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1.
Environ Res ; 250: 118522, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38403148

RESUMEN

Whilst green space has been linked to healthier sleep outcomes, the roles of specific types of nature exposure, potential underlying mechanisms, and between-country variations in nature-sleep associations have received little attention. Drawing on cross-sectional survey data from an 18-country sample of adults (N = 16,077) the current study examined: 1) the relative associations between six different types of nature exposure (streetscape greenery, blue view from home, green space within 1 km, coast within 1 km, green space visits, blue space visits) and insufficient sleep (<6 h vs. 7-10 h per day); 2) whether these relationships were mediated by better mental wellbeing and/or physical activity; and 3) the consistency of these pathways among the different countries. After controlling for covariates, neighbourhood nature measures (green space, coast within 1 km) were not significantly associated with insufficient sleep; but nature visible from home (streetscape greenery, blue views) and recreational visits to green and blue spaces were each associated with less insufficient sleep. Significant nature-sleep associations were mediated, to varying degrees, by better mental wellbeing, but not self-reported physical activity. Country-level heterogeneity in the strength of nature-sleep associations was observed. Increasing nature visible from the home may represent a promising strategy for promoting healthier sleep duration at the population level, whilst nature-based interventions encouraging individuals to spend time in local green/blue spaces may be an appropriate target to assist individuals affected by insufficient sleep.


Asunto(s)
Sueño , Humanos , Masculino , Femenino , Persona de Mediana Edad , Adulto , Estudios Transversales , Salud Mental , Anciano , Adulto Joven , Adolescente , Ejercicio Físico , Naturaleza , Duración del Sueño
2.
Risk Anal ; 44(3): 521-535, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37350030

RESUMEN

Microplastics are receiving growing attention in the public debate, while the scientific assessment of risks of microplastics to ecological and human health is still ongoing. Previous studies suggest concerns among the general public with country-specific differences. However, little is known about the reasoning underlying these concerns. By conducting qualitative interviews with German (n = 15) and Italian citizens (n = 15), this study adopted a cross-national perspective to investigate which concepts shape citizens' perceptions of microplastics. A qualitative content analysis was used, with coding categories and subcategories developed inductively. Results showed that interviewees formed assumptions around microplastics despite own uncertainties, transferred knowledge from macro- to microplastics, and used the concepts of accumulation and dose-response relationship to make sense of the topic. Moreover, they saw the domains of human health and the environment as intertwined and expressed helplessness when discussing solutions to the microplastics issue. Many themes on the topic were similar in both samples, but there were also some differences. For instance, whereas Italian participants talked about marine-related microplastics, German participants talked about airborne sources; also, German participants tended to recognize more strongly the actions their country was putting in place to address the problem. These findings underscore the need for proactive risk communication despite remaining gaps in scientific risk assessment. Beyond providing technical information, communicators should consider the reasoning behind risk perception on microplastics and address scientific uncertainty as well as the interconnectedness between the domains of human health and the environment.


Asunto(s)
Microplásticos , Plásticos , Humanos , Comunicación , Investigación Cualitativa , Italia
3.
Cogn Emot ; : 1-20, 2024 Feb 16.
Artículo en Inglés | MEDLINE | ID: mdl-38362747

RESUMEN

Nature contact has associations with emotional ill-being and well-being. However, the mechanisms underlying these associations are not fully understood. We hypothesised that increased adaptive and decreased maladaptive emotion regulation strategies would be a pathway linking nature contact to ill-being and well-being. Using data from a survey of 600 U.S.-based adults administered online in 2022, we conducted structural equation modelling to test our hypotheses. We found that (1) frequency of nature contact was significantly associated with lesser emotional ill-being and greater emotional well-being, (2) effective emotion regulation was significantly associated with lesser emotional ill-being and greater emotional well-being, and (3) the associations of higher frequency of nature contact with these benefits were partly explained via emotion regulation. Moreover, we found a nonlinear relationship for the associations of duration of nature contact with some outcomes, with a rise in benefits up to certain amounts of time, and a levelling off after these points. These findings support and extend previous work that demonstrates that the associations of nature contact with emotional ill-being and well-being may be partly explained by changes in emotion regulation.

