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Controlling biomolecular-cell interactions is crucial for the design of scaffolds for tissue engineering (TE). Regenerated silk fibroin (RSF) has been extensively used as TE scaffolds, however, RSF showed poor attachment of neuronal cells, such as rat pheochromocytoma (PC12) cells. In this work, amphiphilic peptides containing a hydrophobic isoleucine tail (I3) and laminin or fibronectin derived peptides (IKVAV, PDSGR, YIGSR, RGDS and PHSRN) were designed for promoting scaffold-cell interaction. Three of them (I3KVAV, I3RGDS and I3YIGSR) can self-assemble into nanofibers, therefore, were used to enhance the application of RSF in neuron TE. Live / dead assays revealed that the peptides exhibited negligible cytotoxicity against PC12 cells. The specific interaction between PC12 cells and the peptides were investigate using atomic force microscopy (AFM). The results indicated a synergistic effect in the designed peptides, promoting cellular attachment, proliferation and morphology changes. In addition, AFM results showed that co-assembling peptides I3KVAV and I3YIGSR possesses the best regulation of proliferation and attachment of PC12 cells, consistent with immunofluorescence staining results. Moreover, cell culture with hydrogels revealed that a mixture of peptides I3KVAV and I3YIGSR can also promote 3D neurites outgrowth. The approach of combining two different self-assembling peptides shows great potential for nerve regeneration applications.
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There is evidence that tissue concentrations of mercury (Hg) and selenium (Se) are predicted by numerous dietary, sociodemographic, environmental, and genetic factors. This study aimed to estimate the relative importance of predictors of Hg and Se concentrations in blood samples taken from pregnant women. The Avon Longitudinal Study of Parents and Children (ALSPAC) in the UK measured whole blood Hg and Se concentrations in 3,972 pregnant women. We identified 30 potential predictors of Hg and 24 of Se, which were evaluated using cross-validated random forests to identify the optimal models for predictive power. The relative importance of individual variables was estimated by averaging the added-R2 per predictor. Linkage disequilibrium score regression was used to estimate the variance explained by genotype. A multivariable model of 14 predictors explained 22.4% of Hg variance (95% CI: 13.0 to 37.1), including 6.9% from blood Se and 3.2% from white fish consumption. There were 11 predictors which explained 15.3% of Se variance (CI: 8.9 to 25.9), including 6.4% from blood Hg, 1.3% from blood lead, and 1.3% from oily fish. Measured genetic variation explained 30% of Hg variance (CI: 8.4 to 51.5) and 37.5% of Se (CI: 10.4 to 64.5). A high proportion of Hg and Se variance could be explained from dietary, sociodemographic, metabolic, and genetic factors. Seafood consumption was less predictive of Hg than may be expected and other factors should be considered when determining risk of exposure. There was tentative evidence that genotype is a major contributor to Hg and Se variation, possibly by modifying the efficacy of internal metabolism.
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OBJECTIVE: To investigate the relationship between the dietary approaches to stop hypertension (DASH)-style dietary patterns in childhood and cardiometabolic risk (CMR) in adolescence/early adulthood. DESIGN: Data were obtained from the Avon Longitudinal Study of Parents and Children (ALSPAC) prospective cohort. Diet diary data collected at 7, 10 and 13 years were used to calculate DASH-style diet scores (DDS). Multivariable linear regression models were used to investigate the associations between the DDS at 7, 10 and 13 years and CMR scores, calculated at 17 and 24 years. SETTING: The ALSPAC cohort included children born in south-west England in 1991-1992. PARTICIPANTS: Children with complete dietary, covariate and cardiometabolic data at 17 (n 1,526) and 24 years (n 1,524). RESULTS: A higher DDS at 7 and 10 years was negatively associated with CMR scores at 17 years (ß = -0·64 (95 % CI -1·27, -0·006), Ptrend=0·027 for fifth v. first DDS quintile at 7 years; ß = -0·73 (95 % CI -1·35, -0·12) and Ptrend=0·037 for fifth v. first DDS quintile at 10 years) and at 24 years (ß = -0·92 (95 % CI -1·49, -0·34) Ptrend = 0·001 for fifth v. first DDS quintile at 7 years; ß = -0·60 (95 % CI -1·20, -0·05) Ptrend = 0·092 for fifth v. first DDS quintile at 10 years). No associations were found between the DDS at 13 years and CMR score at 17 and 24 years. CONCLUSION: Greater adherence with a DASH-style diet during childhood was associated with better cardiometabolic health in adolescence/adulthood in the ALSPAC cohort. The components of the DASH diet could be recommended to improve children's cardiometabolic health.
