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1.
Int J Neurosci ; : 1-12, 2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33930999

RESUMO

Background Deficiency of vitamin D along with traumatic brain injury (TBI) augments the risk of injury severity. This possibly affects the therapeutic regimen prescribed for TBI which may pessimistically affects its outcome.Methods Studies literature search was conducted in Google Scholar and PubMed. The inclusions were studies performed clinically on both male and female. All included studies' references were also reviewed to find any additional relevance related to this review. Studies published in English were considered for this review. This review focuses upon the incidence of vitamin D deficiency in TBI and how it affects the Quality of life of the sufferer.Results A total of 176 studies were reviewed and 58 were thoroughly focussed for review as they met inclusion criteria. These studies demonstrate that levels of vitamin D influence the recovery outcome after TBI. Vitamin D deficiency has been found to cause more deterioration in severe TBI than in patients with mild TBI.Conclusion Paucity of vitamin D significantly affects the outcome after brain injury. This clearly validates the necessity for screening of vitamin D levels in neurological deficit in order to reduce the risk of morbidity in terms of neurocognitive disorder.

3.
Front Cell Infect Microbiol ; 11: 596201, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33859951

RESUMO

COVID-19 is a Severe Acute Respiratory Syndrome (SARS), caused by SARS-CoV-2, a novel virus which belongs to the family Coronaviridae. It was first reported in December 2019 in the Wuhan city of China and soon after, the virus and hence the disease got spread to the entire world. As of February 26, 2021, SARS-CoV-2 has infected ~112.20 million people and caused ~2.49 million deaths across the globe. Although the case fatality rate among SARS-CoV-2 patient is lower (~2.15%) than its earlier relatives, SARS-CoV (~9.5%) and MERS-CoV (~34.4%), the SARS-CoV-2 has been observed to be more infectious and caused higher morbidity and mortality worldwide. As of now, only the knowledge regarding potential transmission routes and the rapidly developed diagnostics has been guiding the world for managing the disease indicating an immediate need for a detailed understanding of the pathogen and the disease-biology. Over a very short period of time, researchers have generated a lot of information in unprecedented ways in the key areas, including viral entry into the host, dominant mutation, potential transmission routes, diagnostic targets and their detection assays, potential therapeutic targets and drug molecules for inhibiting viral entry and/or its replication in the host including cross-neutralizing antibodies and vaccine candidates that could help us to combat the ongoing COVID-19 pandemic. In the current review, we have summarized the available knowledge about the pathogen and the disease, COVID-19. We believe that this readily available knowledge base would serve as a valuable resource to the scientific and clinical community and may help in faster development of the solution to combat the disease.


Assuntos
/mortalidade , Saúde Global , Pandemias , China/epidemiologia , Humanos
4.
Environ Pollut ; 281: 116990, 2021 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-33812129

RESUMO

The synergistic photoelectrochemical (PEC) technology is a robust process for the conversion of CO2 into fuels. However, designing a highly efficient UV-visible driven photoelectrocatalyst is still challenging. Herein, a plasmonic Ag NPs modified TiO2/RGO photoelectrocatalyst (Ag-TiO2/RGO) has been designed for the PEC CO2 reduction into selective production of CH3OH. HR-TEM analysis revealed that Ag and TiO2 NPs with average sizes of 4 and 7 nm, respectively, were densely grown on the few-micron-sized 2D RGO nanosheets. The physicochemical analysis was used to determine the optical and textural properties of the Ag-TiO2/RGO nanohybrids. Under VU-Vis light illumination, Ag-TiO2/RGO photocathode possessed a current density of 23.5 mA cm-2 and a lower electrode resistance value of 125 Ω in CO2-saturated 1.0 M KOH-aqueous electrolyte solution. Catalytic studies showed that the Ag-TiO2/RGO photocathode possessed a remarkable PEC CO2 reduction activity and selective production of CH3OH with a yield of 85 µmol L-1 cm-2, the quantum efficiency of 20% and Faradic efficiency of 60.5% at onset potential of -0.7 V. A plausible PEC CO2 reduction mechanism over Ag-TiO2/RGO photocathode is schematically demonstrated. The present work gives a new avenue to develop high-performance and stable photoelectrocatalyst for PEC CO2 reduction towards sustainable liquid fuels production.

