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1.
Ecol Appl ; 33(1): e2726, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36053865

RESUMO

We conducted a range-wide investigation of the dynamics of site-level reproductive rate of northern spotted owls using survey data from 11 study areas across the subspecies geographic range collected during 1993-2018. Our analytical approach accounted for imperfect detection of owl pairs and misclassification of successful reproduction (i.e., at least one young fledged) and contributed further insights into northern spotted owl population ecology and dynamics. Both nondetection and state misclassification were important, especially because factors affecting these sources of error also affected focal ecological parameters. Annual probabilities of site occupancy were greatest at sites with successful reproduction in the previous year and lowest for sites not occupied by a pair in the previous year. Site-specific occupancy transition probabilities declined over time and were negatively affected by barred owl presence. Overall, the site-specific probability of successful reproduction showed substantial year-to-year fluctuations and was similar for occupied sites that did or did not experience successful reproduction the previous year. Site-specific probabilities for successful reproduction were very small for sites that were unoccupied the previous year. Barred owl presence negatively affected the probability of successful reproduction by northern spotted owls in Washington and California, as predicted, but the effect in Oregon was mixed. The proportions of sites occupied by northern spotted owl pairs showed steep, near-monotonic declines over the study period, with all study areas showing the lowest observed levels of occupancy to date. If trends continue it is likely that northern spotted owls will become extirpated throughout large portions of their range in the coming decades.


Assuntos
Estrigiformes , Animais , Probabilidade , Reprodução , Oregon , Washington
2.
J Water Health ; 20(2): 287-299, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36366987

RESUMO

The COVID-19 pandemic has resulted in over 340 million infection cases (as of 21 January 2022) and more than 5.57 million deaths globally. In reaction, science, technology and innovation communities across the globe have organised themselves to contribute to national responses to COVID-19 disease. A significant contribution has been from the establishment of wastewater-based epidemiological (WBE) surveillance interventions and programmes for monitoring the spread of COVID-19 in at least 55 countries. Here, we examine and share experiences and lessons learnt in establishing such surveillance programmes. We use case studies to highlight testing methods and logistics considerations associated in scaling the implementing of such programmes in South Africa, the Netherlands, Turkey and England. The four countries were selected to represent different regions of the world and the perspective based on the considerable progress made in establishing and implementing their national WBE programmes. The selected countries also represent different climatic zones, economies, and development stages, which influence the implementation of national programmes of this nature and magnitude. In addition, the four countries' programmes offer good experiences and lessons learnt since they are systematic, and cover extensive areas, disseminate knowledge locally and internationally and partnered with authorities (government). The programmes also strengthened working relations and partnerships between and among local and global organisations. This paper shares these experiences and lessons to encourage others in the water and public health sectors on the benefits and value of WBE in tackling SARS-CoV-2 and related future circumstances.


Assuntos
COVID-19 , Humanos , COVID-19/epidemiologia , SARS-CoV-2 , Pandemias , Águas Residuárias , África do Sul , Países Baixos/epidemiologia , Turquia/epidemiologia
3.
Ecol Appl ; 31(7): e02398, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34212458

RESUMO

Breeding dispersal, the movement from one breeding territory to another, is rare for philopatric species that evolved within relatively stable environments, such as the old-growth coniferous forests of the Pacific Northwest. Although dispersal is not inherently maladaptive, the consequences of increased dispersal on population dynamics in populations whose historical dispersal rates are low could be significant, particularly for a declining species. We examined rates and possible causes of breeding dispersal based on a sample of 4,118 northern spotted owls (Strix occidentalis caurina) monitored in seven study areas over 28 yr, 1990-2017, in Oregon and Washington, USA. Using a multistate mark-resight analysis, we investigated the potential impacts of an emergent congeneric competitor (barred owl Strix varia) and forest alteration (extrinsic factors), and social and individual conditions (intrinsic factors) on 408 successive and 1,372 nonsuccessive dispersal events between years. The annual probability of breeding dispersal increased for individual owls that had also dispersed in the previous year and decreased for owls on territories with historically high levels of reproduction. Intrinsic factors including pair status, prior reproductive success, and experience at a site, were also associated with breeding dispersal movements. The percent of monitored owls dispersing each year increased from ˜7% early in the study to ˜25% at the end of the study, which coincided with a rapid increase in numbers of invasive and competitively dominant barred owls. We suggest that the results presented here can inform spotted owl conservation efforts as we identify factors contributing to changing rates of demographic parameters including site fidelity and breeding dispersal. Our study further shows that increasing rates of breeding dispersal associated with population declines contribute to population instability and vulnerability of northern spotted owls to extinction, and the prognosis is unlikely to change unless active management interventions are undertaken.