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Abordagens Dietéticas para Conter a Hipertensão , Hipertensão , Criança , Humanos , Adolescente , Adulto , Hipertensão/epidemiologia , Hipertensão/prevenção & controle , Padrões Dietéticos , Coorte de Nascimento , Estudos Prospectivos , Estudos LongitudinaisRESUMO
OBJECTIVE: The National Health Service (NHS) England website provides guidance on foods/drinks to avoid or limit during pregnancy because of microbiological, toxicological or teratogenic hazards. The aims were to determine adherence and whether demographic characteristics were associated with adherence. DESIGN: Cross-sectional study. SETTING: Online survey of postpartum women resident in England during pregnancy. PARTICIPANTS: Recently, postpartum women resident in England during their pregnancy (n 598; median age 33 (IQR 30-36) years) completed an online questionnaire (April-November 2022). Questions included those on consumption of twenty-one food/drink items that the NHS advises pregnant women to avoid/limit. The study is part of the Pregnancy, the Environment And nutRition (PEAR) Study. Summary statistics were used to determine proportions adhering to the guidance. Adjusted logistic regression was used to model the associations of adherence with demographic characteristics. RESULTS: Adherence was generally high (>90 % for eight of ten food/drink items to be avoided). However, among pre-pregnancy consumers, several items were not completely avoided, for example, 81 % (128/158) for game meat/gamebirds, 37 % (176/478) for cured meats and 17 % (81/467) for soft cheeses. Greater educational attainment (e.g. caffeinated soft drinks OR 2·25 (95 % CI 1·28, 3·94)), greater maternal age (e.g. oily fish 1·64 (1·05, 2·56)) and lower parity (e.g. caffeinated coffee 0.28 (0.11, 0.69)) were the most usual characteristics associated with adherence. CONCLUSION: Evidence of concerning levels of non-adherence for some food/drink items suggests a case for more education on some of the guidance, particularly for women with lower educational attainment, greater parity and greater maternal age. Further research on barriers to the implementation of the guidance is needed.
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Alimentos , Medicina Estatal , Feminino , Humanos , Gravidez , Adulto , Estudos Transversais , Inquéritos e Questionários , Bebidas GaseificadasRESUMO
This study examined the relationship between childhood diet quality and arterial stiffness and thickness during adolescence/early adulthood. Participants were from the Avon Longitudinal Study of Parents and Children (ALSPAC) with dietary data at ages 7, 10 and 13 years and pulse wave velocity (PWV) and carotid intima-media thickness (cIMT) at ages 17 and/or 24 years. Diet quality (DQ) was assessed using five scores: a children's Mediterranean-style diet (C-rMED) Z-score, a children's Dietary Inflammatory Z-score (C-DIS), a DASH diet Z-score, a children's Eatwell Guide (C-EWG) Z-score reflecting UK dietary guidelines and a data-driven obesogenic Z-score. Adjusted regression models examined the associations between DQ scores at 7-13 years and PWV and cIMT at 17 and 24 years. In adjusted models, a high v. low Obesogenic Z-score at 7 and 10 years was associated with higher PWV at 17: ß 0.07 (95 % CI 0.01, 0.13) and ß 0.10 (95 % CI 0.04, 0.16), respectively. A high v. low C-rMED Z-score at 7 years was associated with lower PWV at 17 (ß -0.07; 95 % CI -0.14, -0.01). A high (more anti-inflammatory) vs low C-DIS Z-score at 10 years was associated with a lower PWV at 17 years: ß -0.06 (95 % CI -0.12, -0.01). No other associations were observed. In conclusion, an Obesogenic dietary pattern in childhood (7-10 years) was related to increased arterial stiffness, while Mediterranean-style and anti-inflammatory diets were related to decreased arterial stiffness in adolescence. This highlights the importance of establishing healthy dietary habits early in life to protect against vascular damage.