5.
Adv Exp Med Biol ; 1280: 219-230, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33791985

RESUMO

Head and neck squamous cell carcinoma (HNSCC) glycolysis is an important factor for the advancement of the disease and metastasis. Upregulation of glycolysis leads to decreased sensitivity to chemotherapy and radiation. HNSCC cells maintain constitutive glycolytic flux generating metabolic intermediates for the synthesis of amino acids, nucleotides, and fats for cell survival and disease progression. There are several pathways such as PI3K/Akt, EGFR, and JAK-STAT that contribute a major role in metabolic alteration in HNSCC. Recent studies have demonstrated that cancer-associated fibroblasts abundant in the HNSCC tumor microenvironment play a major role in HNSCC metabolic alteration via hepatocyte growth factor (HGF)/c-Met cross signaling. Despite therapeutic advancement, HNSCC lacks broad range of therapeutic interventions for the treatment of the disease. Thus, understanding the different key players involved in glucose metabolism and targeting them would lead to the development of novel drugs for the treatment of HNSCC.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Carcinoma de Células Escamosas/tratamento farmacológico , Linhagem Celular Tumoral , Glicólise , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Humanos , Fosfatidilinositol 3-Quinases/genética , Microambiente Tumoral
6.
Int Orthop ; 2021 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-33835246

RESUMO

PURPOSE: In an observational study, we studied the impact of COVID-19 pandemic on our clinical practice of trauma and orthopaedics, in tertiary care hospital of New Delhi. METHODS: We collated the hospital data for 2019 and 2020 and analyzed and compared it extensively. We looked for the effects of the COVID-19 pandemic on several important clinical practice parameters like outpatient attendance, inpatients admissions, and surgery. The correlation of the number of surgeries done during the pandemic time was done with the number of positive cases in Delhi, monthwise. A trend of recovery was also observed. RESULTS: During the pandemic period, the attendance of outpatients fell by 71.93%, admissions by 59.35%, and surgery by 55.78%. Adult trauma surgery was the least affected (42.21%), followed by arthroscopic surgery (49.81%). Fragility hip fractures requiring bipolar hip arthroplasty were reduced by 34.15%. The maximum adverse impact of the pandemic was seen on arthroplasty surgery (hip > knee), followed by on the paediatric orthopaedic cases, and spinal surgery. We notice a "lazy V-shaped" recovery after the lockdown period. CONCLUSION: COVID-19 pandemic has had a severe impact on all aspects of orthopaedics and trauma's clinical practice in our setup. These adverse effects were maximally seen during the lockdown period, with a reduction of 90.77% in the outpatients, 84.63% in the admissions, and 86.67% in the surgery.

7.
Anim Biotechnol ; : 1-10, 2021 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-33843465

RESUMO

Q fever caused by Coxiella burnetii is an important zoonosis and has great public health significance. A total of 905 clinical samples from 387 cattle [serum (n = 387); vaginal swabs (n = 387); milk (n = 131)] and 59 serum samples from humans were collected from gaushala (cattle shelter) and screened for anti-C. burnetii IgG antibodies in the sera using an indirect-ELISA kit. Further, the samples were tested for C. burnetii DNA employing TaqMan real-time and conventional PCR assays targeting the com1 gene. In ELISA, 9.56% and 6.78% of animal and human sera samples were positive for anti-C. burnetii antibodies, respectively. Upon pathogen detection, 3.87% sera, 1.81% vaginal swabs, and 6.87% milk samples from cattle tested positive in TaqMan real-time PCR and 1.55% sera, 0.52% vaginal swabs, and 3.05% milk samples were found positive in conventional PCR. In humans, one serum sample was positive in both the PCR assays. The PCR positive samples (n = 12) were partially sequenced and the phylogenetic tree was constructed using com1 gene sequences (n = 42) from a different host and geographical areas. The study highlights infection of cattle and their human contacts in gaushala and identifies relationships between strains identified in the gaushala and those in other parts of the globe.

