ABSTRACT
Ramified, polarized protoplasmic astrocytes interact with synapses via perisynaptic astrocyte processes (PAPs) to form tripartite synapses. These astrocyte-synapse interactions mutually regulate their structures and functions. However, molecular mechanisms for tripartite synapse formation remain elusive. We developed an in vitro co-culture system for mouse astrocytes and neurons that induced astrocyte ramifications and PAP formation. Co-cultured neurons were required for astrocyte ramifications in a neuronal activity-dependent manner, and synaptically-released glutamate and activation of astrocytic mGluR5 metabotropic glutamate receptor were likely involved in astrocyte ramifications. Astrocytic Necl2 trans-interacted with axonal Necl3, inducing astrocyte-synapse interactions and astrocyte functional polarization by recruiting EAAT1/2 glutamate transporters and Kir4.1 K+ channel to the PAPs, without affecting astrocyte ramifications. This Necl2/3 trans-interaction increased functional synapse number. Thus, astrocytic Necl2, synaptically-released glutamate and axonal Necl3 cooperatively formed tripartite glutamatergic synapses in vitro. Studies on hippocampal mossy fiber synapses in Necl3 knockout and Necl2/3 double knockout mice confirmed these previously unreported mechanisms for astrocyte-synapse interactions and astrocyte functional polarization in vivo.
Subject(s)
Glutamic Acid , Synapses , Mice , Animals , Synapses/physiology , Mice, Knockout , Glutamic Acid/pharmacology , Astrocytes/physiology , Mossy Fibers, HippocampalABSTRACT
BACKGROUND: Extracellular vesicles (EVs) have received considerable attention as ideal biomarkers for kidney diseases. Most reports have focused on urinary EVs, that are mainly derived from the cells in the urinary tract. However, the detection and the application of kidney-derived EVs in plasma remains uncertain. METHODS: We examined the kidney-derived small EVs (sEVs) in plasma that were supposedly released from renal mesangial and glomerular endothelial cells, using clinical samples from healthy controls and patients with kidney transplants. Plasma from healthy controls underwent ultracentrifugation, followed by on-bead flow cytometry, targeting α8 integrin, an antigen-specific to mesangial cells. To confirm the presence of kidney-derived sEVs in peripheral blood, plasma from ABO-incompatible kidney transplant recipients was ultracentrifuged, followed by western blotting for donor blood type antigens. RESULTS: Immunohistochemistry and immunoelectron microscopy confirmed α8 integrin expression in kidney mesangial cells and their sEVs. The CD9-α8 integrin double-positive sEVs were successfully detected using on-bead flow cytometry. Western blot analysis further revealed transplanted kidney-derived sEVs containing blood type B antigens in non-blood type B recipients, who had received kidneys from blood type B donors. Notably, a patient experiencing graft kidney loss exhibited diminished signals of sEVs containing donor blood type antigens. CONCLUSION: Our findings demonstrate the potential usefulness of kidney-derived sEVs in plasma in future research for kidney diseases.
Subject(s)
Extracellular Vesicles , Kidney Transplantation , Humans , Extracellular Vesicles/metabolism , Male , Female , Middle Aged , Adult , Case-Control Studies , Mesangial Cells/metabolism , Biomarkers/blood , ABO Blood-Group System , Tetraspanin 29/metabolism , Flow Cytometry , Kidney , Endothelial Cells/metabolism , Blood Group IncompatibilityABSTRACT
Climate change should be of special concern for the nephrologist, as the kidney has a critical role in protecting the host from dehydration, but it is also a favorite target of heat stress and dehydration. Here we discuss how rising temperatures and extreme heat events may affect the kidney. The most severe presentation of heat stress is heat stroke, which can result in severe electrolyte disturbance and both acute and chronic kidney disease (CKD). However, lesser levels of heat stress also have multiple effects, including exacerbating kidney disease and precipitating cardiovascular events in subjects with established kidney disease. Heat stress can also increase the risk for kidney stones, cause multiple electrolyte abnormalities and induce both acute and chronic kidney disease. Recently there have been multiple epidemics of CKD of uncertain etiology in various regions of the world, including Mesoamerica, Sri Lanka, India and Thailand. There is increasing evidence that climate change and heat stress may play a contributory role in these conditions, although other causes, including toxins, could also be involved. As climate change worsens, the nephrologist should prepare for an increase in diseases associated with heat stress and dehydration.
