PEGylation of a shell over core-shell MOFs-a novel strategy for preventing agglomeration and synergism in terms of physicochemical and biological properties.

We demonstrate a new strategy of PEGylation over core-shell MOFs of HKUST-1 and Cu-MOF-2 by a solvothermal method. The novel synthesized PEGylated core-shell MOFs has synergistic enhancement in terms of physicochemical and biological properties. FTIR spectroscopy and XRD analysis described the bonding characteristics of the double-shelled-core MOFs PEG@HKUST-1@CuMOF-2 and PEG@CuMOF-2@HKUST-1. XPS and EDAX spectroscopy confirmed the structural features of the PEG@core-shell MOFs. The as-synthesized PEG-modified core-shell MOFs showed a readily identifiable morphology with a reduction in particle size. The significant observation from SEM and TEM was that agglomeration disappeared completely, and the morphology of individual core-shell MOFs was clearly revealed. BET analysis provided the surface characteristics of MOF compounds. The chemical states of frameworks were established by XPS. The designed PEG-modified copper MOFs were evaluated for their activity against Gram-positive (Staphylococcus aureus, Enterococcus faecalis), Gram-negative (Escherichia coli and Klebsiella pneumoniae) bacterial species and activity against fungal species (Aspergillus niger and Candida albicans). This research work highlights a facile and synergistic approach to design promising biocompatible nano-dimensional core-shell MOFs for biological applications.

Characterization of virulence factors and antibiotic resistance pattern of uropathogenic Escherichia coli strains in a tertiary care center.

Background: Urinary tract infections (UTI) are the most prevalent bacterial infection in humans. The uropathogenic E. coli (UPEC) expresses a range of virulence factors that contribute to their pathogenicity . The emergence of multidrug resistance (MDR)-associated UTI is increasing. This study monitors the distribution of virulence factors among UPEC strains to note the antibiogram, outcome and type of associated UTI. Methods: A prospective cross-sectional time-bound study of six months was done on clinically significant urinary isolates of Escherichia coli. Detection of haemolysin production and serum resistance was done by phenotypic methods. Genotypic characterization of the virulence genes ( papC, iutA, hlyA, cnf1) was done by multiplex PCR. Demographic data, clinical history, antibiogram and type of UTI was collected from clinical case records. Results:75 E.coli isolates from patients with suspected UTIs were included. Females had a higher preponderance of UTI (66.7%). 93% of patients were adults and the remaining 7% were from paediatrics.  24 (32%) isolates showed haemolysis by plate haemolysis and all isolates were serum-resistant. Out of 75 isolates, 65 were positive for at least one of four targeted genes, while remaining ten isolates were negative for all four genes. Multidrug resistance was found in 40 (53.3%) isolates. 97.4% of the UTI cases had a favourable clinical outcome at discharge. Mortality due to urosepsis was 2.6%. Conclusion: Association of hemolysin production with resistance to imipenem and norfloxacin in UPEC strains was significant. Presence of hlyA gene is positively associated with ceftazidime resistance. Nitrofurantoin, piperacillin, tazobactam, and cefaperazone sulbactam are possible candidates for empirical therapy of UTIs. Drugs like aminoglycosides, carbapenems and fosfomycin may be used as reserve drugs in the treatment of MDR-UTI. However, inappropriate usage can increase antibiotic resistance. Hence proper selection of antibiotics in hospitals taking into account the local antibiogram is needed to reduce the emergence of antibiotic resistance.

Profile of Secondary Bacterial and Fungal Infections in Hospitalized COVID-19 Patients in a Tertiary Care Centre.

