Does preoperative silodosin administration facilitate ureteral dilatation during flexible ureterorenoscopy? A randomized clinical trial.

PURPOSE: To assess whether preoperative administration of silodosin can facilitate the placement of ureteral access sheath (UAS) prior to flexible ureteroscopy (F-URS) and reduce the occurrence of ureteric injury in challenging cases. METHODS: This prospective randomized clinical trial was carried out on 147 patients diagnosed with upper ureteric stone or stone kidney, non-stented. The patients were randomly divided into two equal groups. Group A (silodosin group) included patients in whom F-URS was done with daily preoperative intake of 8 mg silodosin for 1 week and group B (placebo/control group) included patients in whom F-URS was done with daily preoperative intake of placebo tablets. RESULTS: In group A, a total of 23 (33.3%) experienced ureteral wall injury following UAS insertion, while in group B, this occurred in 40 patients (59.7%). There was a statistically significant difference in the grade of ureteral wall injury between the two groups (P < 0.001). In the multiple regression analysis, age, operative time and silodosin were found to be significant risk factors for ureteral wall injury (P = 0.007, 0.041 and < 0.001, respectively). CONCLUSIONS: The administration of silodosin prior to retrograde intrarenal surgery (RIRS) effectively prevented significant ureteral wall damage and reduced initial postoperative discomfort.

Microwave assisted the short time clean synthesis of 1,3-diketones as building blocks in heterocyclic synthesis: a facile synthesis and antimicrobial evaluation of new dihydropyridine, 4H-pyrane, dihydropyridazine, pyrimidine and pyrazole derivatives.

The compounds bearing naphthalene moiety can be used as medical preparations because of their wide spectrum of biological activity and low toxicity. In this study, a new series of azoles or azines were synthesized from the reaction of the key intermediate 1-(1-hydroxynaphthalen-2-yl)-3-phenylpropane-1,3-dione 3 with a variety of electrophilic and nucleophilic reagents under a variety of mild conditions. The chemical structures of these compounds were confirmed by various spectroscopic methods such as (IR, 1H-NMR, 13C-NMR, mass spectra and elemental analyses). The prepared compounds were screened in vitro for their anti-microbial activity against some species of Gram-positive bacteria (Staphylococcus aureus and Bacillus subtilis) and Gram-negative bacteria (Escherichia coli and Pseudomonas aeuroginosa). Anti-fungal activities of the compounds were tested against yeast and mycelial fungi,Candida albicans and Aspergillus flavus. The antimicrobial activity of this series was showed either weak or moderate activities.

Toll-Like Receptor-4 Antagonist Enhances the Repair of Ultraviolet Radiation-Induced DNA Damage and Augments Anti-Tumor Immune Responses in Mice.

Ultraviolet (UV) irradiation of the skin is related to the development of skin cancer. UVB also causes DNA damage in the form of cyclobutane pyrimidine dimers (CPDs), which can result in stable mutations. Toll-like receptor 4 (TLR4), a component of innate immunity, plays a key role in cancer. Previous studies from our laboratory have observed that TLR4 deficiency resulted in the repair of UVB-induced DNA damage, inhibition of UVB-induced immune suppression, and carcinogenesis. In this study, we determined the efficacy of TLR4 antagonist TAK-242 in regulation of UVB-induced DNA damage, inflammation, and tumor development. Our results indicate that TAK-242 treatment increased the expression of xeroderma pigmentosum group A (XPA) mRNA, resulting in the repair of UVB-induced CPDs in skin of SKH-1 mice. Treatment with TAK-242 also inhibited the activation of NLR family pyrin domain containing 3 (NLRP3) in UVB-exposed skin of SKH-1 mice. Cutaneous carcinogenesis was significantly reduced in mice treated with TAK-242 in comparison to vehicle-treated mice. The proinflammatory cytokines IL-1ß, IL-6, and TNF-α were also found to be significantly greater in vehicle-treated mice than TAK-242-treated mice. Finally, treatment with TAK-242 augmented anti-tumor immune responses in mice. Our data provide further evidence that activation of the TLR4 pathway promotes the development of UV-induced non-melanoma skin cancer mediated at least in part on its negative effects on DNA damage. Moreover, treatment with the TLR4 inhibitor TAK-242 may be effective for prevention of skin cancer.