4.
J Proteome Res ; 22(8): 2629-2640, 2023 08 04.
Artículo en Inglés | MEDLINE | ID: mdl-37439223

RESUMEN

Thermal proteome profiling (TPP) provides a powerful approach to studying proteome-wide interactions of small therapeutic molecules and their target and off-target proteins, complementing phenotypic-based drug screens. Detecting differences in thermal stability due to target engagement requires high quantitative accuracy and consistent detection. Isobaric tandem mass tags (TMTs) are used to multiplex samples and increase quantification precision in TPP analysis by data-dependent acquisition (DDA). However, advances in data-independent acquisition (DIA) can provide higher sensitivity and protein coverage with reduced costs and sample preparation steps. Herein, we explored the performance of different DIA-based label-free quantification approaches compared to TMT-DDA for thermal shift quantitation. Acute myeloid leukemia cells were treated with losmapimod, a known inhibitor of MAPK14 (p38α). Label-free DIA approaches, and particularly the library-free mode in DIA-NN, were comparable of TMT-DDA in their ability to detect target engagement of losmapimod with MAPK14 and one of its downstream targets, MAPKAPK3. Using DIA for thermal shift quantitation is a cost-effective alternative to labeled quantitation in the TPP pipeline.


Asunto(s)
Proteína Quinasa 14 Activada por Mitógenos , Proteoma , Espectrometría de Masas/métodos , Proteoma/análisis , Proteómica/métodos
5.
J Virol ; 96(5): e0133021, 2022 03 09.
Artículo en Inglés | MEDLINE | ID: mdl-35019716

RESUMEN

All viruses must usurp host ribosomes for viral protein synthesis. Dicistroviruses utilize an intergenic region internal ribosome entry site (IGR IRES) to directly recruit ribosomes and mediate translation initiation from a non-AUG start codon. The IGR IRES adopts a three-pseudoknot structure that comprises a ribosome binding domain of pseudoknot II and III (PKII and PKIII), and a tRNA-like anticodon domain (PKI) connected via a short, one to three nucleotide hinge region. Recent cryo-EM structural analysis of the dicistrovirus Taura syndrome virus (TSV) IGR IRES bound to the ribosome suggests that the hinge region may facilitate translocation of the IRES from the ribosomal A to P site. In this study, we provide mechanistic and functional insights into the role of the hinge region in IGR IRES translation. Using the honeybee dicistrovirus, Israeli acute paralysis virus (IAPV), as a model, we demonstrate that mutations of the hinge region resulted in decreased IRES-dependent translation in vitro. Toeprinting primer extension analysis of mutant IRESs bound to purified ribosomes and in rabbit reticulocyte lysates showed defects in the initial ribosome positioning on the IRES. Finally, using a hybrid dicistrovirus clone, mutations in the hinge region of the IAPV IRES resulted in decreased viral yield. Our work reveals an unexpected role of the hinge region of the dicistrovirus IGR IRES coordinating the two independently folded domains of the IRES to properly position the ribosome to start translation. IMPORTANCE Viruses must use the host cell machinery to direct viral protein expression for productive infection. One such mechanism is an internal ribosome entry site that can directly recruit host cell machinery. In this study, we have identified a novel sequence in an IRES that provides insight into the mechanism of viral gene expression. Specifically, this novel sequence promotes viral IRES activity by directly guiding the host cell machinery to start gene expression at a specific site.


Asunto(s)
Dicistroviridae , Sitios Internos de Entrada al Ribosoma , Virosis , Virus , Animales , Dicistroviridae/genética , Dicistroviridae/metabolismo , Sitios Internos de Entrada al Ribosoma/genética , Mutación , Biosíntesis de Proteínas , Conejos , Ribosomas/metabolismo , Proteínas Virales/genética , Proteínas Virales/metabolismo , Virosis/metabolismo , Virosis/virología , Virus/genética
6.
Opt Express ; 31(3): 3549-3564, 2023 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-36785345