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Espessura Intima-Media Carotídea , Rigidez Vascular , Criança , Humanos , Adolescente , Adulto , Estudos Longitudinais , Análise de Onda de Pulso , Artérias Carótidas , Dieta , Anti-InflamatóriosRESUMO
Mercury has high industrial utility and is present in many products, and environmental contamination and occupational exposure are widespread. There are numerous biological systems involved in the absorption, metabolism, and excretion of Hg, and it is possible that some systems may be impacted by genetic variation. If so, genotype may affect tissue concentrations of Hg and subsequent toxic effects. Genome-wide association testing was performed on blood Hg samples from pregnant women of the Avon Longitudinal Study of Parents and Children (n = 2893) and children of the Human Early Life Exposome (n = 1042). Directly-genotyped single-nucleotide polymorphisms (SNPs) were imputed to the Haplotype Reference Consortium r1.1 panel of whole genotypes and modelled againstlog-transformed Hg. Heritability was estimated using linkage disequilibrium score regression. The heritability of Hg was estimated as 24.0% (95% CI: 16.9% to 46.4%) in pregnant women, but could not be determined in children. There were 16 SNPs associated with Hg in pregnant women above a suggestive p-value threshold (p < 1 × 10-5), and 21 for children. However, no SNP passed this threshold in both studies, and none were genome-wide significant (p < 5 × 10-8). SNP-Hg associations were highly discordant between women and children, and this may reflect differences in metabolism, a gene-age interaction, or dose-response effects. Several suggestive variants had plausible links to Hg metabolism, such as rs146099921 in metal transporter SLC39A14, and two variants (rs28618224, rs7154700) in potassium voltage-gated channel genes. The findings would benefit from external validation, as suggestive results may contain both true associations and false positives.
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Estudo de Associação Genômica Ampla , Mercúrio , Gravidez , Criança , Humanos , Feminino , Gestantes , Estudos Longitudinais , GenótipoRESUMO
In 2001 the U.S. Food and Drug Administration (FDA) issued precautionary advice to pregnant women to limit fish consumption over concern that the methylmercury content might harm their children's neurodevelopment. This concern was based largely on results from an epidemiological study of mothers primarily exposed to methylmercury from consuming pilot whale. Subsequently, FDA and the World Health Organization/Food and Agriculture Organization (WHO/FAO) undertook independent assessments of fish consumption that considered net effects from both fish nutrients, primarily omega-3 fatty acids, as beneficial and methylmercury as harmful. Both assessments estimated that when mothers regularly consume fish during pregnancy, their children are likely to have improved neurodevelopment compared to children of non-fish eaters despite their exposure to methylmercury. These estimated improvements included gains of two to over five full scale IQ points from levels of maternal consumption that are achievable in most of the world. Consistent with those estimates, human research on fish consumption and child neurodevelopment from more than 200,000 mother-child pairs now collectively reports 51 beneficial associations with neurodevelopmental outcomes and three adverse associations, the latter with no discernable pattern. These associations include full scale IQ gains similar to, or somewhat higher than, those estimated by FDA and FAO/WHO. Also consistent with the FDA and FAO/WHO estimates, research has reported beneficial associations with fish consumption when pregnant women are exposed to methylmercury from fish in excess of the U.S. Environmental Protection Agency's (EPA) Reference Dose (RfD). Our analysis evaluates how the net effects approach as utilized by FDA and FAO/WHO provides a holistic explanation for these results with implications for public health policy. This concordance of net effects modeling and empirical scientific evidence supports a clarification of current public health recommendations to focus on greater fish consumption by pregnant women for their children's neurodevelopment.