Assuntos
Estrigiformes , Animais , Conservação dos Recursos Naturais , Florestas , Melhoramento Vegetal , Washington
4.
Br J Clin Pharmacol ; 85(3): 601-615, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30552703

RESUMO

AIMS: The aims of this study were to describe the pharmacokinetics of tacrolimus immediately after kidney transplantation, and to develop a clinical tool for selecting the best starting dose for each patient. METHODS: Data on tacrolimus exposure were collected for the first 3 months following renal transplantation. A population pharmacokinetic analysis was conducted using nonlinear mixed-effects modelling. Demographic, clinical and genetic parameters were evaluated as covariates. RESULTS: A total of 4527 tacrolimus blood samples collected from 337 kidney transplant recipients were available. Data were best described using a two-compartment model. The mean absorption rate was 3.6 h-1 , clearance was 23.0 l h-1 (39% interindividual variability, IIV), central volume of distribution was 692 l (49% IIV) and the peripheral volume of distribution 5340 l (53% IIV). Interoccasion variability was added to clearance (14%). Higher body surface area (BSA), lower serum creatinine, younger age, higher albumin and lower haematocrit levels were identified as covariates enhancing tacrolimus clearance. Cytochrome P450 (CYP) 3A5 expressers had a significantly higher tacrolimus clearance (160%), whereas CYP3A4*22 carriers had a significantly lower clearance (80%). From these significant covariates, age, BSA, CYP3A4 and CYP3A5 genotype were incorporated in a second model to individualize the tacrolimus starting dose: [Formula: see text] Both models were successfully internally and externally validated. A clinical trial was simulated to demonstrate the added value of the starting dose model. CONCLUSIONS: For a good prediction of tacrolimus pharmacokinetics, age, BSA, CYP3A4 and CYP3A5 genotype are important covariates. These covariates explained 30% of the variability in CL/F. The model proved effective in calculating the optimal tacrolimus dose based on these parameters and can be used to individualize the tacrolimus dose in the early period after transplantation.


Assuntos
Rejeição de Enxerto/prevenção & controle , Imunossupressores/farmacocinética , Transplante de Rim/efeitos adversos , Modelos Biológicos , Tacrolimo/farmacocinética , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Variação Biológica da População/fisiologia , Simulação por Computador , Citocromo P-450 CYP3A/genética , Relação Dose-Resposta a Droga , Feminino , Rejeição de Enxerto/imunologia , Humanos , Imunossupressores/administração & dosagem , Masculino , Taxa de Depuração Metabólica , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Estudos Prospectivos , Tacrolimo/administração & dosagem , Transplantados , Adulto Jovem
5.
Pharmacol Res ; 130: 303-307, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29501679

RESUMO

The number of elderly people has increased considerably over the last decades, due to a rising life expectancy and ageing populations. As a result, an increased number of elderly with end-stage-renal-disease are diagnosed, for which the preferred treatment is renal transplantation. Over the past years the awareness of the elderly as a specific patient population has grown, which increases the importance of research in this group. Elderly patients often receive kidneys from elderly donors while younger donor kidneys are preferentially reserved for younger recipients. Although the rate of acute rejection after transplantation is lower in the elderly, these rejections may lead to graft loss more frequently, as kidneys from elderly donors have marginal reserve capacity. To prevent acute rejection, immunosuppressive therapy is needed. On the other hand, elderly patients have a higher risk to die from infectious complications, and thus less immunosuppression would be preferable. Immunosuppressive treatment in the elderly is complicated further by changes in the pharmacokinetics and pharmacodynamics, with increasing age. Adjustments in standard immunosuppressive regimes are therefore suggested for this population. An unmet need in transplantation medicine is a tool to guide a personalized approach to immunosuppression. Recently several promising biomarkers that identify injury to the graft at an early stage or predict acute rejection have been identified. Unfortunately, none of these biomarkers were tested specifically in the elderly. We believe there is an urgent need to perform clinical trials investigating novel immunosuppressive regimens in conjunction with biomarker studies in this specific population.


