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1.
Artigo em Inglês | MEDLINE | ID: mdl-34848554

RESUMO

BACKGROUND: Telemedicine for medical abortion care was rapidly introduced in Great Britain in response to the COVID-19 pandemic. A growing body of literature demonstrates that telemedicine abortion care is safe, effective and highly acceptable to patients. Less is known about the perspectives of abortion care providers (ACPs). METHODS: Qualitative research within the telemedicine abortion service in Lothian (Edinburgh and surrounding region), UK. We conducted qualitative in-depth interviews with ACPs between May and July 2020 (doctors, n=6; nurses, n=10) and analysed the data thematically. RESULTS: We present three themes from our qualitative analysis: (1) Selective use of ultrasound - the move away from routine ultrasound for determination of gestational age was generally viewed positively. Initial anxiety about non-detection of ectopic pregnancy and later gestations was expressed by some ACPs, but concerns were addressed through clinical practice and support structures within the clinic. (2) Identifying safeguarding issues - in the absence of visual cues some ACPs reported concerns about their ability to identify safeguarding issues, specifically domestic violence. Conversely it was acknowledged that teleconsultations may improve detection of this in some situations. (3) Provision of information during the consultation - telephone consultations were considered more focused than in-person consultations and formed only part of the overall 'package' of information provided to patients, supplemented by online and written information. CONCLUSIONS: ACPs providing telemedicine abortion care value this option for patients and believe it should remain beyond the COVID-19 pandemic. Safeguarding patients and the selective use of ultrasound can be initially challenging; however, with experience, staff confidence improves.

2.
Mar Pollut Bull ; 173(Pt B): 113113, 2021 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-34768191

RESUMO

Climate change is expected to cause significant changes to rocky shore diversity. This study used outdoor mesocosms to test the predictions that warming and ocean acidification will alter the responses of native Trichomya hirsuta and introduced Mytilus galloprovincialis mussels, and their associated communities of infauna. Experiments consisted of orthogonal combinations of temperature (ambient 22 °C or elevated 25 °C), pCO2 (ambient 400 µatm or elevated 1000 µatm), mussel species (T. hirsuta or M. galloprovincialis), and mussel configuration (native, introduced, or both), with n = 3 replicates. Elevated pCO2 reduced the growth of T. hirsuta but not that of M. galloprovincialis, and warming and pCO2 influenced the infauna that colonised both species of mussels. There was a reduction in infaunal molluscs and an increase in polychaetes; there was, however, no effect on crustaceans. Results from this study suggest that climate-driven changes from one mussel species to another can significantly influence infaunal communities.

3.
J Epidemiol ; 2021 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-34776498

RESUMO

BACKGROUND: The EU LifeCycle Project was launched in 2017 to combine, harmonise, and analyse data from more than 250,000 participants across Europe and Australia, involving cohorts participating in the EU-funded LifeCycle Project. The purpose of this cohort description is to provide a detailed overview over the major measures within mental health domains that are available in 17 European and Australian cohorts participating in the LifeCycle Project. METHODS: Data on cognitive, behavioural and psychological development has been collected on participants from birth until adulthood through questionnaire and medical data. We developed an inventory of the available data by mapping individual instruments, domain types, and age groups, providing the basis for statistical harmonization across mental health measures. RESULTS: The mental health data in LifeCycle contain longitudinal and cross-sectional data for ages 0-18+ years, covering domains across a wide range of behavioural and psychopathology indicators and outcomes (including executive function, depression, ADHD and cognition). These data span a unique combination of qualitative data collected through behavioural/cognitive/mental health questionnaires and examination, as well as data from biological samples and indices in the form of brain imaging (MRI, foetal ultrasound) and DNA methylation data. Harmonized variables on a subset of mental health domains have been developed, providing statistical equivalence of measures required for longitudinal meta-analyses across instruments and cohorts. CONCLUSION: Mental health data harmonized through the LifeCycle project can be used to study life course trajectories and exposure-outcome models that examine early life risk factors for mental illness and develop predictive markers for later-life disease.

