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1.
Inorg Chem ; 2022 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-34990145

RESUMO

An isostructural set of macrocyclic tetra-N-heterocyclic carbene (NHC) complexes were synthesized on late lanthanides including Lu, Yb, Ho, Dy, and Gd. They were characterized by single-crystal X-ray diffraction, multinuclear NMR, electrochemistry, and SQUID magnetometry. Solid-state structures show that all complexes are in a highly distorted square-pyramidal geometry with an axial HMDS ligand. 1H NMR for Lu, Yb, and Dy demonstrates that these geometries are maintained in solution. Electrochemical measurements on the Yb complex show that the NHCs are very strong σ-donors compared to other organometallic Yb complexes. Magnetic measurements of the Yb and Dy complexes reveal slow relaxation of the magnetization in both complexes. The highly anisotropic Dy complex possesses an energy barrier to spin reversal of 52.42 K/36.43 cm-1 and waist-restricted hysteresis up to 2.8 K. Finally, an 18-atom macrocycle variant of the Lu complex was synthesized for comparison in reactivity and stability. These complexes are the first lanthanides prepared with macrocyclic NHCs and suggest that NHCs may be a promising ligand for developing single-molecule magnets.

2.
Spectrochim Acta A Mol Biomol Spectrosc ; 267(Pt 1): 120512, 2022 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-34695714

RESUMO

Quality assurance of finished pharmaceuticals is a necessity in ensuring the safety of consumers. There is a need for low-cost and portable rapid screening methods of pharmaceuticals in resource limited areas. Recent advances in technology have made handheld and low-cost diffuse reflectance spectrometers available to the public. While these handheld spectrometers offer advantages over benchtop spectrometers, the accuracy and repeatability must be assessed before these instruments can be used for quality assurance screening. Here, five handheld spectrometers of the same model were purchased, where an in-house installation qualification and operational qualification (IQOQ) was subsequently established for the instruments. Wavelength and photometric accuracy (and repeatability), spectroscopic noise, stray light, and bandpass were assessed between instruments. Results were found to be consistent between the spectrometers, passing IQOQ procedures, and were determined to be ready for field use. Once the handheld spectrometer's performance was verified, a practical and low-cost daily performance verification was established using common high density polyethylene vial caps on location in South Africa, Thailand, and the United States. A Mahalanobis distance-based classifier found the five spectrometers to be in agreement.


Assuntos
Laboratórios , Espectroscopia de Luz Próxima ao Infravermelho
3.
Pediatr Blood Cancer ; : e29490, 2021 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-34866312

RESUMO

INTRODUCTION: There are clinical reports that the incorporation of dasatinib may increase the frequency of osteonecrosis in acute lymphoblastic leukemia (ALL) treatment regimens. No rigorous testing of this hypothesis is available to guide clinicians. METHODS: We tested whether oral dasatinib increased the frequency of dexamethasone-induced osteonecrosis in a murine model and tested its effects on dexamethasone's antileukemic efficacy in a murine BCR-ABL+ model of ALL. RESULTS: Dasatinib did not change the frequency of osteonecrosis (p = .99) nor of arteriopathy (p = .36) in dexamethasone-treated mice when given at dosages that achieved clinically relevant steady-state dasatinib plasma concentrations of 53.1 ng/ml (95% CI: 43.5-57.3 ng/ml). These dasatinib exposures were not associated with increased dexamethasone plasma exposure in nonleukemia-bearing mice. These same dosages were not associated with any decrement in antileukemic efficacy of dexamethasone in a responsive BCR-ABL+ model of ALL. CONCLUSIONS: Based on the results of our preclinical murine studies, we conclude that dasatinib is unlikely to increase the osteonecrotic effects of dexamethasone in ALL regimens.