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Ácidos Graxos Ômega-3 , Compostos de Metilmercúrio , Animais , Humanos , Feminino , Gravidez , Compostos de Metilmercúrio/toxicidade , Compostos de Metilmercúrio/análise , Alimentos Marinhos/efeitos adversos , Alimentos Marinhos/análise , Peixes , Mães , Contaminação de Alimentos/análiseRESUMO
Polyhydroxyalkanoates are natural, biodegradable, thermoplastic and sustainable polymers with a huge potential in fabrication of bioresorbable implantable devices for tissue engineering. We describe a comparative evaluation of three medium chain length polyhydroxyalkanoates (mcl-PHAs), namely poly(3-hydroxyoctanoate), poly(3-hydroxyoctanoate-co-3-hydoxydecanoate) and poly(3-hydroxyoctanoate-co-3-hydroxydecanoate-co-3-hydroxydodecanoate), one short chain length polyhydroxyalkanoate, poly(3-hydroxybutyrate), P(3HB) and synthetic aliphatic polyesters (polycaprolactone and polylactide) with a specific focus on nerve regeneration, due to mechanical properties of mcl-PHAs closely matching nerve tissues. In vitro biological studies with NG108-15 neuronal cell and primary Schwann cells did not show a cytotoxic effect of the materials on both cell types. All mcl-PHAs supported cell adhesion and viability. Among the three mcl-PHAs, P(3HO-co-3HD) exhibited superior properties with regards to numbers of cells adhered and viable cells for both cell types, number of neurite extensions from NG108-15 cells, average length of neurite extensions and Schwann cells. Although, similar characteristics were observed for flat P(3HB) surfaces, high rigidity of this biomaterial, and FDA-approved polymers such as PLLA, limits their applications in peripheral nerve regeneration. Therefore, we have designed, synthesized and evaluated these materials for nerve tissue engineering and regenerative medicine, the interaction of mcl-PHAs with neuronal and Schwann cells, identifying mcl-PHAs as excellent materials to enhance nerve regeneration and potentially their clinical application in peripheral nerve repair.
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Guidance on foods to limit or avoid in pregnancy is provided on the NHS website for England. Advice on fish consumption is related to exposure to mercury, dioxins and polychlorinated biphenyls, which may have adverse effects on fetal neurodevelopment. Our aim was to provide evidence on the effectiveness of the guidance in minimising exposure to toxins while maximising nutrient intake in a mixed-methods study. An online questionnaire on fish consumption before/during pregnancy was completed by postpartum women (≤12 months) in England (n = 598). A subsample of participants was invited to take part in an interview (n = 14). Women who ate fish before pregnancy reduced their intakes of both oily and white fish during pregnancy, with some avoiding it altogether. Women did not exceed the limit on tinned tuna, but there was evidence of mis-recall on the suggested limit. Overall intakes of fish were below that recommended during pregnancy (36% compliance for pre-pregnancy consumers). Barriers to fish consumption included risk aversion, confusion over specific details of the guidance, cost, availability, family preferences and smell/taste. Clarity and simplicity of the NHS guidance, with an overall message on the number of portions of fish a week advised prominently shown, would help pregnant women to benefit from the nutrients in fish while minimising exposure to toxins. The guidance on the number of cans of tuna advised per week is poorly recalled and needs to be disseminated accurately. The guidance on shark/marlin/swordfish could receive less prominence as it is rarely eaten by pregnant women in England.
