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Serre and Stark succeeded in deciding a basis of the space of modular forms of weight 1/2 over the rational number field. Achimescu and Saha generalized their result to the case of modular forms of weight 1/2 over totally real algebraic number fields. Gove also solved this problem in the case of modular forms of weight 1/2 over imaginary quadratic fields. In this paper, we determine an explicit basis of the space of modular forms of weight 1/2, level c and character ψ over algebraic number fields. We prove our assertion using their arguments and Shimura's transformation formula of theta series over algebraic number fields.

A field experiment was conducted involving deer exclosures and planting of Quercus acutissima, a deciduous oak, to reveal forest recovery patterns and factors following clear-cutting at overcrowded...

The development of pneumococcal conjugate vaccines has substantially decreased the incidence of invasive pneumococcal diseases. However, the incidence of bacteremia due to nonvaccine serotypes has increased. Therefore, it is important to recognize the symptoms and complications of pneumococcal infection to expedite diagnosis. Herein, we report the case of a 22-month-old patient diagnosed with pneumococcal bacteremia who presented with cholestatic jaundice and fever without any other signs of systemic sepsis. The patient's condition improved soon after antibacterial therapy. Other causes of jaundice were possibly ruled out based on the screening test for viral hepatitis, and there were no abnormal findings on abdominal ultrasonography. Therefore, the present case suggests that cholestatic jaundice could be a manifestation of pneumococcal bacteremia.

The appropriate antimicrobial treatment period for febrile urinary tract infection (UTI) can be changed, depending on whether the patient has acute focal bacterial nephritis (AFBN). The aim of this study was to clarify the characteristics of AFBN compared with those of acute pyelonephritis (APN) and establish a strategy to detect AFBN.A total of 77 patients diagnosed with febrile UTI were enrolled. They were divided into APN (n = 64) and AFBN groups (n = 13). The clinical data and other laboratory biomarkers were retrospectively analyzed.The time required for fever resolution after antimicrobial treatment was significantly longer in the AFBN group than in the APN group (2.77 days vs 1.11 days, respectively, P0.001). Also, the time to disappearance of pyuria after antimicrobial treatment was longer in the AFBN group than in the APN group (6.22 days vs 2.32 days, respectively, P = 0.001). Fever lasting1.75 days after antimicrobial treatment had a sensitivity of 92% and specificity of 79% for the detection of AFBN, while pyuria disappearance after 4 days had a sensitivity of 88% and specificity of 85%. When patients fulfilled both cut-offs, the sensitivity and specificity were 89% and 97%.Acute focal bacterial nephritis was associated with fever of significantly longer duration after antimicrobial treatment, and it took a longer time for pyuria to disappear. Children with febrile UTI should be evaluated for AFBN if the fever persists ≥48 h after the initiation of antimicrobial treatment and if pyuria lasts for 4 days.

During the period from January to December 2015, 104 Streptococcus pneumoniae strains, 129 Haemophilus influenzae strains and 54 Moraxella catarrhalis strains isolated from clinical specimens of pediatric infections in the national 16 institutions, studied susceptibilities of total 28 antibiotics, the capsular serotype for S. pneumoniae, the capsular b type and β-lactamase production capability for H. influenzae, and the β-lactamase production capability for M. catarrhalis were measured. In S. pneumoniae, the results showed that 68 strains (65.4%) were PSSP, 32 (30.8%) were PISP, and 4 (3.8%) were PRSP. The susceptibilities of TBPM and GRNX among oral antibiotics, and PAPM among injectable antibiotics demonstrated the lowest value with MIC90 ≤ 0.06 μg/mL. The most frequent distribution of S. pneumoniae serotypes was seen in 15B, followed by 19A, and 35B. Serotype strains contained in 13-valent pneumococcal conjugate vaccine (PCV13) were 19 strains (18.3%). In H. influenzae, the results showed that BLNAS accounted for 40 strains (31.0%), BLNAI for 28 strains (21.7%), BLNAR for 47 strains (36.4%), β-lactamase producing for 14 strains (10.8%). The susceptibilities of quinolones demonstrated the lowest outcome among oral antibiotics with MIC90 ≤ 0.06 μg/mL, and CTRX and TAZ/PIPC (TAZ4 fixed) among injectable antibiotics with MIC of 0.25 μg/mL. There was no detection of capsular type b strains. In M. catarrhalis, all the isolates were β-lactamase producing strains. The susceptibilities of TBPM, CPFX, TFLX and GRNX among oral antibiotics, and TAZ/PIPC (TAZ4 fixed), PAPM, MEPM and DRPM among injectable antibiotics demonstrated the lowest outcome with MIC of ≤0.06 μg/mL.

Lower respiratory tract infections due to respiratory syncytial virus are associated with morbidity and mortality in infants and children. Thus precise elucidation of respiratory syncytial virus lower respiratory tract infection pathophysiology is important.Medical records of hospitalized patients were reviewed. Patients were divided into three groups. Group I: patients who improved without oxygen supply. Group II: patients who received oxygen supply, but not nasal high-flow cannula therapy. Group III: patients who received nasal high-flow cannula. Patients were also divided by age group into the6 months and ≥6 months groups. Parameters for differentiating the severity among groups were then evaluated. Further, serum concentration of high-mobility group box-1 and several cytokines (Inerleukin-6, soluble tumor necrosis factor receptor-1/2, Interleukin-18, Interferon-gamma responsive protein-100) were evaluated.One hundred eighty-nine were enrolled. An analysis of variance for those6 months showed overall differences including younger age, lower pH, and increased partial pressure of carbon dioxide (pCO2), bicarbonate (HCO3-), and base excess at the time of admission. On the other hand, analysis of variance for ≥6 months revealed that, in addition to a lower pH and increased pCO2, patients showed differences including decreased serum total protein and albumin, and increased aspartate aminotransferase (AST), alanin aminotransferase (ALT), lactate dehydrogenase (LDH), Ferritin and C-reactive protein (CRP) levels. Further, evaluation of serum cytokines showed that IL-6, s tumor necrotizing factor receptor-1/2, and high-mobility group box-1 were higher in Group II/III among the ≥6 months age group, but not for those in the6 months group.The pathophysiology of severe respiratory syncytial virus lower respiratory tract infection varies according to the age at onset. In late infancy and childhood, a certain proportion of patients show a hyperinflammatory status.

