Relationship of Metabolic Dysfunction-Associated Steatohepatitis-Related Hepatocellular Carcinoma with Oral and Intestinal Microbiota: A Cross-Sectional Pilot Study.

Background and Objectives: The incidence of metabolic dysfunction-associated steatohepatitis (MASH)-related hepatocellular carcinoma (HCC) is increasing worldwide, alongside the epidemic of obesity and metabolic syndrome. Based on preliminary reports regarding the potential association of HCC and periodontitis, this study aimed to analyze the involvement of periodontal bacteria as well as the oral and intestinal bacterial flora in MASH-related HCC (MASH-HCC). Materials and Methods: Forty-one patients with MASH and nineteen with MASH-HCC participated in the study, completing survey questionnaires, undergoing periodontal examinations, and providing samples of saliva, mouth-rinsed water, feces, and peripheral blood. The oral and fecal microbiome profiles were analyzed by 16S ribosomal RNA sequencing. Bayesian network analysis was used to analyze the causation between various factors, including MASH-HCC, examinations, and bacteria. Results: The genus Fusobacterium had a significantly higher occupancy rate (p = 0.002) in the intestinal microflora of the MASH-HCC group compared to the MASH group. However, Butyricicoccus (p = 0.022) and Roseburia (p < 0.05) had significantly lower occupancy rates. The Bayesian network analysis revealed the absence of periodontal pathogenic bacteria and enteric bacteria affecting HCC. However, HCC directly affected the periodontal bacterial species Porphyromonas gingivalis, Tannerella forsythia, Fusobacterium nucleatum, and Prevotella intermedia in the saliva, as well as the genera Lactobacillus, Roseburia, Fusobacterium, Prevotella, Clostridium, Ruminococcus, Trabulsiella, and SMB53 in the intestine. Furthermore, P. gingivalis in the oral cavity directly affected the genera Lactobacillus and Streptococcus in the intestine. Conclusions: MASH-HCC directly affects periodontal pathogenic and intestinal bacteria, and P. gingivalis may affect the intestinal bacteria associated with gastrointestinal cancer.

Effectiveness of an interdisciplinary home care approach for older adults with chronic conditions: A systematic review and meta-analysis.

The effectiveness of interdisciplinary home healthcare service consisting of at least two or more healthcare providers, such as a nurse, physician and physiotherapist, for community-dwelling older adults remains unclear. This systematic review assesses the effects of interdisciplinary home care on quality of life (QOL) and health outcomes in older adults with chronic conditions using validated tools. Databases were searched using CINAHL Plus with Full Text, PubMed, EMBASE, CENTRAL, PsycINFO, and OpenGrey from inception to January 25, 2021. Eligibility criteria included (i) an interdisciplinary home care approach, (ii) participants aged 65 years and older with chronic conditions, (iii) randomized controlled trials (RCTs), and (iv) original literature in English. The study reviewer's dyad independently screened the literature and assessed the study quality using the Cochrane's Risk of Bias 2 tool. The analysis employed qualitative and quantitative integration and Grading of Recommendations Assessment, Development, and Evaluation. This study included 13 RCTs with 4709 participants. Four RCTs indicated that interdisciplinary home healthcare services reduced hospital admissions during the initial 6 months after the start of home care interventions (risk ratio [RR] = 0.73; 95% confidence interval [CI] = 0.61-0.88; p < 0.001; I2 = 0%). However, evidence certainty was moderate; QOL and mortality showed low certainty; and institutionalization and adherence showed moderate certainty of evidence. This study suggests that the interdisciplinary home care approach reduces hospital admissions but lacks effects on other outcomes. More robust studies are required to evaluate this evidence. Geriatr Gerontol Int 2024; ••: ••-••.

Body Fat Distribution and Left Atrial Reverse Remodeling After Catheter Ablation for Atrial Fibrillation.

