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1.
SSM Qual Res Health ; 2: None, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36531295

RESUMO

The management of uncertainty in clinical practice has been an enduring topic of sociological scholarship. However, little of this addresses how uncertainty and non-knowledge are attributed to the self and other actors. We take the example of checking for developmental dysplasia of the hip (DDH), part of infant screening in UK primary care, to examine the 'double contingency' of attributions of uncertainty and ignorance. Our data come from interviews with parents and General Practitioners (GPs), and observations of the six-week check conducted as part of a study to develop a checklist to aid GPs' diagnostic and referral decisions. Parents' pervasive uncertainties about managing with a new-born infant place them in a trusting relation to biomedicine, in which knowledge about infant hips is delegated to the clinical team: most described themselves as not-knowing about DDH. GPs focus on the uncertainties of applying sensory and experiential knowledge of infant bodies, in a consultation with more diffuse aims than screening for DDH. A prototype checklist, developed by orthopaedic specialists, was an explicit attempt to reduce uncertainty around thresholds for referral. However, using the checklist surfaced multiple logics of uncertainty. It also surfaced attributions of uncertainty and non-knowledge to other actors: orthopaedic specialists' assumptions about GPs' uncertain technical knowledge; GPs' assumptions about orthopaedic specialists' ignorance of the primary care setting; and clinicians' assumptions about the role of parental ignorance. This 'double contingency' of attributions of other actors' non-knowledge is a salient additional dimension to the uncertainty that infuses biomedical practice.

2.
Animals (Basel) ; 12(4)2022 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-35203196

RESUMO

Green sea turtles (Chelonia mydas) are an endangered species, which as juveniles are prone to the debilitating disease green turtle fibropapillomatosis (FP). Previous work has shown an association between reduced immune function and FP. As vitamin D has been linked to immune function in numerous animals, the aim of this study was to compare vitamin D levels in green sea turtles with and without evident FP and determine if exposure to sunlight would influence vitamin D levels and other health parameters. Various health markers, including vitamin D, in turtles with and without evident tumors being treated at a rehabilitation facility in southeast Florida were compared to apparently healthy wild-caught juvenile green turtles. Turtles receiving treatment were housed in tanks exposed to higher or lower levels of sunlight for up to 6 months. Upon intake, tumored individuals had lower plasma vitamin D and ionized calcium levels and higher parathyroid hormone levels when compared to both wild-caught and rehabilitation turtles without evident tumors. Individuals exposed to greater sunlight showed greater increases in plasma vitamin D and a more successful recovery. The results suggest that increasing sun exposure in rehabilitation facilities may enhance health and recovery in green turtles with FP.

3.
JPGN Rep ; 3(2): e190, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-37168924

RESUMO

Some infants aspirate thin liquids and must be fed thickened liquids in order to protect the lungs. However, thickeners have not been fully studied for safety. Xanthan-based thickeners have been implicated in the development of necrotizing enterocolitis and rice cereal-based thickeners have been associated with constipation and excessive weight gain. The aim of this study was to compare rates of adverse events between both thickeners. Methods: Single-center retrospective chart review conducted at a tertiary pediatric care center between January 2013 and July 2017. All infants deemed unsafe for oral feeding and treated with xanthan- or rice cereal-based milk thickeners were included. Data were extracted from the medical records and patients categorized according to the type of thickener. Primary outcome was the occurrence of diarrhea, constipation, overweight, and obesity at 3-6 and 6-12 months after thickener initiation. Appropriate statistical tests were used. In addition, an e-mail was sent to 14 level III Canadian Pediatric hospitals inquiring about their practice. Results: We identified 53 patients to be included in the study; 20 used xanthan-based- and 33 used rice cereal-based milk thickeners. Rates of diarrhea, constipation, overweight, and obesity at 3-6 and 6-12 months after initiation were not different between thickeners. Important variability concerning thickening practices was reported by the 8 centers that responded. Conclusions: In infants treated with milk thickeners, xanthan-based or rice cereal-based thickeners may have similar safety profiles that require further investigation including a larger number of patients.

