Independent insulin signaling modulators govern hot avoidance under different feeding states.

Thermosensation is critical for the survival of animals. However, mechanisms through which nutritional status modulates thermosensation remain unclear. Herein, we showed that hungry Drosophila exhibit a strong hot avoidance behavior (HAB) compared to food-sated flies. We identified that hot stimulus increases the activity of α'ß' mushroom body neurons (MBns), with weak activity in the sated state and strong activity in the hungry state. Furthermore, we showed that α'ß' MBn receives the same level of hot input from the mALT projection neurons via cholinergic transmission in sated and hungry states. Differences in α'ß' MBn activity between food-sated and hungry flies following heat stimuli are regulated by distinct Drosophila insulin-like peptides (Dilps). Dilp2 is secreted by insulin-producing cells (IPCs) and regulates HAB during satiety, whereas Dilp6 is secreted by the fat body and regulates HAB during the hungry state. We observed that Dilp2 induces PI3K/AKT signaling, whereas Dilp6 induces Ras/ERK signaling in α'ß' MBn to regulate HAB in different feeding conditions. Finally, we showed that the 2 α'ß'-related MB output neurons (MBONs), MBON-α'3 and MBON-ß'1, are necessary for the output of integrated hot avoidance information from α'ß' MBn. Our results demonstrate the presence of dual insulin modulation pathways in α'ß' MBn, which are important for suitable behavioral responses in Drosophila during thermoregulation under different feeding states.

Gauze packing may be a better hemostatic method to protect ovarian reserve during laparoscopic endometrioma cystectomy than conventional hemostatic methods.

PURPOSE: To compare the ovarian reserve of different hemostatic methods after laparoscopic endometrioma stripping (LES) and explore which factors may affect ovarian reserve. METHODS: Patients who underwent LES from January 2019 to December 2021 were retrospectively included. Anti-Müllerian hormone (AMH) levels were measured before, and 3 months after surgery to determine changes of serum AMH in each patient. A multivariate linear regression analysis was performed to identify significant factors that were associated with the rate of decline of serum AMH levels at month 3 after surgery. RESULTS: A total of 67 patients who underwent LES were included. Of these patients, 20 with gauze packing, 24 with bipolar dessication (BD), and 23 with suture to achieve hemostasis. The 3 groups were similar in terms of demographics, cyst diameter, and basal AMH levels, except basal hemoglobin levels. At 3 months after surgery, the decline rate of AMH levels was significantly greater in the suture and BD group compared with the gauze packing group [48.2% (interquartile range, IQR, 28.1-67.1) and 31.1% (IQR,14.6-49.1) vs. 15.1% (IQR,1.1-24.5), P = 0.001]. On multivariate regression models, significant predictors of the decline rate of serum AMH levels at 3 months after surgery were hemostatic methods (p < 0.001), basal AMH levels (p = 0.033), and lesion bilaterality (p = 0.017). CONCLUSION: Compared to BD or suturing hemostasis, gauze packing hemostasis led to less damage on ovarian reserve at 3 months after LES. Besides, hemostatic methods, bilateral endometriomas and basal ovarian reserve were independently correlated with the impairment of ovarian reserve after surgery.

3D Interlayer Slidable Multilayer Nano-Graphene Oxide Acrylate Crosslinked Tough Hydrogel.

The design of three-dimensional crosslinked units with a spatial structure is of great significance for improving the mechanical properties of hydrogels. However, almost all the nanocomposites incorporated in hydrogels were defined as rigid nanofillers without further discussion on the potential contribution from the spatial structure change. In this work, the 3D nano chemical crosslinker multilayer graphene oxide acrylate (mGOa) was developed as a pressure-responsive crosslinker to achieve both low elastic modulus and high compression stress by synergizing more polymer chains against the loading force through interlayer sliding. Results showed that the hydrogel crosslinked by only 2 mg/mL mGOa nano chemical crosslinker in the poly(2-hydroxyethyl methacrylate-co-acrylamide) hydrogel (molar ratio: 1:1) can effectively enhance the mechanical strength up to 14.1 ± 2.1 MPa at a high compressive strain (90.6%) with an elastic modulus of less than 0.03 MPa at the initial 5% compression, whereas the hydrogel crosslinked by methacrylated single-layer graphene oxide (sGOa) or a small-molecule chemical crosslinker, N,N'-methylene bisacrylamide, can only reach 2.3 ± 0.8 MPa and 1.4 ± 0.4 MPa, respectively. In addition, the instantaneous modulus of the mGOa crosslinked hydrogel rapidly increased to the peak value with the increase of strain. The repeated compression test of HcA-mGOa hydrogels showed the responsive increase of the modulus, which was promoted by the synergism of polymer chains under compression. This indicated that the interlayer sliding of mGOa is the key contributor to mechanical strength enhancement, which provides a new rationale to design tough hydrogels.

