Pediatric urolithiasis is often associated with a metabolic disease or with a complication of steroid or antiepileptic agent use. Children who are on long-term bed rest or bedridden are also said to ...be at risk for urinary stone formation. Here we report two cases of compromised completely bedridden children with renal stones who achieved stone-free status without any complications through detailed intraoperative management. The patient in case 1 is an 8-year-old compromised bedridden boy with epilepsy, chromosomal abnormalities, and ulcerative colitis. In case 2, the patient is a 9-year-old compromised bedridden girl with hypoxic-ischemic encephalopathy and epilepsy. Both children had recurrent urinary tract infections (UTIs), and lithotripsy was planned for multiple renal stones. The patients were expected to be at high risk of developing a postoperative febrile UTI because they are compromised completely bedridden children. A 9.5/11.5-Fr ureteral access sheath was inserted, and lithotripsy was performed. The irrigation flow rate during lithotripsy was frequently adjusted and aspiration of intrarenal saline as necessary so as not to increase intrarenal pressure, with the aim of preventing postoperative febrile UTI. Stone-free status was achieved in both cases, without any intra and postoperative complications.
•Long-term bed rest or Bedridden children are at high risk of urinary stone formation.•Bedridden children are high risk of developing febrile urinary tract infections.•Adjustment of irrigation flow rate is essential during retrograde intrarenal lithotripsy.
Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic disease characterized by suprapubic pain and lower urinary tract symptoms. Perhaps because of the heterogeneous nature of this ...disease and its multifactorial etiology, clinical trials in allinclusive populations of IC/BPS patients without phenotyping in the last decade have mainly failed to discover new therapeutic modalities of IC/BPS. Thus, phenotyping IC/BPS, aimed at identifying bladder-centric and/or bladder-beyond pathologies, including cystoscopic observation of Hunner or non-Hunner lesions of the bladder mucosa, is particularly important for the future of IC/BPS management. Based on recent discussions at international conferences, including the International Consultation on IC, Japan, it has been proposed that Hunner-lesion IC should be separated from other non-Hunner IC/BPS because of its distinct inflammatory profiles and epithelial denudation compared with non-Hunner IC/BPS. However, there are still no standard criteria for the diagnosis of Hunner lesions other than typical lesions, while conventional cystoscopic observations may miss atypical or small Hunner lesions. Furthermore, diagnosis of the bladder-centric phenotype of IC/BPS requires confirmation that identified mucosal lesions are truly a cause of bladder pain in IC/BPS patients. This review article discusses the current status of IC/BPS pathophysiology and diagnosis, as well as future directions of the proper diagnosis of bladder-centric IC/BPS, in which pathophysiological mechanisms other than those in inflammatory pathways, such as angiogenic and immunogenic abnormalities, could also be involved in both Hunner-lesion IC and non-Hunner IC/BPS. It is hoped that this new paradigm in the pathophysiological evaluation and diagnosis of IC/BPS could lead to pathology-based phenotyping and new treatments for this heterogeneous disease.
Roller chains are commonly used to transmit mechanical power in many kinds of machineries for wide industrial fields. Roller chain manufactures are doing a lot of efforts to improve the wear ...resistance through conventional real chain type wear testing with huge amount of time and cost. In this study, a new wear testing machine is developed to evaluate wear amounts more efficiently without using main chain components such as inner plate, outer plate and roller. The results show that the nearly same amounts of wear rate and wear status can be obtained between the newly developed wear testing machine and the conventional machine. It may be concluded that the newly developed wear testing has sufficient reproducibility and can be used more conveniently for investing roller chains compared to the conventional wear testing machine.
Multidrug resistance, especially carbapenem resistance in
Acinetobacter
bacteria is a global healthcare concern. However, available data on the phenotypic and genotypic characteristics of
...Acinetobacter
isolates from West Africa, including Ghana is scanty. Our aim was to investigate the antibiotic resistance profile and genotypic characteristics of
Acinetobacter
isolates from Ghana and to characterize carbapenemase producers using whole-genome sequencing (WGS). A total of 36
Acinetobacter
isolates collected at three hospitals in Ghana between 2016 and 2017 were analyzed. MICs were determined by commercial antibiotic plates.