Introduction: SARS CoV-2, a novel corona virus, has emerged in December 2019. The COVID-19 associated mortality is documented in elderly with co morbidities. To have better insight on this issue, the secondary bacterial infections with multi-drug-resistant bacteria in COVID-19 patients need to be studied to evaluate the impact of these infections on the outcome. Aim and objectives: To determine the proportion of secondary infections in COVID-19 patients. To study the spectrum of pathogens and antibiogram of the bacteria isolated from secondary infections in such patients. To evaluate the co-existing co-morbidities, treatment and outcome in these patients. Methodology: The retrospective study was conducted in Departments of Medicine and Microbiology, KMC hospitals Attavara and Ambedkar circle, Mangaluru, including all the hospitalized microbiologically confirmed cases of SARS CoV-2 infection. Details pertaining to the study population were collected using a structured proforma. Descriptive data were entered in the form of mean, median and proportions. The categorical values were analyzed using Chi square test. Values of p < 0.05 were considered as statistically significant. Results: Two hundred COVID-19 hospitalized patients were included.28 out of 200 patients (14%) studied developed secondary infections. The types of secondary infections were Respiratory infections (50%), blood stream infections (17%), UTI (14%), Rhinocerebral Zygomycosis (17%). The predominant organisms were Klebsiella pneumoniae (44%), Zygomycetes (17%). The rates of antibiotic resistance in Gram negative bacilli were 33% to Cefuroxime,25% to aminoglycosides and fluoroquinolones and 16% to carbapenems. The mortality of 42.8% was observed in patients with secondary infections. Conclusion: Close monitoring and follow up especially in high-risk group of severe COVID 19 patients is crucial for better management and outcome.

The Profile of Epilepsy and its characteristics in Children with Cerebral Palsy.

PURPOSE: To determine the characteristics of epilepsy in children with Cerebral Palsy (CP) visiting the Pediatric Outpatient Department (OPD) of a tertiary care hospital. METHODS: This cross-sectional study was carried out at a tertiary care pediatric hospital. All children with CP aged between 1 and 12 years seen at this hospital during an 18 months period (January 2018 to July 2019) were included. Children with CP who had seizures were studied in detail. Seizure semiologies were classified according to the International League Against Epilepsy (ILAE) 1981 and 2017 classifications. The severity of seizures was assessed with the Early Childhood Epilepsy Severity Scale (E-Chess). Functional impairment was characterised using the Gross Motor Function Classification System (GMFCS) score. RESULTS: Of 300 children with CP, 207 (69%) were male and 93 (31%) female. The mean age was 45.17±31.12 months. Seizures were present in 79 (26%) children. 89.9% of children had drug-responsive epilepsy, and 10.1% had refractory epilepsy. Seizures were present in 30.4% of children with a spastic hemiplegia CP subtype, 28.7% with spastic quadriplegia, 26.3% with spastic diplegia, 24% with mixed type CP, and 6.3% with dyskinetic CP. On E-Chess assessment, the median score was 8 (4-14). The majority had poor Gross Motor Function Classification System (GMFCS) scores (>III). CONCLUSION: The prevalence of epilepsy in the studied population of children with CP was 26%. The highest incidence of seizures was in the spastic hemiplegia subtype (30.4%). The severity of cortical damage is positively correlated with the risk of having epilepsy. The primary determinant of severity of the GMFCS score was the type of CP and not the presence or absence of epilepsy.

Fungal infections of spine: Case series during the COVID times.

Fungal infections of the spine are a rare occurrence. We report three cases of Spondylodiscitis due to Aspergillus fumigatus, Candida albicans and Scedosporium apiospermum. Case 1:37 year old male, with history of COVID-19 infection one month prior presented with L1-2 Spondylodiscitis. Tissue showed growth of Aspergillus fumigatus. Case 2:75 year old male was admitted with swelling over low back. Pus aspirated from the swelling and tissue sent from operated site showed growth of Candida albicans. Case 3:56 year old known diabetic and end stage renal disease on hemodialysis presented with mid back pain since 2 months. Culture showed growth of Scedosporium apiospermum.

Comprehensive Study of Human FBXW7 Deleterious nsSNP's Functional Inference and Susceptibility to Gynaecological Cancer.

