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1.
Phys Rev Lett ; 130(24): 242501, 2023 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-37390416

RESUMO

Excited-state spectroscopy from the first experiment at the Facility for Rare Isotope Beams (FRIB) is reported. A 24(2)-µs isomer was observed with the FRIB Decay Station initiator (FDSi) through a cascade of 224- and 401-keV γ rays in coincidence with ^{32}Na nuclei. This is the only known microsecond isomer (1 µs≤T_{1/2}<1 ms) in the region. This nucleus is at the heart of the N=20 island of shape inversion and is at the crossroads of the spherical shell-model, deformed shell-model, and ab initio theories. It can be represented as the coupling of a proton hole and neutron particle to ^{32}Mg, ^{32}Mg+π^{-1}+ν^{+1}. This odd-odd coupling and isomer formation provides a sensitive measure of the underlying shape degrees of freedom of ^{32}Mg, where the onset of spherical-to-deformed shape inversion begins with a low-lying deformed 2^{+} state at 885 keV and a low-lying shape-coexisting 0_{2}^{+} state at 1058 keV. We suggest two possible explanations for the 625-keV isomer in ^{32}Na: a 6^{-} spherical shape isomer that decays by E2 or a 0^{+} deformed spin isomer that decays by M2. The present results and calculations are most consistent with the latter, indicating that the low-lying states are dominated by deformation.


Assuntos
Núcleo Celular , Coração , Isótopos , Nêutrons
2.
Phys Rev Lett ; 129(21): 212501, 2022 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-36461950

RESUMO

New half-lives for exotic isotopes approaching the neutron drip-line in the vicinity of N∼28 for Z=12-15 were measured at the Facility for Rare Isotope Beams (FRIB) with the FRIB decay station initiator. The first experimental results are compared to the latest quasiparticle random phase approximation and shell-model calculations. Overall, the measured half-lives are consistent with the available theoretical descriptions and suggest a well-developed region of deformation below ^{48}Ca in the N=28 isotones. The erosion of the Z=14 subshell closure in Si is experimentally confirmed at N=28, and a reduction in the ^{38}Mg half-life is observed as compared with its isotopic neighbors, which does not seem to be predicted well based on the decay energy and deformation trends. This highlights the need for both additional data in this very exotic region, and for more advanced theoretical efforts.

3.
BJOG ; 128(4): 714-726, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32803845

RESUMO

OBJECTIVE: To determine risk-reducing early salpingectomy and delayed oophorectomy (RRESDO) acceptability and effect of surgical prevention on menopausal sequelae/satisfaction/regret in women at increased ovarian cancer (OC) risk. DESIGN: Multicentre, cohort, questionnaire study (IRSCTN:12310993). SETTING: United Kingdom (UK). POPULATION: UK women without OC ≥18 years, at increased OC risk, with/without previous RRSO, ascertained through specialist familial cancer/genetic clinics and BRCA support groups. METHODS: Participants completed a 39-item questionnaire. Baseline characteristics were described using descriptive statistics. Logistic/linear regression models analysed the impact of variables on RRESDO acceptability and health outcomes. MAIN OUTCOMES: RRESDO acceptability, menopausal sequelae, satisfaction/regret. RESULTS: In all, 346 of 683 participants underwent risk-reducing salpingo-oophorectomy (RRSO). Of premenopausal women who had not undergone RRSO, 69.1% (181/262) found it acceptable to participate in a research study offering RRESDO. Premenopausal women concerned about sexual dysfunction were more likely to find RRESDO acceptable (odds ratio [OR] = 2.9, 95% CI 1.2-7.7, P = 0.025). Women experiencing sexual dysfunction after premenopausal RRSO were more likely to find RRESDO acceptable in retrospect (OR = 5.3, 95% CI 1.2-27.5, P < 0.031). In all, 88.8% (143/161) premenopausal and 95.2% (80/84) postmenopausal women who underwent RRSO, respectively, were satisfied with their decision, whereas 9.4% (15/160) premenopausal and 1.2% (1/81) postmenopausal women who underwent RRSO regretted their decision. HRT uptake in premenopausal individuals without breast cancer (BC) was 74.1% (80/108). HRT use did not significantly affect satisfaction/regret levels but did reduce symptoms of vaginal dryness (OR = 0.4, 95% CI 0.2-0.9, P = 0.025). CONCLUSION: Data show high RRESDO acceptability, particularly in women concerned about sexual dysfunction. Although RRSO satisfaction remains high, regret rates are much higher for premenopausal women than for postmenopausal women. HRT use following premenopausal RRSO does not increase satisfaction but does reduce vaginal dryness. TWEETABLE ABSTRACT: RRESDO has high acceptability among premenopausal women at increased ovarian cancer risk, particularly those concerned about sexual dysfunction.