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Mercúrio , Animais , Feminino , Humanos , Gravidez , Ingestão de Alimentos , Alimentos Marinhos/análise , Cuidado Pré-Natal , Inglaterra , Peixes , Contaminação de Alimentos/prevenção & controle , Contaminação de Alimentos/análiseRESUMO
Silane modification is a simple and cost-effective tool to modify existing biomaterials for tissue engineering applications. Aminosilane layer deposition has previously been shown to control NG108-15 neuronal cell and primary Schwann cell adhesion and differentiation by controlling deposition of âNH2 groups at the submicron scale across the entirety of a surface by varying silane chain length. This is the first study toreport depositing 11-aminoundecyltriethoxysilane (CL11) onto aligned Polycaprolactone (PCL) scaffolds for peripheral nerve regeneration. Fibers are manufactured via electrospinning and characterized using water contact angle measurements, atomic force microscopy (AFM), and X-ray photoelectron spectroscopy (XPS). Confirmed modified fibers are investigated using in vitro cell culture of NG108-15 neuronal cells and primary Schwann cells to determine cell viability, cell differentiation, and phenotype. CL11-modified fibers significantly support NG108-15 neuronal cell and Schwann cell viability. NG108-15 neuronal cell differentiation maintains Schwann cell phenotype compared to unmodified PCL fiber scaffolds. 3D ex vivo culture of Dorsal root ganglion explants (DRGs) confirms further Schwann cell migration and longer neurite outgrowth from DRG explants cultured on CL11 fiber scaffolds compared to unmodified scaffolds. Thus, a reproducible and cost-effective tool is reported to modify biomaterials with functional amine groups that can significantly improve nerve guidance devices and enhance nerve regeneration.
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Silanos , Alicerces Teciduais , Alicerces Teciduais/química , Engenharia Tecidual/métodos , Materiais Biocompatíveis/química , Células de Schwann , Nervos Periféricos , Regeneração NervosaRESUMO
Infant-directed speech often has hyperarticulated features, such as point vowels whose formants are further apart than in adult-directed speech. This increased "vowel space" may reflect the caretaker's effort to speak more clearly to infants, thus benefiting language processing. However, hyperarticulation may also result from more positive valence (e.g., speaking with positive vocal emotion) often found in mothers' speech to infants. This study was designed to replicate others who have found hyperarticulation in maternal speech to their 6-month-olds, but also to examine their speech to a non-human infant (i.e., a puppy). We rated both kinds of maternal speech for their emotional valence and recorded mothers' speech to a human adult. We found that mothers produced more positively valenced utterances and some hyperarticulation in both their infant- and puppy-directed speech, compared to their adult-directed speech. This finding promotes looking at maternal speech from a multi-faceted perspective that includes emotional state.
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IMPORTANCE: Distressing sexual problems are a common complaint of menopausal women. In 2013, a Cochrane review assessed the effect of hormone therapy on sexual function in menopausal women; however, new evidence has since been published, which should be considered. OBJECTIVE: This systematic review and meta-analysis aims to update the evidence synthesis on the effect of hormone therapy, compared with control, on sexual function in perimenopausal and postmenopausal women. EVIDENCE REVIEW: Thirteen databases and clinical trial registries (Cochrane Central Register of Controlled Trials, EMBASE, Medical Literature Analysis and Retrieval System Online, PsycINFO, Web of Science, Cumulative Index to Nursing and Allied Health Literature, Literatura Latino-Americana e do Caribe em Ciéncias da Saúde, Database of Abstracts of Reviews of Effects, ClinicalTrials.gov , International Clinical Trials Registry Platform, Iranian Registry of Clinical Trials, Chinese Clinical Trial Registry, ISRCTN) were searched from December 2012 to March 30, 2022. Backward reference searching on all retrieved full texts was also performed. Study quality was assessed using the Cochrane ROB.2 tool. Data were pooled in random-effect model meta-analyses, which included all studies identified in the present search and all studies previously included in the 2013 Cochrane review. FINDINGS: Forty-seven randomized controlled trials (35,912 participants) were included in the systematic review, and 34 randomized controlled trials (15,079 participants) were included in the meta-analysis. The meta-analysis revealed that, in comparison to control, estrogen therapy (standardized mean difference [SMD], 0.16; 95% confidence interval [CI], 0.02 to 0.29; I2 = 59%; 2,925 participants, 16 studies), estrogen plus progestogen therapy (SMD, 0.11; 95% CI, -0.07 to 0.29; I2 = 65%; 2,432 participants, 7 studies), tibolone (SMD, 0.15; 95% CI, 0.02 to 0.28; I2 = 0%; 916 participants, 2 studies), and selective estrogen receptor modulators (SMD, 0.18; 95% CI, 0.06 to 0.30; I2 = 0%; 1,058 participants, 4 studies) may result in no effect to small benefit on sexual function composite score. CONCLUSION AND RELEVANCE: Hormone therapy may slightly improve sexual functioning. This potential small benefit should be considered when discussing treatment options for other menopausal symptoms.