Synthesis and Antimicrobial Evaluation of Some Novel Pyrimidine, Pyrazole, Chromene and Tetrahydrobenzo[b]thiophene Derivatives Bearing Pyrimidinthione Moiety.

AIM AND OBJECTIVE: A novel collection of fused pyrimidine, pyridine, pyrazole, chromene and thiophene derivatives 2-30 have been newly synthesized by using the 1a, b as starting material. Fused pyrane exhibits a range of pharmacological activity such as cancer agents [1], antimicrobial [2-4], antioxidant [5], antiproliferative [6], cytotoxic activity [7], anticipated antitumor [8], antiparkinsonian [9] and anti-inflammatory [10]. Moreover, pyrane derivatives are well known for bacterial biofilm disruptor [11], anticonvulsant [12] and inhibitors of mycobacterium bovis [13]. MATERIALS AND METHODS: All melting points were measured using the Akofler Block instrument and are uncorrected. IR spectra (KBr) were recorded on a FTIR 5300 spectrometer (υ, cm-1). The 1H-NMR spectra were recorded on a Varian Gemini spectrometer. The 1H-NMR spectra were run at 300, 400 MHz and 13C-NMR spectra were run at 100 MHz in DMSO-d6, CDCl3 as solvents. The chemical shifts are expressed in parts per million (ppm) by using tetramethylsilane (TMS) as an internal reference, 1000 EX mass spectrometer at 70 eV. The purity of synthesized compounds was checked by thin-layer chromatography (TLC) (aluminum sheets) using nhexane, EtOAc (9:1, V/V, 7:3 V/V) eluent. Elemental analyses were carried out by the Microanalytical Research Center, Faculty of Science, and Microanalytical Unit, Faculty of Pharmacy, Cairo University, Egypt. RESULTS AND DISCUSSION: A novel series of azoles and azines were designed and prepared via the reaction of 7-amino- 5-(4-chlorophenyl)-4-phenyl-2-thioxo-2,5-dihydro-1H-pyrano- [2,3-d]pyrimidine-6-carbonitrile 1a and 7-amino-4,5- diphenyl-2-thioxo-2,5-dihydro-1H-pyrano[2,3-d]-pyrimidine-6-carbonitrile 1b with some electrophilic and nucleophilic reagents. The structures of target compounds were confirmed by elemental analyses and spectral data. The novel synthesized compounds showed good antimicrobial activity against the previously mentioned microorganisms. CONCLUSION: In conclusion, compounds 1a, 1b underwent ready cyclization to give fused heterocyclic compounds through reaction with different reagents and under different conditions and subjected to antimicrobial screening.

Effects of a Psychoeducational Program on Hemoglobin A1c Level and Health-Related Quality of Life in Patients with Type 2 Diabetes Mellitus, Jazan, Saudi Arabia.

BACKGROUND: Diabetes mellitus (DM) is a growing health problem. Care programs should involve the patients to upgrade their diabetes condition and health-related quality of life (HRQoL). OBJECTIVE: The present study aimed to assess the effects of a psychoeducational intervention program on an indicator of glycemic control and HRQoL among type 2 diabetic patients. METHODS: In this quasi-experimental (pre- and postinterventional) study, 99 outpatients with type 2 diabetes were selected randomly from those attending primary health care centers in Jazan, Saudi Arabia, in 2016. Hemoglobin A1c levels (HbA1c) were measured by the colorimetric method, and HRQoL was assessed by the Arabic version of the RAND 36-Item Health Survey 1.0 (RAND-36). The psychoeducational program was conducted on the participants for 4 weeks, and preprogram findings were compared with the postprogram findings after a 5-month follow-up. RESULTS: After the intervention, there was a statistically significant reduction in the mean value of HbA1c from 9.8 to 7.7 (P < 0.001), and there was significant improvement in the mean scores of the following HRQoL scales: role limitations due to emotional problems, energy/fatigue, emotional well-being, and general health (P < 0.01). In addition, the impact of the program on HRQoL was better among males and among patients who were older than forty years than among women and patients who were forty years old or younger. CONCLUSION: The application of such psychoeducational intervention programs can be helpful in the improvement of HbA1c levels and HRQoL for patients with DM.