4.
Rev Port Cardiol (Engl Ed) ; 40(10): 741-752, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34857112

RESUMO

INTRODUCTION AND OBJECTIVES: Pulmonary endarterectomy (PEA) is a potentially curative procedure in patients with chronic thromboembolic pulmonary hypertension (CTEPH). This study reports the initial experience of a Portuguese PH center with patients undergoing PEA at an international surgical reference center. METHODS: Prospective observational study of consecutive CTEPH patients followed at a national PH center, who underwent PEA at an international surgical reference center between October 2015 and March 2019. Clinical, functional, laboratory, imaging and hemodynamic parameters were obtained in the 12 months preceding the surgery and repeated between four and six months after PEA. RESULTS: 27 consecutive patients (59% female) with a median age of 60 (49-71) years underwent PEA. During a median follow-up of 34 (21-48) months, there was an improvement in functional class in all patients, with only one cardiac death. From a hemodynamic perspective, there was a reduction in mean pulmonary artery pressure from 48 (42-59) mmHg to 26 (22-38) mmHg, an increase in cardiac output from 3.3 (2.9-4.0) L/min to 4.9 (4.2-5.5) L/min and a reduction in pulmonary vascular resistance from 12.1 (7.2-15.5) uW to 3.5 (2.6-5,2) uW. During the follow-up, 44% (n=12) of patients had no PH criteria, 44% (n=12) had residual PH and 11% (n=3) had PH recurrence. There was a reduction of N-terminal pro-B-type natriureticpeptide from 868 (212-1730) pg/mL to 171 (98-382) pg/mL. Rright ventricular systolic function parameters revealed an improvement in longitudinal systolic excursion and peak velocity of the plane of the tricuspid ring from 14 (13-14) mm and 9 (8-10) cm/s to 17 (16-18) mm and 13 (11-15) cm/s, respectively. Of the 26 patients with preoperative right ventricular dysfunction, 85% (n=22) recovered. The proportion of patients on specific vasodilator therapy decreased from 93% to 44% (p<0.001) and the proportion of those requiring oxygen therapy decreased from 52% to 26% (p=0.003). The six-minute walk test distance increased by about 25% compared to the baseline and only eight patients had significant desaturation during the test. CONCLUSION: Pulmonary endarterectomy performed at an experienced high-volume center is a safe procedure with a very favorable medium-term impact on functional, hemodynamic and right ventricular function parameters in CTEPH patients with operable disease. It is possible for PH centers without PEA differentiation to refer patients safely and effectively to an international surgical center in which air transport is necessary.

5.
Sci Total Environ ; 812: 152241, 2021 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-34921881

RESUMO

Increasing usage of both nanomaterials and pharmaceuticals and their unabated release to the marine ecosystem pose a serious concern nowadays. The toxicity of the mixture of TiO2 NPs and tetracycline (TC) in the marine species are not very well covered in prior literature. The current study explores the joint toxic effects of TiO2 NPs and TC in a simulated marine food chain: Chlorella sp. and Artemia salina. Chlorella sp. was interacted with pristine TiO2 NPs (0.05, 05, and 5 mg/L), TC (0.5 mg/L), and their combinations for 48 h. The toxicity induced in Chlorella sp. by pristine TiO2 NPs through oxidative stress and chloroplast damage was not significantly changed in the presence of TC. Principal component analysis for the toxicity parameters revealed a strong association between growth inhibition and adsorption/internalization. In the second trophic level (A. salina), the waterborne exposure of TC additively increased the toxicity of TiO2 NPs. Both adsorption and degradation played a major role in the removal of TC from the suspension, resulting in additive toxic effects in both Chlorella sp. and A. salina. Compared to the waterborne exposure, the foodborne exposure of TiO2 NPs and TC induced lesser toxic effects owing to reduced uptake and accumulation in A. salina. Biomagnification results indicate that the dietary transfer of TiO2 NPs and TC does not pose a serious environmental threat in this two-level marine food chain.