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Perimenopausa , Pós-Menopausa , Feminino , Humanos , Irã (Geográfico) , Estrogênios/uso terapêutico , Estrogênios/farmacologia , MenopausaRESUMO
Research into how alignment to UK dietary guidelines during childhood affects cardiometabolic health is limited. The association between adherence to UK dietary guidelines during childhood and overall cardiometabolic risk (CMR) in adolescence/early adulthood was explored using data from the Avon Longitudinal Study of Parents and Children (ALSPAC). ALSPAC children with diet diaries completed at 7, 10 and 13 years of age, and data on CMR markers at 17 years (n 1940) and 24 years (n 1957) were included. A children's Eatwell Guide (C-EWG) score was created by comparing dietary intakes at each age to UK dietary guidelines for nine foods/nutrients. Cardiometabolic health at 17 and 24 years was assessed using a composite CMR score. Multivariable linear regression models examined associations between C-EWG scores at 7, 10 and 13 years and the CMR score at 17 and 24 years, adjusting for confounders. C-EWG scores were generally low. However, a higher score (adherence to more dietary guidelines) at 7 years old was associated with a lower CMR score at 17 and 24 years: ß -0·13 (95 % CI -0·25, -0·01) and ß -0·25 (95 % CI -0·38, -0·13) for a 1-point increase in C-EWG score, respectively. A higher C-EWG score at 10 years was also associated with a lower CMR z-score at 24 years. No clear associations were evident at other ages. Greater adherence to UK dietary guidelines during mid-childhood was associated with a better overall cardiometabolic profile, suggesting that encouraging children to eat in this way has long-term benefits to health.
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Doenças Cardiovasculares , Pais , Humanos , Adolescente , Criança , Adulto , Estudos Longitudinais , Fatores de Risco , Doenças Cardiovasculares/prevenção & controle , Reino UnidoRESUMO
BACKGROUND: The National Health Service (NHS) website gives guidance for pregnant women in England on foods/drinks to avoid or limit because of microbiological, toxicological or teratogenic hazards. These include, for example, some types of soft cheeses, fish/seafood and meat products. This website and midwives are trusted sources of information for pregnant women, but the ways in which midwives can be supported to provide clear and accurate information are unknown. AIMS: The aims were to: (1) determine midwives' accuracy of recall of information and confidence in delivering the guidance to women; (2) identify barriers to provision; (3) identify the ways in which midwives provide this information to women. METHODS: Registered Midwives practicing in England completed an online questionnaire. Questions included those on what information they provided and their confidence in delivering it, the ways they provided information on foods to avoid/limit, their recall of some of the guidance, and what resources they used. Ethics approval was given by the University of Bristol. RESULTS: More than 10% of midwives (n = 122) were 'Not at all confident/Don't know' in providing advice about ten items, including game meat/gamebirds (42% and 43%, respectively), herbal teas (14%) and cured meats (12%). Only 32% correctly recalled overall advice on eating fish, and only 38% the advice on tinned tuna. The main barriers to provision were lack of time in appointments and lack of training. The most usual methods of disseminating information were verbal (79%) and signposting to websites (55%). CONCLUSION: Midwives were often unconfident about their ability to provide accurate guidance, and recall on items tested was frequently mistaken. Delivery of guidance by midwives on foods to avoid or limit needs to be supported by appropriate training and access to resources, and sufficient time in appointments. Further research on barriers to the delivery and implementation of the NHS guidance is needed.