Subject(s)
Heat Stress Disorders , Nephrology , Renal Insufficiency, Chronic , Humans , Climate Change , Dehydration/complications , Renal Insufficiency, Chronic/complications , Kidney , Heat Stress Disorders/complicationsABSTRACT
AIM: Irrespective of the cause, albumin/proteinuria induces tubulointerstitial damage and accelerates the progression of kidney diseases. Our series of studies demonstrated that proteinuria, an independent prognostic factor for chronic kidney disease (CKD), is correlated with urinary basigin/CD147 (Bsg) levels. We examined the morphology and origin of Bsg in the tubular lumen through the effects of filtered glucose and protein solutes on the tubules. METHODS: Diabetic kidney disease (DKD) patients (N = 50) were treated with spironolactone 25 mg for 4 weeks or by conservative treatment. The associations between urinary Bsg values and clinical indicators were examined. Primary-cultured proximal tubular epithelial cells (PTECs) from human adult kidneys were exposed to high glucose or bovine serum albumin (BSA). RESULTS: In patients with early phase DKD, urinary Bsg levels were closely correlated with proteinuria but not HbA1c. Full-length Bsg on extracellular vesicles (EVs) was investigated primarily in urine collected from DKD patients. EVs obtained from the urine of DKD patients included Bsg and SGLT2 proteins. Notably, spironolactone treatment concomitantly suppressed the release of Bsg-bearing EVs in correlation with decreased albuminuria. Exposure of PTECs to BSA (but not high glucose) enhanced the storage of supernatant Bsg in EVs despite the absence of exposure-specific changes in Bsg transcription. CONCLUSION: Proteinuria induces the release of Bsg-bearing EVs derived from PTECs into the tubular lumen.
Subject(s)
Extracellular Vesicles , Renal Insufficiency, Chronic , Adult , Humans , Albuminuria/drug therapy , Albuminuria/metabolism , Basigin/metabolism , Spironolactone/metabolism , Epithelium/metabolism , Proteinuria , Renal Insufficiency, Chronic/metabolismABSTRACT
INTRODUCTION: Considering that neurodegeneration is an irreversible process, an efficient, low-burden approach to prevent dementia is strongly needed. Here, we show that the daily intake of myricetin normalised cognitive dysfunction in senescence-accelerated mouse prone 8 (SAMP8) mice. METHODS: SAMP8 mice were fed a diet supplemented with myricetin and novel object recognition tests and Y-maze tests were performed. Brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in brains of SAMP8 mice were measured. The phosphorylation level of cAMP-response-element-binding protein (CREB) level in brains of SAMP8 mice were evaluated. Also, SH-SY5Y cells were treated with myricetin and cAMP levels were measured. RESULTS: In SAMP8 mice, neurotrophins, including BDNF and NGF, were downregulated relative to levels in their normal counterparts. In addition, myricetin intake upregulated the phosphorylation of CREB, the major transcription factor for BDNF and NGF. Also, myricetin induced cAMP upregulation, and CREB phosphorylation via a cAMP-dependent protein kinase-dependent manner in SH-SY5Y cells. CONCLUSION: Taken together, myricetin improves cognitive function in SAMP8 mice and upregulates BDNF and NGF.
Subject(s)
Brain-Derived Neurotrophic Factor , Cognition , Flavonoids , Neuroblastoma , Animals , Brain-Derived Neurotrophic Factor/metabolism , Cognition/drug effects , Cyclic AMP Response Element-Binding Protein/metabolism , Flavonoids/pharmacology , Hippocampus/drug effects , Hippocampus/metabolism , Humans , Mice , Nerve Growth Factor/metabolism , Neuroblastoma/metabolismABSTRACT
Newly synthesized naphthalene diimide carrying two ß-cyclodextrins (NDI-ß-CyDs) showed improved specificity for the parallel G-quadruplex structure alongside the hybrid G-quadruplex structure. Specifically, the highest binding affinity of NDI-ß-CyDs for the telomere RNA G-quadruplex was observed. The binding simulation indicated that ß-cyclodextrins might be available for loop nucleobase inclusion under its complex.
