A semiquantitative analysis of reactive astrogliosis demonstrates its correlation with the number of intact motor neurons after transient spinal cord ischemia

ObjectiveWe evaluated the relationship between reactive astrogliosis and delayed motor neuron death after transient spinal cord ischemia in rabbits using a semiquantitative analysis of glial fibrillary acidic protein expression.MethodsSpinal cord ischemia was induced by means of balloon occlusion of the infrarenal aorta for 15 minutes at 39°C in 18 New Zealand white rabbits. At 1, 3, and 7 days after reperfusion, 6 animals at each time point were killed, and the spinal cord was removed for histologic and immunohistochemical study. The variables analyzed were (1) neurologic function (Johnson score) at every 24 hours after reperfusion, (2) the number of intact motor neurons and terminal deoxynucleotidyl transferase–mediated deoxyuridine triphosphate-biotin nick-end labeling–positive positive neurons, and (3) expression of glial fibrillary acidic protein in the gray and white matter, which was expressed as the percentage of stained area.ResultsAll animals presented delayed motor neuron death. The number of intact neurons decreased correlatively with neurologic function. No obvious terminal deoxynucleotidyl transferase–mediated deoxyuridine triphosphate-biotin nick-end labeling–positive cells were observed. Glial fibrillary acidic protein expression increased with time in both the gray and white matter, representing the development of reactive astrogliosis. Significant correlation was found between glial fibrillary acidic protein expression and the number of intact motor neurons on the third day in both the gray (r2 = 0.726, P = .031) and white (r2 = 0.927, P = .002) matter.ConclusionsReactive astrogliosis 3 days after transient spinal cord ischemia correlates with the number of intact motor neurons. Our method for semiquantitative analysis of reactive astrogliosis is simple and reproducible and seems useful for such experimental studies

The pathophysiology of non-steroidal anti-inflammatory drug (NSAID)-induced mucosal injuries in stomach and small intestine

Non-steroidal anti-inflammatory drugs are the most commonly prescribed drugs for arthritis, inflammation, and cardiovascular protection. However, they cause gastrointestinal complications. The pathophysiology of these complications has mostly been ascribed to non-steroidal anti-inflammatory drugs’ action on the cyclooxygenase inhibition and the subsequent prostaglandin deficiency. However, recent clinical demonstrated the prevalence of non-steroidal anti-inflammatory drugs-induced small intestinal mucosal injury is more often than previously expected. In this review, we discuss the defense mechanisms of stomach, and the pathophysiology of non-steroidal anti-inflammatory drugs-induced injury of stomach and small intestine, especially focused on non-steroidal anti-inflammatory drugs’ action on mitochondria

Lansoprazole inhibits mitochondrial superoxide production and cellular lipid peroxidation induced by indomethacin in RGM1 cells

Lansoprazole is effective in healing non-steroidal anti-inflammatory drugs induced ulcers, and antioxidant properties have been thought to play a key role in healing ulcers. We hypothesize that lansoprazole exerts a cytoprotective effect by inhibiting reactive oxygen species leakage from mitochondria and lipid peroxidation. We pretreated gastric epithelial RGM1 cells with lansoprazole and then treated them with indomethacin in vitro. We found that the lansoprazole pretreatment significantly reduced cellular injury, maintained mitochondrial transmembrane potential, and decreased lipid peroxidation. Furthermore, the signal intensity of the electron spin resonance spectrum of the indomethacin-treated mitochondria which were pretreated with lansoprazole showed considerable reduction compared to those without the lansoprazole pretreatment. These results suggest that lansoprazole reduced superoxide production in the mitochondria of indomethacin treated cells, and subsequently inhibited lipid peroxide and cellular injury in gastric epithelial cells

Slope in preload recruitable stroke work relationship predicts survival after left ventriculoplasty and mitral repair in patients with idiopathic cardiomyopathy

