Imine-Linked 2D Conjugated Porous Organic Polymer Films for Tunable Acid Vapor Sensing.

Two-dimensional (2D) films of conjugated porous organic polymers (C-POPs) can translate the rich in-plane functionalities of conjugated frameworks into diverse optical and electronic applications while addressing the processability issues of their crystalline analogs for adaptable device architectures. However, the lack of facile single-step synthetic routes to obtain large-area high-quality films of 2D-C-POPs has limited their application possibilities so far. Here, we report the synthesis of four mechanically robust imine-linked 2D-C-POP free-standing films using a single-step fast condensation route that is scalable and tunable. The rigid covalently bonded 2D structures of the C-POP films offer high stability for volatile gas sensing in harsh environments while simultaneously enhancing site accessibility for gas molecules due to mesoporosity by structural design. Structurally, all films were composed of exfoliable layers of 2D polymeric nanosheets (NSs) that displayed anisotropy from disordered stacking, evinced by out-of-plane birefringent properties. The tunable in-plane conjugation, different nitrogen centers, and porous structures allow the films to act as ultraresponsive colorimetric sensors for acid sensing via reversible imine bond protonation. All the films could detect hydrogen chloride (HCl) gas down to 0.05 ppm, far exceeding the Occupational Safety and Health Administration's permissible exposure limit of 5 ppm with fast response time and good recyclability. Computational insights elucidated the effect of conjugation and tertiary nitrogen in the structures on the sensitivity and response time of the films. Furthermore, we exploited the exfoliated large 2D NSs and anisotropic optoelectronic properties of the films to adapt them into micro-optical and triboelectric devices to demonstrate their real-time sensing capabilities.

Functionality Tuning in Hierarchically Engineered Magnetoelectric Nanocomposites for Energy-Harvesting Applications.

The ß-phase of the copolymer poly(vinylidene fluoride-trifluoroethylene) P(VDF-TrFE) possesses the highest dipole moment among all the functional polymers. It remains a key component of flexible energy-harvesting devices based on piezoelectricity and triboelectricity in the last decade. However, the quest for P(VDF-TrFE)-based magnetoelectric (ME) nanocomposites with enhanced ferroelectric, piezoelectric, and triboelectric properties remains elusive. The magnetostrictive inclusion in the copolymer matrix forms electrically conducting pathways and degrades ß-phase crystallinity significantly, deteriorating the functional properties of the nanocomposite films. To address this issue, we report the synthesis of magnetite (Fe3O4) nanoparticles on micron-scale magnesium hydroxide [Mg(OH)2] templates. These hierarchical structures were incorporated within the P(VDF-TrFE) matrix rendering composites with enhanced energy-harvesting capability. The Mg(OH)2 template prevents the formation of a continuous network of magnetic fillers, leading to lower electrical leakage in the composite. The addition of dual-phase fillers with 5 wt % only increases remanent polarization (Pr) values by ∼44%, owing to the presence of the ß-phase with significant crystallinity and increased interfacial polarization. The composite film exhibits a quasi-superparamagnetic nature and a significant magnetoelectric coupling coefficient (αME) of 30 mV/cm Oe. The film was also employed for triboelectric nanogenerator applications, exhibiting five times higher power density than the pristine film. We finally explored the integration of our ME devices with an internet of things platform to monitor the operational status of electrical appliances remotely. In light of these findings, the present work opens the path for future self-powered, multifunctional, and flexible ME devices with new application domains.

Antioxidant additive melatonin in tris-based egg yolk extender improves post-thaw sperm attributes in Hariana bull.