RESUMEN

Laser induced breakdown spectroscopy is a promising, rapid analysis method for the detection and quantification of Li and its isotopes needed in geochemical, nuclear, and energy storage applications. However, spectral broadening in laser produced plasmas, presence of fine and hyperfine structures, and self-reversal effects make Li isotopic analysis via laser induced breakdown spectroscopy challenging. The present study explores the influence of Ar, N2, and He ambient gases over the pressure range of 0.05 - 100 Torr on line broadening and self-reversal of the Li I transition with the greatest isotopic shift in the VIS spectral region (i.e., ≈670.8 nm, ≈15.8 pm isotopic shift). We perform spatially and temporally resolved optical emission spectroscopy of plasmas produced via laser ablation of LiAlO2 substrates. Our results show that the self-reversal and linewidth is reduced at lower pressures for all gases, and using optimized plasma conditions with chemometric methods, the 6Li/7Li isotopic ratios can be predicted.

7.
Bioorg Med Chem ; 91: 117387, 2023 08 15.
Artículo en Inglés | MEDLINE | ID: mdl-37418825

RESUMEN

Ureas are an important functional group in small molecule drugs as well as having wider applications in organic chemistry. Understanding of their conformation is of critical importance for rational design of urea-containing bioactive compounds. Whilst the conformational preferences of biaryl ureas have been extensively studied, very little attention has been paid to alkylated analogues. We carried out a systematic study of N-aryl (phenyl and pyridyl)-N'-cyclopentyl ureas with differing N-methylation patterns using Well Tempered Metadynamics at a semi-empirical level in implicit water (GBSA) using Well-Tempered Metadynamics to generate their conformational free-energy landscapes. Geometries and energetics of the most relevant configurations are further refined using DFT level of theory. Validation for the computation was obtained by synthesis of all 8 analogues followed by conformational studies by X-ray crystallography and NMR. These findings reveal that the methylation pattern significantly affects the conformational preference of the system. Most notably, N-phenyl-N'-cyclopentyl urea is shown to adopt both the trans-trans, and cis-trans conformations with equal energy and that the cis-trans conformation can be significantly stabilised by the presence of an internal hydrogen bond to the N'-hydrogen. This study will be of utility for the design of N-alkyl-N'-aryl ureas as drug candidates.


Asunto(s)
Hidrógeno , Urea , Conformación Molecular , Espectroscopía de Resonancia Magnética , Hidrógeno/química , Descubrimiento de Drogas
8.
Environ Res ; 232: 116324, 2023 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-37311473

RESUMEN

Rates of living alone, especially in more urbanised areas, are increasing across many industrialised countries, with associated increases in feelings of loneliness and poorer mental health. Recent studies have suggested that access to nature (e.g. parks and green spaces) can reduce the stressors associated with loneliness, partly through providing opportunities to nurture personal relationships (relational restoration) and engage in normative community activities (collective restoration). Such associations might vary across different household compositions and socio-demographic or geographical characteristics, but these have not been thoroughly tested. Using data collected across 18 countries/territories in 2017-2018, we grouped urban respondents into those living alone (n = 2062) and those living with a partner (n = 6218). Using multigroup path modelling, we tested whether the associations between neighbourhood greenspace coverage (1-km-buffer from home) and mental health are sequentially mediated by: (a) visits to greenspace; and subsequently (b) relationship and/or community satisfaction, as operationalisations of relational and collective restoration, respectively. We also tested whether any indirect associations varied among subgroups of respondents living alone. Analyses showed that visiting green space was associated with greater mental well-being and marginally lower odds of using anxiety/depression medication use indirectly, mediated via both relationship and community satisfaction. These indirect associations were equally strong among respondents living alone and those living with a partner. Neighbourhood green space was, additionally, associated with more visits among respondents living with a partner, whereas among those living alone, this was sensitive to the green space metric. Within subgroups of people living alone, few overall differences were found. Some indirect pathways were, nevertheless, stronger in males, under 60-year-olds, those with no financial strain, and residents in warmer climates. In conclusion, supporting those living alone, as well as those living with a partner, to more frequently access their local greenspaces could help improve mental health via promoting relational and collective restoration.