Assuntos
Atitude Frente a Saúde , Neoplasias Ovarianas/prevenção & controle , Ovariectomia/métodos , Salpingectomia/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Predisposição Genética para Doença , Pesquisas sobre Atenção à Saúde , Humanos , Modelos Lineares , Pessoa de Meia-Idade , Neoplasias Ovarianas/genética , Reino Unido , Adulto Jovem
4.
Gen Comp Endocrinol ; 288: 113377, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31881203

RESUMO

The synergy between the genetic potential and the nutrient intake determines the growth performance of meat-type chicken and nutrigenomics approach helps us understand the response of candidate genes of growth in chicken to dietary manipulations. The current study aimed to assess the growth performance and expression of hepatic growth related genes in the naked neck broiler chicken in response to different dietary energy and protein levels with a hypothesis that high plane of nutrition enhances both of these positively. The results revealed that birds have shown significantly better growth performance under high protein (HP) and high energy (HE) dietary regime. The expression profiles of the genes studied revealed upregulation of IGF-1, IGF-2, and GH under dietary HP and HE regime relative to other protein and energy levels with greater upregulation at 3rd week than the 1st and 5th week of age of birds. The IGFR and GHR mRNA expression was significantly higher under HP and HE dietary regimen with an increasing and decreasing trend from 1st to 5th week of age, respectively. A consistent and significant downregulation of IGFBP-2 was observed under HP and HE regime throughout the feeding trial. The myostatin expression was higher at 3rd week of age followed by 1st week expression. The HP and HE as well as LP (Low protein) and HE diet resulted in significant upregulation of myostatin gene expression in liver. In support to the set hypothesis of this study the high protein and high energy diet resulted in better growth performance of broiler chickens with corresponding upregulation of IGF-1, IGF-2, IGFR, GH, GHR, and Myostatin gene expression and downregulation of IGFBP-2 in liver.


Assuntos
Galinhas/crescimento & desenvolvimento , Galinhas/genética , Dieta , Proteínas Alimentares/administração & dosagem , Metabolismo Energético/efeitos dos fármacos , Ração Animal , Fenômenos Fisiológicos da Nutrição Animal/genética , Animais , Galinhas/metabolismo , Proteínas Alimentares/farmacologia , Ingestão de Energia/efeitos dos fármacos , Metabolismo Energético/genética , Feminino , Expressão Gênica/efeitos dos fármacos , Hormônio do Crescimento/genética , Hormônio do Crescimento/metabolismo , Proteína 2 de Ligação a Fator de Crescimento Semelhante à Insulina/genética , Proteína 2 de Ligação a Fator de Crescimento Semelhante à Insulina/metabolismo , Fator de Crescimento Insulin-Like I/genética , Fator de Crescimento Insulin-Like I/metabolismo , Fator de Crescimento Insulin-Like II/genética , Fator de Crescimento Insulin-Like II/metabolismo , Masculino , Distribuição Aleatória , Receptor IGF Tipo 1/genética , Receptor IGF Tipo 1/metabolismo
5.
Photochem Photobiol Sci ; 17(9): 1197-1205, 2018 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-30043019

