Epidemiology of hospitalised paediatric community-acquired pneumonia and bacterial pneumonia following the introduction of 13-valent pneumococcal conjugate vaccine in the national immunisation programme in Japan.

Studies on community-acquired pneumonia (CAP) and pneumococcal pneumonia (PP) related to the 13-valent pneumococcal conjugate vaccine (PCV13) introduction in Asia are scarce. This study aimed to investigate the epidemiological and microbiological determinants of hospitalised CAP and PP after PCV13 was introduced in Japan. This observational hospital-based surveillance study included children aged ⩽15 years, admitted to hospitals in and around Chiba City, Japan. Participants had bacterial pneumonia based on a positive blood or sputum culture for bacterial pathogens. Serotype and antibiotic-susceptibility testing of Streptococcus pneumoniae and Haemophilus influenzae isolates from patients with bacterial pneumonia were assessed. The CAP hospitalisation rate per 1000 child-years was 17.7, 14.3 and 9.7 in children aged <5 years and 1.18, 2.64 and 0.69 in children aged 5-15 years in 2008, 2012 and 2018, respectively. There was a 45% and 41% reduction in CAP hospitalisation rates, between the pre-PCV7 and PCV13 periods, respectively. Significant reductions occurred in the proportion of CAP due to PP and PCV13 serotypes. Conversely, no change occurred in the proportion of CAP caused by H. influenzae. The incidence of hospitalised CAP in children aged ⩽15 years was significantly reduced after the introduction of PCV13 in Japan. Continuous surveillance is necessary to detect emerging PP serotypes.

Split-mouth evaluation of connective tissue graft with or without enamel matrix derivative for the treatment of isolated gingival recession defects in dogs.

OBJECTIVES: The potential additive effect of an enamel matrix derivative (EMD) to a subepithelial connective tissue graft (CTG) for recession coverage is still controversially discussed. Therefore, the aim of this study was to histologically evaluate the healing of gingival recessions treated with coronally advanced flap (CAF) and CTG with or without EMD in dogs. MATERIALS AND METHODS: Gingival recession defects (5 mm wide and 7 mm deep) were surgically created on the labial side of bilateral maxillary canines in 7 dogs. After 8 weeks of plaque accumulation and subsequent 2 weeks of chemical plaque control, the 14 chronic defects were randomized to receive either CAF with CTG (CAF/CTG) or CAF with CTG and EMD (CAF/CTG/EMD). The animals were sacrificed 10 weeks after reconstructive surgery for histologic evaluation. RESULTS: Treatment with CAF/CTG/EMD demonstrated statistically significantly better results in terms of probing pocket depth reduction (P < 0.05) and clinical attachment level gain (P < 0.001). The length of the epithelium was statistically significantly shorter in the CAF/CTG/EMD group than in the CAF/CTG group (1.00 ± 0.75 mm vs. 2.38 ± 1.48 mm, respectively, P < 0.01). Cementum formation was statistically significantly greater in the CAF/CTG/EMD group than following treatment with the CAF/CTG group (3.20 ± 0.89 mm vs. 1.88 ± 1.58 mm, respectively, P < 0.01). The CAF/CTG/EMD group showed statistically significantly greater complete periodontal regeneration (i.e., new cementum, new periodontal ligament, and new bone) than treatment with CAF/CTG (0.54 ± 0.73 mm vs. 0.07 ± 0.27 mm, respectively, P < 0.05). CONCLUSION: Within their limits, the present findings indicate that the additional use of EMD in conjunction with CAF + CTG favors periodontal regeneration in gingival recession defects. CLINICAL RELEVANCE: The present findings support the use of EMD combined with CTG and CAF for promoting periodontal regeneration in isolated gingival recession defects.

Conceptualizing the origin of life in terms of evolution.