4.
Clin Cancer Res ; 2021 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-34716194

RESUMO

PURPOSE: Soft tissue sarcomas (STS) are a rare, heterogeneous group of mesenchymal tumors. For decades the mainstay of treatment for advanced, unresectable STS has been palliative chemotherapy. High levels of activated MET receptor have been reported in various sarcoma cell lines, together with elevated VEGF levels in patients with STS, suggesting that dual targeting of the VEGF and MET pathways with the multi-receptor tyrosine kinase inhibitor cabozantinib would result in clinical benefit in this population. EXPERIMENTAL DESIGN: We performed an open-label, multi-institution, single-arm phase II trial of single-agent cabozantinib in adult patients with advanced STS and progressive disease after at least 1 standard line of systemic therapy. Patients received 60 mg oral cabozantinib once daily in 28-day cycles and dual primary endpoints of overall response rate and 6-month progression free survival (PFS) were assessed. Changes in several circulating biomarkers were assessed as secondary endpoints. RESULTS: Six (11.1%, 95% CI: 4.2%-22.6%) of the 54 evaluable patients enrolled experienced objective responses (all partial responses). Six-month PFS was 49.3% (95% CI: 36.2%-67.3%), with a median time on study of 4 cycles (range, 1-99). The most common grade 3/4 adverse events were hypertension (7.4%) and neutropenia (16.7%). Patients' levels of circulating HGF, soluble MET, and VEGF-A generally increased after a cycle of therapy while soluble VEGFR2 levels decreased, regardless of clinical outcome. CONCLUSION: Cabozantinib single-agent antitumor activity was observed in patients with selected STS histologic subtypes (alveolar soft part sarcoma, undifferentiated pleomorphic sarcoma, extraskeletal myxoid chondrosarcoma, and leiomyosarcoma) highlighting the biomolecular diversity of STS.

5.
Head Neck Pathol ; 2021 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-34618301

RESUMO

Clear cell Odontogenic Carcinoma (CCOC) is an uncommon malignant odontogenic tumor (MOT). It is the fifth most common MOT. A systematic review is presented of reported cases, case series and retrospective studies of CCOC, to determine trends in presentation, diagnostic features, treatment, and patient outcome. Searches of detailed databases were carried out to identify papers reporting CCOC. The variables were demographics, patient symptoms, tumor location, histopathological findings, immunohistochemical studies, treatment, follow-up, and recurrence. 117 cases were identified; CCOC was most frequently seen in mature females 65% (n = 76). The total average age was 55.4 with a range from 17 to 89 years, for females 56.4 and males 53.6 years. The mean size was 3.41 cm. The most common location was in the mandibular body 36.2% (n = 42), followed by the anterior mandible 23.3% (n = 27). The most common clinical presentation was a swelling 80.4% (n = 74), and the main symptom was pain 41.3% (n = 31), followed by painless lesion 24% (n = 18). The most common Immunohistochemistry positive expression was CK19, EMA, and CEA, and for special staining periodic acid Shiff (PAS); 97% of cases were treated surgically. The average follow-up was 30.3 months, and recurrence was reported in 52.4% of the cases. Conclusion: CCOC shows a strong predilection for the body and anterior mandible, and females are more frequently affected. CCOCs can be painful and the principle clinical sign is swelling, CCOCs can metastasize, and the prognosis is fair.

