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1.
Talanta ; 274: 126031, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38574536

RESUMO

Real-time monitoring of nitrite and nitrate is crucial for maintaining soil health and promoting plant growth. In this study, a portable ion-chromatograph (IC, Aquamonitrix) analyser, coupled with a field-applicable ultrasonic-assisted extraction method, was utilised for in-field determination of nitrate and nitrite in soils. This is the first application of this type of analyser to soil nutrients. On-site analysis of soil from a local sports field showed 94.8 ± 4.3 µg g-1 nitrate, with LODs of 32.0 µg g-1 for nitrate and 5.4 µg g-1 for nitrite. The results were in close agreement with those obtained using a conventional lab-based IC. Relative standard deviations (%RSDs) for soil analysis using Aquamonitrix were consistently below 10%. The obtained average recoveries of samples spiked with nitrite were 100% and 104% for the portable IC and conventional IC, respectively. Furthermore, to assess the suitability of portable IC for samples with high organic matter content, various natural organic fertilisers were extracted and analysed. The results showed 16.2 ± 0.7 µg g-1 nitrite and 28.5 ± 5.6 µg g-1 nitrate in sheep manure samples with LODs of 2.0 µg g-1 for nitrite and 12.0 µg g-1 for nitrate. The portable IC system was further demonstrated via real-time on-site analysis of soil pore-water acquired using a portable battery-based ceramic pore-water sampler. A continuous increase in nitrate concentration over time was observed (from 80 to 148 µg mL-1) in the soil pore-water in a vegetable garden four days after heavy rain. Unlike conventionally sampled natural waters, 7-day storage of the studied pore water samples revealed no changes in nitrate concentrations. An average of 558 ± 51 µg mL-1 nitrate was detected in the soil pore-water samples analysed on a spinach farm, immediately after irrigation.

2.
Int J STD AIDS ; 35(1): 71-73, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37728103

RESUMO

People living with HIV (PLWH) are at higher risk of reactivation of Chagas disease, a neglected tropical disease, caused by Trypanosoma cruzi. There are no data from UK HIV clinics on the prevalence of T. cruzi. We implemented T. cruzi screening at our clinic as part of routine care for PLWH with epidemiological risk factors. Among 86 patients screened, none had positive serology: one seropositive patient was identified due to increased clinician awareness. Implementing T. cruzi screening as part of routine clinical care was feasible, though labour intensive and identified at-risk individuals.


Assuntos
Doença de Chagas , Infecções por HIV , Trypanosoma cruzi , Humanos , Trypanosoma cruzi/fisiologia , Doença de Chagas/diagnóstico , Doença de Chagas/epidemiologia , Fatores de Risco , Infecções por HIV/complicações , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Reino Unido/epidemiologia
3.
RSC Med Chem ; 14(5): 934-946, 2023 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-37252102

RESUMO

The phosphatidylinositol 5-phosphate 4-kinases (PI5P4Ks) play a central role in regulating cell signalling pathways and, as such, have become therapeutic targets for diseases such as cancer, neurodegeneration and immunological disorders. Many of the PI5P4Kα inhibitors that have been reported to date have suffered from poor selectivity and/or potency and the availability of better tool molecules would facilitate biological exploration. Herein we report a novel PI5P4Kα inhibitor chemotype that was identified through virtual screening. The series was optimised to deliver ARUK2002821 (36), a potent PI5P4Kα inhibitor (pIC50 = 8.0) which is selective vs. other PI5P4K isoforms and has broad selectivity against lipid and protein kinases. ADMET and target engagement data are provided for this tool molecule and others in the series, as well as an X-ray structure of 36 solved in complex with its PI5P4Kα target.