Background: Emerging evidence suggests a pathophysiological link between obesity and atrial fibrillation (AF). However, the contribution of body fat distribution to left atrial (LA) remodeling and its reversibility remain unclear in nonobese AF patients. Objectives: The purpose of this study was to investigate the association of body fat distribution with LA size and reverse remodeling (LARR). Methods: In total, 116 nonobese patients with AF (88 men, age 63 ± 11 years) who underwent first catheter ablation (CA) were included. Body fat distribution was assessed with bioelectrical impedance, and body fat percentage (BF%) and central fat percentage (CF%) were calculated. Patients were categorized by body size metrics (body mass index [BMI] and waist-to-hip [W/H] ratio) and fat parameters (BF% and CF%). Echocardiography was performed before and 6 months after CA. Multivariable logistic regression was used to examine the association between the 4 metrics (ie, BMI, W/H ratio, BF%, and CF%) and a lack of LARR (<15% reduction or increase in the LA volume index). Results: Body size metrics and adiposity measures were not independently associated with baseline LA size. Six months after CA, the higher W/H ratio and CF% groups exhibited persistent LA enlargement compared to their counterparts (both P < 0.01). In the multivariable analysis, W/H ratio and CF% were associated with a lack of LARR (adjusted ORs of 3.86 and 2.81 per 0.10 and 10% increase, respectively, both P < 0.01). The combined assessment of CF% with W/H ratio provided complementary risk stratification for persistent LA enlargement. Conclusions: Central adiposity was associated with a lack of LARR after CA, highlighting the importance of assessing body fat distribution even in nonobese patients.

Japanese nurses' confidence in their understanding of telenursing via e-learning: A mixed-methods study.

Objective: Telenursing e-learning courses have been shown to enhance nurses' skills and knowledge; however, the subjective learning experience is unclear. In this study, we identified meta-inferences to quantitatively and qualitatively understand this experience, as well as the types of knowledge gained through an e-learning course and how they are linked to each other, in order to enhance nurses' confidence in their understanding of telenursing. Methods: We employed a single-arm intervention with a mixed-methods convergent parallel design. We converged participants' self-reported pre- and post-course confidence scores with their reflections on the learning experience, which were reported qualitatively as improved or unimproved. A total of 143 Japanese nurses with a mean of 20 years of nursing experience participated in this study. Results: Among the participants, 72.7% demonstrated improved confidence in their understanding of telenursing after completing the e-learning course. The baseline confidence score was originally higher in the group that reported unimproved confidence (p < .001). Although there was no statistical difference in the usability and practicality scores between the two groups, the qualitative learning experience in these aspects differed in terms of the depth of knowledge of telenursing obtained. Conclusions: Nurses' quantitative confidence in their understanding of telenursing after course completion was incongruent with their qualitative perspectives of the learning experience. Nursing educators, healthcare policymakers, and other stakeholders should consider that learners' overconfidence in their understanding of telenursing and comprehension of e-learning materials may result in their failure to develop key telenursing competencies, skills, and knowledge.

Identification of citrullinated α1-antitrypsin (A1AT) in saliva in a mouse model of rheumatoid arthritis.

OBJECTIVES: Rheumatoid arthritis (RA) is an autoimmune disease characterized by progressive joint destruction. Early diagnosis and treatment, before joint deformation or destruction occurs, are crucial. Identifying novel biomarkers for RA in saliva could potentially enable early detection of the disease, prior to its onset. METHODS: We conducted a comprehensive proteomic analysis of salivary proteins in a mouse model of RA. Proteins were identified using western blotting and enzyme-linked immunosorbent assay in the serum, saliva, and ankle joints of DBA/1JJmsSlc mice, a model of RA. Ankle joints and submandibular glands were stained with hematoxylin and eosin and immunostained, and the results were compared with those of control mice. RESULTS: Citrullinated alpha-1 antitrypsin (A1AT, 46 kDa) was commonly detected in the saliva, serum, and ankle joints of mice with severe RA and was confirmed through proteomic analysis. Western blotting showed a band corresponding to 46 kDa in the serum, saliva, and ankle joints. Immunostaining of the ankle joints with the A1AT antibody showed a strong positive signal in the synovium. CONCLUSIONS: In DBA/1JJmsSlc mice, cyclic citrullinated peptide antibodies and A1AT may be involved in citrullination and contribute to the development and severity of RA, making them valuable treatment targets requiring further study.

Electromagnetic enhancement spectra of one-dimensional plasmonic hotspots along silver nanowire dimer derived via surface-enhanced fluorescence.

