Fourier-transform microwave spectroscopy of the ClSO radical.

Pure rotational transitions of the ClSO radical have been observed by Fourier-transform microwave spectroscopy. a-type and b-type transitions, for both 35Cl and 37Cl isotopologues, were detected, and the observed very complicated fine and hyperfine components were assigned well. The intensities of the observed spectra of the two isotopologues correspond to the ratio of the isotope abundances of 35Cl and 37Cl. A total of 21 molecular constants were determined precisely for both 35ClSO and 37ClSO, including the rotational constants, centrifugal distortion constants, electronic spin-rotation constants, nuclear spin-rotation constants, magnetic hyperfine constants, and quadrupole coupling constants of chlorine. The molecular constants show ClSO to have the 2A'' electronic ground state with an out-of-plane unpaired electron. The spin density of the chlorine atom is about 10.6%, which is similar to that of the fluorine atom for FSO, about 8%. Results of the ClSO radical are compared with those of other triatomic radicals with similar structures, the XSS, XSO, and XOO radicals with X = H, F, and Cl, leading to a conclusion that the ClSO radical is more like FSO, but fairly different from the FOO and ClOO radicals.

Application of Machine Learning Techniques to Development of Emergency Medical Rapid Triage Prediction Models in Acute Care.

Given the critical and complex features of medical emergencies, it is essential to develop models that enable prompt and suitable clinical decision-making based on considerable information. Emergency nurses are responsible for categorizing and prioritizing injuries and illnesses on the frontlines of the emergency room. This study aims to create an Emergency Medical Rapid Triage and Prediction Assistance model using electronic medical records and machine learning techniques. Patient information was retrieved from the emergency department of a large regional teaching hospital in Taiwan, and five supervised learning techniques were used to construct classification models for predicting critical outcomes. Of these models, the model using logistic regression had superior prediction performance, with an F1 score of 0.861 and an area under the receiver operating characteristic curve of 0.855. The Emergency Medical Rapid Triage and Prediction Assistance model demonstrated superior performance in predicting intensive care and hospitalization outcomes compared with the Taiwan Triage and Acuity Scale and three clinical early warning tools. The proposed model has the potential to assist emergency nurses in executing challenging triage assessments and emergency teams in treating critically ill patients promptly, leading to improved clinical care and efficient utilization of medical resources.

Precision Heart Rate Estimation Using a PPG Sensor Patch Equipped with New Algorithms of Pre-Quality Checking and Hankel Decomposition.

A new method for accurately estimating heart rates based on a single photoplethysmography (PPG) signal and accelerations is proposed in this study, considering motion artifacts due to subjects' hand motions and walking. The method comprises two sub-algorithms: pre-quality checking and motion artifact removal (MAR) via Hankel decomposition. PPGs and accelerations were collected using a wearable device equipped with a PPG sensor patch and a 3-axis accelerometer. The motion artifacts caused by hand movements and walking were effectively mitigated by the two aforementioned sub-algorithms. The first sub-algorithm utilized a new quality-assessment criterion to identify highly noise-contaminated PPG signals and exclude them from subsequent processing. The second sub-algorithm employed the Hankel matrix and singular value decomposition (SVD) to effectively identify, decompose, and remove motion artifacts. Experimental data collected during hand-moving and walking were considered for evaluation. The performance of the proposed algorithms was assessed using the datasets from the IEEE Signal Processing Cup 2015. The obtained results demonstrated an average error of merely 0.7345 ± 8.1129 beats per minute (bpm) and a mean absolute error of 1.86 bpm for walking, making it the second most accurate method to date that employs a single PPG and a 3-axis accelerometer. The proposed method also achieved the best accuracy of 3.78 bpm in mean absolute errors among all previously reported studies for hand-moving scenarios.

Enhanced Thermal Conducting Behavior of Pressurized Graphene-Silver Flake Composites.