4.
Sci Rep ; 13(1): 6512, 2023 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-37081106

RESUMO

With the ever-pressing challenges of societal ageing, robotic technologies for older people are increasingly portrayed as a solution for better independent living for longer. However, the application of human-following robots for elderly citizens has not yet been considered, and any prospective benefits offered by the technology for active ageing have previously been overlooked. This qualitative research aimed to explore older people's needs and requirements towards the human-following robot through the reflexive thematic analysis of semi-structured interview data from 17 independent older adults, supported by a video-based demonstration of the robot. The results indicate that older people believed that human-following robot has the potential to provide social benefits to an independent older adult by encouraging walking trips and prompting social interaction with others in the community. Practical limitations and cost of the robot are barriers to adoption at present. The findings indicate that there is potential for human-following robots to support active ageing, through increasing opportunities for the social participation of an older adult, but further development of the robot is needed for this potential to be realised.


Assuntos
Robótica , Humanos , Idoso , Robótica/métodos , Vida Independente , Envelhecimento , Pesquisa Qualitativa , Tecnologia
5.
Clin Infect Dis ; 77(4): 593-605, 2023 08 22.
Artigo em Inglês | MEDLINE | ID: mdl-37052343

RESUMO

BACKGROUND: There are conflicting data regarding baseline determinants of virological nonsuppression outcomes in persons with human immunodeficiency virus (HIV) starting antiretroviral treatment (ART). We evaluated the impact of different baseline variables in the RESPOND cohort. METHODS: We included treatment-naive participants aged ≥18 who initiated 3-drug ART, in 2014-2020. We assessed the odds of virological suppression (VS) at weeks 48 and 96 using logistic regression. Viral blips, low-level viremia (LLV), residual viremia (RV), and virological failure (VF) rates were assessed using Cox regression. RESULTS: Of 4310 eligible participants, 72% started integrase strand transfer inhibitor (INSTI)-based regimens. At 48 and 96 weeks, 91.0% and 93.3% achieved VS, respectively. At 48 weeks, Kaplan-Meier estimates of rates were 9.6% for viral blips, 2.1% for LLV, 22.2% for RV, and 2.1% for VF. Baseline HIV-1 RNA levels >100 000 copies/mL and CD4+ T-cell counts ≤200/µL were negatively associated with VS at weeks 48 (adjusted odds ratio, 0.51 [95% confidence interval, .39-.68] and .40 [.27-.58], respectively) and 96 and with significantly higher rates of blips, LLV, and RV. CD4+ T-cell counts ≤200/µL were associated with higher risk of VF (adjusted hazard ratio, 3.12 [95% confidence interval, 2.02-4.83]). Results were consistent in those starting INSTIs versus other regimens and those starting dolutegravir versus other INSTIs. CONCLUSIONS: Initial high HIV-1 RNA and low CD4+ T-cell counts are associated with lower rates of VS at 48 and 96 weeks and higher rates of viral blips, LLV, and RV. Low baseline CD4+ T-cell counts are associated with higher VF rates. These associations remain with INSTI-based and specifically with dolutegravir-based regimens. These findings suggest that the impact of these baseline determinants is independent of the ART regimen initiated.


Assuntos
Infecções por HIV , Inibidores de Integrase de HIV , HIV-1 , RNA Viral , Humanos , Linfócitos T CD4-Positivos , Estudos de Coortes , Infecções por HIV/tratamento farmacológico , Inibidores de Integrase de HIV/uso terapêutico , HIV-1/genética , HIV-1/isolamento & purificação , Estudos Prospectivos , Carga Viral , Viremia/tratamento farmacológico , RNA Viral/sangue
6.
Pathogens ; 12(2)2023 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-36839468

RESUMO

The culture media recommended for the isolation and enumeration of the Fusarium spp. lack selectivity for Fusarium graminearum. Five fungicides-Amistar® (250 g·L-1 azoxystrobin), Filan® (500 g·kg-1 boscalid), Comet® 200 (200 g·L-1 pyraclostrobin), Imtrex® (62.5 g·L-1 fluxapyroxad), Poraz® (450 g·L-1 prochloraz)-were investigated for their potential as selective inhibitors in culture media for the isolation of F. graminearum from soil and plant material. Based on the screening, fluxapyroxad was further tested for selective inhibition for the isolation of F. graminearum from soil. Additionally, selective media were compared for the isolation of F. graminearum from plant material. The fungicides tested did not prove to be effective inhibitors for the development of selective media. For the detection of F. graminearum in plant material, Czapek Dox propiconazole dichloran agar was found to be a better medium than Komada's media, as the former resulted in colonies with darker pigmentation over a shorter incubation time and appeared to have a less inhibitory effect on F. graminearum growth.