We developed a spectroscopic method for directly obtaining the spectra of electromagnetic (EM) enhancement of plasmonic hotspots (HSs). The method was applied to one-dimensional (1D) HSs generated between silver nanowire (NW) dimers. The EM enhancement spectra were derived by dividing the spectra of surface-enhanced fluorescence (SEF) from single NW dimers with SEF obtained from large nanoparticle aggregates, where aggregate-by-aggregate variations in the SEF spectra were averaged out. Some NW dimers were found to exhibit EM enhancement spectra that deviated from the plasmon resonance Rayleigh scattering spectra, indicating that their EM enhancement was not generated by superradiant plasmons. These experimental results were examined by numerical calculation based on the EM mechanism by varying the morphology of NW dimers. The calculations reproduced the spectral deviations as the NW diameter dependence of EM enhancement. Phase analysis of the enhanced EM near-fields along the 1D HSs revealed that the dipole-quadrupole coupled plasmon, which is a subradiant mode, mainly generates EM enhancement for dimers with NW diameters larger than ∼80 nm, which was consistent with scanning electron microscopic measurements.

Association of Atrial Fibrillation Progression With Left Atrial Functional Reserve and Its Reversibility.

BACKGROUND: Atrial fibrillation (AF) progression is closely related to heart failure occurrence, and catheter ablation carries a beneficial effect for heart failure prevention. Recently, particular attention has been given to left atrial (LA) function and functional reserve in the pathogenesis linking AF and heart failure, although its significance and reversibility is not well studied. METHODS AND RESULTS: We prospectively investigated 164 patients with AF with normal left ventricular systolic function and free from heart failure who underwent first catheter ablation and pre-/postprocedural echocardiography. Conventional and speckle-tracking echocardiography were performed at rest and during passive leg lifting to assess LA size, LA reservoir strain (LARS), and functional reserve calculated as passive leg lifting-LARS - rest-LARS. Patients were categorized into 3 AF subtypes: paroxysmal AF (N=95), persistent AF (PeAF; N=50), and long-standing persistent AF (LS-PeAF; N=19). The PeAF and LS-PeAF groups had larger LA size and reduced LARS compared with the paroxysmal AF group (all P<0.05). LA functional reserve was significantly impaired in the LS-PeAF group (P=0.003). In multivariable analysis, LS-PeAF and advanced age were significantly associated with impaired LA functional reserve. Among 149 patients with sinus rhythm 1 to 2 days after catheter ablation, LARS was significantly improved in both PeAF and LS-PeAF groups but was still lower than that in the paroxysmal AF group. Sinus rhythm restoration also led to amelioration of LA functional reserve in patients with LS-PeAF. CONCLUSIONS: AF progression was related to impaired LARS and LA functional reserve, and restoration of sinus rhythm might contribute to early LA reverse remodeling.

Prevalence, Associated Factors, and Echocardiographic Estimation of Left Atrial Hypertension in Patients With Atrial Fibrillation.

Background Elevated left atrial (LA) pressure predisposes individuals to the initiation and persistence of atrial fibrillation (AF), and LA hypertension is associated with AF recurrence after catheter ablation (CA). However, the exact frequency and factors associated with LA hypertension are unknown, and its noninvasive estimation is challenging. This study aimed to investigate the prevalence and determinants of LA hypertension in patients with AF who underwent first CA. Methods and Results We examined 183 patients with AF who underwent conventional and speckle-tracking echocardiography before CA to assess LA size, reservoir strain, and stiffness. Direct LA pressure was measured at the time of CA, and LA hypertension was defined as mean LA pressure >15 mm Hg. Thirty-three (18.0%) patients exhibited LA hypertension. Patients with LA hypertension had a significantly larger LA volume index (40.2 [28.4-52.1] versus 34.1 [26.9-42.4] mL/m2, P=0.025), reduced LA reservoir strain (15.1 [10.4-21.7] versus 22.7 [14.4-32.3] %, P=0.002) and increased LA stiffness (0.69 [0.34-0.99] versus 0.36 [0.24-0.54], P<0.001). Multivariable analyses showed that waist circumference, C-reactive protein level, LA reservoir strain, and LA stiffness were independently associated with LA hypertension (all P<0.05), while LA volume and E/e' ratio were not. Among echocardiographic parameters, receiver operating characteristic curve analysis identified LA stiffness as the best predictor of LA hypertension. Conclusions Approximately 20% of patients with AF who underwent CA had LA hypertension. Central obesity and inflammation might be involved in the pathophysiological mechanisms of LA hypertension, and echocardiography-derived LA stiffness may have clinical utility for the detection of LA hypertension before CA.