In the study, melatonin, a known antioxidant pineal peptide was used as an additive in the tris-egg yolk glycerol-based semen extender in Hariana bull semen and post-thaw sperm characters were evaluated. In the study, Group I was a control without melatonin; and Group II, III, and IV were having 0.5 mM, 1 mM, and 2 mM melatonin/80 × 106 spermatozoa, respectively were treatment groups. Thirty-two semen ejaculates from 4 Hariana bulls were processed for freezing and post-thaw sperm characteristics were evaluated. Sperm motility, velocity, the viability with intact membrane, and total antioxidant capacity were markedly (P < 0.05) improved in Group IV compared to all other groups. The lipid peroxidation and total protein carbonylation were substantially (P < 0.05) decreased in Group IV compared to all other groups. The population of cryocapacitated, acrosome-reacted, and apoptotic-like spermatozoa were significantly (P < 0.05) decreased in Group IV. Further, the relative band intensity of 74 kDa protein and percent of spermatozoa showing positive immune reactivity to tyrosine-phosphorylated proteins was decreased in Group IV. The progesterone-receptor ligand binding, in vitro capacitation response, and Vanguard distance were markedly (P < 0.05) improved in Group IV. In summary- Group IV having 2 mM melatonin was found to be optimal in providing cryoprotective effects to Hariana bull spermatozoa after freezing-thawing and can be suitably used as a semen additive during semen cryopreservation.

Robotic re-exploration for post-operative in house complications following robotic pelvic uro-oncologic surgery: Initial experience, tips and tricks.

Purpose: Despite widespread acceptance of robotics in urology, literature on using the minimally invasive approach for management of post robotic surgical complications is limited. Here we describe our experience with tips and tricks for robotic re-exploration of post-operative in house complications following robotic pelvic uro-oncologic surgery. Methods: A retrospective query of prospectively maintained database was done for all patients who underwent robotic - radical cystoprostatectomy (RCP, 437 patients) and radical prostatectomy (RP, 649 patients), from Jan 2015 or March 2021. Clinical details were collected for all who underwent a second robotic procedure during the same hospital admission for any complication related to the primary surgery. Results: Following RCP, 5 patients were re-explored for intestinal obstruction. Surgery was successfully completed in all with a median console time of 80 minutes. Median time to the passage of flatus and discharge from hospital following relook surgery was 3 and 6 days, respectively. Following RP, 3 patients underwent robotic re-exploration (two for reactionary hemorrhage, one for rectal injury). All three cases were managed with a median console time of 75 minutes. Robotic re-exploration was accomplished without extending the skin incision of the index surgery and we did not find an increased incidence of infectious or wound related complications. Conclusion: Robotic re-exploration for select post robotic urologic pelvic oncology surgery complications in the immediate and early post-operative period is feasible in the hands of experienced surgeons. Our experience can help others adopt robotics in such scenarios.

2/1 dose schedule of sunitinib is superior than the 4/2 regimen for the first-line therapy of clear cell metastatic renal cell carcinoma - An Indian experience.

BACKGROUND: Sunitinib remains the first-line treatment for favorable risk metastatic clear cell renal cell cancer (mccRCC). It was conventionally given in the 4/2 schedule; however, toxicity necessitated trying the 2/1 regimen. Regional variations in treatment response and toxicity are known, and there is no data from the Indian subcontinent about the outcomes of the alternative dosing schedule. METHODS: Clinical records of all consecutive adult patients who received sunitinib as first-line therapy for histologically proven mccRCC following cytoreductive nephrectomy from 2010-2018 were reviewed. The primary objective was to determine the progression-free survival (PFS), and the secondary objectives were to evaluate the response rate (objective response rate and clinical benefit rate), toxicity, and overall survival. A list of variables having a biologically plausible association with outcome was drawn and multivariate inverse probability treatment weights (IPTW) analysis was done to determine the absolute effect size of dosing schedules on PFS in terms of "average treatment effect on the treated" and "potential outcome mean." RESULTS: We found 2/1 schedule to be independently associated with higher PFS on IPTW analysis such that if every patient in the subpopulation received sunitinib by the 2/1 schedule, the average time to progression was estimated to be higher by 6.1 months than the 4/2 schedule. We also found 2/1 group to have a lower incidence than the 4/2 group for nearly all ≥ grade 3 adverse effects. Other secondary outcomes were comparable between both treatment groups. CONCLUSION: Sunitinib should be given via the 2/1 schedule in Indian patients.

Introduction to the pathways involved in the activation and regulation of sperm motility: A review of the relevance of ion channels.