We study the traces of Hecke operators acting on the space of Jacobi forms and give the trace formula in the case of general odd squarefree level N by using results of Skoruppa and Zagier. As an application, we obtain some trace relations of them, and construct an isomorphism map from the space of all Jacobi cusp new forms of level N and index 1 having the eigenvalue +1 with respect to any Atkin–Lehner operator on the level to the space of all Jacobi cusp new forms of level 1 and index N whose eigenvalue with respect to any Atkin–Lehner operator on the index is equal to +1.

Universities in the EFL context aim to foster graduates who can use English in the workplace. Regardless, university students’ insufficient amount of out-of-class study time is a major issue. This problem may stem from learners’ lack of learning skills, low levels of learning motivation, and high levels of academic procrastination. Self-coaching skills have the potential to tackle this problem. In this study, we introduce how self-coaching skills training can be applied in the EFL classroom while drawing on relevant literature in ELT. Respecting the diverse characteristics of learners, we grouped participants into different trajectories based on levels of intrinsic motivation, self-regulated learning skills, and academic procrastination tendencies at four different data collection points throughout a required 15-week EFL course. Quantitative data revealed five trajectories in which we examined how self-coaching skills training through self-questioning influenced out-of-class study time in two repr...

We evaluated 24 children with invasive Haemophilus influenzae infections between 2006 and 2015 in Kamikawa subprefecture of Hokkaido, Japan. The most frequent disease was pneumonia in 12 cases (50.0%), followed by meningitis in 7 (29.2%) and bacteremia in 5 (20.8%). Patients ranged in age from 3 months to 12 years of age. Seventeen (70.8%) of the total were less than 2 years old. The incidence rate of H. influenzae infection varied from 15.1 to 36.3 per 100,000 population in the Kamikawa area during the period from 2006 through 2011. The corresponding rate decreased to 10.4 per 100,000 population in 2012, and there were no cases after 2013. Meningitis occurred in 1–2 patients annually from 2006 to 2011, showing an incidence rate of 4–10 per 100,000 population per year, while no cases were reported during or after 2012. No patients with invasive H. influenzae infection died, but sequelae were seen at discharge in 1 patient with meningitis, that had hydrocephalus and developmental delay. In Japan, introduction of the H. influenzae type b (Hib) vaccine was in November 2008. Initially, this vaccination was voluntary, resulting in a low vaccination rate. According to the national policy, and the self-pay burden for vaccination was decreased in December 2010, and the vaccination rate increased markedly to over 90%. This report provides a meaningful demonstration that introduction of the Hib vaccine markedly reduced invasive H. influenzae infections, exerting a beneficial effect in Japan, as it has in the world.

The Japanese Association for Infectious Diseases (JAID) and Japanese Society of Chemotherapy (JSC) announced the “Guide for the Use of Antimicrobial Drugs” in 2001 and the “Guidelines for the Use of Antimicrobial Drugs” in 2005. Subsequently, the “The JAID/JSC guide to clinical management of infectious diseases 2011” was published. With its revision, guidelines were newly prepared. Concerning respiratory infectious diseases, in Japan, the Japanese Respiratory Society published guidelines for the management of community-acquired pneumonia, hospital-acquired pneumonia, respiratory tract infection, and -/nursing and healthcare-associated pneumonia. Furthermore, the Japanese Society of Pediatric Pulmonology and Japanese Society for Pediatric Infectious Diseases announced the “Guidelines for the Management of Respiratory Infectious Diseases in Children in Japan”. Internationally, many guidelines, including those established by the American Thoracic Society and Infectious Diseases Society of America, have been published from various countries. Thereafter, clinical research on respiratory infectious diseases has advanced, leading to the accumulation of many outcomes regarding epidemiology, clinical diagnosis, and treatment. However, the types of microorganisms that cause respiratory infectious diseases have increased with the number of resistant bacteria. In addition, conditions have also varied with causative microorganisms through the recent compromised host's severe status. The place of treatment varies: from the outpatient clinic to the ICU. Physicians responsible for treatment also vary: practitioners, hospital doctors, pulmonologists, emergency physicians, board certified member of JAID, Japanese antimicrobial chemotherapy physician. There are a large number of options of antimicrobial drugs that are available, including new drugs; therapeutic strategies are confused. On the other hand, recently, the entity of PK-PD has been commonly recognized, and the importance of scientifically using antimicrobial drugs has been emphasized. In addition, the Japanese Society of Chemotherapy established a system for antimicrobial chemotherapy-certified physicians, and promoted the widespread, adequate use of antimicrobial drugs. Based on these, the two societies prepared the JAID/JSC Guidelines for the Treatment of Respiratory Infectious Diseases. If specific treatment guidelines can be presented, this may contribute to an improvement in the treatment responses of respiratory infectious diseases, a reduction in health expenditure, and the prevention of resistant bacteria. The guidelines were prepared based on the EBM so that they reflected the management of respiratory infectious diseases in Japan and covered all such diseases in adults and children. To prepare the guidelines, a committee was established in 2012, and a draft was published on homepage based on an approval from the boards of directors at the two societies through a review-based consensus. Opinions were collected from the two societies' members. In Japan, there have been no such guidelines covering respiratory infectious diseases. In the future, with further advances in research, the contents of the guidelines must be revised. However, we successfully provided treatment guidelines that are the most advanced at present. The guidelines were prepared for all clinicians to understand the Treatment of Respiratory Infectious Diseases and manage them with antimicrobial drugs adequately. They do not limit treatment by individual physicians or affect their rights to select it. The guidelines may be commonly applied for respiratory infectious disease management/research/education in Japan, improving the quality of respiratory infectious disease management, preventing an increase in the number of resistant bacteria, and contributing to national health. We hope that the guidelines will be utilized by a large number of clinicians in respiratory infectious disease management. Lastly, we thank the committee members and secretariat staff for their cooperation. 1. Descriptions on the recommendation grade and evidence level Recommendation grade Evidence level A Strongly recommended, I Randomized comparative study B General recommendation II Non-randomized comparative study C Comprehensive evaluation by the attending physician III Case report IV Specialist's opinion Open in a separate window 2. Definition of first- and second-choice drugs First-choice drugs Drugs to be recommended for initial treatment Second-choice drugs Alternative drugs when first-choice drugs cannot be used due to allergy, organ disorder, or local factors Open in a separate window 3. Precautions - In this article, with respect to the administration method (especially doses) of antimicrobial drugs, they are recommended based on sufficient doses. Considering the products adopted at each medical institution, antibiograms, severity, underlying disease, age, and presence or absence of organ disorder, the dose should be increased or decreased if necessary. - The spectra of third-generation cephems for intravenous injection, CTX and CTRX, are similar, but CTX, which is excreted in the kidney, should be primarily used when liver dysfunction is present, and CTRX, which is excreted in bile, should be primarily used when renal dysfunction is present. - As quinolones exhibit antitubercular actions, patients with pulmonary tuberculosis should be excluded for use. 4. A list of antimicrobial drug abbreviations and doses for neonates are presented at the end of this volume.

