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Yang-Da Chen,1 Zhi-Gao Wen,1 Jun-Jie Long,1 Yong Wang2 1Department of Emergency Medicine, Shenzhen Luohu Hospital Group Luohu People’s Hospital (The Third Affiliated Hospital of Shenzhen University), Shenzhen, People’s Republic of China; 2Department of Cardiology, Shenzhen Luohu Hospital Group Luohu People’s Hospital (The Third Affiliated Hospital of Shenzhen University), Shenzhen, People’s Republic of ChinaCorrespondence: Yong Wang, Email drwangyong2016@163.comBackground: Inflammation plays a key role in the pathogenesis of slow coronary flow phenomenon (SCFP). SCFP is a condition that can complicate the management of ischemia and no obstructive coronary arteries (INOCA), making it essential to identify reliable predictors. Although the systemic inflammation response index (SIRI) has been proven to relate to various cardiovascular diseases. However, the predictive value of SIRI for SCFP in patients with INOCA remains unclear.Methods: A total of 1422 patients with INOCA were consecutively included in this study. 89 individuals were diagnosed with SCFP (the SCFP group). A 1:2 age- and -sex-matched patients with INOCA and normal blood flow were selected as the control group (n=178). Plasma neutrophil, monocyte, and lymphocyte counts were collected so as to determine the value of SIRI.Results: Patients with SCFP had an elevated level of body mass index (BMI) and an increased incidence of smoking and diabetes. The SIRI was significantly higher in the SCFP group than in the controls (2.3± 1.3 vs 1.8± 1.3, p=0.002). The SIRI increased as the number of coronary arteries involved in the SCFP increased. Univariate analyses showed that BMI, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and SIRI were associated with SCFP. Multivariate logistic regression analysis revealed that BMI and SIRI were independent predictors of SCFP occurrence. The ROC curve showed that when the SIRI was > 1.140, the sensitivity and specificity were 87.6% and 60.1%, respectively, and the area under the ROC curve (AUC) was 0.644 (95% CI: 0.578– 0.710, P < 0.001).Conclusion: The findings demonstrated that an increased SIRI may have a potential role in distinguishing SCFP in patients with INOCA. SIRI could improve the predictive value of SCFP compared to neutrophils, monocytes, and lymphocytes alone.Keywords: systemic inflammation response index, slow coronary flow phenomenon, ischemia and no obstructive coronary arteries, predictors

Shu-Wen Zang,1 Jun-Jie Long,1 Yong Wang2 1Department of Emergency Medicine, Shenzhen Luohu Hospital Group Luohu People’s Hospital (The Third Affiliated Hospital of Shenzhen University), Shenzhen, People’s Republic of China; 2Department of Cardiology, Shenzhen Luohu Hospital Group Luohu People’s Hospital (The Third Affiliated Hospital of Shenzhen University), Shenzhen, People’s Republic of ChinaCorrespondence: Shu-Wen Zang, Email jzzangshuwen@163.comBackground: Accumulating evidences suggest that low-grade inflammatory response plays a key role in the pathophysiology of coronary slow flow phenomenon (CSFP). As a new hematological inflammatory indicator, the neutrophil percentage to albumin ratio (NPAR) and its role in the occurrence and development of CSFP remains unclear. In this study, we aimed to investigate the predictive value of NPAR in the presence of CSFP in patients with myocardial ischemia and no obstructive coronary arteries (INOCA).Methods: In total, 1323 individuals with INOCA were included in this study. 85 patients developed CSFP were included in the CSFP group. 1:2 age-and sex-matched patients were selected from the absence of CSFP, with normal blood flow, as the control group. Clinical characteristics, laboratory parameters, and angiographic findings were compared between groups. NPAR was also calculated to explore its relationship with CSFP.Results: NPAR was significantly higher in the CSFP patients than in the controls (19.3± 2.5 vs 16.7± 1.8, p< 0.001). The NPAR increased with the number of coronary arteries involved in CSFP. Multivariate logistic regression analysis showed that an elevated NPAR level was an independent predictor of CSFP (OR 1.915, 95% CI 1.612– 2.275, P < 0.001). The ROC curve showed that when NPAR was > 17.39, the sensitivity and specificity were 90.6% and 78.8%, respectively, and the area under the ROC curve (AUC) was 0.860 (95% CI: 0.811– 0.909, P < 0.001). The AUC of neutrophil percentage was 0.845 (95% CI: 0.794– 0.897, p < 0.001), and that of albumin was 0.808 (95% CI: 0.753– 0.864, p < 0.001).Conclusion: Elevated NPAR levels are an independent predictor of CSFP in patients with INOCA. NPAR could improve the predictive value of CSFP compared with neutrophil percentage or albumin ratio alone.Keywords: neutrophil percentage-to-albumin ratio, coronary slow flow phenomenon, myocardial ischemia with no obstructive coronary arteries, predictors

As more attention is placed on designing digital educational games to align with schools' academic aims (e.g., Common Core), questions arise regarding how professional development (PD) may support teachers' using games for instruction and how such integration might impact students' achievement. This study seeks to (a) understand how teachers use PD resources (e.g., technology personnel and game-use workshops) for integration; (b) determine how teachers integrate games into their instruction; and (c) examine how those teaching practices are associated with student achievement. This mixed method study used survey and interview responses from elementary school teachers (n = 863) with access to PD resources for implementing a math game intervention and standardized math-test scores from their second- through sixth-grade students (n = 10,715). Findings showed few teachers sought PD assistance for integration, but many desired such support. Some reported using integrative practices (i.e., referencing game and using game-generated progress reports) to identify struggling students, whereas several found integration challenging. Teachers' reordering of game objectives to align with lessons and viewing of game-based PD videos were associated with increased student math achievement in our OLS-analysis. However, this result was no longer statistically significant within a school fixed-effects model, suggesting school differences may influence how strongly teachers' practices are associated with student achievement.

Regional and global environmental challenges have become increasingly complex and require broader solutions than a single discipline can provide. Although there is a growing need for interdisciplinary research, many graduate education programs still train students within the confines of a particular discipline or specialty. The Ridge 2 Reef research traineeship program at the University of California, Irvine, aimed to provide transferable and interdisciplinary skill training to prepare graduate students from different disciplines to address current and future environmental challenges. The program achieved its goals through a 'culture of improvement' that ensured trainee needs shaped program management and curriculum. Due to trainee feedback and leaders dedicated to program improvement, there was a complete course overhaul during the first two years of the program, resulting in a final curriculum structure that was more effective and aligned with revised program goals. Program evaluations suggest that the flexibility of the program, diversity of training, overhauled courses offered, and partnership-focused opportunities contributed to more confident graduate students who were more broadly trained and better prepared in their chosen environmental career paths. Based on evaluation surveys, graduate students reported significant gains in scientific, technical, and career knowledge as well as transferrable skills in communication, data analysis, leadership, mentoring, and interdisciplinary collaboration. The structure and evolution of the Ridge 2 Reef traineeship can provide a framework for other graduate education programs to better incorporate interdisciplinary training and student feedback, ultimately improving programs and preparing scientists for the 21st century workforce., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Hill et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Pretransplant functional, motor, cognitive, and academic deficits are common in pediatric patients requiring heart transplantation (HT); some persist post-HT. We assessed the association between these quality of life (QoL) deficits and post-HT outcomes., Methods: Using SRTR data 2008-2023, we evaluated the functional, motor, cognitive, and academic status of pediatric HT recipients from listing to 15 years post-HT. We compared all-cause graft survival among patients with vs. without pre-HT deficits using Cox regressions. Among patients with a functioning graft at 1 year, we assessed the association between deficits at that time and subsequent graft failure., Results: In 6153 HT recipients, 85.3% had pre-HT functional status ≤ 80%, 53.1% of patients could not tolerate a full academic load; this decreased to 15.2% and 15.0% postoperatively, and was sustained. Definite or probable cognitive deficits were seen in 17.4% of patients and motor delays in 18.6%; both remained stable post-HT at 18.0% and 16.4%, respectively. Graft survival was worse in those with either pre- or post-HT deficits in functional status. Worse pre-HT functional status was associated with risk of graft failure (adjusted hazard ratio [aHR] per 10% decrease =  1.03 1.06 1.08 , p < 0.001); worse 1-year post-HT functional status was much more strongly associated with risk of graft failure (aHR =  1.13 1.18 1.23 , p < 0.001)., Conclusion: Pediatric HT recipients with decreased functional status are at higher risk for graft failure and mortality. These patients may benefit from early intervention aimed at improving functional status., (© 2024 Wiley Periodicals LLC.)