Assuntos
Imunossupressores/uso terapêutico , Transplante de Rim , Medicina de Precisão , Idoso , Animais , Biomarcadores , Fragilidade , Humanos , Terapia de Imunossupressão , Imunossupressores/farmacologia
6.
Int J Clin Pract ; 67(12): 1342-9, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24246213

RESUMO

BACKGROUND: Pain management in adult patients with concomitant substance use disorders (SUDs) presents a clinical challenge in the absence of objective assessment criteria. Effective pain management is dependent on the clinician's ability to differentiate true pain symptoms from manipulative behaviours. Successful strategies for achieving effective pain control in these patients include implementing a multidisciplinary team approach, use of non-opioid and non-pharmacologic alternatives, and judicious use of opioid analgesics. OBJECTIVE: To describe the implementation of a pharmacist-driven pain management service for patients with concomitant SUDs. METHODS: In an urban teaching hospital located in Trenton, New Jersey, United States, a clinical pharmacist-led pain management service evolved to provide formal consultation. Standardised assessment and treatment approaches were developed to assure consistency. Multidisciplinary education was provided to the medical staff. MAIN OUTCOME MEASURE: The study describes a variety of patterns associated with the program from its pilot period through the first 6 years of service, including opioid utilisation, volume and source of consultations, and multidisciplinary perceptions regarding the program's impact. RESULTS: The establishment of a pharmacist-led pain management consult service successfully addressed patient's needs while modifying drug-seeking behaviours. A significant decrease in opioid usage was noted during the program's pilot period and sustained over time. The program's success has extended the pharmacist's role beyond the program's initial scope to address general pain management needs and to address educational needs of the medical staff. Today, clinical pharmacists are utilised most often for refractory cases for which the most appropriate method of pain management may not be clear.


Assuntos
Analgésicos Opioides/provisão & distribuição , Dor/prevenção & controle , Serviço de Farmácia Hospitalar/estatística & dados numéricos , Transtornos Relacionados ao Uso de Substâncias/complicações , Adulto , Analgésicos Opioides/uso terapêutico , Atenção à Saúde , Hospitalização/estatística & dados numéricos , Hospitais de Ensino/estatística & dados numéricos , Humanos , New Jersey , Manejo da Dor/métodos , Equipe de Assistência ao Paciente/estatística & dados numéricos , Relações Médico-Paciente , Projetos Piloto , Saúde da População Urbana
7.
Int J Tuberc Lung Dis ; 27(3): 209-214, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-36855038

RESUMO

BACKGROUND: TB preventative therapy (TPT) is crucial for reducing the burden of TB in endemic settings. We assessed stigma associated with TPT and the social groups from whom stigma was anticipated.METHODS: We conducted an anonymous cross-sectional survey of community-dwelling adults in rural South Africa. Descriptive statistics, exploratory factor analysis, χ² tests, Kruskal-Wallis tests, and Poisson regression were used to identify factors associated with TPT stigma.RESULTS: The mean age of the 104 participants was 35 years, 65% were female, and 26% had completed secondary school. The vast majority perceived stigma associated with TPT (71%; mean score 1.7, SD ± 1.4). Factor analysis identified a two-factor solution that explained 61.9% of the variance. Being single (P < 0.001), previously screened for TB (P = 0.04), worried about being infected by TB (P = 0.006), and interested in taking TPT (P = 0.01) were associated with higher perceived stigma scores. TPT stigma was perceived among 8%, 16%, and 66% of their family, friends, and other community members, respectively.CONCLUSION: The prevalence of TPT-related stigma in a rural South African community was high. Community members anticipated less stigma from family members compared to other social groups. Global expansion and implementation of TPT will require novel interventions, such as engaging patients´ families to support uptake and promote adherence.


Assuntos
Antibioticoprofilaxia , Antituberculosos , Estigma Social , Tuberculose , Adulto , Feminino , Humanos , Masculino , Estudos Transversais , Análise Fatorial , Família , África do Sul , População Rural , Tuberculose/prevenção & controle , Antituberculosos/uso terapêutico
8.
J Infect Dis ; 203(9): 1337-40, 2011 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-21459819

RESUMO

Naturally acquired immunity to Plasmodium falciparum's asexual blood stage reduces parasite multiplication at microscopically detectable densities. The effect of natural immunity on initial prepatent parasite multiplication during the period following a new infection has been uncertain, contributing to doubt regarding the utility of experimental challenge models for blood-stage vaccine trials. Here we present data revealing that parasite multiplication rates during the initial prepatent period in semi-immune Gambian adults are substantially lower than in malaria-naive participants. This supports the view that a blood-stage vaccine capable of emulating the disease-reducing effect of natural immunity could achieve a detectable effect during the prepatent period.