4.
Sci Rep ; 11(1): 24162, 2021 12 17.
Artigo em Inglês | MEDLINE | ID: mdl-34921188

RESUMO

The southwest coast of Florida experiences annual red tides, a type of harmful algal bloom that results from high concentrations of Karenia brevis. These dinoflagellates release lipophilic neurotoxins, known as brevetoxins, that bind to sodium channels and inhibit their inactivation, resulting in a variety of symptoms that can lead to mass sea turtle strandings. Traditional therapies for brevetoxicosis include standard and supportive care (SSC) and/or dehydration therapy; however, these treatments are slow-acting and often ineffective. Because red tide events occur annually in Florida, our objective was to test intravenous lipid emulsion (ILE) as a rapid treatment for brevetoxicosis in sea turtles and examine potential impacts on toxin clearance rates, symptom reduction, rehabilitation time, and survival rates. Sea turtles exhibiting neurological symptoms related to brevetoxicosis were brought to rehabilitation from 2018-2019. Upon admission, blood samples were collected, followed by immediate administration of 25 mg ILE/kg body mass (Intralipid® 20%) at 1 mL/min using infusion pumps. Blood samples were collected at numerous intervals post-ILE delivery and analyzed for brevetoxins using enzyme-linked immunosorbent assays. In total, nine (four subadults, one adult female, four adult males) loggerheads (Caretta caretta), five (four juvenile, one adult female) Kemp's ridleys (Lepidochelys kempii), and four juvenile green turtles (Chelonia mydas) were included in this study. We found that plasma brevetoxins declined faster compared to turtles that received only SSC. Additionally, survival rate of these patients was 94% (17/18), which is significantly higher than previous studies that used SSC and/or dehydration therapy (47%; 46/99). Nearly all symptoms were eliminated within 24-48 h, whereas using SSC, symptom elimination could take up to seven days or more. The dosage given here (25 mg/kg) was sufficient for turtles in this study, but the use of a higher dosage (50-100 mg/kg) for those animals experiencing severe symptoms may be considered. These types of fast-acting treatment plans are necessary for rehabilitation facilities that are already resource-limited. Intravenous lipid emulsion therapy has the potential to reduce rehabilitation time, save resources, and increase survival of sea turtles and other marine animals experiencing brevetoxicosis.


Assuntos
Doenças dos Animais/tratamento farmacológico , Emulsões Gordurosas Intravenosas/farmacologia , Proliferação Nociva de Algas , Toxinas Marinhas/intoxicação , Oxocinas/intoxicação , Tartarugas , Animais , Florida
5.
Metabolites ; 11(7)2021 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-34357352

RESUMO

Oxidative stress has been acknowledged as a major factor in aging, senescence and neurodegenerative conditions. Mammalian models are susceptible to these stresses following the restoration of oxygen after anoxia; however, some organisms including the freshwater turtle Trachemys scripta can withstand repeated anoxia and reoxygenation without apparent pathology. T. scripta thus provides us with an alternate vertebrate model to investigate physiological mechanisms of neuroprotection. The objective of this study was to investigate the antioxidant methionine sulfoxide reductase system (Msr) in turtle neuronal tissue. We examined brain transcript and protein levels of MsrA and MsrB and examined the potential for the transcription factor FOXO3a to regulate the oxygen-responsive changes in Msr in vitro. We found that Msr mRNA and protein levels are differentially upregulated during anoxia and reoxygenation, and when cells were exposed to chemical oxidative stress. However, while MsrA and MsrB3 levels increased when cell cultures were exposed to chemical oxidative stress, this induction was not enhanced by treatment with epigallocatechin gallate (EGCG), which has previously been shown to enhance FOXO3a levels in the turtle. These results suggest that FOXO3a and Msr protect the cells from oxidative stress through different molecular pathways, and that both the Msr pathway and EGCG may be therapeutic targets to treat diseases related to oxidative damage.

