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1.
Artigo em Inglês | MEDLINE | ID: mdl-34951582

RESUMO

BACKGROUND AND OBJECTIVE: The study aimed to investigate the augmented cytotoxic effects of polymer-coated (poly-lactic-co-glycolic acid-PLGA) gold nanoparticles (GNPs) carrying 5-fluorouracil (5-FU) in the management of lung cancer. MATERIALS AND METHODS: In this study, several formulations were prepared using a double emulsion (water-oil-water) method and evaluated for drug release behavior, compatibility, cell line toxicity (A549), and apoptosis assessment. RESULTS: Characterization results showed spherical polydispersed particles with size 29.11-178.21 nm, polydispersity index (PDI) 0.191-292, and zeta potential (ZP) 11.19-29.21 (-mV), respectively. The optimized polymer-coated 5-FU loaded gold nanoparticles (PFGNPs) illustrated a maximum drug loading (93.09 ± 10.75%) compared to others. The percent cumulative drug release of polymer-coated 5-FU loaded nanoparticles (PFNPs), 5-FU loaded gold nanoparticles (FGNPs), (PFGNPs) and 5-FU solution were 47.87± 1.5, 41.09±1.8, 56.31±1.05, and 98.8±4.2%, respectively, over 10 h. following zero-order release kinetics (except 5-FU solution). From the MTT results, the cytotoxic effect of PFGNPs on the A549 cells was 82.89 % compared to the 5-FU solution (74.91 %). EGFR and KRAS gene expression analysis under the influence of PFNPs, FGNPs, PFGNPs, and 5-FU was studied and observed maximum potency for PFNPs. CONCLUSION: PLGA coated biogenic gold nanoparticles have a combined effect to achieve high drug loading, sustained delivery, improved efficacy, and enhanced permeation. Conclusively, the approach may be promising to control lung cancer with reduced toxicity and improved efficacy.

2.
ACS Infect Dis ; 7(8): 2425-2436, 2021 08 13.
Artigo em Inglês | MEDLINE | ID: mdl-34191496

RESUMO

Commercial carbapenem antibiotics are being used to treat multidrug resistant (MDR) and extensively drug resistant (XDR) tuberculosis. Like other ß-lactams, carbapenems are irreversible inhibitors of serine d,d-transpeptidases involved in peptidoglycan biosynthesis. In addition to d,d-transpeptidases, mycobacteria also utilize nonhomologous cysteine l,d-transpeptidases (Ldts) to cross-link the stem peptides of peptidoglycan, and carbapenems form long-lived acyl-enzymes with Ldts. Commercial carbapenems are C2 modifications of a common scaffold. This study describes the synthesis of a series of atypical, C5α modifications of the carbapenem scaffold, microbiological evaluation against Mycobacterium tuberculosis (Mtb) and the nontuberculous mycobacterial species, Mycobacterium abscessus (Mab), as well as acylation of an important mycobacterial target Ldt, LdtMt2. In vitro evaluation of these C5α-modified carbapenems revealed compounds with standalone (i.e., in the absence of a ß-lactamase inhibitor) minimum inhibitory concentrations (MICs) superior to meropenem-clavulanate for Mtb, and meropenem-avibactam for Mab. Time-kill kinetics assays showed better killing (2-4 log decrease) of Mtb and Mab with lower concentrations of compound 10a as compared to meropenem. Although susceptibility of clinical isolates to meropenem varied by nearly 100-fold, 10a maintained excellent activity against all Mtb and Mab strains. High resolution mass spectrometry revealed that 10a acylates LdtMt2 at a rate comparable to meropenem, but subsequently undergoes an unprecedented carbapenem fragmentation, leading to an acyl-enzyme with mass of Δm = +86 Da. Rationale for the divergence of the nonhydrolytic fragmentation of the LdtMt2 acyl-enzymes is proposed. The observed activity illustrates the potential of novel atypical carbapenems as prospective candidates for treatment of Mtb and Mab infections.