A 4mg/kg dose of tebipenem pivoxil (TBPM-PI) was administered twice daily for 3 days to 34 pediatric patients with pneumonia who had chest X-ray findings indicative of pneumonia and CRP values of at least 3.0 mg/dL. The clinical effects of this regimen were evaluated by retrospectively examining medical charts for the period from April 2012 to March 2015. The patients were 6 months to 8 years old, with serum CRP values ranging from 3.06 to 14.25 mg/dL. Fever resolved within 24 hours and respiratory symptoms improved within 3 to 5 days after the start of treatment in all 34 patients. Although CRP was positive in 28 of 30 patients at the end of the treatment period, none of these children showed worsening of pneumonia. Eight patients (23.5%) experienced adverse drug reactions including diarrhea. These results indicate that a 3-day course of TBPM-PI is useful for treating pediatric pneumonia.

The susceptibility of 1578 Streptococcus pneumoniae strains isolated from pediatric patients at Asahikawa Kosei Hospital between 2011 and 2015 was tested to penicillin G (PCG), cefotaxime (CTX), ceftriaxone (CTRX), cefditoren (CDTR), meropenem (MEPM), erythromycin (EM) and levofloxacin (LVFX). Although no significant differences were observed, the percentage of strains with a minimal inhibitory concentration (MIC) of PCG of0.1pg/mL increased from 55.5% (2011) to 64.0% (2015), whereas that of strains with MIC of ≥2μg/mL decreased from 14.8% to 9.5%. From 2011 to 2015, the percentage of strains with MIC ≤0.12ug/mL increased from 18.9% to 28.9% for CTX, from 20.5% to 30.2% for CTRX, from 29.2% to 40.9% for CDTR, and from 69.6% to 80.6% for MEPM. EM-resistant strains with MIC ≥22μg/mL accounted for as much as approximately 90% each year. One LVFX-resistant strain with MIC 8pg/mL has been detected each year since 2013.

This study targeted patients in the Department of Pediatrics, Asahikawa Kosei Hospital, between January 2002 and December 2013. In patients suspected of having hemolytic streptococcal infection, Group A Streptococcus (GAS) strains isolated from a throat swab were examined for antimicrobial susceptibility testing. The MICs were measured by the broth microdilution method. The annual number of GAS strains examined for antimicrobial susceptibility testing ranged from 28 to 65 strains, for a total of 574 strains. Some of the isolates obtained from 2006 to 2009 and from 2011 to 2013 were analyzed to determine their emm types. An erythromycin (EM) resistant strain was not detected until 2004, but one EM-resistant strain appeared in 2005. Subsequently, EM-resistant strains rapidly increased, and 48 of 65 strains (73.8%) examined in 2009 were resistant. In 2010, the number of EM-resistant strains decreased to 12 of 36 strains (33.3%). However, it gradually increased afterwards, and 37 of 60 strains (61.7%) were resistant in 2013. Out of 574 strains examined, 184 exhibited EM-resistance, and the overall resistance rate was 31.9%. Partitioning the 124 strains examined between 2006 and 2008 according to emm types, only emm28 strains, which exhibited a high resistance rate, and emm12 strains demonstrated resistance. For the 142 strains examined between 2011 and 2013, the resistance rate of emm28 strains was similarly high; the resistance of emm12 strains significantly increased, and emm1 strains exhibited a high resistance rate. The number of emm types associated with the resistant strains increased.

In Japan, the 7-valent pneumococcal conjugate vaccine (PCV-7) became commercially available as a voluntary vaccine in March 2010. It was included in the routine immunization schedule in April 2013 and was replaced by PCV-13 in November 2013. We evaluated 146 cases of invasive pneumococcal disease (IPD) in 142 children (2 developed the disease twice, and 1 developed it three times) treated in the northern district of Hokkaido, Japan from April 2000 to March 2015, before and after the introduction of PCV-7. The incidence rate per 100,000 people aged

