analysis in a Japanese Rural Area.

INTRODUCTION: While there may be differences in the choice of suicide methods between attempters with and those without a history of psychiatric disorders, it is not clear whether these differences predict the actual degree of physical injury. The present study aimed to investigate the association between the history of psychiatric disorder and the degree of physical injury among suicide attempters in a Japanese rural area. METHODS: We conducted a cross-sectional study analyzing secondary data of 806 suicide attempters from April 2012 to March 2022 obtained from a Japanese rural city. The exposure variable was a history of psychiatric disorders. The primary outcome was the degree of physical injury of suicide attempters: moderate and severe. We conducted a multivariate Poisson regression analysis to estimate the prevalence ratios (PRs) and 95% confidence intervals (CIs). RESULTS: Among 806 suicide attempters, a significant negative association between the history of psychiatric disorder and the degree of physical injury was observed (PR = 0.40; 95% CI, 0.28-0.59). Those with and without psychiatric disorders were more likely to choose low- and severe-lethality suicide methods such as drug or psychotropic overdoses and hanging or deep wrist injuries, respectively (P < .001). CONCLUSIONS: The present study highlights the importance of considering suicide attempters, both with and without psychiatric disorders, while formulating targeted suicide prevention strategies.

Designing artificial circadian environments with multisensory cares for supporting preterm infants' growth in NICUs.

Previous studies suggest the importance of stable circadian environments for fetuses to achieve sound physiology and intrauterine development. This idea is also supported by epidemiological and animal studies, in which pregnant females exposed to repeated shifting of light-dark cycles had increased rates of reproductive abnormalities and adverse pregnancy outcomes. In response to such findings, artificial circadian environments with light-dark (LD) cycles have been introduced to NICUs to promote better physical development of preterm infants. Such LD cycles, however, may not be fully effective for preterm infants who are less than 30 weeks gestational age (WGA) since they are too premature to be adequately responsive to light. Instead, circadian rhythmicity of incubated preterm infants less than 30 WGA may be able to be developed through stimulation of the non-visual senses such as touch and sound.

Preterm toddlers have low nighttime sleep quality and high daytime activity.

A number of studies have been made on the sleep characteristics of children born preterm in an attempt to develop methods to address the sleep problems commonly observed among such children. However, the reported sleep characteristics from these studies vary depending on the observation methods used, i.e., actigraphy, polysomnography and questionnaire. In the current study, to obtain reliable data on the sleep characteristics of preterm-born children, we investigated the difference in sleep properties between 97 preterm and 97 term toddlers of approximately 1.5 years of age using actigraphy. Actigraphy units were attached to the toddlers' waists with an adjustable elastic belt for 7 consecutive days, and a child sleep diary was completed by their parents. In the study, we found that preterm toddlers had more nocturnal awakenings and more daytime activity, suggesting that preterm-born children may have a different process of sleep development in their early development.

Pregabalin withdrawal in patients without psychiatric disorders taking a regular dose of pregabalin: A case series and literature review.

Pregabalin is a drug that can cause psychiatric symptoms via pregabalin withdrawal. Prior reports on pregabalin withdrawal have mainly focused on cases with pregabalin dependence or abuse, and little attention has been paid to patients who are prescribed regular doses of pregabalin. Herein, we report three cases of pregabalin withdrawal in patients without psychiatric disorders, taking regular doses of pregabalin, who developed psychiatric symptoms such as insomnia and anxiety after abrupt discontinuation of pregabalin. In addition, we conducted a systematic review of six case reports (previous studies) of pregabalin withdrawal under regular doses of pregabalin. Among the six cases, three patients had no comorbid mental or substance use disorders, the dose of pregabalin ranged from 150 to 600 mg/d, and the duration of pregabalin use ranged from a few weeks to many years. Of these six cases of pregabalin withdrawal, five had psychopathological symptoms, three had vegetative symptoms, and three had neurologic and physical complications. We concluded that since pregabalin withdrawal can occur even with regular doses and short-term use, clinicians must carefully reduce pregabalin doses when reducing or discontinuing treatment, paying close attention to withdrawal symptoms. Our case series sheds light on the scant evidence from previous research on physical dependence in patients who are taking regular doses of pregabalin. Furthermore, our cases were also valuable in demonstrating that pregabalin withdrawal can occur even after a relatively short period of 2 months.

The Usefulness of the Combination of D-Dimer and Soluble Fibrin Monomer Complex for Diagnosis of Venous Thromboembolism in Psychiatric Practice: A Prospective Study.

