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1.
Proc Biol Sci ; 287(1929): 20200562, 2020 06 24.
Artigo em Inglês | MEDLINE | ID: mdl-32546097

RESUMO

Many microbial symbionts have multiple phenotypic consequences for their animal hosts. However, the ways in which different symbiont-mediated phenotypes combine to affect fitness are not well understood. We investigated whether there are correlations between different symbiont-mediated phenotypes. We used the symbiont Spiroplasma, a striking example of a bacterial symbiont conferring diverse phenotypes on insect hosts. We took 11 strains of Spiroplasma infecting pea aphids (Acyrthosiphon pisum) and assessed their ability to provide protection against the fungal pathogen Pandora neoaphidis and the parasitoids Aphidius ervi and Praon volucre. We also assessed effects on male offspring production for five of the Spiroplasma strains. All but one of the Spiroplasma strains provided very strong protection against the parasitoid P. volucre. As previously reported, variable protection against P. neoaphidis and A. ervi was also present; male-killing was likewise a variable phenotype. We find no evidence of any correlation, positive or negative, between the different phenotypes, nor was there any evidence of an effect of symbiont phylogeny on protective phenotype. We conclude that multiple symbiont-mediated phenotypes can evolve independently from one another without trade-offs between them.


Assuntos
Afídeos/microbiologia , Spiroplasma/fisiologia , Animais , Evolução Biológica , Fenótipo , Simbiose
2.
HIV Med ; 21(10): 671-673, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32741092

RESUMO

OBJECTIVES: The aim of the study was to determine whether it is safe to stop secondary prophylaxis in patients with talaromycosis after immune reconstitution with a sustained increase in CD4 count to ≥ 100 cells/µL after antiretroviral therapy (ART). METHODS: A retrospective cohort analysis was performed in HIV-infected patients treated for talaromycosis between June 2009 and June 2017 in Medical Action Myanmar (MAM) clinics. RESULTS: Among a cohort of 5466 HIV-infected patients, 41 patients were diagnosed with and treated for clinical talaromycosis. All the patients were on ART and had a CD4 count < 100 cells/µL. Of these 41 patients, 24 patients (71%) were skin smear positive for talaromycosis, while results were negative in 17 patients. Median CD4 count and haemoglobin concentration were 24 cells/µL and 7.7 g/dL, respectively. Seventy-three per cent (30) were male. Among the 41 patients, 11 (27%) died and six (15%) were transferred to other centres. Twenty-four patients (58% of the total diagnosed) stopped itraconazole secondary prophylaxis after starting active ART with CD4 counts > 100 cells/µL for at least 1 year. Throughout the duration of follow-up post itraconazole cessation, the observed incidence of relapse was zero with a total follow-up of 93.8 person-years (95% confidence interval 0-4 per 100 person-years). The median (25th, 75th percentile) duration of follow-up post-prophylaxis discontinuation was 2.8 (2.1, 6.3) years. CONCLUSIONS: Secondary prophylaxis can be safely stopped in patients with talaromycosis after immune reconstitution with a sustained increase in CD4 count to ≥ 100 cells/µL after highly active antiretroviral therapy.


Assuntos
Terapia Antirretroviral de Alta Atividade/métodos , Infecções por HIV/tratamento farmacológico , Itraconazol/uso terapêutico , Micoses/tratamento farmacológico , Prevenção Secundária/métodos , Adulto , Contagem de Linfócito CD4 , Feminino , Infecções por HIV/imunologia , Humanos , Masculino , Mianmar , Micoses/imunologia , Estudos Retrospectivos , Resultado do Tratamento
3.
Phys Chem Chem Phys ; 22(37): 21504-21511, 2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-32955064

RESUMO

It has recently been demonstrated that N-heterocyclic carbenes (NHCs) form self-assembled monolayers (SAMs) on metal surfaces. Consequently, it is important to both characterize and understand their binding modes to fully exploit NHCs in functional surface systems. To assist with this effort, we have performed first-principles total energy calculations for NHCs on Au(111) and simulations of X-ray absorption near edge structure (XANES). The NHCs we have considered are N,N-dimethyl-, N,N-diethyl-, N,N-diisopropylbenzimidazolylidene (BNHCX, with X = Me, Et, and iPr, respectively) and the bis-BNHCX-Au complexes derived from these molecules. We present a comprehensive analysis of the energetic stability of both the BNHCX and the complexes on Au(111) and, for the former, examine the role of the wing group in determining the attachment geometry. Further structural characterization is performed by calculating the nitrogen K-edge X-ray absorption spectra. Our simulated XANES results give insight into (i) the relationship between the BNHCX/Au geometry and the N(1s) → π*/σ*, pre-edge/near-edge, absorption intensities, and (ii) the contributions of the molecular deformation and molecule-surface electronic interaction to the XANES spectrum. These simulated spectra work not only as a map to the BNHCX conformation, but also, combined with electronic structure calculations, provide a clear understanding of recent experimental XANES findings on BNHCX/Au.