Demonstration of electromagnetic enhancement correlated to optical absorption of single plasmonic system coupled with molecular excitons using ultrafast surface-enhanced fluorescence.

The relationship between the electromagnetic (EM) enhancement of the optical responses of molecules and plasmon resonance has been investigated using Rayleigh scattering or the extinction spectra of plasmonic systems coupled with molecular excitons. However, quantum optics predicts that the EM enhancement of such optical responses, e.g., fluorescence, Raman, and their nonlinear counterparts, is related directly to optical absorption and indirectly to Rayleigh scattering and extinction. To demonstrate this prediction, a micro-spectroscopic method for obtaining Rayleigh scattering, extinction, absorption, and EM enhancement is developed using single-coupled plasmonic systems composed of silver nanoparticle dimers and dye molecules. The EM enhancement is derived from ultrafast surface-enhanced fluorescence. An evaluation of the spectral relationships demonstrates that the EM enhancement can be reproduced better by absorption than by Rayleigh scattering or extinction. This reproduction is phenomenologically confirmed by numerical calculations based on classical electromagnetism, indicating the importance of absorption spectroscopy in coupled plasmonic systems for evaluating EM enhancement.

The Relationship between Changes in Serum Element Concentrations and Pathological Condition and Disease Status in Japanese Multiple Myeloma Patients: A Pilot Study and Literature Review.

BACKGROUND: Multiple myeloma (MM) is a rare cancer, and information on its pathological condition and serum element levels is lacking. In this pilot study, we examined serum element concentrations in Japanese patients with MM by a comprehensive multi-element analysis. METHODS: This is a case-control study of 12 Japanese patients diagnosed with MM at the Nagoya City University Hospital between 2008 and 2013. Blood samples were taken, at the initial diagnosis and at relapse. The serum concentrations of 12 elements were analyzed by inductively coupled plasma mass spectrometry and compared between MM patients and non-MM volunteers. We also analyzed the correlation between serum element concentrations and laboratory values related to disease status and tumor volume of MM. RESULTS: We found that serum chromium (Cr), copper (Cu), molybdenum (Mo), and barium (Ba) concentrations were significantly increased in MM patients. Ba was significantly increased in MM patients, suggesting an association with bone lesions. There was no consistent trend between these elements and existing indices related to MM tumor volume and disease status. CONCLUSIONS: Although this is a pilot study, serum Cr, Cu, Mo, and Ba concentrations were found to be significantly elevated in MM patients. Further studies with large sample sizes are needed, since the changes in serum concentrations of these elements may reflect the pathological condition of MM.

Correlated Polarization Dependences between Surface-Enhanced Resonant Raman Scattering and Plasmon Resonance Elastic Scattering Showing Spectral Uncorrelation to Each Other.

We investigated the origin of the identical polarization angle dependence between surface-enhanced resonant Raman scattering (SERRS) and plasmon resonance elastic scattering (PRES) for two types of single silver nanoparticle aggregates. The first type (Type I), in which the SERRS spectral envelopes are similar to the PRES spectra, shows the identical polarization dependence between the SERRS and PRES. The second type (Type II), in which the SERRS envelopes largely deviate from the PRES spectra, also exhibits identical polarization dependence. Scanning electron microscopy observations indicated that the aggregates were dimers. This unintuitive result was examined by calculating the electromagnetic enhancement by changing the morphology of the dimers. The calculations revealed that the Type I dimer generates SERRS directly by superradiant plasmons. The Type II dimer generates SERRS indirectly via subradiant plasmons, which receive light energy from superradiant plasmons. This indirect SERRS process clarifies that the interaction between the superradiant and subradiant plasmons results in an identical polarization dependence between SERRS and PRES for Type II dimers.

Prevalence of glucose metabolism disorders and its association with left atrial remodelling before and after catheter ablation in patients with atrial fibrillation.