PURPOSE: D-dimer has the advantage of excluding venous thromboembolism (VTE) due to its high sensitivity but is disadvantageous for diagnosing VTE due to its low specificity. A method to increase the usefulness of D-dimer in the diagnosis of VTE is warranted. This study aimed to investigate the usefulness of the combination of D-dimer and soluble fibrin monomer complex (SFMC), which has been suggested as a new candidate marker for VTE, in VTE diagnosis. PATIENTS AND METHODS: This prospective study in 109 subjects was performed at a psychiatric department between August 1, 2017 and December 31, 2019. Subjects' levels of D-dimer and SFMC were measured simultaneously. Plasma levels of D-dimer and SFMC were measured using NANOPIA® D-dimer and NANOPIA® SF. Subjects with positive D-dimer (≥1.0 µg/mL) results underwent contrast computed tomography for confirmation of VTE within 12 hours of D-dimer measurement. A receiver operating characteristic curve analysis was performed to examine the usefulness of SFMC for the diagnosis of VTE. RESULTS: Only 109 of the 783 subjects without symptoms suggestive of VTE participated in the study. Out of 41 subjects with positive D-dimer results, 17 subjects were diagnosed with VTE. A receiver operating characteristic curve analysis was performed to determine cutoff values. The area under the curves was 0.848 for SFMC (p<0.001, 95% CI 0.722 to 0.974), and the optimal cutoff value was 10.0 µg/mL (sensitivity 58.8%, specificity 100%, positive predictive value 100%, negative predictive value 77.4%). CONCLUSION: SFMC was useful for diagnosing VTE in the psychiatric patients with positive D-dimer results.

Association between sleep habits/disorders and emotional/behavioral problems among Japanese children.

Actual sleep status and the association between sleep habits/disorders and emotional/behavioral problems among children in the development stage have not been fully clarified. A questionnaire survey was conducted on the sleep habits/disorders (Brief Child Sleep Questionnaire; BCSQ) and emotional/behavioral problems (Strengths and Difficulties Questionnaire; SDQ) of 87,548 children enrolled in ordinary classes in nine grade levels from the first grade of elementary school to the third grade of junior high school from December 2009 to April 2010. As school grade increased, children's bedtimes were delayed and sleep duration was reduced by 2.0 h over the nine grade levels. Based on the BCSQ, 18.3% of children were judged to have some type of sleep disorder, and about 30% to 40% of children had sleep symptoms at bedtime, during sleep, and at wake time. Multiple regression analysis showed that emotional and behavioral problems were associated with presence of any sleep symptom, longer sleep latency, and longer awake time after sleep onset, whereas total sleep time was not. Sleep symptoms at wake time were most strongly associated with emotional and behavioral problems. Status of sleep habits/disorders should be considered when interpreting emotional/behavioral problems in school-age children.

Severity of Depressive Symptoms is Associated with Venous Thromboembolism in Hospitalized Patients with a Major Depressive Episode.

PURPOSE: A major depressive episode is a risk factor for venous thromboembolism (VTE) in psychiatric inpatients. However, it is unclear whether the severity of depressive symptoms or duration of the current depressive episode is associated with VTE. Further, the VTE prevalence among hospitalized patients with a major depressive episode receiving electroconvulsive therapy is unknown. This retrospective study examined factors associated with VTE among hospitalized patients with a major depressive episode and estimated the prevalence of VTE in such patients who underwent electroconvulsive therapy. PATIENTS AND METHODS: Patients with a major depressive episode hospitalized in the Department of Neuropsychiatry at Akita University Hospital between January 2018 and December 2020 were included. Data from the first week of hospitalization were extracted from medical records. VTE was diagnosed based on the findings of computed tomography. To evaluate whether the severity of depressive symptoms or duration of the current depressive episode was associated with VTE, logistic regression analysis was conducted after adjusting for covariates with known VTE risk factors (antidepressants, antipsychotics, and physical comorbidities). RESULTS: We analyzed 133 patients; of these, 14 were diagnosed with asymptomatic VTE. The severity of depressive symptoms (odds ratio: 1.220, 95% confidence interval: 1.081-1.377, p = 0.001) was significantly associated with VTE. The prevalence of VTE among those receiving electroconvulsive therapy was 35% (7/20). CONCLUSION: The prevalence of VTE was 35% among patients receiving in-hospital electroconvulsive therapy for a major depressive episode. VTE should be considered for hospitalized patients with severe depressive symptoms and patients receiving in-hospital electroconvulsive therapy for a major depressive episode.