Background: Kidney transplant (KT) candidates often experience hospitalizations, increasing their delirium risk. Hospitalizations and delirium are associated with worse post-KT outcomes, yet their relationship with pre-KT outcomes is less clear. Pre-KT delirium may worsen access to KT due to its negative impact on cognition and ability to maintain overall health., Methods: Using a prospective cohort of 2374 KT candidates evaluated at a single center (2009-2020), we abstracted hospitalizations and associated delirium records after listing via chart review. We evaluated associations between waitlist mortality and likelihood of KT with hospitalizations and hospitalized delirium using competing risk models and tested whether associations differed by gerontologic factors., Results: During a median of 1.8 years after listing, 735 (31.0%) candidates had ≥1 hospitalizations. Candidates with less education, frailty, depressive symptoms, and lower extremity function impairment were more likely to be hospitalized. Hospitalization was associated with higher waitlist mortality (aSHR = 3.65, 95% CI: 2.99-4.45) and a lower likelihood of KT (aSHR = 0.74, 95% CI: 0.66-0.84). Among candidates who were hospitalized, 80 (11%) had ≥1 delirium episodes. Candidates who were older, frail, and impaired in lower extremity function were more likely to have delirium, which was associated with higher waitlist mortality (aSHR = 4.87, 95% CI: 3.42-6.93) and a lower likelihood of KT (aSHR = 0.45, 95% CI: 0.27-0.74). The association between hospitalization and KT differed by candidate age (p interaction  < 0.001), with those aged ≥65 having a 61% lower likelihood of KT., Conclusion: Hospitalization and delirium are associated with worse pre-KT outcomes and have serious implications on candidates' access to KT. Providers should work to reduce preventable instances of delirium., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

A novel and eco-friendly approach to modify natural cotton fiber by flash-explosion with a sub- or supercritical fluid of carbon dioxide (sub- or SCF-CO 2 ) for improving its structure and properties was constructed for the first time. The achieved results demonstrate that remarkable improvements in the coloration performance of cotton fiber by 71.1 % and the water retention by 1001.2 % against the control could be readily available by employing the flashily-explosion method at a recommended condition with 4-cycle explosion in sub- or SCF-CO 2 , and system temperature, fluid treatment duration and explosion number exhibited much more pronounced positive influences among all parameters. Additionally, minimal influences from the supercritical explosion on cotton fiber micronaire value, thermal property and tensile breaking strength were also observed. The scanning electron microscopy (SEM) and porosity investigations clearly show that plenty of micropores and/or strip fissures were formed on the fiber surfaces and their inner phases, and notably improved fiber surface area, pore volume and size were also obtained after a subsupercritical flash-explosion. Nuclear magnetic resonance hydrogen spectroscopy ( 1 H NMR) and Fourier transform infrared spectroscopy (FT-IR) analysis disclose that numbers of hydrogen bonds between the fiber macrochains and/or from their intramolecular chains were broken by generating numerous free hydroxyl groups, which reasonably supported the improvements of the dye uptake behaviors and water retention properties, etc. The Energy-dispersive X-ray spectroscopy (EDS) analysis on the fiber cross-sections further confirms that a loosening of the inner aggregation structure of the cotton fiber was achieved after a flash explosion by significantly enhancing its coloration performance, etc. This innovative approach provides a promising idea and possibility as an alternative to chemical methods via mechanically and physically modifying fiber or other materials with sub- or SCF-CO 2 fluid in an eco-friendly and sustainable manner., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: The inflammatory burden index (IBI), a novel inflammation-based indicator, to is associated with the presence and prognosis of various diseases. However, few studies have focused on exploring the relationship between IBI and the coronary slow flow phenomenon (CSFP). In this study, we aimed to investigate the predictive value of IBI for CSFP in patients with chest pain and no obstructive coronary artery disease., Methods: A total of 1126 individuals with chest pain and no obstructive coronary arteries were consecutively included in this study. 71 patients developed CSFP were included in the CSFP group. A 1:2 age- and sex-matched patient with normal blood flow and angiographically proven normal coronary arteries was selected as the control group (n = 142). Plasma C-reactive protein (CRP), neutrophil, and lymphocyte counts were measured to determine the value of IBI., Results: The IBI were significantly higher in the CSFP group than in the controls (21.1 ± 6.5 vs. 14.5 ± 6.4, P < 0.001). The IBI increasedelevated with the increase of the numbers of vessels affected by CSFP. Multivariate logistic regression analysis revealed that IBI and body mass index (BMI) were independent predictors of CSFP. Receiver operating characteristic (ROC) curve analysis showed that when IBI was > 15.74, the sensitivity and specificity were 77.5% and 67.6%, respectively, and the area under the ROC curve (AUC) was 0.799 (95% CI: 0.737-0.862, P<0.001)., Conclusion: The IBI may be an independent predictor of CSFP in patients with chest pain and normal coronary arteries. The IBI could improve the predictive value of CSFP compared with the indicators alone., (© 2024. The Author(s).)

BACKGROUND Recently, the albumin-to-creatinine ratio (ACR) has been suggested as a valuable biomarker for adverse events in acute myocardial infarction. However, the prognostic value of ACR in very elderly patients (≥80 years) with non-ST-elevation acute coronary syndrome (NSTE-ACS) after percutaneous coronary intervention (PCI) remains unclear. MATERIAL AND METHODS A total of 354 very elderly patients with NSTE-ACS who underwent PCI were included in this study and followed up for 1 year. Patients were divided into 3 groups according to ACR tertiles. Logistic regression analysis proportional hazard model was used to determine the prognostic value of ACR. RESULTS Sixty-two patients (17.5%) with 114 major adverse cardiovascular and cerebrovascular events (MACCEs) were recorded during 1-year follow-up. Patients with lower ACR tended to be older and had a lower serum albumin level and higher uric acid and creatinine levels (P<0.05). Moreover, patients with lower ACR levels had elevated all-cause mortality and MACCEs. Kaplan-Meier analysis suggested that patients with a lower ACR had a significantly lower survival rate free of all-cause mortality and MACCEs. Multivariable logistic regression analysis demonstrated that ACR was an independent predictor of all-cause mortality in these patients. ROC analysis showed that when ACR was ≤42.8, sensitivity and specificity were 75.2% and 80.2%, respectively, and the area under the ROC curve was 0.802 (95% CI: 0.745-0.859; P<0.001). CONCLUSIONS A lower ACR was associated with a higher incidence of all-cause mortality in very elderly patients with NSTE-ACS after PCI. The ACR is a promising indicator for risk stratification and prognostic assessment in these individuals.