Assuntos
Imunidade Adaptativa , Malária Falciparum/imunologia , Parasitologia/métodos , Plasmodium falciparum/crescimento & desenvolvimento , Plasmodium falciparum/imunologia , Adulto , Gâmbia , Humanos , Microscopia/métodos
9.
Artigo em Inglês | MEDLINE | ID: mdl-34896787

RESUMO

Haemonchus contortus is arguably one of the most economically important and ubiquitous parasites of livestock globally and commonly involved in cases of anthelmintic resistance. Here, we performed reciprocal genetic crosses using susceptible (MHco3(ISE)) and multiple anthelmintic resistant (MHco18(UGA2004)) H. contortus isolates. Resultant admixed populations were designated MHco3/18 or MHco18/3, where the lead isolate reflects the origin of the females. Three independent filial generations were generated for each cross, which were subjected to bioassays, molecular approaches and population genetic analyses to investigate the phenotypic and genotypic inheritance of benzimidazole (BZ) resistance at each stage. A panel of microsatellite markers confirmed the success of the genetic cross as markers from both parents were seen in the F1 crosses. Egg hatch tests revealed a stark difference between the two F1 crosses with ED50 estimates for MHco18/3 being 9 times greater than those for MHco3/18. Resistance factors based on ED50 estimates ranged from 6 to 57 fold in the filial progeny compared to MHco3(ISE) parents. Molecular analysis of the F167Y and F200Y SNP markers associated with BZ resistance were analysed by pyrosequencing and MiSeq deep amplicon sequencing, which showed that MHco3/18.F1 and MHco18/3.F1 both had similar frequencies of the F200Y resistant allele (45.3% and 44.3%, respectively), whereas for F167Y, MHco18/3.F1 had a two-fold greater frequency of the resistant-allele compared to MHco3/18.F1 (18.2% and 8.8%, respectively). Comparison between pyrosequencing and MiSeq amplicon sequencing revealed that the allele frequencies derived from both methods were concordant at codon 200 (rc = 0.97), but were less comparable for codon 167 (rc = 0.55). The use of controlled reciprocal genetic crosses have revealed a potential difference in BZ resistance phenotype dependent on whether the resistant allele is paternally or maternally inherited. These findings provide new insight and prompt further investigation into the inheritance of BZ resistance in H. contortus.


Assuntos
Anti-Helmínticos , Hemoncose , Haemonchus , Animais , Anti-Helmínticos/farmacologia , Benzimidazóis/farmacologia , Cruzamentos Genéticos , Resistência a Medicamentos/genética , Feminino , Hemoncose/tratamento farmacológico , Hemoncose/epidemiologia , Hemoncose/veterinária , Fenótipo , Polimorfismo de Nucleotídeo Único , Tubulina (Proteína)/genética
10.
Lett Appl Microbiol ; 52(5): 555-8, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21418259

RESUMO

AIMS: Adenovirus contamination can be problematic in various settings including life science laboratories and during pharmaceutical manufacturing processes. Stringent and effective decontamination procedures are necessary to minimize the risk of personnel exposure or product cross-contamination in these settings. Hydrogen peroxide vapour (HPV) is sporicidal, tuberculocidal and fungicidal with proven efficacy against some viruses. We investigate the efficacy of HPV for the inactivation of a recombinant adenovirus. METHODS AND RESULTS: In this study, the survival of a dried recombinant adenovirus (Ad5GFP) was tested before and after HPV exposure to determine the efficacy of HPV at inactivating adenovirus. A>8-log TCID(50) reduction resulted from 45-min exposure to HPV in a microbiological safety cabinet. CONCLUSIONS: HPV is effective for the inactivation of a recombinant adenovirus. SIGNIFICANCE AND IMPACT OF THE STUDY: The results suggest that HPV may be useful for adenovirus decontamination in life science laboratories or in manufacturing facilities.


Assuntos
Adenoviridae/efeitos dos fármacos , Antivirais/farmacologia , Descontaminação/métodos , Peróxido de Hidrogênio/farmacologia
11.
Int Nurs Rev ; 58(1): 109-14, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21281302

RESUMO

OBJECTIVE: This paper describes how nurses in Ghana approach ethical problems. BACKGROUND: The International Council of Nurses' (ICN) Code for Nurses (2006) that serves as the model for professional code of ethics worldwide also acknowledges respect for healthy cultural values. Using the ICN's Code and universal ethical principles as a benchmark, a survey was conducted in 2009 to ascertain how nurses in Ghana respond to ethical and cultural issues in their practice. METHODS: The study was qualitative with 200 participant nurses. Data were obtained through anonymous self-administered questionnaires. Descriptive statistics were used to analyze the data. FINDINGS: Nurses' approaches to ethical problems in Ghana do not always meet expectations of the ICN Code for Nurses. They are also informed by local ethical practices related to the institutional setting and cultural environment in the country. While some cultural values complemented the ICN's Code and universal ethical principles, others conflicted with them. NURSING IMPLICATIONS: These data can assist nurses to provide culturally competent solutions to ethical dilemmas in their practice. Dynamic communication between nurses and patients/clients, intentional study of local cultural beliefs, and the development of ethics education will improve the conformity between universal ethical standards and local cultural values.