8.
Indian J Med Res ; 153(3): 299-310, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33906992

RESUMO

Animal disease surveillance encompasses systematic collection of long-term data on disease events, risk factors and other relevant parameters followed by analyzing the same with reference to temporal and spatial characteristics to arrive at a conclusion so that necessary preventive measures can be taken. In India, the animal disease surveillance is done through National Animal Disease Reporting System, which is a web-based information technology system for disease reporting from States and Union Territories with the aim to record, monitor livestock disease situation and to initiate the preventive and curative action in a swift manner during disease emergencies. National Animal Disease Referral Expert System is a dynamic geographic information system and remote sensing-enabled expert system that captures an incidence of 13 economically important livestock diseases from all over the country and also provides livestock disease forecasting. The laboratories under State and Central governments, several research institutes under the Indian Council of Agricultural Research and veterinary colleges are involved in livestock disease diagnosis including zoonotic diseases. An integrated surveillance system is necessary for early detection of emerging/zoonotic diseases in humans. This review provides information on disease reporting and surveillance systems in animal health sector and the need for One Health approach to improve and strengthen the zoonotic disease surveillance system in India.

9.
J Immunol ; 206(8): 1866-1877, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33811102

RESUMO

HSV-1 infection of the cornea causes a severe immunoinflammatory and vision-impairing condition called herpetic stromal keratitis (SK). The virus replication in corneal epithelium followed by neutrophil- and CD4+ T cell-mediated inflammation plays a dominant role in SK. Although previous studies demonstrate critical functions of type I IFNs (IFN-α/ß) in HSV-1 infection, the role of recently discovered IFN-λ (type III IFN), specifically at the corneal mucosa, is poorly defined. Our study using a mouse model of SK pathogenesis shows that HSV-1 infection induces a robust IFN-λ response compared with type I IFN production at the corneal mucosal surface. However, the normal progression of SK indicates that the endogenous IFN responses are insufficient to suppress HSV-1-induced corneal pathology. Therefore, we examined the therapeutic efficacy of exogenous rIFN-λ during SK progression. Our results show that rIFN-λ therapy suppressed inflammatory cell infiltration in the cornea and significantly reduced the SK pathologic condition. Early rIFN-λ treatment significantly reduced neutrophil and macrophage infiltration, and IL-6, IL-1ß, and CXCL-1 production in the cornea. Notably, the virucidal capacity of neutrophils and macrophages measured by reactive oxygen species generation was not affected. Similarly, ex vivo rIFN-λ treatment of HSV-1-stimulated bone marrow-derived neutrophils significantly promoted IFN-stimulated genes without affecting reactive oxygen species production. Collectively, our data demonstrate that exogenous topical rIFN-λ treatment during the development and progression of SK could represent a novel therapeutic approach to control HSV-1-induced inflammation and associated vision impairment.

10.
J Med Microbiol ; 70(3)2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33739918

RESUMO

Introduction. Carbapenem resistance in Acinetobacter baumannii (A. baumannii) is an emerging global threat.Gap statement. The adaptation strategies of A. baumannii for this emergence as a nosocomial pathogen has been less studied.Aim. This prospective study analysed a sustained outbreak of carbapenem resistant Acinetobacter baumannii (CRAB) in the intensive care unit (ICU) with reference to antimicrobial resistance and virulence in the colonizing and pathogenic isolates under carbapenem stress.Results. The CRAB isolates from initial and sustained outbreak were found harbouring multiple carbapenemase genes. These genes included bla OXA-23 ,bla IMP, bla VIM and bla NDM. From NICU environment three phenotypically carbapenem susceptible isolates were found carrying bla OXA-23, bla IMP, bla VIM genes. Prior imipenem therapy was one of the risk factors (P=0.0016). The outbreak was polyclonal. Under imipenem stress, outbreak isolates showed no loss of carbapenemase genes against stress free conditions (23.7±1.33 days). Biofilm formation increased with imipenem concentration, with outbreak isolates producing highest biomass. While the pathogens showed a slow growth rate on imipenem exposure, the colonisers grew rapidly (P <0.0001).Methods. Sustained outbreak of CRAB was identified in the ICU (July 2015 to December 2017). Risk factors for acquisition of CRAB was studied. A. baumannii isolates were also collected from the environments of ICU and neonatal ICU (NICU) and blood cultures of septic neonates. Isolates were characterized based on antimicrobial susceptibility, genetic profile, integrons carriage and clonality. Biofilm formation and growth kinetics were studied under varying carbapenem stress.Conclusion. Intense carbapenem exposure in the ICU facilitates persistence of CRAB by several adaptations causing sustained outbreaks.