Daytime nap and nighttime breastfeeding are associated with toddlers' nighttime sleep.

The purpose of the present study is to examine the association between toddlers' sleep arrangements and their nighttime sleep duration and other sleep variables. For this investigation, we performed a study in which child activity and sleep levels were recorded using actigraphy. The parents of 1.5-year-old toddlers (n = 106) were asked to attach an actigraphy unit to their child's waist with an adjustable elastic belt and complete a sleep diary for 7 consecutive days. Questionnaires were used to assess the sleep arrangements of the toddlers. There was a significant negative correlation between nap duration and nighttime sleep duration, suggesting that longer nap sleep induces shorter nighttime sleep duration. Among the sleep arrangements, such as nighttime breastfeeding or co-sleeping, only nighttime breastfeeding predicted shorter nighttime sleep duration. Our findings indicate that shorter naps induce a longer nighttime sleep in 1.5-year-old toddlers while nighttime breastfeeding decreases their nighttime sleep duration.

Sleep maturation influences cognitive development of preterm toddlers.

Our recent study on full-term toddlers demonstrated that daytime nap properties affect the distribution ratio between nap and nighttime sleep duration in total sleep time but does not affect the overall total amount of daily sleep time. However, there is still no clear scientific consensus as to whether the ratio between naps and nighttime sleep or just daily total sleep duration itself is more important for healthy child development. In the current study, to gain an answer to this question, we examined the relationship between the sleep properties and the cognitive development of toddlers born prematurely using actigraphy and the Kyoto scale of psychological development (KSPD) test. 101 premature toddlers of approximately 1.5 years of age were recruited for the study. Actigraphy units were attached to their waist with an adjustable elastic belt for 7 consecutive days and a child sleep diary was completed by their parents. In the study, we found no significant correlation between either nap or nighttime sleep duration and cognitive development of the preterm toddlers. In contrast, we found that stable daily wake time was significantly associated with better cognitive development, suggesting that sleep regulation may contribute to the brain maturation of preterm toddlers.

The uterus sustains stable biological clock during pregnancy.

Maternal circadian information has been reported to play an important role in fetal physiology and development. Hormones and nutrition have been mainly investigated as circadian cues from mother to fetus. However, the influences of circadian properties of the pregnant reproductive organs on fetuses have not been fully investigated. To gain an insight on the circadian functions of the reproductive organs, we examined molecular clocks in the pregnant rat uterus and placenta. By using a Period1-luciferase (Per1-luc) rat, whose tissues express luciferase corresponding to activation of Period1, a "key clock gene", we examined the uterus clock during non-pregnancy, on embryonic day 12 (E12), and on E22 (the end of pregnancy) in a light-dark (LD) cycle and constant darkness (DD). By in situ hybridization we further explored Per1 mRNA rhythms in the placenta on E12 and E22. The uterus in vitro showed clear circadian Per1-luc rhythms both in and out of pregnancy, having peaks at around the time corresponding to dusk in LD. Likewise, in DD, the uterus in vitro had the same Per1-luc rhythms. The decidua in LD showed circadian Per1 mRNA rhythms, peaking during night 6 h after dusk, while the decidua in DD showed the same Per1 mRNA rhythms only on E22. In contrast, the labyrinth showed no circadian Per1 mRNA rhythms in LD or DD during pregnancy. These results suggest that the uterus and decidua, a maternally-originated tissue of the placenta, but not the labyrinth, a fetus-originated tissue of the placenta, can provide the fetus with circadian information.

Prevalence of Asymptomatic Venous Thromboembolism in Depressive Inpatients.

PURPOSE: While depression has been recognized as a risk factor for venous thromboembolism (VTE), the prevalence of VTE in depressed inpatients has never been investigated. The aim of this study was thus to examine VTE prevalence and factors associated with VTE in depressed inpatients. PATIENTS AND METHODS: We conducted a retrospective cross-sectional study of consecutive depressed inpatients (n = 94) from January 1, 2018, to June 30, 2019, at the psychiatry department of Akita University Hospital. As part of our clinical routine, depressed inpatients were screened for VTE using D-dimer, and patients who screened positive underwent enhanced CT to examine VTE. A variety of data was extracted from medical records, including, amongst others, age, sex, body mass index, diagnoses of psychiatric disorders, total scores on the 17-item Hamilton Depression Rating Scale, duration of current depressive episode, daily dosages of antidepressants and antipsychotics, catatonia, and physical restraint. RESULTS: VTE was detected in 8.5% of depressed inpatients. There were no significant differences between VTE-positive and VTE-negative inpatients regarding any of the considered factors. CONCLUSION: Our analysis shows a VTE prevalence of 8.5% in depressed inpatients, higher than that of 2.3% reported in a previous study in hospitalized patients with psychiatric disorders including depression. This emphasizes the importance of VTE screening for depressive inpatients.