Correction: EPR detection and characterisation of a paramagnetic Mo(iii) dihydride intermediate involved in electrocatalytic hydrogen evolution.

Correction for 'EPR detection and characterisation of a paramagnetic Mo(iii) dihydride intermediate involved in electrocatalytic hydrogen evolution' by Christopher Prior, et al., Dalton Trans., 2016, 45, 2399-2403.

EPR detection and characterisation of a paramagnetic Mo(iii) dihydride intermediate involved in electrocatalytic hydrogen evolution.

EPR spectroscopy and theoretical data show that the slow heterogeneous electron-transfer kinetics associated with the reduction of an 18-electron Mo(IV) acetato dihydride are a consequence of an η(2)-η(1) rearrangement of the carboxylate ligand which gives a unique paramagnetic 17-electron Mo(III) dihydride.

Solar fuels: photoelectrosynthesis of CO from CO2 at p-type Si using Fe porphyrin electrocatalysts.

Photoelectrocatalytic conversion of CO2 to CO can be driven at a boron-doped, hydrogen terminated, p-type silicon electrode using a meso-tetraphenylporphyrin Fe(III) chloride in the presence of CF3CH2OH as a proton source and 0.1 M [NBu4][BF4]/MeCN/5% DMF (v/v) as the electrolyte. Under illumination with polychromatic light, the photoelectrocatalysis operates with a photovoltage of about 650 mV positive of that for the dark reaction. Carbon monoxide is produced with a current efficiency >90% and with a high selectivity over H2 formation. Photoelectrochemical current densities of 3 mA cm(-2) at -1.1 V versus SCE are typical, and 175 turnovers have been attained over a 6 h period. Cyclic voltammetric data are consistent with a turnover frequency of k(Si)(obs)=0.24×10(4) s(-1) for the photoelectrocatalysis at p-type Si at -1.2 V versus SCE this compares with k(Si)(obs)=1.03×10(4) s(-1) for the electrocatalysis in the dark on vitreous carbon at a potential of -1.85 V versus SCE.

Ferracyclic carbamoyl complexes related to the active site of [Fe]-hydrogenase.

The active site of the [Fe]-hydrogenase features an iron(II) centre bearing cis carbonyl groups and a chelating pyridine-acyl ligand. Reproducing these unusual features in synthetic models is an intriguing challenge, which will allow both better understanding of the enzymatic system and more fundamental insight into the coordination modes of iron. By using the carbamoyl group as a surrogate for acyl, we have been able to synthesize a range of ferracyclic complexes. Initial reaction of Fe(CO)4Br2 with 2-aminopyridine yields a complex bearing a labile solvent molecule, which can be replaced by stronger donors bearing phosphorus atoms to produce a number of derivatives. Introduction of a hydroxy group using this method is unsuccessful both with a free OH group and when this is silyl-protected. In contrast, the analogous reactions starting from 2,6-diaminopyridine does allow synthesis of complexes bearing a pendant basic group.

Incidental hyperdensities within the reticuloendothelial system.

This is a case report of a 79-year-old woman who was found to have numerous hyperdense nodular lesions in the upper abdomen, which were incidentally discovered during routine follow-up of a lung nodule. These hyperdense lesions included a lace-like reticular distribution within the liver, multiple extremely dense lymph nodes, and a shrunken hyperdense spleen. We discuss differential considerations for such a constellation of findings and explain why we believe the findings in this case are consistent with prior thorium dioxide exposure. We conclude with a discussion of the pathophysiology and important complications of thorium dioxide exposure and the best imaging modalities for its detection. We believe that this is an important entity that all physicians should be aware of because even though it is seldom seen today, it has characteristic imaging findings and the correct diagnosis is critical given the increased risk of malignancy for which such patients should be screened for.

Towards alternatives to anodic water oxidation: basket-handle thiolate Fe(III) porphyrins for electrocatalytic hydrocarbon oxidation.