Assuntos
Infecções por Acinetobacter/microbiologia , Acinetobacter baumannii/fisiologia , Adaptação Fisiológica , Carbapenêmicos/farmacologia , Infecção Hospitalar/microbiologia , Surtos de Doenças , Farmacorresistência Bacteriana Múltipla/fisiologia , Infecções por Acinetobacter/tratamento farmacológico , Infecções por Acinetobacter/epidemiologia , Acinetobacter baumannii/efeitos dos fármacos , Acinetobacter baumannii/patogenicidade , Adulto , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Carbapenêmicos/uso terapêutico , Infecção Hospitalar/tratamento farmacológico , Infecção Hospitalar/epidemiologia , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Farmacorresistência Bacteriana Múltipla/genética , Microbiologia Ambiental , Feminino , Genes Bacterianos , Humanos , Imipenem/farmacologia , Imipenem/uso terapêutico , Integrons/genética , Unidades de Terapia Intensiva , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Virulência , beta-Lactamases/genética , beta-Lactamases/metabolismo
12.
Eur J Ophthalmol ; : 11206721211005691, 2021 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-33765847

RESUMO

PURPOSE: To report subthreshold micropulse laser as novel treatment modality for exudative maculopathy associated with adult Coats' disease. METHODS: A 27-year old, young male presented with exudative maculopathy in adult onset Coat's disease with profound diminution of vision. Spectral domain-optical coherence tomogram (SD-OCT) revealed macular oedema with significant subfoveal hard exudates with massive subretinal exudations temporal to macula. He was planned for anti-VEGF injection to treat macular oedema in order to preserve vision but developed conjunctivitis which made any interventional procedure impossible. Patient was managed with subthreshold micro pulse laser using 532 nm green laser. RESULTS: Patient had significant improvement in vision, resolution of macular oedema as well as hard exudate without any adverse effects on fovea. CONCLUSION: Novel treatment approach in form of subthreshold micro pulse laser could be an alternative treatment modality for exudative maculopathy associated with adult onset Coat's disease, especially in cases where other available interventional treatment options are not possible.

13.
Curr Microbiol ; 78(4): 1124-1134, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33687511

RESUMO

Phage display is one of the important and effective molecular biology techniques and has remained indispensable for research community since its discovery in the year 1985. As a large number of nucleotide fragments may be cloned into the phage genome, a phage library may harbour millions or sometimes billions of unique and distinctive displayed peptide ligands. The ligand-receptor interactions forming the basis of phage display have been well utilized in epitope mapping and antigen presentation on the surface of bacteriophages for screening novel vaccine candidates by using affinity selection-based strategy called biopanning. This versatile technique has been modified tremendously over last three decades, leading to generation of different platforms for combinatorial peptide display. The translation of new diagnostic tools thus developed has been used in situations arising due to pathogenic microbes, including bacteria and deadly viruses, such as Zika, Ebola, Hendra, Nipah, Hanta, MERS and SARS. In the current situation of pandemic of Coronavirus disease (COVID-19), a search for neutralizing antibodies is motivating the researchers to find therapeutic candidates against novel SARS-CoV-2. As phage display is an important technique for antibody selection, this review presents a concise summary of the very recent applications of phage display technique with a special reference to progress in diagnostics and therapeutics for coronavirus diseases. Hopefully, this technique can complement studies on host-pathogen interactions and assist novel strategies of drug discovery for coronaviruses.