Assuntos
Características Culturais , Ética em Enfermagem , Adolescente , Adulto , Países em Desenvolvimento , Feminino , Gana , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Pessoa de Meia-Idade , Autonomia Profissional , Competência Profissional , Inquéritos e Questionários
12.
Int Nurs Rev ; 58(2): 218-24, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21554296

RESUMO

AIM: This article is intended to stimulate critical thinking and generate fruitful discussion on nursing practice in Ghana as experienced by the authors. Its rationale is to promote exchange of ideas and creative partnerships to ensure that right decisions are made in preparing competent, adaptable and resourceful nurses who can contribute to health for all in the 21st century. THE PROBLEM: The challenges of nursing education, practice and migration in Ghana seem grim. There is inadequate capacity of training institutions, low staff morale, poor distribution and serious workforce shortages. METHODS: Government reports and policy documents on nursing were sourced from official websites and reviewed and discussed in the context of the international scholarly published literature. OPPORTUNITIES: The authors note that despite the severe crises, a number of opportunities such as improved home-based training, international nursing education partnerships and welfare and human resource development could foster effective nurse retention and managed migration. CONCLUSIONS: To address the issues with nursing health service delivery and nursing shortages in Ghana requires all stakeholders to move beyond the traditional stereotypes and be flexible and forward-looking. Needed policy options include expansion of local nursing education and training capacity, collaborative training opportunities, improving the welfare and retention rates of current staff and international exchange of nurse resources that is mutually beneficial to both source and sink countries.


Assuntos
Educação em Enfermagem , Enfermagem , Atenção à Saúde/economia , Atenção à Saúde/organização & administração , Gana , Gastos em Saúde , Disparidades em Assistência à Saúde , Humanos , Enfermeiras e Enfermeiros/provisão & distribuição , Opinião Pública , População Rural , Responsabilidade Social , Fatores Socioeconômicos
13.
Animal ; 15(4): 100176, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33637437

RESUMO

Given the economic impact of gastrointestinal nematode infection on livestock farming worldwide, and increasing anthelmintic resistance, it is imperative to develop practical, efficient and sustainable control strategies. Targeted selective treatment (TST), whereby anthelmintic treatments are administered to animals individually, based on selection criteria such as weight gain, has been shown to successfully maintain animal productivity whilst reducing the selection pressure for anthelmintic resistance and the economic cost of treatment in experimental and commercial settings. Despite the benefits of the TST approach, the equipment and time required to monitor animals individually make this strategy unsuitable for some farming enterprises. The sentinel group approach aims to maintain the benefits observed using TST whilst reducing these requirements. The study involved two experiments, each following a group of 80 lambs through their first grazing season. Anthelmintic treatment of the whole group was determined by monitoring the weight gain of identified sentinel lambs within it every 2 weeks: when 40% of the sentinel lambs failed to reach their weight gain targets, the whole group was treated. The sentinel lambs consisted of 45% of the group (n = 36) in experiment one and 20% (n = 16) in experiment two. A control group of 20 lambs was co-grazed with the main group during both experiments; in experiment one, the sentinel approach was compared with a TST approach, in which control lambs were treated on an individual basis in response to weight gain. In experiment two, the sentinel approach was compared with conventional prophylaxis, where all lambs in the control group were treated at strategic time points throughout the season (= strategic prophylactic treatment). The sentinel lambs were found to be representative of overall group performance regardless of the proportion of sentinels within the group: they recorded similar growth rates and reached weight gain targets simultaneously at each time point and overall. Live-weight gain was also similar between sentinel and control animals in both experiments. The findings of the current study suggest that monitoring sentinel lambs comprising 20% of a group of grazing lambs is sufficient to determine the need for anthelmintic treatment within the whole group, and that this approach maintains production in line with conventional or TST treatment regimes.