Modern electronics continue to shrink down the sizes while becoming more and more powerful. To improve heat dissipation of electronics, fillers used in the semiconductor packaging process need to possess both high electrical and thermal conductivity. Graphene is known to improve thermal conductivity but suffers from van der Waals interactions and thus poor processibility. In this study, we wrapped silver microflakes with graphene sheets, which can enable intercoupling of phonon- and electron-based thermal transport, to improve the thermal conductivity. Using just 1.55 wt % graphene for wrapping can achieve a 2.64-times greater thermal diffusivity (equivalent to 254.196 ± 10.123 W/m·K) over pristine silver flakes. Graphene-wrapped silver flakes minimize the increase of electrical resistivity, which is one-order higher (1.4 × 10-3 Ω·cm) than the pristine flakes (5.7 × 10-4 Ω·cm). Trace contents of wrapped graphene (<1.55 wt %) were found to be enough to bridge the void between Ag flakes, and this enhances the thermal conductivity. Graphene loading at 3.76 wt % (beyond the threshold of 1.55 wt %) results in the significant graphene aggregation that decreases thermal diffusivity to as low as 16% of the pristine Ag filler. This work recognizes that suitable amounts of graphene wrapping can enhance heat dissipation, but too much graphene results in unwanted aggregation that hinders thermal conducting performance.

Proteomic characterization of arsenic and cadmium exposure in bladder cells.

RATIONALE: Accumulating evidence has linked prolonged exposure to heavy metals to cancer occurrence in the urinary system. However, the specific biological mechanisms responsible for the association of heavy metals with the unusually high incidence of upper tract urothelial carcinoma in Taiwan are complex and incompletely understood. METHODS: To elucidate the specific biological mechanism and identify molecular indicators of the unusually high association of upper tract urothelial carcinoma with heavy metal exposure, protein expression following the treatment of T24 human bladder carcinoma and RT4 human bladder papilloma cell line models with arsenic (As) and cadmium (Cd) was studied. Proteomic changes in these cell models were integrated with data from a human bladder cancer (BLCA) tissue proteome to identify possible protein indicators of heavy metal exposure. RESULTS: After mass spectrometry based proteomic analysis and verification by Western blotting procedures, we identified 66 proteins that were up-regulated and 92 proteins that were down-regulated in RT4 cell extracts after treatment with As or Cd. Some 52 proteins were up-regulated and 136 proteins were down-regulated in T24 cell extracts after treatment with Cd. We further confirmed that down-expression of the PML (promyelocytic leukemia) protein was sustained for at least 75 days after exposure of bladder cells to As. Dysregulation of these cellular proteins by As was associated with three biological pathways. Immunohistochemical analyses of paraffin-embedded BLCA tissue slides confirmed that PML protein expression was decreased in BLCA tumor cells compared with adjacent noncancerous epithelial cells. CONCLUSIONS: These data suggest that PML may play an important role in the pathogenesis of BLCA and may be an indicator of heavy metal exposure in bladder cells.

Development of a Multiplexed Liquid Chromatography Multiple-Reaction-Monitoring Mass Spectrometry (LC-MRM/MS) Method for Evaluation of Salivary Proteins as Oral Cancer Biomarkers.

Multiple (selected) reaction monitoring (MRM/SRM) of peptides is a growing technology for target protein quantification because it is more robust, precise, accurate, high-throughput, and multiplex-capable than antibody-based techniques. The technique has been applied clinically to the large-scale quantification of multiple target proteins in different types of fluids. However, previous MRM-based studies have placed less focus on sample-preparation workflow and analytical performance in the precise quantification of proteins in saliva, a noninvasively sampled body fluid. In this study, we evaluated the analytical performance of a simple and robust multiple reaction monitoring (MRM)-based targeted proteomics approach incorporating liquid chromatography with mass spectrometry detection (LC-MRM/MS). This platform was used to quantitatively assess the biomarker potential of a group of 56 salivary proteins that have previously been associated with human cancers. To further enhance the development of this technology for assay of salivary samples, we optimized the workflow for salivary protein digestion and evaluated quantification performance, robustness and technical limitations in analyzing clinical samples. Using a clinically well-characterized cohort of two independent clinical sample sets (total n = 119), we quantitatively characterized these protein biomarker candidates in saliva specimens from controls and oral squamous cell carcinoma (OSCC) patients. The results clearly showed a significant elevation of most targeted proteins in saliva samples from OSCC patients compared with controls. Overall, this platform was capable of assaying the most highly multiplexed panel of salivary protein biomarkers, highlighting the clinical utility of MRM in oral cancer biomarker research.

Ocular Drug Delivery: Role of Degradable Polymeric Nanocarriers for Ophthalmic Application.