4.
BMC Health Serv Res ; 20(1): 814, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32867837

RESUMO

BACKGROUND: Many women with hyperglycaemia in pregnancy do not receive care during and after pregnancy according to standards recommended in international guidelines. The burden of hyperglycaemia in pregnancy falls disproportionately upon Indigenous peoples worldwide, including Aboriginal and Torres Strait Islander women in Australia. The remote and regional Australian context poses additional barriers to delivering healthcare, including high staff turnover and a socially disadvantaged population with a high prevalence of diabetes. METHODS: A complex health systems intervention to improve care for women during and after a pregnancy complicated by hyperglycaemia will be implemented in remote and regional Australia (the Northern Territory and Far North Queensland). The Theoretical Domains Framework was used during formative work with stakeholders to identify intervention components: (1) increasing workforce capacity, skills and knowledge and improving health literacy of health professionals and women; (2) improving access to healthcare through culturally and clinically appropriate pathways; (3) improving information management and communication; (4) enhancing policies and guidelines; (5) embedding use of a clinical register as a quality improvement tool. The intervention will be evaluated utilising the RE-AIM framework at two timepoints: firstly, a qualitative interim evaluation involving interviews with stakeholders (health professionals, champions and project implementers); and subsequently a mixed-methods final evaluation of outcomes and processes: interviews with stakeholders; survey of health professionals; an audit of electronic health records and clinical register; and a review of operational documents. Outcome measures include changes between pre- and post-intervention in: proportion of high risk women receiving recommended glucose screening in early pregnancy; diabetes-related birth outcomes; proportion of women receiving recommended postpartum care including glucose testing; health practitioner confidence in providing care, knowledge and use of relevant guidelines and referral pathways, and perception of care coordination and communication systems; changes to health systems including referral pathways and clinical guidelines. DISCUSSION: This study will provide insights into the impact of health systems changes in improving care for women with hyperglycaemia during and after pregnancy in a challenging setting. It will also provide detailed information on process measures in the implementation of such health system changes.


Assuntos
Serviços de Saúde do Indígena/organização & administração , Hiperglicemia/terapia , Complicações na Gravidez/terapia , Cuidado Pré-Natal/organização & administração , Adulto , Feminino , Programas Governamentais , Pessoal de Saúde , Humanos , Hiperglicemia/diagnóstico , Programas de Rastreamento , Serviços de Saúde Materna , Assistência Médica , Havaiano Nativo ou Outro Ilhéu do Pacífico , Northern Territory , Gravidez , Gravidez em Diabéticas/diagnóstico , Gravidez em Diabéticas/epidemiologia , Melhoria de Qualidade , Queensland , Encaminhamento e Consulta
5.
Phys Rev Lett ; 121(7): 075001, 2018 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-30169054

RESUMO

A bifurcative step transition from low-density, high-temperature, attached divertor conditions to high-density, low-temperature, detached divertor conditions is experimentally observed in DIII-D tokamak plasmas as density is increased. The step transition is only observed in the high confinement mode and only when the B×∇B drift is directed towards the divertor. This work reports for the first time a theoretical explanation and numerical simulations that qualitatively reproduce this bifurcation and its dependence on the toroidal field direction. According to the model, the bifurcation is primarily driven by the interdependence of the E×B-drift fluxes, divertor electric potential structure, and divertor conditions. In the attached conditions, strong potential gradients in the low field side (LFS) divertor drive E×B-drift flux towards the high field side divertor, reinforcing low density, high temperature conditions in the LFS divertor leg. At the onset of detachment, reduction in the potential gradients in the LFS divertor leg reduce the E×B-drift flux as well, such that the divertor plasma evolves nonlinearly to high density, strongly detached conditions. Experimental estimates of the E×B-drift fluxes, based on divertor Thomson scattering measurements, and their dependence on the divertor conditions are qualitatively consistent with the numerical predictions. The implications for divertor power exhaust and detachment control in the next step fusion devices are discussed.