Introduction: Dietary restrictions for patients with end-stage kidney disease (ESKD) are burdensome. Kidney transplantation (KT) candidates who lack neighborhood resources and are burdened by dietary restrictions may have decreased access to KT., Methods: In our two-center prospective cohort study (2014-2023), 2471 ESKD patients who were evaluated for KT (candidates) reported their perceived burden of dietary restrictions (not at all, somewhat/moderately, or extremely bothered). Neighborhood-level socioeconomic factors were derived from residential ZIP codes. We quantified the association of perceived burden of the dietary restrictions with a chance of listing using Cox models and risk of waitlist mortality using competing risks models. Then we tested whether these associations differed by neighborhood-level socioeconomic factors., Results: At evaluation, 18% of KT candidates felt extremely bothered by dietary restrictions. Those who felt extremely bothered were less likely to be listed for KT (adjusted hazard ratio [aHR] = 0.75, 95% confidence interval [CI]: 0.64-0.87); this association did not differ by neighborhood-level socioeconomic factors. Overall, the burden of dietary restrictions was not associated with waitlist mortality (p = 0.62). However, among candidates living in high food insecurity neighborhoods, those who felt extremely bothered had higher waitlist mortality (adjusted subhazard ratio [aSHR] = 2.07, 95% CI: 1.14-3.75, p [interaction]  = 0.02). The association between dietary burden and waitlist mortality did not differ by neighborhood-level healthy food access., Conclusion: The perceived burden of dietary restrictions is associated with a lower chance of listing for KT, and higher waitlist mortality only among candidates residing in neighborhoods with high food insecurity. Transplant centers should identify vulnerable patients and support them with nutrition education and access to food assistance programs., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: Semaglutide, a glucagon-like peptide-1 receptor agonist is approved for weight loss and diabetes treatment, but limited literature exists regarding semaglutide use in patients with advanced chronic kidney disease (CKD). Therefore, this project assessed the safety and efficacy of semaglutide among patients with estimated glomerular filtration rate (eGFR) 15-29 mL/min/1.73 m 2 (CKD stage 4), eGFR<15 mL/min/1.73 m 2 (CKD stage 5) or on dialysis., Methods: This is a retrospective electronic medical record based analysis of consecutive patients with advanced CKD (defined as CKD 4 or greater) who were started on semaglutide (injectable or oral). Data was collected between January 2018 and January 2023. Investigators verified CKD diagnosis and manually extracted data. Data were analyzed using Fisher's exact test, paired t test, linear mixed effects models and Wilcoxon signed rank test., Results: Seventy-six patients with CKD 4 or greater who initiated semaglutide were included. Most patients had a history of type 2 diabetes mellitus (96.0%), and most were males (53.9%). The mean age was 66.8 y (SD 11.5) with the mean body mass index was 36.2 (SD 7.5). The initial doses were 3 mg orally and 0.25 mg by injection. Maximum prescribed dose was 1 mg (injectable) in 28 (45.2%) patients and 14 mg (orally) in 2 (14.2%) patients. Patients received semaglutide for a median duration of 17.4 (IQR 0.43, 48.8) months. Forty-eight (63.1%) patients reported no adverse effects associated with the therapy. Mean weight decreased from 106.2 (SD 24.2) to 101.3 (SD 27.3) kg (P < .001). Eight patients (16%) with type 2 diabetes mellitus T2DM discontinued insulin after starting semaglutide. Mean hemoglobin A1c (HbA1c) decreased from 8.0% (SD 1.7) to 7.1% (SD 1.3) (P < .001). Adverse effects were the primary reason for semaglutide discontinuation (37.0%), with nausea, vomiting, and abdominal pain being the most common complaints., Conclusions: Based on this retrospective study semaglutide appears to be tolerated by most individuals with CKD 4 or greater despite associated gastrointestinal side effects similar to those observed in patients with better kidney function and leads to an improvement of glycemic control and insulin discontinuation in patients with T2DM. Modest weight loss (approximately 4.6% of the total body weight) was observed on the prescribed doses. Larger prospective randomized studies are needed to comprehensively assess the risks and benefits of semaglutide in patients with CKD 4 or greater and obesity., Competing Interests: Disclosure Dr Aleksandra Kukla participated in NovoNordisk Advisory Board in 2020 but recieved no personal compensation. Dr Matthew M. Clark, Associate Editor, Obesity. Intellectual Property, Phenomix Science, Inc, Pheno-Diet: Individualized Lifestyle Intervention for Obesity Management Based on Obesity Phenotypes., (Copyright © 2024 AACE. Published by Elsevier Inc. All rights reserved.)

