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1.
Cytogenet Genome Res ; : 1-11, 2024 Oct 05.
Article in French | MEDLINE | ID: mdl-39369710

ABSTRACT

BACKGROUND: Our study focuses on Yakutian cattle, a Siberian native breed, examining its inbreeding and diversity through genome-wide analysis of runs of homozygosity (ROHs). Yakutian cattle are adapted to Siberia's harsh sub-arctic conditions, enduring temperatures below -70Ā°C. However, the population genetics studies on this breed are scanty, to document the genetic uniqueness in these cattle. RESULTS: We analyzed 40 Yakutian cattle with strict quality control for ROH detection yielding 683 homozygous segments, averaging 17 per individual with an average length of 9 Mb. ROH regions were found to be involved in important pathways pertaining to cold adaptation. Autozygosity ranged from 1% to 12% of the genome, with a relatively low average inbreeding coefficient (FROH) of 0.057, as compared to other breeds. Also, the different diversity indicators, namely, principal component analysis, heterozygosity, and effective population size analysis, revealed the prevalence of genetic diversity within the breed. CONCLUSION: Our findings on ROH are the first of its kind in Yakutian cattle that support their adaptability to colder environments, as evidenced by low inbreeding and high genetic diversity.

2.
Methods ; 219: 82-94, 2023 11.
Article in English | MEDLINE | ID: mdl-37778659

ABSTRACT

Artificial intelligence (AI), particularly deep learning as a subcategory of AI, provides opportunities to accelerate and improve the process of discovering and developing new drugs. The use of AI in drug discovery is still in its early stages, but it has the potential to revolutionize the way new drugs are discovered and developed. As AI technology continues to evolve, it is likely that AI will play an even greater role in the future of drug discovery. AI is used to identify new drug targets, design new molecules, and predict the efficacy and safety of potential drugs. The inclusion of AI in drug discovery can screen millions of compounds in a matter of hours, identifying potential drug candidates that would have taken years to find using traditional methods. AI is highly utilized in the pharmaceutical industry by optimizing processes, reducing waste, and ensuring quality control. This review covers much-needed topics, including the different types of machine-learning techniques, their applications in drug discovery, and the challenges and limitations of using machine learning in this field. The state-of-the-art of AI-assisted pharmaceutical discovery is described, covering applications in structure and ligand-based virtual screening, de novo drug creation, prediction of physicochemical and pharmacokinetic properties, drug repurposing, and related topics. Finally, many obstacles and limits of present approaches are outlined, with an eye on potential future avenues for AI-assisted drug discovery and design.


Subject(s)
Artificial Intelligence , Machine Learning , Drug Design , Drug Discovery/methods , Pharmaceutical Preparations
3.
Environ Res ; 257: 119331, 2024 Sep 15.
Article in English | MEDLINE | ID: mdl-38851371

ABSTRACT

Toxicological stress in aquatic organisms is caused by the discharge of hundreds of toxic pollutants and contaminants among which the current study concentrates on the toxic effect of non-steroidal anti-inflammatory drug ibuprofen (IBF) and the trace element selenium (Se). In this study, IBF and Se toxicity on freshwater mussel Lamellidens marginalis was studied for 14 days, and in silico predictions for their degradation were made using Molecular modelling and Quantum Mechanical approaches. The degrading propensity of cytochrome c oxidase proteins from Trametes verticillatus and Thauera selenatis (Turkey tail fungi and Gram-negative bacteria) is examined into atom level. The results of molecular modelling study indicate that ionic interactions occur in the T. selenatis-HEME bound complex by Se interacting directly with HEME, and in the T. versicolor-HEME bound complex by IBF bound to a nearby region of HEME. Experimental and theoretical findings suggest that, the toxicological effects of Se and IBF pollution can be reduced by bioremediation with special emphasis on T. versicolor, and T. selenatis, which can effectively interact with Se and IBF present in the environment and degrade them. Besides, this is the first time in freshwater mussel L. marginalis that ibuprofen and selenium toxicity have been studied utilizing both experimental and computational methodologies for their bioremediation study.