7.
Sensors (Basel) ; 23(2)2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36679617

RESUMO

Connected and automated vehicles have the potential to deliver significant environmental, safety, economic and social benefits. The key advancement for automated vehicles with higher levels of automation (SAE Level 4 and over) is fail-operational. One possible solution for the failsafe mode of automated vehicles is a 5G-enabled teleoperation system controlled by remote drivers. However, knowledge is missing regarding understanding of the human-machine interaction in teleoperation from the perspective of remote drivers. To address this research gap, this study qualitatively investigated the acceptance, attitudes, needs and requirements of remote drivers when teleoperating a 5G-enabled Level 4 automated vehicle (5G L4 AV) in the real world. The results showed that remote drivers are positive towards the 5G L4 AV. They would like to constantly monitor the driving when they are not controlling the vehicle remotely. Improving their field of vision for driving and enhancing the perception of physical motion feedback are the two key supports required by remote drivers in 5G L4 AVs. The knowledge gained in this study provides new insights into facilitating the design and development of safe, effective and user-friendly teleoperation systems in vehicle automation.


Assuntos
Condução de Veículo , Veículos Autônomos , Humanos , Automação/métodos , Atitude , Lacunas de Evidências , Acidentes de Trânsito
8.
AIDS ; 37(1): 161-171, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-36250262

RESUMO

OBJECTIVE: Deaths due to suicide, substance use and violence/accident may reflect similar risk factors and overlap in their classification. This study aimed to investigate incidence and risk factors of mortality among people with HIV (PWH) due to these three related causes. DESIGN: Prospectively collected data from PWH at least 18 years old and under active follow-up in the EuroSIDA study from 2007 to 2019 were analysed. METHODS: Cause-specific Cox regression analysis was used to assess risk factors. RESULTS: A total of 17 881 participants were included, comprising 149 327 person-years of follow-up (PYFU). Forty participants died by suicide {incidence rate [IR] [95% confidence interval (CI)]: 0.3/1000 PYFU (0.2, 0.4)} 93 from substance use [IR (95% CI): 0.6/1000 PYFU (0.5, 0.8)], and 57 by violence/accident [IR (95% CI): 0.4/1000 PYFU (0.3, 0.5)]. An AIDS diagnosis within the last 12 months was associated with nine-fold increased risk of suicide vs. no history of AIDS [adjusted hazard ratio (aHR): 9.06; 95% CI: 2.07, 39.7]. Male gender was associated with double the risk of violent/accidental death (aHR: 2.28; 95% CI: 1.09, 4.78). PWH in Eastern Europe and those who acquired HIV by injection drug use (IDU) demonstrated a greater risk of death due to substance use or violence/accident. CONCLUSIONS: The association between a recent diagnosis of AIDS and suicide highlights a critical period for intervention. HIV infection acquired through IDU demonstrated an expected relationship with death due to substance use and violent/accidental deaths. Increased risk of death due to substance use and violence/accident in Eastern Europe demands investigation into specific differences that may drive that association.