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Tocologia , Gestantes , Feminino , Gravidez , Humanos , Cuidado Pré-Natal , Medicina Estatal , InglaterraRESUMO
AIMS: Fully closed-loop insulin delivery has been shown in clinical trials to be safe and improve glucose control compared with standard insulin therapy in the inpatient setting. We investigated the feasibility of implementing the approved CamAPS HX fully closed-loop system in a hospital setting. METHODS: This implementation project was conducted in a large teaching hospital in Cambridge, UK. Healthcare professional training was multimodal including face-to-face workshops, online learning modules and supported by standard operating procedures. Set-up and maintenance of closed-loop devices were undertaken by the inpatient diabetes team. Selection of suitable patients was multidisciplinary and prioritised those with more challenging diabetes management. Demographic and clinical data were collected from electronic health records and diabetes data management platforms. RESULTS: In the 12 months since the closed-loop system was implemented, 32 inpatients (mean ± SD age 61 ± 16 years, 8 females, 24 males) used closed-loop insulin delivery during their admission, across medical and surgical wards in the hospital with a total of 555 days of closed-loop glucose control (median [IQR]: 14 [6, 22] days per inpatient). The time spent in target glucose range 3.9-10.0 mmol/L was 53.3 ± 18.3%. Mean glucose was 10.7 ± 1.9 mmol/L with 46.0 ± 18.2% of time spent with glucose >10.0 mmol/L. Time spent with sensor glucose below 3.9 mmol/L was low (median [IQR]: 0.38 [0.00, 0.85]). There were no episodes of severe hypoglycaemia or diabetic ketoacidosis during closed-loop use. CONCLUSIONS: We have demonstrated that the fully closed-loop system can be safely and effectively implemented by a diabetes outreach team in complex medical and surgical inpatients with challenging glycaemic control.
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Diabetes Mellitus Tipo 1 , Insulina , Masculino , Feminino , Humanos , Pessoa de Meia-Idade , Idoso , Insulina/uso terapêutico , Glicemia , Hipoglicemiantes/uso terapêutico , Pacientes Internados , Diabetes Mellitus Tipo 1/tratamento farmacológico , Resultado do Tratamento , Sistemas de Infusão de Insulina , Estudos Cross-OverRESUMO
Cell metabolism coordinates the biochemical reactions that produce carbon and ATP in order for the cell to proliferate, differentiate, and respond to environmental changes. Cell type determines metabolic demand, so proliferating skeletal progenitors and differentiated osteoblasts exhibit different levels of cell metabolism. Limb regeneration is an energetically demanding process that involves multiple types of tissues and cell functions over time. Dysregulation of cell metabolism in aged mice results in impaired regeneration, a defect that can be rescued in part by the administration of oxaloacetate (OAA). A better understanding of how cell metabolism regulates regeneration in general, and how these changes can be modulated to benefit potential regenerative strategies in the future is needed. Here we sought to better understand the effects of OAA on young mice and determine whether the same mechanism could be tapped to improve regeneration without an aged-defect. We also asked which dosing time periods were most impactful for promoting regenerative outcomes, and whether these effects were sustained after dosing was stopped. Consistent with our findings in aged mice we found that OAA enhanced regeneration by accelerating bone growth, even beyond control measures, by increasing trabecular thickness, decreasing trabecular spacing, and improving the patterning by decreasing the taper, making the regenerated bone more like an unamputated digit. Our data suggests that the decrease in spacing, an improvement over aged mice, may be due to a decrease in hypoxia-driven vasculature. Our findings suggest that OAA, and similar metabolites, may be a strong tool to promote regenerative strategies and investigate the mechanisms that link cell metabolism and regeneration.
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The use of nerve guidance conduits (NGCs) to treat peripheral nerve injuries is a favorable approach to the current "gold standard" of autografting. However, as simple hollow tubes, they lack specific topographical and mechanical guidance cues present in nerve grafts and therefore are not suitable for treating large gap injuries (30-50 mm). The incorporation of intraluminal guidance scaffolds, such as aligned fibers, has been shown to increase neuronal cell neurite outgrowth and Schwann cell migration distances. A novel blend of PHAs, P(3HO)/P(3HB) (50:50), was investigated for its potential as an intraluminal aligned fiber guidance scaffold. Aligned fibers of 5 and 8 µm diameter were manufactured by electrospinning and characterized using SEM. Fibers were investigated for their effect on neuronal cell differentiation, Schwann cell phenotype, and cell viability in vitro. Overall, P(3HO)/P(3HB) (50:50) fibers supported higher neuronal and Schwann cell adhesion compared to PCL fibers. The 5 µm PHA blend fibers also supported significantly higher DRG neurite outgrowth and Schwann cell migration distance using a 3D ex vivo nerve injury model.
