Anticancer behaviour of 2,2'-(pyridin-2-ylmethylene)bis(5,5-dimethylcyclohexane-1,3-dione)-based palladium(II) complex and its DNA, BSA binding propensity and DFT study.

Herein, we report the synthesis and biological evaluation of [Pd(L)(OH2)Cl] complex (where L = 2,2'-(pyridin-2-ylmethylene)bis(5,5-dimethylcyclohexane-1,3-dione) as a novel promising anticancer candidate. The complex was characterized by single-crystal X-ray diffraction and other various spectroscopic techniques. Besides, the optimized structure was determined through DFT calculations revealing that the coordination geometry of [Pd(L)(OH2)Cl] complex is square planar. The binding propensity of [Pd(L)(OH2)Cl] complex with DNA and BSA was assessed by the spectrophotometric method. The antimicrobial profile of the ligand and its [Pd(L)(OH2)Cl] complex was screened against clinically important bacterial strains. [Pd(L)(OH2)Cl] complex showed promising activity against these microorganisms. Pd(L)(OH2)Cl] complex exhibited a potent antiproliferative potential compared to its ligand against different human cancer cells (A549, HCT116, MDA-MB-231, and HepG2) with less toxic effect against normal cells (WI-38). Additionally, [Pd(L)(OH2)Cl] complex exerted its anticancer effects against the most responsive cells (HCT116 cells; IC50 = 11 ± 1 µM) through suppressing their colony-forming capabilities and triggering apoptosis and cell cycle arrest at S phase. Quantitative PCR analysis revealed a remarkable upregulation of the mRNA expression level of p53 and caspase-3 by 4.8- and 5.9-fold, respectively, relative to control. Remarkable binding properties and non-covalent interactions between L and its [Pd(L)(OH2)Cl] complex with the binding sites of different receptors including CDK2, MurE ligase, DNA, and BSA were established using molecular docking. Based on our results, [Pd(L)(OH2)Cl] complex is an intriguing candidate for future investigations as a potential anticancer drug for the treatment of colon cancer.

The impact of unplanned 30-day readmission as a quality indicator in pediatric surgery.

Introduction: Hospital readmission is one of the indicators used to assess quality of service provided in healthcare. Based on accumulated knowledge, risk management teams assess data related to readmissions to find curative solutions for underlying factors. The current article's aim is investigating readmission routes within the workplace in paediatric surgery service during the first 30 days post discharge from Mater Dei Hospital (MDH). Materials and method: A retrospective study of children's hospital readmissions between October 2017 and November 2019 was performed, strictly before COVID-19 pandemic. Demographics and clinical records including age, gender, pre-existing comorbidities, diagnosis during primary admission and readmission, procedure carried out, ASA grade, length of stay, and outcomes were collected. All children re-admitted under a single paediatric surgical department within 30 days from initial admission to tertiary referral hospital were included. Patients undergoing emergency visitation without subsequent admissions were excluded. Readmissions were classified into cohorts: elective and emergency, depending on the nature of primary admission. Contributing factors and outcomes were compared. Results: 935 surgical admissions (221 elective and 714 emergencies) were registered at MDH over the given period, with an average hospital stay of 3.62 days. Total readmission rate was 1.7% (n = 16). 25% (n = 4) of readmissions were post elective, 75% (n = 12) post emergency admission, with an average stay of 4.37 days and no mortalities. 43.7% (n = 7) were re-admissions post-surgical intervention. Further surgical interventions were necessary in 25% (n = 4) of readmitted patients, the remainder (n = 12) treated conservatively. Conclusion: Published reports concerning paediatric surgical readmission rates are limited, challenging healthcare systems. Most readmissions area voidable; therefore, healthcare workers must provide adequate strategies tailored to their resources, efficient multidisciplinary approaches with improved communication to decrease morbidity and prevent readmissions.

Equilibrium Studies on Pd(II)-Amine Complexes with Bio-Relevant Ligands in Reference to Their Antitumor Activity.