6.
J Wildl Dis ; 57(4): 761-772, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34460917

RESUMO

There is a strong correlation between degraded marine habitats and the prevalence of diseases such as green turtle fibropapillomatosis (GTFP) in coastal populations. In GTFP, small to large tumors grow on the turtle's soft tissues and shell, while internal nodules may also occur. The disease primarily affects juvenile green sea turtles (Chelonia mydas) that reside in nearshore waters. As a link has been shown between environmental pollution and immune suppression in a variety of animals, the objective of our research was to compare innate and adaptive immune responsiveness in green sea turtles from a severely degraded and a more pristine habitat, which differ greatly in rates of GTFP. We quantified phagocytosis by flow cytometry and performed in vitro stimulation analysis to measure activity of both the innate and adaptive immune systems in wild-caught Florida green turtles. Sea turtles from the degraded environment, both with and without visible cutaneous tumors, exhibited significantly reduced phagocytosis and stimulation indices than did those from the less polluted environment. Our results suggest that environmental factors may contribute to the development of GTFP and thus can impact the health of sea turtle populations.


Assuntos
Neoplasias Cutâneas , Tartarugas , Animais , Ecossistema , Imunidade , Prevalência , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/veterinária
7.
BMJ Open ; 11(3): e044114, 2021 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-33741671

RESUMO

OBJECTIVES: A compulsory hip check is performed on an infant at 6-8 weeks in primary care for the detection of developmental dysplasia of the hip (DDH). Missed diagnoses and infants incorrectly labelled with DDH remain an important problem. The nature of physician behaviour as a likely source of this problem has not been explored. The aims of this study were to make a behavioural diagnosis of general practitioners (GPs) who perform these hip checks, and identify potential behavioural change techniques that could make the hip checks more effective. DESIGN: Qualitative study with in-depth semistructured interviews of 6-8 weeks checks. We used the Capability, Opportunity, Motivation and Behaviour model in making a behavioural diagnosis and elicited factors that can be linked to improving the assessment. SETTING: Primary care. PARTICIPANTS: 17 GPs (15 female) who had between 5 and 34 years of work experience were interviewed. RESULTS: Capability related to knowledge of evidence-based criteria and skill to identify DDH were important behavioural factors. Both physical (clinic time and space) and social (practice norms), opportunity were essential for optimal behaviour. Furthermore, motivation related to the importance of the 6-8 weeks check and confidence to perform the check and refer appropriately were identified in the behavioural diagnosis. CONCLUSION: Aspects of capability, opportunity and motivation affect GPs' diagnosis and referral behaviours in relation to DDH. The findings from this work extend current knowledge and will inform the development of an intervention aimed at improving the diagnosis of DDH.


Assuntos
Clínicos Gerais , Atenção Primária à Saúde , Terapia Comportamental , Feminino , Humanos , Lactente , Masculino , Motivação , Pesquisa Qualitativa
8.
BJGP Open ; 4(5)2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33144366

RESUMO

BACKGROUND: The Newborn and Infant Physical Examination (NIPE) programme requires all babies to have a comprehensive health check at 6-8 weeks of age. These are typically completed by GPs. Although person-centred care has achieved prominence in maternity care policy in recent years, there is limited empirical evidence on what parents and/or carers expect from the check, and how far experiences meet their needs. AIM:  To explore the expectations and experiences of parents attending their GP for a baby check. DESIGN & SETTING: A qualitative study was undertaken in primary care in London. METHOD: Content analysis was undertaken of transcripts of semi-structured interviews. Interviews were conducted with a total of 16 participants (14 mothers and two fathers) who had recently attended for a 6-week check for their baby. RESULTS: Despite the availability of plentiful sources of general advice on infants' health and development, a thorough check by a trusted GP was an important milestone for most parents. They had few specific expectations of the check in terms of what examinations were undertaken, but even experienced parents anticipated reassurance about their baby's normal development. Many also hoped for reassurance about their own parenting. Parents appreciated GPs who explained what they were doing during the examination; space to raise any concerns; and combined mother and baby checks. Referrals to secondary care were generally experienced as reassuring rather than a source of anxiety. CONCLUSION: The baby check meets needs beyond those of the NIPE screening programme. Protecting the time for a thorough consultation is important for parents at what can be a vulnerable time.