6.
Nutrients ; 13(12)2021 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-34959911

RESUMO

The Portfolio Diet has demonstrated its cardiovascular benefit from interventions, but the association between Portfolio Diet adherence and the risk of all-cause and cause-specific mortality has not been examined in Chinese population. The present study has collected Portfolio Diet adherence (assessed by food frequency questionnaire), lifestyle factors and mortality status of 3991 participants in the Mr. Osteoporosis (OS) and Ms. OS Study. Cox regression models were used to examine the association between the Portfolio Diet adherence and mortality risk (all-cause, cardiovascular disease or cancer). The highest quartile of the Portfolio Diet score was associated with a 28% lower risk of all-cause (hazard ratio, HR: 0.72) and cancer (HR: 0.72) mortality, respectively. The association between Portfolio Diet adherence and cardiovascular disease mortality did not reach statistical significance (HR: 0.90, 95% CI = 0.64, 1.26). Among male participants, the highest adherence to the Portfolio Diet was also associated with a lower risk of all-cause (HR: 0.63) and cancer mortality (HR: 0.59), and there was an inverse association between food sources of plant protein and the risk of cardiovascular mortality (HR: 0.50). However, most associations between the Portfolio Diet and mortality were not significant among females. The protection for cancer mortality risk might reach the plateau at the highest adherence to the Portfolio Diet for females. To conclude, greater adherence to the Portfolio Diet was significantly associated with a lower risk of mortality in Hong Kong older adults, and the associations appeared stronger among males.

7.
Artigo em Inglês | MEDLINE | ID: mdl-34788460

RESUMO

OBJECTIVES: The objective was to review national trends in activity and hospital outcomes in older patients having cardiac surgery over a 15-year time period. METHODS: Data were collected prospectively and uploaded to the National Institute for Cardiovascular Outcomes Research electronically. Data were validated, cleaned and processed using reproducible algorithms. Mortality was death in hospital after index operation. RESULTS: A total of 227 442 cardiac procedures were recorded in patients aged ≥70 years of which 46 354 were in those aged ≥80 years. Overall patients aged ≥70 years represented 43% of all adult cardiac surgery in the most recent study year. The annual proportion of surgery in patients ≥80 years increased from 4.1% to 10.8% between the first and last study years. There has been a significant linear increase in octogenarian valve [ß 67.44, 95% confidence interval (CI) 55.04 to 79.83, P < 0.001] and coronary artery bypass graft surgery (ß 32.53, 95% CI 6.16 to 58.90, P = 0.020) patients. In-hospital mortality reduced significantly for patients aged 70-79 years (ß -0.17, 95% CI -0.20 to -0.13, P < 0.001) and all patients aged ≥80 (ß -0.37, 95% CI -0.45 to -0.30, P < 0.001). The median length of hospital stay was 7 days for 70-79 and 9 days for ≥80 group, compared with 7 days for the whole cohort <70 years. CONCLUSIONS: This study represents the largest complete validated national dataset of cardiac surgery in the entire population of older patients. Octogenarians represent 11% of adult patients having cardiac surgery by the end of the study period, a three-fold increase from the start. In-hospital mortality in patients aged ≥80 years halved during study period to only 4% despite high logistic EuroSCORE of 15%. Cardiac surgery in octogenarians places a higher demand on resources, however, with an increased postoperative length of stay.

8.
EClinicalMedicine ; 41: 101175, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34746726

RESUMO

Background: Surveillance of temporal trends in clinically treated self-harm is an important component of suicide prevention in the dynamic context of COVID-19. There is little evidence beyond the initial months following the onset of the pandemic, despite national and regional restrictions persisting to mid-2021. Methods: Descriptive time series analysis utilizing de-identified, primary care health records of 2.8 million patients from the Greater Manchester Care Record. Frequencies of self-harm episodes between 1st January 2019 and 31st May 2021 were examined, including stratification by sex, age group, ethnicity, and index of multiple deprivation quintile. Findings: There were 33,444 episodes of self-harm by 13,148 individuals recorded during the study period. Frequency ratios of incident and all episodes of self-harm were 0.59 (95% CI 0.51 to 0.69) and 0.69 (CI 0.63 to 0.75) respectively in April 2020 compared to February 2020. Between August 2020 and May 2021 frequency ratios were 0.92 (CI 0.88 to 0.96) for incident episodes and 0.86 (CI 0.84 to 0.88) for all episodes compared to the same months in 2019. Reductions were largest among men and people living in the most deprived neighbourhoods, while an increase in all-episode self-harm was observed for adolescents aged 10-17. Interpretation: Reductions in primary care-recorded self-harm persisted to May 2021, though they were less marked than in April 2020 during the first national lockdown. The observed reductions could represent longer term reluctance to seek help from health services. Our findings have implications for the ability for services to offer recommended care for patients who have harmed themselves.