Assuntos
Carbapenêmicos , Peptidil Transferases , Antibacterianos/farmacologia , Carbapenêmicos/farmacologia , Estudos Prospectivos , Inibidores de beta-Lactamases/farmacologia
3.
Psychol Rep ; : 332941211005115, 2021 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-33789535

RESUMO

Psychosocial stressors and social disadvantages contribute to inequalities in opportunities and outcomes. In the current paper, we use an epidemiological perspective and highlight the role stress plays on individuals by reviewing the outcomes of major stressors such as poverty and unemployment. We further analyzed the psychological and physical cost of these stressors and their long-term impact. We examined the role of universal basic income and closely looked at income experiments that were implemented in the past, in terms of their effectiveness in enhancing the community as well as individual outcomes and propose the UBI as a tool for alleviating the impact of these stressors. At a time when a major pandemic (e.g., COVID-19) threatens economic stability and health globally, we believe the UBI is relevant now, more than ever.

4.
Cells ; 10(4)2021 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-33920786

RESUMO

Nonsteroidal anti-inflammatory drugs cause gastric ulcers and gastritis. No drug that treats GI injury directly stimulates mucosal healing. ZINC40099027 (ZN27) activates focal adhesion kinase (FAK) and heals acute indomethacin-induced small bowel injury. We investigated the efficacy of ZN27 in rat and human gastric epithelial cells and ongoing aspirin-associated gastric injury. ZN27 (10 nM) stimulated FAK activation and wound closure in rat and human gastric cell lines. C57BL/6J mice were treated with 300 mg/kg/day aspirin for five days to induce ongoing gastric injury. One day after the initial injury, mice received 900 µg/kg/6 h ZN27, 10 mg/kg/day omeprazole, or 900 µg/kg/6 h ZN27 plus 10 mg/kg/day omeprazole. Like omeprazole, ZN27 reduced gastric injury vs. vehicle controls. ZN27-treated mice displayed better gastric architecture, with thicker mucosa and less hyperemia, inflammation, and submucosal edema, and lost less weight than vehicle controls. Gastric pH, serum creatinine, serum alanine aminotransferase (ALT), and renal and hepatic histology were unaffected by ZN27. Blinded scoring of pFAK-Y-397 immunoreactivity at the edge of ZN27-treated lesions demonstrated increased FAK activation, compared to vehicle-treated lesions, confirming target activation in vivo. These results suggest that ZN27 ameliorates ongoing aspirin-associated gastric mucosal injury by a pathway involving FAK activation. ZN27-derivatives may be useful to promote gastric mucosal repair.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Aspirina/efeitos adversos , Proteína-Tirosina Quinases de Adesão Focal/metabolismo , Mucosa Gástrica/lesões , Mucosa Gástrica/patologia , Cicatrização/efeitos dos fármacos , Alanina Transaminase/sangue , Animais , Linhagem Celular , Creatinina/sangue , Modelos Animais de Doenças , Ativação Enzimática/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Feminino , Mucosa Gástrica/efeitos dos fármacos , Humanos , Concentração de Íons de Hidrogênio , Hiperemia/patologia , Inflamação/patologia , Antígeno Ki-67/metabolismo , Rim/efeitos dos fármacos , Rim/patologia , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Camundongos , Ratos , Perda de Peso/efeitos dos fármacos
5.
Atten Percept Psychophys ; 83(1): 114-121, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33146816

RESUMO

It has been debated that arousal rather than valence modulates the response-inhibition process. The processing of irrelevant information of happy and angry faces interacts with attention differently. In the present study, arousal-matched irrelevant happy and angry faces were used as stop-signals in the stop-signal paradigm. Participants were required to respond to go-signals (discriminate between X or O). Occasionally, a stop-signal was presented where participants were required to withhold their motor response. Results indicate a significant effect of emotion on response inhibition, which suggests that valence of a stop-signal modulates inhibitory control. More specifically, we found that only irrelevant angry, but not happy, expressions facilitate the response inhibition process. These results have theoretical implications for understanding the nature of emotions and its interaction with cognitive control functions.