9.
Sci Rep ; 10(1): 5012, 2020 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-32193464

RESUMO

Temperature-dependent sex determination, present in most turtle species, is a mechanism that uses temperature to direct the sex of the embryo. The rapid increase of global temperatures highlights the need for a clear assessment of how sex ratios of organisms with TSD are affected. In turtles with TSD, quantifying primary sex ratios is challenging because they lack external dimorphism and heteromorphic sex chromosomes. Here we describe a new technique used to identify sex in neonate turtles of two TSD species, a freshwater turtle (Trachemys scripta) and a marine turtle (Caretta caretta) via analysis of small blood samples. We used an immunoassay approach to test samples for the presence of several proteins known to play an important role in sex differentiation. Our results show that Anti-Mullerian Hormone (AMH) can be reliably detected in blood samples from neonate male turtles but not females and can be used as a sex-specific marker. Verification of sex via histology or laparoscopy revealed that this method was 100% reliable for identifying sex in both T. scripta and C. caretta 1-2 day-old hatchlings and 90% reliable for identifying sex in 83-177 day-old (120-160 g) loggerhead juveniles. The method described here is minimally invasive, and for the first time, greatly enhances our ability to measure neonate turtle sex ratios at population levels across nesting sites worldwide, a crucial step in assessing the impact of climate change on imperiled turtle species.


Assuntos
Animais Recém-Nascidos , Hormônio Antimülleriano/sangue , Imunoensaio/métodos , Análise para Determinação do Sexo/métodos , Temperatura , Tartarugas , Animais , Biomarcadores/sangue , Mudança Climática , Feminino , Masculino , Razão de Masculinidade , Tartarugas/sangue
10.
Artigo em Inglês | MEDLINE | ID: mdl-32044446

RESUMO

The detrimental effects of oxidative stress caused by the accumulation of Reactive Oxygen Species (ROS) factor into aging, senescence and several neurodegenerative diseases. Mammalian models are extremely susceptible to the stresses that follow the restoration of oxygen after anoxia; however some organisms including the freshwater turtle Trachemys scripta can withstand extended anoxia and reoxygenation without apparent pathology. The ability of the turtle to withstand these conditions is thought to be linked to the upregulation of protective mechanisms such as heat shock proteins (HSP) as well as the suppression of ROS formation and the upregulation of antioxidant defenses. One such antioxidant mechanism is the transcription factor Forkhead box O3a (FOXO3a), that has been shown to be activated in several animal models during oxidative stress. In this study, we utilized both the transfection of a plasmid carrying foxo3a and the pharmacological manipulation of foxo3a using the green tea extract Epigallocatechin-3-gallate (EGCG) to investigate the protective role of FOXO3a in the turtle brain. Our studies found that transcript levels of foxo3a were upregulated significantly during reoxygenation with greater increases during chemical oxidative stress. Induction of foxo3a by direct transfection significantly decreased cell death during chemical oxidative stress. Cells treated with EGCG also showed increased foxo3a expression and decreased cell death in the presence of H2O2. These results agree with results seen in other animal models and suggest that EGCG (through the upregulation of foxo3a) may be a therapeutic target against oxidative stress damage that warrants further investigation.


Assuntos
Catequina/análogos & derivados , Proteína Forkhead Box O3/metabolismo , Hipóxia/fisiopatologia , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Oxigênio/metabolismo , Tartarugas/metabolismo , Animais , Catequina/farmacologia , Proteína Forkhead Box O3/genética , Neurônios/metabolismo , Neurônios/patologia , Estresse Oxidativo
11.
BMJ Open Qual ; 9(1)2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31986114