Assuntos
Infecções por HIV , Transtornos Relacionados ao Uso de Substâncias , Masculino , Humanos , Adolescente , Infecções por HIV/complicações , Incidência , Violência , Fatores de Risco , Transtornos Relacionados ao Uso de Substâncias/complicações , Transtornos Relacionados ao Uso de Substâncias/epidemiologia
9.
J Med Chem ; 66(1): 804-821, 2023 01 12.
Artigo em Inglês | MEDLINE | ID: mdl-36516442

RESUMO

Owing to their central role in regulating cell signaling pathways, the phosphatidylinositol 5-phosphate 4-kinases (PI5P4Ks) are attractive therapeutic targets in diseases such as cancer, neurodegeneration, and immunological disorders. Until now, tool molecules for these kinases have been either limited in potency or isoform selectivity, which has hampered further investigation of biology and drug development. Herein we describe the virtual screening workflow which identified a series of thienylpyrimidines as PI5P4Kγ-selective inhibitors, as well as the medicinal chemistry optimization of this chemotype, to provide potent and selective tool molecules for further use. In vivo pharmacokinetics data are presented for exemplar tool molecules, along with an X-ray structure for ARUK2001607 (15) in complex with PI5P4Kγ, along with its selectivity data against >150 kinases and a Cerep safety panel.


Assuntos
Neoplasias , Transdução de Sinais , Humanos , Isoformas de Proteínas , Encéfalo , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/química
10.
Pathogens ; 11(12)2022 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-36558761

RESUMO

Fusarium graminearum is the most important causal agent of head blight in wheat, and stalk and ear rot in maize. A field experiment was conducted to investigate the effect of incorporation of Brassicaceae cover crops on Fusarium graminearum in a wheat-maize rotation. Five species belonging to Brassicaceae (Brassica juncea, Eruca sativa, Raphanus sativus, B. carinata, B. oleracea var. caulorapa L.) were used in the field experiment to investigate their potential to suppress F. graminearum inoculum in soil, disease incidence in maize and to reduce subsequent mycotoxin contamination in maize. Brassica juncea was found to contain the highest glucosinolate concentration in shoots (31 µmol g-1). Severity of ear rot and stalk rot in maize was not significantly reduced in the amended plots. Incorporation of R. sativus 'Terranova' significantly decreased the amount of F. graminearum DNA by 58% compared with the cultivated fallow treatment, however the DNA concentration was not significantly different to fallow uncultivated. Fusarium graminearum DNA and deoxynivalenol in maize was 50% lower after incorporation of B. oleracea var. caulorapa L. compared to after fallow treatment but the difference was not significant. The brassica crops used in the present field experiment were not effective in suppressing F. graminearum, therefore further studies to optimise the current approach are recommended.

11.
Pathogens ; 11(11)2022 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-36365039

RESUMO

Frequent occurrences of high levels of Fusarium mycotoxins have been recorded in Norwegian oat grain. To elucidate the influence of tillage operations on the development of Fusarium and mycotoxins in oat grain, we conducted tillage trials with continuous oats at two locations in southeast Norway. We have previously presented the content of Fusarium DNA detected in straw residues and air samples from these fields. Grain harvested from ploughed plots had lower levels of Fusarium langsethiae DNA and HT-2 and T-2 toxins (HT2 + T2) compared to grain from harrowed plots. Our results indicate that the risk of F. langsethiae and HT2 + T2 contamination of oats is reduced with increasing tillage intensity. No distinct influence of tillage on the DNA concentration of Fusarium graminearum and Fusarium avenaceum in the harvested grain was observed. In contrast to F. graminearum and F. avenaceum, only limited contents of F. langsethiae DNA were observed in straw residues and air samples. Still, considerable concentrations of F. langsethiae DNA and HT2 + T2 were recorded in oat grain harvested from these fields. We speculate that the life cycle of F. langsethiae differs from those of F. graminearum and F. avenaceum with regard to survival, inoculum production and dispersal.