Effect of videourodynamic subtypes on treatment outcomes of female dysfunctional voiding.

INTRODUCTION AND HYPOTHESIS: Dysfunctional voiding (DV) is not uncommon in women and is typically challenging to treat. This study retrospectively investigated the long-term treatment outcomes of DV women with different videourodynamics (VUDS) characteristics. METHODS: Data of women with VUDS-proven DV (n = 302) were retrospectively analyzed. All patients at first received biofeedback pelvic floor muscle training and medications; urethral sphincter botulinum toxin A injection was administered after treatment failure. Long-term follow-up outcomes were graded by global response assessment (GRA) and objective responses of decrease of detrusor pressure (Pdet), increase in maximum flow rate (Qmax) and voiding efficiency (VE). The treatment outcomes were investigated among different VUDS subgroups. RESULTS: Of 302 women, 165 (54.6%) had mid-urethral DV, 117 (38.7%) had distal urethral DV, and 20 (6.6%) had both bladder neck dysfunction (BND) and mid-urethral DV. A total of 170 (56.3%) patients were available for follow-up VUDS after treatment. Pdet was decreased in all three subgroups, but increase in Qmax and VE was only noted in the BND plus DV subgroup. Overall, 120 (70.6%) patients showed improvement (GRA ≥ 1), including 14 with BND plus DV (93.3%), 50 with mid-urethral DV (60.8%) and 56 with distal urethral DV (77.8%) (p = 0.044). All three subgroups showed significant reduction in bladder outlet obstruction index after treatment, with BND plus DV subgroup showing the greatest reduction. CONCLUSIONS: Women with DV have different VUDS characteristics resulting from different pathophysiological mechanisms and treatment results. The VUDS characteristics may help predict treatment outcomes of female DV.

Therapeutic efficacy and cognitive adverse events of overactive bladder medication in patients with central nervous system Disorders-A cohort study.

PURPOSE: This cohort study evaluates therapeutic efficacy and adverse events (AEs) of various overactive bladder (OAB) medications for patients with central nervous system (CNS) disorders. METHODS: Patients with OAB and CNS disorders were prospectively enrolled. They were randomly allocated to 3 different treatment subgroups: (1) mirabegron 50 mg once daily (2) solifenacin 5 mg per day, and (3) combined solifenacin 5 mg and mirabegron 50 mg once daily. Efficacy and safety questionnaires and objective parameters were compared among the subgroups, and subgroups between baseline and 3 and 6 months after treatment. AEs, including cognitive dysfunction, were assessed using the Mini-Mental State Examination (MMSE). RESULTS: 102 patients (mean age, 71.8 ± 8.7 years) were enrolled, including 35, 36, and 31 patients received mirabegron monotherapy, solifenacin monotherapy, and combination therapy, respectively. OAB symptoms scores all significantly improved 3 months after treatment in different subgroup. However, PVR increased and VE decreased significantly after treatment in patients receiving solifenacin monotherapy and combination therapy. Dry mouth and constipation were the most common AEs, especially in the solifenacin and combination subgroups. Mild incidence of AEs was noted in patients receiving mirabegron monotherapy. No significant change in MMSE was noted among the subgroups after treatment. CONCLUSION: OAB medication had good therapeutic efficacy in patients who had OAB with CNS disorders, especially in cerebrovascular accident and parkinsonism. No OAB medication or their combination affected cognitive function, whereas minimal AEs were noted with mirabegron. Mirabegron could be recommended as the first choice for managing OAB in these patients.