To assess the incidence of colonization with group B streptococci (GBS) among neonates as influenced by maternal GBS carriage and intrapartum antibiotic prophylaxis (IAP).Between October 2014 and May 2015, nasopharyngeal and rectal swab samples were collected from 730 neonates at 1 week and 1 month after birth. GBS and capsular serotype were identified by real-time polymerase chain reaction and by culture. IAP at delivery was determined retrospectively from hospital records.Sixty-four neonates (8.8%) were GBS-positive by real-time polymerase chain reaction and culture. Among neonates born to mothers who were GBS carriers (n = 107), 94.4% (101/107) had maternal IAP; 19.6% nonetheless were GBS-positive, compared with 6.5% of neonates born to noncarrier mothers (P .01). Among neonates born to mothers receiving IAP, more were positive only at 1 month of age than at both 1 week and 1 month. The frequency of GBS in neonates born to mothers receiving IAP was significantly lower than that in neonates born to mothers not receiving IAP (P .05). Capsular serotypes V (25%) and III (23.4%) were common, followed by Ib (15.6%), Ia (14.1%), II (7.8%), IV (6.3%), nontypeable (4.7%), and VI and VIII (each 1.6%).Delayed colonization with GBS occurs in infants born to GBS carrier mothers receiving IAP. GBS should be considered in all infants at 1 month after birth with signs of infection.

Background This study examined the trends for the serotypes of S. pneumoniae that have caused infections before (2010) and after (2012) the introduction of PCV-7 in Japan. Methods We examined 458 strains of Streptococcus pneumoniae obtained from 22 pediatric institutions throughout Japan from January to June 2010 (immediately after the introduction of the seven-valent pneumococcal conjugate vaccine [PCV-7]), and 370 strains obtained from 19 institutions from January to June 2012 (after PCV-7 became widely used). The samples were collected from children aged 0–14 years with conditions such as respiratory tract infections (upper airway inflammation, bronchitis, and pneumonia), meningitis, and sepsis. Results The most frequent serotype in the 2010 strains was 19F (17.3%), followed by 6B (16.8%), and 23F (15.1%). The most frequent serotype in the 2012 strains was 6C (10.0%), followed by 19F (9.7%), 15A (8.9%) and 15B (8.9%), indicating a significant change in the distribution. The serotypes contained in PCV-7 were detected in 280 strains (61.1%) in 2010 and in 81 strains (21.9%) in 2012 (P < 0.01). The serotypes contained in PCV-13 were detected in 356 strains (77.7%) in 2010 and in 146 strains (39.5%) in 2012 (P < 0.01). A total of 129 subjects who had not been vaccinated with PCV-7 and 127 subjects who had been vaccinated with PCV-7 at least once, were compared with regard to the 2012 strains. The serotypes contained in PCV-7 were found in 21 strains (16.5%) in those who had been vaccinated and in 37 strains (28.7%) in those who had not been vaccinated (P < 0.05). Conclusions The increased use of PCV-7 led to decreases in the serotypes contained in PCV-13 and increases in the serotypes not contained in PCV-13, suggesting serotype replacement.

Background The frequency of occurrence of pediatric invasive streptococcal infection in Japan has not been studied, therefore the aim of this study was to survey the northern and eastern regions of Hokkaido from 2010 to 2012. Method Survey sheets were sent to the pediatric departments at 17 facilities where children in the subject region can be hospitalized. Responses were obtained from all of the 17 facilities. Results Seven patients developed group A streptococcal infection over the 3 years, and their ages ranged from 1 day after the birth to 15 years old. Sepsis was diagnosed in five children, and empyema and arthritis in the knee were found in one child each, respectively. The number of cases in children under 15 years old was six excluding the child who was 15 years old, and the incidence rate per 100 000 population was 1.00. Eight children developed group B streptococcal infection, and their ages ranged from 0 days to 2 months after birth. Two cases were the early onset type (age within 7 days) and six cases were the late onset type. Five children developed sepsis and three children developed meningitis. The frequency of occurrence was 0.24 per 1000 births; which was 0.06 per 1000 births for the early onset type and was 0.18 per 1000 births for the late onset type. No reports for group C or group G hemolytic streptococcal infection were obtained. Conclusions The incidence rates identified in the present survey are similar to those in other advanced countries, and appear to be valid.

We evaluated the efficacy and safety of a 3-day treatment regimen of tebipenem pivoxil for pediatric community-acquired pneumonia. Tebipenem pivoxil was administered to 49 patients, and its effectiveness was evaluated in 36 patients 2–4 days after initiation of treatment. Thirty-two patients were cured 7–15 days after initiation of treatment. Body temperature was significantly lower on the day following initial administration (median 38.8 to 37.0 °C, n = 33). Leukocyte counts and C-reactive protein levels were significantly reduced by Day 2–4 of treatment (median 16,100 to 7800 white blood cells/μL, and 5.6 to 1.5 mg/dL, respectively; n = 28). Six of the 49 patients had mild diarrhea. Thus, we concluded that 3-day treatment with tebipenem pivoxil was safe and efficacious for treating pediatric community-acquired pneumonia.

Background Congenital cytomegalovirus (CMV) infection and neonatal herpes are major mother-to-child infections, and analyses of the important clinical issues, including risk factors for prognosis, are essential. Methods A secondary survey of congenital CMV infection and neonatal herpes was performed using questionnaires for cases reported in the primary survey between 2006 and 2008. Results Univariate analysis of 71 cases of congenital CMV infection showed that intrauterine growth restriction (IUGR) or other specific findings on fetal ultrasonography (US), microcephaly, intracranial calcification, disseminated intravascular coagulation, abnormal findings on computed tomography, and the use of i.v. gammaglobulin were all significantly correlated with poor outcome (death or severe sequelae). Multivariate analysis showed that only IUGR was significantly associated with poor outcome. Hearing impairment is one of the major abnormalities associated with congenital CMV infection. Automatic auditory brainstem response (automatic ABR) appeared to be useful for detection of hearing impairment in comparison with conventional ABR. Moreover, univariate analysis showed that specific fetal US or abnormal magnetic resonance imaging findings were correlated with sensorineural hearing loss. In 24 cases of neonatal herpes, fever and seizure were correlated with poor outcome on univariate analysis. All patients received acyclovir treatment, although substantial numbers of patients in severe clinical categories (disseminated or central nervous system diseases) received a low dose of acyclovir (