Assuntos
Anti-Helmínticos , Nematoides , Infecções por Nematoides , Doenças dos Ovinos , Animais , Anti-Helmínticos/farmacologia , Anti-Helmínticos/uso terapêutico , Fezes , Infecções por Nematoides/veterinária , Contagem de Ovos de Parasitas/veterinária , Ovinos , Doenças dos Ovinos/tratamento farmacológico , Doenças dos Ovinos/prevenção & controle
14.
J Neonatal Perinatal Med ; 13(1): 81-85, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32280068

RESUMO

OBJECTIVE: The purpose of this study was to describe an identified association between necrotizing enterocolitis (NEC) and prenatal opioid exposure with neonatal abstinence syndrome (NAS) in late preterm and full-term neonates. STUDY DESIGN: In this single-center retrospective cohort study, we analyzed inborn neonates with the diagnosis of NEC discharged from 2012 through 2017. We compared infants with NEC > 35 weeks' gestation to those with NEC<35 weeks' gestation. We compared gestational age, birth weight, age of onset of symptoms, and incidence of prenatal drug exposure between groups. Significance was determined using Mann-Whitney and Fisher's exact tests. RESULTS: Over the study period, 23 infants were identified with NEC, 9 (39%) were babies > 35 weeks at birth and 14 (61%) < 35 weeks. Those > 35 weeks had a higher birth weight, earlier onset of symptoms, and a higher percentage of prenatal exposure to opioids compared to those < 35 weeks' gestation. We further described seven infants with late gestational age onset NEC associated with prenatal opioid exposure. CONCLUSIONS: In this cohort of infants with NEC discharged over a 6 year period we found a higher than expected percentage of infants born at a later gestational age. We speculate that prenatal opioid exposure might be a risk factor for NEC in neonates born at > 35 weeks.


Assuntos
Analgésicos Opioides/efeitos adversos , Enterocolite Necrosante/epidemiologia , Idade Gestacional , Síndrome de Abstinência Neonatal/epidemiologia , Analgésicos Opioides/sangue , Buprenorfina/efeitos adversos , Buprenorfina/sangue , Estudos de Coortes , Feminino , Sangue Fetal , Heroína/efeitos adversos , Heroína/sangue , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Masculino , Metadona/efeitos adversos , Metadona/sangue , Transtornos Relacionados ao Uso de Opioides/epidemiologia , Gravidez , Complicações na Gravidez/epidemiologia , Estudos Retrospectivos
15.
Br J Cancer ; 100(4): 583-9, 2009 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-19209174

RESUMO

Although a key function of cancer genetics services is to provide risk information, to date there has been little consistency in the way in which breast cancer risk perception has been measured. The aims of the study were to measure estimates of (i) population risk, (ii) absolute risk and (iii) comparative risk of developing breast cancer for Ashkenazi Jewish women, and to determine predictors of breast cancer risk perception. Of 152 women, 107 (70%) completed all questions. The mean (s.d.) estimates for population risk, absolute risk and comparative risk were 22.7% (15.9), 31.8% (20.6) and 1.9-fold (1.9), respectively. Most women overestimated population risk. Women at population risk generally overestimated the population risk and their own absolute risk, yet understood they are at the same risk as the population. Those with a family history understood that they are at increased risk, but underestimated the extent to which their familial risk is increased. Anxiety, high estimation of population risk and lesser family history predicted overestimation of absolute risk, whereas high estimation of population risk and a strong family history predicted underestimation of comparative risk.


Assuntos
Neoplasias da Mama/etnologia , Neoplasias da Mama/psicologia , Judeus/psicologia , Adulto , Idoso , Atitude Frente a Saúde , Austrália/epidemiologia , Neoplasias da Mama/epidemiologia , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Percepção , Risco , Inquéritos e Questionários , Saúde da Mulher , Adulto Jovem
16.
J Cell Biol ; 97(3): 749-55, 1983 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-6411740