This review article presents an overview of the equilibrium studies on Pd-amine complexes with bio-relevant ligands in reference to their antitumor activity. Pd(II) complexes with amines of different functional groups, were synthesized and characterized in many studies. The complex formation equilibria of Pd(amine)2+ complexes with amino acids, peptides, dicarboxylic acids and DNA constituents, were extensively investigated. Such systems may be considered as one of the models for the possible reactions occurring with antitumor drugs in biological systems. The stability of the formed complexes depends on the structural parameters of the amines and the bio-relevant ligands. The evaluated speciation curves can help to provide a pictorial presentation of the reactions in solutions of different pH values. The stability data of complexes with sulfur donor ligands compared with those of DNA constituents, can reveal information regarding the deactivation caused by sulfur donors. The formation equilibria of binuclear complexes of Pd(II) with DNA constituents was investigated to support the biological significance of this class of complexes. Most of the Pd(amine)2+ complexes investigated were studied in a low dielectric constant medium, resembling that of a biological medium. Investigations of the thermodynamic parameters reveal that the formation of the Pd(amine)2+ complex species is exothermic.

Probiotic lactic acid bacteria as a means of preventing in vitro urinary catheter colonization and biofilm formation.

BACKGROUND: Catheter-associated urinary tract infections (CAUTIs) are the most common infections found in healthcare facilities. Urinary catheters predispose the development of CAUTIs by destroying natural barriers and providing a source for infection and biofilm formation (BF). This study aimed to evaluate probiotic lactic acid bacteria (LAB) as a means of preventing in vitro urinary catheter colonization and BF. METHODS: Cross-sectional screening, followed by an experimental study, was conducted on 120 catheterized patients admitted to the urology department in a tertiary care hospital for 7 months. The isolated and identified uropathogens were tested for their antimicrobial susceptibility patterns by the disk diffusion method according to Clinical and Laboratory Standards Institute recommendations and examined for their ability to produce biofilms using a microtiter plate (MtP) assay. Five LAB (Lactobacillus acidophilus (L. acidophilus), Bifidobacterium bifidum (B. bifidum), L. paracasei, L. pentosus, and L. plantarum) were identified and examined for preventing in vitro colonization and BF of some isolated uropathogens on Foley urinary catheter surfaces. RESULTS: Of the 120 samples collected, 32.5% were found to be associated with CAUTIs. Of isolated organisms, 74.4% were gram-negative bacilli, while gram-positive cocci represented 14%, and only 11.6% were of the Candida species. About two-thirds of isolated uropathogens were biofilm formers. All five probiotic strains had inhibitory effects on the growth of all the uropathogens tested but with varying intensities according to the duration of application after 2, 4, and 6 days. CONCLUSIONS: The prevalence of CAUTIs was high, and the predominant bacterial isolates were gram-negative bacilli. Many of the studied uropathogens were biofilm formers. The bacterial isolates had a higher prevalence of resistance to commonly prescribed antimicrobial agents. Probiotics have the potential to prevent in vitro urinary catheter colonization and inhibit BF. Pre-coating urinary catheters with probiotics is recommended after ensuring the safety of probiotics' use in vivo by carrying out further large-scale studies.

Oxidative DNA cleavage mediated by a new unexpected [Pd(BAPP)][PdCl4] complex (BAPP = 1,4-bis(3-aminopropyl)piperazine): crystal structure, DNA binding and cytotoxic behavior.

A novel Pd(ii) double complex, [Pd(BAPP)][PdCl4], containing the 1,4-bis(3-aminopropyl)piperazine (BAPP) ligand is investigated. X-ray crystallography of a single crystal confirmed the structure of the [Pd(BAPP)][PdCl4] complex. The spectroscopic behavior was also elucidated using elemental analysis, nuclear magnetic resonance and Fourier-transform infrared spectroscopy, and mass spectrometry. The antimicrobial susceptibility of the [Pd(BAPP)][PdCl4] complex against all tested microbial strains was lower than that of the BAPP ligand except for C. albicans. The cytotoxic impacts of the BAPP ligand and its [Pd(BAPP)][PdCl4] complex were evaluated in vitro for HepG2, CaCo-2 and MCF7 cell lines as well as the WI-38 normal cell line. The anticancer activity was markedly improved by the complexation. The [Pd(BAPP)][PdCl4] complex could selectively inhibit the tested cancer cells in a safe way to the non-tumorigenic cell (WI-38). From the DNA binding studies with ultraviolet-visible spectrophotometry, the [Pd(BAPP)][PdCl4] complex interacts more efficiently with the calf thymus DNA than its BAPP ligand through the intercalative binding mode. In the absence of an external reductant, the [Pd(BAPP)][PdCl4] complex cleaved the intact supercoiled pBR322 DNA under physiological conditions in a concentration-dependent manner. Additionally, electrophoretic experiments were performed in the presence of different radical scavengers, namely DMSO, NaN3 and KI, and ruled out the hydrolytic mechanistic pathway of the reaction and suggested that the oxidative mechanism is the preferred one. The results of the binding affinity of the [Pd(BAPP)][PdCl4] complex to human DNA were modeled using a molecular docking study showing that the complex interacts more strongly with human DNA than the ligand. Finally, an in vitro pharmacokinetic study was assessed through in silico ADME predictions.