RESUMO

The interaction of the cupric ion with esculetin, a dihydroxy coumarin derivative, was studied by absorption and fluorescence spectroscopic methods in aqueous medium. Esculetin formed a complex in the presence of the cupric ion which was characterised by the shift in its absorption band from 350 nm to 389 nm and the quenching of its fluorescence intensity at 466 nm. From Job's plot and fluorescence quenching studies, the stoichiometry of the copper ion and esculetin in the complex was estimated to be 1 : 2 respectively. Interestingly, the incubation of the Cu(ii)-esculetin complex with a thiol peptide, glutathione (GSH), showed restoration of the fluorescence intensity as well as absorption maxima to that of pure esculetin. Incubation with other common thiol and non-sulphur amino acids did not show a similar restoration of the photophysical properties of the complex except in the case of cysteine. Mechanistically, it was evident that two molecules of GSH were consumed in reducing the Cu(ii)-esculetin complex, which subsequently split into the copper ion and esculetin. In this process GSH was converted into oxidised GSH (GSSG) as evident from the mass spectroscopy and HPLC studies. The above florescence regeneration behaviour of the copper-esculetin system in the presence of GSH was also observed in the cellular system using Chinese hamster ovary (CHO) as model cells. In conclusion, these studies may find application in developing sensors for detecting the cellular thiol level.


Assuntos
Cobre/química , Compostos de Sulfidrila/química , Umbeliferonas/química , Animais , Técnicas Biossensoriais , Células CHO , Cricetinae , Cricetulus , Glutationa/química , Íons , Espectrometria de Massas , Estrutura Molecular , Espectrometria de Fluorescência
6.
J Microsc ; 265(2): 232-244, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27779739

RESUMO

Cardiomyopathy and associated heart failure continues to be one of the most severe complications that threaten a large population. Curcumin, one of the three curcuminoids of the spice turmeric, is very well known for a multitude of health benefits and functions. Norepinephrine (NE), a catecholamine and also a stress hormone may cause the cardiomyocytes to develop increased sensitivity to death with its increasing concentrations. In this study, we investigated the cardioprotective effect of curcumin in NE-induced cardiac apoptosis using several fluorescent and nonfluorescent microscopic techniques like DAPI, PI, Giemsa, PicroSirius and TUNEL. The aim of the study was to assess the effect of curcumin in preventing the occurrence of features underlying apoptosis such as nuclear disruption, chromatin condensation, DNA fragmentation and alterations in mitochondrial membrane permeability. Our results show that curcumin protects the cardiomyocytes against apoptosis significantly and also helps them to revert to their normal physiological state. Hence, we propose that curcumin has the potential to act as a therapeutic agent for the attenuation of NE-induced cardiac cell death and modulation of apoptosis in H9c2 cardiomyocytes.


Assuntos
Agonistas alfa-Adrenérgicos/efeitos adversos , Apoptose/efeitos dos fármacos , Cardiotônicos/farmacologia , Curcumina/farmacologia , Miócitos Cardíacos/efeitos dos fármacos , Norepinefrina/efeitos adversos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Humanos , Microscopia , Miócitos Cardíacos/fisiologia
7.
Opt Lett ; 41(7): 1408-11, 2016 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-27192248

RESUMO

A new mechanics of linear mode conversion of terahertz (THz) radiation into THz surface magnetoplasmons on a rippled surface of magnetized n-InSb is proposed. The normally incident THz radiation, polarized in the direction of a ripple wave vector, imparts oscillatory velocity to electrons in the ripple layer. This velocity beats with surface ripple to produce a nonlinear current that resonantly drives the THz surface magnetoplasmons. In the presence of an applied magnetic field, the surface plasmon (SP) mode splits into two modes-an upper mode and a lower mode. The amplitude of the SP for the upper branch mode is higher than that for the lower mode.