RESUMO

BACKGROUND: Transfusion is a common procedure for neonates receiving intensive care management. Recognising a paucity of patient blood management (PBM) programmes in neonates, we aimed to embed blood management and best transfusion principles in the neonatal intensive care unit (NICU) by aligning local policies, providing targeted education and partnering with parents. METHODS: Practice-based evidence for clinical practice improvement (PBE-CPI) methodology was used. Previous hospital accreditation audits were reviewed and a neonate-specific transfusion audit was developed. Audit was performed at baseline and repeated following the intervention period. NICU clinicians received targeted education in obtaining informed consent, prescription and safe administration of blood components during a 'Blood Month' awareness period. A neonate-specific parent handout about transfusion was developed in partnership with parents. A pilot video demonstrating a shared consent discussion was also developed to assist in the consent process. Parents' knowledge, concerns and feedback regarding transfusion practice was sought at baseline (survey) and on project completion (experience trackers). RESULTS: Neonate-specific baseline transfusion audit showed inconsistent consent, monitoring and documentation processes in neonatal transfusions. Post-targeted education audit showed improvement in these parameters. The targeted PBM and transfusion-related education delivered during 'Blood Month' was well-received by staff. Parents' feedback about the NICU transfusion consenting process was consistently positive. NICU medical and nursing clinicians (n=25) surveyed agreed that the parent handout was well set out, easy to understand and recommended that it be used to complement practice. CONCLUSION: PBE-CPI tools aligned with Australian PBM guidelines for clinicians and parents were well-accepted by clinical stakeholders and were associated with practice improvement in PBM awareness and transfusion consent processes. This PBE-CPI project developed NICU-specific consent information, not previously available, by partnering with parents to ensure quality of care in transfusion practice. Adoption of this also helps to meet accreditation for Australian Blood Management Standards. These strategies and tools translate readily into other NICUs to embed and support best PBM and transfusion practice.


Assuntos
Transfusão de Sangue/normas , Prática Clínica Baseada em Evidências/normas , Unidades de Terapia Intensiva Neonatal , Terapia Intensiva Neonatal/normas , Austrália , Pessoal de Saúde/educação , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Consentimento Livre e Esclarecido/normas , Pais/educação , Inquéritos e Questionários
12.
PLoS One ; 15(1): e0227822, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31940417

RESUMO

Peptidylarginine deiminase (PAD) modifies peptidylarginine and converts it to peptidylcitrulline in the presence of elevated calcium. Protein modification can lead to severe changes in protein structure and function, and aberrant PAD activity is linked to human pathologies. While PAD homologs have been discovered in vertebrates-as well as in protozoa, fungi, and bacteria-none have been identified in Drosophila melanogaster, a simple and widely used animal model for human diseases. Here, we describe the development of a human PAD overexpression model in Drosophila. We established fly lines harboring human PAD2 or PAD4 transgenes for ectopic expression under control of the GAL4/UAS system. We show that ubiquitous or nervous system expression of PAD2 or PAD4 have minimal impact on fly lifespan, fecundity, and the response to acute heat stress. Although we did not detect citrullinated proteins in fly homogenates, fly-expressed PAD4-but not PAD2-was active in vitro upon Ca2+ supplementation. The transgenic fly lines may be valuable in future efforts to develop animal models of PAD-related disorders and for investigating the biochemistry and regulation of PAD function.


Assuntos
Drosophila melanogaster/genética , Proteína-Arginina Desiminase do Tipo 2/genética , Proteína-Arginina Desiminase do Tipo 4/genética , Transgenes , Animais , Animais Geneticamente Modificados/genética , Drosophila melanogaster/fisiologia , Feminino , Fertilidade , Resposta ao Choque Térmico , Humanos , Longevidade , Masculino , Regulação para Cima
13.
Womens Health Rep (New Rochelle) ; 1(1): 227-231, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33786484

