Animal infection models using non‐mammals

The use of non‐human animal models for infection experiments is important for investigating the infectious processes of human pathogenic bacteria at the molecular level. Mammals, such as mice and rabbits, are also utilized as animal infection models, but large numbers of animals are needed for these experiments, which is costly, and fraught with ethical issues. Various non‐mammalian animal infection models have been used to investigate the molecular mechanisms of various human pathogenic bacteria, including Staphylococcus aureus, Streptococcus pyogenes, and Pseudomonas aeruginosa. This review discusses the desirable characteristics of non‐mammalian infection models and describes recent non‐mammalian infection models that utilize Caenorhabditis elegans, silkworm, fruit fly, zebrafish, two‐spotted cricket, hornworm, and waxworm

Effects of low-dose/high-dose-rate X-irradiation on oxidative stress in organs following forced swim test and its combined effects on alcohol-induced liver damage in mice

The liver's susceptibility to oxidative stress after a combination of forced swim test (FST) and low-dose-rate gamma-irradiation has been observed. Therefore, this study aims to clarify the effects of low-dose (0.1 and 0.5 Gy)/high-dose-rate (1.2 Gy/min) irradiation on combined oxidative stressors-liver damage associated with FST and alcohol administration. In addition, the effects of similar irradiation on FST-induced immobility, which induces psychomotor retardation, and antioxidative effects on the brain, lungs, liver and kidneys were investigated, and the results were compared with those of a similar previous study that utilized low-dose-rate irradiation. Low-dose/high-dose-rate (especially 0.5 Gy) irradiation temporarily worsened liver antioxidant function and hepatic function with FST- and alcohol administration-related oxidative damage; however, the damages improved soon after. In addition, the increase in total glutathione content in the liver contributed to the early improvement of hepatic functions. However, pre-irradiation did not suppress immobility during the FST. The results also suggested that the effects of low-dose/high-dose-rate irradiation on the antioxidant functions of each organ after the FST were different from those of low-dose/low-dose-rate irradiation. Overall, this study provides further insights into the effects of low-dose irradiation on exposure to a combination of different oxidative stressors. It will also contribute to the elucidation of dose rate effects on oxidative stress in the low-dose irradiation range

Immunomodulatory Effects of Radon Inhalation on Lipopolysaccharide-Induced Inflammation in Mice

Typical indications for radon therapy include autoimmune diseases such as rheumatoid arthritis (RA). We had previously reported that radon inhalation inhibits Th17 immune responses in RA mice by activating Th1 and Th2 immune responses. However, there are no reports on how radon inhalation affects the activated Th1 and Th17 immune responses, and these findings may be useful for identifying new indications for radon therapy. Therefore, in this study, we investigated the effect of radon inhalation on the lipopolysaccharide (LPS)-induced inflammatory response, focusing on the expression of related cytokines and antioxidant function. Male BALB/c mice were exposed to 2000 Bq/m(3) radon for one day. Immediately after radon inhalation, LPS was administered intraperitoneally at 1.0 mg/kg body weight for 4 h. LPS administration increased the levels of Th1- and Th17-prone cytokines, such as interleukin-2, tumor necrosis factor-alpha, and granulocyte-macrophage colony-stimulating factor, compared to no treatment control (sham). However, these effects were suppressed by radon inhalation. IL-10 levels were significantly increased by LPS administration, with or without radon inhalation, compared to sham. However, radon inhalation did not inhibit oxidative stress induced by LPS administration. These findings suggest that radon inhalation has immunomodulatory but not antioxidative functions in LPS-induced injury

Multiacquisition Variable-Resonance Image Combination Selective Can Improve Image Quality and Reproducibility for Metallic Implants in the Lumbar Spine

The aim of this study is to evaluate how metallic artifacts in the lumbar spine can affect images obtained from magnetic resonance (MR) sequences. We performed a phantom experiment by scanning an agar containing an orthopedic metallic implant using 64-channel multidetector row computed tomography (CT) and a 3-tesla MR unit. We compared the reproducibility in each measurement, enlargement or reduction ratio of the CT and MR measurements, and signal deviation in each voxel from the control. The reproducibility on CT and multiacquisition variable-resonance image combination selective (MAVRIC SL) was good, but that on the other MR sequences showed either fixed bias or proportional bias. The reduction ratios of the distance between the nails were significantly smaller in MAVRIC SL than in the other MR sequences after CT measurements (p<0.001, respectively). MAVRIC SL was able to reduce the metallic artifact, permitting observation of the tissue surrounding the metal with good reproducibility