Acinetobacter baumannii
MLST was determined using the Pasteur scheme. WGS of OXA-carbapenemase producers was performed using short- and long-read sequencing strategies. The resistance rate was highest for trimethoprim/sulfamethoxazole (
n
= 22; 61%). Six (16.7%) and eight (22.2%) isolates were resistant to ceftazidime and colistin, respectively. Two (5.6%) isolates were resistant and one (2.8%) isolate had intermediate sensitivity to three carbapenems. Fifteen STs were identified in 24
A. baumannii
isolates including six new STs (ST1467 ∼ ST1472). ST78 was the predominant (
n
= 6) followed by ST1469 (
n
= 3). Four carbapenemase-producing
A. baumannii
isolates also were identified. Isogenic ST103 isolates Ab-B004d-c and Ab-D10a-a harbored
bla
OXA–
23
within Tn
2007
on identical plasmids, pAb-B004d-c_3, and pAb-D10a-a_3. ST1472 isolate Ab-C102 and ST107 isolate Ab-C63 carried
bla
OXA–
58
and
bla
OXA–
420
, a rare
bla
OXA–
58
variant, respectively, within novel genetic contexts. Our results show that
A. baumannii
isolates of diverse and unique genotypes, including OXA-carbapenemase producers, are circulating in Ghana highlighting the need for a wider surveillance of antimicrobial resistance.
Background
Helicobacter cinaedi is an important pathogen that causes bloodstream infections. Owing to the challenges in its culture and identification, its clinical and bacterial characteristics ...remain unknown. Our study aimed to investigate the molecular epidemiology and antimicrobial susceptibility of H cinaedi.
Materials and Methods
From 2003 to 2016, we analyzed 16 non‐repetitive H cinaedi strains, isolated from blood, at the medical hospital of Tokyo Medical and Dental University. Multilocus sequence typing was performed to analyze the genetic relationship across the different isolates. The minimum inhibitory concentrations (MIC) of antibiotics were determined by the agar dilution method.
Results
The median age of subjects in this study was 61 years (range, 18‐84 years). The most common risk factors included the use of steroids (75.0%) and immunosuppressant drugs (37.5%). In addition, the most common symptoms of H cinaedi bacteremia included colitis (37.5%) and cellulitis (31.3%). The infection recurred in three of seven cases (42.8%) that underwent antibiotic therapy for <10 days. The strains were classified into five sequence types (ST), of which, ST 10 (43.8%) and ST 4 (31.3%) were predominant. The MIC90 values of amoxicillin, gentamycin, imipenem, ciprofloxacin, and clarithromycin were 4, 0.5, 0.25, 64, and 128 mg/L, respectively.
Conclusions
Since there is no recommended guideline yet for the choice or duration of antibiotic therapy and antimicrobial break points, our results suggested, for the first time, that prolonged antibiotic therapy, except with ciprofloxacin and clarithromycin, would be required to ensure resolution of symptoms and prevention of recurrence.
Age‐dependent changes of the mandible bone in female F344/N rats, aged 22–1196 days, were analyzed using physiological bone properties and morphology. Bone weight, bone area, bone mineral components, ...and bone mineral density were assessed using dual‐energy X‐ray absorptiometry. The bone weight, bone area, bone mineral components, and bone mineral density increased rapidly until approximately 150 days of age, increased gradually thereafter, and then stabilized or decreased after 910 days of age. The ratio of bone mineral components to bone weight (bone mineral ratio) increased rapidly until approximately 43 days of age and stabilized thereafter. Size of the mandible, which was measured at 13 points on mandible surface, increased with age, and the rate of change showed a similar pattern to the other parameters. From a principal component analysis on morphometric measurements, principal component 1 (size factor) increased proportionally with age, whereas principal component 2 (shape factor) decreased until approximately 88 days of age and then increased after 365 days of age. As a result, the scatter plots for principal component 1 and principal component 2 were V‐shaped, which indicates that the mandible developed in size, with deformation at younger ages, and recovered its original shape later in life. Our results revealed the occurrence of inflection points at approximately 43, 88, 150, 365, and 910 days of age. Some of these ages corresponded to transition points revealed by the age‐dependent changes of the occlusal mandibular condyle and tooth wear in the same rat.
Roseomonas, a genus of pink-pigmented glucose non-fermentative bacteria, has been associated with various primary and hospital-acquired human infections; however, to our knowledge, its nosocomial ...transmission has never been reported. Clinical and epidemiological investigations were carried out after two cases of R. mucosa bacteremia occurred in our hospital in 2018. Environmental samples were taken of environmental surfaces prone to water contamination in the wards and cultured. The two clinical isolates and all environmental isolates that showed growth of pink colonies were identified using matrix-assisted laser desorption/ionization time of flight mass spectrometry and 16S rRNA gene sequencing. Pulse-field gel electrophoresis (PFGE) was performed and fingerprinting software was used to analyze the DNA restriction patterns and determine their similarity. Two patients who developed R. mucosa bacteremia had received care from the same treatment team. Of 126 environmental samples, five showed growth of R. mucosa. Using 80% similarity as the cut-off, PFGE analysis revealed that the isolates from the two patients’ blood cultures and three environmental isolates belonged to the same clone. The hospital water environment was contaminated with the same clone of R. mucosa that caused bacteremia in the two patients, suggesting nosocomial transmission linked to contaminated environment. Increased vigilance is needed to monitor the emergence of Roseomonas in healthcare settings.