Subject(s)
Ibuprofen , Selenium , Water Pollutants, Chemical , Animals , Ibuprofen/toxicity , Ibuprofen/metabolism , Ibuprofen/chemistry , Water Pollutants, Chemical/toxicity , Water Pollutants, Chemical/chemistry , Water Pollutants, Chemical/metabolism , Selenium/toxicity , Selenium/chemistry , Selenium/metabolism , Biodegradation, Environmental , Anti-Inflammatory Agents, Non-Steroidal/toxicity , Anti-Inflammatory Agents, Non-Steroidal/metabolism , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Quantum Theory , Unionidae/metabolism , Bivalvia/drug effects , Bivalvia/metabolism , Models, Molecular , Fresh Water/chemistry
4.
Curr Genomics ; 25(4): 237-260, 2024.
Article in English | MEDLINE | ID: mdl-39156729

ABSTRACT

The fastest way to significantly change the composition of a population is through admixture, an evolutionary mechanism. In animal breeding history, genetic admixture has provided both short-term and long-term advantages by utilizing the phenomenon of complementarity and heterosis in several traits and genetic diversity, respectively. The traditional method of admixture analysis by pedigree records has now been replaced greatly by genome-wide marker data that enables more precise estimations. Among these markers, SNPs have been the popular choice since they are cost-effective, not so laborious, and automation of genotyping is easy. Certain markers can suggest the possibility of a population's origin from a sample of DNA where the source individual is unknown or unwilling to disclose their lineage, which are called Ancestry-Informative Markers (AIMs). Revealing admixture level at the locus-specific level is termed as local ancestry and can be exploited to identify signs of recent selective response and can account for genetic drift. Considering the importance of genetic admixture and local ancestry, in this mini-review, both concepts are illustrated, encompassing basics, their estimation/identification methods, tools/software used and their applications.

5.
Mycoses ; 67(9): e13790, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39278818

ABSTRACT

BACKGROUND AND OBJECTIVES: Candidaemia is a potentially life-threatening emergency in the intensive care units (ICUs). Surveillance using common protocols in a large network of hospitals would give meaningful estimates of the burden of candidaemia and central line associated candidaemia in low resource settings. We undertook this study to understand the burden and epidemiology of candidaemia in multiple ICUs of India, leveraging the previously established healthcare-associated infections (HAI) surveillance network. Our aim was also to assess the impact that the pandemic of COVID-19 had on the rates and associated mortality of candidaemia. METHODS: This study included adult patients from 67 Indian ICUs in the AIIMS-HAI surveillance network that conducted BSI surveillance in COVID-19 and non-COVID-19 ICUs during and before the COVID-19 pandemic periods. Hospitals identified healthcare-associated candidaemia and central line associated candidaemia and reported clinical and microbiological data to the network as per established and previously published protocols. RESULTS: A total of 401,601 patient days and 126,051 central line days were reported during the study period. A total of 377 events of candidaemia were recorded. The overall rate of candidaemia in our network was 0.93/1000 patient days. The rate of candidaemia in COVID-19 ICUs (2.52/1000 patient days) was significantly higher than in non-COVID-19 ICUs (1.05/patient days) during the pandemic period. The rate of central line associated candidaemia in COVID-19 ICUs (4.53/1000 central line days) was also significantly higher than in non-COVID-19 ICUs (1.73/1000 central line days) during the pandemic period. Mortality in COVID-19 ICUs associated with candidaemia (61%) was higher than that in non-COVID-19 ICUs (41%). A total of 435 Candida spp. were isolated. C. tropicalis (26.7%) was the most common species. C. auris accounted for 17.5% of all isolates and had a high mortality. CONCLUSION: Patients in ICUs with COVID-19 infections have a much higher risk of candidaemia, CLAC and its associated mortality. Network level data helps in understanding the true burden of candidaemia and will help in framing infection control policies for the country.


