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An efficient and short synthesis of fused dihydroisoquinolines, diaryl substituted pyridine derivatives in good to high yields has been established by using an environmentally safe, solvent-metal-oxidant-free tandem approach. In this article, we discuss how the electrocyclic reaction is more pronounced in the solid phase in the presence of urea, whereas the typical aza-Michael addition is more prominent in presence of arylamine in the solution phase for 3-(2-formylcycloalkenyl)acrylic ester derivative substrates. The wide range of substrates and urea-promoted neat synthesis made our approach more significant in medical and also analytical science. Moreover, an isoquinoline alkaloid decumbenine B analogue has been synthesized by using our newly developed neat methodology. We have also investigated the photophysical properties of the synthesized fused dihydroisoquinoline derivatives. One of the synthesized molecules was used as a sensor for the selective detection of toxic picric acid. Therefore, the effective neat synthesis and molecular sensing applications of these compounds made our approach more exciting in the field of heterocyclic chemistry., (© 2023 Wiley-VCH GmbH.)

A novel and efficient cerium-catalyzed tandem oxidation and intermolecular ring cyclization of vicinal diols with hydrazones has been achieved for the regioselective synthesis of pyrazole derivatives. The corresponding 1,3-di- and 1,3,5-trisubstituted pyrazoles were obtained in moderate to excellent yields. The reaction has the advantages of mild conditions, easily available starting materials, broad substrate scope and good functional group tolerance.

Background: Opioid-related inpatient hospital stays are increasing at alarming rates. Unidentified and poorly treated opioid withdrawal may be associated with inpatients leaving against medical advice and increased health care utilization. To address these concerns, we developed and implemented a clinical pathway to screen and treat medical service inpatients for opioid withdrawal., Methods: The pathway process included a two-item universal screening instrument to identify opioid withdrawal risk (Opioid Withdrawal Risk Assessment [OWRA]), use of the validated Clinical Opiate Withdrawal Scale (COWS) to monitor opioid withdrawal symptoms and severity, and a 72-h buprenorphine/naloxone-based treatment protocol. Implementation outcomes including adoption, fidelity, and sustainability of this new pathway model were measured. To assess if there were changes in nursing staff acceptability, appropriateness, and adoption of the new pathway process, a cross-sectional survey was administered to pilot four hospital medical units before and after pathway implementation., Results: Between 2016 and 2018, 72.4% (77,483/107,071) of admitted patients received the OWRA screening tool. Of those, 3.0% (2,347/77,483) were identified at risk for opioid withdrawal. Of those 2,347 patients, 2,178 (92.8%) were assessed with the COWS and 29.6% (645/2,178) were found to be in active withdrawal. A total of 49.5% (319/645) patients were treated with buprenorphine/naloxone. Fifty-seven percent (83/145) of nurses completed both the pre- and post-pathway implementation surveys. Analysis of the pre/post survey data revealed that nurse respondents were more confident in their ability to determine which patients were at risk for withdrawal ( p = .01) and identify patients currently experiencing withdrawal ( p < .01). However, they cited difficulty working with the patient population and coordinating care with physicians., Conclusions: Our study demonstrates a process for successfully implementing and sustaining a clinical pathway to screen and treat medical service inpatients for opioid withdrawal. Standardizing care delivery for patients in opioid withdrawal can also improve nursing confidence when working with this complex population.

An amphiphilic phytochemical fraction isolated from methanol extract of Gymnema sylvestre leaf powder contained six terpenoids, two flavonoids, and one alkaloid that induced rapid flip-flop of fluorescent phospholipid analog in the phosphatidyl choline bilayer. Lipid-flipping activity of the methanol-extracted fraction of G. sylvestre (MEFGS) was dose-dependent and time-dependent with a rate constant k = (12.09 ± 0.94) mg -1 min -1 that was saturable at (40 ± 1) % flipping of the fluorescent lipid analogue. Interactions of MEFGS phytochemicals with large unilamelar vesicles led to time-dependent change in their rounded morphology into irregular shapes, indicating their membrane-destabilizing activity. MEFGS exhibited antibacterial activity on Escherichia coli (MTCC-118), Staphylococcus aureus (MTCC-212), and Pseudomonas aeruginosa (MTCC-1035) with IC 50 values 0.5, 0.35, and 0.1 mg/mL, respectively. Phytochemicals in MEFGS increased membrane permeabilization in all three bacteria, as indicated by 23, 17, and 17% increase in the uptake of crystal violet, respectively. MEFGS enhanced membrane damage, resulting in a 3-5 fold increase in leakage of cytosolic ions, 0.5-2 fold increase in leakage of PO 4 - , and 15-20% increase in loss of cellular proteins. MEFGS synergistically increased the efficacy of curcumin, amoxillin, ampicillin, and cefotaxime on S. aureus probably by enhancing their permeability into the bacterium. For the first time, our study reveals that phytochemicals from G. sylvestre enhance the permeability of the bacterial plasma membrane by facilitating flip-flop of membrane lipids. Lipid-flipping phytochemicals from G. sylvestre can be used as adjuvant therapeutics to enhance the efficacy of antibacterials by increasing their bioavailability in the target bacteria., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)

