Association between neonatal phototherapy and sleep: The Japan Environment and Children's Study.

This observational cohort study aimed to evaluate the association between the duration of neonatal phototherapy and sleep-and-wakefulness states at 1 month, 1.5 years, and 3 years of age. We analysed data from 77,876 infants using the Japan Environment and Children's Study, a nationwide birth cohort study. The participants were divided into three groups: no phototherapy, short phototherapy (1-24 h), and long phototherapy (>24 h). Multiple regression analysis was performed to assess the effect of phototherapy duration on infant sleep at each age after adjusting for potential risk factors. A longer duration of phototherapy was associated with a shorter sleep time over 24 h at 1 month of age (ß, -0.62; SE, -0.77 to -0.47) when compared with a shorter duration of, or no, phototherapy, following the adjustment of confounding factors. Contrastingly, the short duration group, when compared with the no phototherapy group, was associated with later sleep onset (ß, 0.04; SE, 0.00-0.08) and later sleep offset (ß, 0.05; SE, 0.01-0.09) at 1.5 years of age. We concluded that the duration of phototherapy may be transiently associated with sleep duration in infants, as emphasised by the shortening of the total sleep time per 24 h at 1 month of age.

Phototherapy and risk of developmental delay: the Japan Environment and Children's Study.

This observational cohort study aimed to examine the association between the duration of phototherapy for neonatal jaundice and the risk of developmental delay at 3 years of age using nationwide birth cohort data. Data from 76,897 infants were analyzed. We divided participants into four groups: no phototherapy, short phototherapy (1-24 h), long phototherapy (25-48 h), and very long phototherapy (> 48 h). The Japanese version of the Ages and Stages Questionnaire-3 was used to evaluate the risk of developmental delay at 3 years of age. Logistic regression analysis was performed to assess the impact of phototherapy duration on the prevalence of developmental delay. After adjustment for potential risk factors, a dose-response relationship was identified between the duration of phototherapy and Ages and Stages Questionnaire-3, and the differences were significant in four domains; odds ratio for communication delay was associated with short, long, and very long phototherapy = 1.10 (95% confidence interval 0.97-1.26), 1.32 (1.04-2.66), and 1.48 (1.11-1.98), respectively; for gross motor delay = 1.01 (0.89-1.15), 1.28 (1.03-2.58), and 1.26 (0.96-1.67); for problem solving delay = 1.13 (1.03-1.25), 1.19 (0.99-1.43), and 1.41 (1.11-1.79); and for personal social delay = 1.15 (0.99-1.32), 1.10 (0.84-1.44), and 1.84 (1.38-2.45). CONCLUSION: Longer duration of phototherapy is a predictive factor for developmental delay, making it important to avoid extended periods of phototherapy. However, whether it increases the prevalence of developmental delay remains unclear. WHAT IS KNOWN: • Phototherapy is a common treatment for neonatal jaundice, associated with both short-term and long-term complications. • However, an association between phototherapy and the prevalence of developmental delay has not been revealed in a large cohort study. WHAT IS NEW: • We identified that a long duration of phototherapy was a predictive factor for developmental delay at 3 years of age. • However, whether a long duration of phototherapy increases the prevalence of developmental delay remains unclear.

The Duration of Neonatal Phototherapy and Allergic Disorders: The Japan Environment and Children's Study.

INTRODUCTION: Currently, the association between the duration of neonatal phototherapy and the risk of allergic disorders has not been reported. This observational cohort study aimed to examine the association between allergic disorders, including food allergies, that are present before 3 years of age and the duration of phototherapy using the nationwide birth cohort data. METHODS: The Japan Environment and Children's Study was a nationwide birth cohort study. Data of 77,064 infants aged 1 year, 1.5 years, 2 years, and 3 years were analyzed. We divided the participants into three groups: no phototherapy, short phototherapy (1-24 h), and long phototherapy (>24 h) and evaluated the cumulative incidence of allergic disorders before 3 years of age, including asthma, atopic dermatitis, and food allergies. Logistic regression analysis was performed to assess the impact of phototherapy duration on the cumulative incidence of allergic disorders. RESULTS: After adjustment for potential risk factors, long phototherapy was found to be positively associated with food allergies at age 2 years (OR: 1.16; 95% CI: 1.01-1.33) and all allergic disorders at age 3 years (OR: 1.12; 95% CI: 1.01-1.24), including food allergies (OR 1.18; 95% CI: 1.04-1.35). CONCLUSION: A long duration of neonatal phototherapy was positively associated with the risk of allergic disorders, especially food allergies.

