Neonatal disseminated herpes simplex virus (HSV) infection is a severe disease with high mortality and morbidity; yet, the pathophysiology remains unclear. Here, we report a male infant with disseminated HSV type 1 (HSV-1) infection, complicated by hemophagocytic lymphohistiocytosis (HLH) and multiple organ failure. The infant, born at 39 weeks of gestation by normal delivery, developed fever (38.5˚C) with the high serum C-reactive protein levels on the 1st day of life, and exhibited tachypnea on the 3rd day. On the 5th day of life, the patient received mechanical ventilation and was transferred to our neonatal ICU. Real-time PCR for HSV-1 DNA revealed an extremely high serum concentration (1.0 × 10⁹ copies/µL), and he was diagnosed with HSV-1 infection. Acyclovir (ACV) and corticosteroid pulse therapies with methylprednisolone were started. Continuous hemodiafiltration (CHDF) using cytokine-absorbing hemofilters was also initiated because of renal failure. These therapies, however, failed to control the disease, and the patient died on the 41st day of life. The dose of ACV on CHDF might not be adequate, although we could not measure the serum ACV concentrations. After the patient’s death, we measured his serum cytokine concentrations taken four times during the clinical course. Serum concentrations of interleukin (IL)-6, IL-10, IL-1β, and interferon (IFN)-γ were elevated at the time of admission and were remarkably decreased by 10 days after treatment. In particular, the concentrations of IL-1β and IFN-γ were lower than the measurable ranges. It is therefore important to measure serum cytokine concentrations in real time to prevent excessive immune suppression.

Heme is one of the key factors involved in the oxidative stress response of cells. The transcriptional repressor Bach1 plays an important role in this response through its heme-binding activity. Heme inhibits the transcriptional-repressor activity of Bach1, and can occur in two binding modes: 5- and 6-coordinated binding. The Cys-Pro (CP) motif has been determined to be the heme-binding motif of Bach family proteins. The sequence of Bach1 includes six CP motifs, and four CP motifs are functional. With the aim of elucidating the molecular mechanism of heme-Bach1 regulation, we conducted biophysical analyses focusing on the C-terminal region of mouse Bach1 (residues 631-739) which is located after the bZip domain and includes one functional CP motif. UV-Vis spectroscopy indicated that the CP motif binds heme via 5-coordinated bond. A mutant, which included a cysteine to alanine substitution at the CP motif, did not show 5-coordination, suggesting that this binding mode is specific to the CP motif. Surface plasmon resonance revealed that the binding affinity and stoichiometry of heme with the Bach1 C-terminal region were K_D = 1.37 × 10^–5 M and 2.3, respectively. The circular dichroism spectrum in the near-UV region exhibited peaks for heme binding to the CP motif. No significant spectral shifts were observed in the far-UV region when samples with and without heme were compared. Therefore, disordered-ordered transition such as “coupled folding and binding” is not involved in the Bach1-heme system. Consequently, the heme response of this C-terminal region is accomplished by disorder-disorder conformational alteration.

Despite the wide variety of international evidence on the relationship between the socioeconomic status (SES) and health outcomes, less is known about the association between SES and healthcare provider practices. We assessed whether patients with a closed hip fracture were treated differently by hospital physicians according to the SES of their residential areas in Japan. Hip fracture is a common cause of hospitalization among the elderly, but the relationship between SES and hip fracture treatment remains unknown in Japan. We employed the Diagnosis Procedure Combination (DPC) database from April 2011 to March 2014. SES of the patient’s residential area was estimated using Census-derived areal deprivation index (ADI). We performed a cross-sectional study of national claims data and analyzed it using cross-classified multilevel models. We used two outcome measures: (i) whether the patient received an operation or was treated by watchful waiting; and (ii) number of waiting days until operation following admission. We identified 95,011 patients admitted to 1,050 hospitals. Of these, 85,480 patients underwent surgery. Low SES of residential areas was not correlated with the chance of undergoing surgery (P = 0.15) but was weakly correlated with longer waiting days (coefficient, 0.03; 95% confidence interval, −0.01 to 0.06; P = 0.08). The difference of waiting days between maximum (10.4) and minimum ADI (–4.0) was marginal (0.39 days). The results indicate the SES of patient’s residential area does not affect the decision of surgical treatment for hip fracture and has ignorable impact on waiting days from hospital admission to surgery.

Infection control in nursery schools and schools is important for community health and the health of children. In Japan, caregivers of children or students usually report the absence due to illness to their attending nurseries or schools, including symptoms and diagnosed diseases. The (Nursery) School Absenteeism Surveillance System, (N)SASSy, covers about 60% of schools and 40% of nurseries in Japan. In this paper, we evaluated the benefits of (N)SASSy as an infection control measure by a public health center. Mito Public Health Center (MPHC) covers 58 nurseries and 186 schools, as of May 2015, and called the nurseries and/or schools to confirm the situation, in case of aberration detected through (N)SASSy. The outcome was defined as the proportion of cluster avoidance by advice from MPHC. A cluster was identified, when the number of patients at the same facility with the same symptom or diagnosed disease was greater than ten during the prior seven days. During the study period (April 2015-March 2016), MPHC advised 85 times, and clusters were avoided 82 times (96.5%). The proportion of cluster avoidance was 100% for fever, enterohemorrhagic Escherichia coli infection, respiratory syncytial virus infection, or streptococcal pharyngitis infection. The proportion of cluster avoidance for diarrhea, vomiting or gastroenteritis infection, mumps, hand-foot-mouth disease (HFMD), and influenza was 78.8, 50.0, 20.0, and 6.7%, respectively. In conclusion, advice from a public health center given by phone based on information from (N)SASSy will be helpful for reducing the number of clusters of infectious diseases, except for HFMD and influenza.

