146 results on '"Nair AV"'
Search Results
2. Relocation of active site carboxylates in major facilitator superfamily multidrug transporter LmrP reveals plasticity in proton interactions
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Nair, AV, Singh, H, Raturi, S, Neuberger, A, Tong, Z, Ding, N, Agboh, K, van Veen, HW, Neuberger, Arthur [0000-0002-7744-6559], Van Veen, Hendrik W. [0000-0002-9658-8077], and Apollo - University of Cambridge Repository
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Lactococcus lactis ,Models, Molecular ,Bacterial Proteins ,Catalytic Domain ,Cations ,Mutation ,Carboxylic Acids ,Membrane Transport Proteins ,Protons ,Protein Structure, Secondary ,Article - Abstract
The expression of polyspecific membrane transporters is one important mechanism by which cells can obtain resistance to structurally different antibiotics and cytotoxic agents. These transporters reduce intracellular drug concentrations to subtoxic levels by mediating drug efflux across the cell envelope. The major facilitator superfamily multidrug transporter LmrP from $\textit{Lactococcus}$ lactis catalyses drug efflux in a membrane potential and chemical proton gradient-dependent fashion. To enable the interaction with protons and cationic substrates, LmrP contains catalytic carboxyl residues on the surface of a large interior chamber that is formed by transmembrane helices. These residues co-localise together with polar and aromatic residues, and are predicted to be present in two clusters. To investigate the functional role of the catalytic carboxylates, we generated mutant proteins catalysing membrane potential-independent dye efflux by removing one of the carboxyl residues in Cluster 1. We then relocated this carboxyl residue to six positions on the surface of the interior chamber, and tested for restoration of wildtype energetics. The reinsertion at positions towards Cluster 2 reinstated the membrane potential dependence of dye efflux. Our data uncover a remarkable plasticity in proton interactions in LmrP, which is a consequence of the flexibility in the location of key residues that are responsible for proton/multidrug antiport.
- Published
- 2016
3. Isolation, characterisation and phylogenetic diversity of culturable bacteria associated with marine microalgae from saline habitats of south India
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Sandhya, SV, primary, Preetha, K, additional, Nair, AV, additional, Antony, ML, additional, and Vijayan, KK, additional
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- 2017
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4. Unusual presentation of chondroblastoma mimicking Trevor's disease
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Nair, AV, primary and Anirudh, S, additional
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- 2017
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5. ACR Appropriateness Criteria((R)) Radiologic Management of Thoracic Nodules and Masses.
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Ray CE Jr, English B, Funaki BS, Burke CT, Fidelman N, Ginsburg ME, Kinney TB, Kostelic JK, Kouri BE, Lorenz JM, Nair AV, Nemcek AA Jr, Owens CA, Saleh AG, Vatakencherry G, and Mohammed TL
- Abstract
Pulmonary and mediastinal masses represent a wide range of pathologic processes with very different treatment options. Although advances in imaging (such as PET and high-resolution CT) help in many cases with the differential diagnosis of thoracic pathology, tissue samples are frequently needed to determine the best management for patients presenting with thoracic masses. There are many options for obtaining tissue samples, each of which has its own set of benefits and drawbacks. The purposes of this report are to present the most current evidence regarding biopsies of thoracic nodules and masses and to present the most appropriate options for select common clinical scenarios. The ACR Appropriateness Criteria((R)) are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. [ABSTRACT FROM AUTHOR]
- Published
- 2012
6. Molecular features and expression kinetics of interleukin-10 gene from the marine teleost, Snubnose pompano (Trachinotus blochii).
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Chakkalakkal GJ, Gopakumar ST, Sharma SRK, Raveendranathan DN, Jagannivasan A, Nair AV, Ramachandran V, and Achamveetil G
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- Animals, Gene Expression Regulation, Vibrio, Fish Proteins genetics, Fish Proteins metabolism, MicroRNAs genetics, Fishes genetics, Fishes immunology, Amino Acid Sequence, Fish Diseases genetics, Fish Diseases immunology, Fish Diseases microbiology, Open Reading Frames genetics, Kinetics, RNA, Messenger genetics, RNA, Messenger metabolism, Vibrio Infections veterinary, Vibrio Infections genetics, Vibrio Infections immunology, Interleukin-10 genetics, Interleukin-10 metabolism, Phylogeny, 3' Untranslated Regions genetics
- Abstract
Background: Interleukin 10 (IL-10) is uniquely positioned in the immune regulation of teleosts. Modifying the IL-10 pathway changes the teleost's disease susceptibility; however, there is no data on its post-transcriptional regulation. Trachinotus blochii is a high-value mariculture species., Methods: The full-length tbil-10 gene was generated through the Rapid Amplification of cDNA Ends-PCR. After the detailed sequence analysis, the identified features were compared with other IL-10 sequences. The gene expressions in healthy and challenged (Vibrio harveyi) fish were studied., Results: The sequence analysis showed an open reading frame of 564 bp and a 3' UTR (untranslated region) of 217 bp. The phylogram revealed an evolutionary distinction between marine and freshwater teleost IL-10. The shorter 3' UTR, additional conserved cysteines capable of forming stable disulphide bonds, and lesser mRNA instability moieties suggest the better structural stability of teleost IL-10 than tetrapods. Results identified 60 miRNA-mRNA duplexes that can regulate IL-10 3' UTR. Nine identified miRNAs are involved in immune response and seven are expressed in macrophages. The gills showed the highest gene expression in healthy fish. The study discovered two IL-10 mRNA transcripts that differed in 5' UTR lengths and thermodynamic ensemble's free energy. There was an increased expression of both tbil-10-mRNA transcripts from 2 to 48 h post-challenge which peaked at 24 h after the challenge, with higher expression of short mRNA transcript., Conclusions: The results gave insights into the structural, functional, post-transcriptional regulatory mechanisms, and expression characteristics of the IL-10 gene in T. blochii., Competing Interests: Declarations. Ethical approval: The ‘European Union’s Animal Experiments Directive 2010/63/E.U.’ and the ‘United Kingdom’s Animals (Scientific Procedures) Act (1986)’ were followed in the handling of live animals (2019). ICAR-CMFRI approved the methods (BT/AAQ/3/SP28267/2018). Consent to participate: Not applicable. Consent for publication: We confirmed that all the authors have read and approved the manuscript. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)
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- 2024
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7. Salmonella Typhimurium effector SseI regulates host peroxisomal dynamics to acquire lysosomal cholesterol.
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Raj D, Nair AV, Singh A, Basu S, Sarkar K, Sharma J, Sharma S, Sharma S, Rathore M, Singh S, Prakash S, Simran, Sahu S, Kaushik AC, Siddiqi MI, Ghoshal UC, Chandra T, Bhosale V, Dasgupta A, Gupta SK, Verma S, Guha R, Chakravortty D, Ammanathan V, and Lahiri A
- Abstract
Salmonella enterica serotype Typhimurium (Salmonella) resides and multiplies intracellularly in cholesterol-rich compartments called Salmonella-containing vacuoles (SCVs) with actin-rich tubular extensions known as Salmonella-induced filaments (SIFs). SCV maturation depends on host-derived cholesterol, but the transport mechanism of low-density lipoprotein (LDL)-derived cholesterol to SCVs remains unclear. Here we find that peroxisomes are recruited to SCVs and function as pro-bacterial organelle. The Salmonella effector protein SseI is required for the interaction between peroxisomes and the SCV. SseI contains a variant of the PTS1 peroxisome-targeting sequence, GKM, localizes to the peroxisomes and activates the host Ras GTPase, ADP-ribosylation factor-1 (ARF-1). Activation of ARF-1 leads to the recruitment of phosphatidylinsolitol-5-phosphate-4 kinase and the generation of phosphatidylinsolitol-4-5-bisphosphate on peroxisomes. This enhances the interaction of peroxisomes with lysosomes and allows for the transfer of lysosomal cholesterol to SCVs using peroxisomes as a bridge. Salmonella infection of peroxisome-depleted cells leads to the depletion of cholesterol on the SCVs, resulting in reduced SIF formation and bacterial proliferation. Taken together, our work identified peroxisomes as a target of Salmonella secretory effectors, and as conveyance of host cholesterol to enhance SCV stability, SIF integrity, and intracellular bacterial growth., Competing Interests: Disclosure and competing interests statement. The authors declare no competing interests., (© 2024. The Author(s).)
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- 2024
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8. Posterior reversible encephalopathy syndrome and parkinsonism as the first manifestation of primary hyperparathyroidism - a report of two cases.
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Rallapalli SS, Rayani M, Ninan GA, Hussain MA, Nair AV, Bal D, Cherian KE, Prabhakar AT, Paul TV, and Thomas N
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- Humans, Female, Adult, Male, Aged, Parkinsonian Disorders etiology, Parkinsonian Disorders complications, Parathyroidectomy, Hypercalcemia etiology, Hypercalcemia complications, Magnetic Resonance Imaging, Hyperparathyroidism, Primary complications, Hyperparathyroidism, Primary surgery, Posterior Leukoencephalopathy Syndrome etiology, Posterior Leukoencephalopathy Syndrome complications
- Abstract
Background/objective: Primary hyperparathyroidism (PHPT) may be asymptomatic or present with renal calculi, secondary osteoporosis, fractures and neuropsychiatric manifestations. Posterior reversible encephalopathy syndrome (PRES) and parkinsonism are atypical manifestations that may be rarely associated with PHPT. We report two patients who presented with the conditions mentioned above., Case Report: The first patient involved a 38-year-old woman who presented with diminution of vision, seizures, altered behavior and hypertension over eight months. An MRI of the brain done had shown vasogenic edema involving the parieto-occipital regions, suggestive of PRES. A metabolic screen revealed PTH-dependent hypercalcemia that was localized to the left inferior parathyroid gland. Following focused parathyroidectomy, there was improvement in sensorium, vision and normalization of blood pressure. The second patient was of a 74-year-old man who presented with progressive extrapyramidal symptoms of gait abnormalities and rigidity since the past eight months. He was initiated on Selegeline and Levodopa for the same purpose, and subsequently reported minimal improvement in symptoms. Investigations revealed PHPT associated with a right inferior parathyroid adenoma. Within two weeks following surgery, there was an improvement in rigidity and gait and he was able to ambulate without support., Discussion: PRES has been reported to occur in the context of preeclampsia, hypertension, infection, sepsis and autoimmune conditions. PRES associated with hypercalcemia is rarely reported. While extra-pyramidally related manifestations are described in hypoparathyroidism, PHPT related parkinsonism is not commonly encountered. Identifying the underlying aetiology and initiation of corrective measures may lead to amelioration of patient symptomatology., Conclusion: The occurrence of PRES and parkinsonism is rare in primary hyperparathyroidism; the two patients described above highlight the importance of screening for hypercalcemia in the setting of neurological manifestations., Competing Interests: Compliance with ethical standards Conflict of interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Ethical disclosure Informed consent was taken from the patient. The authors declare that no patient data appears in the article., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
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- 2024
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9. Study to localize isometric points of anterior band of inferior glenohumeral ligament and to use long head of biceps as a graft: A finite element analysis and arthroscopic cadaveric demonstration.