6.
Cancers (Basel) ; 13(19)2021 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-34638237

RESUMO

Multispectral autofluorescence lifetime imaging (maFLIM) can be used to clinically image a plurality of metabolic and biochemical autofluorescence biomarkers of oral epithelial dysplasia and cancer. This study tested the hypothesis that maFLIM-derived autofluorescence biomarkers can be used in machine-learning (ML) models to discriminate dysplastic and cancerous from healthy oral tissue. Clinical widefield maFLIM endoscopy imaging of cancerous and dysplastic oral lesions was performed at two clinical centers. Endoscopic maFLIM images from 34 patients acquired at one of the clinical centers were used to optimize ML models for automated discrimination of dysplastic and cancerous from healthy oral tissue. A computer-aided detection system was developed and applied to a set of endoscopic maFLIM images from 23 patients acquired at the other clinical center, and its performance was quantified in terms of the area under the receiver operating characteristic curve (ROC-AUC). Discrimination of dysplastic and cancerous from healthy oral tissue was achieved with an ROC-AUC of 0.81. This study demonstrates the capabilities of widefield maFLIM endoscopy to clinically image autofluorescence biomarkers that can be used in ML models to discriminate dysplastic and cancerous from healthy oral tissue. Widefield maFLIM endoscopy thus holds potential for automated in situ detection of oral dysplasia and cancer.

7.
Biomater Sci ; 9(22): 7565-7574, 2021 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-34664567

RESUMO

Polydopamine-assisted modification for bone substitute materials has recently shown great application potential in bone tissue engineering due to its excellent biocompatibility and adhesive properties. A scaffold material's impact on osteoclasts is equally as important as its impact on osteoblasts when considering tissue engineering for bone defect repair, as healthy bone regeneration requires an orchestrated coupling between osteoclasts and osteoblasts. How polydopamine-functionalized bone substitute materials modulate the activity of osteoblast lineage cells has been extensively investigated, but much less is known about their impact on osteoclasts. Moreover, most of the polydopamine-functionalized materials would need to additionally load a biomolecule to exert the modulation on osteoclast activity. Herein, we demonstrated that our biomimetic polydopamine-laced hydroxyapatite collagen (PDHC) scaffold material, which does not need to load additional bioactive agent, is sufficiently able to modulate osteoclast activity in vitro. First, PDHC showed an anti-resorptive potential, characterized by decreased osteoclast differentiation and resorption capacity and changes in osteoclasts' transcriptome profile. Next, cAMP response element-binding protein (CREB) activity was found to mediate PDHC's anti-osteoclastogenic effect. Finally, although PDHC altered clastokines expression pattern of osteoclasts, as revealed by transcriptomic and secretomic analysis, osteoclasts' coupling to osteoblasts was not compromised by PDHC. Collectively, this study demonstrated the PDHC material orients osteoclast behavior to an anti-resorptive pattern without compromising osteoclasts' coupling to osteoblasts. Such a feature is favorable for the net increase of bone mass, which endows the PDHC material with great application potential in preclinical/clinical bone defect repair.


Assuntos
Reabsorção Óssea , Osteoclastos , Biomimética , Diferenciação Celular , Colágeno , Durapatita , Humanos , Indóis , Osteoblastos , Polímeros
8.
Artigo em Inglês | MEDLINE | ID: mdl-34711647