Selective electrocatalytic oxidation of hydrocarbons to alcohols, epoxides or other (higher value) oxygenates should in principal present a useful complementary anodic half-cell reaction to cathodic generation of fuels from water or CO(2) viz. an alternative to oxygen evolution. A series of new basket-handle thiolate Fe(III) porphyrins have been synthesised and shown to mediate anodic oxidation of hydrocarbons, specifically adamantane hydroxylation and cyclooctene epoxidation. We compare yields obtained by electrochemical and chemical oxidation of the thiolate porphyrins and benchmark their behaviour against that of Fe(III) tetraphenyl porphyrin chloride and its tetrapentafluorophenyl analogue.

Solar fuels: visible-light-driven generation of dihydrogen at p-type silicon electrocatalysed by molybdenum hydrides.

We show that a robust molybdenum hydride system can sustain photoelectrocatalysis of a hydrogen evolution reaction at boron-doped, hydrogen-terminated, p-type silicon. The photovoltage for the system is about 600-650 mV and the current densities, which can be sustained at the photocathode in non-catalytic and catalytic regimes, are similar to those at a photoinert vitreous carbon electrode. The kinetics of electrocatalysed hydrogen evolution at the photocathode are also very similar to those measured at vitreous carbon-evidently visible light does not significantly perturb the catalytic mechanism. Importantly, we show that the doped (1-10â€…Ω cm) p-type Si can function perfectly well in the dark as an ohmic conductor and this has allowed direct comparison of the cyclic voltammetric behaviour of the response of the system under dark and illuminated conditions at the same electrode. The p-type Si we have employed optimally harvests light energy in the 600-700 nm region and with 37 mW cm(-2) illumination in this range; the light to electrochemical energy conversion is estimated to be 2.8 %. The current yield of hydrogen under broad tungsten halide lamp illumination at 90 mW cm(-2) is (91±5) % with a corresponding chemical yield of (98±5) %.

Early assessment of the efficacy of digital infrared thermal imaging in pediatric extremity trauma.

Young children or those with intellectual disability with trauma to an extremity often undergo radiographs of the whole limb. The objective of the study was to assess the efficacy of digital infrared thermal images (DITI) in pediatric extremity trauma. We hypothesized fractures to be associated with local hyperthermia, detectable with DITI, which could direct focused radiographs. In this exploratory study, patients seen over a 2-month period in a pediatric emergency department for limb trauma were included if an extremity radiograph was taken on the same day. Patients had DITI of symptomatic and contralateral limbs. The warmest area of each image was compared to the site of pain and/or fracture on the radiograph. Fifty-one patients were enrolled. DITI matched 73% of pain sites. Fractures were seen in 11 patients. DITI matched 7 of 11 (64%) fracture sites. DITI performance in pinpointing the site of injury, although suboptimal, is encouraging for further evaluation.

Treating and downstaging hepatocellular carcinoma in the caudate lobe with yttrium-90 radioembolization.

PURPOSE: This study was designed to determine the technical feasibility, safety, efficacy, and potential to downstage patients to within transplantation criteria when treating patients with hepatocellular carcinoma (HCC) of the caudate lobe using Y90 radioembolization. METHODS: During a 4-year period, 8 of 291 patients treated with radioembolization for unresectable HCC had disease involving the caudate lobe. All patients were followed for treatment-related clinical/biochemical toxicities, serum tumor marker response, and treatment response. Imaging response was assessed with the World Health Organization (WHO) and European Association for the Study of the Liver (EASL) classification schemes. Pathologic response was reported as percent necrosis at explantation. RESULTS: Caudate lobe radioembolization was successfully performed in all eight patients. All patients presented with both cirrhosis and portal hypertension. Half were United Network for Organ Sharing (UNOS) stage T3 (n = 4, 50%). Fatigue was reported in half of the patients (n = 4, 50%). One (13%) grade 3/4 bilirubin toxicity was reported. One patient (13%) showed complete tumor response by WHO criteria, and three patients (38%) showed complete response using EASL guidelines. Serum AFP decreased by more than 50% in most patients (n = 6, 75%). Four patients (50%) were UNOS downstaged from T3 to T2, three of who underwent transplantation. One specimen showed histopathologic evidence of 100% complete necrosis, and two specimens demonstrated greater than 50% necrosis. CONCLUSIONS: Radioembolization with yttrium-90 appears to be a feasible, safe, and effective treatment option for patients with unresectable caudate lobe HCC. It has the potential to downstage patients to transplantation.