RESUMO

We performed electron microscopy of replicas from freeze-fractured retinas exposed during or after fixation to the cholesterol-binding antibiotic, filipin. We observed characteristic filipin-induced perturbations throughout the disk and plasma membranes of retinal rod outer segments of various species. It is evident that a prolonged exposure to filipin in fixative enhances rather than reduces presumptive cholesterol detection in the vertebrate photoreceptor cell. In agreement with the pattern seen in our previous study (Andrews, L.D., and A. I. Cohen, 1979, J. Cell Biol., 81:215-228), filipin-binding in membranes exhibiting particle-free patches seemed largely confined to these patches. Favorably fractured photoreceptors exhibited marked filipin-binding in apical inner segment plasma membrane topologically confluent with and proximate to the outer segment plasma membrane, which was comparatively free of filipin binding. A possible boundary between these differing membrane domains was suggested in a number of replicas exhibiting lower filipin binding to the apical plasma membrane of the inner segment in the area surrounding the cilium. This area contains a structure (Andrews, L. D., 1982, Freeze-fracture studies of vertebrate photoreceptors, In Structure of the Eye, J. G. Hollyfield and E. Acosta Vidrio, editors, Elsevier/North-Holland, New York, 11-23) that resembles the active zones of the nerve terminals for the frog neuromuscular junction. These observations lead us to hypothesize that these structures may function to direct vesicle fusion to occur near them, in a domain of membrane more closely resembling outer than inner segment plasma membrane. The above evidence supports the views that (a) all disk membranes contain cholesterol, but the particle-free patches present in some disks trap cholesterol from contiguous particulate membrane regions; (b) contiguous inner and outer segment membranes may greatly differ in cholesterol content; and (c) the suggested higher cholesterol in the inner segment than in the outer segment plasma membrane may help direct newly inserted photopigment molecules to the outer segment.


Assuntos
Colesterol/metabolismo , Lipídeos de Membrana/metabolismo , Retina/ultraestrutura , Animais , Bufo marinus , Membrana Celular/ultraestrutura , Filipina , Técnica de Fratura por Congelamento , Membranas Intracelulares/ultraestrutura , Camundongos , Rana pipiens , Segmento Externo da Célula Bastonete/ultraestrutura
17.
J Cell Biol ; 81(1): 215-28, 1979 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-314450

RESUMO

The freeze-fracture technique was used to examine the membranes of the photoreceptors of mice and frogs. Particle-free patches were found in the plasma membrane and basal disk membranes of the outer segments of both mice and frogs housed at room temperature, but not in frogs kept in a cold room. These patches were shown not to be artifacts of cryoprotection or fixation, and they persisted when fresh isolated outer segments were frozen by an ultrarapid method. They were also found to persist in mouse rods when retinas were incubated and subsequently fixed at temperatures up to 80 degrees C. Cholesterol was implicated as a significant component of the patches by the observation that, in the outer segments, pits, induced by treatment with the sterol-specific polyene antibiotic filipin, were present in and confined to the particle-free patches. That these lesions are not inherently limited to particle-free membrane areas was evident in the apical plasma membrane of the photoreceptor inner segments, where particles and pits were intermixed. Treatment with saponin, a surface-active agent which specifically complexes cholesterol, resulted in the disappearance of the particle-free patches. Patches were found in basal disks of both mouse and frog rods but not in older disks nearer the pigment epithelium, which indicates that changes occur in the composition of disk membranes and/or in the molecular ordering of their protein and lipid components during the early phase of their transit from the base towards the apex of the outer segment.


Assuntos
Colesterol/análise , Células Fotorreceptoras/ultraestrutura , Animais , Anuros , Membrana Celular/efeitos dos fármacos , Membrana Celular/ultraestrutura , Filipina/farmacologia , Técnica de Fratura por Congelamento , Membranas Intracelulares/efeitos dos fármacos , Membranas Intracelulares/ultraestrutura , Camundongos , Rana pipiens , Saponinas/farmacologia , Temperatura
18.
Science ; 288(5464): 335-9, 2000 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-10764647

RESUMO

Mutations in the copper/zinc superoxide dismutase (SOD1) gene produce an animal model of familial amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disorder. To test a new therapeutic strategy for ALS, we examined the effect of caspase inhibition in transgenic mice expressing mutant human SOD1 with a substitution of glycine to alanine in position 93 (mSOD1(G93A)). Intracerebroventricular administration of zVAD-fmk, a broad caspase inhibitor, delays disease onset and mortality. Moreover, zVAD-fmk inhibits caspase-1 activity as well as caspase-1 and caspase-3 mRNA up-regulation, providing evidence for a non-cell-autonomous pathway regulating caspase expression. Caspases play an instrumental role in neurodegeneration in transgenic mSOD1(G93A) mice, which suggests that caspase inhibition may have a protective role in ALS.