Streptococcus pneumoniae, Haemophilus influenzae, and Mycoplasma pneumoniae are the main pathogens causing community-acquired pneumonia (CAP). We identified S. pneumoniae (n = 241), H. influenzae (n = 123), and M. pneumoniae (n = 54) as causative pathogens from clinical findings and blood tests from pediatric CAP patients (n = 903) between April 2008 and April 2009. Identification of genes mediating antimicrobial resistance by real-time PCR was performed for all isolates of these three pathogens, as was antibiotic susceptibility testing using an agar dilution method or broth microdilution method. The genotypic (g) resistance rate was 47.7 % for penicillin-resistant S. pneumoniae (gPRSP) possessing abnormal pbp1a, pbp2x, and pbp2b genes, 62.6 % for β-lactamase-nonproducing, ampicillin-resistant (gBLNAR) H. influenzae possessing the amino acid substitutions Ser385Thr and Asn526Lys, and 44.4 % for macrolide-resistant M. pneumoniae (gMRMP) possessing a mutation of A2063G, A2064G, or C2617A. Serotype 6B (20.3 %) predominated in S. pneumoniae, followed by 19F (15.4 %), 14 (14.5 %), 23F (12.0 %), 19A (6.2 %), and 6C (5.4 %). Coverage for the isolates by heptavalent pneumococcal conjugate vaccine (PCV7) and PCV13, respectively, was calculated as 68.5 and 80.9 %. A small number of H. influenzae were identified as type b (6.5 %), type e (0.8 %), or type f (0.8 %); all others were nontypeable. Proper use of antibiotics based on information about resistance in CAP pathogens is required to control rapid increases in resistance. Epidemiological surveillance of pediatric patients also is needed to assess the effectiveness of PCV7 and Hib vaccines after their introduction in Japan.

Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of commonly used clinical antimicrobial drugs were examined for 76 strains of Streptococcus pneumoniae isolated between 2006 and 2011 from pediatric patients with invasive pneumococcal infection. Patients from whom bacterial strains were isolated ranged from 4 months to 6 years old and included 50 infants (65.8%) 1 year old and 10 (13.2%) less than 1 year old, i.e., 79.1% of all patients studied. In diagnosis, 38 (50.0%) had occult bacteremia, 34 (44.7%) pneumonia, 3 (3.9%) meningitis, and 1 (1.3%) sepsis. Infections in all but one case who died of sepsis were treated without sequelae. The most frequent capsular serotype among isolates was 6B (20 strains, 26.3%), followed by 19 F (13 strains, 17.1%) and 14 (9 strains, 11.8%). Serotypes for 55 strains (72.4%) corresponded to those contained in heptavalent pneumococcal conjugate vaccine. In classification by resistance based on mutations in penicillin-binding protein genes, 32 were penicillin-resistant S. pneumoniae (42.1%), 35 penicillin intermediate-resistant S. pneumoniae (46.1%), and 11 penicillin-susceptible S. pneumoniae (11.8%). MIC90/MBC90 of drugs were as follows: ampicillin 4/4 microg/mL, cefotaxime 0.5/0.5 microg/mL, ceftriaxone 1/2 microg/ mL, panipenem 0.125/0.125 microg/mL, meropenem 0.5/0.5 microg/mL, and doripenem 0.25/0.25 microg/mL.

We evaluated 24 children with invasive Haemophilus influenzae infections between 2006 and 2015 in Kamikawa subprefecture of Hokkaido, Japan. The most frequent disease was pneumonia in 12 cases (50.0%), followed by meningitis in 7 (29.2%) and bacteremia in 5 (20.8%). Patients ranged in age from 3 months to 12 years of age. Seventeen (70.8%) of the total were less than 2 years old. The incidence rate of H. influenzae infection varied from 15.1 to 36.3 per 100,000 population in the Kamikawa area during the period from 2006 through 2011. The corresponding rate decreased to 10.4 per 100,000 population in 2012, and there were no cases after 2013. Meningitis occurred in 1-2 patients annually from 2006 to 2011, showing an incidence rate of 4-10 per 100,000 population per year, while no cases were reported during or after 2012. No patients with invasive H. influenzae infection died, but sequelae were seen at discharge in 1 patient with meningitis, that had hydrocephalus and developmental delay. In Japan, introduction of the H. influenzae type b (Hib) vaccine was in November 2008. Initially, this vaccination was voluntary, resulting in a low vaccination rate. According to the national policy, and the self-pay burden for vaccination was decreased in December 2010, and the vaccination rate increased markedly to over 90%. This report provides a meaningful demonstration that introduction of the Hib vaccine markedly reduced invasive H. influenzae infections, exerting a beneficial effect in Japan, as it has in the world.

Safety information regarding drug use during pregnancy is insufficient. The present study aimed to establish an optimal signal detection method to identify adverse drug reactions in pregnant women and to evaluate information in the Japanese Adverse Drug Event Report (JADER) database between April 2004 and November 2014. We identified reports on pregnant women using the Standardised MedDRA Queries. We calculated the proportional reporting ratio (PRR) and reporting odds ratio (ROR) of the risk factors for the two known risks of antithyroid drugs and methimazole (MMI) embryopathy, and ritodrine and fetal/infant cardiovascular events. The PRR and ROR values differed between all reports in the JADER database and those on pregnant women, affecting whether signal detection criteria were met. Therefore we considered that reports on pregnant women should be used when risks associated with pregnancy were determined using signal detection. Analyses of MMI embryopathy revealed MMI signals [PRR, 159.7; ROR, 669.9; 95% confidence interval (CI), 282.4-1588.7] but no propylthiouracil signals (PRR, 1.98; ROR, 2.0; 95%CI, 0.3-15.4). These findings were consistent with those of reported risks. Analyses of fetal/infant cardiovascular events revealed ritodrine signals (PRR, 2.1; ROR, 2.1; 95%CI, 1.4-3.3). These findings were also consistent with reported risks. Mining the JADER database was helpful for analyzing adverse drug reactions in pregnant women.