Laparoscopic inguinal hernia repair in children: Article review and the preliminary Maltese experience.

BACKGROUND: In the past two decades, laparoscopy has provided an alternative approach to inguinal hernia repair. The aim of this review is to carry out a retrospective systematic analysis of articles dealing with laparoscopic hernia repair in children and a review of the Maltese experience. METHODS: Data was obtained from publications from 2002 to 2019. The endpoints include: patient demographics, clinical presentations, laparoscopic tools, ports, suture used, technical remarks, length of surgery, hospital stay, complications and follow-up. RESULTS: 32 studies were included with a total of 10,183 patients. Most articles documented the use of 1 port. Length of surgery ranged from an average of 10 to 138 min. Ipsilateral recurrences were reported in 0.83% of cases, while 0.17% required conversion to open. PRELIMINARY MALTESE EXPERIENCE: In our centre, a population of 514, 564 is covered (16% under the age of 18). A total of 14 cases of laparoscopic inguinal hernia repair were carried out from August 2018 till October 2020. The neonatal laparoscopic set-up involves a 30° laparoscope, inserted via a 5 mm umbilical port, with 2 stab incisions allowing the use of 3 mm devices. Intra-corporeal purse string suture technique is used. The length of surgery ranged from 1 hr to 2 hr 30 min. There was 1 case of ipsilateral recurrence and another requiring conversion to open surgery. CONCLUSIONS: Laparoscopic inguinal hernia repair in children is a versatile and safe procedure that can be carried out with minimal complications and low reoperation rates. LEVEL OF EVIDENCE: Level IV.

Gastric antral vascular ectasia in children, rare presentation.

A 14-year-old boy, a known case of perinatal hypoxic cerebral palsy, presented to paediatric emergency with acute melaena and blood staining around feeding gastrostomy site. Physical examination revealed pallor, but no signs of distress with an unremarkable abdominal examination. Routine blood tests revealed normochromic. Abdominal ultrasound scan and Meckel's scan were unremarkable. The patient underwent examination under anaesthesia of the perianal area and joint upper and lower gastrointestinal endoscopy. Streak-like gastritis with no signs of active bleeding lesions were noted and patchy areas of colitis involving the descending and sigmoid colon and the rectum. All clinical findings and evidence-based diagnosis matched gastric antral vascular ectasia. He was successfully managed conservatively with elemental hydrolysed feeding formula.

Outcome of rolled fortified vaginal flap operation on female patients with intrinsic sphincteric deficiency: 2-year follow-up.

INTRODUCTION AND HYPOTHESIS: We evaluate the 2-year outcome of the rolled fortified vaginal flap (RFVF) operation for the treatment of stress urinary incontinence (SUI) due to intrinsic sphincteric deficiency (ISD). METHODS: A prospective study of 20 women suffering from SUI due to ISD was conducted. All patients were subjected to history-taking, clinical examination, cough stress test, and urodynamics. Symptom severity and quality of life (QoL) were assessed using the Arabic version of the International Consultation on Incontinence Questionnaire Urinary Incontinence Short Form (ICIQ-UI-SF). All studied women were followed up for 24 months to detect success rate, any postoperative complications, and reveal changes in the quality of life. RESULTS: Mean age was 53 ± 8 years. Preoperative Valsalva leak point pressure was 50.1 ± 11.3 cmH2O. After a follow-up period of 24 months, only 2 patients (10%) showed mild stress incontinence with mean VLPP 80± 3 cm H2O. Postoperative mean maximum flow rate (Q-max) and mean Pdet-Qmax showed no significant difference from the preoperative results (P = 0.115 and 0.187 respectively). The quality of life domain of the ICIQ-UI-SF decreased significantly from 73.5 ± 12.1% (preoperatively) to 2.6 ± 8.1% (after a 1-year follow-up), P < 0.001 and then showed a slight increase to 4.5 ± 10.6 at 24 months' follow-up. CONCLUSION: The RFVF operation has a success rate of 90% after a 24-month follow-up. It significantly improved the quality of life of women with SUI due to ISD.