AIMS: To investigate the exact prevalence of glucose metabolism disorders, and their impact on left atrial (LA) remodelling and reversibility in patients with atrial fibrillation (AF). METHODS AND RESULTS: We examined 204 consecutive patients with AF who underwent their first catheter ablation (CA). Oral glucose tolerance test was used to evaluate glucose metabolism disorders in 157 patients without known diabetes mellitus (DM). Echocardiography was performed before and 6 months after CA. Oral glucose tolerance test identified abnormal glucose metabolism in 86 patients [11 with newly diagnosed DM, 74 with impaired glucose tolerance (IGT) and 1 with impaired fasting glucose (IFG)]. Ultimately, 65.2% of patients had abnormal glucose metabolism. Diabetes mellitus group had the worst LA reservoir strain and LA stiffness (both P < 0.05), while there was no significant difference in baseline LA parameters between normal glucose tolerance (NGT) group and IGT/IFG group. The prevalence of LA reverse remodelling (≥15% decrease in the LA volume index at 6 months after CA) was significantly higher in NGT group compared with IGT/IFG and DM group (64.1 vs. 38.6 vs. 41.5%, P = 0.006). Both DM and IFG/IGT carry a significant risk of lack of LA reverse remodelling independent of baseline LA size and AF recurrence. CONCLUSION: Approximately 65% of patients with AF who underwent their first CA had abnormal glucose metabolism. Patients with DM had significantly impaired LA function compared with non-DM patients. Impaired glucose tolerance/IFG as well as DM carries significant risk of unfavourable LA reverse remodelling. Our observations may provide valuable information regarding the mechanisms and therapeutic strategies of glucose metabolism-related AF.

Clinical significance of skin autofluorescence for diabetic macroangiopathy and comparison with conventional markers of atherosclerosis: a cross-sectional and prospective study.

Background: Skin autofluorescence (SAF) is a marker for the accumulation of advanced glycation end products (AGEs), and is associated with diabetic macroangiopathy. However, whether SAF is superior to conventional markers of atherosclerosis such as carotid intima-media thickness (IMT) and pulse wave velocity (PWV) in detecting macroangiopathy remains unclear. Methods: We recruited 845 patients with type 2 diabetes enrolled in a community diabetes cohort (ViNA cohort) who had SAF, IMT, and PWV measured at baseline. The prevalence of macroangiopathy at baseline and new cardiovascular events during the 2-year follow-up period was investigated. SAF was measured using an AGE reader. Coronary artery calcification (CAC) was measured by computed tomography in 485 patients. Peripheral artery disease (PAD) was defined as the ankle-brachial blood pressure ratio of ≤ 0.9. Results: SAF, IMT, and PWV were significantly correlated with each other, and age, diabetes duration, and estimated glomerular filtration rate were their strong confounders. SAF was associated with baseline stroke and new stroke after adjusting for confounders, but not with coronary artery disease (CAD) or PAD. The nonsignificant relationship between SAF and CAD was consistent with the relationship between SAF and CAC. Multivariate analysis showed a significant association of SAF with baseline and new stroke independent of IMT and PWV. Maximum-IMT was significantly associated with baseline CAD, PAD, and stroke, but not with a new stroke, whereas PWV was associated with a new stroke. Conclusion: Among diabetic macroangiopathies, SAF is a good stroke biomarker, but not for CAD and PAD. Supplementary Information: The online version contains supplementary material available at 10.1007/s13340-022-00608-8.

Effects of Diabetes and Voluntary Exercise on IgA Concentration and Polymeric Immunoglobulin Receptor Expression in the Submandibular Gland of Rats.