6.
Ann Emerg Med ; 71(1): 109-112, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28559035

RESUMO

The simultaneous use of 2 external defibrillators to administer either dual or sequential cardioversion or defibrillation for refractory cardiac arrhythmias is increasing in both the out-of-hospital and inhospital settings. Using 2 defibrillators to administer higher energy levels than can be achieved with a single defibrillator is considered off-label and is currently not part of published advanced cardiac life support guidelines. We report the first case in which the use of dual-dose cardioversion was associated with external defibrillator damage. Because defibrillator damage, especially if undetected, jeopardizes patient safety and off-label medical product use may void the manufacturer's warranty, this case should urge users to proceed with caution when contemplating this technique.


Assuntos
Desfibriladores , Cardioversão Elétrica/instrumentação , Falha de Equipamento , Taquicardia Ventricular/terapia , Adulto , Cardioversão Elétrica/métodos , Humanos , Masculino
7.
BMC Vet Res ; 13(1): 171, 2017 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-28606148

RESUMO

BACKGROUND: The objective of the current study was to develop a stochastic agent-based model using empirical data from Ontario (Canada) swine sites in order to evaluate different surveillance strategies for detection of emerging porcine reproductive and respiratory syndrome virus (PRRSV) strains at the regional level. Four strategies were evaluated, including (i) random sampling of fixed numbers of swine sites monthly; (ii) risk-based sampling of fixed numbers, specifically of breeding sites (high-consequence sites); (iii) risk-based sampling of fixed numbers of low biosecurity sites (high-risk); and (iv) risk-based sampling of breeding sites that are characterized as low biosecurity sites (high-risk/high-consequence). The model simulated transmission of a hypothetical emerging PRRSV strain between swine sites through three important industry networks (production system, truck and feed networks) while considering sites' underlying immunity due to past or recent exposure to heterologous PRRSV strains, as well as demographic, geographic and biosecurity-related PRRS risk factors. Outcomes of interest included surveillance system sensitivity and time to detection of the three first cases over a period of approximately three years. RESULTS: Surveillance system sensitivities were low and time to detection of three first cases was long across all examined scenarios. CONCLUSION: Traditional modes of implementing high-risk and high-consequence risk-based surveillance based on site's static characteristics do not appear to substantially improve surveillance system sensitivity. Novel strategies need to be developed and considered for rapid detection of this and other emerging swine infectious diseases. None of the four strategies compared herein appeared optimal for early detection of an emerging PPRSV strain at the regional level considering model assumptions, the underlying population of interest, and absence of other forms of surveillance.


Assuntos
Doenças Transmissíveis Emergentes/veterinária , Monitoramento Epidemiológico/veterinária , Modelos Biológicos , Síndrome Respiratória e Reprodutiva Suína/virologia , Vírus da Síndrome Respiratória e Reprodutiva Suína , Animais , Canadá/epidemiologia , Doenças Transmissíveis Emergentes/virologia , Simulação por Computador , Síndrome Respiratória e Reprodutiva Suína/transmissão , Processos Estocásticos , Suínos
8.
Spinal Cord ; 55(4): 383-389, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27596027

RESUMO

STUDY DESIGN: A pilot randomised controlled trial. OBJECTIVES: The aims of this study were to evaluate the effectiveness and participant satisfaction of web-based physiotherapy in people with spinal cord injury (SCI). SETTING: Community patients of a national spinal injury unit in a university teaching hospital, Scotland, UK. METHODS: Twenty-four participants were recruited and randomised to receive 8 weeks of web-based physiotherapy (intervention), twice per week, or usual care (control). Individual exercise programmes were prescribed based on participants' abilities. The intervention was delivered via a website (www.webbasedphysio.com) and monitored and progressed remotely by the physiotherapist. RESULTS: Participants logged on to the website an average of 1.4±0.8 times per week. Between-group differences, although not significant, were more pronounced for the 6-min walk test. Participants were positive about using web-based physiotherapy and stated that they would be happy to use it again and would recommend it to others. Overall, it was rated as either good or excellent. CONCLUSIONS: Web-based physiotherapy was feasible and acceptable for people with SCI. Participants achieved good compliance with the intervention and rated the programme highly and beneficial for health and well-being at various states after injury. The results of this study warrant further work with a more homogeneous sample. SPONSORSHIP: This study was funded by the Queen Elizabeth National Spinal Injuries Unit, Glasgow, UK.