Effects of exercise in combination with autologous bone marrow stem cell transplantation for patients with type 1 diabetes.

Stem cell therapy is a promising approach for the treatment of type 1 diabetes mellitus (T1D). Previous studies recommended regular exercise for the control of T1D. Experimental studies showed that a combination of stem cells and exercise yielded a better outcome. Yet, the effect of exercise programs following stem cell transplantation in patients with T1D has not been investigated. Thus, the current study aimed to examine the effect of a combined exercise program on measures of glycemic control in patients with T1D who received autologous bone marrow stem cell transplantation (ABMSCT). Thirty patients with controlled T1D were assigned into two equal groups. Both groups underwent ABMSCT and received insulin therapy and a diabetic diet regime. Only the exercise group followed the combined exercise program. Outcome measures of glycemic control (i.e. fasting blood glucose level [FBG], post-prandial blood glucose level [PPG], HbA1c, daily insulin dosage, and C-peptide levels) were tested before and after a 3-month rehabilitation period. There were significant (p < 0.05) decreases in all outcome measures except C-peptides after ABMSCT compared with before in both groups. Moreover, there was a significant decrease in the mean value of HbA1c in the exercise group compared with the control group after rehabilitation. Overall, this study strengthens the idea that adding exercise to ABMSCT is important to help control diabetes in patients with T1D.

Protonation equilibria of biologically active ligands in mixed aqueous organic solvents.

The review is mainly concerned with the protonation equilibria of biologically active ligands like amino acids, peptides, DNA constituents, and amino acid esters in nonaqueous media. Equilibrium concentrations of proton-ligand formation as a function of pH were investigated. Also, thermodynamics associated with protonation equilibria were also discussed.

Palladium(II) Complexes Containing Mixed Nitrogen-Sulphur Donor Ligands: Interaction of [Pd(Methionine Methyl Ester)(H2O)2](2+) with Biorelevant Ligands.

Pd(MME)Cl2 complex (MME = methionine methyl ester) was synthesised and characterized by physicochemical measurements. The reaction of [Pd(MME)(H2O)2](2+) with amino acids, peptides, or dicarboxylic acids was investigated at 25°C and 0.1 M ionic strength. Amino acids and dicarboxylic acids form 1 : 1 complexes. Peptides form both 1 : 1 complexes and the corresponding deprotonated amide species. The stability of the complexes formed was determined and the binding centres of the ligands were assigned. Effect of solvent on the stability constant of Pd(MME)-CBDCA complex, taken as a representative example, shows that the complex is more favoured in a medium of low dielectric constant. The concentration distribution diagrams of the complexes were evaluated.

Complex formation equilibria of binary and ternary complexes involving 3,3-bis(1-methylimidazol-2yl)propionic acid and bio-relevant ligands as 1-aminocyclopropane carboxylic acid with reference to plant hormone.

The formation equilibria for the binary complexes of Cu(II) with 1-aminocyclopropane carboxylic acid (ACC) and 3,3-bis(1-methylimidazol-2-yl)propionic acid (BIMP) were investigated. ACC and BIMP form the complexes 110, 120 and 11-1. The ternary complexes of Cu(II) with BIMP and biorelevant ligands as some selected amino acids, peptides and DNA constituents are formed in a stepwise mechanism. The stability constants of the complexes formed were determined and their distribution diagrams were evaluated. The kinetics of hydrolysis of glycine methyl ester in presence of [Cu(BIMP)](+) was investigated by pH-stat technique and the mechanism was discussed.

Bivalent transition metal complexes of cetirizine: spectroscopic, equilibrium studies and biological activity.