Cytomegalovirus (CMV) is an opportunistic pathogen, and careful monitoring of CMV is important for immunocompromised patients. Antigenemia-based CMV monitoring is a standard test used for managing CMV infection in transplant recipients; however, in Japan, there are no reports of CMV monitoring using the standardized test. The utility of a standardized CMV nucleic acid test (NAT) was evaluated during antigenemia-based CMV monitoring after hematopoietic stem cell transplantation (HSCT) or liver transplantation. Blood collection for CMV monitoring was performed under the physician’s instructions depending on the condition of the patient, and CMV NAT and antigenemia was evaluated. For HSCT recipients, blood collection only for NAT was additionally performed during the pre-engraftment phase. The results of the NAT were blinded to those evaluating the results. A total of 34 patients were enrolled (11 HSCT recipients and 23 liver transplant recipients). NAT detected the first CMV episode no later than antigenemia in 2 (18.2%) HSCT recipients and 3 (13.0%) liver transplant recipients, earlier than antigenemia in 3 (27.3%) HSCT recipients and 7 (30.4%) liver transplant recipients, and later than antigenemia in 1 (9.1%) HSCT recipient and 1 (4.3%) liver transplant recipient. In 5 HSCT recipients, NAT was positive during the pre-engraftment phase. Among the 468 blood samples which were evaluated by both NAT and antigenemia, 124 (26.7%) were positive in NAT and 51 (10.9%) were positive in antigenemia. The standardized CMV NAT is useful for accurately diagnosing CMV infection and determining appropriate therapeutic interventions for HSCT recipients and liver transplant recipients.

Encephalitis is an inflammatory process involving the brain parenchyma associated with neurologic dysfunction. The main causes of infectious encephalitis are viruses, including Herpes simplex virus type 1 (HSV-1). As the mortality rate of HSV-1 encephalitis could be reduced with early acyclovir treatment, it is imperative to distinguish HSV-1 encephalitis from other type of viral encephalitis as early as possible. However, sophisticated methods for definitive diagnosis of HSV-1 encephalitis are not readily available. We aimed to explore distinctive clinical and laboratory features of HSV-1 encephalitis. All of the adult patients with viral encephalitis hospitalized between 2011-2017 were enrolled, including 16 patients with HSV-1 encephalitis and 51 patients non-HSV-1 viral encephalitis. Determination of viruses in cerebrospinal fluid was performed by PCR tests. Female sex, hyponatremia, and abnormalities in MRI were independently associated with HSV-1 encephalitis (p < 0.05 for each). In particular, hyponatremia (< 135 mEq/L) was found in nine patients with HSV-1 encephalitis (56.3%) and 10 patients with non-HSV-1 viral encephalitis (19.6%) (p = 0.005). As serum sodium is determined easily and quickly in clinical practice, the presence of hyponatremia among patients with viral encephalitis could be helpful for the early diagnosis of HSV-1 encephalitis before cerebrospinal fluid PCR results were available. Moreover, the presence of positive finding in MRI could further support the diagnosis. This is the first study that compared the serum sodium levels among patients between HSV-1 and non-HSV-1 viral encephalitis. We thus propose the diagnostic value of hyponatremia for HSV-1 encephalitis.

Japan has adopted community-based integrated long-term care, which has shifted the burden of care from institutions to the home. However, family caregivers have received less attention compared with care recipients. Many family caregivers are also older adults, and it is important that caregivers receive appropriate support to alleviate the burden of care. In rural and sub-urban area with limited resources compared to urban area, it is necessary to know which support to be prioritized. Therefore, this study aimed to understand family caregivers’ perceptions of social support, the type and source of support which were considered important, and how it affected their caregiving burden and quality of life (QOL). We conducted a convergent mixed-method study with 174 primary family caregivers of older adults receiving home care in rural and suburb area of Central Japan. The mixed-method approach enabled qualitative data to complement quantitative results. Strong family support and higher education had positive effects on QOL, while higher caregiving burden and longer duration of care had negative effects on QOL. Provision of tangible support from family and healthcare professionals was central in reducing caregiving burden and improving caregivers’ QOL. Support from distant relatives or neighbors, which was deemed inappropriate by caregivers, had a negative effect on caregivers’ emotional status. In conclusion, family caregivers perceived support positively, but the effects depended on who provided support. While tangible support from close family and professionals was perceived positively, support from neighbors or distant relatives should consider caregivers’ needs and condition to avoid a negative impact.

The 2015 Annual report on growth velocity and physiologic status in schoolchildren revealed that the overweight incidence among fifth grade primary school in Aomori Prefecture was higher than the countrywide average. As a pilot study, overweight fifth grade (age, 10 years) children attending the attached primary school of Hirosaki University, Faculty of Education, were recruited in 2016, after which 6-year longitudinal change in physiological status between the first (age, 6 years) and sixth grades (age, 11 years) were evaluated using somatometric data obtained from the annual health checkup conducted each Spring. Of the 80 fifth graders recruited, none of whom had any underlying diseases affecting physiologic status, 6 (7.5%, 3 boys and 3 girls) were deemed overweight. Subsequently, 20 non-overweight children (10 boys and 10 girls) of the same grade were randomly selected for comparison. We used percent degree of overweight (%DO) for evaluating overweight instead of body mass index. Accordingly, compared with controls, overweight children already exhibited significantly greater weight and %DO at the first grade. Moreover, those who remained being overweight by the fourth grade showed %DO that tended to persist thereafter. Most overweight children exhibited increased annual velocity in %DO between the first and third grades. Overweight children showed varied fluctuations in %DO status throughout 6 years of primary school, whereas non-overweight children showed almost stable %DO within the normal range. The present study indicates the importance of early and sustained health education, particularly during the period before primary school entry until at least before fourth grade.