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Nair AV, Thampy J S, Srinath MK, Kumar Mohan P, Rambhojun M, Krishna P, Jangale A, and Khan PS
- Abstract
Background: The inferior glenohumeral ligament (IGHL) comprising the anterior and posterior bands with interposing axillary pouch is an important static stabilizer of anterior translation and external rotation (ER) in the 90-degree abduction position. No literature is available to determine any ideal graft or isometric point for fixation of any graft to replace the functionality of IGHL such that the tensile stress acting on the graft is under the limits of the tensile properties of the graft used for reconstruction., Methods: Using finite element method analysis (FEM) of the long head of the biceps tendon (LHBT) with modeling and simulation process, the ultimate tensile strength of the LHBT at the different clock positions of the humeral head attachment and angular positions of the humerus were determined through a combination of Taguchi Design of Experiments and simulation using ANSYS (Analysis system) software., Results: Through FEM simulations using the ANSYS software, it was concluded that the clock position of 7:30 would be appropriate to fix the biceps Tendon on the humerus. The tensile stress induced in the IGHL at 7:30 on the humerus, at 90° abduction with 90° rotation of the humerus, as well as at 120° abduction with 90° rotation of the humerus was evaluated and validated., Conclusions: Reconstruction of anterior band of IGHL using LHBT in its isometric points found in this study can provide a solution to manage anterior instability anatomically rather than non-anatomical procedures like dynamic anterior stabilization. This will be an anatomical procedure that will bridge the gap between anatomical Bankarts procedure and non-anatomical latarjet procedure. The LHBT can be suitable graft material for the anterior band of the IGHL reconstruction. Our study demonstrated that the most optimal fixation points for the graft, which resulted in the least tensile stress on the LHBT, were found to be at the 3 o'clock position on the glenoid and the 7:30 o'clock position on the humerus., Level of Evidence: LEVEL 5 - methodological verification and validation., Competing Interests: Declaration of competing interest None declared., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
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- 2024
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10. Combating biofilm-associated Klebsiella pneumoniae infections using a bovine microbial enzyme.
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Ramakrishnan R, Nair AV, Parmar K, Rajmani RS, Chakravortty D, and Das D
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- Animals, Cattle, Mice, Microbial Sensitivity Tests, Meropenem pharmacology, Humans, Disease Models, Animal, Biofilms drug effects, Biofilms growth & development, Klebsiella pneumoniae drug effects, Klebsiella Infections microbiology, Klebsiella Infections drug therapy, Anti-Bacterial Agents pharmacology
- Abstract
The emergence of multidrug-resistant Klebsiella pneumoniae poses significant clinical challenges with limited treatment options. Biofilm is an important virulence factor of K. pneumoniae, serving as a protective barrier against antibiotics and the immune system. Here, we present the remarkable ability of a bovine microbial enzyme to prevent biofilm formation (IC
50 2.50 μM) and degrade pre-formed K. pneumoniae biofilms (EC50 1.94 μM) by degrading the matrix polysaccharides. The treatment was effective against four different clinical K. pneumoniae isolates tested. Moreover, the enzyme significantly improved the biofilm sensitivity of a poorly performing broad-spectrum antibiotic, meropenem, and immune cells, resulting in facile biofilm clearance from the mouse wound infection. Notably, well-known powerful enzymes of the same class, cellulase, and α-amylase, were nearly inactive against the K. pneumoniae biofilms. The enzyme exhibited antibiofilm activity without showing toxicity to the mammalian and microbial cells, highlighting the potential of the enzyme for in vivo applications., (© 2024. The Author(s).)- Published
- 2024
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11. Pediatric AC Joint Fracture Dislocation: Arthroscopy-assisted Reduction and Internal Bracing.
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Nair AV, Thampy JS, Rambhojun M, Bharadwaj B, Yoo YS, and Khan PS
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Introduction: Acromioclavicular joint injuries are common injuries around shoulder and comprise around 9-12% and are rare in pediatric population. Many surgeries have been described which include open stabilization, arthroscopic assisted, or complete arthroscopic. We describe our technique of arthroscopic-assisted fixation in AC joint acute injuries, in which we arthroscopically pass fiber tape and tunnels across coracoid base and clavicle to stabilize the upward forces, followed by double breasting for AC joint with fiber tape to balance the horizontal forces., Case Report: A 9-year-old female kid with a history of falls with left shoulder pain and diagnosed with fracture dislocation of the left ac joint. The patient in beach chair position. Arthroscopically, fibertape was passed through a drill hole near to cc ligament and cinch loop was done through it and around coracoid. With a mini-incision, AC joint further stabilized., Conclusion: Similar case reports are very few and arthroscopic management of same is nearly none. Advantages of our procedure are relatively low cost of the implant, and no anchors or metal implants at AC joint to avoid impingement. Open AC joint stabilization addresses the disc in joint. Disadvantages are a long learning curve., Competing Interests: Conflict of Interest: Nil, (Copyright: © Indian Orthopaedic Research Group.)
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- 2024
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12. Degradation of marine crustacean shell wastes through single-stage co-fermentation using proteolytic and chitinolytic bacteria.
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Vakkachan AP, Gopakumar ST, Janardhanan RK, Pootholathil S, Surendran S, Nair AV, Raveendran RK, Suresh G, Subramanian S, and Pananghat V
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- Animals, Fermentation, Biodegradation, Environmental, Animal Shells chemistry, Chitin metabolism, Bacteria metabolism, Proteolysis, Crustacea
- Abstract
Management of crustacean shell waste (SW) through an eco-friendly technique is an environmental obligation to control pollution. The present study showed a novel approach through the simultaneous application of proteolytic and chitinolytic bacteria to effectively degrade unprocessed crustacean SW. For this, the bacteria with concurrent chitinolytic and proteolytic activity (Bacillus subtilis, Priestia megaterium, or Bacillus amyloliquefaciens) were applied either alone or in combination with one proteolytic strain (Paenibacillus alvei) in the unprocessed lobster, crab, and shrimp SW. The method degraded the shells with high deproteinization (> 90%) and demineralization efficiency (> 90%). The degradation was confirmed through scanning electron microscopy. The highest weight loss achieved with shrimp, crab, and lobster shells was 93.67%, 82.60%, and 83.33%, respectively. B. amyloliquefaciens + P. alvei combination produced the highest weight loss in crab and lobster SW, whereas all combinations produced statistically similar weight loss in shrimp SW. There was a concurrent production of N-acetyl glucosamine (up to 532.89, 627.87, and 498.95 mg/g of shrimp, lobster, and crab shell, respectively, with P. megaterium + P. alvei and B. amyloliquefaciens + P. alvei in all SW) and amino acids (4553.8, 648.89, 957.27 μg/g of shrimp, lobster, and crab shells, respectively with B. subtilis + P. alvei in shrimp and B. amyloliquefaciens + P. alvei in crab and lobster). Therefore, it is concluded that, for the first time, efficient degradation of crustacean shell waste was observed using chitinolytic and proteolytic bacterial fermentation with the obtention of byproducts, providing a basis for further application in SW management., Competing Interests: Declarations. Ethical approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests, (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
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- 2024
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13. CRISPR-Cas system positively regulates virulence of Salmonella enterica serovar Typhimurium.
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Sharma N, Das A, Nair AV, Sethi P, Negi VD, Chakravortty D, and Marathe SA
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Background: Salmonella, a foodborne pathogen, possesses a type I-E clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR associated (Cas) system. We investigated the system's role in regulating Salmonella virulence by deleting the CRISPR arrays and Cas operon., Results: Our study demonstrates invasion and proliferation defects of CRISPR-Cas knockout strains in intestinal epithelial cells and macrophages owing to the repression of invasion and virulence genes. However, proliferation defects were not observed in the Gp91
phox-/- macrophages, suggesting the system's role in the pathogens' antioxidant defense. We deduced that the CRISPR-Cas system positively regulates H2 O2 importer (OmpW), catalase (katG), peroxidase (ahpC), and superoxide dismutase (soda and sodCI), thereby protecting the cells from oxidative radicals. The knockout strains were attenuated in in-vivo infection models (Caenorhabditis elegans and BALB/c mice) due to hypersensitivity against antimicrobial peptides, complement proteins, and oxidative stress. The attenuation in virulence was attributed to the suppression of LPS modifying (pmr) genes, antioxidant genes, master regulators, and effectors of the SPI-1 (invasion) and SPI-2 (proliferation) islands in knockout strains. The regulation could be attributed to the partial complementarity of the CRISPR spacers with these genes., Conclusions: Overall, our study extends our understanding of the role of the CRISPR-Cas system in Salmonella pathogenesis and its virulence determinants., (© 2024. The Author(s).)- Published
- 2024
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14. Insights into the methodological perspectives for screening polyunsaturated fatty acids-containing bacteria.