RESUMO

BACKGROUND: The Scottish government introduced legislation during the COVID-19 outbreak to permit medical abortion at home with telemedicine. All women received an initial telephone consultation. For those choosing medical abortion, we provided self-administered medications to eligible women with pregnancies under 12 weeks' gestation. AIMS: To assess adherence to the recommended abortion drug regimen, with particular focus on the number of misoprostol doses used and the interval between mifepristone and misoprostol administration and the induction-expulsion interval. Additionally, to evaluate use of analgesia, antiemetics and antibiotics, and the side effects, pain and bleeding profile of medical abortion at home. METHODS: We conducted a prospective cohort study of 663 women choosing medical abortion at home via telemedicine at an NHS abortion service in Edinburgh, Scotland between 1 April and 9 July 2020. Interviewer-administered questionnaires were completed at telephone follow-up 4 and 14 days following treatment. Outcome measures were self-reported and included use of mifepristone and misoprostol, induction-expulsion interval (time from misoprostol administration until expulsion of pregnancy), antiemetics, antibiotics, analgesia use, pain scores, rates of side effects, bleeding and preparedness for treatment. RESULTS: Among the respondents, 652/663 women (98%) answered at least one questionnaire, and 594/663 (89.6%) used both abortion medications as directed (24-72 hours between medications). The mean (SD) induction-expulsion interval was 4.3 (4.3) hours. Antiemetics were used by 611/663 (92%), 383/599 (64%) completed the course of prophylactic antibiotics, and 616/663 (93%) used analgesia, with mean (SD) worst-pain scores of 6.7 (2.2) out of 10. Regarding side effects, 510/663 (77%) experienced either nausea, vomiting, diarrhoea or headache, 101/663 (15%) experienced headache and 510/663 (77%) experienced bleeding that was heavier than a period; 554/663, (84%) felt prepared for their treatment by teleconsultation. CONCLUSION: Patients are able to correctly self-administer abortion medications following a telemedicine consultation. Further research is required to optimise pain management and gastrointestinal side effects during medical abortion.

9.
Environ Int ; 158: 106933, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34662798

RESUMO

BACKGROUND: The urban environment may influence neurodevelopment from conception onwards, but there is no evaluation of the impact of multiple groups of exposures simultaneously. We investigated the association between early-life urban environment and cognitive and motor function in children. METHODS: We used data from 5403 mother-child pairs from four population-based birth-cohorts (UK, France, Spain, and Greece). We estimated thirteen urban home exposures during pregnancy and childhood, including: built environment, natural spaces, and air pollution. Verbal, non-verbal, gross motor, and fine motor functions were assessed using validated tests at five years old. We ran adjusted multi-exposure models using the Deletion-Substitution-Addition algorithm. RESULTS: Higher greenness exposure within 300 m during pregnancy was associated with higher verbal abilities (1.5 points (95% confidence interval 0.4, 2.7) per 0.20 unit increase in greenness). Higher connectivity density within 100 m and land use diversity during pregnancy were related to lower verbal abilities. Childhood exposure to PM2.5 mediated 74% of the association between greenness during childhood and verbal abilities. Higher exposure to PM2.5 during pregnancy was related to lower fine motor function (-1.2 points (-2.1, -0.4) per 3.2 µg/m3 increase in PM2.5). No associations were found with non-verbal abilities and gross motor function. DISCUSSION: This study suggests that built environment, greenness, and air pollution may impact child cognitive and motor function at five years old. This study adds evidence that well-designed urban planning may benefit children's cognitive and motor development.

10.
Environ Int ; 157: 106853, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34500361

RESUMO

Developing children are particularly vulnerable to the effects of exposure to per- and polyfluoroalkyl substances (PFAS), a group of endocrine disrupting chemicals. We hypothesized that early life exposure to PFASs is associated with poor metabolic health in children. We studied the association between prenatal and postnatal PFASs mixture exposure and cardiometabolic health in children, and the role of inflammatory proteins. In 1,101 mothers-child pairs from the Human Early Life Exposome project, we measured the concentrations of PFAS in blood collected in pregnancy and at 8 years (range = 6-12 years). We applied Bayesian Kernel Machine regression (BKMR) to estimate the associations between exposure to PFAS mixture and the cardiometabolic factors as age and sex- specific z-scores of waist circumference (WC), systolic and diastolic blood pressures (BP), and concentrations of triglycerides (TG), high-density lipoprotein (HDL-C) and low-density lipoprotein (LDL-C) cholesterol. We measured thirty six inflammatory biomarkers in child plasma and examined the underlying role of inflammatory status for the exposure-outcome association by integrating the three panels into a network. Exposure to the PFAS mixture was positively associated with HDL-C and systolic BP, and negatively associated with WC, LDL-C and TG. When we examined the independent effects of the individual chemicals in the mixture, prenatal PFHxS was negatively associated with HDL-C and prenatal PFNA was positively associated with WC and these were opposing directions from the overall mixture. Further, the network consisted of five distinct communities connected with positive and negative correlations. The selected inflammatory biomarkers were positively, while the postnatal PFAS were negatively related with the included cardiometabolic factors, and only prenatal PFOA was positively related with the pro-inflammatory cytokine IL-1beta and WC. Our study supports that prenatal, rather than postnatal, PFAS exposure might contribute to an unfavorable lipidemic profile and adiposity in childhood.