Development of an Integrated High Serum Stability Zwitterionic Polypeptide-Based Nanodrug with Both Rapid Internalization and Endocellular Drug Releasing for Efficient Targeted Chemotherapy.

Chemotherapeutic nanodrugs have to penetrate through many biological barriers before reaching the tumor cells. Thus, high stability of the nanocarrier before reaching tumor cells and fast release of the carried drugs in targeted tumor cells are required. In this work, inspired by the intrinsic zwitterionic surface property, mainly formed by glutamic acid and lysine residues, of the plasma protein surface, the zwitterionic poly(glutamyl lysine-co-aspartic acid-co-cysteine) peptide (P(EK-D-C)) was synthesized for conjugating n-mercaptoalkanoic acid (MA) with different chain lengths on cysteine residues through a disulfide linkage to load hydrophobic doxorubicin (DOX). The results showed that the slightly negative-biased zwitterionic nanodrugs were very stable in both resistance to nonspecific plasma protein adsorption and prevention of premature DOX release at physiological pH 7.4 due to the zwitterionic polypeptide shell and the sharp contrast in polarity between the shell and DOX-loaded core, while they can quickly release the loaded DOX through responding to both low pH values in the endosome/lysosome and high glutathione concentrations in the tumor cell cytoplasm. Furthermore, the enhanced internalization of these nanodrugs led to about 60% higher in vitro cytotoxicity against MCF-7 cells at pH 6.7 than at pH 7.4, whereas the in vitro cytotoxicity of DOX·HCl at pH 6.7 was only 75% of the value at pH 7.4. In vivo results revealed that the stable nanodrugs conjugated with the long hydrophobic 12-mercaptododecanoic acid had higher tumor inhibition rate and lower systematic toxicity on MCF-7 tumor-bearing mice than the less stable nanodrugs conjugated with the short 8-mercaptooctaoic acid and were significantly superior to DOX·HCl. These results indicate that the combination of high stability in circulation and fast release in tumor cells of nanodrugs can enhance high efficacy targeted chemotherapy. This pH/redox-sensitive zwitterionic polypeptide nanocarrier might provide an excellent vehicle for solid tumor treatment.

Development of Nonfouling Zwitterionic Copolymerized Peptides Based on Glutamic Acid and Lysine Dimers for Adjustable Enzymatic Degradation.

Nonspecific protein adsorption-resistant materials, the so-called nonfouling materials, are crucial biomaterials in biomedical applications. Up-to-date, little attention was paid to the biodegradability of these materials. In this work, nonfouling zwitterionic copolymerized peptides composed of the N-l-glumatyl-l-lysine dimer (EK) and δ-l-lysinyl-l-glutamic acid dimer (E-K, glutamic acid with the lysine side chain) at various ratios were synthesized to investigate the enzymatic degradation rate. Two types of proteases (trypsin and alkaline protease), which represent a site-specific and less site-specific cleavage protease, respectively, were used to demonstrate the adjustable degradability by tracking the molecular weight (Mw) at different digestion times. Results showed that higher compositions of the E-K dimer lead to slower degradation rates by both proteases and larger fragments after 120 min digestion. With the composition of the E-K dimer over 50%, the degradation of copolymerized peptides by both proteases becomes very slow. This indicated that the bulky lysinyl side chain on E-K can alter the enzymolysis process for adjusting the enzymatic degradability of the newly synthesized zwitterionic copolymerized peptides, which could be promising candidates for biomedical applications in vivo.

Will detrusor acontractility recover after medical or surgical treatment? A longitudinal long-term urodynamic follow-up.