Assuntos
Anticorpos Antivirais/imunologia , Técnicas de Visualização da Superfície Celular/métodos , /imunologia , Anticorpos Neutralizantes/imunologia , Bacteriófago M13/genética , Bacteriófago M13/metabolismo , Bacteriófago T4/genética , Bacteriófago T4/metabolismo , Bacteriófago T7/genética , Bacteriófago T7/metabolismo , Escherichia coli/genética , Escherichia coli/virologia , Humanos
14.
Trop Doct ; : 49475521998178, 2021 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-33779397

RESUMO

Syphilis has a wide variety of ocular presentations such as anterior or posterior uveitis, chorioretinitis, retinal vasculitis, retinitis, perineuritis, papillitis, retrobulbar neuritis, optic atrophy and optic nerve gumma. Therefore, it is recommended to test every patient with ocular inflammation for syphilis. It is, however, a relatively rare cause of uveitis in HIV disease. A few studies suggested that HIV contributes to the ocular manifestations of syphilis and HIV co-infection in approximately 30%. Acute syphilitic posterior placoid chorioretinopathy is a rare ocular manifestation in immune-competent patients characterised by the development of a deposit in the outer retina. We describe an unusual such presentation with hypopyon.

15.
Mutat Res ; 822: 111741, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33706167

RESUMO

CITED2 is a transcription co-activator that interacts with TFAP2 and CBP/ P300 transcription factors to regulate the proliferation and differentiation of the cardiac progenitor cells. It acts upstream to NODAL-PITX2 pathways and regulates the left-right asymmetry. Both human genetic and model organism studies have shown that altered expression of CITED2 causes various forms of congenital heart disease. Therefore, we sought to screen the coding region of CITED2 to identify rare genetic variants and assess their impact on the structure and function of the protein. Here, we have screened 271 non-syndromic, sporadic CHD cases by Sanger's sequencing method and detected a non-synonymous variant (c.301C>T, p.P101S) and two synonymous variants (c.21C>A, p.A7A; c.627C>G, p.P209P). The non-synonymous variant c.301C>T (rs201639244) is a rare variant with a minor allele frequency of 0.00011 in the gnomAD browser and 0.0018 in the present study. in vitro analysis has demonstrated that p.P101S mutation upregulates the expression of downstream target genes Gata4, Mef2c, Nfatc1&2, Nodal, Pitx2, and Tbx5 in P19 cells. Luciferase reporter assay also demonstrates enhanced activation of downstream target promoters. Further, in silico analyses implicate that increased activity of mutant CITED2 is possibly due to phosphorylation of Serine residue by proline-directed kinases. Homology modeling and alignment analysis have also depicted differences in hydrogen bonding and tertiary structures of wild-type versus mutant protein. The impact of synonymous variations on the mRNA structure of CITED2has been analyzed by Mfold and relative codon bias calculations. Mfold results have revealed that both the synonymous variants can alter the mRNA structure and stability. Relative codon usage analysis has suggested that the rate of translation is attenuated due to these variations. Altogether, our results from genetic screening as well as in vitro and in silico studies support a possible role of nonsynonymous and synonymous mutations in CITED2contributing to pathogenesis of CHD.

16.
Food Res Int ; 140: 109979, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33648214

RESUMO

Pectinases are the emerging enzymes of the biotechnology industry with a 25% share in the worldwide food and beverage enzyme market. These are green and eco-friendly tools of nature and hold a prominent place among the commercially produced enzymes. Pectinases exhibit applications in various industrial bioprocesses, such as clarification of fruit juices and wine, degumming, and retting of plant fibers, extraction of antioxidants and oil, fermentation of tea/coffee, wastewater remediation, modification of pectin-laden agro-industrial waste materials for high-value products biosynthesis, manufacture of cellulose fibres, scouring, bleaching, and size reduction of fabric, cellulosic biomass pretreatment for bioethanol production, etc. Nevertheless, like other enzymes, pectinases also face the challenges of low operational stability, recoverability, and recyclability. To address the above-mentioned problems, enzyme immobilization has become an eminently promising approach to improve their thermal stability and catalytic characteristics. Immobilization facilitates easy recovery and recycling of the biocatalysts multiple times, leading to enhanced performance and commercial feasibility.In this review, we illustrate recent developments on the immobilization of pectinolytic enzymes using polymers and nanostructured materials-based carrier supports to constitute novel biocatalytic systems for industrial exploitability. The first section reviewed the immobilization of pectinases on polymers-based supports (ca-alginate, chitosan, agar-agar, hybrid polymers) as a host matrix to construct robust pectinases-based biocatalytic systems. The second half covers nanostructured supports (nano-silica, magnetic nanostructures, hybrid nanoflowers, dual-responsive polymeric nanocarriers, montmorillonite clay), and cross-linked enzyme aggregates for enzyme immobilization. The biotechnological applications of the resulted immobilized robust pectinases-based biocatalytic systems are also meticulously vetted. Finally, the concluding remarks and future recommendations are also given.