In this opinion piece, we discuss how to place evolution in the context of origin-of-life research. Our discussion starts with a popular definition: 'life is a self-sustained chemical system capable of undergoing Darwinian evolution'. According to this definition, the origin of life is the same as the origin of evolution: evolution is the 'end' of the origin of life. This perspective, however, has a limitation, in that the ability of evolution in and of itself is insufficient to explain the origin of life as we know it, as indicated by Spiegelman's and Lincoln and Joyce's experiments. This limitation provokes a crucial question: What conditions are required for replicating systems to evolve into life? From this perspective, the origin of life includes the emergence of life through evolution: evolution is a 'means' of the origin of life. After reviewing Eigen's pioneering work on this question, we mention our ongoing work suggesting that a key condition might be conflicting multi-level evolution. Taken together, there are thus two questions regarding the origin of life: how evolution gets started, and how evolution produces life. Evolution is, therefore, at the centre of the origin of life, where the two lines of enquiry must meet.This article is part of the themed issue 'Reconceptualizing the origins of life'.

Healing of localized gingival recessions treated with a coronally advanced flap alone or combined with an enamel matrix derivative and a porcine acellular dermal matrix: a preclinical study.

OBJECTIVE: This study aimed to evaluate the effects of a porcine acellular dermal matrix (PADM) with or without an enamel matrix derivative (EMD) on gingival recession defects treated with a coronally advanced flap (CAF) in dogs. MATERIALS AND METHODS: Miller class II gingival recession defects (5 mm wide and 7 mm deep) were surgically created on the labial side of bilateral maxillary canines in 12 dogs. After 8 weeks of plaque accumulation, the 24 chronic defects were randomly assigned to one of the following 4 treatments: CAF, CAF with PADM (CAF/PADM), CAF with EMD (CAF/EMD), and CAF with EMD and PADM (CAF/EMD/PADM). The animals were sacrificed 10 weeks after surgery for histologic evaluation. RESULTS: In all groups, root coverage was obtained to a varying degree. PADM was well incorporated in gingival connective tissue in the CAF/PADM and in the CAF/EMD/PADM groups. The height of newly formed bone was significantly greater in the CAF/EMD/PADM group than in the CAF and CAF/PADM groups. New cementum with periodontal ligament-like tissue was predominantly found in the CAF/EMD and CAF/EMD/PADM groups. The CAF/EMD/PADM group showed the greatest amount of new cementum among the groups examined, although the difference was not statistically significant. CONCLUSION: Within the limitations of the present study, it can be concluded that CAF/EMD/PADM treatment may promote periodontal regeneration in gingival recession defects. CLINICAL RELEVANCE: The present results suggest that the combination of EMD and PADM in conjunction with CAF may represent a promising approach for treating single Miller class II gingival recessions.

Similar in vitro effects and pulp regeneration in ectopic tooth transplantation by basic fibroblast growth factor and granulocyte-colony stimulating factor.

OBJECTIVES: Granulocyte-colony stimulating factor (G-CSF) has been shown to have combinatorial trophic effects with dental pulp stem cells for pulp regeneration. The aim of this investigation is to examine the effects of basic fibroblast growth factor (bFGF) in vitro and in vivo compared with those of G-CSF and to assess the potential utility of bFGF as an alternative to G-CSF for pulp regeneration. MATERIALS AND METHODS: Five different types of cells were examined in the in vitro effects of bFGF on cell migration, proliferation, anti-apoptosis, neurite outgrowth, angiogenesis, and odontogenesis compared with those of G-CSF. The in vivo regenerative potential of pulp tissue including vasculogenesis and odontoblastic differentiation was also compared using an ectopic tooth transplantation model. RESULTS: Basic fibroblast growth factor was similar to G-CSF in high migration, proliferation and anti-apoptotic effects and angiogenic and neurite outgrowth stimulatory activities in vitro. There was no significant difference between bFGF and G-CSF in the regenerative potential in vivo. CONCLUSIONS: The potential utility of bFGF for pulp regeneration is demonstrated as a homing/migration factor similar to the influence of G-CSF.

Speciation in ninespine stickleback: reproductive isolation and phenotypic divergence among cryptic species of Japanese ninespine stickleback.

