Study of transition metal acetylacetonate doped PVC films

PVC is one of the widely used polymers for various applications throughout the world. Various additives are added to modify its properties according to the requirement of a particular product. Doping of the polymer is known to affect its electrochemical properties. In the present work five transition metal acetylacetonate complexes, Tris(acetylacetonato) chromium, Tris(acetylacetonato) cobalt. Bis(acetylacetonato) copper, Bis(acetylacetonato) nickel and Tris(acetylacetonato) iron, were prepared and crystallized. These metal complexes were analysed with IR spectroscopy, and their purity was checked with TLC. PVC was than dopes with 5% of these complexes, and casted into films, by slow heating. The film thickness was measured with micrometer. All the films were transparent and had different colours. The structural changes in doped PVC matrix were studied by IR Spectrophotometer. our experimental investigations show significant changes in the matrix of the doped PVC films. The interpretation of the IR spectra in comparison to the undoped PVC film shows the formation of polyene and alcohol group sequences in doped polymer matix. Formation of alcoholic group was not observed in the PVC film doped with  that the Bis(acetylacetonato) copper. No correlation could be observed between the structural changes in the doped PVC matrix and the periodic position of the metal ions

Synthesis and spectroscopic studies of N, O containing Schiff base ligands and their metal complexes with Zn

In the present work seven Schiff bases have been synthesized by the reaction of anilines and substituted anilines with benzil via condensation reaction. The selected substituted anilines were ortho and meta substituted chloro anilines, ortho and meta substituted methyl anilines and ortho and meta substituted carboxlyic aniline. The substituted anilines were selected to observe the affect of these electron donating and withdrawing group on the Schiff base formation and consequently on the coordination behavior of these ligands with the zinc ion. These Schiff base ligands were complexed with the zinc metal ion. It was observed that all the ligands and complexes formed readily. The resulting Schiff base ligands and their coordination complexes with zinc ion were recrystallized by CH2Cl2/n-hexane (1:10) mixture. All the ligands and zn coordination complexes were characterized by the IR spectroscopy.  The stability of these coordination complexes were observed by UV/Visible spectroscopy. Thermal stability of these complexes was observed by subjecting them to thermogravimetric analysis. Our method of preparation of the Schiff bases and the corresponding metal complexes can be used to prepare similar compounds

Preparation, Characterization and Application of Vitamin-E fortified Nanocoatings on Fresh-cut Apples

Fresh-cut apples have a very low shelf life due to high vulnerability to oxidation in open air. The aim of the present work was to prepare enriched nanocoatings to increase not only the shelf life of the fruit, but to add to it nutritive values as well. Hence, four different edible coatings were prepared containing vitamin-E nanoemulsion. Vitamin-E nanoemulsion was successfully prepared by EPI (Emulsion Phase Inversion) method and the particles size distribution was checked by DLS (Dynamic Light Scattering) method. Potassium Sorbate and Calcium Chloride were added, respectively, as antimicrobial and antioxidant agents. In one coating, fresh lemon juice was used in place of ascorbic acid for comparison. To reduce respiration and water vapor permeability, methyl cellulose and stearic acid were added in different ratios to all the four coatings. Prepared coatings were then applied on freshly-cut apple pieces using dip method. Various characterization parameters were performed to analyze the quality of vitamin-E fortified edible nanocoatings such as weight loss, titrateable acidity, total soluble solids, and total phenolics for two weeks. In addition, antimicrobial activity of the prepared edible coatings was done using LBA (Luria Bertani Agar) culture media. All the coatings showed good results but the coating containing fresh lemon juice gave comparatively better results

Antioxidant, Cytotoxic, and Antimicrobial Potential of Silver Nanoparticles Synthesized using Tradescantia pallida Extract