Background and Objectives: Patients with diabetes are more susceptible to upper respiratory tract infections (URTIs) because they are easily infected. Salivary IgA (sali-IgA) levels play a major role in transmitting URTIs. Sali-IgA levels are determined by salivary gland IgA production and polymeric immunoglobulin receptor (poly-IgR) expression. However, it is unknown whether salivary gland IgA production and poly-IgR expression are decreased in patients with diabetes. While exercise is reported to increase or decrease the sali-IgA levels, it is unclear how exercise affects the salivary glands of patients with diabetes. This study aimed to determine the effects of diabetes and voluntary exercise on IgA production and poly-IgR expression in the salivary glands of diabetic rats. Materials and Methods: Ten spontaneously diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats (eight-week-old) were divided into two groups of five rats each: a non-exercise group (OLETF-C) and a voluntary wheel-running group (OLETF-E). Five Long-Evans Tokushima Otsuka (LETO) rats without diabetes were bred under the same conditions as the OLETF-C. Sixteen weeks after the study began, the submandibular glands (SGs) were collected and analyzed for IgA and poly-IgR expression levels. Results: IgA concentrations and poly-IgR expression levels in SGs were lower in OLETF-C and OLETF-E than in LETO (p < 0.05). These values did not differ between the OLETF-C and OLETF-E. Conclusions: Diabetes decreases IgA production and poly-IgR expression in the salivary glands of rats. Moreover, voluntary exercise increases sali-IgA levels but does not increase IgA production and poly-IgR expression in the salivary glands of diabetic rats. Increasing IgA production and poly-IgR expression in the salivary glands, which is reduced in diabetes, might require slightly higher-intensity exercise than voluntary exercise under the supervision of a doctor.

Clinical influence of multiplex polymerase chain reaction routine uses in urgent pediatric admissions.

BACKGROUND: The coronavirus disease 2019 outbreak has prompted some hospitals to implement screening tests upon admission since 2020. FilmArray® Respiratory 2.1 Panel (FilmArray) is a multiplex polymerase chain reaction (PCR) test with high sensitivity and specificity for detecting respiratory pathogens. We aimed to assess the clinical influence of the routine use of FilmArray for pediatric patients, including those without symptoms suggestive of an infection. METHODS: We conducted a single-center retrospective observational study, which investigated patients aged ≤15 years who underwent FilmArray on admission in 2021. We collected the patients' epidemiological information, symptoms, and FilmArray results from their electronic health records. RESULTS: A positive result was observed in 58.6% of patients admitted to the general ward or intensive care unit (ICU) but only in 1.5% of patients in the neonatal ward. Among the patients admitted to the general ward or ICU who tested positive, 93.3% had symptoms suggestive of infections, 44.6% had a sick contact before admission, and 70.5% had siblings. However, 62 (28.2%) out of 220 patients without the four (fever, respiratory, gastrointestinal, and dermal) symptoms also had positive results. Among them, 18 patients with adenovirus and three with respiratory syncytial virus were isolated to private rooms. However, 12 (57.1%) patients were discharged without symptoms suggestive of viral infection. CONCLUSION: Multiplex PCR routine use for all inpatients may lead to excessive management of positive cases because FilmArray cannot quantify microorganisms. Thus, targets for testing should be considered carefully based on patients' symptoms and histories of sick contacts.

Toward a New Era of SERS and TERS at the Nanometer Scale: From Fundamentals to Innovative Applications.

Surface-enhanced Raman scattering (SERS) and tip-enhanced Raman scattering (TERS) have opened a variety of exciting research fields. However, although a vast number of applications have been proposed since the two techniques were first reported, none has been applied to real practical use. This calls for an update in the recent fundamental and application studies of SERS and TERS. Thus, the goals and scope of this review are to report new directions and perspectives of SERS and TERS, mainly from the viewpoint of combining their mechanism and application studies. Regarding the recent progress in SERS and TERS, this review discusses four main topics: (1) nanometer to subnanometer plasmonic hotspots for SERS; (2) Ångström resolved TERS; (3) chemical mechanisms, i.e., charge-transfer mechanism of SERS and semiconductor-enhanced Raman scattering; and (4) the creation of a strong bridge between the mechanism studies and applications.

Changes in zinc and manganese concentrations in cisplatin-induced acute kidney injury.