9.
Dalton Trans ; 50(47): 17625-17634, 2021 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-34806099

RESUMO

A series of amine bisphenol (ABP) pro-ligands featuring amino acid ester pendant arms were prepared. Optimisation of the synthetic method allowed the facile incorporation of naturally occurring, chiral amino acids into the ABP scaffold with minimal racemisation. Reaction of the pro-ligands (LH2) with Pd(OAc)2, in the presence of amines, led to the formation of complexes with an unprecedented pincer-like O,N,O coordination mode around the PdII centre. The complexations in the presence of trialkylamines (NR3) afforded a mixture of LPdNR3 and LPdNHR2 species. The latter was shown to form via an ambient-temperature C-N cleavage involving unstable Pd(OAc)2(NHR2)2 intermediates. Using pyridine as base eliminated this dealkylation and resulted in the exclusive formation of LPd(py) complexes in high yields. In total, seven novel PdII ABP complexes were prepared, exhibiting distorted square-planar geometries with the asymmetric ligand moieties orientated towards the metal centre. The air- and moisture-stable LPd(py) complexes were successfully employed as catalysts in two types of C-C coupling reactions. The Suzuki-Miyaura coupling of 4'-bromoacetophenone and phenylboronic acid reached high yields (up to 81%), while a scope of further alkyl bromides was also efficiently converted using low catalyst loadings (1 mol%) and mild temperatures (40 °C). Furthermore, a Pd-pyridine complex achieved high activity in the Mizoroki-Heck coupling of styrene and 4'-bromoacetophenone.

10.
J Thorac Dis ; 13(10): 5670-5682, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34795917

RESUMO

Background: Significant bleeding following cardiac surgery is a recognised complication, associated with a requirement for re-exploration and blood transfusion, both associated with increased morbidity and early mortality. The aim of this study was to examine the impact of the volume of early postoperative bleeding on long-term survival for patients undergoing coronary artery bypass grafting (CABG). Methods: A retrospective analysis was performed of patients undergoing first-time isolated CABG at a single centre between January 2003 and April 2013, conditional from 30-day survival. Results: Six thousand two hundred and sixty-five patients were analysed, with a mean Logistic EuroSCORE of 4.9%. The mean age was 67.8 years. Median follow-up was 11.5 years. The overall 10- and 15-year survival was 70.6% and 51.9% respectively. Following surgery, 4.6% (n=291) required return to theatre for re-exploration, and 43.6% (n=2,733) received at least one red cell transfusion. In multivariable analysis, the strongest correlates of mortality were age, smoking history, BMI, COPD, renal impairment, preoperative left ventricular function and preoperative haemoglobin (Hb) level. Twelve-hour blood loss was an additional predictor of inferior long-term survival. Five-year survival was 89.6% for patients with <500 mL blood loss, 86.8% for 500-1,000 mL and 83.8% for >1,000 mL. Re-exploration and receiving blood transfusion were not associated with reduced long-term survival. Conclusions: Significant 12-hour blood loss is associated with inferior long-term survival following CABG. This observation supports efforts aimed at improving intra-operative haemostasis and aggressive management of patients with early signs of bleeding.