To participate in sperm-oocyte fusion, spermatozoa need to be motile. In the testes, spermatozoa are immotile, although these gametes acquire the capacity for motility during the transit through the epididymis. During the period of epididymal transport from the male genital tract to the female genital tract, spermatozoa exhibit various types of motility that are regulated by complex signalling and communication mechanisms. Because motility is very dynamic, it can be affected by small changes in the external or internal environment of spermatozoa within a very short time. This indicates that regulatory membrane proteins, known as sperm ion channels, are involved in the regulation of sperm motility. Research results from studies, where there was use of electrophysiological, pharmacological, molecular and knock-out approaches, indicate ion channels are possibly involved in the regulation of sperm membrane polarisation, intracellular pH, motility, energy homeostasis, membrane integrity, capacitation, hyperactivity, acrosome reaction and fertilisation processes. In this review, there is summarisation of the key functions that ion channels have in the regulation, initiation, maintenance, and modulation of sperm motility. In addition, in this review there is highlighting of novel insights about the pathways of ion channels that are activated in spermatozoa while these gametes are located in the oviduct leading to the fertilisation capacity of these cells.

Interplay mechanisms between progesterone and endocannabinoid receptors in regulating bull sperm capacitation and acrosome reaction.

After ejaculation, sperm show a limited capacity for transcription and translation. In the oviduct, most of the signalling in sperm is nongenomic and is mediated through membrane receptors. Studies have shown that the cation channel of sperm (CatSper), cAMP, cGMP, protein kinases, and tyrosine phosphorylation are involved in the nongenomic signalling of progesterone (P4) in sperm. However, it is not known whether there is an interplay between P4 and cannabinoid receptors 1 and 2 (CB1 and CB2), transient receptor potential vanilloid 1 (TRPV1), CatSper channels, cAMP, inositol trisphosphate receptor (IP3R), and mitogen-activated protein kinase (MAPK); these potential regulators are involved in the regulation of capacitation and the acrosome reaction. In the present study, selective blockers of CB1, CB2, TRPV1, CatSper channels, cAMP, protein kinase A (PKA), IP3R, and MAPK were used to identify their involvement in P4-mediated bull sperm capacitation and the acrosome reaction. Selective blocking of any one of the molecules caused a significant reduction in P4 signalling (p < 0.05). Interestingly, blocking these molecules in combination followed by treatment with P4 resulted in the complete absence of capacitation and the acrosome reaction. Blocking a single receptor was not able to eliminate the P4-induced capacitation and the acrosome reaction. In addition to the CB1 and CB2 receptors, there may be other signalling pathways that mediate P4 signalling. In conclusion, P4 signalling exhibited interplay with the cannabinoid receptors. The regulation of sperm capacitation and the acrosome reaction also involved cAMP, PKA, l-type and T-type calcium channels, TRPV1, inositol trisphosphate, and MAPK.

Curcumin in a tris-based semen extender improves cryosurvival of Hariana bull spermatozoa.

In this study, the cryoprotective potential of natural antioxidant curcumin in Hariana bull semen was evaluated as an additive in a tris-based extender with the assessment of motility and motion parameters of spermatozoa, membrane intactness, progesterone-receptor binding, protein carbonyl content, cervical mucus penetration, cryocapacitation-associated and apoptotic-like changes. The collected ejaculates were divided into five groups in the tris-based extender (control without curcumin-I, 10 µM-II, 25 µM-III, 50 µM-IV and 75µM-V) and were cryopreserved. Groups II and III containing 10 and 25 µM curcumin substantially (p < .05) improved the post-thaw sperm parameters like viability, motility, and velocity parameters; intact acrosome and membrane; lowered protein carbonyl content; DNA fragmentation and cryocapacitation-associated changes in comparison to control. It was interesting to note that early apoptotic-like changes in sperm cells were significantly (p < .05) decreased in Group II along with an increase in a higher population of sperm cells having high mitochondrial transmembrane potential. Higher progesterone-receptor binding, Vanguard distance and in vitro capacitation response were observed only in Group II (10µM) compared to other groups. In conclusion, curcumin in a semen extender manifests cryoprotective effects and may be incorporated at 10 µM concentration in a Hariana bull semen extender for better post-thaw sperm quality.