Silver nanoparticles have received much attention, due to their wide range of biological applications as an alternative therapy for disease conditions utilizing the nanobiotechnology domain for synthesis. The current study was performed to examine the antioxidant, anticancer, antibacterial, and antifungal potential of biosynthesized silver nanoparticles (TpAgNPs) using plant extract. The TpAgNPs were produced by reacting the Tradescantia pallida extract and AgNO3 solution in nine various concentration ratios subjected to bioactivities profiling. According to the current findings, plant extract comprising phenolics, flavonoids, and especially anthocyanins played a critical role in the production of TpAgNPs. UV–visible spectroscopy also validated the TpAgNP formation in the peak range of 401–441 nm. Further, the silver ion stabilization by phytochemicals, face-centered cubic structure, crystal size, and spherical morphology of TpAgNPs were analyzed by FTIR, XRD, and SEM. Among all TpAgNPs, the biosynthesized TpAgNP6 with a medium concentration ratio (5:10) and the plant extract had effective antioxidant potentials of 77.2 ± 1.0% and 45.1 ± 0.5% free radical scavenging activity, respectively. The cytotoxic activity of TpAgNP6 in comparison to plant extract for the rhabdomyosarcoma cell line was significantly the lowest with IC50 values of 81.5 ± 1.9 and 90.59 ± 1.6 μg/ml and cell viability % of 24.3 ± 1.62 and 27.4 ± 1.05, respectively. The antibacterial and antifungal results of TpAgNPs revealed significant improvement in comparison to plant extract, i.e., minimum inhibition concentration (MIC) 64 μg/ml against Gram-negative Pseudomonas aeruginosa while, in the case of antifungal assay, TpAgNP6 was active against Candida parapsilosis. These TpAgNPs play a crucial role in determining the therapeutic potential of T. pallida due to their biological efficacy

Effect of early tranexamic acid administration on mortality, hysterectomy, and other morbidities in women with post-partum haemorrhage (WOMAN): an international, randomised, double-blind, placebo-controlled trial

Background Post-partum haemorrhage is the leading cause of maternal death worldwide. Early administration of tranexamic acid reduces deaths due to bleeding in trauma patients. We aimed to assess the effects of early administration of tranexamic acid on death, hysterectomy, and other relevant outcomes in women with post-partum haemorrhage. Methods In this randomised, double-blind, placebo-controlled trial, we recruited women aged 16 years and older with a clinical diagnosis of post-partum haemorrhage after a vaginal birth or caesarean section from 193 hospitals in 21 countries. We randomly assigned women to receive either 1 g intravenous tranexamic acid or matching placebo in addition to usual care. If bleeding continued after 30 min, or stopped and restarted within 24 h of the first dose, a second dose of 1 g of tranexamic acid or placebo could be given. Patients were assigned by selection of a numbered treatment pack from a box containing eight numbered packs that were identical apart from the pack number. Participants, care givers, and those assessing outcomes were masked to allocation. We originally planned to enrol 15 000 women with a composite primary endpoint of death from all-causes or hysterectomy within 42 days of giving birth. However, during the trial it became apparent that the decision to conduct a hysterectomy was often made at the same time as randomisation. Although tranexamic acid could influence the risk of death in these cases, it could not affect the risk of hysterectomy. We therefore increased the sample size from 15 000 to 20 000 women in order to estimate the effect of tranexamic acid on the risk of death from post-partum haemorrhage. All analyses were done on an intention-to-treat basis. This trial is registered with ISRCTN76912190 (Dec 8, 2008); ClinicalTrials.gov, number NCT00872469; and PACTR201007000192283. Findings Between March, 2010, and April, 2016, 20 060 women were enrolled and randomly assigned to receive tranexamic acid (n=10 051) or placebo (n=10 009), of whom 10 036 and 9985, respectively, were included in the analysis. Death due to bleeding was significantly reduced in women given tranexamic acid (155 [1·5%] of 10 036 patients vs 191 [1·9%] of 9985 in the placebo group, risk ratio [RR] 0·81, 95% CI 0·65–1·00; p=0·045), especially in women given treatment within 3 h of giving birth (89 [1·2%] in the tranexamic acid group vs 127 [1·7%] in the placebo group, RR 0·69, 95% CI 0·52–0·91; p=0·008). All other causes of death did not differ significantly by group. Hysterectomy was not reduced with tranexamic acid (358 [3·6%] patients in the tranexamic acid group vs 351 [3·5%] in the placebo group, RR 1·02, 95% CI 0·88–1·07; p=0·84). The composite primary endpoint of death from all causes or hysterectomy was not reduced with tranexamic acid (534 [5·3%] deaths or hysterectomies in the tranexamic acid group vs 546 [5·5%] in the placebo group, RR 0·97, 95% CI 0·87-1·09; p=0·65). Adverse events (including thromboembolic events) did not differ significantly in the tranexamic acid versus placebo group. Interpretation Tranexamic acid reduces death due to bleeding in women with post-partum haemorrhage with no adverse effects. When used as a treatment for postpartum haemorrhage, tranexamic acid should be given as soon as possible after bleeding onset. Funding London School of Hygiene & Tropical Medicine, Pfizer, UK Department of Health, Wellcome Trust, and Bill & Melinda Gates Foundation