Asunto(s)
Salud Mental , Parques Recreativos , Masculino , Humanos , Ambiente en el Hogar , Satisfacción Personal , Bienestar Psicológico , Características de la Residencia
9.
BMC Nephrol ; 24(1): 43, 2023 02 24.
Artículo en Inglés | MEDLINE | ID: mdl-36829135

RESUMEN

BACKGROUND: Treatment of end-stage kidney disease (ESKD) with hemodialysis requires surgical creation of an arteriovenous (AV) vascular access-fistula (AVF) or graft (AVG)-to avoid (or limit) the use of a central venous catheter (CVC). AVFs have long been considered the first-line vascular access option, with AVGs as second best. Recent studies have suggested that, in older adults, AVGs may be a better strategy than AVFs. Lacking evidence from well-powered randomized clinical trials, integration of these results into clinical decision making is challenging. The main objective of the AV Access Study is to compare, between the two types of AV access, clinical outcomes that are important to patients, physicians, and policy makers. METHODS: This is a prospective, multicenter, randomized controlled trial in adults ≥ 60 years old receiving chronic hemodialysis via a CVC. Eligible participants must have co-existing cardiovascular disease, peripheral arterial disease, and/or diabetes mellitus; and vascular anatomy suitable for placement of either type of AV access. Participants are randomized, in a 1:1 ratio, to a strategy of AVG or AVF creation. An estimated 262 participants will be recruited across 7 healthcare systems, with average follow-up of 2 years. Questionnaires will be administered at baseline and semi-annually. The primary outcome is the rate of CVC-free days per 100 patient-days. The primary safety outcome is the cumulative incidence of vascular access (CVC or AV access)-related severe infections-defined as access infections that lead to hospitalization or death. Secondary outcomes include access-related healthcare costs and patients' experiences with vascular access care between the two treatment groups. DISCUSSION: In the absence of studies using robust and unbiased research methodology to address vascular access care for hemodialysis patients, clinical decisions are limited to inferences from observational studies. The goal of the AV Access Study is to generate evidence to optimize vascular access care, based on objective, age-specific criteria, while incorporating goals of care and patient preference for vascular access type in clinical decision-making. TRIAL REGISTRATION: This study is being conducted in accordance with the tenets of the Helsinki Declaration, and has been approved by the central institutional review board (IRB) of Wake Forest University Health Sciences (approval number: 00069593) and local IRB of each participating clinical center; and was registered on Nov 27, 2020, at ClinicalTrials.gov (NCT04646226).


Asunto(s)
Fístula Arteriovenosa , Derivación Arteriovenosa Quirúrgica , Fallo Renal Crónico , Humanos , Anciano , Persona de Mediana Edad , Estudios Prospectivos , Derivación Arteriovenosa Quirúrgica/métodos , Diálisis Renal/métodos , Fallo Renal Crónico/terapia , Estudios Retrospectivos , Resultado del Tratamiento , Ensayos Clínicos Controlados Aleatorios como Asunto , Estudios Multicéntricos como Asunto
10.
Vet Anaesth Analg ; 50(1): 98-101, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36463017

RESUMEN

OBJECTIVE: To evaluate latency and duration of a brachial plexus block technique in eastern box turtles performed with 2% lidocaine at three dose rates. STUDY DESIGN: Prospective, randomized, blinded crossover study. ANIMALS: Adult eastern box turtles, two for drug dose evaluation and a group of six (three male, three female) weighing 432 ± 40 g (mean ± standard deviation) for the main study. METHODS: Animals were randomly assigned to four brachial plexus blocks with lidocaine at 5, 10 and 20 mg kg-1 or 0.9% saline (treatments LID5, LID10, LID20 and CON, respectively), separated by 1 week. Treatment side was randomized and blocks were performed unilaterally. Baseline observations of mentation, heart rate (HR), respiratory rate (fR), skin temperature and limb response to manipulation or toe pinch were evaluated. Assessments were made every 10 minutes until 1 hour of normal sensory and motor function to the treated thoracic limb, or for a total of 2 hours if no block was evident. RESULTS: Motor and sensory blockade was achieved in treatments LID10 and LID20 in one turtle, with a latency of 10 minutes and duration of 50 minutes for both doses. Raising of the ipsilateral lower palpebra occurred with both blocks. Turtles administered lidocaine experienced higher HR compared with CON, and HR decreased over time for all individuals. Mentation and fR were not changed with any lidocaine dose. CONCLUSIONS: The technique was unreliable in producing brachial plexus motor and sensory blockade at the lidocaine doses evaluated in this study. HR was higher in lidocaine-administered turtles but remained within normal limits for the species. No change in mentation or fR was observed among treatments. CLINICAL RELEVANCE: General anesthesia with systemic analgesia is recommended for surgical procedures involving the chelonian thoracic limb. Further studies are needed to optimize a brachial plexus block in this species.