Pitcher pot neourethral modification of ileal orthotopic neobladder achieves satisfactory long-term functional and quality of life outcomes with low clean intermittent self-catheterization rate.

Objective: To describe a decade of our experience with a neo-urethral modification of ileal orthotopic neobladder (pitcher pot ONB). Multiple investigators have reported similar modifications. However, long-term longitudinal functional and quality of life (QOL) outcomes are lacking. Methods: Prospectively maintained hospital registry for 238 ONB patients comprising a mix of open and robotic surgery cohorts from 2007 to 2017, and minimum of 2 years of follow-up was retrospectively queried. QOL was evaluated using Bladder Cancer Index (BCI). Longitudinal trends of QOL domain parameters were analysed. List of perioperative variables that have a biologically plausible association with continence, potency, and post-operative BCI QOL sexual, urinary, and bowel domain scores was drawn. Variables included surgery type, Body Mass Index (BMI), T and N stage, neurovascular bundle (NVB) sparing, age, and related pre-operative BCI QOL domain score. Prognostic associations were analysed using multivariable Cox proportional hazard models and multilevel mixed-effects modeling. Results: The study comprised 80 and 158 patients who underwent open and robotic sandwich technique cohorts, respectively. Open surgery was associated with significantly higher "any" complication (40% vs 27%, P-value .050) and "major" complication rate (15% vs 11%, P-value .048). All patients developed a bladder capacity >400 cc with negligible post-void residual urine, and all but one patient achieved spontaneous voiding by the end of study period (<1% clean intermittent self-catheterization [CISC] rate). By 15 months, QOL for all three domains had recovered to reach a plateau. About 45% of patients achieved potency, and the median time to achieve day and night time continence was 9 and 12 months respectively. Lower age and NVBs spared during surgery were found to be significantly associated with the earlier achievement of potency, day and night time continence, as well as better urinary and sexual summary QOL scores. Conclusions: Pitcher pot neobladder achieves satisfactory long-term functional and QOL outcomes with negligible CISC rate. Results were superior with incremental nerves spared during surgery.

Adjuvant radiation compares favorably to chemotherapy in patients with carcinoma penis and nodal positivity restricted to groin.

OBJECTIVES: To compare overall survival (OS) between adjuvant radiation, chemotherapy and chemoradiation (CCRT) postsurgery for node-positive patients with carcinoma penis. METHODS: Prospectively maintained registry for 45 patients receiving adjuvant treatment following lymph node dissection from 2011 to 2017, having minimum 6 months follow-up and more than 2 positive inguinal nodes was analyzed. Patients without pelvic nodal positivity (n= 32) were treated by radiotherapy (RT) (n = 25) or chemotherapy (n = 7); CCRT (n = 6) or chemotherapy (n = 7) was used in patients with positive pelvic nodes (n = 13). Data was collected for age, comorbidities, body mass index, tobacco exposure, treatment modality, tumor grade, pathological T and N stage, and extra-nodal extension. OS was compared between different treatment modalities stratifying patients with and without pelvic nodal positivity. Multivariate cox proportional hazard analysis was used to narrow down remaining variables and Inverse Probability Treatment Weights modeling was used to determine average treatment effect. RESULTS: About 12 of 14 patients in the chemotherapy group received both cisplatin and paclitaxel. Pathological T stage, N stage and extra-nodal extension had significant association with OS on multivariate analysis. Among patients with nodal positivity restricted to groin the estimated average OS when all patients received adjuvant RT was 1,438 days (95% confidence interval [CI] 1,256-1,619 days, Pvalue <0.0001). The estimated average OS if all patients received chemotherapy was lower by 1,007 days (95% CI 810-1,202 days, P value <0.0001). Among patients with positive pelvic nodes the estimated average OS when all patients received adjuvant CCRT was 467 days (95% CI 368-566 days, P value <0.0001). The estimated average OS difference if all patients received chemotherapy was 17 days (95% CI -144 to 178 days, Pvalue 0.21). CONCLUSION: In patients with nodal positivity limited to groin, adjuvant RT proved superior to chemotherapy. Among patients with pelvic nodal positivity, CCRT offers no significant OS advantage over combination chemotherapy.