Assuntos
Ácidos Alcanossulfônicos , Doenças Cardiovasculares , Poluentes Ambientais , Fluorcarbonetos , Teorema de Bayes , Poluentes Ambientais/toxicidade , Feminino , Fluorcarbonetos/toxicidade , Humanos , Inflamação/induzido quimicamente , Gravidez
11.
Nat Commun ; 12(1): 5387, 2021 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-34508071

RESUMO

Photosynthesis and respiration rely upon a proton gradient to produce ATP. In photosynthesis, the Respiratory Complex I homologue, Photosynthetic Complex I (PS-CI) is proposed to couple ferredoxin oxidation and plastoquinone reduction to proton pumping across thylakoid membranes. However, little is known about the PS-CI molecular mechanism and attempts to understand its function have previously been frustrated by its large size and high lability. Here, we overcome these challenges by pushing the limits in sample size and spectroscopic sensitivity, to determine arguably the most important property of any electron transport enzyme - the reduction potentials of its cofactors, in this case the iron-sulphur clusters of PS-CI (N0, N1 and N2), and unambiguously assign them to the structure using double electron-electron resonance. We have thus determined the bioenergetics of the electron transfer relay and provide insight into the mechanism of PS-CI, laying the foundations for understanding of how this important bioenergetic complex functions.


Assuntos
Proteínas de Bactérias/metabolismo , Metabolismo Energético , Proteínas Ferro-Enxofre/metabolismo , Complexo de Proteína do Fotossistema I/metabolismo , Proteínas de Bactérias/isolamento & purificação , Proteínas de Bactérias/ultraestrutura , Espectroscopia de Ressonância de Spin Eletrônica , Transporte de Elétrons , Proteínas Ferro-Enxofre/ultraestrutura , Complexo de Proteína do Fotossistema I/isolamento & purificação , Complexo de Proteína do Fotossistema I/ultraestrutura , Synechocystis/metabolismo
12.
Anal Chem ; 93(37): 12574-12581, 2021 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-34496203

RESUMO

Previous studies on scanning electrochemical microscopy (SECM) imaging with nonlocal continuous line probes (CLPs) have demonstrated the ability to increase areal imaging rates by an order of magnitude compared to SECM based on conventional ultramicroelectrode (UME) disk electrodes. Increasing the linear scan speed of the CLP during imaging presents an opportunity to increase imaging rates even further but results in a significant deterioration in image quality due to transport processes in the liquid electrolyte. Here, we show that compressed sensing (CS) postprocessing can be successfully applied to CLP-based SECM measurements to reconstruct images with minimal distortion at probe scan rates greatly exceeding the conventional SECM ″speed limit″. By systematically evaluating the image quality of images generated by adaptable postprocessing CS methods for CLP-SECM data collected at varying scan rates, this work establishes a new upper bound for CLP scan rates. While conventional SECM imaging typically uses probe scan speeds characterized by Péclet numbers (Pe) < 1, this study shows that CS postprocessing methods can allow for an accurate image reconstruction for Pe approaching 5, corresponding to an order of magnitude increase in the maximum probe scan speed. This upper limit corresponds to the onset of chaotic convective flows within the electrolyte for the probes investigated in this work, highlighting the importance of considering hydrodynamics in the design of fast-scanning probes.


