Design, synthesis and biological activities of 5Hdibenzo[ b,f]azepine-5-carboxamide derivatives; Targeted hippocampal trypsin inhibition as a novel approach to treat epileptogenesis

Purpose: To synthesize anticonvulsant drug derivatives that target protease-activated receptor generated epileptic seizures.Method: Varieties of carbamazepine-based Schiff bases were designed with different aldehydes and ketones, and evaluated for in silico computer-aided drug design prediction of absorption, distribution, metabolism and excretion (ADME), and potential drug targets. The resultant compounds were synthesized and characterized by various spectroscopic techniques, including FTIR, 1H-NMR and 13CNMR, analysis. Thereafter, they were screened for antimicrobial, antioxidant and anticonvulsant potential.Results: Prominent anti-protease potential was shown by C7 and C3 compounds and the order of activity was C7 > C3 > C5 > C2 > C6 > C4 > C2 > C1 (p < 0.05). The anticonvulsant activity of C7 and C5 was comparable with the standard drug; C3, C4, C6 and C8 had mild activity while C1 and C4 showed the least activity. The synthesized compounds exhibited significant (p < 0.05) antioxidant potential (rank order: C3 > C4 > C5 > C7 > C8 > C6 > C1 > C2) and antimicrobial activity against S.aureus and B. bronchiseptica (rank order: C5 > C2 > C8 > C1 > C4 > C3 > C7).Conclusion: Synthesized derivatives retained their potential for anticonvulsant and antitrypsin activity, unlike their mother moiety, i.e., carbamazepine. The additional antibacterial activity effectively treats neurological disorders associated with bacterial infections

AI in Bioinformatics

In bioinformatics science and computational molecular biology, artificial intelligence (AI) has rapidly gained interest. With the availability of numerous types of AI algorithms, it has become prevalent for researchers to use off-shelf programmes to identify their datasets and mine them. At present, researchers are facing difficulties in selecting the right approach that could be extended to a given data collection, with numerous intelligent approaches available in the literature. Researchers need instruments that present the data in an intuitive manner, annotated with meaning, precision estimates, and description. In the fields of bioinformatics and computational molecular biology (DNA sequencing), this article seeks to review the use of AI. These fields have evolved from the needs of biologists to use the large volumes of data continuously obtained in genomic science and to better understand them. For several approaches to bioinformatics and DNA sequencing, the fundamental impetus is the evolution of species and the difficulty of dealing with incorrect results. The type of software programmes developed by the scientific community to search, identify and mine numerous usable biological databases are also mentioned in this article, simulating biological experiments with and without mistakes. The review of antibody-antigen interactions and their diversity, and the study of epidemiological evidence that can help forecast antibody-antigen interactions and the induction of broadly neutralising antibodies are important questions to be answered in the field of vaccinology

Synthesis and characterization of some new Schiff base derivatives of gabapentin, and assessment of their antibacterial, antioxidant and anticonvulsant activities

Purpose: To synthesize and characterize some new gabapentin Schiff base derivatives, and to assess their antibacterial, antioxidant and antiepileptic activities.Methods: Four Schiff base derivatives of gabapentin, termed G1, G2, G3 and G4, were synthesized by condensation with benzoin, vanillin, acetophenone, and benzophenone, respectively. Their chemical identities were established by FTIR, 1 H NMR and 13C NMR techniques. The new compounds were screened for antibacterial activity using agar well method, antioxidant activity by DPPH assay, and anticonvulsant activity against pentylenetetrazole (PTZ) induced seizures in mice.Results: All the compounds showed antibacterial activity against the test strains to variable degrees, while the parent drug did not exhibit antibacterial activity. The zones of inhibition of compound G2 against Micrococcus luteus (36.2 ± 1.0 mm) and Serratia marcescens (28.2 ± 1.0 mm), and of compound G4 against Stenotrophomonas maltophilia (36.8 ± 1.0 mm) were larger compared to thestandard drug, doxycycline, exhibiting zones of inhibition 28.2 ± 1.3, 28.2 ± 0.9 and 20.0 ± 0.9 mm, respectively. In addition, compounds G1 and G2 possessed significantly greater (p < 0.05) radical scavenging activity (82.3 ± 1.8 and 92.3 ± 2.2 %, respectively) than the precursor drug, gabapentin (63.2± 2.6 %). The seizure scores for compounds G1 (0.7 ± 0.06) and G2 (0.9 ± 0.07) were comparable(p ˃ 0.05) with gabapentin (0.8 ± 0.06), while compounds G3 and G4 were less active (p < 0.05) than gabapentin.Conclusion: Compounds G1 and G2 exhibit good antibacterial and antioxidant activities while retaining the anticonvulsant activity of the parent drug, gabapentin, thus making them suitable candidates for further development for the treatment of neurodegenerative pathologies associated with bacterial infections. Keywords: Gabapentin, Antibacterial, Seizures, Antioxidant, Anticonvulsan

