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%).
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.
•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.
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.
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.
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.
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.
•A fully integrated system and user interface, named Mirror-LAPS, was established for bioimaging.•By means of a FPGA, the volume of this Mirror-LAPS system is only 11 % than conventional one.•The ...location, area, and resolution of pixels of sensing image are easily, quickly and flexibly adjusted.•The cellular metabolism of HK2 cells for different cell numbers and glucose concentrations is virtually demonstrated.
A fully integrated system and user interface, named Mirror-LAPS, was established for chemical imaging of diffusion-based reactions and bioimaging, e.g., cellular metabolism imaging in situ, with advantages of portability, real-time monitoring and flexible control. By means of a field programmable gate array (FPGA), a minimized drive circuit and an illumination path integrated into the hardware, the volume and cost of this Mirror-LAPS system are only 11 % and 75 %, respectively, those of the conventional LAPS system. 2D images can be easily constructed based on the combination of the measured photocurrent with automatic digitization and recorded coordinates for each pixel in the frame. The time to image one pixel under the optimized parameters with a periods per pixel (PPP) of 64 is approximately 6.6 ms. The location, area, and resolution of pixels can be easily, quickly and flexibly adjusted in the user interface to obtain 2D images and a real-time video. The cellular metabolism of HK2 cellsfor different cell numbers and glucose concentrations is virtually demonstrated by this Mirror-LAPS system by the color changes in 2D images for the first time, which could provide a reliable platform in a cell culturing space for cell-based research.
Osteoporosis is a systemic skeletal disorder characterized by a decrease in bone mass and microarchitectural deterioration of bone tissue. The World Health Organization has defined osteoporosis as a ...decrease in bone mass (50%) and bony quality (50%). Vitamin D, a steroid hormone, is crucial for skeletal health and in mineral metabolism. Its direct action on osteoblasts and osteoclasts and interaction with nonskeletal tissues help in maintaining a balance between bone turnover and bone growth. Vitamin D affects the activity of osteoblasts, osteoclasts, and osteocytes, suggesting that it affects bone formation, bone resorption, and bone quality. At physiological concentrations, active vitamin D maintains a normal rate of bone resorption and formation through the RANKL/OPG signal. However, active vitamin D at pharmacological concentration inhibits bone resorption at a higher rate than that of bone formation, which influences the bone quality and quantity. Nutritional vitamin D rather than active vitamin D activates osteoblasts and maintains serum 25(OH)D3 concentration. Despite many unanswered questions, much data support nutritional vitamin D use in osteoporosis patients. This article emphasizes the role of nutritional vitamin D replacement in different turnover status (high or low bone turnover disorders) of osteoporosis together with either anti-resorptive (Bisphosphonate, Denosumab et.) or anabolic (Teriparatide) agents when osteoporosis persists.
•Osteoporosis is composed by quality and quantity of bone mass.•Treatment for osteoporosis should be focused on the bone turnover rate in order to normalize the bone remodeling.•Nutritional vitamin D is an important regulator to maintain the bone remodeling due to its pleotropic effect.
Background: The treatment modalities and outcomes of geriatric patients with hepatocellular carcinoma (HCC) remain controversial. This retrospective observational cohort study compared the outcomes ...of HCC between geriatric and younger patients. Methods: The medical records of patients with HCC managed between January 2001 and December 2017 were retrieved from the Chang Gung Memorial Hospital Research Database. Patients were stratified by age into two groups: a geriatric group (65−75 years) and a younger group (<65 years). The two groups were matched through 1:2 propensity score matching (PSM) according to sex, cardiovascular disease, cerebrovascular attack, diabetes mellitus, cirrhosis, hepatitis, and hypertension. Results: Of the 11,033 patients with HCC, 2147 patients aged 65−75 years and 4294 patients aged <65 years were identified after 1:2 PSM. The Kaplan−Meier model revealed that the HCC outcomes in patients older than 65 years were not significantly different after 3 years (p = 0.060). Consistent results were also obtained when the laboratory data associated with HCC incidence were included in the Fine−Gray competing risk model after 1:2 PSM (p = 0.1695). The major risk factors for HCC survival were systemic immune-inflammation index (SII) ≥ 610 × 109 cells/L, advanced tumor stage, and model for end-stage liver disease (MELD) score, etc. Conclusion: Age was not an independent factor for mortality in patients with HCC in the first 3 years. Geriatric patients with HCC should be as aggressively managed as younger patients.
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