Ocular drug delivery has been a major challenge for clinical pharmacologists and biomaterial scientists due to intricate and unique anatomical and physiological barriers in the eye. The critical requirement varies from anterior and posterior ocular segments from a drug delivery perspective. Recently, many new drugs with special formulations have been introduced for targeted delivery with modified methods and routes of drug administration to improve drug delivery efficacy. Current developments in nanoformulations of drug carrier systems have become a promising attribute to enhance drug retention/permeation and prolong drug release in ocular tissue. Biodegradable polymers have been explored as the base polymers to prepare nanocarriers for encasing existing drugs to enhance the therapeutic effect with better tissue adherence, prolonged drug action, improved bioavailability, decreased toxicity, and targeted delivery in eye. In this review, we summarized recent studies on sustained ocular drug/gene delivery and emphasized on the nanocarriers made by biodegradable polymers such as liposome, poly lactic-co-glycolic acid (PLGA), chitosan, and gelatin. Moreover, we discussed the bio-distribution of these nanocarriers in the ocular tissue and their therapeutic applications in various ocular diseases.

Comparative Tissue Proteomics of Microdissected Specimens Reveals Novel Candidate Biomarkers of Bladder Cancer.

More than 380,000 new cases of bladder cancer are diagnosed worldwide, accounting for ∼150,200 deaths each year. To discover potential biomarkers of bladder cancer, we employed a strategy combining laser microdissection, isobaric tags for relative and absolute quantitation labeling, and liquid chromatography-tandem MS (LC-MS/MS) analysis to profile proteomic changes in fresh-frozen bladder tumor specimens. Cellular proteins from four pairs of surgically resected primary bladder cancer tumor and adjacent nontumorous tissue were extracted for use in two batches of isobaric tags for relative and absolute quantitation experiments, which identified a total of 3220 proteins. A DAVID (database for annotation, visualization and integrated discovery) analysis of dysregulated proteins revealed that the three top-ranking biological processes were extracellular matrix organization, extracellular structure organization, and oxidation-reduction. Biological processes including response to organic substances, response to metal ions, and response to inorganic substances were highlighted by up-expressed proteins in bladder cancer. Seven differentially expressed proteins were selected as potential bladder cancer biomarkers for further verification. Immunohistochemical analyses showed significantly elevated levels of three proteins-SLC3A2, STMN1, and TAGLN2-in tumor cells compared with noncancerous bladder epithelial cells, and suggested that TAGLN2 could be a useful tumor tissue marker for diagnosis (AUC = 0.999) and evaluating lymph node metastasis in bladder cancer patients. ELISA results revealed significantly increased urinary levels of both STMN1 and TAGLN2 in bladder cancer subgroups compared with control groups. In comparisons with age-matched hernia urine specimens, urinary TAGLN2 in bladder cancer samples showed the largest fold change (7.13-fold), with an area-under-the-curve value of 0.70 (p < 0.001, n = 205). Overall, TAGLN2 showed the most significant overexpression in individual bladder cancer tissues and urine specimens, and thus represents a potential biomarker for noninvasive screening for bladder cancer. Our findings highlight the value of bladder tissue proteome in providing valuable information for future validation studies of potential biomarkers in urothelial carcinoma.

Over-expression of cofilin-1 suppressed growth and invasion of cancer cells is associated with up-regulation of let-7 microRNA.

Cofilin-1, a non-muscle isoform of actin regulatory protein that belongs to the actin-depolymerizing factor (ADF)/cofilin family is known to affect cancer development. Previously, we found that over-expression of cofilin-1 suppressed the growth and invasion of human non-small cell lung cancer (NSCLC) cells in vitro. In this study, we further investigated whether over-expression of cofilin-1 can suppress tumor growth in vivo, and performed a microRNA array analysis to better understand whether specific microRNA would be involved in this event. The results showed that over-expression of cofilin-1 suppressed NSCLC tumor growth using the xenograft tumor model with the non-invasive reporter gene imaging modalities. Additionally, cell motility and invasion were significantly suppressed by over-expressed cofilin-1, and down-regulation of matrix metalloproteinase (MMPs) -1 and -3 was concomitantly detected. According to the microRNA array analysis, the let-7 family, particularly let-7b and let-7e, were apparently up-regulated among 248 microRNAs that were affected after over-expression of cofilin-1 up to 7 days. Knockdown of let-7b or let-7e using chemical locked nucleic acid (LNA) could recover the growth rate and the invasion of cofilin-1 over-expressing cells. Next, the expression of c-myc, LIN28 and Twist-1 proteins known to regulate let-7 were analyzed in cofilin-1 over-expressing cells, and Twist-1 was significantly suppressed under this condition. Up-regulation of let-7 microRNA by over-expressed cofilin-1 could be eliminated by co-transfected Twist-1 cDNA. Taken together, current data suggest that let-7 microRNA would be involved in over-expression of cofilin-1 mediated tumor suppression in vitro and in vivo.