RESUMO

Background: Pain with intrauterine device (IUD) insertion is identified as a barrier to uptake of this highly effective long-acting reversible contraceptive. Several studies have assessed the efficacy of interventions to alleviate patient discomfort associated with IUD insertion, but no interventions have been clearly shown to improve procedural pain. The aim of this study was to determine whether use of a cold compress on the abdomen during IUD insertion reduces pain. Materials and Methods: This was a prospective randomized control trial of women presenting to Virginia Commonwealth University for insertion of IUD from September 2016 to October 2017. A power analysis determined that 69 subjects were needed in each arm to detect a 30% reduction in pain with a power of 80%, significance value of p < 0.05. One hundred forty-two participants were consented for the study, 69 were randomized to the control group, which received the usual management, and 73 were randomized to the study group, which received a cold compress to the abdomen before the procedure. In addition to data on the difference from pre- to postprocedure pain scales, we collected information regarding inserting provider type, gravidity/parity, body mass index, demographic information (age, race, insurance type, and level of education), history of IUD placement or cervical procedure, history of chronic pain, and the use of regular pain medications (defined as more than once per week). Statistical analysis was accomplished using t-test and chi square tests. Results: There was no difference in pre and postinsertional pain in those who received a cold compress versus the control during insertion of an IUD (3.4 vs. 3.5). The insertional pain was rated at 4.3 and 4.6 for patients who received the cold compress and the control group, respectively (p = 0.805). Conclusion: Although a cold compress is a simple, inexpensive, and safe method of pain control, this study shows no reduction in insertional pain for IUD placement.

14.
Free Radic Res ; 53(11-12): 1144-1154, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31775527

RESUMO

Extensive research has shown that oxidative stress is strongly associated with aging, senescence and several diseases, including neurodegenerative and psychiatric disorders. Oxidative stress is caused by the overproduction of reactive oxygen species (ROS) that can be counteracted by both enzymatic and nonenzymatic antioxidants. One of these antioxidant mechanisms is the widely studied methionine sulfoxide reductase system (Msr). Methionine is one of the most easily oxidized amino acids and Msr can reverse this oxidation and restore protein function, with MsrA and MsrB reducing different stereoisomers. This article focuses on experimental and genetic research performed on Msr and its link to brain diseases. Studies on several model systems as well as genome-wide association studies are compiled to highlight the role of MSRA in schizophrenia, Alzheimer's disease, and Parkinson's disease. Genetic variation of MSRA may also contribute to the risk of psychosis, personality traits, and metabolic factors.


Assuntos
Encefalopatias/enzimologia , Metionina Sulfóxido Redutases/metabolismo , Antioxidantes/metabolismo , Variação Genética/genética , Humanos , Metionina Sulfóxido Redutases/genética , Estresse Oxidativo
15.
Ecotoxicology ; 28(9): 1085-1104, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31559558

RESUMO

Many species of marine life in southwestern Florida, including sea turtles, are impacted by blooms of the toxic dinoflagellate, Karenia brevis. Sublethal exposure to toxins produced by K. brevis has been shown to impact sea turtle health. Since all sea turtles in the Gulf of Mexico have protected status, a freshwater turtle, Trachemys scripta, was used as a model for immune system effects following experimental exposure to a predominant brevetoxin congener in K. brevis blooms, PbTx-3. Exposure to PbTx-3 was oral or intratracheal and health effects were assessed using a suite of immune function parameters: innate immune function (phagocytosis, plasma lysozyme activity), adaptive immune function (lymphocyte proliferation), and measures of oxidative stress (superoxide dismutase (SOD) and glutathione-S-transferase (GST) activity in plasma). Inflammation was also measured using plasma protein electrophoresis. In addition, differential expression of genes in peripheral blood leukocytes was determined using suppression subtractive hybridization followed by real-time PCR of specific genes. The primary immune effects of sublethal brevetoxin exposure in T. scripta following PbTx-3 administration, appear to be an increase in oxidative stress, a decrease in lysozyme activity, and modulation of immune function through lymphocyte proliferation responses. Plasma protein electrophoresis showed a decreased A:G ratio which may indicate potential inflammation. Genes coding for oxidative stress, such as thioredoxin and GST, were upregulated in exposed animals. That sublethal brevetoxin exposures impact immune function components suggests potential health implications for sea turtles naturally exposed to toxins. Knowledge of physiological stressors induced by brevetoxins may contribute to the ultimate goal of developing directed treatment strategies in exposed animals for reduced mortality resulting from red tide toxin exposure in sea turtles.