AIMS: Patients with urinary retention due to detrusor acontractility (DA) might regain voiding efficiency (VE) after treatment. This study investigated the long-term outcomes and predictors of recovery following treatment. METHODS: A total of 32 patients with DA were retrospectively identified and enrolled. DA was defined by Pdet .Qmax = 0 cmH2 O and postvoid residual (PVR) > 300 ml determined through videourodynamic study (VUDS). All patients received medical or surgical treatment and were followed up for at least 3 months, during which repeat VUDS was conducted. Detrusor contractility recovery was confirmed when patients were able to void with a Pdet .Qmax ≥ 10 cmH2 O after treatment. RESULTS: Our patients comprised 22 women and 10 men (mean age, 73.2 ± 9.7 years; mean follow-up duration, 1.6 ± 1.8 [0.3-7.4] years). Follow-up VUDS revealed that 14 (43.9%) patients recovered from detrusor contractility, with five patients recovering within 1 year and nine after 1 year. Pdet .Qmax , voided volume, PVR, maximum flow rate, and VE significantly improved in both the recovery and nonrecovery groups. The recovery group had significantly better VE (p = .039) and significantly lower bladder compliance (74.2 ± 83.2 vs. 119 ± 82.6; p = .007) than the nonrecovery group. Receiver operating characteristic (ROC) analysis revealed an optimum bladder compliance cutoff value of <80 ml/cmH2 O for predicting detrusor contractility recovery with an area under the ROC curve of 0.780. CONCLUSIONS: Among the included patients with DA, 43.9% had detrusor contractility recovery after treatment, with bladder compliance of <80 ml/cmH2 O predicting bladder function recovery.

Development of a Negative-Biased Zwitterionic Polypeptide-Based Nanodrug Vehicle for pH-Triggered Cellular Uptake and Accelerated Drug Release.

Albumin mimics could be an attractive platform for nanodrug carriers through systematic administration because of high safety and plentiful properties to be adjusted for a high drug efficacy, such as pH-triggered targeting cellular uptake and drug release. In this work, negative-biased zwitterionic nanodrug carriers based on zwitterionic polypeptide chains that mimic albumin were prepared, which have an outermost layer of zwitterionic glutamic acid (E) and lysine (K) pairs with a small amount of aspartic acid (D) to adjust the overall ζ potential. On the other hand, doxorubicin (Dox) was encapsulated in a hydrophobic core by 11-maleimidoundecanoic acid covalently linked with additional cysteine (C) residues on the polypeptide. The results show that the negative-biased zwitterionic nanodrug carriers can sensitively enhance the cellular uptake in responding to a pH change from 7.4 to 6.7 without reversing the ζ potential to a positive charge, leading to accelerating the Dox release rate in a slightly acidic environment through the polypeptide secondary structure change. Moreover, the anionic nanodrug carrier can also be easily enzymatically digested by trypsin for quick drug release. In short, this negative-biased zwitterionic nanodrug delivery vector could be an ideal candidate for a safer tumor inhibition with a high efficacy than conventional synthetic polymer-based ones.

Resistance to Long-Term Bacterial Biofilm Formation Based on Hydrolysis-Induced Zwitterion Material with Biodegradable and Self-Healing Properties.

Long-term resistance of biomaterials to the bacterial biofilm formation without antibiotic or biocide is highly demanded for biomedical applications. In this work, a novel biodegradable biomaterial with excellent capability to prevent long-term bacterial biofilm formation is prepared by the following two steps. Ethylcarboxybetaine ester analogue methacrylate (ECBEMA), poly(ethylene glycol) monomethacrylate (PEGMA), and 3-methacryloxypropyletris(trimethylsiloxy)silane (TRIS) were copolymerized to obtain p(ECBEMA-PEGMA-TRIS) (PEPT). Then, PEPT was cross-linked by isocyanate-terminated polylactic acid (IPDI-PLA-IPDI) to obtain the final PEPTx-PLAy (x and y are the number-average molecular weights (Mn) of PEPT and PLA, respectively) with optimal mechanical strength and adjustable surface regeneration rate. Static contact angle measurement, protein adsorption measurement, and attenuated total reflectance infrared (ATR-IR) results show that the PEPT19800-PLA800 film surface can generate a zwitterionic layer to resist nonspecific protein adsorption after surface hydrolysis. Quartz crystal microbalance with dissipation (QCM-D) results indicates that the PEPT19800-PLA800 film can undergo gradual degradation of the surface layer at the lowest swelling rate. Particularly, this material can efficiently resist the bacterial biofilm formation of both Gram-positive bacteria and Gram-negative bacteria over 14 and 6 days, respectively. Moreover, the material also shows an ideal self-healing feature to adapt to harsh conditions. Thus, this nonfouling material shows great potential in biomedical applications and marine antifouling coatings without antibiotic or biocide.

Silk-Inspired ß-Peptide Materials Resist Fouling and the Foreign-Body Response.