Regulation of ectopic heterochromatin-mediated epigenetic diversification by the JmjC family protein Epe1

H3K9 methylation (H3K9me) is a conserved marker of heterochromatin, a transcriptionally silent chromatin structure. Knowledge of the mechanisms for regulating heterochromatin distribution is limited. The fission yeast JmjC domain-containing protein Epe1 localizes to heterochromatin mainly through its interaction with Swi6, a homologue of heterochromatin protein 1 (HP1), and directs JmjC-mediated H3K9me demethylation in vivo. Here, we found that loss of epe1 (epe1Delta) induced a red-white variegated phenotype in a red-pigment accumulation background that generated uniform red colonies. Analysis of isolated red and white colonies revealed that silencing of genes involved in pigment accumulation by stochastic ectopic heterochromatin formation led to white colony formation. In addition, genome-wide analysis of red- and white-isolated clones revealed that epe1Delta resulted in a heterogeneous heterochromatin distribution among clones. We found that Epe1 had an N-terminal domain distinct from its JmjC domain, which activated transcription in both fission and budding yeasts. The N-terminal transcriptional activation (NTA) domain was involved in suppression of ectopic heterochromatin-mediated red-white variegation. We introduced a single copy of Epe1 into epe1Delta clones harboring ectopic heterochromatin, and found that Epe1 could reduce H3K9me from ectopic heterochromatin but some of the heterochromatin persisted. This persistence was due to a latent H3K9me source embedded in ectopic heterochromatin. Epe1H297A, a canonical JmjC mutant, suppressed red-white variegation, but entirely failed to remove already-established ectopic heterochromatin, suggesting that Epe1 prevented stochastic de novo deposition of ectopic H3K9me in an NTA-dependent but JmjC-independent manner, while its JmjC domain mediated removal of H3K9me from established ectopic heterochromatin. Our results suggest that Epe1 not only limits the distribution of heterochromatin but also controls the balance between suppression and retention of heterochromatin-mediated epigenetic diversification

Methicillin Resistance Alters the Biofilm Phenotype and Attenuates Virulence in Staphylococcus aureus Device-Associated Infections

Clinical isolates of Staphylococcus aureus can express biofilm phenotypes promoted by the major cell wall autolysin and the fibronectin-binding proteins or the icaADBC-encoded polysaccharide intercellular adhesin/poly-N-acetylglucosamine (PIA/PNAG). Biofilm production in methicillin-susceptible S. aureus (MSSA) strains is typically dependent on PIA/PNAG whereas methicillin-resistant isolates express an Atl/FnBP-mediated biofilm phenotype suggesting a relationship between susceptibility to β-lactam antibiotics and biofilm. By introducing the methicillin resistance gene mecA into the PNAG-producing laboratory strain 8325-4 we generated a heterogeneously resistant (HeR) strain, from which a homogeneous, high-level resistant (HoR) derivative was isolated following exposure to oxacillin. The HoR phenotype was associated with a R602H substitution in the DHHA1 domain of GdpP, a recently identified c-di-AMP phosphodiesterase with roles in resistance/tolerance to β-lactam antibiotics and cell envelope stress. Transcription of icaADBC and PNAG production were impaired in the 8325-4 HoR derivative, which instead produced a proteinaceous biofilm that was significantly inhibited by antibodies against the mecA-encoded penicillin binding protein 2a (PBP2a). Conversely excision of the SCCmec element in the MRSA strain BH1CC resulted in oxacillin susceptibility and reduced biofilm production, both of which were complemented by mecA alone. Transcriptional activity of the accessory gene regulator locus was also repressed in the 8325-4 HoR strain, which in turn was accompanied by reduced protease production and significantly reduced virulence in a mouse model of device infection. Thus, homogeneous methicillin resistance has the potential to affect agr- and icaADBC-mediated phenotypes, including altered biofilm expression and virulence, which together are consistent with the adaptation of healthcare-associated MRSA strains to the antibiotic-rich hospital environment in which they are frequently responsible for device-related infections in immuno-compromised patients