Among patients awaiting kidney transplantation (KT), sexual dysfunction is common owing to end-stage kidney disease, but may improve post-KT. Leveraging a 2-center prospective study, 2422 adult KT candidates and 490 adult KT recipients (May 2014 to December 2023) were identified. Using the Kidney Disease Quality of Life Short Form, participants reported on the negative impact of sexual dysfunction due to end-stage kidney disease (ie, sexual bother) at KT evaluation, admission, and post-KT follow-ups. Using mixed-effect logistic regression models, we estimated odds and trajectories for odds of sexual bother. At evaluation, 46.1% of male and 29.6% of female candidates reported sexual bother; 39.0% and 34.5%, respectively, had been sexually active in the past 4 weeks. At admission, 53.8% male and 27.0% female recipients reported sexual bother; 41.6% and 41.8%, respectively, had been sexually active in the past 4 weeks. The estimated prevalence of sexual bother decreased during the first 3 years post-KT (odds ratio per year: 0.39; 95% CI: 0.25-0.60). Sexual activity increased and peaked 1-year post-KT. At 3 years post-KT, 48.9% of male and 50.0% of female recipients were sexually active. Sexual bother is common pre-KT and improves post-KT, and sexual activity increases post-KT. Sexual health is important and should be considered during KT management., Competing Interests: Declaration of competing interests The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation., (Copyright © 2024 American Society of Transplantation & American Society of Transplant Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: The incidence and mortality of lung cancer have increased annually. Accurate diagnosis can help improve therapeutic efficacy of interventions and prognosis. Percutaneous lung biopsy is a reliable method for the clinical diagnosis of lung cancer. Ultrasound-guided percutaneous lung biopsy technology has been widely promoted and applied in recent years., Aim: To investigate the diagnostic value of contrast-enhanced ultrasound (CEUS)-guided percutaneous biopsy in peripheral pulmonary lesions., Methods: We retrospectively collected data on 237 patients with peripheral thoracic focal lesions who underwent puncture biopsy at Wuxi People's Hospital. The patients were randomly divided into two groups: The CEUS-guided before lesion puncture group (contrast group) and conventional ultrasound-guided group (control group). Analyze the diagnostic efficacy of the puncture biopsy, impact of tumor size, and number of puncture needles and complications were analyzed and compared between the two groups., Results: Accurate pathological results were obtained for 92.83% (220/237) of peripheral lung lesions during the first biopsy, with an accuracy rate of 95.8% (113/118) in the contrast group and 89.9% (107/119) in the control group. The difference in the area under the curve (AUC) between the contrast and the control groups was not statistically significant (0.952 vs 0.902, respectively; P > 0.05). However, when the lesion diameter ≥ 5 cm, the diagnostic AUC of the contrast group was higher than that of the control group (0.952 vs 0.902, respectively; P < 0.05). In addition, the average number of puncture needles in the contrast group was lower than that in the control group (2.58 ± 0.53 vs 2.90 ± 0.56, respectively; P < 0.05)., Conclusion: CEUS guidance can enhance the efficiency of puncture biopsy of peripheral pulmonary lesions, especially for lesions with a diameter ≥ 5 cm. Therefore, CEUS guidance has high clinical diagnostic value in puncture biopsy of peripheral focal lung lesions., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Introduction: Adults residing in deprived neighborhoods face various socioeconomic stressors, hindering their likelihood of receiving live-donor kidney transplantation (LDKT) and preemptive kidney transplantation (KT). We quantified the association between residential neighborhood deprivation index (NDI) and the likelihood of LDKT/preemptive KT, testing for a differential impact by race and ethnicity., Methods: We studied 403 937 adults (age ≥ 18) KT candidates (national transplant registry; 2006-2021). NDI and its 10 components were averaged at the ZIP-code level. Cause-specific hazards models were used to quantify the adjusted hazard ratio (aHR) of LDKT and preemptive KT across tertiles of NDI and its 10 components., Results: Candidates residing in high-deprivation neighborhoods were more likely to be female (40.1% vs. 36.2%) and Black (41.9% vs. 17.7%), and were less likely to receive both LDKT (aHR = 0.66, 95% confidence interval [CI]: 0.64-0.67) and preemptive KT (aHR = 0.60, 95% CI: 0.59-0.62) than those in low-deprivation neighborhoods. These associations differedby race and ethnicity (Black: aHR LDKT  = 0.58, 95% CI: 0.55-0.62; aHR preemptive KT  = 0.68, 95% CI: 0.63-0.73; P interactions : LDKT < 0.001; Preemptive KT = 0.002). All deprivation components were associated with the likelihood of both LDKT and preemptive KT (except median home value): for example, higher median household income (LDKT: aHR = 1.08, 95% CI: 1.07-1.09; Preemptive KT: aHR = 1.10, 95% CI: 1.08-1.11) and educational attainments (≥high school [LDKT: aHR = 1.17, 95% CI: 1.15-1.18; Preemptive KT: aHR = 1.23, 95% CI: 1.21-1.25])., Conclusion: Residence in socioeconomically deprived neighborhoods is associated with a lower likelihood of LDKT and preemptive KT, differentially impacting minority candidates. Identifying and understanding which neighborhood-level socioeconomic status contributes to these racial disparities can be instrumental in tailoring interventions to achieve health equity in LDKT and preemptive KT., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The impact of bariatric surgery (BS) on kidney transplantation (KT) outcomes in patients with obesity remains controversial. We systematically searched MEDLINE, EMBASE, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials for studies reporting outcomes of KT recipients that underwent prior BS. Common/random effects meta-analyses were performed to obtain summary ratios of the postoperative outcomes. Eighteen eligible studies involving 315 patients were identified. Sleeve gastrectomy was the most common BS type (65.7%) followed by Roux-en-Y gastric bypass (27.6%) and gastric banding (4.4%). Across studies that provided the data, the %excess weight loss from BS to KT was 62.79% (95% confidence interval [CI], 52.01-73.56; range, 46.2%-80.3%). The rates of delayed graft function and acute rejection were 16% (95% CI, 7%-28%) and 16% (95% CI, 11%-23%) in 14 and 11 studies that provided this data, respectively. The rates of wound, urinary, and vascular complications following KT were 5% (95% CI, 0%-13%),19% (95% CI, 2%-42%), and 2% (95% CI, 0%-5%), in 12, 9, and 11 studies that provided this data, respectively. Follow-up time after KT was reported in 11 studies (61.1%) and ranged from 16 mo to >5 y. Graft loss was reported in 14 studies with an average of 3% (95% CI, 1%-6%). Four studies that included a comparator group of patients with obesity who did not undergo BS before KT showed comparable outcomes between the groups. We conclude that currently there is a paucity of robust evidence to suggest that pretransplant BS has a major effect on post-KT outcomes. High-quality studies are needed to fully evaluate the impact of BS on KT outcomes., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Older compatible living donor kidney transplant (CLDKT) recipients have higher mortality and death-censored graft failure (DCGF) compared to younger recipients. These risks may be amplified in older incompatible living donor kidney transplant (ILDKT) recipients who undergo desensitization and intense immunosuppression. In a 25-center cohort of ILDKT recipients transplanted between September 24, 1997, and December 15, 2016, we compared mortality, DCGF, delayed graft function (DGF), acute rejection (AR), and length of stay (LOS) between 234 older (age ≥60 years) and 1172 younger (age 18-59 years) recipients. To investigate whether the impact of age was different for ILDKT recipients compared to 17 542 CLDKT recipients, we used an interaction term to determine whether the relationship between posttransplant outcomes and transplant type (ILDKT vs CLDKT) was modified by age. Overall, older recipients had higher mortality (hazard ratio: 1.63 2.07 2.65 , P < .001), lower DCGF (hazard ratio: 0.36 0.53 0.77 , P = .001), and AR (odds ratio: 0.39 0.54 0.74 , P < .001), and similar DGF (odds ratio: 0.46 1.03 2.33 , P = .9) and LOS (incidence rate ratio: 0.88 0.98 1.10 , P = 0.8) compared to younger recipients. The impact of age on mortality (interaction P = .052), DCGF (interaction P = .7), AR interaction P = .2), DGF (interaction P = .9), and LOS (interaction P = .5) were similar in ILDKT and CLDKT recipients. Age alone should not preclude eligibility for ILDKT., (Copyright © 2023 American Society of Transplantation & American Society of Transplant Surgeons. Published by Elsevier Inc. All rights reserved.)