Metal complexes of cetirizine·2HCl (CTZ=2-[2-[4-[(4-chlorophenyl)phenyl methyl]piperazine-1-yl]-ethoxy]acetic acid, dihydrochloride have been prepared and characterized by elemental analyses, IR, solid reflectance, magnetic moment, molar conductance, and UV-Vis spectra. The analytical data of the complexes show the formation of 1:2 [M:L] ratio, where M represents Ni(II), Co(II) and Cu(II) ions, while L represents the deprotonated CTZ ligand. IR spectra show that CTZ is coordinated to the metal ions in a monodentate manner through carboxylate-O atom. Protonation equilibria of CTZ and its metal complexation by some divalent metal ions were determined in aqueous solution at constant ionic strength (0.1 M NaCl) using an automatic potentiometric technique. Thermodynamic parameters for the protonation equilibria of CTZ were calculated and discussed. The stability order of M(II)-CTZ complexes were found to obey Mn(2+)

Speciation studies of diorganotin(IV) complexes with 3,3-bis(1-methylimidazol-2-yl)propionate--displacement reaction by DNA constituents.

The interaction of 3,3-bis(1-methylimidazol-2-yl)propionate (BIMP) with dimethyltin(IV) dichloride (DMT), dibutyltin(IV) dichloride (DBT), and diphenyltin(IV) dichloride (DPT) is investigated at 25°C and 0.1 M ionic strength in water for dimethyltin(IV), and in a 50% dioxane-water mixture for dibutyltin(IV) and diphenyltin(IV). The stepwise formation constants of the 1 : 1 and 1 : 2 complexes formed in solution are calculated from potentiometric measurements using the nonlinear least-square program MINIQUAD-75. The concentration distribution of the various complex species is evaluated as a function of pH. Displacement reactions of the coordinated 3,3-bis(1-methylimidazol-2-yl)propionate by inosine and inosine-5'-monophosphate are investigated from calculations based upon equilibrium properties.

Thermodynamic Investigation and Mixed Ligand Complex Formation of 1,4-Bis-(3-aminopropyl)-piperazine and Biorelevant Ligands.

Thermodynamic parameters for protonation of 1,4-bis(3-aminopropyl)-piperazine (BAPP) and its metal complexation with some divalent metal ions were determined in aqueous solution at constant ionic strength (0.1 M NaNO(3)) using a potentiometric technique. The order of -ΔG(0) and -ΔH(0) was found to obey Co(2+) < Ni(2+) < Cu(2+) > Zn(2+), in accordance with the Irving-Williams order. The formation equilibria of zinc (II) complexes and the ternary complexes Zn(BAPP)L, where L = amino acid, amides, or DNA constituents), have been investigated. Ternary complexes are formed by a simultaneous mechanism. The concentration distribution of the complexes in solution was evaluated as a function of pH. Stoichiometry and stability constants for the complexes formed are reported and discussed. The stability of ternary complexes was quantitatively compared with their corresponding binary complexes in terms of the parameter Δlog K.

Synthesis, characterization, biological activity and equilibrium studies of metal(II) ion complexes with tridentate hydrazone ligand derived from hydralazine.

In the present study, a new hydrazone ligand (2-((2-phthalazin-1-yl)hydrazono)methyl)phenol) prepared by condensation of hydralazine (1-Hydralazinophthalazine) with salicylaldehyde (SAH). The synthesized SAH-hydrazone and its metal complexes have been characterized by elemental analyses, IR, (1)H NMR, solid reflectance, magnetic moment, molar conductance, mass spectra, UV-vis and thermal analysis (TGA). The analytical data of the complexes show the formation of 1:1 [M:L] ratio, where M represents Ni(II), Co(II) and Cu(II) ions, while L represents the deprotonated hydrazone ligand. IR spectra show that SAH is coordinated to the metal ions in a tridentate manner through phthalazine-N, azomethine-N and phenolic-oxygen groups. The ligand and their metal chelates have been screened for their antimicrobial activities using the disc diffusion method against the selected bacteria and fungi. Proton-ligand association constants of (SAH) and the stepwise stability constants of its metal complexes are determined potentiometrically in 0.1 M NaNO(3) at different temperatures and the corresponding thermodynamic parameters were derived and discussed. The order of -ΔG° and -ΔH° were found to obey Mn(2+)

Thermodynamics of the interaction of ruthenium(III) polyaminecarboxylate complexes with bio-relevant ligands. Deactivation of the complexes as NO scavengers by thiol ligands.