Objective: Comparing the efficacy, safety and outcome of percutaneous intrervention for Budd-Chiari Syndrome (BCS) patients with bilirubin less than 3 and 3-6 mg dl -1 ., Methods and Materials: 188 BCS patients having serum bilirubin ≤6 mg dl -1 and underwent percutaneous interventions were divided into two groups based on bilirubin level: 151 patients having bilirubin <3 mg dl -1 were included in Group 1; and 37 patients having bilirubin 3-6 mg dl -1 were included in Group 2. Both group were compare for technical success (successful recanalization of hepatic venous stenosis or creation of portocaval shunt with post-procedure gradient ≤5 mm of Hg), Safety (procedure-related mortality/morbidity or patient required transplantation) and outcome (resolution of clinical symptoms and survival)., Results: Technical success was 94.7% in Group 1-89.1% in Group 2 with overall success rate was 93.6%. No significant differences observed between the two groups in regards to procedure related complication. Overall transplant-free survival at 1 and 5 years after intervention in both groups was 96.3 and 91.2% respectively. 1-year and 5-year survivals in Group 1 was 96.7%, and 93.1%, whereas Group 2 was 94.6 and 90.1% with no statically significantly difference between the two groups ( p = 0.59). Percutaneous intervention results are good in patients having bilirubin up to 6 mg dl -1 , i.e . mild to moderate liver dysfunctions., Conclusion: Technical success, survival and outcome of percutaneous intervention in BCS patients having serum bilirubin 3-6 mg dl -1 was comparable to patients having bilirubin level <3 mg dl -1 ., Advances in Knowledge: Percutaneous intervention treatment is suitable for treatment for symptomatic BCS patients having bilirubin up to 6 mg  dl -1 .

Background: Use of suxamethonium is associated with an increase in intraocular pressure (IOP) and may be harmful for patients with penetrating eye injuries. The purpose of our study was to observe the efficacy of dexmedetomidine for prevention of rise in IOP associated with the administration of suxamethonium and endotracheal intubation., Methods: Sixty-six American Society of Anaesthesiologists I or II patients undergoing general anaesthesia for non-ophthalmic surgery were included in this randomized, prospective, clinical study. Patients were allocated into three groups to receive 0.4 μg/kg dexmedetomidine (group D4), 0.6 μg/kg dexmedetomidine (group D6) or normal saline (group C) over a period of 10 min before induction. IOP, heart rate and mean arterial pressure were recorded before and after the premedication, after induction, after suxamethonium injection and after endotracheal intubation., Results: Fall in IOP was observed following administration of dexmedetomidine. IOP increased in all three groups after suxamethonium injection and endotracheal intubation, but it never crossed the baseline value in group D4 as well as in group D6. Fall in mean arterial pressure was noticed after dexmedetomidine infusion, especially in the D6 group., Conclusion: Dexmedetomidine (0.6 μg/kg as well as 0.4 μg/kg body weight) effectively prevents rise of IOP associated with administration of suxamethonium and endotracheal intubation. However, dexmedetomidine 0.6 μg/kg may cause significant hypotension. Thus, dexmedetomidine 0.4 μg/kg may be preferred for prevention of rise in IOP.