Millions of tons of feather are produced worldwide each year and considered as a solid waste owing to technical or cost constraints to provide valuable functional characteristics. In this study, a novel and ecofriendly method to recycle waste feather and obtain a type of explosion down via flash explosion with a supercritical fluid of carbon dioxide (SCF-CO 2 ) was developed for the first time. The effects of flash explosion parameters on the structures and properties of feather were explored by orthogonal experiments. A mechanism involving two-step procedures for the developed SCF-CO 2 flash explosion is proposed. The obtained results indicate that reinforcements of flash explosion conditions, particularly the system pressure, were readily conducive to transfer the original feather to a soft down with an improved separation ratio, as well as easily weaken or break hydrogen and disulfide bonds associated in feather macromolecules. Moreover, efficient modifications of the physical characteristics, structures and surface morphologies of the waste feather were obtained by the SCF flash explosion to produce a uniform, slender and fibrous explosion down, as demonstrated by scanning electron microscopy, Fourier-transform infrared spectroscopy, and X-ray diffraction analysis. Further tests on the SCF explosion down treated at 70.0 °C at 15.0 MPa for 30.0 min and at 90.0 °C at 20.0 MPa for 20.0 min showed remarkable enhancements in warmth retention along with comparable thermal degradation nature, as well as enhanced softness, down-proof, and other service properties in comparison to the original feather. The SCF-CO 2 flash explosion is a promising approach with environment-friendly characteristics to obtain high efficiency and quality of the explosion down by recycling of waste feather., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Steatotic livers represent a potentially underutilized resource to increase the donor graft pool; however, 1 barrier to the increased utilization of such grafts is the heterogeneity in the definition and the measurement of macrovesicular steatosis (MaS). Digital imaging software (DIS) may better standardize definitions to study posttransplant outcomes. Using HALO, a DIS, we analyzed 63 liver biopsies, from 3 transplant centers, transplanted between 2016 and 2018, and compared macrovesicular steatosis percentage (%MaS) as estimated by transplant center, donor hospital, and DIS. We also quantified the relationship between DIS characteristics and posttransplant outcomes using log-linear regression for peak aspartate aminotransferase, peak alanine aminotransferase, and total bilirubin on postoperative day 7, as well as logistic regression for early allograft dysfunction. Transplant centers and donor hospitals overestimated %MaS compared with DIS, with better agreement at lower %MaS and less agreement for higher %MaS. No DIS analyzed liver biopsies were calculated to be >20% %MaS; however, 40% of liver biopsies read by transplant center pathologists were read to be >30%. Percent MaS read by HALO was positively associated with peak aspartate aminotransferase (regression coefficient= 1.04 1.08 1.12 , p <0.001), peak alanine aminotransferase (regression coefficient = 1.04 1.08 1.12 , p <0.001), and early allograft dysfunction (OR= 1.10 1.40 1.78 , p =0.006). There was no association between HALO %MaS and total bilirubin on postoperative day 7 (regression coefficient = 0.99 1.01 1.04 , p =0.3). DIS provides reproducible quantification of steatosis that could standardize MaS definitions and identify phenotypes associated with good clinical outcomes to increase the utilization of steatite livers., (Copyright © 2023 American Association for the Study of Liver Diseases.)

Objective: This study aimed to investigate the correlation of serum octapeptide cholecystokinin-8 (CCK-8), substance P (SP), and 5-hydroxytryptryptamine (5-HT) values with depression levels in patients with post-stroke depression (PSD). It also aimed to explore the potential approach for the early diagnosis of PSD., Patients and Methods: A correlation research between patients' biochemical indicators and depression levels was performed among 70 stroke patients during hospitalization from June 2021 to February 2022. The 70 stroke patients were selected and divided into post-stroke depression and non-depression groups according to the Hamilton Depression Scale (HAMD) score. The concentrations of CCK-8, SP, and 5-HT in both groups were measured, and the relationship between the values of CCK-8, SP, 5-HT and the depression levels was analyzed., Results: Among the 70 stroke survivors, 35 were in the depression group and 35 were in the non-depression group. Significant differences were observed in the concentration of CCK-8, SP, and 5-HT between the patients in the depression and non-depression group (p < 0.05). Accompanied by an increase in the depression level, the SP value gradually increased, but the CCK-8 and 5-HT values gradually decreased. Spearman correlation analysis indicated that the order of the correlation between CCK-8, 5-HT, SP, and the depression levels was CCK-8 > SP > 5-HT., Conclusions: All the CCK-8, SP and 5-HT values were correlated with the depression levels in stroke survivors. Furthermore, the correlation between CCK-8, SP, and post-stroke depression levels was higher than that of 5-HT, suggesting that the early diagnosis of PSD may be reflected more precisely through the detection of CCK-8, and SP values, thus providing potential priority for biochemical detection in the diagnosis of PSD.

Ecological restoration frequently involves the addition of native plants, but the effectiveness (in terms of plant growth, plant survival, and cost) of using seeds versus container plants has not been studied in many plant communities. It is also not known if plant success would vary by species or based on functional traits. To answer these questions, we added several shrub species to a coastal sage scrub restoration site as seeds or as seedlings in a randomized block design. We measured percent cover, density, species richness, size, survival, and costs. Over the two years of the study, shrubs added to the site as seeds grew more and continued to have greater density than plants added from containers. Seeded plots also had greater native species richness than planted plots. However, shrubs from containers had higher survival rates, and percent cover was comparable between the planted and seeded treatments. Responses varied by species depending on functional traits, with deep-rooted evergreen species establishing better from container plants. Our cost analysis showed that it is more expensive to use container plants than seed, with most of the costs attributed to labor and supplies needed to grow plants. Our measurements of shrub density, survival, species richness, and growth in two years in our experimental plots lead us to conclude that coastal sage scrub restoration with seeds is optimal for increasing density and species richness with limited funds, yet the addition of some species from container plants may be necessary if key species are desired as part of the project objectives., Competing Interests: The authors have declared that no competing interests exist.