Although similar patterns of phenotypic diversification are often observed in phylogenetically independent lineages, differences in the magnitude and direction of phenotypic divergence have been also observed among independent lineages, even when exposed to the same ecological gradients. The stickleback family is a good model with which to explore the ecological and genetic basis of parallel and nonparallel patterns of phenotypic evolution, because there are a variety of populations and species that are locally adapted to divergent environments. Although the patterns of phenotypic divergence as well as the genetic and ecological mechanisms have been well characterized in threespine sticklebacks, Gasterosteus aculeatus, we know little about the patterns of phenotypic diversification in other stickleback lineages. In eastern Hokkaido, Japan, there are three species of ninespine sticklebacks, Pungitius tymensis and the freshwater type and the brackish-water type of the P. pungitius-P. sinensis species complex. They utilize divergent habitats along coast-stream gradients of rivers. Here, we investigated genetic, ecological and phenotypic divergence among three species of Japanese ninespine sticklebacks. Divergence in trophic morphology and salinity tolerance occurred in the direction predicted by the patterns observed in threespine sticklebacks. However, the patterns of divergence in armour plate were different from those previously found in threespine sticklebacks. Furthermore, the genetic basis of plate variation may differ from that in threespine sticklebacks. Because threespine sticklebacks are well-established model for evolutionary research, the sympatric trio of ninespine sticklebacks will be an invaluable resource for ecological and genetic studies on both common and lineage-specific patterns of phenotypic diversification.

Effects of EMD in combination with bone swaging and calcium phosphate bone cement on periodontal regeneration in one-wall intrabony defects in dogs.

BACKGROUND AND OBJECTIVE: Although the application of EMD is a widely accepted periodontal-regenerative therapy, its effects on noncontained intrabony defects are unpredictable because of the lack of a space-making property. The combined use of EMD and autogenous bone grafts reportedly stimulates significant periodontal regeneration in intrabony defects. The aim of the present study was to evaluate the effects of EMD in combination with bone swaging (BS) and injectable calcium phosphate bone cement (CPC), which was placed into the spaces between the grafted swaged bone and the proximal host bone, on periodontal healing in one-wall intrabony defects in dogs. MATERIAL AND METHODS: One-wall intrabony defects (3 mm wide and 5 mm deep) were surgically created on the mesial and distal sides of the bilateral mandibular premolars in four dogs. The 16 defects were assigned to one of the following treatments: EMD only, BS only, EMD with BS (EMD + BS), or EMD with BS and CPC (EMD + BS + CPC). The animals were killed 8 wk after surgery for histologic evaluation. RESULTS: The height of newly formed bone was significantly greater in the EMD + BS + CPC group (3.73 ± 0.30 mm) than in the BS-only (2.74 ± 0.33 mm; p < 0.05) and EMD + BS (2.88 ± 0.98 mm; p < 0.05) groups. The area of newly formed bone was significantly larger in the EMD + BS + CPC group (5.68 ± 1.66 mm(2)) than in the EMD-only (3.68 ± 0.33 mm(2); p < 0.05), BS-only (3.48 ± 1.26 mm(2); p < 0.05) and EMD + BS (3.38 ± 1.37 mm(2); p < 0.05) groups. The EMD-only (4.63 ± 0.42 mm), EMD + BS (4.67 ± 0.30 mm) and EMD + BS + CPC (4.78 ± 0.54 mm) groups showed significantly greater cementum formation than did the BS-only group (3.93 ± 0.56 mm; p < 0.05). CONCLUSION: These results indicate that treatment with EMD + BS + CPC promotes favorable periodontal healing in one-wall intrabony defects in dogs.

Atomic-scale study of TiO2-GR nanohybrid formation by ALD: the effect of the gas phase precursor.

In the present work, we report on a theoretical-computational study of the growth mechanism of the TiO2-Graphene nanohybrid by atomic layer deposition. Hydroxyl groups (OH) are anchoring sites for interacting with the main ALD titanium precursors (Tetrakis (dimethylamino) Titanium, Titanium Tetrachloride, and Titanium Isopropoxide). Results demonstrate that the chemical nature of the precursor directly affects the reaction mechanism in each ALD growth step. Tetrakis(dimethylamino)titanium is the precursor that presents a higher affinity (lower energy barriers for the reaction) to hydroxylated graphene in the growth process. A complete reaction mechanism for each precursor was proposed. The differences between precursors were discussed through the non-covalent interactions index. Finally, the water molecules help reduce the energy barriers and consequently favor the formation of the TiO2-graphene nanohybrid.

