Surface‐enhanced Raman spectroscopy (SERS)‐based biosensors have attracted much attention for their label‐free detection, ultrahigh sensitivity, and unique molecular fingerprinting. In this study, a ...wafer‐scale, ultrasensitive, highly uniform, paper‐based, portable SERS detection platform featuring abundant and dense gold nanopearls with narrow gap distances, are prepared and deposited directly onto ultralow‐surface‐energy fluorosilane‐modified cellulose fibers through simple thermal evaporation by delicately manipulating the atom diffusion behavior. The as‐designed paper‐based SERS substrate exhibits an extremely high Raman enhancement factor (3.9 × 1011), detectability at sub‐femtomolar concentrations (single‐molecule level) and great signal reproductivity (relative standard deviation: 3.97%), even when operated with a portable 785‐nm Raman spectrometer. This system is used for fingerprinting identification of 12 diverse analytes, including clinical medicines (cefazolin, chloramphenicol, levetiracetam, nicotine), pesticides (thiram, paraquat, carbaryl, chlorpyrifos), environmental carcinogens (benzoapyrene, benzog,h,iperylene), and illegal drugs (methamphetamine, mephedrone). The lowest detection concentrations reach the sub‐ppb level, highlighted by a low of 16.2 ppq for nicotine. This system appears suitable for clinical applications in, for example, i) therapeutic drug monitoring for individualized medication adjustment and ii) ultra‐early diagnosis for pesticide intoxication. Accordingly, such scalable, portable and ultrasensitive fibrous SERS substrates open up new opportunities for practical on‐site detection in biofluid analysis, point‐of‐care diagnostics and precision medicine.
A facile, scalable fabrication strategy for developing an ultrasensitive surface‐enhanced Raman spectroscopy (SERS) detection platform that serves as a rapid, label‐free point of care diagnostics device. Highly dense Au nanopearl arrays with narrow gap distances are formed directly through thermal evaporation on hydrophobic cellulose fibers to achieve excellent portable SERS performance (enhancement factor: 3.9 x 1011; detection limit: sub‐femtomolar single molecule level; reproductivity relative standard deviation ≤ 4%).
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The development of sodium-glucose transporter 2 inhibitor (SGLT2i) broadens the therapeutic strategies in treating diabetes mellitus. By inhibiting sodium and glucose reabsorption from the proximal ...tubules, the improvement in insulin resistance and natriuresis improved the cardiovascular mortality in diabetes mellitus (DM) patients. It has been known that SGLT2i also provided renoprotection by lowering the intraglomerular hypertension by modulating the pre- and post- glomerular vascular tone. The application of SGLT2i also provided metabolic and hemodynamic benefits in molecular aspects. The recent DAPA-CKD trial and EMPEROR-Reduced trial provided clinical evidence of renal and cardiac protection, even in non-DM patients. Therefore, the aim of the review is to clarify the hemodynamic and metabolic modulation of SGLT2i from the molecular mechanism.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The population of patients with hepatocellular carcinoma (HCC) overlaps to a high degree with those for chronic kidney disease (CKD) and end-stage renal disease (ESRD). The degrees of renal ...dysfunction vary, from the various stages of CKD to dialysis-dependent ESRD, which often affects the prognosis and treatment choice of patients with HCC. In addition, renal dysfunction makes treatment more difficult and may negatively affect treatment outcomes. This study summarized the possible causes of the high comorbidity of HCC and renal dysfunction. The possible mechanisms of CKD causing HCC involve uremia itself, long-term dialysis status, immunosuppressive agents for postrenal transplant status, and miscellaneous factors such as hormone alterations and dysbiosis. The possible mechanisms of HCC affecting renal function include direct tumor invasion and hepatorenal syndrome. Finally, we categorized the risk factors that could lead to both HCC and CKD into four categories: Environmental toxins, viral hepatitis, metabolic syndrome, and vasoactive factors. Both CKD and ESRD have been reported to negatively affect HCC prognosis, but more research is warranted to confirm this. Furthermore, ESRD status itself ought not to prevent patients receiving aggressive treatments. This study then adopted the well-known Barcelona Clinic Liver Cancer guidelines as a framework to discuss the indicators for each stage of HCC treatment, treatment-related adverse renal effects, and concerns that are specific to patients with pre-existing renal dysfunction when undergoing aggressive treatments against CKD and ESRD. Such aggressive treatments include liver resection, simultaneous liver kidney transplantation, radiofrequency ablation, and transarterial chemoembolization. Finally, focusing on patients unable to receive active treatment, this study compiled information on the latest systemic pharmacological therapies, including targeted and immunotherapeutic drugs. Based on available clinical studies and Food and Drug Administration labels, this study details the drug indications, side effects, and dose adjustments for patients with renal dysfunction. It also provides a comprehensive review of information on HCC patients with renal dysfunction from disease onset to treatment.