The functions of implants like medical devices are often compromised by the host's foreign-body response (FBR). Herein, we report the development of low-FBR materials inspired by serine-rich sericin from silk. Poly-ß-homoserine (ß-HS) materials consist of the hydrophilic unnatural amino acid ß-homoserine. Self-assembled monolayers (SAMs) of ß-HS resist adsorption by diverse proteins, as well as adhesion by cells, platelets, and diverse microbes. Experiments lasting up to 3 months revealed that, while implantation with control PEG hydrogels induced obvious inflammatory responses, collagen encapsulation, and macrophage accumulation, these responses were minimal with ß-HS hydrogels. Strikingly, the ß-HS hydrogels induce angiogenesis in implant-adjacent tissues. Molecular dynamics simulations indicated that the low FBR performance of ß-HS results from what we term "dual hydrogen bonding hydration", wherein both the backbone amide groups and the sidechain hydroxyl groups of ß-HS undergo hydration.

Development of Zwitterionic Polypeptide Nanoformulation with High Doxorubicin Loading Content for Targeted Drug Delivery.

Much attention has been drawn to targeted nanodrug delivery systems due to their high therapeutic efficacy in cancer treatment. In this work, doxorubicin (DOX) was incorporated into a zwitterionic arginyl-glycyl-aspartic acid (RGD)-conjugated polypeptide by an emulsion solvent evaporation technique with high drug loading content (45%) and high drug loading efficiency (95%). This zwitterionic nanoformulation showed excellent colloidal stability at high dilution and in serum. The pH-induced disintegration and enzyme-induced degradation of the nanoformulation were confirmed by dynamic light scattering and gel permeation chromatography. Efficient internalization of DOX in the cells and high antitumor activity in vitro was observed. Compared with the free drug, this nanoformulation showed higher accumulation in tumor and lower systemic toxicity in vivo. The DOX-loaded zwitterionic RGD-conjugated polypeptide vesicles show potential application for targeted drug delivery in the clinic.

Simple Thermal Pretreatment Strategy to Tune Mechanical and Antifouling Properties of Zwitterionic Hydrogels.

Zwitterionic hydrogels are promising biomaterials because of their high water content, three-dimensional network structure, and antifouling property. However, it still remains unclear about how mechanical properties of zwitterionic hydrogels affect their antifouling property. In this work, we propose a simple, thermal-pretreatment method to fabricate poly(sulfobetaine methacrylate) (pSBMA) hydrogels with varied mechanical properties that can be readily tuned by thermal pretreatment time and cross-linker density, as well as to correlate their mechanical property with antifouling property. The resulting thermal-treated pSBMA hydrogels show significantly enhanced mechanical properties with tunable compressive modulus and elastic modulus as compared to the untreated hydrogels. A combination of ELISA investigations and short-term cell adhesion assays also confirm that pSBMA hydrogels exhibit superior antifouling properties to resist protein adsorption and cell adhesion. Further analysis shows a linear inversion correlation between elastic modulus and protein adsorption of pSBMA hydrogels, i.e., the hydrogel with the higher elastic modulus exhibits the lower protein adsorption (the better antifouling property). This work not only provides a simple thermal-pretreatment strategy for fabricating pSBMA hydrogels, but also demonstrates multifunctional properties of the pSBMA hydrogels, which possess a great potential to fulfill some biomedical applications.

Ultra-small biocompatible jujube polysaccharide stabilized platinum nanoclusters for glucose detection.

The development of noble ultra-small biocompatible Pt nanoclusters (Pt NCs) for glucose detection has been drawing great attention. Herein, ultra-small biocompatible jujube polysaccharide (JP) stabilized platinum nanoclusters (Ptn-JP NCs) are prepared using natural JP as a reducing and solubilizing agent. Ptn-JP NCs were studied for the colorimetric detection of glucose. Ptn-JP NCs (n = 50, 200 and 400) had an average particle diameter of 1-2 nm. Particularly, the measurements of hydrodynamic sizes of Ptn-JP NCs indicated that they maintained good stability in solution for one week. Pt200-JP NCs showed good biocompatibility, and were not toxic against HeLa cells at a high concentration of 400 µg mL-1. Furthermore, Pt200-JP NCs catalyzed the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) with H2O2 to produce blue oxidized TMB (oxTMB). This reaction followed typical Michaelis-Menten kinetics. More importantly, the glucose concentration could be sensitively detected by the color change, and this process was not interfered by other sugars. The linear range for glucose concentration was from 0.01 to 1 mM with a detection limit of 5.47 µM. The glucose concentrations of real samples of serum using Pt200-JP NCs were 9.2, 4.9 and 6.5 mM, respectively. The prepared Ptn-JP NCs have great potential in various biomedical detection methods.

