Validation of pediatric index of mortality 2 (PIM2) in a single pediatric intensive care unit in Japan

Objective  

The Pediatric Index of Mortality 2 (PIM2), one of the key mortality prediction models for children in intensive care units, has not been validated in Japan. The purpose of this study was to validate the performance of PIM2 in a population of patients admitted to one pediatric intensive care unit (PICU) in Japan.     

Current treatments of rheumatoid arthritis: from the 'NinJa' registry

In this review, recent changes in both treatments and outcomes of rheumatoid arthritis (RA) in Japan were analyzed by viewing the National Database of Rheumatic Diseases by iR-net, one of the largest clinical databases for RA patients in Japan. Regarding drug therapy, the use of methotrexate has been continuously increasing and has established a place as an anchor drug in the treatment of RA among other nonbiologic disease-modifying antirheumatic drugs; however, the dosage used is still significantly less compared with that of western countries. In addition to methotrexate, the use of tacrolimus has increased gradually. The most prominent observed change is a rapid increase in the use of biologics, which rose to stardom in the treatment of RA in Japan and western countries. These changes in drug therapy could allow us to control RA disease activity more tightly. In line with this, the outcomes of patients with RA in Japan have been improving continuously, both clinically and functionally. Subsequently, the use of both NSAIDs and corticosteroids has decreased. In addition, overall rates of joint operations related to RA have also decreased; in particular, a significant decrease was noticed in the incidence of joint replacement and synovectomy. Overall, the trends in treatments and subsequent outcomes for RA in Japan have exactly followed those seen in western countries.     

Spatio-temporal control of hepatic stellate cell-endothelial cell interactions for reconstruction of liver sinusoids in vitro

Vascularization of engineered tissues in vitro remains a major challenge in liver tissue engineering. Liver microvessels, termed liver sinusoids, have highly specialized structures, and recapturing these sinusoidal structures is essential for reconstruction of functional liver tissue in vitro. Liver sinusoids are composed of hepatocytes, hepatic stellate cells (HSCs), and endothelial cells (ECs). Direct HSC-EC contacts are increasingly recognized for their roles in EC capillary morphogenesis. However, the hypothetical role of HSC-EC contacts in morphogenesis remains unclear in hepatocyte-HSC-EC triculture. In the present study, we first determined the effects of direct HSC-EC contacts on EC capillary morphogenesis using a hepatocyte-HSC-EC triculture model where HSC behavior was spatially controlled to achieve HSC-mediated proximal layers of hepatocytes and ECs. EC capillary morphogenesis was induced by overlaying Matrigel on an EC layer. Direct HSC-EC contacts inhibited EC capillary morphogenesis, suggesting that the HSC-EC contacts may be an important factor in capillary formation. We next tested the hypothesis that, in addition to spatial control, temporal control of HSC behavior is also important in achieving capillary morphogenesis in the triculture. ECs responded to the induction of capillary morphogenesis before the formation of direct HSC-EC contacts, while the ECs remained to form monolayers when capillary morphogenesis was induced after the HSC-EC contacts were established. When capillary morphogenesis was successfully achieved in the triculture, HSCs tended to preferably localize near the preformed capillary-like structures, resulting in the reconstruction of liver sinusoidal structures. In these structures, hepatocyte maturation was induced. Our findings indicate that control, both spatial and temporal, of HSC behavior is a key engineering strategy for the vascularization of engineered liver tissue in vitro.     

Isolation and characterization of H6N1 and H9N2 avian influenza viruses from Ducks in Hanoi, Vietnam

We report the genetic characterization of low pathogenic avian influenza (LPAI) viruses isolated from domestic ducks in northern Vietnam in 2009. In total, 22 influenza A viruses consisting of 21 H6N1 subtypes and one H9N2 subtype were isolated from 1488 ducks collected in February, March, and April 2009, accounting the overall virus isolation rate for 1.5%. No H5N1 strain was isolated in this study. Phylogenetic analysis indicated that all the eight genes of the H6N1 and H9N2 subtypes analyzed in this study were similar to those isolated in Korea, southeast China and northern Japan, and wild birds which migrate along the coastal East Asian Flyway are estimated to transmit these viruses. There was no evidence that the H6N1 and H9N2 subtypes share the gene segments with H5N1 subtypes. However, it is important to monitor the prevalence and genetical backgrounds of LPAI viruses among poultry in an area where several different influenza A subtypes are in circulation.     