Delayed presentation of forgotten thyroid goiter - 25 years after thyroidectomy

Forgotten goiter is a rare occurrence (2 - 16% of retrosternal thyroid cases) that depicts recurrence of retrosternal thyroid mass due to growth of remnant thyroid tissue overlooked during an initial thyroidectomy. The patient is a 59-year female who presented with dyspnea and stridor 25 years after total thyroidectomy. She was diagnosed as having a mediastinal mass on radiographic imaging. There were only localized pressure symptoms due to mass effect. The mass was excised employing an extra-cervical approach and using a partial sternotomy. The profuse extension of thyroid tissue, adherent to vital structures in the thorax and the extra-cervical thyroidectomy was a novel experience. The mass was completely excised and the patient\u27s symptoms alleviated after the surgery. The patient recovered without any complications and there was no recurrence at 1 year of follow-up

The Role of Radiology (X-Ray versus Computed Tomography) in Medicolegal Cases Presented at a Tertiary Care Hospital in Pakistan

Objectives:  A prospective observational study was aimed to assess the role of plain radiographs and computed tomography in detecting head injuries presented at the medicolegal office at the Forensics and Radiology Departments, Gambat Medical Hospital, Sindh. Material and Methods:  All cases referred from the Medicolegal Office (MLO) with head injury were included. All victims underwent X-ray head and computed tomography skull was done with 1 or 1.5 cm thick axial sections without administration of intravenous contrast. The radiological reports of X-ray head and CT scans were documented and comparatively evaluated. Results:  Mean age was 38.63 ± 3.91 years. In 51 (45.13%) cases, X-ray was able to detect skull fracture, while CT scan detected 64(56.64%) skull fractures. There were 54 (84.3%) true positives, 3 (2.6%) false positives, 10(8.8%) false negatives, and 40 (40.7%) true negatives. The accuracy of X-ray to detect skull fracture was 88.50%. Conclusion:  X-ray had a sensitivity and specificity of 84.38% and 93.88%, respectively. It is a reliable tool to detect skull fractures in victims of assault in comparison with CT scans. X-ray is also associated with low dose radiation exposure as compared with CT scan which delivers 70 times more exposure than the former

Enhancement of solubility and dissolution rate of ebastine fast-disintegrating tablets by solid dispersion method