Assuntos
Imunidade Inata/efeitos dos fármacos , Toxinas Marinhas/toxicidade , Tartarugas/fisiologia , Animais , Toxinas Marinhas/química , Oxocinas/química , Testes de Toxicidade
16.
Health Place ; 58: 102166, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31325811

RESUMO

This paper focuses on the planning of New Towns in the UK in order to explore what the design and planning of urban spaces can tell us about which populations and their health matter and are prioritized, at different points in time. We concentrate on how ageing was conceptualized, and what this tells us about how ageing societies and bodies are accounted for and understood. Through the dynamic evolution of people and place, we can also come to see that what was once viewed as health promoting can become entangled with the causes of ill health. We recommend further multidisciplinary research into the planning of future cities and urban environments.


Assuntos
Planejamento de Cidades , Envelhecimento Saudável , Pesquisa , Saúde da População Urbana , Inglaterra , Humanos
17.
Artigo em Inglês | MEDLINE | ID: mdl-31150868

RESUMO

The anoxia-tolerant fruit fly, Drosophila melanogaster, has routinely been used to examine cellular mechanisms responsible for anoxic and oxidative stress resistance. Nitric oxide (NO), an important cellular signaling molecule, and its downstream activation of cGMP-dependent protein kinase G (PKG) has been implicated as a protective mechanism against ischemic injury in diverse animal models from insects to mammals. In Drosophila, increased PKG signaling results in increased survival of animals exposed to anoxic stress. To determine if activation of the NO/cGMP/PKG pathway is protective at the cellular level, the present study employed a pharmacological protocol to mimic hypoxic injury in Drosophila S2 cells. The commonly used S2 cell line was derived from a primary culture of late stage (20-24 h old) Drosophila melanogaster embryos. Hypoxic stress was induced by exposure to either sodium azide (NaN3) or cobalt chloride (CoCl2). During chemical hypoxic stress, NO/cGMP/PKG activation protected against cell death and this mechanism involved modulation of downstream mitochondrial ATP-sensitive potassium ion channels (mitoKATP). The cellular protection afforded by NO/cGMP/PKG activation during ischemia-like stress may be an adaptive cytoprotective mechanism and modulation of this signaling cascade could serve as a potential therapeutic target for protection against hypoxia or ischemia-induced cellular injury.


Assuntos
Proteínas Quinases Dependentes de GMP Cíclico/metabolismo , GMP Cíclico/metabolismo , Drosophila melanogaster/citologia , Hipóxia/metabolismo , Óxido Nítrico/metabolismo , Animais , Hipóxia Celular/efeitos dos fármacos , Linhagem Celular , Cobalto/toxicidade , GMP Cíclico/análogos & derivados , GMP Cíclico/farmacologia , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/efeitos dos fármacos , Ativação Enzimática , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Canais de Potássio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Estresse Fisiológico
18.
Nat Med ; 25(6): 1012-1021, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31142849

RESUMO

The incidence of preterm birth exceeds 10% worldwide. There are significant disparities in the frequency of preterm birth among populations within countries, and women of African ancestry disproportionately bear the burden of risk in the United States. In the present study, we report a community resource that includes 'omics' data from approximately 12,000 samples as part of the integrative Human Microbiome Project. Longitudinal analyses of 16S ribosomal RNA, metagenomic, metatranscriptomic and cytokine profiles from 45 preterm and 90 term birth controls identified harbingers of preterm birth in this cohort of women predominantly of African ancestry. Women who delivered preterm exhibited significantly lower vaginal levels of Lactobacillus crispatus and higher levels of BVAB1, Sneathia amnii, TM7-H1, a group of Prevotella species and nine additional taxa. The first representative genomes of BVAB1 and TM7-H1 are described. Preterm-birth-associated taxa were correlated with proinflammatory cytokines in vaginal fluid. These findings highlight new opportunities for assessment of the risk of preterm birth.