8.
Appl Microbiol Biotechnol ; 100(15): 6827-6835, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27075739

RESUMO

Ensiling is a feed preservation method of moist forage crops that generally depends on naturally developing lactic acid bacteria to convert water-soluble carbohydrates into organic acids. While bacterial community dynamics have been previously assessed in bench-scale and pilot ensiling facilities, almost no studies have assessed the microbiomes of large-scale silage facilities. This study analyzed bacterial community composition in mature silage from bunker silos in three commercial production centers as related to pH, organic matter, volatile fatty acid composition, and spatial distribution within the ensiling bunker. It revealed significant physicochemical differences between "preserved" regions situated in the center and along the walls of the silage bunkers that were characterized by high concentrations of lactic acid and other volatiles and pH values below 5, and "spoiled" regions in the corners (shoulders) of the bunkers that had low lactic acid concentrations and high pH values. Preserved silage was dominated (>90 %) by lactic acid bacteria and characterized by high similarity and low taxonomic diversity, whereas spoiled silage had highly diverse microbiomes with low abundances of lactic acid bacteria (<5 %) that were sometimes characterized by high levels of Enterobacteriaceae. Spatial position had a much stronger impact on the microbial community composition than feedstock type, sampling date, or production center location supporting previous studies demonstrating that ecology and not geography is a major driver of environmental microbiomes.


Assuntos
Lactobacillus/metabolismo , Microbiota/genética , Silagem/microbiologia , Biodiversidade , Metabolismo dos Carboidratos , Carboidratos , Produtos Agrícolas/metabolismo , Enterobacteriaceae/isolamento & purificação , Fermentação , Sequenciamento de Nucleotídeos em Larga Escala , Ácido Láctico , Lactobacillus/genética , Lactobacillus/isolamento & purificação , RNA Ribossômico 16S/genética
9.
Eur J Vasc Endovasc Surg ; 47(4): 367-73, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24491283

RESUMO

OBJECTIVES: Ultrasound (US) is non-invasive and cost-effective for screening abdominal aortic aneurysms (AAAs) but there is no universally accepted method to measure the aortic diameter. This study evaluates the accuracy, reproducibility, and repeatability of three methods: inner-to-inner (ITI), leading-to-leading edge (LTL), and outer-to-outer (OTO). The secondary objective of this study was to determine whether aneurysm size or grade of operator had any effect on either intra- or inter-observer variability. METHODS: Fifty static US images were measured by six assessors (2 vascular radiologists, 2 interventional radiology trainees, and 2 sonographers) on two separate occasions 6 weeks apart. Repeatability and reproducibility were calculated and compared with computed tomography (CT) as the gold standard. RESULTS: All three methods have high repeatability and reproducibility when static images are used. The inter-observer reproducibility coefficients between assessors were 0.48 cm, 0.35 cm, and 0.34 cm for ITI, LTL and OTO, respectively. The intra-observer repeatability coefficients between assessors were 0.30 cm, 0.20 cm, and 0.19 cm for ITI, LTL and OTO, respectively. The mean difference between CT and OTO, LTL, and ITI was 1 mm, 3 mm, and 5 mm, respectively (all underestimations) (p < .0001). CONCLUSIONS: US consistently underestimates aortic size when compared with CT, with ITI demonstrating the greatest underestimation (on average 5 mm). In the UK, this underestimation by the NHS Abdominal Aortic Aneurysm screening programme reduces the sensitivity of the screening test and may impact on the way in which vascular specialists interpret the findings of the screening programme.


Assuntos
Aneurisma da Aorta Abdominal/diagnóstico por imagem , Humanos , Variações Dependentes do Observador , Reprodutibilidade dos Testes , Tomografia Computadorizada por Raios X/métodos , Ultrassonografia , Reino Unido
10.
Opt Lett ; 38(18): 3475-7, 2013 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-24104791

RESUMO

Terahertz (THz) surface plasmon generation via nonlinear mixing of laser eigenmodes in an optical fiber coated with ultrathin metal foil and possessing a dielectric constant ripple of wave number q is investigated. The fiber supports THz surface plasma wave (SPW) with plasmon resonance in the THz domain and is controllable by film thickness. The lasers exert a difference frequency ponderomotive force on the electrons of the metal film. The ponderomotive force induces a nonlinear current driving the difference frequency THz SPW. THz amplitude to laser amplitude ratio of the order ∼10(-2) can be achieved by CO2 laser in megawatt range.