Background Spirometry is the most widely used pulmonary function test and the measured values of spirometric parameters need to be evaluated using reference values predicted for the corresponding race, sex, age, and height. However, none of the existing reference equations for Japanese children covers the entire age range of 6–18 years. The Japanese Society of Pediatric Pulmonology had organized a working group in 2006, in order to develop a new set of national standard reference equations for commonly used spirometric parameters that are applicable through the age range of 6–18 years. Methods Quality assured spirometric data were collected through 2006–2008, from 14 institutions in Japan. We applied multiple regression analysis, using age in years (A), square of age (A2), height in meters (H), square of height (H2), and the product of age and height (AH) as explanatory variables to predict forced vital capacity (FVC), forced expiratory volume in 1 sec (FEV1), peak expiratory flow (PEF), forced expiratory flow between 25% and 75% of the FVC (FEF25–75%), instantaneous forced expiratory flow when 50% (FEF50%) or 75% (FEF75%) of the FVC have been expired. Results Finally, 1,296 tests (674 boys, 622 girls) formed the reference data set. Distributions of the percent predicted values did not differ by ages, confirming excellent fit of the prediction equations throughout the entire age range from 6 to 18 years. Cut-off values (around 5 percentile points) for the parameters were also determined. Conclusions We recommend the use of this new set of prediction equations together with suggested cut-off values, for assessment of spirometry in Japanese children and adolescents. Pediatr Pulmonol. 2013; 48:35–44. © 2012 Wiley Periodicals, Inc.

Streptococcus pyogenes is the bacterium most frequently isolated from patients with pharyngitis. Although various antibiotics including penicillin are effective, antibiotic treatment failure in cases of streptococcal pharyngitis have been reported. Herein, we investigated mechanisms associated with recurrent streptococcal pharyngitis. Clinically isolated S. pyogenes strains showed serotype-specific features, with emm12 strains most frequently detected and emm6 strains more likely to produce biofilm. The architectures of formed biofilms were observed using a fluorescence microscope with Live/Dead staining. Furthermore, various cationic antimicrobial peptides were tested to evaluate their inhibitory activities toward biofilms formed by S. pyogenes. After treatments with high concentrations of antibiotics, S. pyogenes survived in biofilm even when dead bacterial cells covered the surface. Other findings demonstrated that some antimicrobial peptides have inhibitory effects on forming and formed biofilm. Moreover, emm4, emm6, and emm75 strains showed significantly higher levels of invasion capacity into Detroit 562 cells than strains with other genotypes. Additionally, more than half of the strains temporarily escaped killing by penicillin alone by internalization into epithelial cells, even when the antibiotic concentration used was greater than the 10-fold minimum inhibitory concentration (MIC) for planktonic S. pyogenes. Also, combined administrations of multiple antibiotics were more effective to eradicate strains more likely to be internalized. Finally, flow cytometric analyses demonstrated that emm12 strains with higher invasive capabilities expressed PrtF1 protein on the bacterial surface. These findings suggest that S. pyogenes isolated from patients with recurrent streptococcal pharyngitis have emm type-specific features that allow escape from eradication by antibiotics.

There are several reports suggesting that genetic factors contribute to the severity of infection with the respiratory syncytial virus (RSV). Infants hospitalized with lower respiratory tract infection (LRTI) due to RSV are at a significantly increased risk for both recurrent wheezing and childhood asthma. Uteroglobin-related protein 1 (UGRP1) is a secretory protein expressed in the airways, and speculated to have anti-inflammatory activity. The presence of the -112G/A polymorphism in the UGRP1 promoter was found to have a significant correlation with asthma phenotype. Also plasma UGRP1 levels were shown to be associated both with this polymorphism and the severity of asthma. The study population consisted of 62 previously healthy infants, ≤12 months of age, who were hospitalized with RSV LRTI, and a control group of 99 healthy adults. Genotyping was performed by restriction fragment length polymorphism. UGRP1 serum levels were determined using ELISA. There were no significant differences in the overall distribution of UGRP1 -112G/A polymorphism genotypes or alleles between the hospitalized infants and healthy adults. A comparison of serum UGRP1 concentration measured at the time of admission and discharge between patients with and without the -112A allele revealed that there was no relation between the presence of the -112A allele and serum UGRP1 in hospitalized infants with RSV infection. Furthermore, there was no relationship between severity of RSV infection and genotype or serum UGRP1 concentration. These results suggest that UGRP1 does not have a major role in the development of severe RSV infection.

Streptococcus pyogenes causes a broad spectrum of acute infections and is the bacterium most frequently isolated from patients with pharyngitis. A number of antibiotics including penicillin have been shown to be effective, although antibiotic treatment failure in cases of streptococcal pharyngitis have been reported. Herein, we aimed to elucidate the features of recurrent strains using clinical isolates. Ninety-three S. pyogenes organisms were obtained from Japanese patients with recurrent pharyngitis. Following genetic characterization, M-type isolates from patients with recurrent pharyngitis differed from those obtained at initial onset in 11 of 49 episodes, and pulsed field gel electrophoresis analysis showed different patterns in those cases. Additionally, spe genotyping revealed that the Spe type of the strains obtained at secondary onset corresponded with those from the initial onset in 22 cases. Furthermore, antibiotic susceptibility testing revealed that more than half of the strains were resistant to macrolides and lincosamides, which was a much greater ratio as compared with the strains obtained from initial onsets in previous studies. Our results suggest that recurrence and reinfection are often confused during the diagnosis of repetitive and persistent streptococcal pharyngitis. Moreover, the present S. pyogenes organisms were less susceptible to antibiotics, which raises caution about their appropriate use in clinical practice.