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Ramachandran V, Gopakumar ST, Ramachandra KSS, Chandrasekar S, Tejpal CS, Nair AV, Pootholathil S, Sreenath KR, Nithyashree JK, and Achamveetil G
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- Hydrogen Peroxide metabolism, Gas Chromatography-Mass Spectrometry, Fatty Acids, Unsaturated metabolism, Bacteria metabolism, Bacteria isolation & purification
- Abstract
Polyunsaturated fatty acids (PUFA) are vital molecules in the pharmaceutical, medical, and nutritional industries. Exploration of bacterial strains capable of producing significant amounts of PUFAs offers a promising avenue for biotechnological applications and industrial-scale production. However, an extensive screening of several samples from diverse sources is highly needed to identify a potential strain. The present study provides the results of the evaluation of 15 different screening methodologies (including changes in existing protocols in terms of reagent concentration, incubation temperature and time) for identifying PUFA-producing bacteria in comparison to the gold standard method (Gas chromatography-mass spectrometry), for the first time. The results determined the most effective techniques for each critical PUFA, leading to an optimized screening process that saves time and resources. The H
2 O2 plate assay using 0.5% or 1% H2 O2 for 72 & 96 h of incubation at 15 °C consistently outperformed others for finding bacteria containing total nutritionally important long chain-PUFA (LC-PUFA), linoleic acid, and arachidonic acid. Whereas the 2,3,5-triphenyl tetrazolium chloride broth assay at 10-15 °C was the most effective and semiquantitative screening methodology for eicosapentaenoic acid (EPA) and alpha-linolenic acid-containing bacteria. Apart from the methodological perspectives, the study also revealed certain potential strains to be targeted in the ongoing research on PUFA-containing bacteria. Further, the manuscript forms the first report on the presence of docosahexaenoic acid (DHA) in Shewanella decolorationis, EPA in Psychrobacter maritimus and Micrococcus aloeverae, and both EPA and DHA in Arthrobacter rhombi. Altogether, the paper generates several thought-provoking insights on the methodological perspectives and identifies potential PUFA-containing bacteria with practical applications in future bacteria-based PUFA research., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)- Published
- 2024
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15. In vitro efficacy of aquaculture antimicrobials and genetic determinants of resistance in bacterial isolates from tropical aquaculture disease outbreaks.
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Gopakumar ST, Ramachandra KSS, Gangadharan S, Nair AV, Sachidanandan S, Prasad V, Purakal LV, Chakkalakkal GJ, and Patil PK
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- Animals, Disease Outbreaks, Drug Resistance, Bacterial genetics, Thiamphenicol analogs & derivatives, Thiamphenicol pharmacology, Oxytetracycline pharmacology, Oxolinic Acid pharmacology, Vibrio drug effects, Vibrio genetics, Vibrio isolation & purification, India epidemiology, Streptococcus agalactiae drug effects, Streptococcus agalactiae genetics, Streptococcus agalactiae isolation & purification, Enrofloxacin pharmacology, Photobacterium drug effects, Photobacterium genetics, Photobacterium isolation & purification, Drug Resistance, Multiple, Bacterial genetics, Aquaculture, Microbial Sensitivity Tests, Fish Diseases microbiology, Anti-Bacterial Agents pharmacology, Fishes microbiology
- Abstract
Understanding the efficacy of antimicrobials against pathogens from clinical samples is critical for their responsible use. The manuscript presents in vitro efficacy and antimicrobial resistance (AMR) genes in seven species of fish pathogens from the disease outbreaks of Indian aquaculture against oxytetracycline, florfenicol, oxolinic acid, and enrofloxacin. In vitro efficacy was evaluated by minimum inhibitory concentration and minimum bactericidal concentration. The gene-specific PCR screened AMR genes against quinolones (qnrA, qnrB, and qnrS) and tetracyclines (tetM, tetS, tetA, tetC, tetB, tetD, tetE, tetH, tetJ, tetG, and tetY). The results showed that Aeromonas veronii (45%) showed the maximum resistance phenotype, followed by Streptococcus agalactiae (40%), Photobacterium damselae (15%), Vibrio parahaemolyticus (10%), and Vibrio vulnificus (5%). There was no resistance among Vibrio harveyi and Vibrio alginolyticus against the tested antimicrobials. The positive association between tetA, tetB, tetC, tetM, or a combination of these genes to oxytetracycline resistance and qnrS to quinolone resistance indicated their potential in surveillance studies. The prevalence of resistance phenotypes (16.43%) and evaluated AMR genes (2.65%) against aquaculture antimicrobials was low. The resistance phenotype pattern abundance was 0.143. All the isolates showed susceptibility to florfenicol. The results help with the appropriate drug selection against each species in aquaculture practices., (© The Author(s) 2024. Published by Oxford University Press on behalf of Applied Microbiology International.)
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- 2024
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16. Making Waves: A justice-centred framework for wastewater-based public health surveillance.
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Arefin MR, Prouse C, Wittmer J, Amin N, Assunção M, Benezra A, Chaudhuri A, Diamond M, Harshe S, Hill-Tout K, Koetz V, Larsen D, Mansfeldt C, Melgaço L, Nainani D, Nair AV, Naughton CC, O'Donnell M, Reimer C, Robinson P, Shelley J, and Srikantalah V
- Subjects
- Public Health Surveillance methods, Humans, Social Justice, Public Health, Environmental Monitoring methods, Wastewater
- Abstract
Since 2020 wastewater-based surveillance has quickly been established as an effective and cost-efficient tool for monitoring public health. In this Making Waves article, we argue that these programs must be grounded in principles of justice to achieve global water and health equity. Ethics initiatives to date have focused primarily on privacy, legality, and institutionalised research reviews, often, if not exclusively, in North America and Western Europe. We draw from our interdisciplinary, multisectoral, and international expertise and experience to develop a justice-centred framework for wastewater-based surveillance. First, we identify common concerns across diverse surveillance programs including: defining community, transparency and accountability, and uneven geographies. Second, we draw on political theorist Nancy Fraser's framework of justice to evaluate site-specific practices identifying maldistribution, misrecognition, and exclusion. We suggest that Fraser's framework offers a common approach for evaluating just outcomes rather than specific regulations for governing wastewater surveillance across different and unequal contexts., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Mohammed Rafi Arefin and Carolyn Prouse reports financial support was provided by Government of Canada Social Sciences and Humanities Research Council. Mohammed Rafi Arefin and Carolyn Prouse reports financial support was provided by Urban Studies Foundation. Pamela Robinson reports a relationship with Government of Canada Social Sciences and Humanities Research Council that includes: funding grants. Colleen C. Naughton reports a relationship with University of California Merced that includes: funding grants. David Larsen reports a relationship with New York State Department of Health that includes: funding grants. David Larsen reports a relationship with Syracuse University that includes: funding grants. David Larsen reports a relationship with United States Center for Disease Control that includes: funding grants. David Larsen reports a relationship with Dexter Network that includes: consulting or advisory. David Larsen reports a relationship with Bill & Melinda Gates Foundation that includes: non-financial support. Dhiraj Nainani reports a relationship with Campus for Research Excellence And Technological Enterprise (National Research Foundation, Prime Minister's Office, Singapore) that includes: funding grants. Dhiraj Nainani reports a relationship with Singapore Centre for Environmental Life Sciences Engineering (Singapore Ministry of Education and National Research Foundation) that includes: funding grants. Cresten Mansfeldt reports a relationship with National Science Foundation that includes: funding grants and non-financial support. Cresten Mansfeldt reports a relationship with American Society for Microbiology that includes: funding grants and non-financial support. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2025
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17. Classification and Communication of Critical Findings in Emergency Radiology: A Scoping Review.
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Corallo L, Macdonald DB, Eldehimi F, Nair AV, and Mitchell S
- Abstract
Purpose: To identify the published standards for the classification and communication of critical actionable findings in emergency radiology and the associated facilitators and barriers to communication and message management or dissemination of such findings., Materials and Methods: Search terms for resources pertaining to critical findings (CFs) in emergency radiology were applied to two databases (PubMed, Embase). Screening of hits using the following pre-established inclusion and exclusion criteria were performed by three analysts with subsequent consensus discussion for discrepancies: (1) the resources include any standards for the classification and communication of imaging findings as critical, or (2) the resource discusses any facilitators to the communication of CFs, or (3) the resource discusses any barriers to the communication of CFs. Resources with explicit focus on a pediatric population or predominant focus on artificial intelligence or natural language processing were omitted. Accompanying gray literature search was used to expand included resources. Data extraction included year, country, resource type, scope or purpose, participants, context, standards to identifying or communicating CFs, facilitators and barriers, method type, recommendations, applicability, and disclosures., Results: Seventy-six resources were included in the final analysis, including 16 societal or commission guidelines. Among the guidelines, no standardized list of CFs was identified, with typical recommendations suggesting application of a local policy. Communication standards included direct closed-loop communication for high acuity findings, with more flexible communication channels for less acute findings. Applied interventions for CFs management most frequently fell into four categories: electronic (n = 10), hybrid (ie, electronic or administrative) (n = 3), feedback or education (n = 5), and administrative (n = 4)., Conclusion: There are published standards, policies, and interventions for the management of CFs in emergency radiology. Three-tier stratification (eg, critical, urgent, incidental) based on time sensitivity and severity is most common with most CFs necessitating closed-loop communication. Awareness of systemic facilitators and barriers should inform local policy development. Electronic and administrative communication pathways are useful adjuncts. Further research should offer comparative analyses of different CF interventions with regard to cost-effectiveness, notification time, and user feedback., (Copyright © 2024 American College of Radiology. Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
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18. Diagnosis and treatment approach of delayed presentation of anterior branch axillary nerve injury following shoulder dislocation: case report.
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Chinraj AK, Sait A, Raju A, Meleppuram JJ, Thankappan A, Nair AV, and Khan PS
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- Humans, Male, Middle Aged, Axilla diagnostic imaging, Treatment Outcome, Radial Nerve diagnostic imaging, Radial Nerve injuries, Radial Nerve surgery, Shoulder Dislocation complications, Wounds and Injuries diagnostic imaging, Wounds and Injuries etiology, Wounds and Injuries surgery
- Abstract
In this case report, a unique instance of delayed isolated anterior branch axillary nerve injury following shoulder dislocation is highlighted. The patient, a 55-year-old manual laborer, presented with severe deltoid wasting and reduced power 18 months postdislocation, necessitating a specialized treatment approach. The use of axillary nerve neurolysis and an innovative upper trapezius to anterior deltoid transfer via a subacromial path posterior to the clavicle, facilitated by an autologous semitendinosus graft, resulted in significant improvement with 160 degrees of abduction and Grade 4+ power Medical Research Council grading (MRC) at the 5-year follow-up., Competing Interests: Declaration of competing interest The authors declare that no financial interests/personal relationships exist to be considered as potential competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
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19. Functional OmpA of Salmonella Typhimurium provides protection from lysosomal degradation and inhibits autophagic processes in macrophages.