Cisplatin (CDDP) is a widely used anticancer drug, but acute kidney injury (AKI) is one of the most important dose-limiting factors. Trace metal elements are present in various concentrations in the body and play an important role in maintaining normal vital functions. However, the relationship between CDDP-induced AKI and trace metal elements is unknown. In this study, we cultured human renal proximal tubular epithelial cells in the presence of CDDP (0, 12.5, 25, 50 µM) and analyzed the concentration of trace elements in medium after 24 h. We found that CDDP significantly increased the concentrations of zinc (Zn) and manganese (Mn) in medium and significantly decreased them in lysate. Therefore, we examined the effects of CDDP (3 mg/kg, i.p.) administration on serum and urinary Zn and Mn concentrations in rats. The results showed that urinary excretion of Zn and Mn increased in CDDP-treated rats 5 days after administration. Also, 5 days after administration, pyknosis, nuclear loss, loss of the brush border membrane, and DNA fragmentation were observed, and serum creatinine and blood urea nitrogen levels were found to be significantly increased. These data suggested that 24-h excretion of Zn and Mn might reflect on CDDP induced nephropathy. Monitoring urinary Zn and Mn excretion may be beneficial in detecting AKI, but further studies are needed for clinical application.

High preoperative serum strontium levels increase the risk of acute kidney injury after cardiopulmonary bypass.

BACKGROUND: Acute kidney injury (AKI) is a common complication of cardiac surgeries. The incidence of AKI after cardiac surgeries using cardiopulmonary bypass (CPB-AKI) is high, emphasizing the need to determine strategies to prevent CPB-AKI. This study investigates the correlation between CPB-AKI and trace metal levels in clinical and animal studies. METHODS: Samples and clinical data were obtained from 74 patients from the Nagoya City University Hospital and Okazaki City Hospital. Blood samples were collected before, immediately after, and 2 h after CPB withdrawal. Trace metal levels were measured using inductively coupled plasma mass spectrometry. Sr or vehicle treatment was orally administered to the rats to determine if Sr was associated with CPB-AKI. After the treatment, ischemia-reperfusion (IR) injury was induced, and serum creatinine (SCr) and blood urea nitrogen (BUN) levels were measured. RESULTS: In this clinical study, the incidence of CPB-AKI was found to be 28% (21/74). The body mass index and estimated glomerular filtration rate were significantly different in patients with AKI. The intensive care unit and hospital stay were longer in AKI patients than in non-AKI patients. The Na, Fe, and Sr levels were significantly higher in AKI patients before CPB. Also, Fe and Sr were higher immediately after CPB withdrawal, and Sr was higher 2 h after CPB withdrawal in AKI patients. Animal studies showed that Sr-treated rats had significantly increased SCr and BUN levels than vehicle-treated rats at 24 h post-IR injury. CONCLUSIONS: High preoperative serum Sr levels may be associated with CPB-AKI.

In Vitro and In Vivo Pharmacological Profiles of DS-1211, a Novel Potent, Selective, and Orally Bioavailable Tissue-Nonspecific Alkaline Phosphatase Inhibitor.

Inhibition of tissue-nonspecific alkaline phosphatase (TNAP) may prevent ectopic soft tissue calcification by increasing endogenous pyrophosphate (PPi). DS-1211 is a potent and selective novel small molecule TNAP inhibitor with well-characterized pharmacokinetics (PKs) in rodent and monkey. Herein, we report a comprehensive summary of studies establishing the pharmaceutical profile of DS-1211. In vitro studies characterized the mode of inhibition and inhibitory effects of DS-1211 on three human alkaline phosphatase (ALP) isozymes-TNAP, human intestinal ALP, human placental ALP-and on ALP activity across species in mouse, monkey, and human plasma. In vivo PK and pharmacodynamic (PD) effects of a single oral dose of DS-1211 in mice and monkeys were evaluated, including biomarker changes in PPi and pyridoxal 5'-phosphate (PLP). Oral bioavailability (BA) was determined through administration of DS-1211 at a 0.3-mg/kg dose in monkeys. In vitro experiments demonstrated DS-1211 inhibited ALP activity through an uncompetitive mode of action. DS-1211 exhibited TNAP selectivity and potent inhibition of TNAP across species. In vivo studies in mice and monkeys after single oral administration of DS-1211 showed linear PKs, with dose-dependent inhibition of ALP activity and increases in plasma PPi and PLP. Inhibitory effects of DS-1211 were consistent in both mouse and monkey. Mean absolute oral BA was 73.9%. Overall, in vitro and in vivo studies showed DS-1211 is a potent and selective TNAP inhibitor across species. Further in vivo pharmacology studies in ectopic calcification animal models and clinical investigations of DS-1211 in patient populations are warranted. © 2022 Daiichi Sankyo, Inc. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).