Analyzing Monthly Blood Test Data to Forecast 30-Day Hospital Readmissions among Maintenance Hemodialysis Patients.

Background: The increase in the global population of hemodialysis patients is linked to aging demographics and the prevalence of conditions such as arterial hypertension and diabetes mellitus. While previous research in hemodialysis has mainly focused on mortality predictions, there is a gap in studies targeting short-term hospitalization predictions using detailed, monthly blood test data. Methods: This study employs advanced data preprocessing and machine learning techniques to predict hospitalizations within a 30-day period among hemodialysis patients. Initial steps include employing K-Nearest Neighbor (KNN) imputation to address missing data and using the Synthesized Minority Oversampling Technique (SMOTE) to ensure data balance. The study then applies a Support Vector Machine (SVM) algorithm for the predictive analysis, with an additional enhancement through ensemble learning techniques, in order to improve prediction accuracy. Results: The application of SVM in predicting hospitalizations within a 30-day period among hemodialysis patients resulted in an impressive accuracy rate of 93%. This accuracy rate further improved to 96% upon incorporating ensemble learning methods, demonstrating the efficacy of the chosen machine learning approach in this context. Conclusions: This study highlights the potential of utilizing machine learning to predict hospital readmissions within a 30-day period among hemodialysis patients based on monthly blood test data. It represents a significant leap towards precision medicine and personalized healthcare for this patient group, suggesting a paradigm shift in patient care through the proactive identification of hospitalization risks.

Risk factors for hemorrhagic complications following robotic-assisted partial nephrectomy.

BACKGROUND: The aim of this study was to analyze the risk factors for hemorrhagic complications in patients who underwent robotic-assisted partial nephrectomy. METHODS: We retrospectively reviewed the records of 260 patients who underwent robotic-assisted partial nephrectomy. Hemorrhagic complications were defined as bleeding, hematoma, or arteriovenous fistula requiring hemostatic medication, blood transfusion, or therapeutic intervention. Hemorrhagic complications were graded according to the modified Clavien classification system, and the hemorrhagic complication group comprised only those complications with Clavien grade II or higher. Thereafter, we investigated the presence of any relevant association between perioperative factors and hemorrhagic complications. RESULTS: Of 260 patients included in the study, 32 (12.3%) had hemorrhagic complications. The postoperative hemoglobin level was significantly lower in the hemorrhagic complication group than in the group without complications. The hemorrhagic complication group had significantly more essential blood loss and a significantly longer length of hospital stay. In the univariate analysis, type 2 diabetes mellitus, Radius-scores tumor size as maximal diameter exophytic/endophytic properties of the tumor nearness of the deepest portion of the tumor to the collecting system or renal sinus anterior (a)/posterior (p) descriptor location relative to the polar line., sum of the renal size plus renal sinus involvement in the PADUA score is a simple anatomical system that can be used to predict the risk of surgical and medical perioperative complications in patients undergoing open NSS, prolonged console time (>180 minutes), prolonged warm ischemic time (>25 minutes), and method of pedicle control were statistically significant risk factors. In the multivariate logistic regression analysis, warm ischemic time >25 minutes was the only significant risk factor for hemorrhagic complications (odds ratio, 3.51; 95% confidence interval, 1.28-9.59; p = 0.01). CONCLUSION: Patients who undergo robotic-assisted partial nephrectomy with a warm ischemic time >25 minutes are significantly more likely to have hemorrhagic complications and should hence receive careful perioperative follow-up.

The Influence of the COVID-19 Pandemic on Emergency Medical Services to Out-of-Hospital Cardiac Arrests in a Low-Incidence Urban City: An Observational Epidemiological Analysis.