Atomic-scale visualization of topological spin textures in the chiral magnet MnGe.

Topological spin textures in chiral magnets such as manganese germanide (MnGe) are of fundamental interest and may enable magnetic storage and computing technologies. Our spin-polarized scanning tunneling microscopy images of MnGe thin films reveal a variety of textures that are correlated to the atomic-scale structure. Our images indicate helical stripe domains, in contrast to bulk, and associated helimagnetic domain walls. In combination with micromagnetic modeling, we can deduce the three-dimensional (3D) orientation of the helical wave vectors, and we find that three helical domains can meet in two distinct ways to produce either a "target-like" or a "π-like" topological spin texture. The target-like texture can be reversibly manipulated through either current/voltage pulsing or applied magnetic field, which represents a promising step toward future applications.

Expression of Tn and sialyl Tn antigens in synovial tissues in rheumatoid arthritis.

OBJECTIVES: The carbohydrate chains represented by mucins (MUCs) are expressed by a variety of normal and malignant secretory epithelial cells and induce a variety of immunoreactions. Tn and sialyl Tn antigens are tumour-associated carbohydrate antigens which are borne on the core proteins of mucins. The purpose of this study is to investigate the existence of tumour-associated carbohydrate antigens in rheumatoid arthritis (RA). METHODS: . We examined the expression of Tn and sialyl Tn antigens in synovial tissues from RA and osteoarthritis (OA) patients by immunohistochemistry. In addition, mucins from synovial fluid (SF) from RA patients are purified by gel filtration and density gradient ultracentrifugation and the existence of these antigens examined by dot and Western blotting. RESULTS: We found that Tn and sialyl Tn antigens were strongly expressed in synovial cells and infiltrating mononuclear cells on the sublining layer and lymphoid follicles in synovial tissues in RA compared with those in osteoarthritis. Tn and sialyl Tn antigens were detected in purified mucins of SF from RA patients. CONCLUSIONS: Tumour-like synovial hyperplasia cells expressed Tn and sialyl Tn antigens. This finding suggests that the mucins exhibiting with abnormal glycosylation may be in part responsible for synovial hyperplasia, leading to the joint destruction in the pathogenesis of RA.

Relationship between the prognosis of periodontitis and occlusal force during the maintenance phase--a cohort study.

BACKGROUND AND OBJECTIVE: Few studies have longitudinally investigated the relationship between periodontal disease progression and occlusal factors in individual subjects during the maintenance phase of periodontal therapy. The aim of this cohort study was to investigate the relationship between biting ability and the progression of periodontal disease in the maintenance phase. MATERIAL AND METHODS: A total of 194 patients were monitored for 3 years during the maintenance phase of periodontal therapy. The subjects with disease progression (Progress group) were defined based on the presence of >or= 2 teeth demonstrating a longitudinal loss of proximal attachment of >or= 3 mm or tooth-loss experience as a result of periodontal disease during the study period. The subjects with high occlusal force were diagnosed as men who showed an occlusal force of more than 500 N and women who showed an occlusal force of more than 370 N. The association between biting ability and the progression of periodontitis was investigated using logistic regression analysis. RESULTS: There were 83 subjects in the Progress group and 111 subjects in the Non-progress group. A backward, stepwise logistic regression model showed that the progression of periodontal disease was significantly associated with the presence of one or more teeth with a high clinical attachment level (CAL) of >or= 7 mm (odds ratio: 2.397; 95% confidence interval: 1.306-4.399) ( p = 0.005) and low occlusal force (odds ratio: 2.352; 95% confidence interval: 1.273-4.346) ( p = 0.006). CONCLUSION: The presence of one or more teeth with a high CAL of >or= 7 mm and low occlusal force might be possible risk factors for periodontal progression in the maintenance phase of periodontal therapy.

The association of periodontal disease with oral malodour in a Japanese population.