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Traumatismos dos Nervos Periféricos , Traumatismos dos Nervos Periféricos/terapia , Células de Schwann/citologia , Adesão Celular , Poli-Hidroxialcanoatos/química , Elétrons , Animais , Camundongos , Células Cultivadas , Movimento CelularRESUMO
Children who are picky eaters often develop feeding difficulties during preschool years. These difficulties may persist into adolescence in some children. The study aim was to examine feeding difficulties and maternal feeding strategies longitudinally from age 5.5-8.5 years in relation to persistent picky eating. Picky eating behaviour in children enrolled in the Avon Longitudinal Study of Parents and Children was assessed using questionnaires between 2 and 5.5 years of age. Feeding behaviours were evaluated using questionnaires between 5.5 and 8.5 years. Data were analysed using adjusted logistic regression models. Of the 7405 children with data on picky eating 1926 (26%) were classified as never picky eaters, 385 (5%) were non-persistent picky eaters and 564 (8%) were persistent picky eaters. At 5.5, 7 and 8.5 years both persistent picky eaters and non-persistent picky eaters were more likely than never picky eaters to indicate difficulties in eating what the mother wanted, deliberately eat insufficiently, refuse to eat what was on offer, be choosy, not over-eat, and be difficult to get into routine, but with the likelihood decreasing with age (e.g. in persistent picky eaters vs non-picky eaters: refused to eat offered food OR 44.2 (95% CI 29.1, 67.0) at 5.5 years, 15.5 (11.5, 20.8) at 7 years and 14.1 (10.7, 18.6) at 8.5 years). The families of children who are picky eaters at the time of entering the school system should be offered reassurance that the feeding difficulties are likely to slowly resolve over time.
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Preferências Alimentares , Mães , Feminino , Adolescente , Pré-Escolar , Criança , Humanos , Estudos Longitudinais , Pais , Alimentos , Comportamento Alimentar , Inquéritos e QuestionáriosRESUMO
AIM/OBJECTIVE: This study evaluates the effectiveness and users' experience of using live stream technology to conduct workplace observation assessments of trainee dental nurses. Information on the usability, accessibility, and general satisfaction of this technological technique were collected. MATERIALS AND METHODS: This nationwide cross-sectional survey was conducted in Scotland and included one focus group and three online questionnaires with qualitative and quantitative questions. The quantitative responses were described using standard descriptive analysis, while the quantitative data were investigated using thematic analysis. RESULTS: Eighty-one trainee dental nurses, 35 clinicians and 19 assessors participated in this study. Live stream observation was generally well received by the trainee dental nurses and clinicians, who thought that it had helped increase their confidence to perform practical skills. The assessors also stated that overall satisfaction was high, and that live stream observation met their expectations for efficacy. However, several technical challenges, such as network issues were brought up by responders. CONCLUSION: This study provides evidence that workplace observation assessments can be performed in the future by using live stream technology. However, additional investigation and comparison will aid in determining the most effective way of using this approach and providing feedback to promote learning among dental trainees.
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Glacial lake outburst floods (GLOFs) represent a major hazard and can result in significant loss of life. Globally, since 1990, the number and size of glacial lakes has grown rapidly along with downstream population, while socio-economic vulnerability has decreased. Nevertheless, contemporary exposure and vulnerability to GLOFs at the global scale has never been quantified. Here we show that 15 million people globally are exposed to impacts from potential GLOFs. Populations in High Mountains Asia (HMA) are the most exposed and on average live closest to glacial lakes with ~1 million people living within 10 km of a glacial lake. More than half of the globally exposed population are found in just four countries: India, Pakistan, Peru, and China. While HMA has the highest potential for GLOF impacts, we highlight the Andes as a region of concern, with similar potential for GLOF impacts to HMA but comparatively few published research studies.