Asunto(s)
Bloqueo del Plexo Braquial , Tortugas , Masculino , Femenino , Animales , Lidocaína , Bloqueo del Plexo Braquial/veterinaria , Bloqueo del Plexo Braquial/métodos , Anestésicos Locales , Estudios Cruzados , Estudios Prospectivos
11.
J Contemp Dent Pract ; 24(10): 809-812, 2023 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-38152915

RESUMEN

AIM: To evaluate the cystic changes in the radiographically normal dental follicle associated with impacted mandibular third molar. MATERIALS AND METHODS: This study was conducted on 80 patients. Samples were selected using a convenient sampling technique from the patients who had impacted mandibular third molars in Pell and Gregory's positions B and C, with follicular space less than 2.5 mm in diameter. After surgical removal of an impacted tooth, the dental follicle was sent for histopathologic evaluation. RESULTS: Pathologic alterations were found in 19% of cases out of 80 samples. Odontogenic keratocystic and dentigerous cystic changes were found in 7% of cases. A statistically significant cystic alteration was found in female patients and distoangular impacted teeth. CONCLUSION: This study shows a significant cystic alteration in the radiologically normal dental follicles. Clinical and radiographic features alone may not be a reliable indicator of the absence of pathology. Early intervention of impacted teeth will help to reduce morbidity due to the development of pathology. CLINICAL SIGNIFICANCE: This study will help educate patients on the risks of retaining impacted teeth, based on scientific facts, in order to minimize the risks and to assess the correlation of pathologic alterations with the depth of impaction and angular position of the impacted tooth.


Asunto(s)
Tercer Molar , Diente Impactado , Humanos , Femenino , Tercer Molar/diagnóstico por imagen , Tercer Molar/patología , Diente Impactado/diagnóstico por imagen , Diente Impactado/cirugía , Saco Dental/patología , Diente Molar/patología , Mandíbula/patología
12.
Cancer ; 128(13): 2455-2462, 2022 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-35417565

RESUMEN

BACKGROUND: Young adults and other working-age adults with cancer are at risk for cancer-related financial toxicity (FT), including material hardships, depletion of coping resources, and psychological burden. This study compares FT domains in young adults (18-39 years old) (YAs), other working-age adults (40-64 years old), and older adults (≥65 years old) receiving cancer care. METHODS: A total of 311 adults were surveyed using the multi-domain Economic Strain and Resilience in Cancer instrument measuring FT (0-10 score indicating least to greatest FT; score ≥5 severe FT). Participants were receiving ambulatory care from March-September 2019. Associations of age with overall FT and material hardship, coping resource depletion, and psychological burden FT domains were tested using Kruskal-Wallis and χ2 tests and multivariable generalized linear models with gamma distribution. RESULTS: YAs (median age, 31.5 years) comprised 9.6% of the sample; other working-age adults comprised 56.9%. Overall, material, coping, and psychological FT scores were worse in younger age adults versus older adults (P < .001 in all multivariable models). Compared with older adults, younger age adults demonstrated worse material hardship (median scores, 3.70 vs 4.80 vs 1.30 for YAs, other working-age, and older adults, respectively; P < .001), coping resource depletion (4.50 vs 3.40 vs 0.80; P < .001), and psychological burden (6.50 vs 7.00 vs 1.00; P < .001). Fifty percent of YAs had severe overall FT versus 40.7% of other working-age adults and 9.6% of older adults (P < .001). CONCLUSIONS: Younger age adults with cancer bore disproportionate FT. Interventions to address unmet needs are critical components for addressing FT in this population.