11.
PLoS Med ; 18(11): e1003823, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34739480

RESUMO

BACKGROUND: Healthcare workers (HCWs) and ethnic minority groups are at increased risk of COVID-19 infection and adverse outcomes. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination is now available for frontline UK HCWs; however, demographic/occupational associations with vaccine uptake in this cohort are unknown. We sought to establish these associations in a large UK hospital workforce. METHODS AND FINDINGS: We conducted cross-sectional surveillance examining vaccine uptake amongst all staff at University Hospitals of Leicester NHS Trust. We examined proportions of vaccinated staff stratified by demographic factors, occupation, and previous COVID-19 test results (serology/PCR) and used logistic regression to identify predictors of vaccination status after adjustment for confounders. We included 19,044 HCWs; 12,278 (64.5%) had received SARS-CoV-2 vaccination. Compared to White HCWs (70.9% vaccinated), a significantly smaller proportion of ethnic minority HCWs were vaccinated (South Asian, 58.5%; Black, 36.8%; p < 0.001 for both). After adjustment for age, sex, ethnicity, deprivation, occupation, SARS-CoV-2 serology/PCR results, and COVID-19-related work absences, factors found to be negatively associated with vaccine uptake were younger age, female sex, increased deprivation, pregnancy, and belonging to any non-White ethnic group (Black: adjusted odds ratio [aOR] 0.30, 95% CI 0.26-0.34, p < 0.001; South Asian: aOR 0.67, 95% CI 0.62-0.72, p < 0.001). Those who had previously had confirmed COVID-19 (by PCR) were less likely to be vaccinated than those who had tested negative. Limitations include data being from a single centre, lack of data on staff vaccinated outside the hospital system, and that staff may have taken up vaccination following data extraction. CONCLUSIONS: Ethnic minority HCWs and those from more deprived areas as well as younger staff and female staff are less likely to take up SARS-CoV-2 vaccination. These findings have major implications for the delivery of SARS-CoV-2 vaccination programmes, in HCWs and the wider population, and should inform the national vaccination programme to prevent the disparities of the pandemic from widening.


Assuntos
Vacinas contra COVID-19/farmacologia , COVID-19/prevenção & controle , Pessoal de Saúde/estatística & dados numéricos , SARS-CoV-2/patogenicidade , Vacinação/estatística & dados numéricos , COVID-19/epidemiologia , Atenção à Saúde/estatística & dados numéricos , Humanos , Grupos Minoritários , Reino Unido/epidemiologia
12.
Diagn Progn Res ; 5(1): 16, 2021 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-34620253

RESUMO

BACKGROUND: Patients presenting with chest pain represent a large proportion of attendances to emergency departments. In these patients clinicians often consider the diagnosis of acute myocardial infarction (AMI), the timely recognition and treatment of which is clinically important. Clinical prediction models (CPMs) have been used to enhance early diagnosis of AMI. The Troponin-only Manchester Acute Coronary Syndromes (T-MACS) decision aid is currently in clinical use across Greater Manchester. CPMs have been shown to deteriorate over time through calibration drift. We aim to assess potential calibration drift with T-MACS and compare methods for updating the model. METHODS: We will use routinely collected electronic data from patients who were treated using TMACS at two large NHS hospitals. This is estimated to include approximately 14,000 patient episodes spanning June 2016 to October 2020. The primary outcome of acute myocardial infarction will be sourced from NHS Digital's admitted patient care dataset. We will assess the calibration drift of the existing model and the benefit of updating the CPM by model recalibration, model extension and dynamic updating. These models will be validated by bootstrapping and one step ahead prequential testing. We will evaluate predictive performance using calibrations plots and c-statistics. We will also examine the reclassification of predicted probability with the updated TMACS model. DISCUSSION: CPMs are widely used in modern medicine, but are vulnerable to deteriorating calibration over time. Ongoing refinement using routinely collected electronic data will inevitably be more efficient than deriving and validating new models. In this analysis we will seek to exemplify methods for updating CPMs to protect the initial investment of time and effort. If successful, the updating methods could be used to continually refine the algorithm used within TMACS, maintaining or even improving predictive performance over time. TRIAL REGISTRATION: ISRCTN number: ISRCTN41008456.