Assuntos
Ira , Expressão Facial , Atenção , Emoções , Felicidade , Humanos
6.
Front Digit Health ; 3: 590194, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34977855

RESUMO

Machine Learning (ML) has been a useful tool for scientific advancement during the COVID-19 pandemic. Contact tracing apps are just one area reaping the benefits, as ML can use location and health data from these apps to forecast virus spread, predict "hotspots," and identify vulnerable groups. However, to do so, it is first important to ensure that the dataset these apps yield is accurate, free of biases, and reliable, as any flaw can directly influence ML predictions. Given the lack of criteria to help ensure this, we present two requirements for those exploring using ML to follow. The requirements we presented work to uphold international data quality standards put forth for ML. We then identify where our requirements can be met, as countries have varying contact tracing apps and smartphone usages. Lastly, the advantages, limitations, and ethical considerations of our approach are discussed.

7.
Front Med (Lausanne) ; 7: 590265, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33344477

RESUMO

The rise of the coronavirus disease 2019 (COVID-19) in a digital world has expectedly called upon technologies, such as wearables and mobile devices, to work in conjunction with public health interventions to tackle the pandemic. One significant example of this integration is the deployment of proximity tracking apps on smartphones to enhance traditional contact tracing methods. Many countries have adopted proximity tracking apps; however, there is a large degree of global differentiation in the voluntariness of the apps. Further, the concept of a mandatory policy-forcing individuals to use the apps-has been met with ethical concerns (e.g., privacy and liberty). While ethical considerations surrounding deployment have been put forth, such as by the World Health Organization, ethical justifications for a mandatory policy are lacking. Here, we use the Faden-Shebaya framework, which was formed to justify public health interventions, to determine if the compulsory use of proximity tracking apps is ethically appropriate. We show that while theoretically justified, due to the current state of proximity tracking applications and societal factors, it is difficult to defend a mandatory policy in practice.

8.
Oxid Med Cell Longev ; 2020: 6501294, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32774681

RESUMO

Pseudoalteromonas espejiana (P. espejiana) is a marine bacterium known for its high resistance to alkalinity. The ability of P. espejiana to reduce Au (III) and biosynthesize gold nanoparticles (AuNPs) is found positive and was confirmed using UV-VIS, EDS, SEM, and TEM studies. Previously, many studies have been reported regarding the crystalline nature of AuNPs; therefore, this research aims at studying the crystal growth behaviour of AuNPs through DLS and TEM studies. Spherically shaped and monodispersed, AuNPs ranging between 5 to 160 nm were obtained with an average particle size of 62 nm. Also, to achieve maximum production of AuNPs, the reaction kinetic study was performed using an ICP-OES method and the effect of various parameters including pH, temperature, rpm, and concentration of substrate was analyzed. During the biosynthesis process, an appropriate phase of nucleation, crystal growth, and saturation was observed and this helped to determine the rate constants and order of reaction. The parameters such as pH profile (pH 9), temperature (30°C), agitation speed (150 rpm), and enzyme substrate ratio (2 : 3) were found to be the best fits for maximum production of low size AuNPs. This demonstrates that in initial few hours, a quick conversion of the ionic gold precursor takes place into metallic gold nuclei, trailed by crystal growth via coalescence of small nuclei. Subsequently, it can be concluded that coalescence processes drive the crystal growth process of AuNPs over a time interval and finally leads to saturation and no newer particle formation in the solution.


Assuntos
Ouro/química , Nanopartículas Metálicas/química , Pseudoalteromonas
9.
Front Psychol ; 11: 714, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32373034

RESUMO

The present paper discusses how cultural context can be used as an essential tool in the diagnosis of mental disorders as well as in segregating individuals with normal or abnormal personality functioning. Further, such information about the culture can be used to diagnose individuals specifically with borderline personality disorder (BPD). BPD is a mental illness marked by impulsivity and instability in interpersonal relationships, moods, and self-image. We discuss how culture shapes patterns of behavior in the individual with BPD. An extensive review of manifestation of BPD in eastern countries suggests that culture and social norms are the two crucial factors, which can differentiate normal and abnormal behavioral patterns in BPD. For example, the social norms shape and give directions to our interpersonal functioning, emotions are experienced within the cultural context and expressed accordingly, and self is a reflection and representation of one's culture. Hence, these constructs of BPD (such as interpersonal functioning, emotions, and self) indicate that they are experienced differently in different cultures and vary on the continuum of normal to abnormal personality functioning. The cultural manifestation of BPD helps to understand the specific profile of the three constructs of BPD in an eastern culture like India. A synthesis of studies on prevalence, development, and symptom presentation of BPD in the Indian context is emphasized to support the personality functioning within the constructs of BPD. The literature review indicates that BPD research in India is based only on a few cases and a tiny sample of such patients. However, studies on BPD in the cultural context are minimal and incomprehensive. Hence, it suggests the importance of more empirical studies concerning the appropriate diagnosis of BPD within the cultural context of India.