Subject(s)
G-Quadruplexes , beta-Cyclodextrins , Imides/chemistry , Ligands , Naphthalenes , RNA , Telomere/geneticsABSTRACT
Lotus japonicus is a model legume that accumulates 8-hydroxyflavonol derivatives, such as gossypetin (8-hydroxyquercetin) 3-O-glycoside, which confer the yellow color to its petals. An enzyme, flavonoid 8-hydroxylase (F8H; LjF8H), is assumed to be involved in the biosynthesis, but the specific gene is yet to be identified. The LjF8H cDNA was isolated as a flavin adenine dinucleotide (FAD)-binding monooxygenase-like protein using flower buds and flower-specific EST data of L. japonicus. LjF8H is a single copy gene on chromosome III consisting of six exons. The conserved FAD- and NAD(P)H-dependent oxidase motifs were found in LjF8H. Phylogenetic analysis suggested that LjF8H is a member of the flavin monooxygenase group but distinctly different from other known flavonoid oxygenases. Analysis of recombinant yeast microsome expressing LjF8H revealed that the enzyme catalyzed the 8-hydroxylation of quercetin. Other flavonoids, such as naringenin, eriodictyol, apigenin, luteolin, taxifolin and kaempferol, also acted as substrates of LjF8H. This broad substrate acceptance was unlike known F8Hs in other plants. Interestingly, flavanone and flavanonol, which have saturated C-C bond at positions 2 and 3 of the flavonoid C-ring, produced 6-hyroxylflavonoids as a by-product of the enzymatic reaction. Furthermore, LjF8H only accepted the 2S-isomer of naringenin, suggesting that the conformational state of the substrates might affect product specificity. The overexpression of LjF8H in Arabidopsis thaliana and Petunia hybrida synthesized gossypetin and 8-hydroxykaempferol, respectively, indicating that LjF8H was functional in plant cells. In conclusion, this study represents the first instance of cloning and identification of F8Hs responsible for gossypetin biosynthesis.
Subject(s)
Flavonoids/metabolism , Lotus/enzymology , Mixed Function Oxygenases/metabolism , Plant Proteins/metabolism , Lotus/genetics , Lotus/metabolism , Mixed Function Oxygenases/genetics , Organisms, Genetically Modified , Phylogeny , Plant Proteins/genetics , Saccharomyces cerevisiaeABSTRACT
A fast response potentiometric flow-through pH sensor was applied for organic acid determination. The analyte response with the pH sensor was obtained by eluent pH modification following ion exclusion chromatography with HClO4 as an eluent. The response characteristics depend on the adjusted baseline pH. The baseline pH adjustment was successfully done with an ammonia permeation device without solution mixing, which may cause analyte dilution, dispersion, and mixing noise. After pH adjustment, the pH response was universal to the equivalent of introduced analyte acids because the pH response was obtained by the titration of the permeant ammonia by the analytes. The average of limit of detections (S/N = 3) was 0.06 mM for seven target organic acids. Furthermore, the pH response follows the theoretical pH calculation with the concentrations of the eluent, pH modifier, and analyte. Thus, the analyte concentration in the sample can be theoretically calculated from the pH response without calibration by the analyte standard. Predicted concentrations of injected standards were within 5% of the actual standard concentration. Additionally, analysis of real samples was performed and compared with the conventional post-column reaction with a bromothymol blue (BTB) method. The results obtained with the present system (absolute quantification with theoretical calculation) and conventional BTB method agreed within 10% of errors.