Single onabotulinumtoxinA 200U dose improved clinical symptoms but not urothelial dysfunction in neurogenic detrusor overactivity due to spinal cord injury.

OBJECTIVE: To evaluate the changes in urothelial dysfunction protein expressions in bladder after onabotulinumtoxin injection and correlate that with clinical outcomes in spinal cord injury (SCI) patients. METHODS: Twenty-six patients with neurogenic detrusor overactivity (NDO) and urinary incontinence due to suprasacral SCI were treated with onabotulinumtoxinA 200U detrusor injection. Urodynamic studies and bladder biopsies were obtained at baseline, 3, and 6 months after treatment. Biopsy tissues were investigated for E-cadherin, zonula occludens-1 (ZO-1), mast cell activity, and urothelial cell apoptosis, sensory protein expression including purinergic receptor P2X3, endothelial NOS, inducible NOS, ß3-adrenoceptors, and muscarinic receptors M2 and M3. Differences in functional protein expression between controls and SCI patients and between successful and failed treatment groups were analyzed. RESULTS: SCI patients had significantly lower E-cadherin, higher mast cell activity, increased apoptosis, decreased M3 and eNOS expressions than the controls at baseline. Of the 26 patients, 17 (65%) showed improvement in bladder capacity by >50% at 3 months; however, improvement declined by 6 months after treatment. The urothelial expression of E-cadherin and ZO-1 increased at 3 months but had declined at 6 months. The urothelial sensory protein expression did not change significantly after treatment. M3 receptor density was significantly decreased in SCI patients at baseline and patients with treatment success 3 months after injection (p = 0.01). CONCLUSION: A single injection of onabotulinumtoxinA 200U improved clinical symptoms but did not significantly alter urothelial sensory protein expression. The results imply that a single 200U onabotulinumtoxinA dose might not be adequate for urothelial dysfunction in NDO. IRB: TCGH 098-53.

Development of a Smart Helmet for Strategical BCI Applications.

Conducting electrophysiological measurements from human brain function provides a medium for sending commands and messages to the external world, as known as a brain-computer interface (BCI). In this study, we proposed a smart helmet which integrated the novel hygroscopic sponge electrodes and a combat helmet for BCI applications; with the smart helmet, soldiers can carry out extra tasks according to their intentions, i.e., through BCI techniques. There are several existing BCI methods which are distinct from each other; however, mutual issues exist regarding comfort and user acceptability when utilizing such BCI techniques in practical applications; one of the main challenges is the trade-off between using wet and dry electroencephalographic (EEG) electrodes. Recently, several dry EEG electrodes without the necessity of conductive gel have been developed for EEG data collection. Although the gel was claimed to be unnecessary, high contact impedance and low signal-to-noise ratio of dry EEG electrodes have turned out to be the main limitations. In this study, a smart helmet with novel hygroscopic sponge electrodes is developed and investigated for long-term usage of EEG data collection. The existing electrodes and EEG equipment regarding BCI applications were adopted to examine the proposed electrode. In the impedance test of a variety of electrodes, the sponge electrode showed performance averaging 118 kΩ, which was comparable with the best one among existing dry electrodes, which averaged 123 kΩ. The signals acquired from the sponge electrodes and the classic wet electrodes were analyzed with correlation analysis to study the effectiveness. The results indicated that the signals were similar to each other with an average correlation of 90.03% and 82.56% in two-second and ten-second temporal resolutions, respectively, and 97.18% in frequency responses. Furthermore, by applying the proposed differentiable power algorithm to the system, the average accuracy of 21 subjects can reach 91.11% in the steady-state visually evoked potential (SSVEP)-based BCI application regarding a simulated military mission. To sum up, the smart helmet is capable of assisting the soldiers to execute instructions with SSVEP-based BCI when their hands are not available and is a reliable piece of equipment for strategical applications.