Subject(s)
COVID-19 , Candidemia , Cross Infection , Intensive Care Units , Humans , COVID-19/epidemiology , Candidemia/epidemiology , India/epidemiology , Intensive Care Units/statistics & numerical data , Male , Middle Aged , Female , Adult , Cross Infection/epidemiology , SARS-CoV-2 , Aged , Catheter-Related Infections/epidemiology , Catheter-Related Infections/microbiology , Pandemics
6.
Plant Foods Hum Nutr ; 2024 Aug 17.
Article in English | MEDLINE | ID: mdl-39153163

ABSTRACT

Understanding the nutritional diversity in Perilla (Perilla frutescens L.) is essential for selecting and developing superior varieties with enhanced nutritional profiles in the North Eastern Himalayan (NEH) region of India. In this study, we assessed the nutritional composition of 45 diverse perilla germplasm collected from five NEH states using standard protocols and advanced analytical techniques. Significant variability was observed in moisture (0.39-11.67%), ash (2.59-7.13%), oil (28.65-74.20%), protein (11.05-23.15%), total soluble sugars (0.34-3.67%), starch (0.01-0.55%), phenols (0.03-0.87%), ferric reducing antioxidant power (0.45-1.36%), palmitic acid (7.06-10.75%), stearic acid (1.96-2.29%), oleic acid (8.11-13.31%), linoleic acid (15.18-22.74%), and linolenic acid (55.47-67.07%). Similarly, significant variability in mineral content (ppm) was also observed for aluminium, calcium, cobalt, chromium, copper, iron, potassium, magnesium, manganese, molybdenum, sodium, nickel, phosphorus, and zinc. Multivariate analyses, including hierarchical clustering analysis (HCA) and principal component analysis (PCA), revealed the enriched nutritional diversity within the germplasm. Correlation analysis indicated significant positive and negative relationships between nutritional parameters, indicating potential biochemical and metabolic interactions present in the perilla seeds. TOPSIS-based ranking identified promising genotypes for functional foods, pharmaceuticals, and nutritional applications. This study provides a first in-depth report of the nutritional composition and diversity of perilla germplasm in the NEH region, thus aiding in the identification of superior varieties for food and nutritional diversification and security.

7.
J Cell Biochem ; 124(1): 127-145, 2023 01.
Article in English | MEDLINE | ID: mdl-36502494

ABSTRACT

Numerous pathogens affecting human is present in the flavivirus family namely west nile, dengue, yellow fever, and zika which involves in development of global burden and distressing the environment economically. Till date, no approved drugs are available for targeting these viruses. The threat which urged the identification of small molecules for the inhibition of these viruses is the spreading of serious viral diseases. The recent outbreak of zika and dengue infections postured a solemn risk to worldwide public well-being. RNA-dependent RNA polymerase (RdRp) is the supreme adaptable enzymes of all the RNA viruses which is responsible for the replication and transcription of genome among the structural and nonstructural proteins of flaviviruses. It is understood that the RdRp of the flaviviruses are similar stating that the japanese encephalitis and west nile shares 70% identity with zika whereas the dengue serotype 2 and 3 shares the identity of 76% and 81%, respectively. In this study, we investigated the binding site of four flaviviral RdRp and provided insights into various interaction of the molecules using the computational approach. Our study helps in recognizing the potent compounds that could inhibit the viral protein as a common inhibitor. Additionally, with the conformational stability analysis, we proposed the possible mechanism of inhibition of the identified common small molecule towardĀ RdRp of flavivirus. Finally, this study could be an initiative for the identification of common inhibitors and can be explored further for understanding the mechanism of action through in vitro studies for the study on efficacy.


Subject(s)
Drug Repositioning , Flavivirus , RNA-Dependent RNA Polymerase , Humans , Dengue/drug therapy , Flavivirus/drug effects , Flavivirus/enzymology , RNA-Dependent RNA Polymerase/antagonists & inhibitors , RNA-Dependent RNA Polymerase/metabolism , Viral Proteins/metabolism , Zika Virus/drug effects , Zika Virus/enzymology , Zika Virus Infection/drug therapy
8.
Lancet ; 400(10369): 2250-2260, 2022 12 17.
Article in English | MEDLINE | ID: mdl-36528378

ABSTRACT

Louis Pasteur has long been heralded as one of the fathers of microbiology and immunology. Less known is Pasteur's vision on infection prevention and control (IPC) that drove current infection control, public health, and much of modern medicine and surgery. In this Review, we revisited Pasteur's pioneering works to assess progress and challenges in the process and technological innovation of IPC. We focused on Pasteur's far-sighted conceptualisation of the hospital as a reservoir of microorganisms and amplifier of transmission, aseptic technique in surgery, public health education, interdisciplinary working, and the protection of health services and patients. Examples from across the globe help inform future thinking for IPC innovation, adoption, scale up and sustained use.