Paramagnetic bridging hydrides of relevance to catalytic hydrogen evolution at metallosulfur centers.

Paramagnetic hydrides are likely intermediates in hydrogen-evolving enzymic and molecular systems. Herein we report the first spectroscopic characterization of well-defined paramagnetic bridging hydrides. Time-resolved FTIR spectroelectrochemical experiments on a subsecond time scale revealed that single-electron transfer to the µ-hydride di-iron dithiolate complex 1 generates a 37-electron valence-delocalized species with no gross structural reorganization of the coordination sphere. DFT calculations support and (1)H and (2)H EPR measurements confirmed the formation an S = ½ paramagnetic complex (g = 2.0066) in which the unpaired spin density is essentially symmetrically distributed over the two iron atoms with strong hyperfine coupling to the bridging hydride (A(iso) = -75.8 MHz).

Protonation of [FeFe]-hydrogenase sub-site analogues: revealing mechanism using FTIR stopped-flow techniques.

The formation of transient metal hydride(s) at the metallo-sulfur active sites of [FeFe]-hydrogenase is implicated in both hydrogen evolution and uptake reactions. Stopped-flow spectroscopic techniques can provide insight into the reactivity patterns of model {2Fe2S} sub-sites towards protons, and this information contributes to understanding the nature of the biological systems. In this study we have focussed on the influence of the nature of the bridging dithiolate ligand in influencing the kinetics and activation energy parameters for protonation in synthetic sub-sites including Fe2{micro-[S(CH2)(n)S]}(CO)4(PMe3)2 [n = 2, ethane-1,2-dithiolate (edt) or n = 3, propane-1,3-dithiolate (pdt)], Fe2[(micro-SCH2)2NH](CO)4(PMe3)2 and (NEt4)2{Fe2[(micro-SCH2)2NH](CO)4(CN)2}. Notably we find that (i) the presence of a nitrogen in the dithiolate bridge does not accelerate metal-metal bond protonation, and that (ii) immobilisation of (NEt4)2[Fe2(micro-pdt)(CO)4(CN)2] in a polymer matrix stabilises otherwise short-lifetime protonation products.

Radioembolization results in longer time-to-progression and reduced toxicity compared with chemoembolization in patients with hepatocellular carcinoma.

BACKGROUND & AIMS: Chemoembolization is one of several standards of care treatment for hepatocellular carcinoma (HCC). Radioembolization with Yttrium-90 microspheres is a novel, transarterial approach to radiation therapy. We performed a comparative effectiveness analysis of these therapies in patients with HCC. METHODS: We collected data from 463 patients who were treated with transarterial locoregional therapies (chemoembolization or radioembolization) over a 9-year period. We excluded patients who were not appropriate for comparison and analyzed data from 245 (122 who received chemoembolization and 123 who received radioembolization). Patients were followed for signs of toxicity; all underwent imaging analysis at baseline and follow-up time points. Overall survival was the primary outcome measure. Secondary outcomes included safety, response rate, and time-to-progression. Uni- and multivariate analyses were performed. RESULTS: Abdominal pain and increased transaminase activity were more frequent following chemoembolization (P < .05). There was a trend that patients treated with radioembolization had a higher response rate than with chemoembolization (49% vs 36%, respectively, P = .104). Although time-to-progression was longer following radioembolization than chemoembolization (13.3 months vs 8.4 months, respectively, P = .046), median survival times were not statistically different (20.5 months vs 17.4 months, respectively, P = .232). Among patients with intermediate-stage disease, survival was similar between groups that received chemoembolization (17.5 months) and radioembolization (17.2 months, P = .42). CONCLUSIONS: Patients with HCC treated by chemoembolization or radioembolization with Yttrium-90 microspheres had similar survival times. Radioembolization resulted in longer time-to-progression and less toxicity than chemoembolization. Post hoc analyses of sample size indicated that a randomized study with > 1000 patients would be required to establish equivalence of survival times between patients treated with these two therapies.