The temperature distribution at depth is a key variable when assessing the potential of a supercritical geothermal resource as well as a conventional geothermal resource. Data-driven estimation by a ...machine-learning approach is a promising way to estimate temperature distributions at depth in geothermal fields. In this study, we developed two methodologies—one based on Bayesian estimation and the other on neural networks—to estimate temperature distributions in geothermal fields. These methodologies can be used to supplement existing temperature logs, by estimating temperature distributions in unexplored regions of the subsurface, based on electrical resistivity data, observed geological/mineralogical boundaries, and microseismic observations. We evaluated the accuracy and characteristics of these methodologies using a numerical model of the Kakkonda geothermal field, Japan, where a temperature above 500 °C was observed below a depth of about 3.7 km. When using geological and geophysical knowledge as prior information for the machine learning methods, the results demonstrate that the approaches can provide subsurface temperature estimates that are consistent with the temperature distribution given by the numerical model. Using a numerical model as a benchmark helps to understand the characteristics of the machine learning approaches and may help to identify ways of improving these methods.
Overcoming cisplatin (CDDP) resistance is a major issue in urothelial cancer (UC), in which CDDP‐based chemotherapy is the first‐line treatment. WEE1, a G2/M checkpoint kinase, confers ...chemoresistance in response to genotoxic agents. However, the efficacy of WEE1 blockade in UC has not been reported. MK‐1775, a WEE1 inhibitor also known as AZD‐1775, blocked proliferation of UC cell lines in a dose‐dependent manner irrespective of TP53 status. MK‐1775 synergized with CDDP to block proliferation, inducing apoptosis and mitotic catastrophe in TP53‐mutant UC cells but not in TP53‐WT cells. Knocking down TP53 in TP53‐WT cells induced synergism of MK‐1775 and CDDP. In UMUC3 cell xenografts and two patient‐derived xenograft lines with MDM2 overexpression, in which the p53/cell cycle pathway was inactivated, AZD‐1775 combined with CDDP suppressed tumor growth inducing both M‐phase entry and apoptosis, whereas AZD‐1775 alone was as effective as the combination in RT4 cell xenografts. Drug susceptibility assay using an ex vivo cancer tissue‐originated spheroid system showed correlations with the in vivo efficacy of AZD‐1775 alone or combined with CDDP. We determined the feasibility of the drug susceptibility assay using spheroids established from UC surgical specimens obtained by transurethral resection. In conclusion, WEE1 is a promising therapeutic target in the treatment of UC, and a highly specific small molecule inhibitor is currently in early phase clinical trials for cancer. Differential antitumor efficacy of WEE1 blockade alone or combined with CDDP could exist according to p53/cell cycle pathway activity, which might be predictable using an ex vivo 3D primary culture system.
WEE1 inhibitor and cisplatin (CDDP) in combination was significantly more effective than the single treatments. Drug susceptibility assay using an ex vivo cancer tissue‐originated spheroid system showed correlations with the in vivo efficacy of AZD‐1775 alone or combined with CDDP.
BackgroundClear cell renal cell carcinoma (ccRCC) displays heterogeneity in appearance—a distinctive pale clear to eosinophilic cytoplasm; however, little is known about the underlying mechanisms and ...clinical implications. We investigated the role of these eosinophilic features in ccRCC on oncological outcomes and response to tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs).MethodsOne-hundred and thirty-eight ccRCC cases undergoing radical surgery (cohort 1) and 54 metastatic ccRCC cases receiving either TKIs or ICIs (cohort 2) were included. After histological evaluation, all cases were divided into three phenotypes based on the eosinophilic features at the highest-grade area: clear, mixed, or eosinophilic type. Gene expression and immunohistochemical analyses were performed to explore the potential mechanisms of these phenotypes in cohort 1. Further, the association of the three phenotypes with the best objective response to TKI or ICI, clinical benefit (complete/partial response or stable disease), and overall survival (OS) was assessed in cohort 2.ResultsThe clear type was significantly associated with increased hypoxia as well as angiogenesis gene signatures compared with the eosinophilic type. Gene signatures and protein expression related to effector T cell and immune checkpoint molecules were elevated to a greater extent in the eosinophilic type, followed by the mixed and clear types. The mixed and eosinophilic types exhibited greater PBRM1-negativity and increased prevalence of the epithelial-mesenchymal transition gene signature than the clear type. In the mixed/eosinophilic types of cohort 2, significant clinical benefit was observed in the ICI therapy group versus the TKI therapy group (p=0.035), and TKI therapy vs ICI therapy was an independent factor for worse prognosis of OS (HR 3.236; p=0.012).ConclusionThe histological phenotype based on the eosinophilic features, which are linked to major immunological mechanisms of ccRCC, was significantly correlated with therapeutic efficacy.
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