Postural change for supine position does not disturb toddlers' nap.

This study examined whether forced postural change from prone to supine during toddlers' nap, a preventative measure taken in Japan for sudden unexplained death in childhood (SUDC), disturbs toddlers' sleep. When the "Back to Sleep" campaign (BSC) was introduced to Japan in 1996, its recommendations were also applied to infants aged 1 year old and over with the expectation that the BSC recommendations may also contribute to a decrease in the occurrence rate of SUDC. Since then, Japanese nurseries have routinely conducted sleeping position checks and positional adjustments of toddlers every 5-10 min during naps. A total of 52 toddlers (age 18.4 ± 3.3 months, means ± SD) were continuously monitored for 8 h during daytime at nursery schools for wake-sleep status and body position (prone, supine and lateral) with actigraphs and 3-orthogonal-axis accelerometers. Out of the 52 toddlers, 24 toddlers adopted prone positions during naps, which were adjusted by nursery staff back to supine. When nursery staff manually changed the toddlers position from prone to supine, the toddlers either did not wake or woke only briefly (3.1 ± 4.9 min) and returned to sleep soon after the positional change. Our study indicates that manual change of toddlers' sleeping position from prone to supine, a potential SUDC prevention method, does not disturb toddlers' sleep during their naps.

Constant light desynchronizes mammalian clock neurons.

Circadian organization can be disrupted by constant light, resulting in behavioral arrhythmicity or 'splitting' of rhythms of activity and rest. By imaging molecular rhythms of individual clock neurons in explanted mouse clock nuclei, we now find that constant light desynchronizes clock neurons but does not compromise their ability to generate circadian rhythms. Cellular synchrony within clock nuclei is disrupted during arrhythmicity, whereas neurons in the left and right clock nuclei cycle in antiphase during 'splitting.'

The shape of disposable diaper affects spontaneous movements of lower limbs in young infants.

This study examined the characteristics of young infants' lower limb spontaneous movements based on differences in shape of diapers. Twenty-seven healthy infants (103 ± 16.3 days old) were enrolled in this study. We measured the spontaneous movements of their lower limbs in four conditions (Naked, wearing Normal type diapers, wearing Type A diapers, and wearing Type B diapers). The Normal diaper has a wider waist belt than the Type A diaper, and the Type B diaper has a narrower crotch area than the Type A diaper. We observed them in seven indices (the velocity of lower limb movements, the trajectory area of knee movement in the sagittal plane and the frontal plane, the distance between both knees and between side of abdomen and knee, and correlation of velocities between side of abdomen and knee and between left and right ankles). The results showed that the velocity of the lower limb movements in the Naked condition was higher than when wearing Normal diapers. The value for the trajectory area of knee movement in sagittal plane, which reflects the range of lower leg lifting movements and closeness of such movements to the trunk, for the Type B diaper condition was higher than that for the Normal diaper condition. This result indicates that the shape of the diaper affects the spontaneous movements of the lower limbs of young infants.

Entrainment of the Circadian Clock in Neural Stem Cells by Epidermal Growth Factor is Closely Associated with ERK1/2-mediated Induction of Multiple Clock-related Genes.