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Characterization of Synaptic Transmission Abnormalities in Neurological Disorders of the Presynaptic Terminal

Seminal methodological advancements in the field of human genetics now allow for low-cost sequencing of complete coding genomes, and rich sources of corresponding data now exist for healthy and patient cohorts, allowing for the identification of possibly pathogenic variations. However, lagging behind is the identification of mechanisms by which such variations lead to disease, both at the molecular and cellular levels. Multiple genetic studies of neurodevelopmental and neuropsychiatric disorders now point to a central role of synaptic transmission in the etiology of such disorders. This project aims to shed light on molecular mechanisms and synaptic transmission abnormalities underlying a novel disorder of the presynaptic terminal – associated with variations in the UNC13A gene that translates into the Munc13-1 protein. Munc13-1 is a large, multi-domain protein absolutely essential for priming synaptic vesicles (SV) to the active zone plasma membrane. The absence of Munc13-1 in mice leads to severely compromised synaptic transmission that is lethal. Evidence also exists pointing to the fact that Munc13-1 is pivotal for nervous system function in humans. Recently, the first patient with a de novo variant in the Munc13-1 protein, was described. The patient phenotype was characterized by a dyskinetic movement disorder, developmental delay and autism. The patient variant, P814L, leads to a gain of function of both excitatory and inhibitory synaptic transmission – neurons expressing this variant exhibited an increase in the basal SV release probability and aberrant patterns of short-term synaptic plasticity during trains of action potentials. Following this publication, a collaboration with the group of Prof. Dr. med. Anita Rauch from the Institute of Medical Genetics at the University of Zurich was initiated. This research group excels in the collection of patient data and in in-depth genetic analysis of human material. By now, around 40 patients were identified, who carry de novo or biallelic variants in the UNC13A gene, presenting with variable neurological and neuropsychiatric conditions. The patient variants are distributed over the entire Munc13-1 protein sequence and in every functional domain. In this thesis, I am presenting electrophysiological and immunocytochemistry data analysing the functional consequences of five patient variants, characterized using the mouse hippocampal autaptic neuron culture system. One variant mirroring the phenotype of the previously reported P814L mutation confirms the reproducibility of our experimental system and its ability to accurately capture a phenotypic-functional relationship. Beyond that, I distinguish two distinct mechanisms in disease. One group of patients accumulating in the highly conserved C2B-MUN-Linker domain elicits a gain of function in synaptic transmission properties. In contrast, a second group of patients accumulates on the less conserved N-terminus and displays a loss of function phenotype in our electrophysiological measurements. My findings uncover two distinct mechanisms governing disease manifestation in UNC13A patients, and emphasize the significance of genetic variants in synaptic proteins as causal for brain disorders.2023-01-1

Reply to Comments on Proteomic Investigations of Two Pakistani Naja Snake Venom Species Unravel the Venom Complexity, Posttranslational Modifications, and Presence of Extracellular Vesicles. Toxins 2020, 12, 669

We appreciate the commentary on our article, and we would like to take the opportunity to address several points raised in the reviewers’ commentary [...

Snake Venom Peptides: Tools of Biodiscovery

Nature endowed snakes with a lethal secretion known as venom, which has been fine-tuned over millions of years of evolution. Snakes utilize venom to subdue their prey and to survive in their natural habitat. Venom is known to be a very poisonous mixture, consisting of a variety of molecules, such as carbohydrates, nucleosides, amino acids, lipids, proteins and peptides. Proteins and peptides are the major constituents of the dry weight of snake venoms and are of main interest for scientific investigations as well as for various pharmacological applications. Snake venoms contain enzymatic and non-enzymatic proteins and peptides, which are grouped into different families based on their structure and function. Members of a single family display significant similarities in their primary, secondary and tertiary structures, but in many cases have distinct pharmacological functions and different bioactivities. The functional specificity of peptides belonging to the same family can be attributed to subtle variations in their amino acid sequences. Currently, complementary tools and techniques are utilized to isolate and characterize the peptides, and study their potential applications as molecular probes, and possible templates for drug discovery and design investigations