The (pyridylazo)oxime ligand (C(5)H(4)N)N=NC(=NOH)C(6)H(4)R(p), HRL (R = H, Me), has been synthesized with the objective of promoting the very rare mononuclear oximato-O coordination. The synthesis involves hydrazone nitrosation. HRL reacts with M(ClO(4))(2).6H(2)O, affording [M(RL)(2)] (M = Mn, Fe), and X-ray structure determinations have indeed revealed the presence of the desired oximato-O coordination mode in the distorted octahedral MN(4)O(2) sphere characterized by a 2-fold axis of symmetry relating the two tridentate ligands, all chelate rings being five-membered. The M-N and M-O distances are relatively short (1.84-1.99 Å), consistent with spin-pairing (M = Mn, S = (1)/(2); M = Fe, S = 0). The M-N bond length trend, Mn(II) > Fe(II), is in accord with the larger radius of the low-spin Mn(II) atom. The M-O length order is, however, Mn(II) < Fe(II). This reversal occurs because of the rigidity of the ligand skeleton. Significant M-azo back-bonding is present (N=N length approximately 1.30 Å). [Mn(RL)(2)] displays hyperfine-split axial EPR spectra (g( parallel) approximately 1.98, g( perpendicular) approximately 2.06, A( parallel) approximately 170 G, A( perpendicular) approximately 65 G) in frozen solution as well as in polycrystalline [Fe(RL)(2)] lattices. The quasireversible Fe(III)/Fe(II) couple of [Fe(RL)(2)] has E(1/2) approximately 0.7 V. The oxidized complex [Fe(RL)(2)]PF(6) has been electrosynthesized. It is low-spin (S = (1)/(2)) and displays axial EPR spectra (g( parallel) approximately 1.98, g( perpendicular) approximately 2.14) in frozen solution. The Mn(II) --> Mn(III) oxidation ( approximately 1.0 V) in [Mn(RL)(2)] is irreversible. Crystal data for [Mn(HL)(2)].CH(2)Cl(2): crystal system monoclinic, space group I2/a, a = 14.142(7) Å, b = 10.721(7) Å, c = 16.933(10) Å, beta = 93.01(4) degrees, Z = 4. Crystal data for [Fe(HL)(2)].CH(2)Cl(2): crystal system monoclinic, space group I2/a, a = 14.254(6) Å, b = 10.742(6) Å, c = 16.719(8) Å, beta = 92.35(4) degrees, Z = 4.

The first azo-imine chelate system, Pd(N(H)C(R)NNPh)(2) (Pd(RA)(2)), has been isolated in the form of diamagnetic solids by the 6e(-)-6H(+) reduction of bis(phenylazooximato)palladium(II), Pd(N(O)C(R)NNPh)(2) (abbreviated Pd(RB)(2)), with ascorbic acid in a mixed solvent (R = Ph, alpha-naphthyl). Selected spectral features are described. The X-ray structures of Pd(PhA)(2) and Pd(PhB)(2) have revealed trans-planar geometry consistent with metal oxidation state of +2. Bond length trends within the chelate rings are rationalized in terms of steric and electronic factors. In Pd(PhA)(2) a total of 10 ligand pi electrons are present, each formally monoanionic ligand contributing five. Model EHMO studies have revealed that the filled HOMO (a(u)) in Pd(RA)(2) is a bonding combination of two ligand pi orbitals with large azo contributions. The LUMO (b(g)) is roughly the corresponding antibonding combination. The outer pi-electron configuration of Pd(RA)(2) is (a(u))(2)(b(g))(0). Four successive voltammetric responses, two oxidative and two reductive, are observed. The E(1/2) range is -1.3 to +0.8 V vs SCE for Pd(PhA)(2) in a 1:9 MeCN-CH(2)Cl(2) mixture (Pt electrode). EPR and electronic spectra of the electrogenerated one-electron-oxidized complex Pd(PhA)(2)(+) are described. The azo-imine system is compared with imine-imine and azo-azo systems. Crystal data for the complexes are as follows. Pd(PhA)(2): crystal system monoclinic; space group C2/c; a = 18.167(5) Å, b = 7.420(3) Å, c = 16.527(6) Å; beta = 92.70(3) degrees; V = 2225(1) Å(3); Z = 4; R = 2.61%, R(w) = 3.58%. Pd(PhB)(2): crystal system monoclinic; space group P2(1)/n; a = 5.735(5) Å, b = 10.797(6) Å, c = 18.022(11) Å; beta = 97.73(6) Å; V = 1105(1) Å(3); Z = 2; R = 3.37%; R(w) = 3.40%.