Studies into the association between hypertensive disorders during pregnancy and end-stage renal disease are limited. We investigated the risk of end-stage renal disease after delivery among women ...with hypertensive disorders during pregnancy.
We used insurance claims data from 1998 to 2009 to identify 26,651 women aged 19-40 years old who experienced hypertensive disorders during pregnancy; these women had no history of hypertension, diabetes, kidney disease or lupus. We also randomly selected 213,397 women without hypertensive disorders during pregnancy as a comparison cohort; the frequency was matched by age and index year of pregnancy. We compared the incidence of end-stage renal disease in the 2 cohorts. We calculated hazard ratios (HRs) and 95% confidence intervals (CIs) after controlling for demographic and clinical factors.
Women with hypertensive disorders during pregnancy had a greater risk of chronic kidney disease and end-stage renal disease, with adjusted HRs of 9.38 (95% CI 7.09-12.4) and 12.4 (95% CI 8.54-18.0), respectively, after controlling for urban status, coronary artery disease, congestive heart failure, hyperlipidemia and abruption. The HR for end-stage renal disease was 2.72 (95% CI 1.76-4.22) after we also controlled for hypertension and diabetes. Women with preeclampsia or eclampsia had a higher risk of end-stage renal disease (adjusted HR 14.0, 95% CI 9.43-20.7) than women who had gestational hypertension only (adjusted HR 9.03, 95% CI 5.20-15.7).
Women with hypertensive disorders during pregnancy were at a high risk of end-stage renal disease. The risk was much greater for women who had preeclampsia or eclampsia than those who had gestational hypertension only.
•The efficiency of IGZO LAPS has been improved by square wave and a duty cycle of 40% compared to sine wave in a setting of 365 nm LED.•Photocurrent and power consumption are 42.2 % higher and 16.2 ...% lower than the conventional setup of a sine wave.•The drawbacks of 365 nm LED for IGZO LAPS can be reduced by 405 and 435 nm LED.•A laser light source with a wavelength of 405 nm is proven for a better spatial resolution in the 2D image by the small spot size.•The pH sensitivity and linearity are 60.1 mV/pH and 99.9 % in a case of the duty cycle 40 % of 405 nm LED..
Indium Gallium Zinc Oxide (IGZO) on Indium Tin Oxide (ITO) glass has been applied as the semiconductor substrate of a light-addressable potentiometric sensor (LAPS) with the advantages of immunity to room light inference and high photocurrent. For the first time, investigations into this IGZO LAPS including two-dimensional (2D) chemical imaging and reduction of the potential biorelative damage induced by the requirement of an ultraviolet (UV) light source are presented in this study. For the spatial resolution, a smaller aperture for the light spot provided by a light emitting diode (LED) makes the photocurrent decrease. To overcome this natural limitation, the type of AC modulation of light source is changed from a sine wave to a square wave with different duty cycles. The photocurrent and power consumption of a 365 nm LED with square wave and a duty cycle of 40 % are 42.2 % higher and 16.2 % lower than those of the conventional setup of a sine wave, respectively. The pH sensitivity, linearity, hysteresis and drift are comparable. The illumination wavelengths of 365, 405 and 435 nm are studied for photoresponse. 405 nm illumination with acceptable pH sensing performance can be suggested for IGZO LAPS for less bio damage concern. Additionally, a laser with a wavelength of 405 nm with spot size of 25 μm and scanning step of 2 μm is proven to have a clear pattern recognition down to 50 μm in 2D image. Further optimization of the spot size of the laser, thickness and composition of IGZO are suggested for better spatial resolution.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The aim of the study is to investigate the effects of icodextrin on the risks of death, technique failure and the first episode of peritonitis in peritoneal dialysis (PD) patients.
From medical ...records of a medical center in Taiwan, a total of 725 newly diagnosed end-stage kidney disease patients receiving PD for at least 90 days from January 1, 2007 to December 31, 2018 were identified. These patients were grouped as 190 icodextrin users and 535 non-users. Users were defined as utilization of icodextrin for ≥ 50% of their PD duration. The use of icodextrin was considered a time-varying exposure in the Cox proportional hazard model. The risks of death, technique failure and the first episode of peritonitis were compared between two cohorts by the end of 2018.