Background: Robot-assisted gait training has been confirmed to have beneficial effect on the rehabilitation of stroke patients. An exoskeleton robot, named BEAR-H1, is designed to help stroke patients with walking disabilities., Methods: 17 subjects in experimental group and 15 subjects in control group completed the study. The experimental group received 30 minutes of BEAR-H1 assisted gait training(BAGT), and the control group received 30 minutes of conventional training, 5 times/week for 4weeks. All subjects were evaluated with 6-minute walk test (6MWT), Fugl-Meyer Assessment for lower extremity (FMA-LE), Functional Ambulatory Classification (FAC), Modified Ashworth Scale (MAS), and gait analysis at baseline and after 4 weeks intervention., Results: The improvements of 6MWT, FMA-LE, gait speed, cadence, step length and cycle duration in BAGT group were more noticeable than in the control group. However, there was no difference in the assessment of MAS between two groups., Conclusions: Our results showed that BAGT is an effective intervention to improve the motor and walking ability during 4 weeks training for subacute stroke patients., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Incompatible living donor kidney transplant recipients (ILDKTr) have pre-existing donor-specific antibody (DSA) that, despite desensitization, may persist or reappear with resulting consequences, including delayed graft function (DGF) and acute rejection (AR). To quantify the risk of DGF and AR in ILDKT and downstream effects, we compared 1406 ILDKTr to 17 542 compatible LDKT recipients (CLDKTr) using a 25-center cohort with novel SRTR linkage. We characterized DSA strength as positive Luminex, negative flow crossmatch (PLNF); positive flow, negative cytotoxic crossmatch (PFNC); or positive cytotoxic crossmatch (PCC). DGF occurred in 3.1% of CLDKT, 3.5% of PLNF, 5.7% of PFNC, and 7.6% of PCC recipients, which translated to higher DGF for PCC recipients (aOR =  1.03 1.68 2.72 ). However, the impact of DGF on mortality and DCGF risk was no higher for ILDKT than CLDKT (p interaction > .1). AR developed in 8.4% of CLDKT, 18.2% of PLNF, 21.3% of PFNC, and 21.7% of PCC recipients, which translated to higher AR (aOR PLNF =  1.45 2.09 3.02 ; PFNC =  1.67 2.40 3.46 ; PCC =  1.48 2.24 3.37 ). Although the impact of AR on mortality was no higher for ILDKT than CLDKT (p interaction = .1), its impact on DCGF risk was less consequential for ILDKT (aHR =  1.34 1.62 1.95 ) than CLDKT (aHR =  1.96 2.29 2.67 ) (p interaction = .004). Providers should consider these risks during preoperative counseling, and strategies to mitigate them should be considered., (© 2020 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Kidneys from older (age ≥50 years) donation after cardiac death (DCD50) donors are less likely to be transplanted due to inferior posttransplant outcomes. However, candidates who decline a DCD50 offer must wait for an uncertain future offer. To characterize the survival benefit of accepting DCD50 kidneys, we used 2010-2018 Scientific Registry for Transplant Recipients (SRTR) data to identify 92 081 adult kidney transplantation candidates who were offered a DCD50 kidney that was eventually accepted for transplantation. DCD50 kidneys offered to candidates increased from 590 in 2010 to 1441 in 2018. However, 34.6% of DCD50 kidneys were discarded. Candidates who accepted DCD50 offers had 49% decreased mortality risk (adjusted hazard ratio [aHR] 0.46 0.51 0.55 , cumulative mortality at 6-year 23.3% vs 34.0%, P < .001) compared with those who declined the same offer (decliners). Six years after their initial DCD50 offer decline, 43.0% of decliners received a deceased donor kidney transplant (DDKT), 6.3% received living donor kidney transplant (LDKT), 22.6% died, 22.0% were removed for other reasons, and 6.0% were still on the waitlist. Comparable survival benefit was observed even with DCD donors age ≥60 (aHR: 0.42 0.52 0.65 , P < .001). Accepting DCD50 kidneys was associated with a substantial survival benefit; providers and patients should consider these benefits when evaluating offers., (© 2020 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Accurate pathogenicity prediction of missense variants is critically important in genetic studies and clinical diagnosis. Previously published prediction methods have facilitated the interpretation of missense variants but have limited performance. Here, we describe MVP (Missense Variant Pathogenicity prediction), a new prediction method that uses deep residual network to leverage large training data sets and many correlated predictors. We train the model separately in genes that are intolerant of loss of function variants and the ones that are tolerant in order to take account of potentially different genetic effect size and mode of action. We compile cancer mutation hotspots and de novo variants from developmental disorders for benchmarking. Overall, MVP achieves better performance in prioritizing pathogenic missense variants than previous methods, especially in genes tolerant of loss of function variants. Finally, using MVP, we estimate that de novo coding variants contribute to 7.8% of isolated congenital heart disease, nearly doubling previous estimates.

Infections remain a major threat to successful kidney transplantation (KT). To characterize the landscape and impact of post-KT infections in the modern era, we used United States Renal Data System (USRDS) data linked to the Scientific Registry of Transplant Recipients (SRTR) to study 141 661 Medicare-primary kidney transplant recipients from January 1, 1999 to December 31, 2014. Infection diagnoses were ascertained by International Classification of Diseases, Ninth Revision (ICD-9) codes. The cumulative incidence of a post-KT infection was 36.9% at 3 months, 53.7% at 1 year, and 78.0% at 5 years. The most common infections were urinary tract infection (UTI; 46.8%) and pneumonia (28.2%). Five-year mortality for kidney transplant recipients who developed an infection was 24.9% vs 7.9% for those who did not, and 5-year death-censored graft failure (DCGF) was 20.6% vs 10.1% (P < .001). This translated to a 2.22-fold higher mortality risk (adjusted hazard ratio [aHR]: 2.15 2.22 2.29 , P < .001) and 1.92-fold higher DCGF risk (aHR: 1.84 1.91 1.98 , P < .001) for kidney transplant recipients who developed an infection, although the magnitude of this higher risk varied across infection types (for example, 3.11-fold higher mortality risk for sepsis vs 1.62-fold for a UTI). Post-KT infections are common and substantially impact mortality and DCGF, even in the modern era. Kidney transplant recipients at high risk for infections might benefit from enhanced surveillance or follow-up to mitigate these risks., (© 2020 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background: Donor livers with ≥30% macrosteatosis (steatotic livers) represent a possible expansion to the donor pool, but are frequently discarded as they are associated with an increased risk of mortality and graft loss. We hypothesized that there are certain recipient phenotypes that would tolerate donor steatosis well, and are therefore best suited to receive these grafts., Methods: Using national registry data from the Scientific Registry of Transplant Recipients between 2006 and 2017, we compared 2048 liver transplant recipients of steatotic livers with 69 394 recipients of nonsteatotic (<30%) livers. We identified recipient factors that amplified the impact of donor steatosis on mortality and graft loss using interaction analysis, classifying recipients without these factors as preferred recipients. We compared mortality and graft loss with steatotic versus nonsteatotic livers in preferred and nonpreferred recipients using Cox regression., Results: Preferred recipients of steatotic livers were determined to be first-time recipients with a model for end-stage liver disease 15-34, without primary biliary cirrhosis, and not on life support before transplant. Preferred recipients had no increased mortality risk (hazard ratio [HR]: 0.921.041.16; P = 0.5) or graft loss (HR: 0.931.031.15; P = 0.5) with steatotic versus nonsteatotic livers. Conversely, nonpreferred recipients had a 41% increased mortality risk (HR: 1.171.411.70; P < 0.001) and 39% increased risk of graft loss (HR: 1.161.391.66; P < 0.001) with steatotic versus nonsteatotic livers., Conclusions: The risks of liver transplantation with steatotic donor livers could be minimized by appropriate recipient matching.

Background: Steatotic donor livers (SDLs, ≥30% macrosteatosis on biopsy) are often declined, as they are associated with a higher risk of graft loss, even though candidates may wait an indefinite time for a subsequent organ offer. We sought to quantify outcomes for transplant candidates who declined or accepted an SDL offer., Methods: We used Scientific Registry of Transplant Recipients offer data from 2009 to 2015 to compare outcomes of 759 candidates who accepted an SDL to 13 362 matched controls who declined and followed candidates from the date of decision (decline or accept) until death or end of study period. We used a competing risk framework to understand the natural history of candidates who declined and Cox regression to compare postdecision survival after declining versus accepting (ie, what could have happened if candidates who declined had instead accepted)., Results: Among those who declined an SDL, only 53.1% of candidates were subsequently transplanted, 23.8% died, and 19.4% were removed from the waitlist. Candidates who accepted had a brief perioperative risk period within the first month posttransplant (adjusted hazard ratio [aHR]: 2.493.494.89, P < 0.001), but a 62% lower mortality risk (aHR: 0.310.380.46, P < 0.001) beyond this. Although the long-term survival benefit of acceptance did not vary by candidate model for end-stage liver disease (MELD), the short-term risk period did. MELD 6-21 candidates who accepted an SDL had a 7.88-fold higher mortality risk (aHR: 4.807.8812.93, P < 0.001) in the first month posttransplant, whereas MELD 35-40 candidates had a 68% lower mortality risk (aHR: 0.110.320.90, P = 0.03)., Conclusions: Appropriately selected SDLs can decrease wait time and provide substantial long-term survival benefit for liver transplant candidates.