13.
BMC Med Res Methodol ; 21(1): 207, 2021 10 09.
Artigo em Inglês | MEDLINE | ID: mdl-34627166

RESUMO

BACKGROUND: Network Meta-Analysis (NMA) is a key component of submissions to reimbursement agencies world-wide, especially when there is limited direct head-to-head evidence for multiple technologies from randomised controlled trials (RCTs). Many NMAs include only data from RCTs. However, real-world evidence (RWE) is also becoming widely recognised as a valuable source of clinical data. This study aims to investigate methods for the inclusion of RWE in NMA and its impact on the level of uncertainty around the effectiveness estimates, with particular interest in effectiveness of fingolimod. METHODS: A range of methods for inclusion of RWE in evidence synthesis were investigated by applying them to an illustrative example in relapsing remitting multiple sclerosis (RRMS). A literature search to identify RCTs and RWE evaluating treatments in RRMS was conducted. To assess the impact of inclusion of RWE on the effectiveness estimates, Bayesian hierarchical and adapted power prior models were applied. The effect of the inclusion of RWE was investigated by varying the degree of down weighting of this part of evidence by the use of a power prior. RESULTS: Whilst the inclusion of the RWE led to an increase in the level of uncertainty surrounding effect estimates in this example, this depended on the method of inclusion adopted for the RWE. 'Power prior' NMA model resulted in stable effect estimates for fingolimod yet increasing the width of the credible intervals with increasing weight given to RWE data. The hierarchical NMA models were effective in allowing for heterogeneity between study designs, however, this also increased the level of uncertainty. CONCLUSION: The 'power prior' method for the inclusion of RWE in NMAs indicates that the degree to which RWE is taken into account can have a significant impact on the overall level of uncertainty. The hierarchical modelling approach further allowed for accommodating differences between study types. Consequently, further work investigating both empirical evidence for biases associated with individual RWE studies and methods of elicitation from experts on the extent of such biases is warranted.


Assuntos
Projetos de Pesquisa , Viés , Humanos , Metanálise em Rede
14.
ERJ Open Res ; 7(4)2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34646880

RESUMO

The average rate of new #CTEPH referrals has dropped by 32% in the UK during the pandemic, despite the high incidence of #COVID19 related pulmonary emboli. There have been no recorded new cases of CTEPH caused by COVID-19. A prospective study is underway. https://bit.ly/37msP2G.

15.
Genome Med ; 13(1): 170, 2021 10 28.
Artigo em Inglês | MEDLINE | ID: mdl-34711268

RESUMO

BACKGROUND: Metastatic breast cancer is a deadly disease with a low 5-year survival rate. Tracking metastatic spread in living patients is difficult and thus poorly understood. METHODS: Via rapid autopsy, we have collected 30 tumor samples over 3 timepoints and across 8 organs from a triple-negative metastatic breast cancer patient. The large number of sites sampled, together with deep whole-genome sequencing and advanced computational analysis, allowed us to comprehensively reconstruct the tumor's evolution at subclonal resolution. RESULTS: The most unique, previously unreported aspect of the tumor's evolution that we observed in this patient was the presence of "subclone incubators," defined as metastatic sites where substantial tumor evolution occurs before colonization of additional sites and organs by subclones that initially evolved at the incubator site. Overall, we identified four discrete waves of metastatic expansions, each of which resulted in a number of new, genetically similar metastasis sites that also enriched for particular organs (e.g., abdominal vs bone and brain). The lung played a critical role in facilitating metastatic spread in this patient: the lung was the first site of metastatic escape from the primary breast lesion, subclones at this site were likely the source of all four subsequent metastatic waves, and multiple sites in the lung acted as subclone incubators. Finally, functional annotation revealed that many known drivers or metastasis-promoting tumor mutations in this patient were shared by some, but not all metastatic sites, highlighting the need for more comprehensive surveys of a patient's metastases for effective clinical intervention. CONCLUSIONS: Our analysis revealed the presence of substantial tumor evolution at metastatic incubator sites in a patient, with potentially important clinical implications. Our study demonstrated that sampling of a large number of metastatic sites affords unprecedented detail for studying metastatic evolution.