Effect of dietary zinc deficiency on ischemic vulnerability of the brain

Deficiency of zinc, which modulates glutamate release, might increase ischemic vulnerability of the brain. We examined effects of dietary zinc deficiency for 2 weeks on ischemic vulnerability in several brain regions using dynamic positron autoradiography technique and [¹⁸F]2-fluoro-2-deoxy-d-glucose with rat brain slices. In the normal diet group, the cerebral glucose metabolic rate (CMRglc) was not significantly different from that of the ischemia-unloaded control even after the loading of ischemia for 45 min. However, in the zinc-deficient diet group, CMRglc was significantly lower than that of the ischemia-unloaded control after loading of ischemia for 45 min. With treatment of MK-801 (NMDA receptor antagonist) from the start of ischemia loading, CMRglc was not significantly different from that of the ischemia-unloaded control. These findings, obtained for all analyzed brain regions, suggest that dietary zinc deficiency increased ischemic vulnerability in the brain, and that glutamate might contribute to this effect through activation of the NMDA receptor.     

Early rehabilitation with weight-bearing standing-shaking-board exercise in combination with electrical muscle stimulation after anterior cruciate ligament reconstruction

The objective of early rehabilitation after anterior cruciate ligament (ACL) reconstruction is to increase the muscle strength of the lower extremities. Closed kinetic chain (CKC) exercise induces co-contraction of the agonist and antagonist muscles. The purpose of this study was to compare the postoperative muscle strength/mass of subjects who performed our new CKC exercise (new rehabilitation group:group N) from week 4, and subjects who received traditional rehabilitation alone (traditional rehabilitation group:group T). The subjects stood on the device and maintained balance. Then, low-frequency stimulation waves were applied to 2 points each in the anterior and posterior region of the injured thigh 3 times a week for 3 months. Measurement of muscle strength was performed 4 times (before the start, and then once a month). Muscle mass was evaluated in CT images of the extensor and flexor muscles of 10 knees (10 subjects) in each group. The injured legs of group N showed significant improvement after one month compared to group T. The cross-sectional area of the extensor muscles of the injured legs tended to a show a greater increase at 3 months in group N. This rehabilitation method makes it possible to contract fast-twitch muscles, which may be a useful for improving extensor muscle strength after ACL reconstruction.     

Evaluation of short-term clinical efficacy of 3-day therapy with azithromycin in comparison with 5-day cefcapene-pivoxyl for acute streptococcal tonsillopharyngitis in primary care

Group A streptococcal (GAS) tonsillopharyngitis is one of the few conditions for which antibiotics are advocated among common upper respiratory infections. Although a 3-day course of azithromycin is attracting attention as a treatment of choice for the condition, it is not clear if the efficacy of the treatment is comparable with that of treatment with cephalosporins. A prospective, randomized, comparative multicenter study was conducted to compare the efficacy of azithromycin (AZM) given once daily for 3 days with that of cefcapene-pivoxyl (CFPN-PI) divided into three daily doses for 5 days. 88 patients (male: 38, mean age: 16.5) were treated with AZM and 69 (male: 34, mean age: 16.9) with CFPN-PI. The symptoms of all but 5 (2 for AZM and 3 for CFPN-PI) of the patients were resolved by the 8th day of the treatment. By the 4th day of the treatment, criteria for clinical efficacy were fulfilled in 71 (80.7%) subjects who were treated with AZM and in 48 (67.6%) of those treated with CFPN-PI (p = 0.07). The same figures on the 8th day of the treatment were 86 (97.7%) and 68 (95.8%), respectively (p = 0.66), confirming there was no significant difference in clinical efficacy between the two treatments. Mild adverse reactions were reported by two patients treated with AZM and by none treated with CFPN-PI. The clinical efficacy of a 3-day course with AZM was comparable with that of a 5-day course of CFPN-PI for GAS tonsillopharyngitis.     

Deletion of the ubiquitin ligase Nedd4L in lung epithelia causes cystic fibrosis-like disease

Cystic fibrosis is caused by impaired ion transport due to mutated cystic fibrosis transmembrane conductance regulator, accompanied by elevated activity of the amiloride-sensitive epithelial Na(+) channel (ENaC). Here we show that knockout of the ubiquitin ligase Nedd4L (Nedd4-2) specifically in lung epithelia (surfactant protein C-expressing type II and Clara cells) causes cystic fibrosis-like lung disease, with airway mucus obstruction, goblet cell hyperplasia, massive inflammation, fibrosis, and death by three weeks of age. These effects of Nedd4L loss are likely caused by enhanced ENaC function, as reflected by increased ENaC protein levels, increased lung dryness at birth, amiloride-sensitive dehydration of lung explants, and elevated ENaC currents in primary alveolar type II cells analyzed by patch clamp recordings. Moreover, the lung defects were rescued with administration of amiloride into the lungs of young knockout pups via nasal instillation. Our results therefore suggest that the ubiquitin ligase Nedd4L can suppress the onset of cystic fibrosis symptoms by inhibiting ENaC in lung epithelia.