Steatotic donor livers (SDLs) (macrosteatosis ≥30%) represent a possible donor pool expansion, but are frequently discarded due to a historical association with mortality and graft loss. However, changes in recipient/donor demographics, allocation policy, and clinical protocols might have altered utilization and outcomes of SDLs. We used Scientific Registry of Transplant Recipients data from 2005 to 2017 and adjusted multilevel regression to quantify temporal trends in discard rates (logistic) and posttransplant outcomes (Cox) of SDLs, accounting for Organ Procurement Organization-level variation. Of 4346 recovered SDLs, 58.0% were discarded in 2005, versus only 43.1% in 2017 (P < .001). SDLs were always substantially more likely discarded versus non-SDLs, although this difference decreased over time (adjusted odds ratio in 2005-2007: 13.15 15.28 17.74 ; 2008-2011: 11.77 13.41 15.29 ; 2012-2014: 9.87 11.37 13.10 ; 2015-2017: 7.79 8.89 10.15 , P < .001 for all). Conversely, posttransplant outcomes of recipients of SDLs improved over time: recipients of SDLs from 2012 to 2017 had 46% lower risk of mortality (adjusted hazard ratio [aHR]: 0.43 0.54 0.68 , P < .001) and 47% lower risk of graft loss (aHR: 0.42 0.53 0.67 , P < .001) compared to 2005 to 2011. In fact, in 2012 to 2017, recipients of SDLs had equivalent mortality (aHR: 0.90 1.04 1.21 , P = .6) and graft loss (aHR: 0.90 1.04 1.20 , P = .6) to recipients of non-SDLs. Increasing utilization of SDLs might be a reasonable strategy to expand the donor pool., (© 2019 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Objective: Rhizoctonia solani is a soil-borne fungal pathogen of many important crop plants. In rice, R. solani causes sheath blight disease, which results in devastating grain yield and quality losses. Few methods are available to control this pathogen and classic single gene resistance mechanisms in rice plants have not been identified. We hypothesize that alternate means of control are available in the environment including free-living amoebae. Amoebae are soil-, water- and air-borne microorganisms that are predominantly heterotrophic. Many amoeba species are mycophagous, and several harm their prey using mechanisms other than phagocytosis. Here, we used light and scanning electron microscopy to survey the interactions of R. solani with four amoeba species, with the goal of identifying amoebae species with potential for biocontrol., Results: We observed a wide range of responses during interactions of R. solani with four different free-living amoebae. Two Acanthamoeba species encyst in co-cultures with R. solani at higher rates than medium without R. solani. Vermamoeba vermiformis (formerly Hartmanella vermiformis) attach to R. solani mycelium and are associated with mycelial shriveling and perforations of fungal cell walls, indicating an antagonistic interaction. No phenotypic changes were observed in co-cultures of Dictyostelium discoideum and R. solani.

There is a large body of preclinical literature suggesting that exposure to general anesthetic agents during early life may have harmful effects on brain development. Patients in intensive care settings are often treated for prolonged periods with sedative medications, many of which have mechanisms of action that are similar to general anesthetics. Using in vivo studies of the mouse hippocampus and an in vitro rat cortical neuron model we asked whether there is evidence that repeated, long duration exposure to midazolam, a commonly used sedative in pediatric intensive care practice, has the potential to cause lasting harm to the developing brain. We found that mice that underwent midazolam sedation in early postnatal life exhibited deficits in the performance on Y-maze and fear-conditioning testing at young adult ages. Labeling with a nucleoside analog revealed a reduction in the rate of adult neurogenesis in the hippocampal dentate gyrus, a brain region that has been shown to be vulnerable to developmental anesthetic neurotoxicity. In addition, using immunohistochemistry for synaptic markers we found that the number of presynaptic terminals in the dentate gyrus was reduced, while the number of excitatory postsynaptic terminals was increased. These findings were replicated in a midazolam sedation exposure model in neurons in culture. We conclude that repeated, long duration exposure to midazolam during early development has the potential to result in persistent alterations in the structure and function of the brain.

Disperse reactive dyes with appropriate chemical structure are key for the coloration of natural fibers in the water-free environmentally friendly medium of supercritical carbon dioxide with various advantages. The objective of this work is to design and synthesize a novel anthraquinonoid disperse reactive dye involving a versatile bridge group to improve the coloration properties of the dye in supercritical carbon dioxide. Cross-coupling condensation based on an Ullmann reaction between N -phenylethylenediamine and 1-chloroanthraquinone in a ligand-free system is investigated by optimizing the synthesis parameters. Notable influences are observed from the dosages of N , N -dimethyl formamide and potassium hydroxide, as well as the system temperature and reaction duration, on the isolated yield of the dye precursor. An optimized process is also recommended for synthesizing the designed novel dye. Then, the chemical structure, color characteristics, and coloration properties of the obtained dye are further investigated and successfully characterized by utilizing Fourier-transform infrared analysis, 1 H and 13 C nuclear magnetic resonance spectroscopy, UV-vis absorption spectroscopy, elemental analysis, and liquid chromatography-mass spectrometry. Additionally, practical coloration experiments are performed with cotton, silk, and wool in a supercritical carbon dioxide medium.

Background: Free-living amoebae (FLA) are voracious feeders, consuming bacteria and other microbes during colonization of the phytobiome. FLA are also known to secrete bacteriocidal or bacteriostatic compounds into their growth environment., Methodology and Principal Findings: Here, we explore the impacts of co-cultivation of five FLA species, including Acanthamoeba castellanii, A. lenticulata, A. polyphaga, Dictyostelium discoideum and Vermamoeba vermiformis, on survival of two devastating bacterial pathogens of rice, Xanthomonas oryzae pathovars (pv.) oryzae and oryzicola. In co-cultivation assays, the five FLA species were either bacteriostatic or bactericidal to X. oryzae pv. oryzae and X. oryzae pv. oryzicola. Despite these effects, bacteria were rarely detected inside amoebal cells. Furthermore, amoebae did not disrupt X. oryzae biofilms. The bactericidal effects persisted when bacteria were added to a cell-free supernatant from amoebal cultures, suggesting some amoebae produce an extracellular bactericidal compound., Conclusions/significance: This work establishes novel, basal dynamics between important plant pathogenic bacteria and diverse amoebae, and lays the framework for future mechanistic studies., Competing Interests: The authors have declared that no competing interests exist.

A large amount of hemiplegic survivors are suffering from motor impairment. Ankle rehabilitation exercises act an important role in recovering patients' walking ability after stroke. Currently, patients mainly perform ankle exercise to reobtain range of motion (ROM) and strength of the ankle joint under a therapist's assistance by manual operation. However, therapists suffer from high work intensity, and most of the existed rehabilitation devices focus on ankle functional training and ignore the importance of neurological rehabilitation in the early hemiplegic stage. In this paper, a new robotic ankle rehabilitation platform (RARP) is proposed to assist patients in executing ankle exercise. The robotic platform consists of two three-DOF symmetric layer-stacking mechanisms, which can execute ankle internal/external rotation, dorsiflexion/plantarflexion, and inversion/eversion exercise while the rotation center of the distal zone of the robotic platform always coincides with patients' ankle pivot center. Three exercise modes including constant-speed exercise, constant torque-impedance exercise, and awareness exercise are developed to execute ankle training corresponding to different rehabilitation stages. Experiments corresponding to these three ankle exercise modes are performed, the result demonstrated that the RARP is capable of executing ankle rehabilitation, and the novel awareness exercise mode motivates patients to proactively participate in ankle training.