17.
J Xray Sci Technol ; 29(2): 373-382, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33554936

RESUMO

The main objective of this work is to explore the X-ray interaction properties of P2O5- SnCl2-SnO bioactive glass system using Photon Shielding and Dosimetry (Phys-X/PSD) software in the energy range 10-150 keV. The study of these parameters will have applications in various fields of nuclear medicine, medical technology, and other medical applications. The value of mass attenuation coefficients (µm) and effective atomic numbers (Zeff) decrease whereas the value of mean free path as well as half value layer increases with rises in energy in the selected energy range. The study results indicate that bioactive glass composition of T2 of chemical composition (35P2O5- 55SnCl2-10SnO) possesses the lowest value of mean free path (MFP), and highest value of µm, and Zeff, among the chemical composition.

18.
Glia ; 69(6): 1494-1514, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33586813

RESUMO

The role of microglia in mediating age-related changes in cognition and hippocampal synaptic function was examined by microglial depletion and replenishment using PLX3397. We observed age-related differences in microglial number and morphology, as well as increased Iba-1 expression, indicating microglial activation. PLX3397 treatment decreased microglial number, with aged rats exhibiting the lowest density. Young rats exhibited increased expression of pro-inflammatory cytokines during depletion and repopulation and maintenance of Iba-1 levels despite reduced microglial number. For aged rats, several cytokines increased with depletion and recovered during repopulation; however, aged rats did not fully recover microglial cell number or Iba-1 expression during repopulation, with a recovery comparable to young control levels rather than aged controls. Hippocampal CA3-CA1 synaptic transmission was impaired with age, and microglial depletion was associated with decreased total synaptic transmission in young and aged rats. A robust decline in N-methyl-d-aspartate-receptor-mediated synaptic transmission arose in young depleted rats specifically. Microglial replenishment normalized depletion-induced synaptic function to control levels; however, recovery of aged animals did not mirror young. Microglial depletion was associated with decreased context-object discrimination memory in both age groups, which recovered with microglial repopulation. Aged rats displayed impaired contextual and cued fear memory, and microglial replenishment did not recover their memory to the level of young. The current study indicates that cognitive function and synaptic transmission benefit from the support of aged microglia and are hindered by removal of these cells. Replenishment of microglia in aging did not ameliorate age-related cognitive impairments or senescent synaptic function.