10.
3 Biotech ; 9(11): 399, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31656737

RESUMO

The goal of this research was to explore the preliminary anticancer properties of five plants namely Calotropis procera, Moringa oleifera, Millettia pinnata, Basela alba and Euphorbia neriifolia available in Jharkhand which is used for the medicinal purpose by local tribes. In the present study, plant leaves from five species were collected, dried and extracted with solvents of increasing polarity, followed by assessment of their cytotoxicity in A549 non-small-cell lung cancer cells. In the antimicrobial assay, the methanol extract of the M. pinnata leaves exhibited comparatively higher zone of inhibition of 0.7 ± 0.20 cm against a Salmonella typhi culture than the other extracts. M. pinnata leaves extract also displayed the maximum percentage inhibition in the DPPH, 83.97 ± 0.01 FRAP, 193.14 ± 3.01 mM assays. Furthermore, the cytotoxicity of the chloroform (37.45 ± 1.04) and ethyl acetate extracts (34.20 ± 0.81) of M. pinnata against A549 cells was found relatively higher with respect to another extract. In contrast, a study with the L132 normal epithelial lung cell line revealed less toxicity from the chloroform extract (0.33 ± 0.19) compared to the ethyl acetate extract (6.65 ± 0.59). Based on these findings, phytochemical investigation on chloroform and ethyl acetate extract of M. pinnata was performed using UPLC-ESI-MS/MS analysis revealing the presence of ß-sitosterol, lanceolatin B, karanjin, and stigmasterol. Congruently, a complete phytochemical and cytotoxic investigation of the M. pinnata extract constituents might infer the potency of this extract/s as anticancer, antioxidant and antimicrobial agents.

11.
Prog Brain Res ; 247: 23-46, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31196436

RESUMO

Most of the previous research in the area of cognitive psychology or cognitive neuroscience focused on studying negative emotions and argued that the negative emotional stimuli capture attention involuntarily as compared to neutral stimuli. However, in the last decades, researchers started paying attention in studying positive emotions also as positive emotions have evolutionary significance and are essential for many aspects of our life. The theme of this chapter is to present an overview of research in the area of positive emotions, and make a case that positively-valenced stimulus is prioritized over others. Primarily, when attentional resources are not constrained, many studies have shown that similar to negative stimuli, positive stimuli also capture attention automatically irrespective of whether they are relevant or irrelevant to the primary task. It suggests a fundamental prioritization of these stimuli by the cognitive/motivational system. However, when attentional resources are constrained, only positive or high rewarding stimuli win the competition for attentional resources compared to negative or stimuli associated with high punishment. Positive or high rewarding stimuli also receive priority in temporal selection, when attention is constrained. Theoretical implications of these results have been discussed. Possible cognitive and neural mechanisms have been proposed underlying these effects.


Assuntos
Atenção/fisiologia , Emoções/fisiologia , Motivação/fisiologia , Recompensa , Cognição/fisiologia , Humanos , Estimulação Luminosa/métodos
12.
ACS Chem Biol ; 14(5): 949-958, 2019 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-30969758