Assuntos
Diagnóstico por Imagem , Processamento de Imagem Assistida por Computador , Eletrodos , Microscopia Eletroquímica de Varredura , Cintilografia
13.
Int J Behav Nutr Phys Act ; 18(1): 117, 2021 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-34488785

RESUMO

BACKGROUND: In England, the onset of COVID-19 and a rapidly increasing infection rate resulted in a lockdown (March-June 2020) which placed strict restrictions on movement of the public, including children. Using data collected from children living in a multi-ethnic city with high levels of deprivation, this study aimed to: (1) report children's self-reported physical activity (PA) during the first COVID-19 UK lockdown and identify associated factors; (2) examine changes of children's self-reported PA prior to and during the first UK lockdown. METHODS: This study is part of the Born in Bradford (BiB) COVID-19 Research Study. PA (amended Youth Activity Profile), sleep, sedentary behaviours, daily frequency/time/destination/activity when leaving the home, were self-reported by 949 children (9-13 years). A sub-sample (n = 634) also self-reported PA (Physical Activity Questionnaire for Children) pre-pandemic (2017-February 2020). Univariate analysis assessed differences in PA between sex and ethnicity groups; multivariable logistic regression identified factors associated with children's PA. Differences in children's levels of being sufficiently active prior to and during the lockdown were examined using the McNemar test; and multivariable logistic regression was used to identify factors explaining change. RESULTS: During the pandemic, White British (WB) children were more sufficiently active (34.1%) compared to Pakistani Heritage children (PH) (22.8%) or 'Other' ethnicity children (O) (22.8%). WB children reported leaving the home more frequently and for longer periods than PH and O children. Modifiable variables related to being sufficiently active were frequency, duration, type of activity, and destination away from the home environment. There was a large reduction in children being sufficiently active during the first COVID-19 lockdown (28.9%) compared to pre-pandemic (69.4%). CONCLUSIONS: Promoting safe extended periods of PA everyday outdoors is important for all children, in particular for children from ethnic minority groups. Children's PA during the first COVID-19 UK lockdown has drastically reduced from before. Policy and decision makers, and practitioners should consider the findings in order to begin to understand the impact and consequences that COVID-19 has had upon children's PA which is a key and vital behaviour for health and development.


Assuntos
COVID-19/prevenção & controle , Controle de Doenças Transmissíveis , Grupos Étnicos , Exercício Físico , Autorrelato , Adolescente , COVID-19/epidemiologia , Criança , Estudos Transversais , Feminino , Habitação , Humanos , Estudos Longitudinais , Masculino , Grupos Minoritários , SARS-CoV-2 , Reino Unido/epidemiologia
14.
Wellcome Open Res ; 6: 32, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34522788

RESUMO

Background: The coronavirus disease 2019 (COVID-19) pandemic has resulted in thousands of deaths in the UK. Those with existing comorbidities and minority ethnic groups have been found to be at increased risk of mortality. We wished to determine if there were any differences in intensive care unit (ICU) admission and 30-day hospital mortality in a city with high levels of deprivation and a large community of people of South Asian heritage.  Methods: Detailed information on 622 COVID-19-positive inpatients in Bradford and Calderdale between February-August 2020 were extracted from Electronic Health Records. Logistic regression and Cox proportional hazards models were used to explore the relationship between ethnicity with admission to ICU and 30-day mortality, respectively accounting for the effect of demographic and clinical confounders. Results: The sample consisted of 408 (70%) White, 142 (24%) South Asian and 32 (6%) other minority ethnic patients. Ethnic minority patients were younger, more likely to live in deprived areas, and be overweight/obese, have type 2 diabetes, hypertension and asthma compared to white patients, but were less likely to have cancer (South Asian patients only) and COPD. Male and obese patients were more likely to be admitted to ICU, and patients of South Asian ethnicity, older age, and those with cancer were less likely. Being male, older age, deprivation, obesity, and cancer were associated with 30-day mortality. The risk of death in South Asian patients was the same as in white patients HR 1.03 (0.58, 1.82). Conclusions: Despite South Asian patients being less likely to be admitted to ICU and having a higher prevalence of diabetes and obesity, there was no difference in the risk of death compared to white patients. This contrasts with other findings and highlights the value of studies of communities which may have different ethnic, deprivation and clinical risk profiles.