Background: The research reported here sought to evaluate whether a dedicated education programme in vision awareness improved the knowledge and skills of autism support practitioners in identifying visual impairment in autistic people with intellectual disabilities and providing better support to those individuals identified as visually impaired., Methods: Researchers undertook a mixed methods evaluation. A survey questionnaire was devised and administered before and after training and focus groups were undertaken in order to gain qualitative data relating how practitioners implemented their learning in practice., Results: Knowledge confidence and practice confidence scores of participants were significantly improved by the programme, which maintained its impact one year on. Practitioners reported increased access to optometry, changes to support practice and improvements to service environments as a result of the training., Conclusion: Autism support practitioners' skills in identifying and supporting people with visual impairments were demonstrably enhanced through dedicated vision training., (© 2017 John Wiley & Sons Ltd.)

The emergence of multi- and extensively-drug resistant tubercular (MDR- and XDR-TB) strains of mycobacteria has limited the use of existing therapies, therefore new drugs are needed. Dihydrofolate reductase (DHFR) has recently attracted much attention as a target for the development of anti-TB agents. This study aimed to develop selective M. tuberculosis DHFR inhibitors using rationale scaffolding design and synthesis, phenotype-oriented screening, enzymatic inhibitory study, whole cell on-target validation, molecular modeling, and in vitro DMPK determination to derive new anti-TB agents. 2,4-diamino-1-phenyl-1,3,5-triazaspiro[5.5]undeca-2,4-dienes 20b and 20c were identified as selective M. tuberculosis DHFR inhibitors, showing promising antimycobacterial activities (MIC 50 : 0.01 μM and MIC 90 : 0.025 μM on M. tuberculosis H37Rv). This study provided compelling evidence that compound 20b and 20c exerted whole cell antimycobacterial activity through DHFR inhibition. In addition, these two compounds exhibited low cytotoxicity and low hemolytic activity. The in vitro DMPK and physiochemical properties suggested their potential in vivo efficacy., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Mutations in the proline-rich transmembrane protein 2 (PRRT2) are associated with paroxysmal kinesigenic dyskinesia (PKD) and several other paroxysmal neurological diseases, but the PRRT2 function and pathogenic mechanisms remain largely obscure. Here we show that PRRT2 is a presynaptic protein that interacts with components of the SNARE complex and downregulates its formation. Loss-of-function mutant mice showed PKD-like phenotypes triggered by generalized seizures, hyperthermia, or optogenetic stimulation of the cerebellum. Mutant mice with specific PRRT2 deletion in cerebellar granule cells (GCs) recapitulate the behavioral phenotypes seen in Prrt2-null mice. Furthermore, recording made in cerebellar slices showed that optogenetic stimulation of GCs results in transient elevation followed by suppression of Purkinje cell firing. The anticonvulsant drug carbamazepine used in PKD treatment also relieved PKD-like behaviors in mutant mice. Together, our findings identify PRRT2 as a novel regulator of the SNARE complex and provide a circuit mechanism underlying the PRRT2-related behaviors.

Importance: Prescription opioid analgesics play an important role in the treatment of postoperative pain; however, unused opioids may be diverted for nonmedical use and contribute to opioid-related injuries and deaths., Objective: To quantify how commonly postoperative prescription opioids are unused, why they remain unused, and what practices are followed regarding their storage and disposal., Evidence Review: MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials were searched from database inception to October 18, 2016, for studies describing opioid oversupply for adults after a surgical procedure. The primary outcome-opioid oversupply-was defined as the number of patients with either filled but unused opioid prescriptions or unfilled opioid prescriptions. Two reviewers independently screened studies for inclusion, extracted data, and assessed the study quality., Findings: Six eligible studies reported on a total of 810 unique patients (range, 30-250 patients) who underwent 7 different types of surgical procedures. Across the 6 studies, 67% to 92% of patients reported unused opioids. Of all the opioid tablets obtained by surgical patients, 42% to 71% went unused. Most patients stopped or used no opioids owing to adequate pain control, and 16% to 29% of patients reported opioid-induced adverse effects. In 2 studies examining storage safety, 73% to 77% of patients reported that their prescription opioids were not stored in locked containers. All studies reported low rates of anticipated or actual disposal, but no study reported US Food and Drug Administration-recommended disposal methods in more than 9% of patients., Conclusions and Relevance: Postoperative prescription opioids often go unused, unlocked, and undisposed, suggesting an important reservoir of opioids contributing to nonmedical use of these products, which could cause injuries or even deaths.

Gram-negative bacterial pathogens of plants and animals employ type III secreted effectors to suppress innate immunity. Most characterized effectors work through modification of host proteins or transcriptional regulators, although a few are known to modify small molecule targets. The Xanthomonas type III secreted avirulence factor AvrRxo1 is a structural homolog of the zeta toxin family of sugar-nucleotide kinases that suppresses bacterial growth. AvrRxo1 was recently reported to phosphorylate the central metabolite and signaling molecule NAD in vitro, suggesting that the effector might enhance bacterial virulence on plants through manipulation of primary metabolic pathways. In this study, we determine that AvrRxo1 phosphorylates NAD in planta, and that its kinase catalytic sites are necessary for its toxic and resistance-triggering phenotypes. A global metabolomics approach was used to independently identify 3'-NADP as the sole detectable product of AvrRxo1 expression in yeast and bacteria, and NAD kinase activity was confirmed in vitro. 3'-NADP accumulated upon transient expression of AvrRxo1 in Nicotiana benthamiana and in rice leaves infected with avrRxo1-expressing strains of X. oryzae. Mutation of the catalytic aspartic acid residue D193 abolished AvrRxo1 kinase activity and several phenotypes of AvrRxo1, including toxicity in yeast, bacteria, and plants, suppression of the flg22-triggered ROS burst, and ability to trigger an R gene-mediated hypersensitive response. A mutation in the Walker A ATP-binding motif abolished the toxicity of AvrRxo1, but did not abolish the 3'-NADP production, virulence enhancement, ROS suppression, or HR-triggering phenotypes of AvrRxo1. These results demonstrate that a type III effector targets the central metabolite and redox carrier NAD in planta, and that this catalytic activity is required for toxicity and suppression of the ROS burst.

The results of previous studies evaluated the accuracy of serum, and urinary measurements of cytokeratin-19 fragment (CYFRA 21-1) for the diagnosis of bladder cancer were inconsistent. We read with great interest the recent systematic review of diagnostic accuracy of CYFRA 21-1 for bladder cancer by Huang et al. The systematic analysis demonstrated that the pooled sensitivities and specificities for serum and urine CYFRA 21-1 were 0.42 (95 % confidence interval (CI), 0.33-0.51), 0.82 (95 % CI, 0.70-0.90), 0.94 (95 % CI, 0.90-0.96), and 0.80 (95 % CI, 0.73-0.86), respectively. Areas under the summary receiver-operating-characteristic curves for serum and urine CYFRA 21-1 were 0.88 (95 % CI, 0.85-0.91) and 0.87 (95%CI, 0.84-0.90), respectively. The authors considered that both serum and urine CYFRA 21-1 served as efficient indexes for bladder-cancer diagnosis. We congratulate and applaud their important work, but several important issues should be noted.