12.
Sensors (Basel) ; 22(21)2022 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-36366119

RESUMO

The rate of urbanization in Europe is increasing rapidly. Traffic congestion has become one of the biggest challenges for cities. Additionally, thousands of people die each year in accidents on European roads. In addition, road transport is one of the biggest reasons for the increase in air pollution and greenhouse gases in Europe. To solve these problems, cooperative intelligent transport systems (C-ITS) have accelerated in Europe, after more than ten years of research and development. The European Commission has carried out significant work in this field in recent years and has prepared a strategy document for the deployment of C-ITS services in Europe. The Commission considers that C-ITS have significant potential in reducing the negative effects of road traffic and expects these systems to deploy rapidly in European cities. However, in order to achieve this, it is imperative to clearly identify the needs of cities in implementing and managing these systems, the extent to which these systems will respond to different mobility problems of the cities, and the important barriers to widespread deployment. This study focused on qualitatively examining the C-ITS deployment from the stakeholder perspective. The knowledge generated is useful to facilitate the large-scale future deployment of C-ITS.


Assuntos
Poluição do Ar , Humanos , Cidades , Europa (Continente) , Meios de Transporte
13.
Antibiotics (Basel) ; 11(9)2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-36140028

RESUMO

Fusarium graminearum is a globally important cereal pathogen, causing head blight in wheat, resulting in yield losses and mycotoxin contamination. Currently, triazole fungicides are used to suppress Fusarium graminearum, however, the declining effectiveness of triazoles and concerns over the safety of pesticides have led to the pursuit of safe alternative crop protection strategies such as biofumigation. In the present study, species belonging to Brassicaceae (Brassica juncea, Raphanus sativus, Eruca sativa) were assessed for their biofumigation potential against F. graminearum and the glucosinolate profile of the brassicas was determined. In Petri dishes, mycelial plugs of Fusarium graminearum were exposed to frozen/defrosted leaf discs of brassicas collected at early-leaf, stem-extension, and early-bud stages. Additionally, F. graminearum inoculum was incubated in soil amended with chopped tissues of brassicas in a closed jar experiment. Glucosinolate analysis of the leaf tissue of brassicas revealed that the total glucosinolate concentration of B. juncea 'Brons' increased with advancing growth stage (24.5-51.9 µmol g-1). Brassica juncea leaf discs were effective against mycelial growth, while the sinigrin content in the leaf tissue corresponded to the level of suppression. At the stem-extension and early-bud stages, B. juncea 'Brons' showed 87-90% suppression with four leaf discs, and 100% suppression with eight leaf discs. Brassica juncea 'Caliente Rojo' leaf discs collected at the stem-extension stage showed 94% inhibition with eight discs. In the closed jar experiment, each brassica species significantly suppressed F. graminearum inoculum by 41-55%. The findings suggest that the brassica species investigated in the present study could be effective in reducing the inoculum of F. graminearum in soil prior to cereal production.

14.
AIDS Res Ther ; 19(1): 38, 2022 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-35933352

RESUMO

INTRODUCTION: Data on safety and effectiveness of RPV from the real-world setting as well as comparisons with other NNRTIs such as efavirenz (EFV) remain scarce. METHODS: Participants of EuroSIDA were included if they had started a RPV- or an EFV-containing regimen over November 2011-December 2017. Statistical testing was conducted using non-parametric Mann-Whitney U test and Chi-square test. A logistic regression model was used to compare participants' characteristics by treatment group. Kaplan-Meier analysis was used to estimate the cumulative risk of virological failure (VF, two consecutive values > 50 copies/mL). RESULTS: 1,355 PLWH who started a RPV-based regimen (11% ART-naïve), as well as 333 initiating an EFV-containing regimen were included. Participants who started RPV differed from those starting EFV for demographics (age, geographical region) and immune-virological profiles (CD4 count, HIV RNA). The cumulative risk of VF for the RPV-based group was 4.5% (95% CI 3.3-5.7%) by 2 years from starting treatment (71 total VF events). Five out of 15 (33%) with resistance data available in the RPV group showed resistance-associated mutations vs. 3/13 (23%) among those in the EFV group. Discontinuations due to intolerance/toxicity were reported for 73 (15%) of RPV- vs. 45 (30%) of EFV-treated participants (p = 0.0001). The main difference was for toxicity of central nervous system (CNS, 3% vs. 22%, p < 0.001). CONCLUSION: Our estimates of VF > 50 copies/mL and resistance in participants treated with RPV were similar to those reported by other studies. RPV safety profile was favourable with less frequent discontinuation due to toxicity than EFV (especially for CNS).