AIM: The purpose of this study was to evaluate the association between oral malodour and periodontal disease, and to determine the effect of periodontal therapy on oral malodour. MATERIALS AND METHODS: Oral malodour parameters, including volatile sulphur compound (VCS) measurement, methyl mercaptan/hydrogen sulphide ratio by gas chromatography, organoleptic testing, tongue coating score, and periodontal parameters were evaluated in 823 patients complaining of oral malodour. Amongst these patients, 89 with oral pathogenic halitosis received tongue cleaning and periodontal therapy. Oral malodour and periodontal parameters were measured at baseline and after treatment. RESULTS: Amongst 823 patients, 102 were diagnosed with gingivitis and 721 with periodontitis. VCS levels and periodontal parameters increased according to the severity of oral malodour. Organoleptic testing significantly correlated with periodontal probing depth and a percentage of periodontal pocket depth ≥4mm (r=0.40 and 0.39 respectively). There were significant correlations between methyl mercaptan/hydrogen sulphide ratio and periodontal parameters. Significant decrease in oral malodour and periodontal parameters in 89 patients with oral pathogenic halitosis was also observed after periodontal treatment. CONCLUSIONS: Oral malodour is associated with periodontal disease, and periodontal therapy combined with tongue cleaning is beneficial for oral pathogenic halitosis.

Simplified stress analysis on the temporomandibular joint in Class III patients with and without mandibular asymmetry using a rigid body spring model.

OBJECTIVE: Aim of this study was to investigate the differences in stress on the temporomandibular joint (TMJ) between Class III patients with and without mandibular asymmetry using a rigid body spring model (RBSM). DESIGN: Menton (Me), the centre point of occlusal force on the line that connected the bilateral buccal cusps of the second molars and the most lateral, superior and medial points of the condyle were plotted on frontal cephalograms, and stress on the condyles was calculated with the 2-dimensional RBSM program of fortran. SETTING AND SAMPLE POPULATION: Eighty Japanese patients with diagnosed mandibular prognathism were divided into two groups, a symmetry group and asymmetry group on the basis of the Mx-Md midline position. OUTCOME MEASURE: The degree (force partition) of the resultant force, the direction (angulation) and displacement (X, Y) of each condyle were calculated. The horizontal displacement vector (u), the vertical displacement vector (v) and rotation angle (theta) of the mandibular body at Menton were also calculated. RESULTS: There were significant differences between the deviated and non-deviated sides of both groups regarding resultant force (symmetry group: p = 0.0372, asymmetry group: p = 0.0054), X (symmetry group: p < 0.0001, asymmetry group: p = 0.0001) and Y (symmetry group: p = 0.0354, asymmetry group: p = 0.0043). For angulation, there was a significant difference between the deviated and non-deviated sides in the asymmetry group (p = 0.0095). CONCLUSION: The results of this study suggest that difference in stress angulation on the condyles could be associated with asymmetry in mandibular prognathism.

Symmetric Peripheral Running Sutures are Superior to Asymmetric Peripheral Running Sutures for Increasing the Tendon Strength in Flexor Tendon Repair.

BACKGROUND: The fatigue strength of three peripheral suture techniques for flexor tendon repair was compared by cyclic loading of the repairs in the porcine flexor digitorum tendon. METHODS: Thirty-six tendons were sutured using only peripheral sutures with 6-0 Nylon. An initial cyclic load of 10 N for 500 cycles was applied and increased by 10 N for an additional 500 cycles at each new load until rupture. RESULTS: The fatigue strength of the symmetric running peripheral suture was 85.0% and 144.8% greater than that of the two kinds of the asymmetric running peripheral sutures. CONCLUSIONS: Symmetric running sutures can enhance the suture strength and appears to be a useful technique for increasing the strength of the peripheral suture.

Brodie's Abscess of the Radius in a Child.

We herein report an unusual case of Brodie's abscess of the radius in a child. A 13-year-old boy presented with pain on his right distal forearm. A plain radiograph showed an 8 cm translucent lesion in the distal radius. MRI showed a penumbra sign on the T1-weighted image, hyperintensity on T2-weighted images, and ring enhancement on the contrast-enhanced T1 image. 18F-FDG PET/CT images showed an uptake at the margin of the radius. Curettage and iliac cancellous bone grafting were undertaken for Brodie's abscess. Bacteriological examinations were found to be negative, however, the pathologic diagnosis showed chronic osteomyelitis. Eight months after surgery, the patient was asymptomatic and there was no sign of recurrence of infection. For Brodie's abscess in a child, thorough debridement is mandatory in addition to cancellous bone grafting. Brodie's abscess should be considered in the differential diagnosis of a patient who presents with forearm pain and exhibit the radiolucent osteolytic lesion on simple radiography.