- Author
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Roy Chowdhury A, Hajra D, Mukherjee D, Nair AV, and Chakravortty D
- Abstract
Our previous study showed that OmpA-deficient Salmonella Typhimurium (STM) failed to retain LAMP-1, quit Salmonella-containing vacuole (SCV) and escaped to the host cytosol. Here we show that the cytosolic population of STM ΔompA sequestered autophagic markers, syntaxin17 and LC3B in a sseL-dependent manner and initiated lysosomal fusion. Moreover, inhibition of autophagy using bafilomycinA1 restored its intracellular proliferation. Ectopic overexpression of OmpA in STM ΔsifA restored its vacuolar niche and increased interaction of LAMP-1, suggesting a sifA-independent role of OmpA in maintaining an intact SCV. The OmpA extracellular loops impaired the LAMP-1 recruitment to SCV and caused bacterial release into the cytosol of macrophages, but unlike STM ΔompA, they retained their outer membrane stability and didn't activate the lysosomal degradation pathway aiding in their intra-macrophage survival. Finally, OmpA extracellular loop mutations protected the cytosolic STM ΔsifA from the lysosomal surveillance, revealing a unique OmpA-dependent strategy of STM for its intracellular survival., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)
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- 2024
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20. Challenges and Solutions: Total Knee Replacement in Patients with Chronic Lymphatic Filariasis: A Case Report.
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C A, Raju A, Meleppuram JJ, Nair AV, Mundakkal A, Thankappan A, and Khan PS
- Subjects
- Humans, Female, Middle Aged, Osteoarthritis, Knee surgery, Osteoarthritis, Knee complications, Chronic Disease, Arthroplasty, Replacement, Knee, Elephantiasis, Filarial surgery, Elephantiasis, Filarial complications
- Abstract
Case: A 59-year-old woman with a history of left knee pain exacerbated by lymphatic filariasis underwent successful total knee replacement (TKR) for advanced osteoarthritis. Postoperatively, diligent adherence to compression bandaging, physiotherapy, and lymphatic flow promotion resulted in no lymphedema progression. During the 5-year follow-up, the patient showed improved Knee injury and Osteoarthritis Outcome Score and stable implant., Conclusions: Currently, there are no established protocols or formulated guidelines for TKR in patients with chronic filariasis. The preoperative lymphedema prevention must be tailor-made for each patient in the context of advanced osteoarthritis based on the functional lymphatic vessel status., Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJSCC/C359)., (Copyright © 2024 by The Journal of Bone and Joint Surgery, Incorporated.)
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- 2024
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21. Clinical and radiological outcome following arthroscopic Latarjet with cerclage FiberTape fixation with a minimum 1-year follow-up.
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Nair AV, Panakkal JJ, Mohan PK, Rambhojan M, Thampy J S, and Khan PS
- Abstract
Background: The rates of implant-related complications are significant following the Latarjet procedure using metal screws in patients with recurrent shoulder dislocation and bone loss. The purpose of this study is to evaluate the short-term outcome following the arthroscopic Latarjet procedure using cerclage FiberTape (Arthrex, Naples, FL, USA) combined with remplissage and capsulolabral repair. It was hypothesized that performing the procedure with cerclage FiberTape would provide sturdy fixation, comparable to the conventional method of using metal screws, while averting hardware-related complications attributed to the latter in published literature., Methods: A prospective study was performed in a single institution between 2020 and 2022, with all surgeries performed by a single fellowship-trained shoulder surgeon who has ample experience in performing arthroscopic screw Latarjet procedures. Patient demographics, number of dislocations before surgery, arm dominance, ligamentous laxity, type of sporting activity, Instability Severity Index Score, and percentage of bone loss on the glenoid and humeral sides were recorded. The patients were followed up with visual analog scale, American Shoulder and Elbow Surgeons score, Rowe score, and Walch-Duplay score preoperatively and postoperatively. The coracoid graft position, healing, and remodeling were assessed with computed tomography scans at 3 months postoperatively. Minimum clinical follow-up was for a period of one year., Results: Overall, 10 patients (all males, average age 28 ± 8.8 years) were operated on with an arthroscopic Latarjet procedure using cerclage FiberTape. The minimum follow-up period was 12 months, and the mean follow-up was 13.2 months. The median and individual visual analog scores during arm motion, American Shoulder and Elbow Surgeons scores, Rowe scores, and Walch-Duplay scores improved in the follow-up period. Computed tomography scans at 3 months showed flushed graft position in 5 patients, medial graft position in two patients, and three patients showed graft nonunion with migration. Out of 10 patients, seven had good graft union in follow-up scans. None of the patients required revision surgery. All three patients with graft nonunion were kept under follow-up beyond the study period for recurrence of instability., Conclusion: Our study demonstrated that arthroscopic Latarjet using cerclage FiberTape fixation combined with remplissage and capsulolabral repair resulted in high rate of graft loosening and migration (30%). Nonetheless, patients in whom the coracoid graft had united, as well as those in whom it had not, all had good to excellent functional and clinical outcomes, no complications, and did not require any revision surgery., (© 2024 The Author(s).)
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- 2024
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22. Salmonella Typhimurium employs spermidine to exert protection against ROS-mediated cytotoxicity and rewires host polyamine metabolism to ameliorate its survival in macrophages.
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Nair AV, Singh A, Rajmani RS, and Chakravortty D
- Subjects
- Animals, Mice, Polyamines metabolism, Phagocytosis drug effects, Salmonella Infections microbiology, Salmonella Infections metabolism, NADPH Oxidases metabolism, NADPH Oxidases genetics, Host-Pathogen Interactions, Spermidine Synthase metabolism, Spermidine Synthase genetics, Oxidative Stress drug effects, Salmonella typhimurium metabolism, Salmonella typhimurium drug effects, Spermidine metabolism, Macrophages microbiology, Macrophages metabolism, Macrophages drug effects, Reactive Oxygen Species metabolism, Bacterial Proteins metabolism, Bacterial Proteins genetics, NADPH Oxidase 2, Membrane Proteins
- Abstract
Salmonella infection entails a cascade of attacks and defence measures. After breaching the intestinal epithelial barrier, Salmonella is phagocytosed by macrophages, where the bacteria encounter multiple stresses, to which it employs relevant countermeasures. Our study shows that, in Salmonella, the polyamine spermidine activates a stress response mechanism by regulating critical antioxidant genes. Salmonella Typhimurium mutants for spermidine transport and synthesis cannot mount an antioxidative response, resulting in high intracellular ROS levels. These mutants are also compromised in their ability to be phagocytosed by macrophages. Furthermore, it regulates a novel enzyme in Salmonella, Glutathionyl-spermidine synthetase (GspSA), which prevents the oxidation of proteins in E. coli. Moreover, the spermidine mutants and the GspSA mutant show significantly reduced survival in the presence of hydrogen peroxide in vitro and reduced organ burden in the mouse model of Salmonella infection. Conversely, in macrophages isolated from gp91phox
-/- mice, we observed a rescue in the attenuated fold proliferation previously observed upon infection. We found that Salmonella upregulates polyamine biosynthesis in the host through its effectors from SPI-1 and SPI-2, which addresses the attenuated proliferation observed in spermidine transport mutants. Thus, inhibition of this pathway in the host abrogates the proliferation of Salmonella Typhimurium in macrophages. From a therapeutic perspective, inhibiting host polyamine biosynthesis using an FDA-approved chemopreventive drug, D, L-α-difluoromethylornithine (DFMO), reduces Salmonella colonisation and tissue damage in the mouse model of infection while enhancing the survival of infected mice. Therefore, our work provides a mechanistic insight into the critical role of spermidine in stress resistance of Salmonella. It also reveals a bacterial strategy in modulating host metabolism to promote their intracellular survival and shows the potential of DFMO to curb Salmonella infection., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)- Published
- 2024
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23. Arthroscopic double row partial articular supraspinatus tendon avulsion bridge repair technique for shoulder: A transtendinous approach.
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Raju A, Meleppuram JJ, Thankappan A, Nair AV, Yoo YS, and Khan PS
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- Humans, Rotator Cuff surgery, Shoulder Joint surgery, Male, Suture Anchors, Treatment Outcome, Tendon Injuries surgery, Female, Range of Motion, Articular, Arthroscopy methods, Rotator Cuff Injuries surgery, Suture Techniques
- Abstract
Partial articular supraspinatus tendon avulsion (PASTA) lesions, a subset of partial rotator cuff tears, pose a surgical challenge, disrupting the integrity of the supraspinatus tendon. Transtendinous repair is the preferred choice in young individuals for limiting tear progression and preserving intact, high-quality cuff tissue, thus preventing tendon shortening, as compared to the tear completion and repair technique. Our approach leverages these advantages, specifically those indicated for Ellman's Grade 3 tears and cases where conservative treatments have failed. In our technique, we employ progressive dilation, anchor drill sleeve insertion to facilitate medial row anchor placement, followed by percutaneous spinal needles for suture shuttling, and finally locking sliding knots for compressive medial row repair, followed by lateral row fixation for additional stability. This method accelerates rehabilitation and restores optimal shoulder function., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
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- 2024
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24. Comparison of rituximab efficacy in treatment-naive and refractory inflammatory myopathies: experiences from a tertiary care centre.