19.
J Periodontal Res ; 2021 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-33559894

RESUMO

OBJECTIVE: Periodontitis is one the most common chronic inflammatory conditions, resulting in destruction of tooth-supporting tissues and leading to tooth loss. Porphyromonas gingivalis activates host macrophages to secrete pro-inflammatory cytokines and elicit tissue damage, in part by inducing NF-kappa-B transactivation. Since NFκB transactivation is negatively regulated by the Nicotinamide adenine dinucleotide (NAD)-dependent deacetylase enzyme Sirt1, we sought to assess if RAW264.7 macrophages exposed to P. gingivalis demonstrate impaired Sirt1 activity, to ultimately induce a pro-inflammatory response. METHODS: RAW264.7 macrophages were incubated with heat- killed P. gingivalis for 2, 4, 8, and 24 h. Stimulated RAW264.7 were assessed for TNFα expression via PCR, ELISA, and ChIP analysis. Following the activation of RAW264.7 macrophages, immunoblot analysis was executed to detect modifications in Sirt1 and the NFκB subunit RelA that is essential for NFκB transcriptional activity. RESULTS: TNFα expression was elevated 4 h after exposure to P. gingivalis. ChIP confirmed that RelA was enriched in the mouse TNFα promoter 4 h following stimulation, which correlated with the increased TNFα mRNA levels. Preceding TNFα expression, we detected Phosphoserine 536 and acetylated lysine 310 of RelA after 2 hours exposure with P. gingivalis. Moreover, reduced Sirt1 activity was associated with its cleavage in RAW264.7 protein extracts, after 2 hours of P. gingivalis exposure. Blocking TLR2/4 signaling prevented Sirt1 cleavage, loss of deacetylase activity, and TNFα secretion, while co-administering CA074Me (a cathepsin B inhibitor) with P. gingivalis reduced RelA promoter enrichment, resulting in impaired TNFα expression. CONCLUSIONS: Together, the results suggest that P. gingivalis induces TNFα expression, at least in part, by enhancing cleavage of Sirt1 via a TLR-dependent signaling circuit.

20.
BMJ Open ; 11(2): e043837, 2021 02 22.
Artigo em Inglês | MEDLINE | ID: mdl-33619195

RESUMO

OBJECTIVES: Healthcare personnel (HCP) are at an increased risk of acquiring COVID-19 infection especially in resource-restricted healthcare settings, and return to homes unfit for self-isolation, making them apprehensive about COVID-19 duty and transmission risk to their families. We aimed at implementing a novel multidimensional HCP-centric evidence-based, dynamic policy with the objectives to reduce risk of HCP infection, ensure welfare and safety of the HCP and to improve willingness to accept and return to duty. SETTING: Our tertiary care university hospital, with 12 600 HCP, was divided into high-risk, medium-risk and low-risk zones. In the high-risk and medium-risk zones, we organised training, logistic support, postduty HCP welfare and collected feedback, and sent them home after they tested negative for COVID-19. We supervised use of appropriate personal protective equipment (PPE) and kept communication paperless. PARTICIPANTS: We recruited willing low-risk HCP, aged <50 years, with no comorbidities to work in COVID-19 zones. Social distancing, hand hygiene and universal masking were advocated in the low-risk zone. RESULTS: Between 31 March and 20 July 2020, we clinically screened 5553 outpatients, of whom 3012 (54.2%) were COVID-19 suspects managed in the medium-risk zone. Among them, 346 (11.4%) tested COVID-19 positive (57.2% male) and were managed in the high-risk zone with 19 (5.4%) deaths. One (0.08%) of the 1224 HCP in high-risk zone, 6 (0.62%) of 960 HCP in medium-risk zone and 23 (0.18%) of the 12 600 HCP in the low-risk zone tested positive at the end of shift. All the 30 COVID-19-positive HCP have since recovered. This HCP-centric policy resulted in low transmission rates (<1%), ensured satisfaction with training (92%), PPE (90.8%), medical and psychosocial support (79%) and improved acceptance of COVID-19 duty with 54.7% volunteering for re-deployment. CONCLUSION: A multidimensional HCP-centric policy was effective in ensuring safety, satisfaction and welfare of HCP in a resource-poor setting and resulted in a willing workforce to fight the pandemic.


Assuntos
Transmissão de Doença Infecciosa do Paciente para o Profissional , Corpo Clínico Hospitalar , Doenças Profissionais , Adulto , /prevenção & controle , /transmissão , Países em Desenvolvimento , Feminino , Hospitais Universitários/organização & administração , Humanos , Transmissão de Doença Infecciosa do Paciente para o Profissional/prevenção & controle , Masculino , Corpo Clínico Hospitalar/estatística & dados numéricos , Modelos Organizacionais , Doenças Profissionais/epidemiologia , Doenças Profissionais/prevenção & controle , Política Organizacional , Equipamento de Proteção Individual , Estudos Prospectivos , Medição de Risco , Centros de Atenção Terciária/organização & administração
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