Subject(s)
Organic Chemicals , Calibration , Hydrogen-Ion Concentration , Reference StandardsABSTRACT
BACKGROUND: The Moncrief-Popovich technique of peritoneal catheter implantation has beneficial effects for peritoneal dialysis (PD) initiation. However, it might increase the risk of peritoneal catheter obstruction by fibrin clots, because the catheter is buried under the skin for several weeks to months. Effects of treatment of intraluminal occlusion of PD catheters with tissue plasminogen activator, recommended by the International Society for Peritoneal Dialysis guidelines/recommendations are reportedly limited. We investigated the effectiveness of the 'alpha-replacer' (JMS, Tokyo, Japan) for PD catheter obstruction. METHODS: We retrospectively analyzed a total of 193 patients in whom PD was initiated. PD catheters were embedded using the Moncrief-Popovich technique in 130 of these patients. We assessed the occurrence rates of peritoneal catheter obstruction and the utility of the alpha-replacer for treating intraluminal catheter occlusion by fibrin clots. RESULTS: Catheter obstruction occurred in eight cases with embedded catheters, one due to omental wrapping and the others due to fibrin clots, in which median catheter burial durations were 477 (interquartile range [IQR], 226-510) days. All catheter obstructions due to fibrin clots were successfully treated with the alpha-replacer, leading to improved catheter drainage. The median amount of contrast agent used in catheterography was 10 (IQR 9-10) mL, which did not adversely affect residual renal function. There were no complications. No recurrence occurred during the observation period (median 111, IQR 55.5-141 months). CONCLUSION: Our results suggest that treatment with the alpha-replacer is a safe and effective treatment option for intraluminal obstruction of PD catheters by fibrin clots.
Subject(s)
Catheter Obstruction/etiology , Catheterization/instrumentation , Catheters, Indwelling/adverse effects , Fibrin/metabolism , Kidney Diseases/therapy , Peritoneal Dialysis/instrumentation , Adult , Aged , Catheterization/adverse effects , Equipment Design , Female , Humans , Kidney Diseases/diagnosis , Kidney Diseases/physiopathology , Male , Middle Aged , Peritoneal Dialysis/adverse effects , Radiography, Interventional , Retrospective Studies , Time Factors , Treatment OutcomeABSTRACT
Podocytes, which are susceptible to injury by various stimuli and stress, are critical regulators of proteinuric kidney diseases, regardless of the primary disease and pathogenesis. We further confirmed a significant correlation between urinary CD147/basigin (Bsg) levels and proteinuria in patients with focal segmental glomerulosclerosis. However, the molecular mechanism of podocyte injury involving Bsg is not fully understood. Here, the involvement of Bsg in the pathogenesis of podocyte injury was elucidated. Healthy podocytes rarely express Bsg protein. In two independent mouse models, including adriamycin-induced nephropathy and Nω-nitro-l-arginine methyl ester (l-name)-induced endothelial dysfunction, Bsg induction in injured podocytes caused podocyte effacement, which led to development of proteinuria. Bsg silencing in cultured podocytes exposed to transforming growth factor-ß suppressed focal adhesion rearrangement and cellular motility via the activation of ß1 integrin-focal adhesion kinase-matrix metallopeptidase signaling. In addition, induction of vascular endothelial growth factor and endothelin-1, which are implicated in podocyte-to-endothelial cross-communication, was lower in the supernatants of cultured Bsg-silenced podocytes stimulated with transforming growth factor-ß. In this setting, Bsg may be involved in a physiological positive feedback loop that accelerates podocyte cell motility and depolarization. The current study thus suggests that Bsg silencing via suppression of ß1 integrin-focal adhesion kinase-matrix metallopeptidase signaling may be an attractive therapeutic strategy for the maintenance of podocytes in patients with proteinuric kidney diseases.