15.
Somatosens Mot Res ; 38(3): 202-213, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34387144

RESUMO

Aim of the study: The purpose of this study was to investigate the effects of receptor density in the glabrous skin of the hand on the perception of the roughness of a textured surface.Materials and methods: This was done by having observers make magnitude estimates of the perceived roughness of raised-dot surfaces at the fingertip, with its high receptor density, and the thenar eminence, with its much lower receptor density.Results: Judgments of perceived roughness averaged over the inter-dot spacings (0.8-5.9 mm) employed in the study did not differ significantly between the two sites, which suggested that roughness perception is not exclusively dependent upon a neural code involving variation in the activity levels of the nerve fibers of spatially distributed receptors, as is the case in spatial discrimination tasks such as spatial-gap detection, grove-orientation discrimination and letter recognition. This hypothesis was further supported by the finding that the elimination of temporal cues by preventing movement of the skin over the raised-dot surface drastically impaired judgments of perceived roughness at the thenar but had little effect on judgments of perceived roughness at the fingertip.Conclusion: These findings suggested that the neural code for perceived roughness at the fingertip is mediated primarily by spatial variation in the activity levels of spatially distributed receptors whereas the neural code for perceived roughness at the thenar is mediated primarily by temporal variation in the activity levels of individual receptors.

16.
ACS Sens ; 6(8): 2787-2801, 2021 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-34351759

RESUMO

Skin-interfaced wearable systems with integrated colorimetric assays, microfluidic channels, and electrochemical sensors offer powerful capabilities for noninvasive, real-time sweat analysis. This Perspective details recent progress in the development and translation of novel wearable sensors for personalized assessment of sweat dynamics and biomarkers, with precise sampling and real-time analysis. Sensor accuracy, system ruggedness, and large-scale deployment in remote environments represent key opportunity areas, enabling broad deployment in the context of field studies, clinical trials, and recent commercialization. On-body measurements in these contexts show good agreement compared to conventional laboratory-based sweat analysis approaches. These device demonstrations highlight the utility of biochemical sensing platforms for personalized assessment of performance, wellness, and health across a broad range of applications.


Assuntos
Suor , Dispositivos Eletrônicos Vestíveis , Microfluídica , Pele
17.
Clin Exp Allergy ; 51(11): 1438-1448, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34363720

RESUMO

BACKGROUND: Higher risks of asthma have been observed in children with prenatal exposure to antibiotics and during early life compared with those who have not. However, the causality of such associations is unclear. OBJECTIVE: To assess whether exposure to antibiotics in early life had a causal effect in increasing the risk of asthma in children diagnosed at 5-8 years of life, and the impact in the target population. METHODS: Data were from electronic health records and questionnaires for children and their mothers in the Born in Bradford birth cohort. Exposure variables were prescriptions of systemic antibiotics to the mother during pregnancy (prenatal) and to the children at 0-24 months of life (postnatal). We assessed the association in 12,476 children with several approaches to deal with different sources of bias (triangulation): the interactions with mother's ethnicity, mode of delivery, and between prenatal and postnatal exposures; dose-response; and estimated the population attributable risk. RESULTS: There was an association between prenatal exposure at 7-27 days before the child's birth and asthma (adjusted OR = 1.40; 1.05, 1.87), but no association with the negative control exposure (before pregnancy) (adjusted OR = 0.99 (0.88, 1.12)). For postnatal exposure, the adjusted OR was 2.00 (1.71, 2.34), and for sibling analysis, it was 1.99 (1.00, 3.93). For postnatal exposure, the risk of asthma increased with the number of prescriptions. The observed effect of both exposures was lower among children with mothers of Pakistani ethnicity, but inconclusive (p > .25). The interaction between prenatal and postnatal exposures was also inconclusive (p = .287). The population attributable risk of postnatal exposure for asthma was 4.6% (0.1% for prenatal). CONCLUSIONS: We conclude that the associations between both late-pregnancy prenatal exposure to antibiotics and postnatal exposure to antibiotics and an increased risk of asthma are plausible and consistent with a causal effect.