The mitotic activity of certain tissues in the body is closely associated with circadian clock function. However, the effects of growth factors on the molecular clockwork are not fully understood. Stimulation of neural stem cells (NSCs) with epidermal growth factor (EGF), a well-known mitogen, is known to cause synchronized cell cycle progression with a period of approximately 24 h, closely associated with the Per2 gene expression rhythm. Here, we examined the effects of EGF on the molecular clockwork of NSCs. Treatment of cultured NSCs derived from embryonic mouse forebrain with EGF (20 ng/mL) caused a phase shift in the PER2::LUCIFERASE bioluminescence rhythm in a stimulation time-dependent manner. The EGF phase-response curve differed from that of forskolin (FK)-a well-known chemical resetting stimulus-both in the advance/delay ratio and stimulation time-dependency. PCR array analysis followed by quantitative PCR validation demonstrated that EGF treatment transiently induced multiple clock-related genes including Per1, Per2, Dec1, e4bp4, and Noct, whereas FK treatment induced a limited number of genes (Per1 and Dec1), suggesting that the mode of entrainment of NSC molecular clock was different for EGF and FK. EGF led to gene induction in the presence of cycloheximide, suggesting that de novo protein synthesis is unnecessary. Pretreatment with the MEK1/2 inhibitor U0126 significantly suppressed the acute induction of Per2, Dec1, and Noct by EGF and also abolished the EGF-induced phase shift of the PER2::LUCIFERASE rhythm in NSCs. These results suggest a unique effect of EGF on the molecular clockwork of NSCs.

Combined effects of body position and sleep status on the cardiorespiratory stability of near-term infants.

The purpose of this study was to determine the effects of body position (prone, supine and lateral) together with sleep status (wake and sleep) on the cardiorespiratory stability of near-term infants. A total of 53 infants (gestational age at birth 33.2 ± 3.5 weeks; birth weight 1,682 ± 521 g; gestational age at recording 38.6 ± 2.1 weeks; weight at recording: 2,273 ± 393 g) were monitored for 24 hours for clinically significant apnea (>15 seconds), bradycardia (<100 bpm), and oxygen desaturation (SpO2 < 90%) in alternating body positions (prone, supine and lateral) by cardiorespiratory monitors and 3-orthogonal-axis accelerometers. Sleep status of the infants was also continuously monitored by actigraphs. No apnea was observed. During wake, severe bradycardia was most frequently observed in the lateral position while, during sleep, severe bradycardia was most frequently observed in the supine position. Desaturation was most frequently observed in the supine and lateral positions during both wake and sleep. Our study suggests that the cardiorespiratory stability of infants is significantly compromised by both body position and sleep status. During both wake and sleep, prone position induces the most stable cardiorespiratory functions of near-term infants.

TSH and PRL, side-effect markers in aripiprazole treatment: adjunctive aripiprazole-induced thyrotropin oversuppression in a young man with schizophrenia.

A 26-year-old Japanese man was admitted to our unit with exacerbated paranoid schizophrenia. Prior to his admission, daily administration of olanzapine had been sufficient to maintain a partial remission of his schizophrenia, but due to an exacerbation of his delusions, he had then also been prescribed aripiprazole, which had been followed by no improvement in symptoms and a gradual further exacerbation of auditory delusions. Physical examinations, brain MRI and neurophysiological assessment were unremarkable. Blood analysis, however, revealed extremely low thyroid-stimulating hormone (TSH) and prolactin-releasing hormone (PRL) concentration. Interestingly, after aripiprazole discontinuation, he returned to partial remission with an increase in plasma TSH and PRL concentration.

Potential New Non-Invasive Therapy Using Artificial Oxygen Carriers for Pre-Eclampsia.

The molecular mechanisms of pre-eclampsia are being increasingly clarified in animals and humans. With the uncovering of these mechanisms, preventive therapy strategies using chronic infusion of adrenomedullin, vascular endothelial growth factor-121 (VEGF-121), losartan, and sildenafil have been proposed to block narrow spiral artery formation in the placenta by suppressing related possible factors for pre-eclampsia. However, although such preventive treatments have been partly successful, they have failed in ameliorating fetal growth restriction and carry the risk of possible side-effects of drugs on pregnant mothers. In this study, we attempted to develop a new symptomatic treatment for pre-eclampsia by directly rescuing placental ischemia with artificial oxygen carriers (hemoglobin vesicles: HbV) since previous data indicate that placental ischemia/hypoxia may alone be sufficient to lead to pre-eclampsia through up-regulation of sFlt-1, one of the main candidate molecules for the cause of pre-eclampsia. Using a rat model, the present study demonstrated that a simple treatment using hemoglobin vesicles for placental ischemia rescues placental and fetal hypoxia, leading to appropriate fetal growth. The present study is the first to demonstrate hemoglobin vesicles successfully decreasing maternal plasma levels of sFlt-1 and ameliorating fetal growth restriction in the pre-eclampsia rat model (p < 0.05, one-way ANOVA). In future, chronic infusion of hemoglobin vesicles could be a potential effective and noninvasive therapy for delaying or even alleviating the need for Caesarean sections in pre-eclampsia.