Subject(s)
Basigin/deficiency , Focal Adhesion Kinase 1/metabolism , Glomerulosclerosis, Focal Segmental/metabolism , Podocytes/metabolism , Proteinuria/metabolism , Signal Transduction , Adult , Animals , Disease Models, Animal , Doxorubicin/adverse effects , Doxorubicin/pharmacology , Female , Glomerulosclerosis, Focal Segmental/chemically induced , Glomerulosclerosis, Focal Segmental/pathology , Humans , Male , Mice , Mice, Knockout , NG-Nitroarginine Methyl Ester/pharmacology , Podocytes/pathology , Proteinuria/chemically induced , Proteinuria/pathologyABSTRACT
A 59-year-old woman unaware of having diabetes was transferred due to coma. Upon discovery at home, her consciousness on the Glasgow Coma Scale was E1V2M4, BP 95/84 mmHg, body temperature 34.7°C. On arrival at ER, height was 1.63 m, weight 97 kg, plasma glucose (PG) 1,897 mg/dL, HbA1c 13.6%, osmolality 421 mosm/kg, arterial pH 7.185, lactate 6.34 mmol/L, ß-hydroxybutyrate 7.93 mmol/L. With saline and regular insulin infusion, PG was lowered to 1,440 mg/dL at 2 hours and then to 250 mg/dL by Day 3, and consciousness normalized by Day 5. On admission, serum immunoreactive insulin (IRI) was undetectable (<0.03 U/mL), C-peptide immunoreactivity (CPR) undetectable (<0.003 ng/mL), and anti-glutamic acid decarboxylase antibody negative. Following the above-described treatment, fasting PG was 186 mg/dL and CPR 1.94 ng/mL, respectively, on Day 14; 2-h post-breakfast PG 239 mg/dL and CPR 6.28 ng/mL, respectively, on Day 18. The patient discharged on Day 18 with 1,800 kcal diet, 32 U insulin glargine and 40 mg gliclazide. Fifteen months later at outpatient clinic, her HbA1c was 6.9% and 2-h post-breakfast PG 123 mg/dL and CPR 5.30 ng/dL with 750 mg metformin, 10 mg gliclazide and 18 U insulin glargine. Transient, but total cessation of insulin secretion was documented in a patient with type 2 diabetes under severe metabolic decompensation. Swift, sustained recovery of insulin release indicated that lack of insulin at the time of emergency was due to secretory failure, i.e., unresponsive exocytotic machinery or depletion of releasable insulin, rather than loss of beta cells.
Subject(s)
C-Peptide/metabolism , Diabetes Mellitus, Type 2/metabolism , Diabetic Coma/metabolism , Insulin/metabolism , Acidosis, Lactic/complications , Acidosis, Lactic/metabolism , Acidosis, Lactic/therapy , Blood Glucose/metabolism , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/therapy , Diabetic Coma/etiology , Diabetic Coma/therapy , Female , Fluid Therapy , Glycated Hemoglobin/metabolism , Humans , Hyperglycemia/complications , Hyperglycemia/metabolism , Hyperglycemia/therapy , Hypoglycemic Agents/therapeutic use , Insulin Secretion , Insulin-Secreting Cells/metabolism , Ketosis/complications , Ketosis/metabolism , Ketosis/therapy , Middle Aged , Pancreatitis/etiology , Pancreatitis/metabolismABSTRACT
BACKGROUND: While hand and ultrasonic scalers are the primary tools used for the removal of dental calculus in periodontal treatment, many studies have shown that they also damage the enamel surface. We have developed a novel actuator-driven pulsed water jet (ADPJ) system, which has the ability to selectively remove materials depending on their stiffness. Considering the different material properties between teeth and dental calculus, it might be possible to develop the ADPJ to remove dental calculus without damage to the tooth's enamel surface using a suitable jet pressure. Therefore, the aim of this study was to assess the effectiveness of the ADPJ in removing dental calculus, and the surface features of the teeth after its use. METHODS: A total of 93 artificial teeth coated with artificial dental calculus were examined in this study. The weights of 90 teeth were measured before and after the use of ADPJ, which had an applied voltage setting of 150, 200, or 240 V. The three remaining teeth were instrumented with a conventional hand scaler, ultrasonic scaler, or ADPJ (set at 240 V). Damage to the artificial tooth surfaces was evaluated using 5% Evans blue dye under an optical microscope. Furthermore, apatite pellets, which are utilized as experimental substitutes for natural teeth, were assessed after the use of ADPJ and both conventional scalers. RESULTS: The ADPJ significantly reduced the amount of artificial calculus, and the removal rate was dependent on the applied voltage. No damage was observed on the surface of the artificial tooth and apatite pellet following the use of ADPJ, in contrast to the conventional scalers. CONCLUSIONS: The results of this study demonstrate the in vitro effectiveness of ADPJ in the removal of dental calculus, without causing damage to tooth surfaces.