We evaluated 103 cases of invasive pneumococcal disease (IPD) encountered in 99 children (two developed the disease twice and one, three times) treated in the northern district of Hokkaido (Kamikawa and Soya subprefecture) from April 2000 until March 2010, before the introduction of the 7-valent pneumococcal conjugate vaccine. The main diseases were as follows: pneumonia, 54 cases (52.9%); occult bacteremia, 34 cases (33.3%); meningitis, five cases (4.9%). There were 42 cases during the first half of the study period (from April 2000 to March 2005) and 61 during the second half (from April 2005 to March 2010). The IPD morbidity rate for the 10-year period was 41.3 per 100,000 population in children

An evaluation committee studied the relationship between initial treatment drug and prognosis in 339 of 466 subjects with bacterial meningitis treated at 108 institutions between April 2004 and January 2007, after excluding those with uncertain diagnosis or non-assessable records. Prognosis was considered unfavorable if meningitis sequelae such as quadriplegia, deafness, or epilepsy were present in 3- month follow-up; Based on this definition, 43 (12.7%) had a poor prognosis. No significant relationship was seen between unfavorable prognosis and age or causative pathogen. More had an unfavorable prognosis if treatment was initiated 4 days or later after onset. The percentage with an unfavorable prognosis was 6.4% (4/64) in the group administered combined panipenem/betamipron (PAPM/BP) plus ceftriaxone (CTRX), 10.5% (6/57) administered MEPM plus cefotaxime (CTX), 14.0% (7/50) administered meropenem (MEPM) plus CTRX, and none of the 23 administered CTRX alone. The percentage with an unfavorable prognosis was 26.2% (11/42) in those administered MEPM, significantly higher than that in those administered PAPM/BP plus CTRX, MEPM plus CTX, or CTRX alone (p < 0.05). We concluded that in initial treatment, it would be more desirable to use MEPM combined with another drug than alone.

Background. The ratio of CA-MRSA in children with impetigo has been increasing in Japan.Methods. Antimicrobial susceptibilities of 136S. aureusisolates from children with impetigo were studied. Furthermore, molecular epidemiological analysis and virulence gene analysis were performed.Results. Of the 136S. aureusisolates, 122 (89.7%) were MSSA and 14 (10.3%) were MRSA. Of the 14 MRSA strains, 11 belonged to CC89 (ST89, ST91, and ST2117) and carried diverse types of SCCmec: type II (IIb: 3 strains; unknown subtype: 4 strains), type IVa (2 strains), and unknown type (2 strains). The remaining three strains exhibited CC8 (ST-8)-SCCmectype VIa, CC121 (ST121)-SCCmectype V, and CC5 (ST5)-nontypeable SCCmecelement, respectively. None werelukS-PV-lukF-PV gene positive. Gentamicin- and clarithromycin-resistant strains were frequently found in both MRSA and MSSA.Conclusions. PVL-negative CC89-SCCmectype II strains are the most predominant strains among the CA-MRSA strains circulating in the community in Japan.

To describe clinical aspects of pandemic (H1N1) 2009 virus–associated pneumonia in children, we studied 80 such children, including 17 (21%) with complications, who were admitted to 5 hospitals in Japan during August–November 2009 after a mean of 2.9 symptomatic days. All enrolled patients recovered (median hospitalization 6 days). Timely access to hospitals may have contributed to favorable outcomes.

We investigated the validity and efficiency of a survey using sight per unit effort (SPUE) of sika deer and shrub-layer decline rank (SDR), which is an index of decline in the physical structure of a whole stand caused by sika deer, based on data collected on a broad scale. This survey was to be used to manage a deer population in order to conserve a forest ecosystem. First, we evaluated the spatial and temporal scales of deer density that are most appropriate for predicting decline in the status of understory vegetation. The model with SPUE calculated in a buffer with a radius of 4.5 km using data for the past 4 years was found to be the best. We showed that our knowledge of the relationship between deer density and status of shrub-layer vegetation is improved by identifying the most suitable spatial and temporal scales of SPUE for predicting SDR. Next, we quantified the effects of SPUE and environmental components on SDR in stands. We found that SPUE had the greatest effect on SDR among all explanatory variables. Moreover, the area under the curve (AUC) was large in a model that only used SPUE (AUC = 0.718). This result suggests that the variation in SDR among stands was explained well by SPUE regardless of differences in the forest environment. Furthermore, we identified the effective values of SPUE for preventing shrub-layer vegetation from declining through deer density control. We conclude that a management system based on SPUE and SDR is a simple and valid method for managing deer populations in order to conserve forest ecosystems.

For 345 stands of deciduous hardwood forest in Hyogo Prefecture, Western Japan, we assessed the decline of shrub-layer vegetation due to sika deer in each stand by using the shrub-layer decline rank (SDR), determined by combining the shrub-layer vegetation cover and the presence of signs of grazing by sika deer in a stand. Since there was a geographical correlation between SDR and sighting per unit effort (SPUE), which is an index of the relative density of sika deer, it appeared that decline of shrub-layer vegetation in a stand can be accurately evaluated by SDR. There were correlations between SDR and several variables that indicate the status of components in forests (presence of saplings of tall trees, occurrence of bark stripping of tall trees, proportion of bark-stripped stems of Clethra barvinervis, decline of subtree-layer vegetation by bark stripping, cover of litter on the ground, and area of soil surface erosion). These results indicate that the status of these components changes with decline of shrub-layer vegetation by sika deer grazing. It is thought that such synchronizations are caused by sika deer grazing or a direct or indirect effect by decline of shrub-layer vegetation due to sika deer. Therefore, it is reasonable to assess decline in physical structure due to sika deer for stands of deciduous hardwood forests according to SDR.