Assuntos
Microbiota , Nascimento Prematuro/microbiologia , Vagina/microbiologia , Adulto , Negro ou Afro-Americano , Biodiversidade , Estudos de Coortes , Citocinas/metabolismo , Feminino , Interações entre Hospedeiro e Microrganismos/imunologia , Humanos , Recém-Nascido , Mediadores da Inflamação/metabolismo , Estudos Longitudinais , Metagenômica , Microbiota/genética , Microbiota/imunologia , Nascimento Prematuro/etiologia , Nascimento Prematuro/imunologia , Fatores de Risco , Estados Unidos , Vagina/imunologia , Adulto Jovem
19.
Nat Med ; 25(6): 1001-1011, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31142850

RESUMO

The microbiome of the female reproductive tract has implications for women's reproductive health. We examined the vaginal microbiome in two cohorts of women who experienced normal term births: a cross-sectionally sampled cohort of 613 pregnant and 1,969 non-pregnant women, focusing on 300 pregnant and 300 non-pregnant women of African, Hispanic or European ancestry case-matched for race, gestational age and household income; and a longitudinally sampled cohort of 90 pregnant women of African or non-African ancestry. In these women, the vaginal microbiome shifted during pregnancy toward Lactobacillus-dominated profiles at the expense of taxa often associated with vaginal dysbiosis. The shifts occurred early in pregnancy, followed predictable patterns, were associated with simplification of the metabolic capacity of the microbiome and were significant only in women of African or Hispanic ancestry. Both genomic and environmental factors are likely contributors to these trends, with socioeconomic status as a likely environmental influence.


Assuntos
Microbiota , Gravidez/fisiologia , Vagina/microbiologia , Adulto , Negro ou Afro-Americano , Biodiversidade , Estudos de Coortes , Estudos Transversais , Feminino , Hispânico ou Latino , Interações entre Hospedeiro e Microrganismos/genética , Interações entre Hospedeiro e Microrganismos/fisiologia , Humanos , Microbiota/genética , Microbiota/fisiologia , Classe Social , População Branca
20.
J Zoo Wildl Med ; 50(1): 33-44, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31120660

RESUMO

Harmful algal blooms (HABs) occur when excess nutrients allow dinoflagellates to reproduce in large numbers. Marine animals are affected by blooms when algal toxins are ingested or inhaled. In the Gulf of Mexico, near annual blooms of Karenia brevis release a suite of compounds (brevetoxins) that cause sea turtle morbidity and mortality. The primary treatment at rehabilitation facilities for brevetoxin-exposed sea turtles is supportive care, and it has been difficult to design alternative treatment strategies without an understanding of the effects of brevetoxins in turtles in vivo. Previous studies using the freshwater turtle as a model species showed that brevetoxin-3 impacts the nervous and muscular systems, and is detoxified and eliminated primarily through the liver, bile, and feces. In this study, freshwater turtles (Trachemys scripta) were exposed to brevetoxin (PbTx-3) intratracheally at doses causing clear systemic effects, and treatment strategies aimed at reducing the postexposure neurological and muscular deficits were tested. Brevetoxin-exposed T. scripta displayed the same behaviors as animals admitted to rehabilitation centers for toxin exposure, ranging from muscle twitching and incoordination to paralysis and unresponsiveness. Two treatment regimes were tested: cholestyramine, a bile acid sequestrant; and an intravenous lipid emulsion treatment (Intralipidt) that provides an expanded circulating lipid volume. Cholestyramine was administered orally 1 hr and 6 hr post PbTx-3 exposure, but this regime failed to increase toxin clearance. Animals treated with Intralipid (100 mg/kg) 30 min after PbTx-3 exposure had greatly reduced symptoms of brevetoxicosis within the first 2 hr compared with animals that did not receive the treatment, and appeared fully recovered within 24 hr compared with toxin-exposed control animals that did not receive Intralipid. The results strongly suggest that Intralipid treatment for lipophilic toxins such as PbTx-3 has the potential to reduce morbidity and mortality in HAB-exposed sea turtles.


Assuntos
Emulsões Gordurosas Intravenosas/uso terapêutico , Toxinas Marinhas/toxicidade , Neurotoxinas/toxicidade , Oxocinas/toxicidade , Intoxicação/veterinária , Substâncias Protetoras/uso terapêutico , Tartarugas/fisiologia , Animais , Resina de Colestiramina/uso terapêutico , Intoxicação/tratamento farmacológico
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