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Manwatkar A, Naresh K, Mathew J, Nair AV, Goel R, Yadav B, Prakash JAJ, Das JK, and Sivadasan A
- Abstract
Objectives: To find out if Rituximab (RTX) is effective in "treatment naive" idiopathic inflammatory myopathies (IIM), and whether there could be differential treatment responses between the "treatment naive" and treatment "refractory" IIM., Methods: Data obtained from a prospectively maintained database comprising patients with IIM treated with rituximab. Patient details were obtained at baseline, 3-months, 6-months intervals, and subsequent follow up visits. Treatment response was categorised as improved, worsening, or stable based on manual muscle testing (MMT8) scores, patient global and physician global improvement (PtGA and PGA) for skin and joint symptoms improvement and spirometry at 6 months. The time to clinical improvement and remission were noted and survival analysis curves were constructed., Results: 60 patients with IIM (including 18 with anti-SRP myopathy) were included, out of which 33 who received RTX were treatment naïve. The remaining 27 were started on rituximab for refractory myopathy. Mean age was 39 years (SD12.58) in "treatment-naive" group and 43 years (SD 12.12) in "refractory" group. At 6 months of follow up, 48/55 (87%) patients showed response, 31/31 (100%) in "treatment-naive" and 17/24 (70%) in "refractory" cases, p 0.006*. In refractory group, 7 (29%) had stable disease. The mean changes in MMT8 were significantly more in the "treatment-naive" treatment group (13.41(SD 7.31) compared with "refractory" IIM 8.33 (SD 7.92) (p= 0.017*). Majority of patients were able to reduce dose below 5 mg/day before 6 months. No major adverse events were reported over the median follow-up of 24 (IQR 36) months., Conclusions: Rituximab is effective and safe across the spectrum of IIM. Early use in disease is associated with better outcomes., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
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- 2024
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25. Anterior Approach to Retracted Anterosuperior Cuff Tear With Biceps Superior Capsular Reconstruction and Subscapularis Release and Repair With Transosseous Equivalent Double-Row Repair.
- Author
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Nair AV, Thampy J S, Rambhojun M, Bharadwaj B, and Khan PS
- Abstract
The incidence of a subscapularis tear combined with any other rotator cuff tear is around 19% to 49% among all rotator cuff lesions. On the contrary, less attention has been given to the treatment of anterosuperior rotator cuff tears, particularly by arthroscopic methods. Subscapularis lesions are hard to access and require advanced surgical technique along with optimum visualization to achieve an anatomic repair. Use of an anterior portal helps in obtaining a good visualization with a 30° arthroscope in viewing the tendon along its axis as well as the posterior, superior, and anterior sides. Incorporation of the biceps tendon along with supraspinatus repair helps strengthen the supraspinatus repair as well as preserve the acromiohumeral index. Double-row repair of both subscapularis and supraspinatus ensures an adequate bone bed for tendon healing., Competing Interests: All authors (A.V.N., ST.J. M.R., B.B. P.S.K) declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)
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- 2024
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26. Chronic Distal Biceps Tendon Rupture: A Case Report of Single-Incision Repair With Tightrope and Flexor Carpi Radialis Autograft Augmentation.
- Author
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Kannan A, Raju A, Nair AV, Yoo Y, Sait A, Meleppuram JJ, and Khan PS
- Abstract
A 48-year-old male presented with weakness in right upper limb flexion and supination three months post-road traffic accident and was diagnosed with a complete distal bicep tendon rupture. Urgent single-incision surgical repair augmented with the flexor carpi radialis tendon was performed using the tightrope reconstruction method for stability. This case underscores the importance of prompt recognition and intervention for distal biceps tendon tears to prevent long-term functional impairment, emphasizing the critical role of surgical reattachment. Delayed medical care may compromise work capabilities and surgical success., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Kannan et al.)
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- 2024
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27. Arthroscopic Fixation of Acute Large Bony Bankart with Suture-assisted Reduction and Screw Fixation - Surgical Technique.
- Author
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Nair AV, J ST, Rambhojun M, Mohan PK, George J, and Khan PS
- Abstract
Introduction: Glenoid rim fractures with Bankart lesions are called bony Bankart lesions and are associated with persistent glenohumeral joint instability. Acute bony Bankart lesions can be treated by various arthroscopic techniques. Here, we present a technique of arthroscopic bony Bankart repair using suture-assisted reduction and screw fixation., Discussion: The conventional suture anchor repair does not provide compression of the fractured fragment, and the bony piece may tilt because of the single-point fixation., Conclusion: This procedure can achieve firm compression between the bony fragments and prevent rotation of fragment during screw fixation to the glenoid. The capsular plication distributes the loads to the surrounding soft tissues. Hence, this procedure should be offered to all patients presenting acutely with a large bony Bankart of size >25% of glenoid width, as it is minimally invasive as well as provides excellent outcomes and anatomical union., Competing Interests: Conflict of Interest: Nil, (Copyright: © Indian Orthopaedic Research Group.)
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- 2024
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28. Addition to "Regioselective 1,2-Alkylboration of Benzylidenecyclopropanes: Access to Csp 3 -Enriched Cyclopropyl Boronic Esters".
- Author
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Mondal PP, Nair AV, Sasidaran M, Chungath AA, Suman SP, Kuniyil R, and Sahoo B
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- 2024
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29. Spermidine constitutes a key determinant of motility and attachment of Salmonella Typhimurium through a novel regulatory mechanism.
- Author
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Nair AV, Singh A, Devasurmutt Y, Rahman SA, Tatu US, and Chakravortty D
- Subjects
- Animals, Mice, Bacterial Proteins genetics, Bacterial Proteins metabolism, Flagellin genetics, Polyamines metabolism, Gene Expression Regulation, Bacterial, Salmonella typhimurium metabolism, Spermidine metabolism
- Abstract
Spermidine is a poly-cationic molecule belonging to the family of polyamines and is ubiquitously present in all organisms. Salmonella synthesizes, and harbours specialized transporters to import spermidine. A group of polyamines have been shown to assist in Salmonella Typhimurium's virulence and regulation of Salmonella pathogenicity Inslad 1 (SPI-1) genes and stress resistance; however, the mechanism remains elusive. The virulence trait of Salmonella depends on its ability to employ multiple surface structures to attach and adhere to the surface of the target cells before invasion and colonization of the host niche. Our study discovers the mechanism by which spermidine assists in the early stages of Salmonella pathogenesis. For the first time, we report that Salmonella Typhimurium regulates spermidine transport and biosynthesis processes in a mutually inclusive manner. Using a mouse model, we show that spermidine is critical for invasion into the murine Peyer's patches, which further validated our in vitro cell line observation. We show that spermidine controls the mRNA expression of fimbrial (fimA) and non-fimbrial adhesins (siiE, pagN) in Salmonella and thereby assists in attachment to host cell surfaces. Spermidine also regulated the motility through the expression of flagellin genes by enhancing the translation of sigma-28, which features an unusual start codon and a poor Shine-Dalgarno sequence. Besides regulating the formation of the adhesive structures, spermidine tunes the expression of the two-component system BarA/SirA to regulate SPI-1 encoded genes. Thus, our study unravels a novel regulatory mechanism by which spermidine exerts critical functions during Salmonella Typhimurium pathogenesis., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier GmbH. All rights reserved.)
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- 2024
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30. "De Novo" Hypercapnic Respiratory Failure Unmasking Neuromuscular Disorders: Experiences From a Tertiary Care Center and Review of Literature.
- Author
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Nair AV, Kandagaddala M, Sivadasan A, Prabhakar AT, Nair S, Mathew V, Aaron S, and Alexander M
- Subjects
- Humans, Female, Middle Aged, Tertiary Care Centers, Retrospective Studies, Neuromuscular Diseases complications, Neuromuscular Diseases diagnosis, Respiratory Insufficiency diagnosis, Respiratory Insufficiency etiology, Bulbar Palsy, Progressive
- Abstract
Objectives: Neuromuscular disorders could have respiratory involvement early or late into illness. Rarely, patients may present with a hypercapnic respiratory failure (with minimal motor signs) unmasking an underlying disease. There are hardly any studies which have addressed the spectrum and challenges involved in management of this subset, especially in the real-world scenario., Methods: A retrospective study comprising consecutive patients hospitalized with hypercapnic respiratory failure as the sole/dominant manifestation. The clinical-electrophysiological spectrum, phrenic conductions, diaphragm thickness, and outcomes were analyzed., Results: Twenty-seven patients were included, the mean age was 47.29 (SD 15.22) years, and the median duration of respiratory symptoms was 2 months (interquartile range [IQR] 1-4). Orthopnea was present in 23 patients (85.2%) and encephalopathy in 8 patients (29.6%). Phrenic nerve latencies and amplitudes were abnormal in 83.3% and 95.6%, respectively. Abnormal diaphragm thickness was noted in 78.5%. Based on a comprehensive electrophysiological strategy and paraclinical tests, an etiology was established in all. Reversible etiologies were identified in 17 patients (62.9%). These included myasthenia gravis (anti-AChR and MuSK), inflammatory myopathy, riboflavin transporter deficiency neuronopathy, Pompe disease, bilateral phrenic neuritis, and thyrotoxicosis. Respiratory onset motor neuron disease was diagnosed in 8 patients (29.6%). Despite diaphragmatic involvement, a functional respiratory recovery was noted at discharge (45%) and last follow-up (60%). Predictors for good outcomes included female sex, normal nerve conductions, and recent-onset respiratory symptoms., Discussion: A good functional recovery was noted in most of the patients including respiratory onset motor neuron disease. A systematic algorithmic approach helps in proper triaging, early diagnosis, and treatment. Clinical and electrodiagnostic challenges and observations from a tertiary care referral center are discussed., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)
- Published
- 2024
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31. Regioselective 1,2-Alkylboration of Benzylidenecyclopropanes: Access to Csp 3 -Enriched Cyclopropyl Boronic Esters.
- Author
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Mondal PP, Nair AV, Sasidaran M, Chungath AA, Suman SP, Kuniyil R, and Sahoo B
- Abstract
We describe a novel, regioselective alkylboration of versatile (hetero)benzylidenecyclopropanes with β-H-containing alkyl iodides and bis(pinacolato)diboron enabled by copper catalysis. This three-component method allows for consecutive B-Csp
3 and Csp3 -Csp3 bond formation to access Csp3 -enriched diverse tertiary cyclopropyl boronic esters with broad functionality tolerance, and the so-formed C-B bond is amenable to further structural diversification. Radical clock experiment, Hammett analysis, and DFT calculation suggest a mechanism of polar, rather than radical manifold, and SN 2-type C-C bond formation was found to be the rate-limiting step instead of migratory alkene insertion.- Published
- 2024
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32. All-arthroscopic versus mini-open double row rotator cuff repair - A prospective randomised control study based on functional and radiological outcomes.