Zwitterion-like, Charge-Balanced Ultrathin Layers on Polymeric Membranes for Antifouling Property.

Zwitterions of charge-balanced units have super-low fouling properties induced by ionic solvation, but their extensive applications in polymeric substrates are strictly constrained by current constructing strategies. A zwitterion-like, charge-balanced ultrathin layer with high antifouling capacity was covalently constructed on delicate aromatic polyamide (PA) reverse osmosis (RO) membranes via a mild and solvent-free grafting-to strategy. Two oppositely charged commercial short-chain carbonyl alkenes, 2-acrylamido-2-methylpropanesulfonic acid (AMPS) and methacryloxyethyltrimethylammonium chloride (DMC), were directly mixed-grafted with amino groups on PA RO membrane surface via Michael addition. Under ambient temperature and pressure, these oppositely charged compounds were assembled into a zwitterion-like, charge-balanced ultrathin layer. The dynamic fouling experiments indicated that the modified membrane exhibited strong antifouling properties and excellent permeation recovery abilities. Surface characterization revealed that the selective layer thickness and surface roughness were not measurably changed. More meaningful is that the typical ridge-and-valley surface structure and the excellent separation performance were both well preserved after modification. This opens a universal avenue to construct a zwitterion-like, ultrathin antifouling layer on the delicate polymer substrate without compromising its original matrix structure and performance, which has promising application in areas of biosensors, tissue engineering, and biomaterials.

Therapeutic effect of urethral sphincter onabotulinumtoxinA injection for urethral sphincter hyperactivity.

PURPOSE: Urethral sphincter hyperactivity resulting in voiding dysfunction is frequently encountered. Medical treatment might not achieve a satisfactory result. OnabotlinumtoxinA urethral sphincter injection relaxes sphincter tonicity and possibly resumes efficient voiding. This study analyzed the treatment outcomes and predictor for successful onabotulinumtoxinA treatment on these patients. METHODS: Patients with voiding dysfunction due to urethral sphincter hyperactivity and treated with injections of 100 U onabotulinumtoxinA into the urethral sphincter were retrospectively reviewed. Treatment outcomes were assessed 1 month after injection using the Global Response Assessment and were analyzed by demographic and baseline video-urodynamic characteristics. RESULTS: Of the 95 patients included, satisfactory outcomes were reported in 58 (61.1%) patients. Treatment outcome was not related to age, gender, or voiding dysfunction subtype. Patients with satisfactory outcomes had a significantly smaller volume at first sensation of filling (P = 0.046), greater detrusor pressure (P = 0.027), higher maximum flow rate (P = 0.017), and smaller post-void residual (P = 0.006). In multivariate analysis, an open bladder neck during voiding was the only predictor for successful outcome (88% in satisfactory outcome, 12% in failure outcome, P < 0.001). Patients with non-neurogenic voiding dysfunction had a significantly longer therapeutic duration than those with neurogenic voiding dysfunction (9.55 ± 4.18 vs 7.44 ± 2.91 months, P = 0.033). Increased urinary incontinence was reported in 18 patients, including 6 with stress urinary incontinence and 12 with urgency urinary incontinence. CONCLUSION: Subjective improvement was reported in 61.1% of patients with voiding dysfunction due to urethral sphincter hyperactivity after onabotulinumtoxinA urethral sphincter injection. An open bladder neck during voiding at baseline predicts a successful outcome.

Polycystic ovary syndrome is associated with anogenital distance, a marker of prenatal androgen exposure.