Subject(s)
Infection Control , Public Health , Humans , History, 19th Century , Interdisciplinary Studies , Health Education , France
9.
Mol Pharm ; 20(1): 663-679, 2023 01 02.
Article in English | MEDLINE | ID: mdl-36413707

ABSTRACT

Rutin (RUT) is a flavonoid obtained from a natural source and is reported for antithrombotic potential, but its delivery remains challenging because of its poor solubility and bioavailability. In this research, we have fabricated novel rutin loaded liposomes (RUT-LIPO, nontargeted), liposomes conjugated with RGD peptide (RGD-RUT-LIPO, targeted), and abciximab (ABX-RUT-LIPO, targeted) by ethanol injection method. The particle size, ƎĀ¶ potential, and morphology of prepared liposomes were analyzed by using DLS, SEM, and TEM techniques. The conjugation of targeting moiety on the surface of targeted liposomes was confirmed by XPS analysis and Bradford assay. In vitro assessment such as blood clot assay, aPTT assay, PT assay, and platelet aggregation analysis was performed using human blood which showed the superior antithrombotic potential of ABX-RUT-LIPO and RGD-RUT-LIPO liposomes. The clot targeting efficiency was evaluated by in vitro imaging and confocal laser scanning microscopy. A significant (P < 0.05) rise in the affinity of targeted liposomes toward activated platelets was demonstrated that revealed their remarkable potential in inhibiting thrombus formation. Furthermore, an in vivo study executed on Sprague Dawley rats (FeCl3 model) demonstrated improved antithrombotic activity of RGD-RUT-LIPO and ABX-RUT-LIPO compared with pure drug. The pharmacokinetic study performed on rats demonstrates the increase in bioavailability when administered as liposomal formulation as compared to RUT. Moreover, the tail bleeding assay and clotting time study (Swiss Albino mice) indicated a better antithrombotic efficacy of targeted liposomes than control preparations. Additionally, biocompatibility of liposomal formulations was determined by an in vitro hemolysis study and cytotoxicity assay, which showed that they were hemocompatible and safe for human use. A histopathology study on rats suggested no severe toxicity of prepared liposomal formulations. Thus, RUT encapsulated nontargeted and targeted liposomes exhibited superior antithrombotic potential over RUT and could be used as a promising carrier for future use.


Subject(s)
Liposomes , Thrombosis , Mice , Rats , Humans , Animals , Drug Delivery Systems/methods , Fibrinolytic Agents/pharmacology , Rutin , Rats, Sprague-Dawley , Oligopeptides , Thrombosis/drug therapy
10.
Health Expect ; 26(2): 892-904, 2023 04.
Article in English | MEDLINE | ID: mdl-36721315