- Author
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Jithesh K, Meleppuram JJ, Raju A, Nair AV, Mundakkal A, Thankappan A, Thammanassery PK, and Khan PS
- Abstract
Purpose: In an era where arthroscopic rotator cuff repair is dominant in the United States (77.9 % preference) compared to open surgery (53.33 %), a shift towards minimally invasive All-Arthroscopic (AA) techniques over classical Mini-Open (MO) repair is emerging. This study explores current trends in shoulder procedures in India and compares functional outcomes and radiological repair integrity between AA and MO techniques, which are understudied in the Indian context., Methodology: In this prospective study, 60 patients (30 in the AA group and 30 in the MO group) with rotator cuff tears underwent assessment. Pre/post-operative clinical evaluations and 12-month follow-ups using UCLA and Oxford Shoulder Score, along with preoperative MRI and postoperative USG, were conducted., Results: At one-year follow-up, the AA group showed better functional outcomes (53.3 % excellent/good vs. 30.0 % in MO). No significant radiological differences (Sugaya grading) were found. Tear size was comparable with no association with functional/radiological outcomes., Conclusion: The AA group demonstrated favourable functional outcomes, matched to MO group findings, which is in accordance with global studies. Despite higher costs, the increasing popularity of AA in India is justified by enhanced results and reduced postoperative discomfort., (© 2024 Professor P K Surendran Memorial Education Foundation. Published by Elsevier B.V. All rights reserved.)
- Published
- 2024
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33. Arthroscopic Double-Row Rotator Cuff Repair With Biceps Augmentation.
- Author
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Mundakkal A, Panakkal JJ, Nair AV, Ahammad S, Meleppuram JJ, and Khan PS
- Abstract
Arthroscopic repair of chronic retracted rotator cuff tears remains challenging to shoulder arthroscopy surgeons. With the recent technical advances, most of the massive rotator cuff tears are managed successfully. The biceps tendon is highly vascular and a rich source of tenocytes and fibroblasts, which can promote biological healing. In massive degenerate rotator cuff tears in which the rotator cuff tissue can be released and fixed onto the footprint without much tissue tension, long head of the biceps tendon can act as an augment providing structural support to the poor-quality rotator cuff tissue and also enhancing the healing process. In this Technical Note, we describe arthroscopic rotator cuff repair using biceps augmentation for a massive degenerate rotator cuff tear with the excursion of the cuff onto the footprint with minimal tissue tension., (© 2023 The Authors.)
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- 2024
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34. Arthroscopic Superior Capsular Reconstruction Using Hybrid Autologous Fascia Lata and the Long Head of Biceps Tendon Graft: the Central Beam Concept.
- Author
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Nair AV, Mohan PK, Krishna P, Jangale A, Kareemulla S, Rambhojun M, and Thampy S
- Abstract
Superior capsular reconstruction is a joint salvage treatment option for retracted irreparable rotator cuff tears in relatively young patients. Various graft options have been described in the literature, including autologous fascia lata graft, synthetic graft, and dermal patches. Superior capsular reconstruction using long head of biceps tendon autograft alone has also been described by few authors. In this technical note, we describe a modified technique of performing arthroscopic superior capsular reconstruction using both fascia lata graft and the intra articular portion of the long head of biceps tendon. Our technique resembles central beam concept over which the fascia lata graft is anchored, providing good structural support to the graft and enabling graft healing and improved clinical outcomes., (© 2023 The Authors.)
- Published
- 2023
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35. All Arthroscopic Salvage Technique for Intraoperative Vertical Split Coracoid Graft Fracture in Latarjet Procedure-Technical Note.
- Author
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Nair AV, Mohan PK, Krishna P, Jangale A, Kareemulla S, Goud N, and Thampy S
- Abstract
Intraoperative vertical coracoid graft fractures during the Latarjet procedure are well-described complications, which typically have a poor prognosis or may necessitate further iliac crest bone grafting for stabilization. The vertical split coracoid fractures are reasoned to be caused by excessive tightening of the screws, poor bone quality, especially in females and the smaller dimension of the coracoid graft. In this technical note, we propose an arthroscopic salvage technique for salvaging the fractured coracoid graft and to avoid the need for additional bone graft, thereby reducing morbidity to the patient. We use two double-loaded, all-suture anchors (Stryker, India) on either side of the split coracoid graft, and double-pulley configuration of suture tightening is done, providing compression and stability to the fractured graft., Competing Interests: The authors report no conflicts of interest in the authorship and publication of this article. Full ICMJE author disclosure forms are available for this article online, as supplementary material., (© 2023 The Authors.)
- Published
- 2023
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36. Decoding the invasive nature of a tropical pathogen of concern: The invasive non-Typhoidal Salmonella strains causing host-restricted extraintestinal infections worldwide.
- Author
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Hajra D, Nair AV, and Chakravortty D
- Subjects
- Infant, Newborn, Humans, Salmonella genetics, Anti-Bacterial Agents pharmacology, Africa, Salmonella Infections epidemiology, Typhoid Fever
- Abstract
Invasive-Non-Typhoidal Salmonella (iNTS) are the major cause of health concern in the low-income, under-developed nations in Africa and Asia that lack proper sanitation facilities. Around 5% of the NTS cases give rise to invasive, extraintestinal diseases leading to focal infections like osteomyelitis, meningitis, osteoarthritis, endocarditis and neonatal sepsis. iNTS serovars like S. Typhimurium, S. Enteritidis, S. Dublin, S. Choleraesuis show a greater propensity to become invasive than others which hints at the genetic basis of their emergence. The major risk factors attributing to the invasive diseases include immune-compromised individuals having co-infection with malaria or HIV, or suffering from malnutrition. The rampant use of antibiotics leading to the emergence of multi-drug resistant strains poses a great challenge in disease management. An extensive understanding of the iNTS pathogenesis and its epidemiology will open up avenues for the development of new vaccination and therapeutic strategies to restrict the spread of this neglected disease., Competing Interests: Declaration of Competing Interest The authors are unaware of any conflicting interests and thereby declare no conflict of interest., (Copyright © 2023 Elsevier GmbH. All rights reserved.)
- Published
- 2023
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37. Biocompatible zeolite-dye composites with anti-amyloidogenic properties.
- Author
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Siposova K, Huntosova V, Sedlakova D, Macajova M, Bilcik B, Nair AV, Nair S, Hovhannisyan V, Chen SJ, and Musatov A
- Subjects
- Humans, Animals, Coloring Agents chemistry, Amyloid chemistry, Insulin chemistry, Indoles chemistry, Indoles pharmacology, Cell Line, Tumor, Zeolites chemistry, Zeolites pharmacology, Biocompatible Materials chemistry, Biocompatible Materials pharmacology
- Abstract
One of the most attractive approaches in biomedicine and pharmacy is the application of multifunctional materials. The mesoporous structure of clinoptilolite (CZ) absorbs various types of substances and can be used as a model for studying the carriers for targeted drug delivery with controlled release. CZ-dye composites are fabricated by incorporation into clinoptilolite pores commonly used dyes, aluminum phthalocyanine, zinc porphine, and hypericin. We examined and compared the effect of pure dyes and CZ-dye composites on insulin amyloidogenesis. The formation of insulin amyloid fibrils and the disassembly of preformed fibrils is significantly affected by any of the three compounds, however, the strongest effect is observed for aluminum phthalocyanine indicating a structurally-dependent anti-amyloidogenic activity of the dyes. The incorporation of dyes into CZ particles resulted in enhanced anti-amyloidogenic activity in comparison to pure CZ particles. The cell metabolic activity, biocompatibility and fluorescence biodistribution of the dyes entrapped in the composites were tested in vitro (U87 MG cells) and in vivo in the quail chorioallantoic membrane model. Considering the photoactive properties of the dyes used, we assume their applicability in photodiagnostics and photodynamic therapy. It can also be expected that their anti-amyloidogenic potential can be enhanced by photodynamic effect., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)
- Published
- 2023
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38. Photoactivable AIEgen-based Lipid-Droplet-Specific Drug Delivery Model for Live Cell Imaging and Two-Photon Light-Triggered Anticancer Drug Delivery.
- Author
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Singh AK, Mengji R, Nair AV, Shah SS, Avijit J, and Singh NDP
- Subjects
- Oleic Acid analysis, Drug Delivery Systems, Lipid Droplets chemistry, Antineoplastic Agents chemistry
- Abstract
Lipid droplets (LDs) are dynamic complex organelles involved in various physiological processes, and their number and activity are linked to multiple diseases, including cancer. In this study, we have developed LD-specific near-infrared (NIR) light-responsive nano-drug delivery systems (DDSs) based on chalcone derivatives for cancer treatment. The reported nano-DDSs localized inside the cancer microenvironment of LDs, and upon exposure to light, they delivered the anticancer drug valproic acid in a spatiotemporally controlled manner. The developed systems, namely, 2'-hydroxyacetophenone-dimethylaminobenzaldehyde-valproic ( HA-DAB-VPA ) and 2'-hydroxyacetophenone-diphenylaminobenzaldehyde-valproic ( HA-DPB-VPA ) ester conjugates, required only two simple synthetic steps. Our reported DDSs exhibited interesting properties such as excited-state intramolecular proton transfer (ESIPT) and aggregation-induced emission (AIE) phenomena, which provided advantages such as AIE-initiated photorelease and ESIPT-enhanced rate of photorelease upon exposure to one- or two-photon light. Further, colocalization studies of the nano-DDSs by employing two cancerous cell lines (MCF-7 cell line and CT-26 cell line) and one normal cell line (HEK cell line) revealed LD concentration-dependent enhanced fluorescence intensity. Furthermore, systematic investigations of both the nano-DDSs in the presence and absence of oleic acid inside the cells revealed that nano-DDS HA-DPB-VPA accumulated more selectively in the LDs. This unique selectivity by the nano-DDS HA-DPB-VPA toward the LDs is due to the hydrophobic nature of the diphenylaminobenzaldehyde (mimicking the LD core), which significantly leads to the aggregation and ESIPT (at 90% volume of f
w , ΦF = 20.4% and in oleic acid ΦF = 24.6%), respectively. Significantly, we used this as a light-triggered anticancer drug delivery model to take advantage of the high selectivity and accumulation of the nano-DDS HA-DPB-VPA inside the LDs. Hence, these findings give a prototype for designing drug delivery models for monitoring LD-related intracellular activities and significantly triggering the release of LD-specific drugs in the biological field.- Published
- 2023
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39. Hoffman syndrome with the classic sign of myoedema and an unusual finding of systolic heart failure.