Subject(s)
Dental Calculus , Ultrasonic Therapy , Dental Calculus/therapy , Dental Scaling , Humans , Microscopy , Tooth Root , WaterABSTRACT
Obesity and metabolic syndrome are well-known risk factors for chronic kidney disease (CKD); however, less is known about the mechanism(s) by which metabolic syndrome might accelerate kidney disease. We hypothesized that metabolic syndrome should accelerate the development of kidney disease and that it might be associated with alterations in energy metabolism. We studied the pound mouse (which develops early metabolic syndrome due to a leptin receptor deletion) and wild-type littermates and compared the level of renal injury and muscle wasting after equivalent injury with oral adenine. Renal function, histology, and biochemical analyses were performed. The presence of metabolic syndrome was associated with earlier development of renal disease (12 mo) and earlier mortality in pound mice compared with controls. After administration of adenine, kidney disease was worse in pound mice, and this was associated with greater tubular injury with a decrease in kidney mitochondria, lower tissue ATP levels, and worse oxidative stress. Pound mice with similar levels of renal function as adenine-treated wild-type mice also showed worse sarcopenia, with lower tissue ATP and intracellular phosphate levels. In summary, our data demonstrate that obesity and metabolic syndrome accelerate the progression of CKD and worsen CKD-dependent sarcopenia. Both conditions are associated with renal alterations in energy metabolism and lower tissue ATP levels secondary to mitochondrial dysfunction and reduced mitochondrial number.
Subject(s)
Energy Metabolism , Kidney/metabolism , Mitochondria/metabolism , Obesity/complications , Obesity/metabolism , Renal Insufficiency, Chronic/complications , Renal Insufficiency, Chronic/metabolism , Adenine/toxicity , Adenosine Triphosphate/metabolism , Animals , Kidney Function Tests , Kidney Tubules/pathology , Mice , Mice, Inbred C57BL , Mice, Obese , Sarcopenia/etiology , Sarcopenia/metabolismABSTRACT
An epidemic of chronic kidney disease of unknown etiology (Mesoamerican nephropathy) has emerged in hot regions of Central America. We have demonstrated that dehydration associated with recurrent heat exposure causes chronic kidney disease in animal models. However, the independent influence of core body temperature on kidney injury has not been explored. In the present study, we tested the hypothesis that kidney injury could be accelerated by increasing body temperature independent of external temperature. Wild-type mice were exposed to heat (39.5°C, 30 min, 2 times daily) with or without the mitochondrial uncoupling agent 2,4-dinitrophenol (DNP) for 10 days. Core temperature, renal function, proteinuria, and renal histological and biochemical analyses were performed. Isolated mitochondria markers of oxidative stress were evaluated from kidney tissue. DNP increased body core temperature in response to heat by 1°C (42 vs. 41°C), which was transient. The mild increase in temperature correlated with worsening albuminuria (R = 0.715, P < 001), renal tubular injury, and interstitial infiltration of monocytes/macrophages. Tubular injury was marked in the outer medulla. This was associated with a reduction in kidney tissue ATP levels (nonheated control: 16.71 ± 1.33 nmol/mg and DNP + heat: 13.08 ± 1.12 nmol/mg, P < 0.01), reduced mitochondria, and evidence for mitochondrial oxidative stress. The results of the present study suggest that kidney injury in heat stress is markedly worsened by increasing core temperature. This is consistent with the hypothesis that clinical and subclinical heat stroke may play a role in Mesoamerican nephropathy.