Artificial hydrogenases: assembly of an H-cluster analogue within a functionalised poly(pyrrole) matrix.

We show that a redox active {Fe(4)S(4)}(2+)-cubane assembly covalently bound within a cysteinyl-alkylammonium functionalised polypyrrole can be modified with a diiron dithiolate carbonyl unit to give an artificial hydrogenase H-cluster framework confined within the polymer matrix.

Safety of yttrium-90 microsphere radioembolization in patients with biliary obstruction.

PURPOSE: There are few data on radioembolization in the setting of biliary obstruction. The present study was performed to assess the safety of yttrium-90 ((90)Y) radioembolization in the setting of tumor-related biliary obstruction and total bilirubin levels of 2 mg/dL or lower. MATERIALS AND METHODS: Twelve patients with liver tumors underwent 19 treatment sessions with (90)Y to the obstructed liver lobe or segment. Initial bilirubin level was 2 mg/dL or lower in all cases. Measured outcomes included pre- and posttreatment white blood cell (WBC) count, total bilirubin level, and alkaline phosphatase (ALP) level. Bilirubin toxicities and biliary complications were assessed according to Common Toxicity Criteria, version 3.0. RESULTS: Lobar or segmental (90)Y was successful in all cases. Pre- and posttreatment median WBC counts (5.3 vs 5.3; P = .490), bilirubin levels (1.0 vs 1.1; P = .460), and ALP levels (195 vs 146; P = .712) showed no differences. One case of grade 3 bilirubin toxicity was noted in a patient with liver hilar nodal progression and subsequent biliary obstruction requiring external drainage. Complete resolution of biliary obstruction was seen after (90)Y treatment in one case of metastatic colorectal carcinoma at 1 month follow-up. No biliary complications (infection, sepsis, biliary necrosis, biloma formation, abscess development, or biliary stricture) were encountered in this cohort during an overall median follow-up time of 22.9 months. CONCLUSIONS: The use of (90)Y glass microspheres demonstrated a good safety profile in the setting of tumor-related biliary obstruction in patients with normal or near-normal bilirubin levels in this series, without evidence of therapy-related progressive leukocytosis, bilirubin increase, or infectious or biliary complications after treatment.

Chemoembolization for hepatocellular carcinoma: comprehensive imaging and survival analysis in a 172-patient cohort.

PURPOSE: To determine comprehensive imaging and long-term survival outcome following chemoembolization for hepatocellular carcinoma (HCC). MATERIALS AND METHODS: One hundred seventy-two patients with HCC treated with chemoembolization were studied retrospectively in an institutional review board approved protocol; this study was HIPAA compliant. Baseline laboratory and imaging characteristics were obtained. Clinical and laboratory toxicities following treatment were assessed. Imaging characteristics following chemoembolization were evaluated to determine response rates (size and necrosis) and time to progression (TTP). Survival from the time of first chemoembolization treatment was calculated. Subanalyses were performed by stratifying the population according to Child-Pugh, United Network for Organ Sharing, and Barcelona Clinic for Liver Cancer (BCLC) staging systems. RESULTS: Cirrhosis was present in 157 patients (91%); portal hypertension was present in 139 patients (81%). Eleven patients (6%) had metastases at baseline. Portal vein thrombosis was present in 11 patients (6%). Fifty-five percent of patients experienced some form of toxicity following treatment; 21% developed grade 3 or 4 bilirubin toxicity. Post-chemoembolization response was seen in 31% and 64% of patients according to size and necrosis criteria, respectively. Median TTP was 7.9 months (95% confidence interval: 7.1, 9.4) but varied widely by stage. Median survival was significantly different between patients with BCLC stages A, B, and C disease (stage A, 40.0 months; B, 17.4 months; C, 6.3 months; P < .0001). CONCLUSION: The determination of TTP and survival in patients with HCC is confounded by tumor biology and background cirrhosis; chemoembolization was shown to be a safe and effective therapy in patients with HCC.