The conversion of prion protein (PrP) from the monomeric cellular isoform to the oligomeric pathological isoform is a crucial event in the pathogenesis of prion diseases. To investigate oligomer formation of PrP, enhanced green fluorescent protein (EGFP)-tagged PrP (EGFP-PrP) without the glycosylphosphatidylinositol (GPI) anchor was prepared and the oligomerization of EGFP-PrP induced by sodium dodecyl sulphate (SDS) was monitored by fluorescence correlation spectroscopy (FCS). The FCS analysis indicated that soluble oligomers were formed at 0.011% SDS. Furthermore, the combination of fluorescence cross-correlation spectroscopy (FCCS) and a panel of anti-PrP monoclonal antibodies (mAbs) revealed the conformational changes in PrP. Our studies provide a method to analyze conformational changes of proteins in solution.

Streptococcus agalactiae isolates ( n = 189) from patients with invasive infections were analyzed for capsular type by PCR, for antimicrobial susceptibility, and for the presence of resistance genes. In contrast to the predominance of capsular type III in children, types Ib and V were most common among adults. All 45 levofloxacin-resistant strains had two amino acid substitutions, Ser 81 Leu in the gyrA gene and Ser 79 Phe in the parC gene, and showed similar pulsed-field gel electrophoresis patterns.

We applied the direct immunoperoxidase method to estimate the susceptibility to IDU of 17 strains of the virus which were isolated from the patients with active epithelial lesions of herpetic keratitis. All the strains were found to be sensitive below the IDU concentration of 5 micrograms/ml. The findings obtained by this method were in good agreement with those by the fluorescent antibody technique. The present method is specific and simple. It offers clear-cut interpretation and a permanent record of the results.

Hepatic artery and portal vein thrombosis are devastating complications of partial liver transplantation. Early detection of inflow complications is important, as re-reconstruction can salvage the graft. Near-infrared spectroscopy or laser Doppler flowmetry can be used to detect tissue oxygenation or microcirculation on the liver surface. The aim of this study was to examine which of these two methods better detects changes in hepatic inflow. Sangen-strain pigs (n = 5) were used. The tips of the near-infrared spectroscopy and laser Doppler flowmetry probes were placed separately on the surface of the right liver. Inflow to the liver was controlled during the following seven conditions: control (not clamped), half- and totally clamped portal vein, half- and totally clamped hepatic artery, and half- and totally clamped portal vein and artery. Tissue blood flow was calculated using laser Doppler flowmetry. Oxyhemoglobin, deoxyhemoglobin, and the tissue oxygenation index were measured and calculated using a near-infrared spectroscopy system. The tissue blood flow and oxygenation index could not be used to differentiate between the half-clamped portal vein, half-clamped hepatic artery, and totally clamped portal vein conditions. The oxyhemoglobin minus deoxyhemoglobin value was significantly decreased after half or total clamping of the portal vein or hepatic artery (p

We evaluated the beta-lactamase-producing ability and resistance to 20 antibacterial agents of 448 clinically isolated strains of Haemophilus influenzae accumulated from October 2000 to July 2001 (phase 1) and of 376 different strains accumulated from January to June 2004 (phase 2), from institutions that participated in a nationwide Drug-Resistant Pathogen Surveillance Group in Pediatric Infectious Disease. Between phase 1 and phase 2 the proportion of beta-lactamase-negative ampicillin (ABPC)-susceptible (BLNAS) strains declined from 62.9% to 34.3%; the proportions of beta-lactamase-positive ABPC-resistant (BLPAR) strains were 8.3% and 6.4% in phases 1 and 2, but the proportion of beta-lactamase-negative ABPC-resistant (BLNAR) strains increased from 28.8% in phase 1 to 59.3% in phase 2. Comparison of the MIC(90) values of the antibacterial agents for H. influenzae in phase 1 and phase 2 showed that cefcapene, cefpodoxime, ceftriaxone, panipenem, and clarithromycin kept the same level, while cefdinir, faropenem, and rokitamycin showed 2-fold to 8-fold decreases. With the exception of the above antibiotics, all of the other antibacterial agents tested showed 2-fold to 4-fold increases. The MIC(90) values of the beta-lactam drugs for BLNAR were 2-fold to 32-fold higher than the values for BLNAS. The proportion of BLNAR H. influenzae strains rose dramatically over the 3 years between phases 1 and 2. In relation to age, prior administration of antibacterial agents, and attendance at a day nursery as background factors, no significant differences between BLNAS and BLNAR were detected in phase 1. In the phase 2 survey, the proportion of BLNAR strains showed significant differences between children under 3 years and those aged 3 years or more, and there were also significant differences according to whether antibacterial agents, especially beta-lactams, had been administered previously. No significant difference was found in resistant bacteria according to whether or not a child had attended a day nursery.

Recurrent Group A Streptococcus (GAS) infection was defined as a case in which GAS infection was suspected during June 2006-December 2008 and GAS was detected more than 2 times by throat culture. T serotype and emn genotype were investigated for GAS bacteria isolated from children with recurrent GAS infection. Bacteria gene homology was studied using pulsed-field gel electrophoresis (PFGE). Of the 43 cases of GAS infection in 21 children used as subjects, 20 had GAS infection 2 times and one 3 times. A comparison of the first and second infection in subjects (and the second and third for the child with 3), bacteria isolated from 11 cases had coincident properties and those from the remaining 11 not-coincident. The mean period of first and second infections (second and third for the child with 3) was 29.1 +/- 17.1 days for the coincident group and 215.2 +/- 187.8 days for the not-coincident group. A significant group difference in period was seen (p = 0.0013). Ten of 12 children with recurrent GAS infection within 8 weeks of the first infection and one of 10 who had it more than 8 weeks after that were included in the coincident group, indicating a significant difference (p = 0.0028).

ヌートリアは，毛皮用の家畜として日本に導入された。本稿では，兵庫県における急激な分布と被害の拡大の過程について報告する。アンケート調査の結果，2007年には，兵庫県内の4195集落のうち2349 集落でヌートリアの目撃あるいは被害が確認されていることがわかった。有害捕獲等による捕獲数は，1007頭であった。捕獲努力量は，より深刻な農業被害をもたらすアライグマと比べると少なかった。