Subject(s)
Fever , Heat-Shock Response , Kidney Diseases/etiology , 2,4-Dinitrophenol/toxicity , Animals , Gene Expression Regulation , HSP70 Heat-Shock Proteins/genetics , HSP70 Heat-Shock Proteins/metabolism , Kidney Medulla , Male , Mice , Mitochondria , Time FactorsABSTRACT
BACKGROUND: Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infection has recently become a challenging problem worldwide and in Japan. We experienced 10 pediatric patients infected with CA-MRSA and hospitalized from 2011 to 2014 in a tertiary care hospital in Saitama, Japan, and assessed the characteristic of the strains using a whole genome sequencing (WGS)-based approach. METHODS: CA-MRSA strains isolated from infected patients who required hospitalization for treatment were evaluated in this study. Antimicrobial susceptibility tests, molecular typing by PCR and pulse-field gel electrophoresis (PFGE) were performed to characterize MRSA strains. WGS was performed for detailed genetic analysis. RESULTS: A total of 582 MRSA strains (35.2%) were identified among 1625 S. aureus strains collected during the study period. Ten MRSA strains (1.7%) were defined as CA-MRSA clinically, and all were isolated from pediatric patients. All strains mainly caused purulent lymphadenitis, were susceptible to fluoroquinolone and tetracycline, exhibited sequence type (ST) 834 or its single-locus variants and contained staphylococcal cassette chromosome mec (SCCmec) type IVc. Phylogenic analysis by PFGE and WGS revealed close relatedness of all strains, with the number of single nucleotide polymorphisms ranging from 35 to 119 by WGS. Out of the ten strains, nine possessed the genomic island SaPISaitama2 containing tst, sec and sel genes. SaPISaitama2 comprises a mosaic of genomic islands SaPIm4 and SaPIm1 harbored by a hospital-associated MRSA strain Mu50. CONCLUSIONS: This study describes a regional outbreak of ST834-related CA-MRSA in children with a unique pathogenicity island in Japan. Pediatric patient tropism of this clone could be enhanced by susceptibility to fluoroquinolones and tetracyclines, which cannot be prescribed to children.
Subject(s)
Community-Acquired Infections , Disease Outbreaks/statistics & numerical data , Methicillin-Resistant Staphylococcus aureus , Staphylococcal Infections , Anti-Bacterial Agents/pharmacology , Child , Cohort Studies , Community-Acquired Infections/epidemiology , Community-Acquired Infections/microbiology , Humans , Japan/epidemiology , Methicillin-Resistant Staphylococcus aureus/drug effects , Methicillin-Resistant Staphylococcus aureus/genetics , Methicillin-Resistant Staphylococcus aureus/pathogenicity , Microbial Sensitivity Tests , Staphylococcal Infections/epidemiology , Staphylococcal Infections/microbiologyABSTRACT
A majority of the potential health benefits of green tea, including the potential to prevent cognitive decline, have been attributed to epigallocatechin gallate (EGCG). Sunrouge is a green tea cultivar that contains EGCG and several other bioactive components such as quercetin, myricetin, cyanidin and delphinidin. We compared the effects of Sunrouge and Yabukita, the most popular Japanese green tea cultivar, on cognitive function in the senescence-accelerated mouse Prone8. These mice were fed an experimental diet containing Sunrouge extract (SRE) or Yabukita extract (YBE). SRE feeding significantly prevented cognitive decline, whereas YBE feeding had little effect. Moreover, SRE feeding prevented elevation of the amyloid-ß42 level while improving the gene expression of neprilysin and decreasing beta-site APP-cleaving enzyme 1 in the brain. These preventive effects of SRE against cognitive decline were attributed to the characteristic composition of Sunrouge and strongly suggest that consumption of this cultivar could protect against age-related cognitive decline.