Nationwide Actions Against Heart Failure Pandemic in Japan　- What Should We Do From Academia?

Heart failure pandemic is rapidly approaching in Japan, requiring nationwide actions. In particular, the Japanese Circulation Society and related societies launched the Stroke and Cardiovascular Disease Control Act, which was passed by the National Diet, as the first ever legislative policy measure against stroke and cardiovascular disease. In association with this, actions against heart failure pandemic from the scientific field are also important. Because heart failure pandemic is a critical problem not only in Japan but also in many developed countries, we believe the nationwide approach, as summarized here, will greatly contribute to the development of cardiovascular medicine, particularly the management and treatment of heart failure worldwide.

Cell-Type-Specific Contributions of Medial Prefrontal Neurons to Flexible Behaviors.

Behavioral flexibility and impulse control are necessary for successful execution of adaptive behavior. They are impaired in patients with damage to the prefrontal cortex (PFC) and in some clinically important conditions, such as obsessive-compulsive disorder. Although the medial prefrontal cortex (mPFC) has been investigated as a critical structure for behavioral flexibility and impulse control, the contribution of the underlying pyramidal neuron cell types in the mPFC remained to be understood. Here we show that interneuron-mediated local inactivation of pyramidal neurons in the mPFC of male and female mice induces both premature responses and choice bias, and establish that these impulsive and compulsive responses are modulated independently. Cell-type-specific photoinhibition of pyramidal deep layer corticostriatal or corticothalamic neurons reduces behavioral flexibility without inducing premature responses. Together, our data confirm the role of corticostriatal neurons in behavioral flexibility and demonstrate that flexible behaviors are also modulated by direct projections from deep layer corticothalamic neurons in the mPFC to midline thalamic nuclei.SIGNIFICANCE STATEMENT Behavioral flexibility and impulse control are indispensable for animals to adapt to changes in the environment and often affected in patients with PFC damage and obsessive-compulsive disorder. We used a probabilistic reversal task to dissect the underlying neural circuitry in the mPFC. Through characterization of the three major pyramidal cell types in the mPFC with optogenetic silencing, we demonstrated that corticostriatal and corticothalamic but not corticocortical pyramidal neurons are temporally recruited for behavioral flexibility. Together, our findings confirm the role of corticostriatal projections in cognitive flexibility and identify corticothalamic neurons as equally important for behavioral flexibility.

The endogenous danger signal uric Acid augments contact hypersensitivity responses in mice.

OBJECTIVE: The danger hypothesis proposes that the immune system responds not only to foreign antigens but also to damaged cells or tissues. Recently, uric acid crystals (monosodium urate, MSU) from necrotic cell lysates were identified as a danger signal for dendritic cells (DCs). Our aim was to determine whether MSU modulates immune responses in the skin. METHOD: We analyzed the effect of MSU on trinitrochlorobenzene-induced contact hypersensitivity responses using BALB/c mice administered potassium oxonate, an uricase inhibitor, to prevent MSU degradation. Ear swelling response after elicitation and activation profiles of DCs and T cells in draining lymph nodes after sensitization were assessed. RESULTS: Intradermal administration of MSU augmented the ear swelling response in potassium oxonate-administered mice and enhanced expression of CD86 and CD40 molecules on DCs in the lymph nodes. Activation of DCs was followed by an increase in CD69+ and CD44+ T cells in CD4+ and/or CD8+ subsets in the lymph nodes 4 days after trinitrochlorobenzene sensitization. CONCLUSION: These observations demonstrate that MSU is an endogenous danger signal, which augments the contact hypersensitivity response in mice. MSU released from damaged skin may act as an endogenous adjuvant to augment immune response.