AbstractBackgroundLeft ventriculoplasty (LVP) and mitral valve plasty (MVP) are sometimes effective for patients with idiopathic dilated cardiomyopathy (DCM) who are not eligible for heart transplantation. Strict patient selection is warranted for these controversial procedures.Methods and resultsThe subjects were 18 patients with idiopathic DCM and mitral regurgitation who had not been indicated for heart transplantation due to either older age or patient refusal, and who underwent LVP and MVP. Their mean age was 57±14 years and 50% were dependent on catecholamine infusion. The preload recruitable stroke work (PRSW) relationship and its slope (Mw) were estimated by a single-beat technique using transthoracic echocardiography. There were one 30-day mortality and six (33%) hospital deaths due to heart failure. The one-year survival rate was 50%. Left ventricular end-diastolic dimension (LVDd) decreased from 77±11 to 68±11mm (p=0.001) whereas the ejection fraction did not change. Preoperative Mw was significantly higher in one-year survivors than that in non-survivors (54±17ergcm−3103 vs. 31±10ergcm−3103, p=0.005). Preoperative LVDd was not different between the groups. The cut-off value of 42ergcm−3103 for Mw predicted one-year survival with high sensitivity (100%) and specificity (77%).ConclusionsMw, the slope in the PRSW relationship, may predict survival after LVP and MVP in patients with idiopathic DCM

Complete Genome Sequence of blaIMP–6-Positive Metakosakonia sp. MRY16-398 Isolate From the Ascites of a Diverticulitis Patient

A novel species of carbapenemase-producing Enterobacteriaceae (CPE) was isolated from a patient diagnosed with sigmoid colon diverticulitis. At first, laboratory testing suggested it was Klebsiella oxytoca or Pantoea sp.; however, a complete genome sequence of the isolate, MRY16-398, revealed that it could be novel species, most similar to [Kluyvera] intestini, of which taxonomic nomenclature is still under discussion. Orthologous conserved gene analysis among 42 related bacterial strains indicated that MRY16-398 was classified as the newly proposed genus Metakosakonia. Further, MRY16-398 was found to harbor the blaIMP-6 gene-positive class 1 integron (In722) in plasmid pMRY16-398_2 (IncN replicon, 47.4 kb in size). This finding implies that rare and opportunistic bacteria could be potential infectious agents. In conclusion, our results highlight the need for continuous monitoring for CPE even in nonpathogenic bacteria in the nosocomial environment

Finite temperature effects on the structural stability of Si-doped HfO2_{2} using first-principles calculations

The structural stabilities of the monoclinic and tetragonal phases of Si-doped HfO$_{2}$ at finite temperatures were analyzed using a computational scheme to assess the effects of impurity doping. The finite temperature effects considered in this work represented lattice vibration and impurity configuration effects. The results show that 6% Si doping stabilizes the tetragonal phase at room temperature, although a higher concentration of Si is required to stabilize the tetragonal phase at zero temperature. These data indicate that lattice vibration and impurity configuration effects are important factors determining structural stability at finite temperatures.Comment: 5 pages, 3 figure

DIP/WISH deficiency enhances synaptic function and performance in the Barnes maze

<p>Abstract</p> <p>Background</p> <p>DIP (diaphanous interacting protein)/WISH (WASP interacting SH3 protein) is a protein involved in cytoskeletal signaling which regulates actin cytoskeleton dynamics and/or microtubules mainly through the activity of Rho-related proteins. Although it is well established that: 1) spine-head volumes change dynamically and reflect the strength of the synapse accompanying long-term functional plasticity of glutamatergic synaptic transmission and 2) actin organization is critically involved in spine formation, the involvement of DIP/WISH in these processes is unknown.</p> <p>Results</p> <p>We found that DIP/WISH-deficient hippocampal CA1 neurons exhibit enhanced long-term potentiation via modulation of both pre- and post-synaptic events. Consistent with these electrophysiological findings, DIP/WISH-deficient mice, particularly at a relatively young age, found the escape hole more rapidly in the Barnes maze test.</p> <p>Conclusions</p> <p>We conclude that DIP/WISH deletion improves performance in the Barnes maze test in mice probably through increased hippocampal long-term potentiation.</p