11.
J Postgrad Med ; 59(2): 145-8, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23793319

RESUMO

Fungal ball (mycetoma/aspergilloma) is a saprophytic fungal infection that colonizes pre-existing lung cavities. Reported literature suggests its development in cystic lesions/cavitation associated with tuberculosis, sarcoidosis, bronchiectasis, lung abscess, and cavitating neoplasm to name a few. Coexistence of aspergilloma with idiopathic pulmonary fibrosis (IPF) has not been reported in literature so far, to the best of our knowledge. We hereby report the case of a 55-year-old female with IPF having fungal ball.


Assuntos
Fibrose Pulmonar Idiopática/complicações , Pneumopatias Fúngicas/complicações , Aspergilose Pulmonar/complicações , Tosse/etiologia , Feminino , Humanos , Fibrose Pulmonar Idiopática/diagnóstico , Pessoa de Meia-Idade , Aspergilose Pulmonar/diagnóstico
12.
Reprod Domest Anim ; 48(2): 278-83, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22805579

RESUMO

In the present study, the expression profile of luteinizing hormone receptor (LHR) was investigated in the ovary, magnum and uterus and in hierarchcal follicles (F-1, F-2, F-3 and F-4) of hens subjected to moulting to establish their involvement in moulting and presence in non-gonadal tissues. Fifty-two layers (72 weeks) were subjected to moult for a period of 14 days. Four birds were sacrificed each time on 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 14 days of moulting, and samples (ovary, magnum, uterus and hierarchal follicles) were collected aseptically for the quantitative study by real-time polymerase chain reaction. The ovary, isthmus, uterus and magnum weight reduced significantly during induced moulting. From the 4 DOM, this reduction was drastic and reached approximately 80% of original weight in the case of ovary, isthmus and magnum and approximately 65% of original weight in the case of uterus on 14 DOM. Ovarian yellow follicles decreased gradually from 1 DOM to 4 DOM, after that no normal yellow follicle was observed in moulted bird. The number of atretic follicles increased gradually during the course of induced moulting, reaching the peak at 5 DOM. The LHR mRNA was detected in non-gonadal tissues like magnum and uterus. The LHR expression was significantly (p < 0.05) down regulated in ovary, magnum and uterus throughout the treatment. These results indicated that LHR may have a role in reproductive tissue regression during moulting.


Assuntos
Galinhas/fisiologia , Muda/fisiologia , Folículo Ovariano/metabolismo , Oviductos/metabolismo , Receptores do LH/metabolismo , Transcriptoma , Animais , Feminino , Regulação da Expressão Gênica/fisiologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Receptores do LH/genética
13.
Front Microbiol ; 14: 1171104, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37455718

RESUMO

Agricultural areas exhibiting numerous abiotic stressors, such as elevated water stress, temperatures, and salinity, have grown as a result of climate change. As such, abiotic stresses are some of the most pressing issues in contemporary agricultural production. Understanding plant responses to abiotic stressors is important for global food security, climate change adaptation, and improving crop resilience for sustainable agriculture, Over the decades, explorations have been made concerning plant tolerance to these environmental stresses. Plant growth-promoting rhizobacteria (PGPR) and their phytohormones are some of the players involved in developing resistance to abiotic stress in plants. Several studies have investigated the part of phytohormones in the ability of plants to withstand and adapt to non-living environmental factors, but very few have focused on rhizobacterial hormonal signaling and crosstalk that mediate abiotic stress tolerance in plants. The main objective of this review is to evaluate the functions of PGPR phytohormones in plant abiotic stress tolerance and outline the current research on rhizobacterial hormonal communication and crosstalk that govern plant abiotic stress responses. The review also includes the gene networks and regulation under diverse abiotic stressors. The review is important for understanding plant responses to abiotic stresses using PGPR phytohormones and hormonal signaling. It is envisaged that PGPR offer a useful approach to increasing plant tolerance to various abiotic stresses. However, further studies can reveal the unclear patterns of hormonal interactions between plants and rhizobacteria that mediate abiotic stress tolerance.