Study question: Is the presence of polycystic ovary syndrome (PCOS) associated with anogenital distance (AGD), a biomarker for the prenatal hormonal environment? Summary answer: The presence of PCOS is associated with longer AGD. What is known already: Although the aetiology of PCOS is unclear, emerging data suggest that the natural history of PCOS may originate from intrauterine life. Prenatal exposure to androgen hormones is considered an important factor of PCOS. AGD is the distance measured from the anus to the genital tubercle and there is considerable evidence in humans and animals to support AGD as a sensitive biomarker of prenatal androgen activity. Study design, size, duration: This case-control study of 156 PCOS patients and 180 reproductively healthy women (control subjects) was performed from October 2015 to July 2016. Participants/materials, setting, methods: The patients and controls were recruited from the out-patient Department of Gynecology of Sun Yat-sen Memorial Hospital. Participants completed health questionnaires and provided a blood sample for evaluation of serum reproductive hormone profiles. Anthropometric indices of AGDAF (anus-fourchette) and AGDAC (anus-clitoris) were measured in all subjects. We used logistic regression to estimate the association between the presence of PCOS and AGD measurements while accounting for important confounders, including age and BMI. Multiple linear regression was used to analyse the relationships between PCOS characteristics (e.g. polycystic ovaries and total testosterone (T)) and two measurements of AGD in the PCOS group and controls. Main results and the role of chance: Overall, logistic regression showed that women with AGDAF in the highest tertile were 18.8 times (95% CI 9.6-36.6; P < 0.001) more likely to have PCOS compared with those in the lowest tertile. Women with AGDAC in the highest tertile were 6.7 times (95% CI 3.7-12.1; P < 0.001) more likely to have PCOS than those in the lowest tertile. In the PCOS group, multiple linear regression analyses revealed that both AGD measurements were positively associated with T levels (ß = 0.246 for AGDAC, ß = 0.368 for AGDAF; P = 0.003 and P < 0.001, respectively), and AGDAF was positively associated with the presence of polycystic ovaries (ß = 0.279; P < 0.001). In the controls, a positive association was found only between T levels with AGDAF (ß = 0.177, P = 0.020), whereas no associations were found between the remaining covariates and AGD measurements. Limitations, reasons for caution: As this was an observational study, causal inference cannot be obtained. Wider implications of the findings: This study suggests that PCOS may originate in intrauterine life, and be affected by prenatal exposure to androgens. Study funding/competing interest(s): This study was supported by funds obtained from the Science Technology Research Project of Guangdong Province (2010B031600058 and 2015A030310083) and the Major Science Technology Research Project of Guangdong Province (ZKM05602S). The authors have no competing interests to declare. Trial registration number: Not applicable.

The prognostic value of the preoperative c-reactive protein/albumin ratio in ovarian cancer.

BACKGROUND: Inflammation plays an important role in the pathogenesis of ovarian cancer. This study sought to investigate the association between the preoperative c-reactive protein/albumin ratio (CRP/Alb) and oncological outcomes in ovarian cancer patients. METHODS: Two hundred patients with histologically verified ovarian cancer between June 2006 and July 2012 were retrospectively reviewed. Overall survival was evaluated by the Kaplan-Meier method and log-rank test. The significance of risk factors for overall survival was evaluated with the Cox proportional hazards model. Additionally, area under the receiver operating characteristic curve (AUC) was used to compare the predictive ability of CRP/Alb, Glasgow Prognostic Score (GPS), modified GPS (mGPS), neutrophil lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR), prognostic index (PI) and prognostic nutritional index (PNI). RESULTS: The optimal cutoff value of CRP/Alb was 0.68. Increased CRP/Alb (≥0.68) was associated with advanced stage, residual tumor, ascites, elevated serum carbohydrate antigen(CA)-125 level, GPS, and mGPS (all p < 0.05). Patients with high CRP/Alb had poor overall survival compared to those with low CRP/Alb (p < 0.001). Multivariable analysis showed that CRP/Alb (Hazard Ratio (HR) 1.330, 95% confidence interval (CI) 1.131-1.564, p = 0.001), tumor stage (HR 1.577, 95% CI 1.189-2.091, p = 0.002), residual tumor (HR 2.337, 95% CI 1.518-3.597, p < 0.001) and age (HR 1.017, 95% CI 1.000-1.035, p = 0.046) were independent prognostic factors for overall survival. Additionally, the CRP/Alb showed greater AUC values at 1 year (0.692), 3 years (0.659), and 5 years (0.682) than GPS, mGPS and PNI. CONCLUSIONS: The CRP/Alb is a novel independent marker of poor prognosis among ovarian cancer patients and shows superior prognostic ability compared to the established inflammation-based prognostic indices.