RESUMO

Conventional treatments to combat the tuberculosis (TB) epidemic are falling short, thus encouraging the search for novel antitubercular drugs acting on unexplored molecular targets. Several whole-cell phenotypic screenings have delivered bioactive compounds with potent antitubercular activity. However, their cellular target and mechanism of action remain largely unknown. Further evaluation of these compounds may include their screening in search for known antitubercular drug targets hits. Here, a collection of nearly 1400 mycobactericidal compounds was screened against Mycobacterium tuberculosis NaMN adenylyltransferase ( MtNadD), a key enzyme in the biogenesis of NAD cofactor that was recently validated as a new drug target for dormant and active tuberculosis. We found three chemotypes that efficiently inhibit MtNadD in the low micromolar range in vitro. SAR and cheminformatics studies of commercially available analogues point to a series of benzimidazolium derivatives, here named N2, with bactericidal activity on different mycobacteria, including M. abscessus, multidrug-resistant M. tuberculosis, and dormant M. smegmatis. The on-target activity was supported by the increased resistance of an M. smegmatis strain overexpressing the target and by a rapid decline in NAD(H) levels. A cocrystal structure of MtNadD with N2-8 inhibitor reveals that the binding of the inhibitor induced the formation of a new quaternary structure, a dimer-of-dimers where two copies of the inhibitor occupy symmetrical positions in the dimer interface, thus paving the way for the development of a new generation of selective MtNadD bioactive inhibitors. All these results strongly suggest that pharmacological inhibition of MtNadD is an effective strategy to combat dormant and resistant Mtb strains.


Assuntos
Antituberculosos/farmacologia , Mycobacterium tuberculosis/efeitos dos fármacos , NAD/antagonistas & inibidores , Nicotinamida-Nucleotídeo Adenililtransferase/antagonistas & inibidores , Farmacorresistência Bacteriana , Testes de Sensibilidade Microbiana , Mycobacterium tuberculosis/crescimento & desenvolvimento , Mycobacterium tuberculosis/metabolismo , NAD/biossíntese , Nicotinamida-Nucleotídeo Adenililtransferase/metabolismo , Relação Estrutura-Atividade
13.
J Immunol ; 202(10): 2924-2944, 2019 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-30988120

RESUMO

Clonal expansion of B cell chronic lymphocytic leukemia (B-CLL) occurs within lymphoid tissue pseudofollicles. IL-15, a stromal cell-associated cytokine found within spleens and lymph nodes of B-CLL patients, significantly boosts in vitro cycling of blood-derived B-CLL cells following CpG DNA priming. Both IL-15 and CpG DNA are elevated in microbe-draining lymphatic tissues, and unraveling the basis for IL-15-driven B-CLL growth could illuminate new therapeutic targets. Using CpG DNA-primed human B-CLL clones and approaches involving both immunofluorescent staining and pharmacologic inhibitors, we show that both PI3K/AKT and JAK/STAT5 pathways are activated and functionally important for IL-15→CD122/ɣc signaling in ODN-primed cells expressing activated pSTAT3. Furthermore, STAT5 activity must be sustained for continued cycling of CFSE-labeled B-CLL cells. Quantitative RT-PCR experiments with inhibitors of PI3K and STAT5 show that both contribute to IL-15-driven upregulation of mRNA for cyclin D2 and suppression of mRNA for DNA damage response mediators ATM, 53BP1, and MDC1. Furthermore, protein levels of these DNA damage response molecules are reduced by IL-15, as indicated by Western blotting and immunofluorescent staining. Bioinformatics analysis of ENCODE chromatin immunoprecipitation sequencing data from cell lines provides insight into possible mechanisms for STAT5-mediated repression. Finally, pharmacologic inhibitors of JAKs and STAT5 significantly curtailed B-CLL cycling when added either early or late in a growth response. We discuss how the IL-15-induced changes in gene expression lead to rapid cycling and possibly enhanced mutagenesis. STAT5 inhibitors might be an effective modality for blocking B-CLL growth in patients.


Assuntos
Ciclina D2/imunologia , Dano ao DNA/imunologia , Interleucina-15/imunologia , Leucemia Linfocítica Crônica de Células B/imunologia , Proteínas Proto-Oncogênicas c-akt/imunologia , Fator de Transcrição STAT5/imunologia , Transdução de Sinais/imunologia , Proteínas Adaptadoras de Transdução de Sinal/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteínas Mutadas de Ataxia Telangiectasia/imunologia , Proteínas de Ciclo Celular/imunologia , Linhagem Celular Tumoral , Feminino , Regulação Neoplásica da Expressão Gênica/imunologia , Humanos , Leucemia Linfocítica Crônica de Células B/patologia , Masculino , Pessoa de Meia-Idade , Proteína 1 de Ligação à Proteína Supressora de Tumor p53/imunologia , Regulação para Cima/imunologia
16.
J Contemp Dent Pract ; 20(12): 1402-1405, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32381840