14.
Eye (Lond) ; 2023 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-38066111

RESUMO

BACKGROUND: Understanding and mitigating the societal economic impact of vision impairment (VI) is important for achieving the Sustainable Development Goals. AIM: To estimate the prevalent societal economic impact of presenting VI in Trinidad and Tobago using bottom-up cost and utilisation data from the 2014 National Eye Survey of Trinidad and Tobago. METHODS: We took a societal perspective to combine comprehensive, individual-level cost and utilisation data, with population-based prevalence estimates for VI, and additional data from a contemporaneous national eyecare system survey. We included direct (medical and non-medical) and indirect (productivity loss) costs, and intangible losses in total cost estimates, presented in 2014 Trinidad & Tobago (TT) dollars and UK sterling equivalent. We considered but excluded transfer payments and dead weight losses. Sensitivity analyses explored impact on total cost of parameter uncertainty and assumptions. RESULTS: Individual utilisation and cost data were available for 65.5% (n = 2792/4263) and 59.0% (n = 2516/4263) eligible participants aged ≥40 years, respectively. Participant mean age was 58.4(SD 11.8, range 40-103) years, 56.3% were female. We estimated total societal cost of VI in 2014 at UK£365,650,241 (TT$3,842,324,655), equivalent to £675 per capita (population ≥40 years). Loss of wellbeing accounted for 73.3%. Excluding this, the economic cost was UK£97,547,222 (TT$1,025,045,399), of which indirect costs accounted for 70.5%, followed by direct medical costs (17.9%), and direct non-medical costs (11.6%). CONCLUSION: This study provides a comprehensive estimate of the economic impact of vision loss in a Caribbean country, and highlights the extent to which affected individuals and their families bear the societal economic cost of vision impairment.

15.
J Bacteriol ; 194(24): 6790-801, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23042997

RESUMO

Rhodococcus equi is a facultative intracellular, Gram-positive, soilborne actinomycete which can cause severe pyogranulomatous pneumonia with abscessation in young horses (foals) and in immunocompromised people, such as persons with AIDS. All strains of R. equi isolated from foals and approximately a third isolated from humans contain a large, ~81-kb plasmid which is essential for the intramacrophage growth of the organism and for virulence in foals and murine in vivo model systems. We found that the entire virulence plasmid could be transferred from plasmid-containing strains of R. equi (donor) to plasmid-free R. equi strains (recipient) at a high frequency and that plasmid transmission reestablished the capacity for intracellular growth in macrophages. Plasmid transfer required living cells and cell-to-cell contact and was unaffected by the presence of DNase, factors pointing to conjugation as the major means of genetic transfer. Deletion of a putative relaxase-encoding gene, traA, located in the proposed conjugative region of the plasmid, abolished plasmid transfer. Reversion of the traA mutation restored plasmid transmissibility. Finally, plasmid transmission to other Rhodococcus species and some additional related organisms was demonstrated. This is the first study showing a virulence plasmid transfer in R. equi, and it establishes a mechanism by which the virulence plasmid can move among bacteria in the soil.


Assuntos
Conjugação Genética , Plasmídeos/genética , Rhodococcus equi/genética , Rhodococcus equi/patogenicidade , Infecções por Actinomycetales/microbiologia , Infecções por Actinomycetales/patologia , Infecções por Actinomycetales/veterinária , Animais , Proteínas de Bactérias/genética , DNA Bacteriano/genética , Desoxirribonucleases/metabolismo , Transferência Genética Horizontal , Doenças dos Cavalos/microbiologia , Cavalos , Macrófagos/microbiologia , Análise de Sequência de DNA
16.
Parasite Immunol ; 34(10): 464-72, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22803643

RESUMO

Dendritic cells (DC) play a pivotal role in regulating immunity, establishing immunologically privileged tissue microenvironments and maintaining homoeostasis. It is becoming increasingly clear that one key mechanism that mediates many DC functions is production of the immunomodulatory enzyme indoleamine 2,3-dioxygenase (IDO). For pathogens that cause chronic infection, exploitation of host DCs is a solution to establish and persist within a host. Leishmania parasites cause a range of clinical manifestations, all involving chronic infection, and are proficient at avoiding immune responses. We demonstrate here that infection of human myeloid-derived DC with L. major and L. donovani induces IDO expression using a mechanism that involves autocrine or paracrine stimulation with a DC-secreted factor. Leishmania-induced IDO suppresses allogeneic and tetanus toxoid-specific lymphocyte proliferation, an inhibition that is reversed with the IDO inhibitor, 1-methyl tryptophan (1-MT). Furthermore, IDO expression by human DC does not require live Leishmania infection, as parasite lysates also up-regulate IDO mRNA production. Our data suggest that one mechanism Leishmania parasites utilize to circumvent immune clearance may be to promote the induction of IDO among host DC within the infection microenvironment.