Cancer is one of the world's major causes of mortality, and it plays a most important role in the world's declining life expectancy. F-box and WD-40 domain protein 7 (FBXW7), a typical participant of the F-box family of proteins, has been considered as an anti-tumor protein and one of the maximum deregulated ubiquitin-proteasome system proteins in uterine carcinosarcoma, endometrial clear cell carcinoma and cervical carcinoma with the greatest prevalence of alterations. FBXW7 variants with known clinical significance, as well as non-synonymous single nucleotide polymorphisms (nsSNPs) in the F-Box and WD40 domains, were evaluated using functionality prediction web resources. Upon analysing the seventy-three deleterious nsSNP's impact on protein stability and function, we identified that forty-one nsSNPs of WD40 domain and three of F-Box domain imply decreased stability of the FBXW7 structure. Next to TP53 and PTEN, FBXW7 was reported with the highest percentage of arginine substitution among mutations related to cancer. The current research concentrated on two arginine residue locations (Arg465, Arg505) within the WD40-repeat domain, which is vital for substrate binding. Computational analysis revealed significant deviation in stability and structural configuration of mutants R505L, R465H, R465P, R505G, R505C, R465C, R505S and R505L structures. Protein-protein interaction network of FBXW7 populated with promising hub proteins NOTCH1, c-Myc, CCNE1, STYX, KLG5, SREB1, NFKB2, SKP1 and CUL1; thus, alteration in the FBXW7 leads to aberration in their signalling pathways as well as their substrate binding ability makes this protein as attractive target for personalized therapeutic intervention.

Approaches for Head and Neck Cancer Research - Current Status and the Way Forward.

Head and neck cancers (HNCs) are seeing an increasing trend in their prevalence among both genders and are the seventh most common cancer type occurring at the global level. Studies addressing both the cancer cell physiology and individual differences in response to a specific treatment modality should be understood for arriving at effective treatment and management of the HNCs. In this article, we discuss the trends in HNC research and their various approaches starting from 2D in vitro models, which are the traditional experimental materials to recently established Cancer-Tissue Originated Spheroids (CTOS) distinctly contributing towards personalized or precision medicine.

ß-Defensin from the Asian Sea Bass, Lates calcarifer: Molecular Prediction and Phylogenetic Analysis.

Antimicrobial peptides (AMPs) are an important element of the innate immune system of all living organisms and serve as a barrier that safeguards the organisms against a wide range of pathogens. Fishes are proven to be a prospective source of AMPs, and ß-defensins form an important family of AMPs with potent antimicrobial, chemotactic and immunomodulatory activities. The present study reports a ß-defensin AMP sequence (Lc-BD) from the Asian sea bass, Lates calcarifer, a commercially important fish species in tropical and subtropical regions of Asia and the Pacific. A 202-bp cDNA fragment with an open reading frame encoding 63 amino acids (aa) was obtained from the mRNA of gill tissue by RT-PCR. The deduced aa sequence of Lc-BD possessed a signal and a mature peptide region with 20 and 43 aa residues, respectively. Lc-BD was characterized at the molecular level, and a molecular weight of 5.24 kDa and a net charge of +4.5 was predicted for the mature peptide. The molecular characterization of Lc-BD revealed the presence of three intramolecular disulphide bonds involving the six conserved cysteine residues in the sequence, and the phylogenetic analysis of Lc-BD showed a close relationship with ß-defensins from fishes like Siniperca chuatsi, Argyrosomus regius, Trachinotus ovatus and Oplegnathus fasciatus.

Molecular and Functional Characterization of an Anti-lipopolysaccharide Factor Mm-ALF from Speckled Shrimp Metapenaeus monoceros.