Identification of Inhibitors of Integrin Cytoplasmic Domain Interactions With Syk.

Leukocyte inflammatory responses require integrin cell-adhesion molecule signaling through spleen tyrosine kinase (Syk), a non-receptor kinase that binds directly to integrin ß-chain cytoplasmic domains. Here, we developed a high-throughput screen to identify small molecule inhibitors of the Syk-integrin cytoplasmic domain interactions. Screening small molecule compound libraries identified the ß-lactam antibiotics cefsulodin and ceftazidime, which inhibited integrin ß-subunit cytoplasmic domain binding to the tandem SH2 domains of Syk (IC50 range, 1.02-4.9 µM). Modeling suggested antagonist binding to Syk outside the pITAM binding site. Ceftazidime inhibited integrin signaling via Syk, including inhibition of adhesion-dependent upregulation of interleukin-1ß and monocyte chemoattractant protein-1, but did not inhibit ITAM-dependent phosphorylation of Syk mediated by FcγRI signaling. Our results demonstrate a novel means to target Syk independent of its kinase and pITAM binding sites such that integrin signaling via this kinase is abrogated but ITAM-dependent signaling remains intact. As integrin signaling through Syk is essential for leukocyte activation, this may represent a novel approach to target inflammation.

Milli-Watt Power Harvesting from Dual Triboelectric and Piezoelectric Effects of Multifunctional Green and Robust Reduced Graphene Oxide/P(VDF-TrFE) Composite Flexible Films.

For a variety of mechanical energy harvesting as well as biomedical device applications, flexible energy devices are useful which require the development of environment-friendly and robust materials and devices. In this manuscript, we demonstrate a lead-free, facile, low-cost, sol-gel-processed reduced graphene oxide (rGO)/P(VDF-TrFE) nanocomposite with multipurpose capability demonstration as a piezoelectric nanogenerator (PENG) and hybrid piezoelectric triboelectric nanogenerator (HPTENG) devices. The structural analysis of the materials shows that the interactions between the rGO and P(VDF-TrFE) matrix help in breaking the centrosymmetry of rGO, resulting in a strong enhancement in the piezoelectric, ferroelectric, and triboelectric properties of composites over pristine P(VDF-TrFE) films. In the case of PENG, the composite devices showed >22 times improvement in the piezoelectric output voltage over the pristine P(VDF-TrFE) PENG device with the highest output voltage of 89.7 V for the 0.5 wt % rGO composite. Also, HPTENG devices based on composite films generated an average VOC of 227 V, much higher than the pristine P(VDF-TrFE)-based devices. Maximum output power densities measured were 0.28 W/cm3 and 0.34 mW/cm3 for hybrid piezoelectric-triboelectric and piezoelectric devices, respectively. The triboelectric devices demonstrated lighting of 45 blue light-emitting diodes directly, connected in series, by harvesting mechanical energy generated by repeated finger tapping. The study highlights the promise of rGO/P(VDF-TrFE) composites for PENG and HPTENG devices with dramatically improved electrical output.

Utility of anteroposterior diameter ratio of tumor and abdomen for laparoscopic approach for radical nephrectomy in large renal masses.