Assuntos
Células Dendríticas/enzimologia , Células Dendríticas/parasitologia , Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo , Leishmania donovani/imunologia , Leishmania major/imunologia , Adulto , Proliferação de Células , Células Cultivadas , Células Dendríticas/imunologia , Humanos , Linfócitos/imunologia
17.
Cureus ; 14(5): e25349, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35761910

RESUMO

Background No-reflow phenomenon (NRP) remains a challenge in ST-elevation myocardial infarction (STEMI) patients. We determined the efficacy and safety of early intracoronary administration of nicorandil as an adjunct to primary percutaneous coronary intervention (pPCI) in STEMI patients to reduce the risk of NRP. Materials and methods In this single-center case-control prospective study, 100 STEMI patients who underwent pPCI had thrombectomy performed using a suction catheter, and tirofiban (10 mg/kg) was injected distal to the vascular lesion. All patients were divided into two groups. Group A was a treatment group (nicorandil, n=50) and group B was a control group (placebo, n=50). The primary endpoint was the composite endpoint of in-hospital cardiovascular mortality or unscheduled re-hospitalization due to deterioration of congestive heart failure that was assessed with the help of brain natriuretic peptide (BNP), left ventricular end-diastolic diameter (LVEDD), and left ventricular ejection fraction at six months following pPCI. The secondary endpoints were thrombolysis in myocardial infarction (TIMI) flow grade, TIMI myocardial perfusion grade (TMPG), the incidence of reperfusion arrhythmias like ventricular tachycardia and ventricular fibrillation, and ST segment elevation resolution (STR) on ECG following pPCI. Results The in-hospital cardiovascular mortality and re-hospitalization rates were 2% and 6% in the nicorandil group, whereas it was 6% and 14% in the control group. On the 180th day of admission, the nicorandil group had significantly lower values of brain natriuretic peptide (348.45±112.32 pg/ml vs. 541.11±152.68 pg/ml, p=0.021) and left ventricular end-diastolic diameter (54.12±3.56 mm vs. 60.62±4.98 mm, p=0.011) than the control group. Nicorandil group had a significantly higher number of patients who attained TIMI 3 (p=0.022), TMPG 3 (p=0.034), and STR (p=0.008) than the control group. Ventricular arrhythmia was significantly lower in the nicorandil group than in the control group at 24 hours following pPCI (p=0.012). Conclusion Early intracoronary administration of nicorandil during pPCI may decrease the occurrence of NRP, in-hospital cardiovascular mortality, and re-hospitalization rates, as well as improve coronary blood flow and reduce reperfusion arrhythmia in STEMI patients.