Compared to the non-users, the icodextrin users had significant lower risks of mortality (6.5 vs.7.2 per 100 person-years; adjusted HR = 0.62, 95% CI = 0.42-0.91) and technique failure (12.7 vs. 15.2 per 100 person-years; adjusted HR = 0.61, 95% CI = 0.47-0.81), and the first peritonitis episode (5.0 vs. 17.0 per 100 person-years; adjusted HR = 0.22, 95% CI = 0.14-0.35). The risk of peritonitis reduced further in icodextrin users with diabetes and with cardiovascular disease.
Icodextrin was associated with lower risks of mortality, technique failure, and the first episode of peritonitis.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
This study analysed the clinical patterns and outcomes of elderly patients with organophosphate intoxication. A total of 71 elderly patients with organophosphate poisoning were seen between ...2008 and 2017. Patients were stratified into two subgroups: survivors (n = 57) or nonsurvivors (n = 14). Chlorpyrifos accounted for 33.8% of the cases, followed by methamidophos (12.7%) and mevinphos (11.3%). Mood, adjustment and psychotic disorder were noted in 39.4%, 33.8% and 2.8% of patients, respectively. All patients were treated with atropine and pralidoxime therapies. Acute cholinergic crisis developed in all cases (100.0%). The complications included respiratory failure (52.1%), aspiration pneumonia (50.7%), acute kidney injury (43.7%), severe consciousness disturbance (25.4%), shock (14.1%) and seizures (4.2%). Some patients also developed intermediate syndrome (15.5%) and delayed neuropathy (4.2%). The nonsurvivors suffered higher rates of hypotension (
P
< 0.001), shock (
P
< 0.001) and kidney injury (
P
= 0.001) than survivors did. Kaplan–Meier analysis indicated that patients with shock suffered lower cumulative survival than did patients without shock (log-rank test,
P
< 0.001). In a multivariate-Cox-regression model, shock was a significant predictor of mortality after intoxication (odds ratio 18.182, 95% confidence interval 2.045–166.667,
P
= 0.009). The mortality rate was 19.7%. Acute cholinergic crisis, intermediate syndrome, and delayed neuropathy developed in 100.0%, 15.5%, and 4.2% of patients, respectively.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Background
Alveolar bone and cementum share many biological and developmental similarities. The mineralizing effect of calcitriol has been previously reported. Yet, its cemento‐inductivity has not ...been confirmed. This study evaluated the potential cemento‐inductivity effect of calcitriol and enamel matrix derivative (EMD) on human periodontal ligament‐derived cells (hPDLCs).
Methods
The hPDLCs obtained from extracted third molars or premolars were cultured with calcitriol, or EMD. Cementogenic gene expression was examined using real‐time quantitative reverse transcription polymerase chain reaction. Expression analysis also included cementoblast‐specific markers, cementum protein 1 (CEMP1), cementum attachment protein (CAP), and recently reported cementoblast‐enriched genes, secreted frizzled related protein 1 (SFRP1), and Dickkopf‐related protein 1 (DKK1). Mineralization capacities were evaluated by alkaline phosphatase (ALP) activity, Alizarin Red, and Von Kossa staining followed by scanning electron microscope imaging and element mapping.
Results
Among tested conditions, 10 nM calcitriol enhanced most cementogenic gene expression, transforming growth factor‐β1, bone morphogenetic proteins (BMP‐2 and BMP‐4), core‐binding factor subunit alpha‐1/Runt‐related transcription factor 2, Type I collagen, ALP, bone sialoprotein, osteopontin), osteocalcin, CEMP1, and CAP, and Wnt signaling negative modulators, SFRP1 and DKK1, along with highest ALP activity and mineralization formation in hPDLCs. However, only moderate CEMP1 protein was observed. In contrast, EMD stimulated stronger CEMP1 and CAP protein, but presented weaker mineralization capacity, hinting at the possibility that strong stimulation of mineralization might dominate cemetogenic specific factors and vice versa.
Conclusions
Calcitriol demonstrated not only great osteoinductivity, but also the potential to induce cementogenic gene expression by initiating hPDLC differentiation and promoting mineralization. Compared with calcitriol, EMD promoted cemento‐inductivity in hPDLCs at a later time point via highly expressed CEMP1 and CAP protein, but with less mineralization. Thus, calcitriol and EMD could provide differential enhancement of cemento‐induction and mineralization, likely acting at various differentiation stages.
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BFBNIB, CMK, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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