Asunto(s)
Estrés Financiero , Neoplasias , Adaptación Psicológica , Adolescente , Adulto , Anciano , Costo de Enfermedad , Gastos en Salud , Humanos , Persona de Mediana Edad , Neoplasias/psicología , Encuestas y Cuestionarios , Adulto Joven
13.
J Clin Microbiol ; 60(1): e0139821, 2022 01 19.
Artículo en Inglés | MEDLINE | ID: mdl-34669460

RESUMEN

Fourier transform infrared (FTIR) spectroscopy has demonstrated applicability as a reagent-free whole-organism fingerprinting technique for both microbial identification and strain typing. For routine application of this technique in microbiology laboratories, acquisition of FTIR spectra in the attenuated total reflectance (ATR) mode simplifies the FTIR spectroscopy workflow, providing results within minutes after initial culture without prior sample preparation. In our previous central work, 99.7% correct species identification of clinically relevant yeasts was achieved by employing an ATR-FTIR-based method and spectral database developed by our group. In this study, ATR-FTIR spectrometers were placed in 6 clinical microbiology laboratories over a 16-month period and were used to collect spectra of routine yeast isolates for on-site identification to the species level. The identification results were compared to those obtained from conventional biochemical tests and/or matrix-assisted laser desorption/ionization-time of flight mass spectrometry. Isolates producing discordant results were reanalyzed by routine identification methods, ATR-FTIR spectroscopy, and PCR gene sequencing of the D1/D2 and internal transcribed spacer (ITS) regions. Among the 573 routine clinical yeast isolates collected and identified by the ATR-FTIR-based method, 564 isolates (98.4%) were correctly identified at the species level, while the remaining isolates were inconclusive with no misidentifications. Due to the low prevalence of Candida auris in routine isolates, additional randomly selected C. auris (n = 24) isolates were obtained for evaluation and resulted in 100% correct identification. Overall, the data obtained in our multicenter evaluation study using multiple spectrometers and system operators indicate that ATR-FTIR spectroscopy is a reliable, cost-effective yeast identification technique that provides accurate and timely (∼3 min/sample) species identification promptly after the initial culture.


Asunto(s)
Levaduras , Análisis de Fourier , Humanos , Espectroscopía Infrarroja por Transformada de Fourier/métodos , Levaduras/aislamiento & purificación
14.
Glob Environ Change ; 74: 102497, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-36406626

RESUMEN

Extensive ecosystem degradation and increasing urbanization are altering human relationships with nature. To explore these trends, we created a transdisciplinary, narrative-led podcast series produced by the BBC, called Forest 404. The series explored the implications of a world without nature. An online experimental component mobilized audience participation (n = 7,596) to assess responses to natural soundscapes with and without abiotic, biotic, and poetic elements across five biomes. Conditions featuring the sounds of wildlife, such as bird song, were perceived to be more psychologically restorative than those without. Participants' personal lived experiences were strongly related to these outcomes; those who had memories triggered by the sounds were more likely to find them psychologically restorative and exhibited a greater motivation to preserve them. Moreover, the effects of both soundscape composition and memories on preservation behavior were partially mediated by restorative potential; respondents were more likely to want to protect the sounds they heard if they thought they might offer therapeutic outcomes. Our findings highlight the value of art-science collaborations and demonstrate how maintaining contact with the natural world can promote wellbeing and foster behaviors that protect planetary health.

15.
Regul Toxicol Pharmacol ; 131: 105132, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35217105

RESUMEN

A novel approach was developed to help characterize the biokinetics of the cosmetic ingredient, phenoxyethanol, to help assess the safety of the parent and its major stable metabolite. In the first step of this non-animal tiered approach, primary human hepatocytes were used to confirm or refute in silico predicted metabolites, and elucidate the intrinsic clearance of phenoxyethanol. A key result was the identification of the major metabolite, phenoxyacetic acid (PAA), the exposure to which in the kidney was subsequently predicted to far exceed that of phenoxyethanol in blood or other tissues. Therefore, a novel aspect of this approach was to measure in the subsequent step the formation of PAA in the cells dosed with phenoxyethanol that were used to provide points of departure (PoDs) and express the intracellular exposure as the Cmax and AUC24. This enabled the calculation of the intracellular concentrations of parent and metabolite at the PoD in the cells used to derive this value. These concentrations can be compared with in vivo tissue levels to conclude on the safety margin. The lessons from this case study will help to inform the design of other non-animal safety assessments.