- Author
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Paul A, Nair AV, Krupa J, and Iyadurai R
- Subjects
- Humans, Male, Hypertrophy, Muscle Weakness, Adult, Heart Failure, Systolic, Muscular Diseases diagnosis
- Abstract
A man in his 20s presented with a 6-year history of calf muscle hypertrophy, proximal muscle weakness and muscle cramps. Along with this, he also had patchy hair loss, facial puffiness and slurring of speech. On examination, he had mild symmetrical proximal muscle weakness, a delayed relaxation phase of his deep tendon reflexes and a rare neurological sign of myoedema. His laboratory investigations revealed elevated thyroid-stimulating hormone levels with high creatine kinase levels, and an echocardiogram showed left ventricular systolic dysfunction. He was diagnosed with Hoffman syndrome, a rare pseudohypertrophic myopathy associated with severe and prolonged hypothyroidism. He had an excellent response to thyroid hormone replacement., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2023. No commercial re-use. See rights and permissions. Published by BMJ.)
- Published
- 2023
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40. Arthroscopic Salvage Procedure for Iatrogenic Conjoint Tendon Avulsion Fracture Following Arthroscopic Latarjet Procedure Using Double Sling Fixation Technique - A Case Report.
- Author
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Nair AV, Mohan PK, Jangale A, Krishna P, and Goud N
- Abstract
Introduction: We present a case report of an iatrogenic conjoint tendon avulsion fracture following arthroscopic Latarjet and salvage technique to address the complication with a novel double sling technique., Case Report: A 16-year-old male patient who presented with recurrent instability of the right shoulder was counseled for an arthroscopic Latarjet procedure, taking account of critical glenoid bone loss and his contact sporting activities. An intraoperative coracoid tip fracture occurred, which was managed with the double sling technique. At 1-year follow-up, the patient has made a good recovery with a full range of movements and a stable shoulder; the CT scans showed a well-approximated coracoid tip fragment., Conclusion: Iatrogenic intraoperative coracoid graft fractures during arthroscopic Latarjet can be managed depending on the site of the fracture and quality of the bone. The double sling fixation technique helps in maintaining the sling action of the conjoint tendon in patients with recurrent instability., Competing Interests: Conflict of Interest: Nil, (Copyright: © Indian Orthopaedic Research Group.)
- Published
- 2023
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41. Absence of proline-peptide transporter YjiY in Salmonella Typhimurium leads to secretion of factors which inhibits intra-species biofilm formation.
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Chandra K, Nair AV, Chatterjee R, Muralidhara P, Singh A, Kamanna S, Tatu US, and Chakravortty D
- Subjects
- Humans, Membrane Transport Proteins metabolism, Biofilms, Proline metabolism, Salmonella typhimurium genetics, Salmonella typhimurium metabolism, Typhoid Fever
- Abstract
Salmonella is a genus of widely spread Gram negative, facultative anaerobic bacteria, which is known to cause ¼th of diarrheal morbidity and mortality globally. It causes typhoid fever and gastroenteritis by gaining access to the host gut through contaminated food and water. Salmonella utilizes its biofilm lifestyle to strongly resist antibiotics and persist in the host. Although biofilm removal or dispersal has been studied widely, the inhibition of the initiation of Salmonella Typhimurium (STM WT) biofilm remains elusive. This study demonstrates the anti-biofilm property of the cell-free supernatant obtained from a carbon-starvation induced proline peptide transporter mutant (STM ΔyjiY) strain. The STM ΔyjiY culture supernatant primarily inhibits biofilm initiation by regulating biofilm-associated transcriptional network that is reversed upon complementation (STM ΔyjiY:yjiY). We demonstrate that abundance of FlgM correlates with the absence of flagella in the STM ΔyjiY supernatant treated WT cells. NusG works synergistically with the global transcriptional regulator H-NS. Relatively low abundances of flavoredoxin, glutaredoxin, and thiol peroxidase might lead to accumulation of ROS within the biofilm, and subsequent toxicity in STM ΔyjiY supernatant. This work further suggests that targeting these oxidative stress relieving proteins might be a good choice to reduce Salmonella biofilm., Competing Interests: Competing Interests The authors declare no competing interests., (Copyright © 2023 Elsevier GmbH. All rights reserved.)
- Published
- 2023
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42. Syntaxin 3 SPI-2 dependent crosstalk facilitates the division of Salmonella containing vacuole.
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Chatterjee R, Nair AV, Singh A, Mehta N, Setty SRG, and Chakravortty D
- Subjects
- Animals, Mice, Bacterial Proteins genetics, Bacterial Proteins metabolism, Cell Communication, Qa-SNARE Proteins genetics, Qa-SNARE Proteins metabolism, SNARE Proteins metabolism, Salmonella metabolism, Vacuoles microbiology
- Abstract
Intracellular membrane fusion is mediated by membrane-bridging complexes of soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs). SNARE proteins are one of the key players in vesicular transport. Several reports shed light on intracellular bacteria modulating host SNARE machinery to establish infection successfully. The critical SNAREs in macrophages responsible for phagosome maturation are Syntaxin 3 (STX3) and Syntaxin 4 (STX4). Reports also suggest that Salmonella actively modulates its vacuole membrane composition to escape lysosomal fusion. Salmonella containing vacuole (SCV) harbours recycling endosomal SNARE Syntaxin 12 (STX12). However, the role of host SNAREs in SCV biogenesis and pathogenesis remains unclear. Upon knockdown of STX3, we observed a reduction in bacterial proliferation, which is concomitantly restored upon the overexpression of STX3. Live-cell imaging of Salmonella-infected cells showed that STX3 localises to the SCV membranes and thus might help in the fusion of SCV with intracellular vesicles to acquire membrane for its division. We also found the interaction STX3-SCV was abrogated when we infected with SPI-2 encoded Type 3 secretion system (T3SS) apparatus mutant (STM ∆ssaV) but not with SPI-1 encoded T3SS apparatus mutant (STM ∆invC). These observations were also consistent in the mice model of Salmonella infection. Together, these results shed light on the effector molecules secreted through T3SS encoded by SPI-2, possibly involved in interaction with host SNARE STX3, which is essential to maintain the division of Salmonella in SCV and help to maintain a single bacterium per vacuole., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
- Published
- 2023
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43. Salmonella Typhimurium PgtE is an essential arsenal to defend against the host resident antimicrobial peptides.
- Author
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Chatterjee R, Chowdhury AR, Nair AV, Hajra D, Kar A, Datey A, Shankar S, Mishra RK, Chandra N, and Chakravortty D
- Subjects
- Animals, Humans, Mice, Macrophages, Mice, Inbred C57BL, Antimicrobial Peptides, Bacterial Proteins genetics, Bacterial Proteins metabolism, Peptide Hydrolases genetics, Peptide Hydrolases metabolism, Salmonella typhimurium metabolism, Bacterial Outer Membrane Proteins genetics, Bacterial Outer Membrane Proteins metabolism, Endopeptidases genetics, Endopeptidases metabolism
- Abstract
Salmonella enterica serovar Typhimurium is a common cause of gastroenteritis in humans and occasionally causes systemic infection. Salmonella's ability to survive and replicate within macrophages is an important characteristic during systemic infection. The outer membrane protease PgtE of S. enterica is a member of the Omptin family of outer membrane aspartate proteases which has well-characterized proteolytic activities in-vitro against a wide range of physiologically relevant substrates. However, no study has been done so far that draws a direct correlation between these in-vitro observations and the biology of the pathogen in-vivo. The main goals of this study were to characterize the pathogenesis-associated functions of pgtE and study its role in the intracellular survival and in-vivo virulence of Salmonella Typhimurium. Our study elucidated a possible role of Salmonella Typhimurium pgtE in combating host antimicrobial peptide- bactericidal/ permeability increasing protein (BPI) to survive in human macrophages. The pgtE-deficient strain of Salmonella showed attenuated proliferation and enhanced colocalization with BPI in U937 and Thp1 cells. In the presence of polymixin B, the attenuated in-vitro survival of STM ΔpgtE suggested a role of PgtE against the antimicrobial peptides. In addition, our study revealed that compared to the wild type Salmonella, the pgtE mutant is replication-deficient in C57BL/6 mice. Further, we showed that PgtE interacts directly with several antimicrobial peptides (AMPs) in the host gut. This gives the pathogen a survival advantage and helps to mount a successful infection in the host., Competing Interests: Declaration of Competing Interest The authors are unaware of any conflicting interests and declare no conflict of interest., (Copyright © 2023 Elsevier GmbH. All rights reserved.)
- Published
- 2023
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44. ESIPT-, AIE-, and AIE + ESIPT-Based Light-Activated Drug Delivery Systems and Bioactive Donors for Targeted Disease Treatment.
- Author
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Singh AK, Nair AV, Shah SS, Ray S, and Singh NDP
- Subjects
- Protons, Drug Delivery Systems, Antineoplastic Agents pharmacology
- Abstract
Targeted release of bioactive molecules for therapeutic purposes is a key area in the biomedical field that is growing quickly, where bioactive molecules are released passively or actively from drug delivery systems (DDSs) or bioactive donors. In the past decade, researchers have identified light as one of the prime stimuli that can implement the efficient spatiotemporally targeted delivery of drugs or gaseous molecules with minimal cytotoxicity and a real-time monitoring ability. This perspective emphasizes recent advances in the photophysical properties of ESIPT- (excited-state intramolecular proton transfer), AIE- (aggregation-induced emission), and AIE + ESIPT-attributed light-activated delivery systems or donors. The three major sections of this perspective describe the distinctive features of DDSs and donors concerning their design, synthesis, photophysical and photochemical properties, and in vitro and in vivo studies demonstrating their relevance as carrier molecules for releasing cancer drugs and gaseous molecules in the biological system.