Assuntos
Fármacos Anti-HIV , Infecções por HIV , HIV-1 , Fármacos Anti-HIV/efeitos adversos , Infecções por HIV/tratamento farmacológico , HIV-1/genética , Humanos , Rilpivirina/uso terapêutico , Resultado do Tratamento , Carga Viral
15.
Sci Rep ; 12(1): 11645, 2022 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-35804087

RESUMO

The emergence of the level 3 automated vehicles (L3 AVs) can enable drivers to be completely disengaged from driving and safely perform other non-driving related tasks, but sometimes their takeover of control of the vehicle is required. The takeover of control is an important human-machine interaction in L3 AVs. However, little research has focused on investigating the effect of gender on takeover performance. In order to fill this research gap, a driving simulator study with 76 drivers (33 females and 43 males) was conducted. The participants took over control from L3 AVs, and the timing and quality of takeover were measured. The results show that although there was no significant difference in most of the measurements adopted to quantify takeover performance between female and male. Gender did affect takeover performance slightly, with women exhibited slightly better performance than men. Compared to men, women exhibited a smaller percentage of hasty takeovers and slightly faster reaction times as well as slightly more stable operation of the steering wheel. The findings highlight that it is important for both genders to recognise they can use and interact with L3 AVs well, and more hands-on experience and teaching sessions could be provided to deepen their understanding of L3 AVs. The design of the car interiors of L3 AVs should also take into account gender differences in the preferences of users for different non-driving related tasks.


Assuntos
Condução de Veículo , Veículos Autônomos , Desempenho Psicomotor , Condução de Veículo/psicologia , Feminino , Humanos , Masculino , Desempenho Psicomotor/fisiologia , Tempo de Reação/fisiologia , Fatores Sexuais
16.
Toxins (Basel) ; 14(5)2022 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-35622560

RESUMO

Over recent decades, the Norwegian cereal industry has had major practical and financial challenges associated with the occurrence of Fusarium head blight (FHB) pathogens and their associated mycotoxins in cereal grains. Deoxynivalenol (DON) is one of the most common Fusarium-mycotoxins in Norwegian oats, however T-2 toxin (T2) and HT-2 toxin (HT2) are also commonly detected. The aim of our study was to rank Nordic spring oat varieties and breeding lines by content of the most commonly occurring Fusarium mycotoxins (DON and HT2 + T2) as well as by the DNA content of their respective producers. We analyzed the content of mycotoxins and DNA of seven fungal species belonging to the FHB disease complex in grains of Nordic oat varieties and breeding lines harvested from oat field trials located in the main cereal cultivating district in South-East Norway in the years 2011-2020. Oat grains harvested from varieties with a high FHB resistance contained on average half the levels of mycotoxins compared with the most susceptible varieties, which implies that choice of variety may indeed impact on mycotoxin risk. The ranking of oat varieties according to HT2 + T2 levels corresponded with the ranking according to the DNA levels of Fusarium langsethiae, but differed from the ranking according to DON and Fusarium graminearum DNA. Separate tests are therefore necessary to determine the resistance towards HT2 + T2 and DON producers in oats. This creates practical challenges for the screening of FHB resistance in oats as today's screening focuses on resistance to F. graminearum and DON. We identified oat varieties with generally low levels of both mycotoxins and FHB pathogens which should be preferred to mitigate mycotoxin risk in Norwegian oats.