Asunto(s)
Cosméticos , Glicoles de Etileno , Cosméticos/toxicidad , Glicoles de Etileno/toxicidad , Humanos , Medición de Riesgo
16.
Blood ; 133(16): 1729-1741, 2019 04 18.
Artículo en Inglés | MEDLINE | ID: mdl-30755422

RESUMEN

Somatically acquired mutations in PHF6 (plant homeodomain finger 6) frequently occur in hematopoietic malignancies and often coincide with ectopic expression of TLX3. However, there is no functional evidence to demonstrate whether these mutations contribute to tumorigenesis. Similarly, the role of PHF6 in hematopoiesis is unknown. We report here that Phf6 deletion in mice resulted in a reduced number of hematopoietic stem cells (HSCs), an increased number of hematopoietic progenitor cells, and an increased proportion of cycling stem and progenitor cells. Loss of PHF6 caused increased and sustained hematopoietic reconstitution in serial transplantation experiments. Interferon-stimulated gene expression was upregulated in the absence of PHF6 in hematopoietic stem and progenitor cells. The numbers of hematopoietic progenitor cells and cycling hematopoietic stem and progenitor cells were restored to normal by combined loss of PHF6 and the interferon α and ß receptor subunit 1. Ectopic expression of TLX3 alone caused partially penetrant leukemia. TLX3 expression and loss of PHF6 combined caused fully penetrant early-onset leukemia. Our data suggest that PHF6 is a hematopoietic tumor suppressor and is important for fine-tuning hematopoietic stem and progenitor cell homeostasis.


Asunto(s)
Células Madre Hematopoyéticas/citología , Proteínas de Homeodominio/metabolismo , Leucemia/etiología , Proteínas Represoras/fisiología , Animales , Carcinogénesis , Regulación de la Expresión Génica , Humanos , Ratones , Ratones Noqueados , Receptores de Interferón , Proteínas Represoras/genética , Proteínas Supresoras de Tumor
17.
Eur Radiol ; 31(5): 2788-2797, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33128187

RESUMEN

OBJECTIVES: To determine the test-retest reproducibility and observer variability of CMR-derived LA function, using (i) LA strain (LAS) and strain rate (LASR), and (ii) LA volumes (LAV) and emptying fraction (LAEF). METHODS: Sixty participants with and without cardiovascular disease (aortic stenosis (AS) (n = 16), type 2 diabetes (T2D) (n = 28), end-stage renal disease on haemodialysis (n = 10) and healthy volunteers (n = 6)) underwent two separate CMR scans 7-14 days apart. LAS and LASR, corresponding to LA reservoir, conduit and contractile booster-pump function, were assessed using Feature Tracking software (QStrain v2.0). LAEF was calculated using the biplane area length method (QMass v8.1). Both were assessed using 4- and 2-chamber long-axis standard steady-state free precession cine images, and average values were calculated. Intra- and inter-observer variabilities were assessed in 10 randomly selected participants. RESULTS: The test-retest reproducibility was moderate to poor for all strain and strain rate parameters. Overall, strain and strain rate corresponding to reservoir phase (LAS_r, LASR_r) were the most reproducible, yielding the smallest coefficient of variance (CoV) (29.9% for LAS_r, 28.9% for LASR_r). The test-retest reproducibility for LAVs and LAEF was good: LAVmax CoV = 19.6% ICC = 0.89, LAVmin CoV = 27.0% ICC = 0.89 and total LAEF CoV = 15.6% ICC = 0.78. The inter- and intra-observer variabilities were good for all parameters except for conduit function. CONCLUSION: The test-retest reproducibility of LA strain and strain rate assessment by CMR utilising Feature Tracking is moderate to poor across disease states, whereas LA volume and emptying fraction are more reproducible on CMR. Further improvements in LA strain quantification are needed before widespread clinical application. KEY POINTS: • LA strain and strain rate assessment using Feature Tracking on CMR has moderate to poor test-retest reproducibility across disease states. • The test-retest reproducibility for the biplane method of assessing LA function is better than strain assessment, with lower coefficient of variances and narrower limits of agreement on Bland-Altman plots. • Biplane LA volumetric measurement also has better intra- and inter-observer variability compared to strain assessment.