Complications Associated With Spine Surgery in Patients Aged 80 Years or Older: Japan Association of Spine Surgeons with Ambition (JASA) Multicenter Study

Study Design:Retrospective study of registry data.Objectives:Aging of society and recent advances in surgical techniques and general anesthesia have increased the demand for spinal surgery in elderly patients. Many complications have been described in elderly patients, but a multicenter study of perioperative complications in spinal surgery in patients aged 80 years or older has not been reported. Therefore, the goal of the study was to analyze complications associated with spine surgery in patients aged 80 years or older with cervical, thoracic, or lumbar lesions.Methods:A multicenter study was performed in patients aged 80 years or older who underwent 262 spinal surgeries at 35 facilities. The frequency and severity of complications were examined for perioperative complications, including intraoperative and postoperative complications, and for major postoperative complications that were potentially life threatening, required reoperation in the perioperative period, or left a permanent injury.Results:Perioperative complications occurred in 75 of the 262 surgeries (29%) and 33 were major complications (13%). In multivariate logistic regression, age over 85 years (hazard ratio [HR] = 1.007, P = 0.025) and estimated blood loss ≥500 g (HR = 3.076, P = .004) were significantly associated with perioperative complications, and an operative time ≥180 min (HR = 2.78, P = .007) was significantly associated with major complications.Conclusions:Elderly patients aged 80 years or older with comorbidities are at higher risk for complications. Increased surgical invasion, and particularly a long operative time, can cause serious complications that may be life threatening. Therefore, careful decisions are required with regard to the surgical indication and procedure in elderly patients

Risk Factors for Delirium After Spine Surgery in Extremely Elderly Patients Aged 80 Years or Older and Review of the Literature: Japan Association of Spine Surgeons with Ambition Multicenter Study

Study Design:Retrospective database analysis.Objective:Spine surgeries in elderly patients have increased in recent years due to aging of society and recent advances in surgical techniques, and postoperative complications have become more of a concern. Postoperative delirium is a common complication in elderly patients that impairs recovery and increases morbidity and mortality. The objective of the study was to analyze postoperative delirium associated with spine surgery in patients aged 80 years or older with cervical, thoracic, and lumbar lesions.Methods:A retrospective multicenter study was performed in 262 patients 80 years of age or older who underwent spine surgeries at 35 facilities. Postoperative complications, incidence of postoperative delirium, and hazard ratios of patient-specific and surgical risk factors were examined.Results:Postoperative complications occurred in 59 of the 262 spine surgeries (23%). Postoperative delirium was the most frequent complication, occurring in 15 of 262 patients (5.7%), and was significantly associated with hypertension, cerebrovascular disease, cervical lesion surgery, and greater estimated blood loss (P < .05). In multivariate logistic regression using perioperative factors, cervical lesion surgery (odds ratio = 4.27, P < .05) and estimated blood loss ≥300 mL (odds ratio = 4.52, P < .05) were significantly associated with postoperative delirium.Conclusions:Cervical lesion surgery and greater blood loss were perioperative risk factors for delirium in extremely elderly patients after spine surgery. Hypertension and cerebrovascular disease were significant risk factors for postoperative delirium, and careful management is required for patients with such risk factors

Bone morphogenetic proteins in tissue engineering: the road from laboratory to clinic, part II (BMP delivery)

Bone morphogenetic proteins (BMPs) are cytokines with a strong effect on bone and cartilage growth and with important roles during embryonic patterning and early skeletal formation. BMPs have promising potential for clinical bone and cartilage repair, working as powerful boneinducing components in diverse tissue-engineering products. Synthetic polymers, natural origin polymers, inorganic materials and composites may be used as carriers for the delivery of BMPs. Carriers range from nanoparticles to complex three-dimensional (3D) scaffolds, membranes for tissue-guided regeneration, biomimetic surfaces and smart thermosensitive hydrogels. Current clinical uses include spinal fusion, healing of long bone defects and craniofacial and periodontal applications, amongst others. BMP-2 and BMP-7 have recently received approval by the US Food and Drug Administration (FDA) for specific clinical cases, delivered in absorbable collagen sponges. Considering the expanding number of publications in the field of BMPs, there are prospects of a brilliant future in the field of regenerative medicine of bone and cartilage with the use of BMPs