Subject(s)
Aging/psychology , Cognition Disorders/prevention & control , Dietary Supplements , Tea/chemistry , Acetylcholinesterase/metabolism , Amyloid beta-Peptides/metabolism , Amyloid beta-Protein Precursor/metabolism , Animals , Brain/enzymology , Enzymes/genetics , Enzymes/metabolism , Male , Mice , Mice, Mutant Strains , Neprilysin/genetics , Peptide Fragments/metabolismSubject(s)
Clostridioides difficile , Clostridium Infections , Infection Control , Humans , Clostridium Infections/prevention & control , Clostridium Infections/microbiology , Cross Infection/prevention & control , Cross Infection/microbiology , Infection Control/methods , Japan/epidemiology , Societies, MedicalABSTRACT
The worldwide increase in temperature has resulted in a marked increase in heat waves (heat extremes) that carries a markedly increased risk for morbidity and mortality. The kidney has a unique role not only in protecting the host from heat and dehydration but also is an important site of heat-associated disease. Here we review the potential impact of global warming and heat extremes on kidney diseases. High temperatures can result in increased core temperatures, dehydration, and blood hyperosmolality. Heatstroke (both clinical and subclinical whole-body hyperthermia) may have a major role in causing both acute kidney disease, leading to increased risk of acute kidney injury from rhabdomyolysis, or heat-induced inflammatory injury to the kidney. Recurrent heat and dehydration can result in chronic kidney disease (CKD) in animals and theoretically plays a role in epidemics of CKD developing in hot regions of the world where workers are exposed to extreme heat. Heat stress and dehydration also has a role in kidney stone formation, and poor hydration habits may increase the risk for recurrent urinary tract infections. The resultant social and economic consequences include disability and loss of productivity and employment. Given the rise in world temperatures, there is a major need to better understand how heat stress can induce kidney disease, how best to provide adequate hydration, and ways to reduce the negative effects of chronic heat exposure.
Subject(s)
Heat Stress Disorders/epidemiology , Renal Insufficiency, Chronic/epidemiology , Climate Change , Dehydration , Heat Stress Disorders/etiology , Hot Temperature , Humans , Renal Insufficiency, Chronic/etiologyABSTRACT
Limited dorsal myeloschisis (LDM) and congenital dermal sinus (CDS) originate from incomplete disjunction between the cutaneous and neural ectoderms. Some LDM stalks have been found to have elements of a CDS or dermoid cyst. We surgically treated a saccular lesion in the lumbosacral region of a 7-day-old male neonate. Although fetal magnetic resonance imaging (MRI) failed to reveal a stalk, postnatal MRI including three-dimensional heavily T2-weighted imaging demonstrated a stalk originating from the lumbar cord and extending caudally to enter the lumbosacral meningocele sac. During untethering surgery, we found that the stalk was slender, with a diameter of 0.7-0.8 mm, but otherwise appeared to be a typical LDM stalk. Histopathological examination revealed that the fibrocollagenous stalk contained glial fibrillary acidic protein-immunopositive neuroglial tissues and stratified squamous epithelium. The present report describes the first documented case of a stalk with combined features of saccular LDM and CDS in a neonate. Since cutaneous ectodermal tissue is likely to remain in the remnant stalk, this patient requires careful monitoring to detect the potential development of a dermoid cyst.
Subject(s)
Dermoid Cyst/diagnostic imaging , Dermoid Cyst/surgery , Lumbar Vertebrae/diagnostic imaging , Lumbar Vertebrae/surgery , Spina Bifida Occulta/diagnostic imaging , Spina Bifida Occulta/surgery , Adult , Dermoid Cyst/complications , Female , Humans , Infant, Newborn , Magnetic Resonance Imaging/methods , Male , Pregnancy , Prenatal Diagnosis/methods , Spina Bifida Occulta/complicationsABSTRACT
The scintillating grid illusion is a geometric visual illusion where illusory dark spots are perceived on white circular patches that are located at the intersections of a grid pattern. Previous studies have measured the perceived strength of the illusory spots by varying stimulus and viewing conditions, to elucidate the mechanisms underlying the illusion; however, findings remain inconclusive. In the present study, we measured the perceived size of the illusory spots, in addition to their perceived strength, by varying the size of the geometric components and the orientation of the stimulus, to further investigate the mechanism behind this illusion. We found that the dependency of perceived spot size on the change of the stimulus parameters is dissociated from that of the perceived spot strength. The perceived size of the illusory spots linearly correlated with the size of the white patches and was less dependent on the width of the grid bars and the orientation of the stimulus, while the perceived strength was characterized by a quadratic relationship with patch size and bar width and was monotonically modulated depending on the orientation of the stimuli. These results suggest that different factors separately constrain size and strength within the processes that elicit the illusory spots. We propose that the mechanism underlying the scintillating grid illusion is based on the interruption of the surface formation process of white patches by the interference of the orientation signals of gray bars.