Assuntos
Micotoxinas , Toxina T-2 , Avena/microbiologia , Grão Comestível/química , Micotoxinas/análise , Melhoramento Vegetal , Toxina T-2/análogos & derivados , Toxina T-2/análise
17.
J Med Chem ; 65(4): 3359-3370, 2022 02 24.
Artigo em Inglês | MEDLINE | ID: mdl-35148092

RESUMO

Phosphatidylinositol 5-phosphate 4-kinases (PI5P4Ks) are emerging as attractive therapeutic targets in diseases, such as cancer, immunological disorders, and neurodegeneration, owing to their central role in regulating cell signaling pathways that are either dysfunctional or can be modulated to promote cell survival. Different modes of binding may enhance inhibitor selectivity and reduce off-target effects in cells. Here, we describe efforts to improve the physicochemical properties of the selective PI5P4Kγ inhibitor, NIH-12848 (1). These improvements enabled the demonstration that this chemotype engages PI5P4Kγ in intact cells and that compounds from this series do not inhibit PI5P4Kα or PI5P4Kß. Furthermore, the first X-ray structure of PI5P4Kγ bound to an inhibitor has been determined with this chemotype, confirming an allosteric binding mode. An exemplar from this chemical series adopted two distinct modes of inhibition, including through binding to a putative lipid interaction site which is 18 Å from the ATP pocket.


Assuntos
Trifosfato de Adenosina/metabolismo , Fosfotransferases (Aceptor do Grupo Álcool)/antagonistas & inibidores , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/farmacologia , Quinazolinas/síntese química , Quinazolinas/farmacologia , Tiofenos/síntese química , Tiofenos/farmacologia , Regulação Alostérica/efeitos dos fármacos , Ligação Competitiva , Cristalografia por Raios X , Humanos , Modelos Moleculares , Simulação de Acoplamento Molecular , Fosfotransferases (Aceptor do Grupo Álcool)/química , Especificidade por Substrato
18.
Toxins (Basel) ; 14(1)2022 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-35051011

RESUMO

Fusarium head blight (FHB) is an important disease of small grain cereals worldwide, resulting in reduced yield and quality as well as the contamination of harvested grains with mycotoxins. The key mycotoxin of concern is deoxynivalenol (DON), which has legislative and advisory limits in numerous countries. Cereal growers have a number of control options for FHB including rotation, cultivation, and varietal resistance; however, growers are still reliant on fungicides applied at flowering as part of an IPM program. Fungicides currently available to control FHB are largely restricted to triazole chemistry. This study conducted three field experiments to compare a new co-formulation of pydiflumetofen (a succinate dehydrogenase inhibitor (SDHI) with the tradename ADEPIDYN™) and prothioconazole (a triazole) against current standard fungicides at various timings (flag leaf fully emerged, mid-head emergence, early flowering, and late flowering) for the control of FHB and DON. Overall, the co-formulation showed greater efficacy compared to either pydiflumetofen alone or current fungicide chemistry. This greater activity was demonstrated over a wide range of spray timings (flag leaf fully emerged to late flowering). The availability of an SDHI with good activity against FHB and the resulting DON contamination of harvested grain will give growers an additional tool within an IPM program that will provide a greater flexibility of spray application windows and reduce fungicide resistance selection pressure.


Assuntos
Fungicidas Industriais/farmacologia , Fusarium/efeitos dos fármacos , Micotoxinas/biossíntese , Doenças das Plantas/prevenção & controle , Triazóis/farmacologia , Tricotecenos/metabolismo , Triticum/microbiologia , Grão Comestível/microbiologia , Pirazóis/farmacologia , Fatores de Tempo
19.
Sex Transm Infect ; 97(8): 613-618, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-33431606

