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