The Emergency Medical Services (EMS) system faced overwhelming challenges during the coronavirus disease 2019 (COVID-19) pandemic. However, further information is required to determine how the pandemic affected the EMS response and the clinical outcomes of out-of-hospital cardiac arrest (OHCA) patients in COVID-19 low-incidence cities. A retrospective study was conducted in Chiayi, Taiwan, a COVID-19 low-incidence urban city. We compared the outcomes and rescue records before (2018-2019) and during (2020-2021) the COVID-19 pandemic. A total of 567 patients before and 497 during the pandemic were enrolled. Multivariate analysis revealed that the COVID-19 pandemic had no significant influence on the achievement of return of spontaneous circulation (ROSC) and sustained ROSC but was associated with lower probabilities of survival to discharge (aOR = 0.43, 95% CI: 0.21-0.89, p = 0.002) and discharge with favorable neurologic outcome among OHCA patients (aOR = 0.35, 95% CI: 0.16-0.77, p = 0.009). Patients' ages and OHCA locations were also discovered to be independently related to survival results. The overall impact of longer EMS rescue times on survival outcomes during the pandemic was not significant, with an exception of the specific group that experienced prolonged rescue times (total EMS time > 21 min).

REST-repressed lncRNA LINC01801 induces neuroendocrine differentiation in prostate cancer via transcriptional activation of autophagy.

The association between REST reduction and the development of neuroendocrine prostate cancer (NEPC), a novel drug-resistant and lethal variant of castration-resistant prostate cancer (CRPC), is well established. To better understand the mechanisms underlying this process, we aimed to identify REST-repressed long noncoding RNAs (lncRNAs) that promote neuroendocrine differentiation (NED), thus facilitating targeted therapy-induced resistance. In this study, we used data from REST knockdown RNA sequencing combined with siRNA screening to determine that LINC01801 was upregulated and played a crucial role in NED in prostate cancer (PCa). Using The Cancer Genome Atlas (TCGA) prostate adenocarcinoma database and CRPC samples collected in our laboratory, we demonstrated that LINC01801 expression is upregulated in NEPC. Functional experiments revealed that overexpression of LINC01801 had a slight stimulatory effect on the NED of LNCaP cells, while downregulation of LINC01801 significantly inhibited the induction of NED. Mechanistically, LINC01801 is transcriptionally repressed by REST, and transcriptomic analysis revealed that LINC01801 preferentially affects the autophagy pathway. LINC01801 was found to function as a competing endogenous RNA (ceRNA) to regulate the expression of autophagy-related genes by sponging hsa-miR-6889-3p in prostate cancer cells. In conclusion, our data expand the current knowledge of REST-induced NED and highlight the contribution of the REST-LINC01801-hsa-miR-6889-3p axis to autophagic induction, which may provide promising avenues for therapeutic opportunities.

Comparative and targeted proteomic analyses of urinary microparticles from bladder cancer and hernia patients.

Bladder cancer is a common urologic cancer whose incidence continues to rise annually. Urinary microparticles are an attractive material for noninvasive bladder cancer biomarker discovery. In this study, we applied isotopic dimethylation labeling coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS) to discover bladder cancer biomarkers in urinary microparticles isolated from hernia (control) and bladder cancer patients. This approach identified 2964 proteins based on more than two distinct peptides, of which 2058 had not previously been reported as constituents of human urine exosomes/microparticles. A total of 107 differentially expressed proteins were identified as candidate biomarkers. Differences in the concentrations of 29 proteins (41 signature peptides) were precisely quantified by LC-MRM/MS in 48 urine samples of bladder cancer, hernia, and urinary tract infection/hematuria. Concentrations of 24 proteins changed significantly (p<0.05) between bladder cancer (n=28) and hernia (n=12), with area-under-the-curve values ranging from 0.702 to 0.896. Finally, we quantified tumor-associated calcium-signal transducer 2 (TACSTD2) in raw urine specimens (n=221) using a commercial ELISA and confirmed its potential value for diagnosis of bladder cancer. Our study reveals a strong association of TACSTD2 with bladder cancer and highlights the potential of human urinary microparticles in the noninvasive diagnosis of bladder cancer.

Validation of ICD-9-CM and ICD-10-CM Diagnostic Codes for Identifying Patients with Out-of-Hospital Cardiac Arrest in a National Health Insurance Claims Database.