RESUMO

BACKGROUND: Chlorhexidine is considered one of the options for the management of periodontal diseases. This present study was conducted to assess the usefulness of controlled-release chlorhexidine chip in addition to scaling and root planning (SRP) while comparing with SRP alone in the treatment of chronic periodontitis clinically, microbiologically and radiographically. MATERIALS AND METHODS: This study included 20 patients age ranged from 30 to 55 years with chronic periodontitis. A total of 40 sites were selected. Two bilateral pockets with probing depth 4-6 mm were put in test and control groups in all subjects. SRP plus Periochip™ was used in the test group and SRP alone in the control group. In all subjects, all the analysis such as clinical parameters, the radiographic and anaerobic culture of P. gingivalis, T. denticola, and T. forsythia were performed and compared in both groups at baseline and 3 months interval. RESULTS: There was a significant improvement in all clinical and radiographic parameters in the test group in comparison to control group. Total colony counts also reduced significantly. At baseline, Tf was recovered from 15 test group sites and 16 control group sites, Pg from 14 test group and 14 control group sites, Td from 16 test group and 15 control group sites. At 3 months, Tf was recovered from 4 test group and 10 control group sites, Pg from 3 test group and 9 control group sites, Td from 4 test group and 8 control group site. CONCLUSION: Periochip™ placement as an adjunct to SRP, showed promising results when compared to SRP alone. CLINICAL SIGNIFICANCE: Periochip is considered the best treatment option in the treatment of chronic periodontitis.


Assuntos
Anti-Infecciosos Locais , Periodontite Crônica , Adulto , Clorexidina , Preparações de Ação Retardada , Raspagem Dentária , Humanos , Pessoa de Meia-Idade
17.
Mar Drugs ; 17(12)2019 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-31888140

RESUMO

Tuberculosis is the leading cause of death due to infectious disease worldwide. There is an urgent need for more effective compounds against this pathogen to control the disease. Investigation of the anti-mycobacterial activity of a deep-water sponge of the genus Plakina revealed the presence of a new steroidal alkaloid of the plakinamine class, which we have given the common name plakinamine P. Its structure is most similar to plakinamine L, which also has an acyclic side chain. Careful dissection of the nuclear magnetic resonance data, collected in multiple solvents, suggests that the dimethyl amino group at the 3 position is in an equatorial rather than axial position unlike previously reported plakinamines. Plakinamine P was bactericidal against M. tuberculosis, and exhibited moderate activity against other mycobacterial pathogens, such as M. abscessus and M. avium. Furthermore, it had low toxicity against J774 macrophages, yielding a selectivity index (SI, or IC50/MIC) of 8.4. In conclusion, this work provides a promising scaffold to the tuberculosis drug discovery pipeline. Future work to determine the molecular target of this compound may reveal a pathway essential for M. tuberculosis survival during infection.


Assuntos
Alcaloides/química , Alcaloides/farmacologia , Antituberculosos/farmacologia , Mycobacterium tuberculosis/efeitos dos fármacos , Esteroides/química , Esteroides/farmacologia , Antituberculosos/química , Estrutura Molecular
18.
Psychol Res ; 83(8): 1798-1807, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29797045

RESUMO

Stimuli that reliably herald the availability of rewards or punishers can acquire value associations, potentially imbuing them with emotional significance and attentional prioritization. Previous work has shown that an emotional stimulus (prime) presented just prior to an attention-demanding task disrupts performance in a lateralized manner that is independent of the prime's emotional valence. Here, we asked whether neutral stimuli with acquired value associations would similarly disrupt attention. In two experiments, adult participants first learned to associate specific face or chair stimuli with a high or low probability of either winning or losing points. These conditioned stimuli then served as primes in a speeded letter-search task. Primes with high versus low outcome probability, regardless of valence, slowed search for targets appearing in the left but not the right visual hemifield, mirroring previous results using emotional primes, and suggesting that motivational mechanisms that compete for control with non-emotional cognitive processes are right-lateralized in the human brain.