18.
Regul Toxicol Pharmacol ; 125: 105004, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34256083

RESUMO

In 2017, the European Union (EU) Committee for Risk Assessment (RAC) recommended the classification of metallic cobalt (Co) as Category 1B with respect to its carcinogenic and reproductive hazard potential and Category 2 for mutagenicity but did not evaluate the relevance of these classifications for patients exposed to Co-containing alloys (CoCA) used in medical devices. CoCA are inherently different materials from Co metal from a toxicological perspective and thus require a separate assessment. CoCA are biocompatible materials with a unique combination of properties including strength, durability, and a long history of safe use that make them uniquely suited for use in a wide-range of medical devices. Assessments were performed on relevant preclinical and clinical carcinogenicity and reproductive toxicity data for Co and CoCA to meet the requirements under the EU Medical Device Regulation triggered by the ECHA re-classification (adopted in October 2019 under the 14th Adaptation to Technical Progress to CLP) and to address their relevance to patient safety. The objective of this review is to present an integrated overview of these assessments, a benefit-risk assessment and an examination of potential alternative materials. The data support the conclusion that the exposure to CoCA in medical devices via clinically relevant routes does not represent a hazard for carcinogenicity or reproductive toxicity. Additionally, the risk for the adverse effects that are known to occur with elevated Co concentrations (e.g., cardiomyopathy) are very low for CoCA implant devices (infrequent reports often reflecting a unique catastrophic failure event out of millions of patients) and negligible for CoCA non-implant devices (not measurable/no case reports). In conclusion, the favorable benefit-risk profile also in relation to possible alternatives presented herein strongly support continued use of CoCA in medical devices.

19.
BMC Med ; 19(1): 166, 2021 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-34289836

RESUMO

BACKGROUND: Multiple omics technologies are increasingly applied to detect early, subtle molecular responses to environmental stressors for future disease risk prevention. However, there is an urgent need for further evaluation of stability and variability of omics profiles in healthy individuals, especially during childhood. METHODS: We aimed to estimate intra-, inter-individual and cohort variability of multi-omics profiles (blood DNA methylation, gene expression, miRNA, proteins and serum and urine metabolites) measured 6 months apart in 156 healthy children from five European countries. We further performed a multi-omics network analysis to establish clusters of co-varying omics features and assessed the contribution of key variables (including biological traits and sample collection parameters) to omics variability. RESULTS: All omics displayed a large range of intra- and inter-individual variability depending on each omics feature, although all presented a highest median intra-individual variability. DNA methylation was the most stable profile (median 37.6% inter-individual variability) while gene expression was the least stable (6.6%). Among the least stable features, we identified 1% cross-omics co-variation between CpGs and metabolites (e.g. glucose and CpGs related to obesity and type 2 diabetes). Explanatory variables, including age and body mass index (BMI), explained up to 9% of serum metabolite variability. CONCLUSIONS: Methylation and targeted serum metabolomics are the most reliable omics to implement in single time-point measurements in large cross-sectional studies. In the case of metabolomics, sample collection and individual traits (e.g. BMI) are important parameters to control for improved comparability, at the study design or analysis stage. This study will be valuable for the design and interpretation of epidemiological studies that aim to link omics signatures to disease, environmental exposures, or both.


Assuntos
Diabetes Mellitus Tipo 2 , MicroRNAs , Criança , Estudos de Coortes , Estudos Transversais , Metilação de DNA , Humanos
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