ABSTRACT

OBJECTIVE: The irrational use of antibiotics is a leading contributor to antibiotic resistance. Antibiotic stewardship (AS) interventions predominantly focus on prescribers. This study investigated the influence and participation of inpatients in infection-related care, including antibiotic decision-making, within and across two tertiary hospitals in South Africa (Cape Town) and India (Kerala). METHODS: Through ethnographic enquiry of clinical practice in surgical pathways, including direct nonparticipant observation of clinical practices, healthcare worker (HCW), patient and carer interactions in surgical ward rounds and face-to-face interviews with participants (HCWs and patients), we sought to capture the implicit and explicit influence that patients and carers have in infection-related care. Field notes and interview transcripts were thematically coded, aided by NVivo 12Ā® Pro software. RESULTS: Whilst observational data revealed the nuanced roles that patients/carers play in antibiotic decision-making, HCWs did not recognize these roles. Patients and carers, though invested in patient care, are not routinely involved, nor are they aware of the opportunities for engagement in infection-related decision-making. Patients associated clinical improvement with antibiotic use and did not consider hospitalization to be associated with infection acquisition or transmission, highlighting a lack of understanding of the threat of infection and antibiotic resistance. Patients' economic and cultural positionalities may influence their infection-related behaviours. In the study site in India, cultural norms mean that carers play widespread but unrecognized roles in inpatient care, participating in infection prevention activities. CONCLUSION: For patients to have a valuable role in AS and make informed decisions regarding their infection-related care, a mutual understanding of their role in this process among HCWs and patients is crucial. The observed differences between the two study sites indicate the critical need for understanding and addressing the contextual drivers that impact effective patient-centred healthcare delivery. PATIENT OR PUBLIC CONTRIBUTION: Ethnographic observations and interviews conducted in this study involved patients as participants. Patients were recruited for interviews after obtaining signed informed consent forms. Patients' identities were completely anonymized when presenting the study findings.


Subject(s)
Health Personnel , Inpatients , Humans , South Africa , Anti-Bacterial Agents , Tertiary Care Centers
11.
Anim Biotechnol ; 34(8): 3545-3554, 2023 Dec.
Article in English | MEDLINE | ID: mdl-36794377

ABSTRACT

India has a centuries-old tradition of sheep production and breeding that accomplish economic, agricultural, and religious roles. In addition to the 44 registered sheep breeds, there is a fat-tailed sheep population referred to as Dumba. This study evaluated genetic variation in Dumba sheep and its differentiation from other Indian sheep breeds using mitochondrial DNA and genomic microsatellite loci. Haplotype and nucleotide diversity based on mitochondrial DNA analysis revealed substantially high maternal genetic diversity in Dumba sheep. Major ovine haplogroups A and B observed in sheep populations across the globe registered their presence in the Dumba sheep. The molecular genetic analysis using microsatellite markers also showed high measures of allele (10.125 Ā± 0.762) and gene diversity (0.749 Ā± 0.029). Results correspond to the non-bottleneck population that is near mutation-drift equilibrium despite some deficiency in the number of heterozygotes (FIS = 0.043 Ā± 0.059). Phylogenetic clustering confirmed Dumba to be a distinct population. Results of this study endow authorities with critical information imperative for sustainable utilization and conservation of Indian fat-tailed sheep, which is considered to be an untapped genetic resource contributing to the food security, livelihood, and economic sustainability of rural households in marginal areas of the country.


Subject(s)
DNA, Mitochondrial , Genetic Variation , Sheep/genetics , Animals , Genetic Variation/genetics , Phylogeny , DNA, Mitochondrial/genetics , Microsatellite Repeats/genetics , India
12.
Clin Infect Dis ; 74(11): 2067-2076, 2022 06 10.
Article in English | MEDLINE | ID: mdl-34665855

ABSTRACT

Rapid diagnostic tests (RDTs) facilitate fast and accurate identification of infectious disease microorganisms and are a valuable component of multimodal antimicrobial stewardship (AMS) programs but are currently underutilized in the Asia-Pacific region. An experienced group of infectious diseases clinicians, clinical microbiologists, and a clinical pharmacist used a modified Delphi consensus approach to construct 10 statements, aiming to optimize the utility and applicability of infection-related RDTs for AMS in the Asia-Pacific region. They provide guidance on definition, types, optimal deployment, measuring effectiveness, and overcoming key challenges. The Grading of Recommendations Assessment, Development, and Evaluation system was applied to indicate the strength of the recommendation and the quality of the underlying evidence. Given the diversity of the Asia-Pacific region, the trajectory of RDT development will vary widely; the collection of local data should be prioritized to allow realization and optimization of the full benefits of RDTs in AMS.