Assuntos
Atenção/fisiologia , Comportamento de Escolha , Cognição/fisiologia , Percepção Visual/fisiologia , Adulto , Aprendizagem por Associação , Emoções , Face , Feminino , Humanos , Masculino , Motivação , Reconhecimento Psicológico , Adulto Jovem
19.
Mar Drugs ; 16(10)2018 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-30308948

RESUMO

There is an acute need for new and effective agents to treat infectious diseases. We conducted a screening program to assess the potential of mangrove-derived endophytic fungi as a source of new antibiotics. Fungi cultured in the presence and absence of small molecule epigenetic modulators were screened against Mycobacterium tuberculosis and the ESKAPE panel of bacterial pathogens, as well as two eukaryotic infective agents, Leishmania donovani and Naegleria fowleri. By comparison of bioactivity data among treatments and targets, trends became evident, such as the result that more than 60% of active extracts were revealed to be selective to a single target. Validating the technique of using small molecules to dysregulate secondary metabolite production pathways, nearly half (44%) of those fungi producing active extracts only did so following histone deacetylase inhibitory (HDACi) or DNA methyltransferase inhibitory (DNMTi) treatment.


Assuntos
Doenças Transmissíveis/tratamento farmacológico , Endófitos/metabolismo , Fungos/metabolismo , Animais , Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Linhagem Celular , Descoberta de Drogas/métodos , Inibidores de Histona Desacetilases/farmacologia , Metiltransferases/antagonistas & inibidores , Camundongos
20.
J Appl Clin Med Phys ; 19(6): 99-108, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30221462

RESUMO

PURPOSE: The aim of this project was to design and manufacture a cost-effective end-to-end (E2E) phantom for quantifying the geometric and dosimetric accuracy of a linear accelerator based, multi-target single-isocenter (MTSI) frameless stereotactic radiosurgery (SRS) technique. METHOD: A perspex Multi-Plug device from a Sun Nuclear ArcCheck phantom (Sun Nuclear, Melbourne, FL) was enhanced to make it more applicable for MTSI SRS E2E testing. The following steps in the SRS chain were then analysed using the phantom: magnetic resonance imaging (MRI) distortion, planning computed tomography (CT) scan and MRI image registration accuracy, phantom setup accuracy using CBCT, dosimetric accuracy using ion chamber, planar film dose measurements and coincidence of linear accelerator mega-voltage (MV), and kilo-voltage (kV) isocenters using Winston-Lutz testing (WLT). RESULTS: The dedicated E2E phantom was able to successfully quantify the geometric and dosimetric accuracy of the MTSI SRS technique. MRI distortions were less than 0.5 mm, or half a voxel size. The average MRI-CT registration accuracy was 0.15 mm (±0.31 mm), 0.20 mm (±0.16 mm), and 0.39 mm (±0.11 mm) in the superior/inferior, left/right and, anterior/posterior directions, respectively. The phantom setup accuracy using CBCT was better than 0.2 mm and 0.1°. Point dose measurements were within 5% of the treatment planning system predicted dose. The comparison of planar film doses to the planning system dose distributions, performed using gamma analysis, resulted in pass rates greater than 97% for 3%/1 mm gamma criteria. Finally, off-axis WLT showed MV/kV coincidence to be within 1 mm for off-axis distances up to 60 mm. CONCLUSION: A novel, versatile and cost-effective phantom for comprehensive E2E testing of MTSI SRS treatments was developed, incorporating multiple detector types and fiducial markers. The phantom is capable of quantifying the accuracy of each step in the MTSI SRS planning and treatment process.


Assuntos
Tomografia Computadorizada de Feixe Cônico/métodos , Imageamento por Ressonância Magnética/métodos , Neoplasias/cirurgia , Aceleradores de Partículas/normas , Imagens de Fantasmas , Radiocirurgia/métodos , Planejamento da Radioterapia Assistida por Computador/métodos , Humanos , Processamento de Imagem Assistida por Computador/métodos , Dosagem Radioterapêutica , Radioterapia de Intensidade Modulada/métodos
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