RESUMO

OBJECTIVE: The aim of this report is to investigate the nature of the relationship between depression and condomless sex (CLS) among gay, bisexual and other men who have sex with men (GBMSM). METHODS: Data are from the Antiretrovirals, Sexual Transmission Risk and Attitude (ASTRA) study of people living with HIV and attending one of eight HIV outpatient clinics in England (2011-2012) and the Attitudes to and Understanding of Risk of Acquisition of HIV (AURAH) study of HIV-negative/unknown status individuals attending one of 20 genitourinary medicine clinics in England (2013-2014). This analysis included GBMSM only. For each study, the prevalence of depressive symptoms (Patient Health Questionnaire-9 score ≥10) was presented according to three categories of sex in the past 3 months (considering anal/vaginal sex with men/women and anal sex with men in separate definitions): (1) no sex, (2) condom-protected sex only and (3) CLS. Multinomial logistic regression with 'condom-protected sex only' as the reference group was used to adjust for age and (for ASTRA participants) time since HIV diagnosis. RESULTS: There were opposing associations of depression with recent sexual behaviour: the prevalence of depression was higher among those who reported no sex and those who reported CLS, compared with those who reported condom-protected sex only. Among the 2170 HIV-positive GBMSM in ASTRA, considering anal/vaginal sex with men/women, the prevalence of depressive symptoms was 32%, 20% and 28%, respectively, among men reporting no sex (n=783), condom-protected sex only (n=551) and CLS (n=836) (global p<0.001). Among the 1477 HIV-negative GBMSM in AURAH, the prevalence of depressive symptoms was 12%, 8% and 13%, respectively, for no sex (n=137), condom-protected sex only (n=487) and CLS (n=853) (global p=0.017). Patterns were similar after adjustment and when only considering anal sex between men. CONCLUSIONS: Depression may be linked both to lack of sexual activity and to sexual risk taking. When investigating associations between depression and CLS, it is important to separate out individuals reporting condom-protected sex only from those reporting no sex.


Assuntos
Instituições de Assistência Ambulatorial/estatística & dados numéricos , Bissexualidade/estatística & dados numéricos , Depressão/epidemiologia , Homossexualidade Masculina/estatística & dados numéricos , Comportamento Sexual/psicologia , Sexo sem Proteção/estatística & dados numéricos , Adulto , Estudos Transversais , Inglaterra/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Assunção de Riscos , Parceiros Sexuais , Inquéritos e Questionários
20.
Front Public Health ; 9: 806168, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34988058

RESUMO

Background: Medication adherence can prevent health risks, but many patients do not adhere to their prescribed treatment. Our recent trial found that a digital intervention was effective at improving medication adherence in non-adherent patients with Hypertension or Type 2 Diabetes; but we do not know how it brought about behavioural changes. This research is a post-trial process evaluation of the mechanism by which the intervention achieved its intended effects. Methods: A mixed methods design with quantitative and qualitative evidence synthesis was employed. Data was generated by two studies. Study 1 used questionnaires to measure the underlying mechanisms of and the medication adherence behaviour, and digital logfiles to objectively capture intervention effects on the process of behaviour change. Multilevel regression analysis on 57 complete intervention group cases tested the effects of the intervention at modifying the mechanism of behaviour change and in turn at improving medication adherence. Study 2 used in depth interviews with a subsample of 20 intervention patients, and eight practise nurses. Thematic analysis provided evidence about the overarching intervention functions and recommendations to improve intervention reach and impact in primary care. Results: Study 1 found that intervention effectiveness was significantly associated with positive changes in the underlying mechanisms of behaviour change (R2 = 0.26, SE = 0.98, P = 0.00); and this effect was heightened twofold when the tailored intervention content and reporting on medication taking (R2 = 0.59, SE = 0.74, P = 0.00) was interested into the regression model. Study 2 suggested that the intervention supported motivation and ability to adherence, although clinically meaningful effects would require very brief medication adherence risk appraisal and signposting to ongoing digitally delivered behavioural support during clinical consultations. Conclusion: This post trial process evaluation used objective methods to capture the intervention effect on the mechanisms of behaviour change to explain intervention effectiveness, and subjective accounts to explore the circumstances under which these effects were achieved. The results of this process evaluation will inform a large scale randomised controlled trial in primary care.


Assuntos
Diabetes Mellitus Tipo 2 , Hipertensão , Diabetes Mellitus Tipo 2/tratamento farmacológico , Humanos , Adesão à Medicação , Atenção Primária à Saúde , Inquéritos e Questionários
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