Subject(s)
Antimicrobial Stewardship , Asia , Consensus , Delphi Technique , Diagnostic Techniques and Procedures , Humans
13.
Ann Surg ; 275(2): e345-e352, 2022 02 01.
Article in English | MEDLINE | ID: mdl-33973886

ABSTRACT

OBJECTIVE: Surgical site infection (SSI) prevention remains significant, particularly in the era of antimicrobial resistance. Feedback on practices and outcomes is known to be key to reduce SSI rates and optimize antibiotic usage. However, the optimal method, format and frequency of feedback for surgical teams remains unclear. The objective of the study is to understand how data from surveillance and audit are fed back in routine surgical practice. METHODS: A systematic scoping review was conducted, using well-established implementation science frameworks to code the data. Two electronic health-oriented databases (MEDLINE, EMBASE) were searched to September 2019. We included studies that assessed the use of feedback as a strategy either in the prevention and management of SSI and/or in the use of antibiotics perioperatively. RESULTS: We identified 21 studies: 17 focused on SSI rates and outcomes and 10 studies described antimicrobial stewardship for SSI (with some overlap in focus). Several interventions were reported, mostly multimodal with feedback as a component. Feedback was often provided in written format (62%), either individualized (38%) or in group (48%). Only 25% of the studies reported that feedback cascaded down to the frontline perioperative staff. In 65% of the studies, 1 to 5 implementation strategies were used while only 5% of the studies reported to have utilized more than 15 implementation strategies. Among studies reporting antibiotic usage in surgery, most (71%) discussed compliance with surgical antibiotic prophylaxis. CONCLUSIONS: Our findings highlight the need to provide feedback to all levels of perioperative care providers involved in patient care. Future research in this area should report implementation parameters in more detail.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Drug Utilization/standards , Feedback , Surgical Wound Infection/prevention & control , Antibiotic Prophylaxis , Humans
14.
Scand J Immunol ; 95(1): e13115, 2022 Jan.
Article in English | MEDLINE | ID: mdl-34758123

ABSTRACT

Wiskott-Aldrich syndrome (WAS) also called the eczema-thrombocytopenia-immunodeficiency syndrome is a primary immunodeficiency disease with X-linked recessive inheritance caused by mutations in the WAS protein (WASp) gene and characterized by thrombocytopenia with reduced platelet volume, eczema, immunodeficiency, and increased risk of malignant tumours. The mutations will lead to separate WAS severity which can be typical severe 'classical' WAS or less severe 'non-classical' WAS. This article will review and analyse clinical and immune characteristics of five unrelated Chinese families harbouring classical and non-classical WAS. The expression of WASp was detected in the peripheral blood monocytes (PBMC) by flow cytometry, and five mutations were found by WAS gene sequencing, one of which had not been reported in the literature, namely frameshift mutation c.1240_1247delCCACTCCC (p. P414Sfs*41).


Subject(s)
Leukocytes, Mononuclear/metabolism , Mutation/genetics , Wiskott-Aldrich Syndrome Protein/genetics , Wiskott-Aldrich Syndrome/immunology , China , DNA Mutational Analysis , Eczema , Family , Female , Humans , Infant , Leukocytes, Mononuclear/immunology , Male , Mean Platelet Volume , Thrombocytopenia , Wiskott-Aldrich Syndrome/genetics
15.
Fish Shellfish Immunol ; 121: 183-196, 2022 Feb.
Article in English | MEDLINE | ID: mdl-34971736

ABSTRACT

Analyzing the health benefits of any two immunostimulants (synbiotics) in combined form and information on their interactions gain more visibility in the usage of synbiotics in aquafarms. With this intention, the current work explores the immunostimulant effect and structural interaction of synbiotic (Ɵ-1, 3 glucan binding protein from marine crab, Portunus pelagicus (PpƟ-GBP) and Bacillus licheniformis) on Oreochromis mossambicus. The experimental diet was prepared with PpƟ-GBP and B. licheniformis, and nourished to the fingerlings of O. mossambicus for 30 days. After the experimental trial, a higher growth rate and immune reactions (lysozyme, protease, myeloperoxidase and alkaline phosphatase activity) were noticed in the fish nourished with synbiotic (B. licheniformis and PpƟ-GBP) enriched diet. Moreover, the synbiotic enriched diet elevated the antioxidant responses like glutathione peroxidase (GSH-Px) and catalase (CAT) activity in the experimental diet-nurtured fish. At the end of the feed trial, synbiotic diet nourished fish shows an increased survival rate during Aeromonas hydrophila infection, reflecting the disease resistance potential of experimental fish. Also, the interaction between PpƟ-GBP and Bacillus licheniformis was analyzed through computational approaches. The results evidenced that, PpƟ-GBP interacts with the B. licheniformis through sugar-based ligand, Ɵ-glucan through a hydrogen bond with a good docking score. Thus, the synbiotic diet would be an effective immunostimulant to strengthen the fish immune system for better productivity.