Purpose: To investigate the efficiency of different solubilizing agents in improving solubility as well as dissolution rate of ebastine (a BCS class II drug) by incorporating prepared solid dispersion into fast disintegrating tablets.Method: The solubility of ebastine was determined in distilled water, lipids and solubilizing agents. Subsequently, the binary solid dispersions were prepared by kneading method using varying weight ratios of ebastine and solubilizing agents. The solid dispersions were then incorporated into fast disintegrating tablets (SD-FDT). Central composite rotatable design (CCD) was used to determine the impact of super disintegrating agents on disintegration time and friability of tablets. The solubility and dissolution rate of developed SD-FDT were compared with a marketed brand. The solid dispersion particles were characterized by Fourier-transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), powder x-ray diffraction (P-XRD) and scanning electron microscopy (SEM).Results: The saturated solubility of pure ebastine in water was 0.002 ± 0.041 mg/ml while the aqueous solubility of EBT/poloxamer solid dispersion SET3 (P) was 0.018 ± 2.510 mg/ml; on the other hand, EBT/soluplus solid dispersion SET1(S) has an aqueous solubility of 0.242 ± 1.390 mg/ml. Within 30 min, drug release was 14.00 ± 1.77, 78.00 ± 2.31 and 98.70 ± 2.54 % from pure EBT, SET3 (P) and SET1(S), respectively.Conclusion: The solubility and dissolution rate of ebastine has been successfully enhanced by incorporating its solid dispersion in fast-disintegrating tablets (SD-FDT). Keywords: Ebastine, Solid dispersion, Poloxamer 188, Soluplus, Solubility, Dissolutio

Multisystem inflammatory syndrome (MIS-C) in Pakistani children: A description of the phenotypes and comparison with historical cohorts of children with Kawasaki disease and myocarditis

Objectives: To determine clinical, laboratory features and outcomes of Multisystem Inflammatory Syndrome in children (MIS-C) and its comparison with historic Kawasaki Disease (KD) and Viral Myocarditis (VM) cohorts.Methods: All children (1 month- 18 years) who fulfilled the World Health Organization criteria of MIS-C presenting to two tertiary care centers in Karachi from May 2020 till August 31st were included. KD and VM admitted to one of the study centers in the last five years prior to this pandemic, was compared to MIS-C.Results: Thirty children with median age of 24 (interquartile range (IQR)1-192) months met the criteria for MIS-C. Three phenotypes were identified, 12 patients (40%) with KD, ten (33%) VM and eight (26%) had features of TSS. Echocardiography showed coronary involvement in 10 (33%), and moderate to severe Left Ventricular dysfunction in 10 (33%) patients. Steroids and intravenous immunoglobulins (IVIG) were administered to 24 (80%) and 12 (41%) patients respectively while 7 (23%) received both. Overall, 20% children expired. During the last five years, 30 and 47 children were diagnosed with KD and VM, respectively. Their comparison with MIS-C group showed lymphopenia, thrombocytosis, and higher CRP as well as more frequent atypical presentation in MIS-C KD group with less coronary involvement. The MIS-C VM was more likely to present with fulminant myocarditis.Conclusions: Our MIS-C cohort is younger with higher mortality compared to previous reports. MIS-C is distinct from historic cohorts of KD and VM in both in clinical features and outcomes

A Comparative Study of the Effect of Non-Antibiotic Feed Additives on Experimental Colonization of Salmonella Enterica Serovar Enteridis and Intestinal Pathomorphology in Broiler Chickens

ABSTRACT The objective of this study was to evaluate the effect of eubiotics on the intestinal morphology of broilers. For this purpose, 125 birds were divided into six groups with two replicates each (10 birds in each replicate). Group A was given a Basal diet. All groups except group A were challenged with Salmonella enterica serovar Enteritidis. Group B was provided the basal diet, group C was fed a Probiotic-added diet; group D was fed a Prebiotics-based diet; group E was given essential oils plus the basal diet; and group F was provided with organic acids plus the basal diet. Two separate experiments were carried out for Salmonella recovery, checking the cecal tonsils and conducting an intestinal pathomorphic evaluation. Villus length, villus width, villus surface area, and crypt depth were measured by micrometry. There was an overall improvement (p<0.05) in intestinal morphometric parameters for all the treatment groups except for the negative control group, which showed the lowest villus height and villus depth values. Maximum villus height (p<0.05) of the duodenum was achieved by group E, which was fed a diet containing essential oils, whereas a maximum villus surface area index (p<0.05) was recorded for the birds of Group D, which were fed a diet containing prebiotics. Maximum villus height (p<0.05) and surface area index in ileum mucosa was recorded (p<0.05) in the birds of group D (treated with prebiotics). It is concluded that there is an overall increase in the gut histology of broilers fed non-antibiotic based feed

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London