18.
Vaccine X ; 12: 100216, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36164460

RESUMO

Background: Combination vaccines reduce the number of pediatric injections but must be as safe, immunogenic, and effective as each of the individual vaccines given separately. Additionally, consistency in manufacturing lots is essential for WHO prequalification. This study aimed to establish the lot-to-lot consistency of a fully liquid, hexavalent diphtheria (D)-tetanus (T)-whole-cell pertussis (wP)-inactivated poliovirus (IPV)-hepatitis B (HB)-Haemophilus influenzae b (PRP-T) (DTwP-IPV-HB-PRP∼T) vaccine and to demonstrate non-inferiority to licensed DTwP-HB-PRP∼T and IPV vaccines. Methods: A Phase III, randomized, active-controlled, and open-label study was conducted at multiple centers across India. Healthy infants who had received a birth dose of oral poliovirus vaccine and hepatitis B vaccine received one of three lots of DTwP-IPV-HB-PRP∼T or separate DTwP-HB-PRP∼T and IPV vaccines at 6-8, 10-12, and 14-16 weeks of age. Oral rotavirus vaccine was co-administered at 6-8 weeks of age and 10-12/14-16 weeks of age. DTwP-IPV-HB-PRP∼T lot-to-lot consistency and non-inferiority (pooled DTwP-IPV-HB-PRP∼T) versus DTwP-HB-PRP∼T and IPV post-third dose were assessed using seroprotection rates (anti-D, anti-T, anti-HBs, anti-PRP, anti-polio 1, 2, 3) and adjusted geometric mean concentrations (anti-PT, anti-FIM). Safety was assessed by parental reports. Results: Lot-to-lot consistency was demonstrated for DTwP-IPV-HB-PRP∼T and non-inferiority versus DTwP-HB-PRP∼T and IPV was confirmed with 95% CIs for seroprotection rate differences and adjusted geometric mean concentration ratios within pre-defined clinical margins. Pooled seroprotection rate was ≥ 99.7% for anti-D ≥ 0.01 IU/mL, anti-T ≥ 0.01 IU/mL, anti-HBs ≥ 10 mIU/mL, anti-PRP ≥ 0.15 µg/mL, and anti-polio 1, 2, and 3 ≥ 8 (1/dil) and vaccine response rate was 83.9% for anti-PT and 97.7% for anti-FIM. There were no safety concerns. Conclusions: Immunogenicity of three lots of the fully liquid DTwP-IPV-HB-PRP∼T vaccine was consistent and non-inferior to licensed comparators following vaccination at 6-8, 10-12, and 14-16 weeks of age. There were no safety concerns and no evidence of any effect of co-administration with rotavirus vaccine.

19.
Epigenetics ; 16(10): 1053-1070, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-33054565

RESUMO

Here we report epigenomic and transcriptomic changes in a prototypical J774 macrophage after engulfing talc or titanium dioxide particles in presence of estrogen. Macrophages are the first immune cells to engage and clear particles of various nature. A novel paradigm is emerging, that exposure to so-called 'inert' particulates that are considered innocuous is not really free of consequences. We hypothesized that especially the insoluble, non-digestible particles that do not release a known hazardous chemical can be underappreciated agents acting to affect the regulation inside macrophages upon phagocytosis. We performed gene chip microarray profiling and found that talc alone, and especially with oestrogen, has induced a substantially more prominent gene expression change than titanium dioxide; the affected genes were involved in pathways of cell proliferation, immune response and regulation, and, unexpectedly, enzymes and proteins of epigenetic regulation. We therefore tested the DNA methylation profiles of these cells via epigenome-wide bisulphite sequencing and found vast epigenetic changes in hundreds of loci, remarkably after a very short exposure to particles; ELISA assay for methylcytosine levels determined the particles induced an overall decrease in DNA methylation. We found a few loci where both the transcriptional changes and epigenetic changes occurred in the pathways involving immune and inflammatory signalling. Some transcriptomic and epigenomic changes were shared between talc and titanium dioxide, however, it is especially interesting that each of the two particles of similar size and insoluble nature has also induced a specific pattern of gene expression and DNA methylation changes which we report here.


Assuntos
Epigenômica , Transcriptoma , Metilação de DNA , Epigênese Genética , Macrófagos
20.
Phys Rev Lett ; 105(11): 117201, 2010 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-20867601

RESUMO

We study the effect of coupling magnetic impurities to the honeycomb lattice spin-1/2 Kitaev model in its spin-liquid phase. We show that a spin-S impurity coupled to the Kitaev model is associated with an unusual Kondo effect with an intermediate coupling unstable fixed point Kc∼J/S separating topologically distinct sectors of the Kitaev model. We also show that the massless spinons in the spin-liquid mediate an interaction of the form Siα2Sjß2/Rij3 between distant impurities unlike the usual dipolar RKKY interaction SiαSjα/Rij3 noted in various 2D impurity problems with a pseudogapped density of states of the spin bath. Furthermore, this long-range interaction is possible only if the impurities (a) couple to more than one neighboring spin on the host lattice and (b) the impurity spin S≠1/2.

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