Comparative analysis of hypermethylation of cell cycle control and DNA-mismatch repair genes in low-density and CD34+ bone marrow cells from patients with myelodysplastic syndrome.

Hypermethylation of CpG islands within the promoter region is one of the mechanisms by which genes are inactivated and may be one of the reason for silencing of cell cycle control or DNA-mismatch repair genes in myelodysplastic syndrome (MDS). Since the function of cell cycle control genes including the cyclin-dependent kinase inhibitors known as p15(INK4b) and p16(INK4a), as well as p14(ARF) which blocks MDM-2 (an inhibitor of p53), the retinoblastoma (RB1) protein and the mismatch repair gene MGMT is critical for hematopoietic proliferation and differentiation, we performed methylation specific polymerase chain reaction (MSP) in low-density, non-adherent bone marrow cells from 49 patients with MDS. In addition, expression of p15(INK4b) and RB1 was analysed by quantitative real-time PCR. From selected patients, we analyzed the methylation pattern of cell cycle control genes in CD34+ bone marrow cells. Thirty-nine of 49 cases (80%) had at least one of five genes methylated in our MDS samples by analysing low-density non-adherent bone marrow cells. The frequency of p15(INK4b) methylation was 34 of 49 samples (69%). The incidence of methylation of both p14(ARF) and p16(INK4a) was four of 49 (8%). RB1 gene was methylated in seven samples (14%) and each patient had RA. Interestingly, none of these genes were methylated in the purified CD34+ hematopoietic stem cells from the MDS patients. Furthermore, all our RARS patients had a methylated p15(INK4b) promoter correlating with non-detectable expression of this gene in bone marrow cells from those patients. These results indicate that hypermethylation of cell cycle control genes in MDS may occur late during the differentiation of myelodysplastic stem cells.

Asymmetric six-strand core sutures enhance tendon fatigue strength and the optimal asymmetry.

Under cyclic loading, we recorded the fatigue strength of a six-strand tendon repair with different symmetry in the lengths of suture purchase in two stumps of 120 dental rolls and in 30 porcine tendons. First, the strengths of the repairs with 1, 2, 3, 4 and 5 mm asymmetry were screened using the dental rolls. The asymmetric core suture repairs were then made with a Kessler repair of equal suture purchase (10 mm) in two tendon stumps, and shifting two other Kessler repairs by 1, 3 or 5 mm, respectively, along the longitudinal axis of the tendon in relation to the first (symmetric) Kessler repair. The core repairs with 3 mm or more asymmetry in suture purchases in two tendon ends showed significantly greater fatigue strength and significantly smaller gaps compared with 1 mm asymmetry in core suture repair. Our results support that asymmetric placement of core sutures in two tendon ends favour resisting gapping at the repair site and 3 mm or more asymmetry is needed to produce such beneficial effects.

Radiation inactivation target-size analysis of soluble guanylate cyclase.

The soluble form of guanylate cyclase, which is a heterodimer of two subunits with molecular weights of 82,000 and 70,000, was analyzed by radiation inactivation experiments to determine its functional size. Lyophilized crude extract from rat lung or the purified enzyme were irradiated with different doses from 60Co gamma-rays, and the residual activities were measured in the presence or absence of a potent activator, sodium nitroprusside. The target sizes for the basal activity and for the activity in the presence of sodium nitroprusside were calculated from the decay curve was 77 and 192 kDa, respectively, on the crude enzyme, or as 71 and 163 kDa, respectively, on the purified enzyme. The size for the activatable form of the enzyme was more than twice that of the basal activity and close to the size of the holoenzyme, implying that the enzyme activity must reside on one of the subunits and the activation by sodium nitroprusside requires interaction of both subunits.