The acid-base and complex-formation equilibria of [Ru(H(2)dtpa)(H(2)O)], where dtpa = diethylenetriaminepentaacetate, with a series of bio-relevant ligands having various functional groups, viz. thiol, amine, imidazole and carboxylate, were investigated using potentiometric and spectrophotometric techniques. The pK(a) values for [Ru(H(2)dtpa)(H(2)O)] were found to be 2.28 and 3.48 for the uncoordinated carboxylic acid groups and 8.83 for the coordinated water molecule. The complexes formed are of 1:1 stoichiometry and their formation-constants were determined. The effect of dioxane on the acid-base and complex-formation equilibria of the Ru(III) complex was studied. The displacement reaction of coordinated NO by the investigated ligands showed that thiols can compete with NO in their reaction with [Ru(III)(dtpa)(H(2)O)](2-). The results reveal that the Ru(III) complex is deactivated as a NO scavenger by thiolate ligands.

Synthesis, characterization, equilibrium study and biological activity of Cu(II), Ni(II) and Co(II) complexes of polydentate Schiff base ligand.

Schiff base ligand, 1,4-bis[(2-hydroxybenzaldehyde)propyl]piperazine (BHPP), and its Cu(II), Ni(II) and Co(II) metal complexes were synthesized and characterized by elemental analysis, magnetic susceptibility, molar conductance and spectral (IR and UV-vis) studies. The ground state of BHPP ligand was investigated using the BUILDER module of MOE. Metal complexes are formed in the 1:1 (M:L) ratio as found from the elemental analysis and found to have the general formula [ML]·nH(2)O, where M=Co(II), Ni(II) and Cu(II), L=BHPP. In all the studied complexes, the (BHPP) ligand behaves as a hexadentate divalent anion with coordination involving the two azomethine nitrogen's, the two nitrogen atoms of piperazine ring and the two deprotonated phenolic OH-groups. The magnetic and spectral data indicates octahedral geometry of metal(II) complexes. The ligand and their metal chelates have been screened for their antimicrobial activities using the disc diffusion method against the selected bacteria and fungi. They were found to be more active against Gram-positive than Gram-negative bacteria. Protonation constants of (BHPP) ligand and stability constants of its Cu(2+), Co(2+) and Ni(2+) complexes were determined by potentiometric titration method in 50% DMSO-water solution at ionic strength of 0.1 M sodium nitrate. It has been observed that the protonated Schiff base ligand (BHPP) have four protonation constants. The divalent metal ions Cu(2+), Ni(2+) and Co(2+) form 1:1 complexes.

Synthesis and structural characterization of Pd(N,N-dimethylaminopropylamine)Cl2 complex--the interaction with bio-relevant ligands with reference to the effect of cysteine on the deactivation of metal-based drug.

The synthesis and X-ray structural characterization of Pd(DMPA)Cl(2) complex, where DMPA=N,N-dimethylaminopropylamine, is reported. The complex crystallizes in the space group P2(1)/c, a=8.8923(4), b=10.9050(5), c=11.5006(7) Å, ß=120.00(18)°, V=948.25(8) Å(3), Z=4. The palladium centre has a typical square-planar geometry with a tetrahedral distortion. Stoichiometry and stability constants of the complexes formed between [Pd(DMPA)(H(2)O)(2)](2+) and some selected DNA constituents and cytsteine are investigated at 25 °C and at constant 0.1M ionic strength. The concentration distribution diagrams of the various species formed are evaluated. The equilibrium constants for the displacement of coordinated ligands as inosine by cysteine are calculated. The results are expected to contribute to the chemistry of tumour therapy.

Thermodynamics of the interaction of Pd(dmen)(H2O)2²âº with bio-relevant ligands with reference to the deactivation of metal-based drug by thiol ligands.

Pd(dmen)Cl(2) complex was synthesized and characterized, where dmen=N,N-dimethylethylenediamine. Stoichiometry and stability constants of the complexes formed between [Pd(dmen)(H(2)O)(2)](2+) and various biologically relevant ligands such as amino acids, peptides and dicarboxylic acids are investigated at 25 °C and at constant 0.1M ionic strength. The concentration distribution diagrams of the various species formed are evaluated. The equilibrium constants for the displacement of coordinated ligands as inosine, glycine or methionine by cysteine are calculated. The results are expected to contribute to the chemistry of tumour therapy.