- Published
- 2023
- Full Text
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45. Intracellular sites of AQP2 S256 phosphorylation identified using inhibitors of the AQP2 recycling itinerary.
- Author
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Cheung PW, Boukenna M, Babicz RSE, Mitra S, Kay A, Paunescu TC, Baylor N, Liu CS, Nair AV, Bouley R, and Brown D
- Subjects
- Animals, LLC-PK1 Cells, Phosphorylation, Swine, Vasopressins pharmacology, Vasopressins metabolism, Intracellular Space metabolism, Aquaporin 2 genetics, Aquaporin 2 metabolism, Serine metabolism
- Abstract
Vasopressin (VP)-regulated aquaporin-2 (AQP2) trafficking between cytoplasmic vesicles and the plasma membrane of kidney principal cells is essential for water homeostasis. VP affects AQP2 phosphorylation at several serine residues in the COOH-terminus; among them, serine 256 (S256) appears to be a major regulator of AQP2 trafficking. Mutation of this serine to aspartic acid, which mimics phosphorylation, induces constitutive membrane expression of AQP2. However, the intracellular location(s) at which S256 phosphorylation occurs remains elusive. Here, we used strategies to block AQP2 trafficking at different cellular locations in LLC-PK1 cells and monitored VP-stimulated phosphorylation of S256 at these sites by immunofluorescence and Western blot analysis with phospho-specific antibodies. Using methyl-β-cyclodextrin, cold block or bafilomycin, and taxol, we blocked AQP2 at the plasma membrane, in the perinuclear trans -Golgi network, and in scattered cytoplasmic vesicles, respectively. Regardless of its cellular location, VP induced a significant increase in S256 phosphorylation, and this effect was not dependent on a functional microtubule cytoskeleton. To further investigate whether protein kinase A (PKA) was responsible for S256 phosphorylation in these cellular compartments, we created PKA-null cells and blocked AQP2 trafficking using the same procedures. We found that S256 phosphorylation was no longer increased compared with baseline, regardless of AQP2 localization. Taken together, our data indicate that AQP2 S256 phosphorylation can occur at the plasma membrane, in the trans -Golgi network, or in cytoplasmic vesicles and that this event is dependent on the expression of PKA in these cells. NEW & NOTEWORTHY Phosphorylation of aquaporin-2 by PKA at serine 256 (S256) occurs in various subcellular locations during its recycling itinerary, suggesting that the protein complex necessary for AQP2 S256 phosphorylation is present in these different recycling stations. Furthermore, we showed, using PKA-null cells, that PKA activity is required for vasopressin-induced AQP2 phosphorylation. Our data reveal a complex spatial pattern of intracellular AQP2 phosphorylation at S256, shedding new light on the role of phosphorylation in AQP2 membrane accumulation.
- Published
- 2023
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46. Arthroscopic Subscapularis Tendon Repair Using the Lasso-Loop Technique Through Anterolateral Viewing Portal.
- Author
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Mundakkal A, Kanakkayil MM, Nambiar R, Sait A, Nair AV, Yoo YS, and Khan PS
- Abstract
The subscapularis is the strongest muscle among the rotator cuff muscles, and it provides a coupled balanced force across the glenohumeral joint by resisting the infraspinatus in axial plane and the shearing force of deltoid in the coronal plane. It is important to repair subscapularis tears to maintain the coupled balanced force. Subscapularis tendon tears are difficult to diagnose and treat. Only a small portion of the subscapularis tendon is visualized during routine arthroscopy, as it is largely covered by the middle and inferior glenohumeral ligaments. Various repair techniques have been described in the literature. Here, we describe the anterolateral viewing portal for better visualization of subscapularis and our preferred technique, the lasso-loop technique, which provides better tissue grip and improved functional outcome., (© 2022 The Authors.)
- Published
- 2022
- Full Text
- View/download PDF
47. Salmonella Typhimurium U32 peptidase, YdcP, promotes bacterial survival by conferring protection against in vitro and in vivo oxidative stress.
- Author
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Hajra D, Nair AV, Roy Chowdhury A, Mukherjee S, Chatterjee R, and Chakravortty D
- Subjects
- Humans, Animals, Mice, Hydrogen Peroxide, Mice, Inbred C57BL, Oxidative Stress, Bacteria, NADPH Oxidases genetics, Mice, Inbred BALB C, Peptide Hydrolases, Salmonella typhimurium genetics
- Abstract
YdcP, a U32 peptidase, is characterized as a putative collagenase with a role in several bacterial infections. However, its role in the pathogenesis of Salmonella Typhimurium remains elusive. Here, we investigated the role of U32 peptidase, YdcP, in the intracellular survival of S. Typhimurium (STM). Our study revealed a novel function of YdcP in protecting wild-type Salmonella from in vitro and in vivo oxidative stress. The ydcP knockout strain showed attenuated intracellular proliferation within the murine and human macrophages. Incubation of wild-type Salmonella with H
2 O2 induced the transcript level expression of ydcP. Moreover, deleting ydcP increased the susceptibility of the bacteria to in vitro oxidative stress. STM ΔydcP showed increased colocalization with the gp91phox subunit of the NADPH phagocytic oxidase in RAW264.7 cells. Further, we observed a reduction in the expression of bacterial anti-oxidant genes in STM ΔydcP growing within the RAW264.7 cells. The delay in the death of BALB/c mice infected with STM ΔydcP proved the association of ydcP with the in vivo pathogenesis of Salmonella. Finally, the attenuated growth of the ydcP mutant in wild-type C57BL/6 mice and the recovery of their growth inhibition in gp91phox-/- C57BL/6 mice endorsed the role of ydcP in protecting Salmonella from in vivo oxidative stress. Together, our study depicts a novel role of Salmonella Typhimurium YdcP, a putative U32 peptidase in rendering protection against oxidative stress., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)- Published
- 2022
- Full Text
- View/download PDF
48. [Spectrum of opportunistic fungal lung co-infections in COVID-19: What the radiologist needs to know].
- Author
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Nair AV, Ramanathan S, Sanghavi P, Manchikanti V, Satheesh S, Al-Heidous M, Jajodia A, and Macdonald DB
- Abstract
Fungal lung co-infections associated with COVID-19 may occur in severely ill patients or those with underlying co-morbidities, and immunosuppression. The most common invasive fungal infections are caused by aspergillosis, mucormycosis, pneumocystis, cryptococcus, and candida. Radiologists integrate the clinical disease features with the CT pattern-based approach and play a crucial role in identifying these co-infections in COVID-19 to assist clinicians to make a confident diagnosis, initiate treatment and prevent complications., (© 2022 SERAM. Published by Elsevier España, S.L.U. All rights reserved.)
- Published
- 2022
- Full Text
- View/download PDF
49. Dynamic Anterior Stabilization Using Transosseous Bone Tunnel Technique With the Adjustable Loop Length Cortical Button Incorporating High-Strength Suture Augmentation for Recurrent Shoulder Instability.
- Author
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Nair AV, Mohan PK, Jangale A, Kuntwad V, Kumar MP, Goud N, and Sreekumar S
- Abstract
Dynamic anterior stabilization using the long head of the biceps tendon is a recently described technique in the management of recurrent shoulder dislocation with subcritical bone loss. This technique involves the transfer of the long head of the biceps to the glenoid, providing sling and hammock effect. The long head of the biceps (LHB) tendon fixation can be accomplished with a variety of implants. We present a modified fixation technique of LHB tendon using transosseous bone tunnel with the adjustable loop length cortical button, incorporating high-strength suture augmentation device in a patient with recurrent glenohumeral instability with limited glenoid bone loss and an engaging Hill-Sachs defect in the humeral head., (© 2022 The Authors.)
- Published
- 2022
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- View/download PDF
50. Drug-dependent inhibition of nucleotide hydrolysis in the heterodimeric ABC multidrug transporter PatAB from Streptococcus pneumoniae.
- Author
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Guffick C, Hsieh PY, Ali A, Shi W, Howard J, Chinthapalli DK, Kong AC, Salaa I, Crouch LI, Ansbro MR, Isaacson SC, Singh H, Barrera NP, Nair AV, Robinson CV, Deery MJ, and van Veen HW
- Subjects
- Adenosine Triphosphate metabolism, Ethidium metabolism, Hydrolysis, Nucleotides metabolism, ATP-Binding Cassette Transporters chemistry, Streptococcus pneumoniae genetics, Streptococcus pneumoniae metabolism
- Abstract
The bacterial heterodimeric ATP-binding cassette (ABC) multidrug exporter PatAB has a critical role in conferring antibiotic resistance in multidrug-resistant infections by Streptococcus pneumoniae. As with other heterodimeric ABC exporters, PatAB contains two transmembrane domains that form a drug translocation pathway for efflux and two nucleotide-binding domains that bind ATP, one of which is hydrolysed during transport. The structural and functional elements in heterodimeric ABC multidrug exporters that determine interactions with drugs and couple drug binding to nucleotide hydrolysis are not fully understood. Here, we used mass spectrometry techniques to determine the subunit stoichiometry in PatAB in our lactococcal expression system and investigate locations of drug binding using the fluorescent drug-mimetic azido-ethidium. Surprisingly, our analyses of azido-ethidium-labelled PatAB peptides point to ethidium binding in the PatA nucleotide-binding domain, with the azido moiety crosslinked to residue Q521 in the H-like loop of the degenerate nucleotide-binding site. Investigation into this compound and residue's role in nucleotide hydrolysis pointed to a reduction in the activity for a Q521A mutant and ethidium-dependent inhibition in both mutant and wild type. Most transported drugs did not stimulate or inhibit nucleotide hydrolysis of PatAB in detergent solution or lipidic nanodiscs. However, further examples for ethidium-like inhibition were found with propidium, novobiocin and coumermycin A1, which all inhibit nucleotide hydrolysis by a non-competitive mechanism. These data cast light on potential mechanisms by which drugs can regulate nucleotide hydrolysis by PatAB, which might involve a novel drug binding site near the nucleotide-binding domains., (© 2022 The Authors. The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)
- Published
- 2022
- Full Text
- View/download PDF
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