Assuntos
Clorometilcetonas de Aminoácidos/farmacologia , Esclerose Lateral Amiotrófica/tratamento farmacológico , Esclerose Lateral Amiotrófica/enzimologia , Caspase 1/metabolismo , Caspases/metabolismo , Neurônios Motores/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Clorometilcetonas de Aminoácidos/administração & dosagem , Clorometilcetonas de Aminoácidos/uso terapêutico , Substituição de Aminoácidos , Esclerose Lateral Amiotrófica/patologia , Animais , Apoptose/efeitos dos fármacos , Caspase 1/genética , Caspase 3 , Inibidores de Caspase , Caspases/genética , Inibidores de Cisteína Proteinase/administração & dosagem , Inibidores de Cisteína Proteinase/farmacologia , Inibidores de Cisteína Proteinase/uso terapêutico , Modelos Animais de Doenças , Progressão da Doença , Ativação Enzimática , Regulação Enzimológica da Expressão Gênica , Humanos , Injeções Intraventriculares , Interleucina-1/metabolismo , Masculino , Camundongos , Camundongos Transgênicos , Neurônios Motores/enzimologia , Neurônios Motores/patologia , Degeneração Neural , Fármacos Neuroprotetores/administração & dosagem , Fármacos Neuroprotetores/uso terapêutico , Desempenho Psicomotor , Medula Espinal/enzimologia , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo , Superóxido Dismutase-1
19.
Int J Obstet Anesth ; 38: 37-45, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30509680

RESUMO

BACKGROUND: A structured approach to hemorrhagic emergencies in obstetrics has gained popularity with the implementation of massive hemorrhage protocols. The trauma literature suggests that routine quality reviews should be in place to improve patient outcomes. The aim of this study was to develop quality indicators and assess compliance by the clinical team. METHODS: A multidisciplinary team set the institutional quality indicators for the massive hemorrhage protocol review. A retrospective review of all obstetrical massive hemorrhage protocol activation events from September 2010 to January 2015 was performed. All protocol events occurred before the creation of the quality indicators. Data were retrieved from patient records. RESULTS: There were 17 (0.09%) protocol activations for 19 790 deliveries during the study period. All 17 (100%) patients received at least one unit of red blood cells. Overactivation, defined as the transfusion of <2 units of red blood cells, occurred in two cases (12%). Common causes of non-compliance were: 24% (4/17) temperature monitoring, 18% (3/17) lactate measurement, 41% (7/17) arterial blood gas sampling, and 18% (3/17) hemoglobin maintenance within the target range of 55-95 g/L. Admission to intensive care and peripartum hysterectomy occurred in 12 and 5 cases (71% and 29%), respectively. CONCLUSIONS: Suboptimal compliance was found in multiple areas, which may be attributable to the low frequency of activation of our massive haemorrhage protocol in obstetrics. The quality targets identified in this report can act as a basis for other institutions developing quality indicators to evaluate performance.


Assuntos
Protocolos Clínicos , Fidelidade a Diretrizes/estatística & dados numéricos , Complicações do Trabalho de Parto/terapia , Hemorragia Pós-Parto/terapia , Controle de Qualidade , Indicadores de Qualidade em Assistência à Saúde/estatística & dados numéricos , Adulto , Transfusão de Sangue/métodos , Parto Obstétrico , Feminino , Humanos , Complicações do Trabalho de Parto/diagnóstico , Hemorragia Pós-Parto/diagnóstico , Gravidez , Estudos Retrospectivos , Adulto Jovem
20.
Int J Obstet Anesth ; 39: 60-67, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30772121

RESUMO

BACKGROUND: Paper-based charts remain the principal means of documenting the vital signs of hospitalised pregnant and postnatal women. However, poor chart design may contribute to both incorrect charting of data and clinical responses. We decided to identify design faults that might have an adverse clinical impact. METHODS: One hundred and twenty obstetric early warning charts and escalation protocols from consultant-led maternity units in the United Kingdom and the Channel Islands were analysed using an objective and systematic approach. We identified design errors that might impede their successful use (e.g. generate confusion regarding vital sign documentation, hamper the recognition of maternal deterioration, cause a failure of the early warning system or of any clinical response). RESULTS: We found 30% (n=36/120) of charts contained at least one design error with the potential to confuse staff, render the charts difficult to use or compromise patient safety. Amongst the most common areas were inadequate patient identification, poor use of colour, illogical weighting, poor alignment and labelling of axes, and the opportunity for staff to 'game' the escalation. CONCLUSIONS: We recommend the urgent development of an evidence-based, standardised obstetric observation chart, which integrates 'human factors' and user experience. It should have a clear layout and style, appropriate colour scheme, correct language and labelling, and the ability for vital signs to be documented accurately and quickly. It should incorporate a suitable early warning score to guide clinical management.


Assuntos
Consultores , Sinais Vitais , Feminino , Humanos , Gravidez , Reino Unido
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