16.
Part Fibre Toxicol ; 18(1): 35, 2021 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-34496914

RESUMO

BACKGROUND: Today, cosmetic products are very popular with both men and women to improve their appearance and increase their social acceptability. RESULTS: In this study, nano-sized (30-300 nm) plastic particles were isolated from the commercial face-scrubs and treated on the human keratinocytes. The observed adherence of polyethylene nano-plastics (PENPs), polystyrene NPs (PSNPs), and face-scrubs isolated nano-plastics (NPs) on the keratin layer reveals a significant attachment of NPs from the cosmetics that are applied on the skin for a short duration. This attachment property could facilitate further adherence of protein molecules on NPs and the protein-corona formation. The protein-corona mimics protein aggregates, thereby triggers macropinocytosis, followed by the macropinolysosomal process in the cell. These internalized NPs induced the concentration-dependent cytotoxic, cytostatic and cytoprotective activity in keratinocytes. Both single dose and chronic long-term exposure of lethal and sub-lethal concentrations of NPs resulted in oxidative stress-mediated down-regulation of cell growth and proliferation inhibition. Autophagic structures and premature aging were also observed using an electron microscopy and a senescence marker, respectively in the NPs internalized HaCaT cells incubated in a fresh, NPs-free medium. CONCLUSION: Though 2D culture models have many limitations, it produces significant conceptual advancements. This work provides an insight into the NPs concentration-dependent regulatory, cytoprotective, and cytotoxic effects in HaCaT cells. However, 3D model studies are required to identify the detailed mechanisms of NPs toxicity and cytoprotective events in cells at the molecular level.


Assuntos
Nanopartículas Metálicas , Nanopartículas , Coroa de Proteína , Humanos , Queratinócitos , Microplásticos , Plásticos
17.
Obes Rev ; 22(11): e13330, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34494363

RESUMO

Nuts are recommended for cardiovascular health, yet concerns remain that nuts may contribute to weight gain due to their high energy density. A systematic review and meta-analysis of prospective cohorts and randomized controlled trials (RCTs) was conducted to update the evidence, provide a dose-response analysis, and assess differences in nut type, comparator and more in subgroup analyses. MEDLINE, EMBASE, and Cochrane were searched, along with manual searches. Data from eligible studies were pooled using meta-analysis methods. Interstudy heterogeneity was assessed (Cochran Q statistic) and quantified (I2 statistic). Certainty of the evidence was assessed by Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Six prospective cohort studies (7 unique cohorts, n = 569,910) and 86 RCTs (114 comparisons, n = 5873) met eligibility criteria. Nuts were associated with lower incidence of overweight/obesity (RR 0.93 [95% CI 0.88 to 0.98] P < 0.001, "moderate" certainty of evidence) in prospective cohorts. RCTs presented no adverse effect of nuts on body weight (MD 0.09 kg, [95% CI -0.09 to 0.27 kg] P < 0.001, "high" certainty of evidence). Meta-regression showed that higher nut intake was associated with reductions in body weight and body fat. Current evidence demonstrates the concern that nut consumption contributes to increased adiposity appears unwarranted.