Asunto(s)
Función del Atrio Izquierdo , Diabetes Mellitus Tipo 2 , Atrios Cardíacos/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética , Imagen por Resonancia Cinemagnética , Variaciones Dependientes del Observador , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados
18.
Appl Microbiol Biotechnol ; 105(1): 417-427, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33263791

RESUMEN

Bioremediation systems represent an environmentally sustainable approach to degrading industrially generated thiocyanate (SCN-), with low energy demand and operational costs and high efficiency and substrate specificity. However, heavy metals present in mine tailings effluent may hamper process efficiency by poisoning thiocyanate-degrading microbial consortia. Here, we experimentally tested the tolerance of an autotrophic SCN--degrading bacterial consortium enriched from gold mine tailings for Zn, Cu, Ni, Cr, and As. All of the selected metals inhibited SCN- biodegradation to different extents, depending on concentration. At pH of 7.8 and 30 °C, complete inhibition of SCN- biodegradation by Zn, Cu, Ni, and Cr occurred at 20, 5, 10, and 6 mg L-1, respectively. Lower concentrations of these metals decreased the rate of SCN- biodegradation, with relatively long lag times. Interestingly, the microbial consortium tolerated As even at 500 mg L-1, although both the rate and extent of SCN- biodegradation were affected. Potentially, the observed As tolerance could be explained by the origin of our microbial consortium in tailings derived from As-enriched gold ore (arsenopyrite). This study highlights the importance of considering metal co-contamination in bioreactor design and operation for SCN- bioremediation at mine sites. KEY POINTS: • Both the efficiency and rate of SCN- biodegradation were inhibited by heavy metals, to different degrees depending on type and concentration of metal. • The autotrophic microbial consortium was capable of tolerating high concentrations of As, potential having adapted to higher As levels derived from the tailings source.


Asunto(s)
Metales Pesados , Contaminantes del Suelo , Procesos Autotróficos , Biodegradación Ambiental , Metales Pesados/análisis , Metales Pesados/toxicidad , Consorcios Microbianos , Contaminantes del Suelo/análisis , Tiocianatos
19.
Health Promot Int ; 36(4): 1126-1139, 2021 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-33367651

RESUMEN

Natural environments can be used to promote health through facilitating recreational walking. However, efforts to encourage this often neglect messages identified in psychological research that are effective at influencing intentions to walk. This is despite the National Institute for Health and Care Excellence stating that promotional efforts should utilize theoretical frameworks of behaviour change and be targeted towards less active adults. As an illustrative example, this experiment compared a prototypical recreational walking brochure with an "enhanced" version including such persuasive messages on people's intentions to walk for recreation in natural environments. The enhanced brochure heightened intentions for inexperienced recreational walkers through our hypothesized mechanisms, but appeared to dissuade already-experienced walkers. Optimal messaging strategies in recreational walking brochures require tailoring to more and less active readerships. Guidelines are provided for authors of recreational walking brochures, though the principles and techniques could easily be extended to other means of outdoor walking promotion.


Asunto(s)
Folletos , Caminata , Adulto , Ambiente , Promoción de la Salud , Humanos , Intención
20.
Int J Mol Sci ; 22(14)2021 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-34299180

RESUMEN

This special issue on Advances in Kinase Drug Discovery provides a selection of research articles and topical reviews covering all aspects of drug discovery targeting the phosphotransferase enzyme family [...].


Asunto(s)
Descubrimiento de Drogas/métodos , Inhibidores de Proteínas Quinasas/uso terapéutico , Publicaciones , Humanos
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