Subject(s)
Adjuvants, Immunologic , Bacillus licheniformis , Carrier Proteins/immunology , Fish Diseases , Lectins/immunology , Tilapia , Aeromonas hydrophila , Animal Feed/analysis , Animals , Antioxidants/metabolism , Bacillus licheniformis/immunology , Diet/veterinary , Disease Resistance , Synbiotics
16.
Mol Divers ; 26(3): 1893-1913, 2022 Jun.
Article in English | MEDLINE | ID: mdl-34686947

ABSTRACT

The global spread of COVID-19 has raised the importance of pharmaceutical drug development as intractable and hot research. Developing new drug molecules to overcome any disease is a costly and lengthy process, but the process continues uninterrupted. The critical point to consider the drug design is to use the available data resources and to find new and novel leads. Once the drug target is identified, several interdisciplinary areas work together with artificial intelligence (AI) and machine learning (ML) methods to get enriched drugs. These AI and ML methods are applied in every step of the computer-aided drug design, and integrating these AI and ML methods results in a high success rate of hit compounds. In addition, this AI and ML integration with high-dimension data and its powerful capacity have taken a step forward. Clinical trials output prediction through the AI/ML integrated models could further decrease the clinical trials cost by also improving the success rate. Through this review, we discuss the backend of AI and ML methods in supporting the computer-aided drug design, along with its challenge and opportunity for the pharmaceutical industry. From the available information or data, the AI and ML based prediction for the high throughput virtual screening. After this integration of AI and ML, the success rate of hit identification has gained a momentum with huge success by providing novel drugs.


Subject(s)
Artificial Intelligence , COVID-19 Drug Treatment , Drug Design , Drug Industry , Humans , Machine Learning
17.
Molecules ; 27(20)2022 Oct 19.
Article in English | MEDLINE | ID: mdl-36296652

ABSTRACT

To date, there are no antimicrobial agents available in the market that have absolute control over the growing threat of bacterial strains. The increase in the production capacity of antibiotics and the growing antibacterial resistance of bacteria have majorly affected a variety of businesses and public health. Bimetallic nanoparticles (NPs) with two separate metals have been found to have stronger antibacterial potential than their monometallic versions. This enhanced antibacterial efficiency of bimetallic nanoparticles is due to the synergistic effect of their participating monometallic counterparts. To distinguish between bacteria and mammals, the existence of diverse metal transport systems and metalloproteins is necessary for the use of bimetallic Au-Ag NPs, just like any other metal NPs. Due to their very low toxicity toward human cells, these bimetallic NPs, particularly gold-silver NPs, might prove to be an effective weapon in the arsenal to beat emerging drug-resistant bacteria. The cellular mechanism of bimetallic nanoparticles for antibacterial activity consists of cell membrane degradation, disturbance in homeostasis, oxidative stress, and the production of reactive oxygen species. The synthesis of bimetallic nanoparticles can be performed by a bottom-up and top-down strategy. The bottom-up technique generally includes sol-gel, chemical vapor deposition, green synthesis, and co-precipitation methods, whereas the top-down technique includes the laser ablation method. This review highlights the key prospects of the cellular mechanism, synthesis process, and antibacterial capabilities against a wide range of bacteria. Additionally, we also discussed the role of Au-Ag NPs in the treatment of multidrug-resistant bacterial infection and wound healing.