INTRODUCTION: Laparoscopic radical nephrectomy (LRN) is now increasingly done for tumors larger than 10 cm. Despite selection of favorable cases, LRN may not be successful due to lack of adequate working space with large tumors. We describe a new feature on Contrast Enhanced Computed Tomography (CECT) abdomen to predict feasibility of LRN for large renal masses between 10 and 15 cm. METHODS: From January 2005 to December 2015, renal tumors between 10 and 15 cm were selected retrospectively for LRN. Patients with retroperitoneal lymphadenopathy, Inferior vena cava (IVC) thrombus and involvement of adjacent organs were excluded. Anteroposterior (AP) diameter ratio of renal tumor and abdomen (APROTA) was calculated by dividing the maximum AP diameter of tumor along with normal renal parenchyma, by the AP diameter of abdomen on CECT. The patients were stratified into two groups: Group A (successful LRN) and Group B (conversion to open surgery) and outcomes were compared. The reasons for conversion were also noted. RESULTS: Of 29 patients, 16 (55.2%) had successful LRN (Group A), while 13 (44.8%) had conversion to open surgery (group B). The median tumor size in Group A was 11.3 ± 1.8 cm and in Group B was 13.6 ± 1.26 cm. Eleven of 13 patients had conversion due to large tumor size causing failure to progress. Two conversions were due to bleeding and injury to the colon each. There was a significant difference in the APROTA in group A and B [0.43 ± 0.09 in group A and 0.64 ± 0.14 in group B (p = 0.0001)]. CONCLUSIONS: Patients with APROTA of more than 0.65 are unlikely to have successful outcome with LRN.

Ureterocalicostomy for Reconstruction of Complicated Ureteropelvic Junction Obstruction in Adults: Long-Term Outcome and Factors Predicting Failure in a Contemporary Cohort.

PURPOSE: Ureterocalicostomy is a well established treatment option in patients who have recurrent ureteropelvic junction obstruction with postoperative fibrosis and a relatively inaccessible renal pelvis. We evaluated the long-term outcome of ureterocalicostomy and factors predicting its failure. MATERIALS AND METHODS: We retrospectively analyzed data on 72 patients who underwent open or laparoscopic ureterocalicostomy from 2000 to 2014. Variables that may affect the outcomes of ureterocalicostomy were assessed with regard to primary pathology findings, patient age, serum creatinine, preoperative renal size (less than and greater than 15 cm), renal cortical thickness (less than and greater than 5 mm), hydronephrosis grade and preoperative renal function (glomerular filtration rate less than and greater than 20 ml/minute/1.73 m2). The surgery outcome was calculated in terms of success or failure. Factors predicting failure were evaluated by univariate and multivariate analysis. Failure was defined as an additional procedure required postoperatively due to persistent symptoms and/or followup renal scan showing persistent significant obstruction with deterioration of renal function on at least 2 occasions 3 months apart. Patients with less than 2-year followup were excluded from study. RESULTS: We analyzed data on 72 patients who underwent ureterocalicostomy during this period. Mean ± SD age of the study group was 28.9 ± 12.3 years and mean baseline serum creatinine was 1.1 ± 0.3 mg/dl. The mean glomerular filtration rate was 27.8 ± 11.6 ml/minute/1.73 m2 and mean cortical thickness of the operated kidney was 7 ± 3.86 mm. Common indications for ureterocalicostomy were failed previous pyeloplasty and/or endopyelotomy in 35 patients (48.6%) and secondary ureteropelvic junction obstruction after pyelolithotomy or percutaneous nephrolithotomy in 24 (33.3%). The most common complication was urinary tract infection, which was seen in 22 patients (30.6%). At a mean followup of 60.3 ± 13.6 months 50 patients (69.5%) had a successful outcome. Treatment failed in 22 patients (30.5%), including 6 who required nephrectomy, while 13 were treated with frequent changes of Double-J® stents or with balloon dilation. In 3 patients ureterocalicostomy was repeated. The rate of failed ureterocalicostomy was higher in patients with a low preoperative glomerular filtration rate (less than 20 ml/minute/1.73 m2), attenuated cortical thickness (less than 5 mm) and higher creatinine (greater than 1.7 mg/dl) on univariate analysis. However, on multivariate analysis poor cortical thickness and a low glomerular filtration rate were independent predictors of failure. CONCLUSIONS: Ureterocalicostomy is an acceptable salvage option with a satisfactory long-term outcome. Patients with a low preoperative glomerular filtration rate (less than 20 ml/minute/1.73 m2) and a thinned out cortex (less than 5 mm) showed a poor outcome after ureterocalicostomy.