Anti-lipopolysaccharide factors (ALFs) are antimicrobial peptides of approximately 100 amino acid residues with a broad spectrum of antimicrobial activity. It is an amphipathic peptide with an N-terminal hydrophobic region and a lipopolysaccharide binding domain (LBD). In the present study, we report an isoform of the anti-lipopolysaccharide factor (Mm-ALF) from the speckled shrimp, Metapenaeus monoceros. A 359 bp cDNA encoded 119 amino acids, and the sequence showed 99.16% similarity to ALF from the shrimp Fenneropenaeus indicus. The mature peptide of 94 amino acids has a net charge of +8, molecular weight 10.62 kDa, and pI 10.11. The mature peptide Mm-ALF was recombinantly expressed in E. coli Rosetta-gami cells, and the peptide was isolated and purified. The rMm-ALF exhibited notable antibacterial activity against Gram-positive (Staphylococcus aureus and Bacillus cereus) and Gram-negative (Escherichia coli, Edwardsiella tarda, Aeromonas hydrophila, Pseudomonas aeruginosa, Vibrio parahaemolyticus, Vibrio harveyi, Vibrio alginolyticus, Vibrio proteolyticus, Vibrio cholerae and Vibrio fluvialis) bacteria.

Mycotic keratitis due to Cylindrocarpon lichenicola: Successful salvage of the eye.

We hereby report a successfully salvaged eye due to mycotic keratitis by Cylindrocarpon lichenicola in a 60-year-old female from Kasaragod (Kerala). The patient came with a history of pain, photophobia and decreased vision of the right eye. The microbiological investigations of the corneal scraping revealed C. lichenicola. C. lichenicola is a soil saprophyte. Since the ulcer worsened paracentesis followed by therapeutic keratoplasty and adjunct therapy with natamycin drops, voriconazole drops and oral ketoconazole was given. We stress that evidence-based timely medical and surgical intervention helped in the restoration of the vision in an infected eye.

Role of Antisperm Antibodies in Infertility, Pregnancy, and Potential forContraceptive and Antifertility Vaccine Designs: Research Progress and Pioneering Vision.

Sperm of humans, non-human primates, and other mammalian subjects is considered to be antigenic. The effect of changes in autoimmunity on reproductive cells such as spermatozoa and oocytes play a critical but indistinct role in fertility. Antisperm antibodies (ASAs) are invariably present in both females and males. However, the degree of ASA occurrence may vary according to individual and gender. Although the extent of infertility due to ASAs alone is yet to be determined, it has been found in almost 9-12% of patients who are infertile due to different causes. Postcoital presence of spermatozoa in the reproductive tract of women is not a contributory factor in ASA generation. However, ASA generation may be induced by trauma to the vaginal mucosa, or by anal or oral sex resulting in the deposition of sperm inside the digestive tract. It is strongly believed that, in humans and other species, at least some antibodies may bind to sperm antigens, causing infertility. This form of infertility is termed as immunological infertility, which may be accompanied by impairment of fertility, even in individuals with normozoospermia. Researchers target ASAs for two major reasons: (i) to elucidate the association between ASAs and infertility, the reason ASAs causes infertility, and the mechanism underlying ASA-mediated infertility; and (ii) to assess the potential of ASAs as a contraceptive in humans in case ASAs influences infertility. Therefore, this review explores the potential application of ASAs in the development of anti-spermatozoa vaccines for contraceptive purposes. The usefulness of ASAs for diagnosing obstructive azoospermia, salpingitis, and oligoasthenoteratozoospermia has been reviewed extensively. Important patents pertaining to potential candidates for spermatozoa-derived vaccines that may be utilized as contraceptives are discussed in depth. Antifertility vaccines, as well as treatments for ASA-related infertility, are also highlighted. This review will address many unresolved issues regarding mechanisms involving ASAs in the diagnosis, as well as prognoses, of male infertility. More documented scientific reports are cited to support the mechanisms underlying the potential role of ASA in infertility. The usefulness of sperm antigens or ASAs (recombinant) in human and wild or captive animal contraceptive vaccines has been revealed through research but is yet to be validated via clinical testing.