Subject(s)
Metal Nanoparticles , Metalloproteins , Animals , Humans , Silver/pharmacology , Metal Nanoparticles/therapeutic use , Anti-Bacterial Agents/pharmacology , Reactive Oxygen Species/pharmacology , Drug Resistance, Bacterial , Gold/pharmacology , Bacteria , Nanotechnology , Mammals
18.
J Clin Pediatr Dent ; 46(3): 188-191, 2022 May 01.
Article in English | MEDLINE | ID: mdl-35830633

ABSTRACT

The present case report highlights the management of a 6 years old female child who suffered oral and maxillofacial injury due to explosion of a fire cracker inside the mouth which was managed by primary closure after complete debridement and to prevent the post treatment microstomia, a modified microstomia prevention intraoral prosthetic appliance was given and followed up for 15 months.


Subject(s)
Burns , Maxillofacial Injuries , Microstomia , Burns/complications , Burns/therapy , Child , Face , Female , Humans , Maxillofacial Injuries/complications , Maxillofacial Injuries/surgery , Microstomia/etiology , Microstomia/prevention & control
19.
J Clin Pediatr Dent ; 46(1): 20-23, 2022 Jan 01.
Article in English | MEDLINE | ID: mdl-35311980

ABSTRACT

The succedaneous permanent teeth develop in close proximity to primary teeth. They can get accidentally luxated or avulsed during the extraction of primary teeth. The purpose of this paper was to describe a case of a 14-year-old boy with an "iatrogenic avulsion" of an immature mandibular second premolar during the extraction of a primary mandibular second molar. The case was managed successfully with replantation technique within 30 minutes of extra oral period and followed up for 5 years. The replanted tooth remained clinically asymptomatic, showed continued root development and eruption and remained vital. This paper had also discussed about the modifications in extraction technique to avoid the iatrogenic avulsion of permanent tooth bud during extraction of primary teeth.


Subject(s)
Molar , Tooth Eruption , Adolescent , Bicuspid/surgery , Follow-Up Studies , Humans , Male , Tooth Germ
20.
BMC Infect Dis ; 21(1): 425, 2021 May 06.
Article in English | MEDLINE | ID: mdl-33957894

ABSTRACT

BACKGROUND: Candida auris infections are an emerging global threat with poor clinical outcome, high mortality rate, high transmission rate and outbreak potential. The objective of this work is to describe a multidisciplinary approach towards the investigation and containment of a Candida auris outbreak and the preventive measures adopted in a resource limited setting. METHODS: This outbreak investigational study was conducted at a 1300-bedded tertiary care academic hospital in South India. The study included 15 adult inpatients with laboratory confirmed Candida auris isolates. The outbreak cluster was identified in adult patients admitted from September 2017 to 2019. The system response consisted of a critical alert system for laboratory confirmed Candida auris infection and multidisciplinary 'Candida auris care team' for patient management. The team implemented stringent Infection Prevention and Control (IPC) measures including patient cohorting, standardized therapy and decolonization, staff training, prospective surveillance and introduction of Candida auris specific care bundle. RESULTS: Two outbreak clusters were identified; first cluster occurring between October and November 2017 and the second cluster in May 2018. The cohorts consisted of 7 and 8 Candida auris positive patients in the first and second waves of the outbreak respectively with a total survival rate of 93% (14/15). Deployment of containment measures led to gradual decline in the incidence of adult Candida auris positive cases and prevented further cluster formation. CONCLUSIONS: The sustained implementation of guideline and evidence-based IPC measures and training of healthcare workers for improving awareness on systematically following standardized protocols of Candida auris related IPC practices successfully contained Candida auris outbreaks at our hospital. This demonstrates the feasibility of establishing a multidisciplinary model and bundling of practices for preventing Candida auris outbreaks in a Low- and Middle-income country.


Subject(s)
Antifungal Agents/therapeutic use , Candidiasis, Invasive/drug therapy , Candidiasis, Invasive/epidemiology , Infection Control/methods , Adult , Aged , Aged, 80 and over , Candidiasis, Invasive/prevention & control , Disease Outbreaks , Humans , Incidence , India/epidemiology , Intensive Care Units/statistics & numerical data , Male , Middle Aged , Mortality , Prospective Studies , Tertiary Care Centers/statistics & numerical data , Treatment Outcome
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