Assuntos
Nozes , Obesidade , Peso Corporal , Humanos , Obesidade/epidemiologia , Obesidade/prevenção & controle , Sobrepeso , Ensaios Clínicos Controlados Aleatórios como Assunto
18.
Anal Chem ; 93(40): 13534-13538, 2021 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-34582180

RESUMO

The proliferation of N-heterocyclic carbene (NHC) self-assembled monolayers (SAMs) on gold surfaces stems from their exceptional stability compared to conventional thiol-SAMs. The prospect of biological applications for NHC-SAMs on gold shows the need for biocompatible techniques (e.g., large biomolecule detection and high throughput) that assesses SAM molecular composition. Herein, we demonstrate that laser desorption ionization mass spectrometry (LDI-MS) is a powerful and facile probe of NHC surface chemistry. LDI-MS of prototypical imidazole-NHC- and benzimidazole-NHC-functionalized AuNPs yields exclusively [NHC2Au]+ ions and not larger gold clusters. Employing benzimidazole-NHC isotopologues, we explore how monolayers pack on a single AuNP and the lability of the NHCs once ligated. Quantitative analysis of the homoleptic and heteroleptic [NHC2Au]+ ions is performed by comparing to a binomial model representative of a randomized monolayer. Lastly, the reduction of nitro-NHC-AuNPs to amine-NHC-AuNPs is tracked via LDI-MS signals, illustrating the ability of LDI-MS to probe postsynthetic modifications of the anchored NHCs, which is critical for current and future applications of NHC surfaces.


Assuntos
Ouro , Nanopartículas Metálicas , Lasers , Espectrometria de Massas , Metano/análogos & derivados
19.
Int J Sports Physiol Perform ; : 1-10, 2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34583327

RESUMO

PURPOSE: Mental fatigue is emerging as an important consideration for elite sporting performance, yet it is rarely monitored. The present study assessed changes in mental fatigue in professional team-sport athletes across 2 seasons and examined the relationship between mental fatigue and other athlete self-report measures of well-being. METHODS: Elite netballers contracted to all teams competing in Australia's premier professional netball competition during the 2018 and 2019 seasons (N = 154) participated. Using 5-point Likert scales, mental fatigue, fatigue (physical), tiredness, sleep quality, stress, mood, and motivation were assessed daily across 2 seasons composed of 14 round and finals series. RESULTS: The ratings of mental fatigue significantly changed during both seasons. In 2018, lower ratings of mental fatigue were reported in round 1 versus 3, 4, 6, 8, and 14; round 7 versus 6; and round 6 versus 10 (P < .05). In 2019, lower ratings of mental fatigue were identified for round 1 versus 3, 9, 10 to 14, and semifinal; round 2 versus 10 to 13; and 5 versus 10 to 12 (P < .05). Ordinal regression revealed significant differences between mental fatigue and physical fatigue (P < .001), tiredness (P < .001), stress (P < .001), mood (P < .001), and motivation (P < .05). CONCLUSIONS: The present study found mental fatigue to significantly fluctuate across a season in elite netballers. Moreover, perceived mental fatigue differed from physical fatigue, tiredness, stress, mood, and motivation. The data impress the need for mental fatigue to be included as an independent measure of athlete well-being. Monitoring of mental fatigue can allow practitioners to implement strategies to manage its influence on performance.

20.
Nutrients ; 13(9)2021 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-34579120

RESUMO

The glycaemic index (GI) is a food metric that ranks the acute impact of available (digestible) carbohydrates on blood glucose. At present, few countries regulate the inclusion of GI on food labels even though the information may assist consumers to manage blood glucose levels. Australia and New Zealand regulate GI claims as nutrition content claims and also recognize the GI Foundation's certified Low GI trademark as an endorsement. The GI Foundation of South Africa endorses foods with low, medium and high GI symbols. In Asia, Singapore's Healthier Choice Symbol has specific provisions for low GI claims. Low GI claims are also permitted on food labels in India. In China, there are no national regulations specific to GI; however, voluntary claims are permitted. In the USA, GI claims are not specifically regulated but are permitted, as they are deemed to fall under general food-labelling provisions. In Canada and the European Union, GI claims are not legal under current food law. Inconsistences in food regulation around the world undermine consumer and health professional confidence and call for harmonization. Global provisions for GI claims/endorsements in food standard codes would be in the best interests of people with diabetes and those at risk.


Assuntos
Dieta , Análise de Alimentos , Saúde Global , Índice Glicêmico , Rotulagem de Alimentos , Humanos
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