Purpose: Taiwan's national health insurance (NHI) database is a valuable resource for large-scale epidemiological and long-term survival research for out-of-hospital cardiac arrest (OHCA). We developed and validated case definition algorithms for OHCA based on the International Classification of Diseases (ICD) diagnostic codes and billing codes for NHI reimbursement. Patients and Methods: Claims data and medical records of all emergency department visits from 2010 to 2020 were retrieved from the hospital's research-based database. Death-related diagnostic codes and keywords were used to identify potential OHCA cases, which were ascertained by chart reviews. We tested the performance of the developed OHCA algorithms and validated them on an external dataset. Results: The algorithm defining OHCA as any cardiac arrest (CA)-related ICD code in the first three diagnosis fields performed the best with a sensitivity of 89.5% (95% confidence interval [CI], 88.2-90.7%), a positive predictive value (PPV) of 90.6% (95% CI, 89.4-91.8%), and a kappa value of 0.900 (95% CI, 0.891-0.909). The second-best algorithm consists of any CA-related ICD code in any diagnosis field with a billing code for triage acuity level 1, achieving a sensitivity of 85.6% (95% CI, 84.1-87.0%), a PPV of 93.6% (95% CI, 92.5-94.5), and a kappa value of 0.894 (95% CI, 0.884-0.903). Both algorithms performed well in external validation. In subgroup analyses, the former algorithm performed the best in adult patients, outpatient claims, and during the ICD-9 era. The latter algorithm performed the best in the inpatient claims and during the ICD-10 era. The best algorithm for identifying pediatric OHCAs was any CA-related ICD code in the first three diagnosis fields with a billing code for triage acuity level 1. Conclusion: Our results may serve as a reference for future OHCA studies using the Taiwan NHI database.

Volatility in coral cover erodes niche structure, but not diversity, in reef fish assemblages.

The world's coral reefs are experiencing increasing volatility in coral cover, largely because of anthropogenic environmental change, highlighting the need to understand how such volatility will influence the structure and dynamics of reef assemblages. These changes may influence not only richness or evenness but also the temporal stability of species' relative abundances (temporal beta-diversity). Here, we analyzed reef fish assemblage time series from the Great Barrier Reef to show that, overall, 75% of the variance in abundance among species was attributable to persistent differences in species' long-term mean abundances. However, the relative importance of stochastic fluctuations in abundance was higher on reefs that experienced greater volatility in coral cover, whereas it did not vary with drivers of alpha-diversity. These findings imply that increased coral cover volatility decreases temporal stability in relative abundances of fishes, a transformation that is not detectable from static measures of biodiversity.

Sequential detection of dopamine and L-DOPA by a 2,3-dopa-dioxygenase from Streptomyces sclerotialus.

A variety of enzyme-based colorimetric biosensors have been developed for clinical practice; however, these methods will only become cost-effective when they are able to process multiple samples with a high degree of sensitivity. In this study, a novel heat-stable enzyme, 2,3-dopa-dioxygenase from the thermophilic bacterium Streptomyces sclerotialus (SsDDO), was used in the development of a protein- and cell-based biosensor for the detection of L-DOPA for the first time. SsDDO catalyzes the oxidative cleavage of L-DOPA forms linear semialdehyde (AHMS) and cyclizes to a 3-carboxy-3-hydroxyallylidene-3,4-dihydropyrrole-2-carboxylic acid (CHAPCA). We next derivatized CHAPCA by reacting with 3-aminobenzoic acid (MABA) to yield a red-fluorescent pigment. Overall, the detection of L-DOPA via the red fluorescent signal can be completed in only 30 min. We also developed a sequential analysis method to detect the coexistence of dopamine and L-DOPA with a high degree of sensitivity using the dual-fluorescent signals to monitor the therapy of patients with Parkinson's disease treated with L-DOPA. The robustness and applicability of the system were further validated in serum. In addition, paper microfluidics modified with chitosan was applied for fast and cost-effective analysis of dopamine and L-DOPA in the mixed solutions.

Risk factors for pharmacotherapy for storage symptoms after transurethral resection of the prostate in patients with benign prostatic hyperplasia.