Complete Genome Sequence and Characterization of Linezolid-Resistant Enterococcus faecalis Clinical Isolate KUB3006 Carrying a cfr(B)-Transposon on Its Chromosome and optrA-Plasmid

Linezolid (LZD) has become one of the most important antimicrobial agents for infections caused by gram-positive bacteria, including those caused by Enterococcus species. LZD-resistant (LR) genetic features include mutations in 23S rRNA/ribosomal proteins, a plasmid-borne 23S rRNA methyltransferase gene cfr, and ribosomal protection genes (optrA and poxtA). Recently, a cfr gene variant, cfr(B), was identified in a Tn6218-like transposon (Tn) in a Clostridioides difficile isolate. Here, we isolated an LR Enterococcus faecalis clinical isolate, KUB3006, from a urine specimen of a patient with urinary tract infection during hospitalization in 2017. Comparative and whole-genome analyses were performed to characterize the genetic features and overall antimicrobial resistance genes in E. faecalis isolate KUB3006. Complete genome sequencing of KUB3006 revealed that it carried cfr(B) on a chromosomal Tn6218-like element. Surprisingly, this Tn6218-like element was almost (99%) identical to that of C. difficile Ox3196, which was isolated from a human in the UK in 2012, and to that of Enterococcus faecium 5_Efcm_HA-NL, which was isolated from a human in the Netherlands in 2012. An additional oxazolidinone and phenicol resistance gene, optrA, was also identified on a plasmid. KUB3006 is sequence type (ST) 729, suggesting that it is a minor ST that has not been reported previously and is unlikely to be a high-risk E. faecalis lineage. In summary, LR E. faecalis KUB3006 possesses a notable Tn6218-like-borne cfr(B) and a plasmid-borne optrA. This finding raises further concerns regarding the potential declining effectiveness of LZD treatment in the future

Psychiatric intervention and repeated admission to emergency centres due to drug overdose

Self-harm, with or without suicidal intent, substantially increases the risk of future suicide and is known to be the strongest predictor of completed suicide. Furthermore, repetition of self-harm is common: 16% of patients who self-harmed were found to repeat a similar episode within 1 year. Repetition of self-harm increases the risk of completed suicide. One study found overdose to be the most prevalent type of suicide attempt that required admission, and approximately 80% of self-harm episodes have been reported to involve overdose. It is therefore necessary to prevent the repetition of self-harm by drug overdose. According to clinical guidelines on the management of self-harm published in 2004, it is recommended that every patient presenting to hospital with self-harm should undergo a psychosocial assessment by specialists before being discharged. Despite this recommendation, some studies have found that many patients, especially those with repeated self-harm did not actually receive such assessments. That would suggest that the guideline has not been widely used – possibly because it was not based on firm evidence. There is a lack of data on the influence of psychosocial assessments on preventing repetition of self-harm. Some studies have suggested that such assessments do have an influence, but they were based on a small sample size or on a small number of highly advanced institutions. The present study focused on patients with drug overdose who were admitted to emergency centres. Using a national in-patient database in Japan, it aimed to investigate whether psychiatric intervention before discharge was associated with reduced patient readmissions with drug overdose.UTokyo Research掲載「過量服薬による入院患者と精神科医による診察の関係」 URI: http://www.u-tokyo.ac.jp/ja/utokyo-research/research-news/psychiatric-intervention-and-repeated-emergency-admission-due-to-drug-overdose.htmlUTokyo Research "Psychiatric intervention and repeated emergency admission due to drug overdose" URI: http://www.u-tokyo.ac.jp/en/utokyo-research/research-news/psychiatric-intervention-and-repeated-emergency-admission-due-to-drug-overdose.htm