OBJECTIVES: Postoperative persistence of storage symptoms after transurethral resection of the prostate (TURP) is bothersome, and evidence of its cause is sparse. We sought to analyze risk factors for using antimuscarinics or beta-3 agonists after TURP in benign prostatic hyperplasia (BPH) patients. METHODS: BPH patients who underwent TURP and were followed up for >6 months after surgery were retrospectively enrolled. Postoperative pharmacotherapy for storage symptoms was defined as the prescription of antimuscarinics or beta-3 agonists within 3 months after TURP for >3 months. Preoperative and perioperative variables were evaluated for their effect on the postoperative prescription of antimuscarinics or beta-3 agonists. RESULTS: Of the 376 patients, 45 (12.0%) received postoperative pharmacotherapy for storage symptoms. Patients who underwent bipolar TURP were significantly more likely to receive postoperative pharmacotherapy than those who underwent monopolar TURP (15.7% vs 6.9%; P = 0.01). Significantly more patients with intravesical prostatic protrusions >1 cm used postoperative pharmacotherapy than those with protrusions of ≤1 cm (14.4% vs 5.2% respectively; P = 0.02). Multivariate logistic regression analysis revealed age >75 years (odds ratio [OR] 3.04; 95% CI 1.29-7.16; P = 0.011), intravesical prostatic protrusion >1 cm (OR, 3.48; 95% CI, 1.32-9.15; P = 0.012), and bipolar transurethral resection (OR 4.25; 95% CI 1.53-11.80; P = 0.005) as significant risk factors for postoperative pharmacotherapy. CONCLUSIONS: Advanced age, intravesical prostatic protrusion, and bipolar TURP were significantly associated with postoperative pharmacotherapy for storage symptoms after TURP in BPH patients. Therefore, patients with these risk factors might be informed about the risk of postoperative storage symptoms that may require medications after TURP.

Evaluation of Topical and Subconjunctival Injection of Hyaluronic Acid-Coated Nanoparticles for Drug Delivery to Posterior Eye.

Posterior eye diseases, such as age-related macular degeneration and diabetic retinopathy, are difficult to treat due to ineffective drug delivery to affected areas. Intravitreal injection is the primary method for posterior eye drug delivery; however, it is usually accompanied by complications. Therefore, an effective and non-invasive method is required. Self-assembling nanoparticles (NPs) made from gelatin-epigallocatechin gallate (EGCG) were synthesized (GE) and surface-decorated with hyaluronic acid (HA) for drug delivery to the retinal/choroidal area. Different HA concentrations were used to prepare NPs with negative (GEH-) or positive (GEH+) surface charges. The size/zeta potential and morphology of the NPs were characterized by a dynamic light scattering (DLS) system and transmission electron microscope (TEM). The size/zeta potential of GEH+ NPs was 253.4 nm and 9.2 mV. The GEH- NPs were 390.0 nm and -35.9 mV, respectively. The cytotoxicity was tested by adult human retinal pigment epithelial cells (ARPE-19), with the results revealing that variant NPs were non-toxicity at 0.2-50 µg/mL of EGCG, and that the highest amount of GEH+ NPs was accumulated in cells examined by flowcytometry. Topical delivery (eye drops) and subconjunctival injection (SCI) methods were used to evaluate the efficiency of NP delivery to the posterior eyes in a mouse model. Whole eyeball cryosections were used to trace the location of fluorescent NPs in the eyes. The area of fluorescent signal obtained in the posterior eyes treated with GEH+ NPs in both methods (eye drops: 6.89% and SCI: 14.55%) was the greatest when compared with other groups, especially higher than free dye solution (2.79%). In summary, GEH+ NPs can be transported to the retina by eye drops and SCI; in particular, eye drops are a noninvasive method. Furthermore, GEH+ NPs, characterized by a positive surface and HA decoration, could facilitate drug delivery to the posterior eye as a useful drug carrier.

Proline in transmembrane domain of type II protein DPP-IV governs its translocation behavior through endoplasmic reticulum.

A transmembrane domain (TMD) at the N-terminus of a membrane protein is a signal sequence that targets the protein to the endoplasmic reticulum (ER) membrane. Proline is found more frequently in TM helices compared to water-soluble helices. To investigate the effects of proline on protein translocation and integration in mammalian cells, we made proline substitutions throughout the TMD of dipeptidyl peptidase IV, a type II membrane protease with a single TMD at its N-terminus. The proteins were expressed and their capacities for targeting and integrating into the membrane were measured in both mammalian cells and in vitro translation systems. Three proline substitutions in the central region of the TMD resulted in various defects in membrane targeting and/or integration. The replacement of proline with other amino acids of similar hydrophobicity rescued both the translocation and anchoring defects of all three proline mutants, indicating that conformational change caused by proline is a determining factor. Increasing hydrophobicity of the TMD by replacing other residues with more hydrophobic residues also effectively reversed the translocation and integration defects. Intriguingly, increasing hydrophobicity at the C-terminal end of the TMD rescued much more effectively than it did at the N-terminal end. Thus, the effect of proline on translocation and integration of the TMD is not determined solely by its conformation and hydrophobicity, but also by the location of proline in the TMD, the location of highly hydrophobic residues, and the relative position of the proline to other proline residues in the TMD.