Assuntos
Terapia por Exercício/métodos , Internet , Traumatismos da Medula Espinal/reabilitação , Telerreabilitação/métodos , Centros Médicos Acadêmicos , Estudos de Viabilidade , Feminino , Humanos , Entrevistas como Assunto , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Fisioterapeutas , Projetos Piloto , Pesquisa Qualitativa , Escócia , Traumatismos da Medula Espinal/psicologia , Inquéritos e Questionários , Resultado do Tratamento , Teste de Caminhada
9.
Clin Exp Immunol ; 186(3): 336-346, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27506421

RESUMO

Carriage of certain inhibitory natural killer (NK) cell receptor (iNKR)/HLA ligand pairs is associated with protection from infection and slow time to AIDS implicating NK cells in HIV control. NK cells acquire functional potential through education, which requires the engagement of iNKRs by their human leucocyte antigen (HLA) ligands. HIV infection down-regulates cell surface HLA-A/B, but not HLA-C/E. We investigated how NK cell populations expressing combinations of the iNKRs NKG2A, KIR2DL3 (2DL3) and KIR3DL1 (3DL1) responded to autologous HIV infected CD4 (iCD4) cells. Purified NK cells from HIV-uninfected individuals were stimulated with autologous HIV iCD4 or uninfected CD4 T cells. Using flow cytometry we gated on each of the 8 NKG2A+/- 2DL3+/- 3DL1+/- populations and analysed all possible combinations of interferon (IFN)-γ, CCL4 and CD107a functional subsets responding to iCD4 cells. Infected CD4 cells induced differential frequencies of NKG2A+/- 2DL3+/- 3DL1+/- populations with total IFN-γ+ , CCL4+ and CD107a+ functional profiles. 2DL3+ NKG2A+ NK cells had a higher frequency of responses to iCD4 than other populations studied. A higher frequency of 2DL3+ NK cells responded to iCD4 from individuals that were not HLA-C1 homozygotes. These results show that 2DL3+ NK cells are mediators of HIV-specific responses. Furthermore, responses of NK cell populations to iCD4 are influenced not only by NK cell education through specific KIR/HLA pairs, but also by differential HIV-mediated changes in HLA expression.


Assuntos
Quimiocina CCL4/metabolismo , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Receptores KIR2DL3/metabolismo , Receptores KIR3DL1/metabolismo , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD4-Positivos/virologia , Células Cultivadas , Genótipo , Infecções por HIV/genética , Infecções por HIV/imunologia , Infecções por HIV/metabolismo , HIV-1/imunologia , Antígenos HLA/genética , Antígenos HLA/imunologia , Antígenos HLA-C/genética , Antígenos HLA-C/imunologia , Homozigoto , Humanos , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/metabolismo , Ativação Linfocitária , Receptores KIR2DL3/genética , Receptores KIR3DL1/genética
10.
Support Care Cancer ; 24(2): 629-636, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26143037

RESUMO

PURPOSE: Radiotherapy-induced xerostomia (RIX) is the most common permanent side effect of radiotherapy (RT) to the head and neck (H&N). There is no effective topical treatment. LMS-611 is a mimetic of a natural lamellar body which prevents thick secretions like saliva from congesting organs. The primary objective of this study was to assess saliva properties before and during RT to the H&N. The secondary objectives were to re-assess saliva properties with the addition of LMS-611, measure inter-patient variability, correlate patient-reported symptoms with laboratory measurements and design subsequent first-in-human clinical trial of LMS-611. METHODS: Patients with H&N cancer receiving RT as primary treatment were recruited. Patients completed the Groningen RIX (GRIX) questionnaire and provided saliva samples at baseline and weeks 2, 4 and 6 of RT. Saliva adhesiveness and viscosity were tested by measuring time taken to travel 5 cm down an inclined plane. RESULTS: Thirty patients were enrolled. The inclined plane test (IPT) results (s) were as follows: baseline 31.3, week 2 49.7, week 4 51.1 and week 6 55.7. Wide inter-patient variability was seen at baseline. GRIX scores increased as RT progressed. Spearman rank correlation coefficient of inclined plane tests with GRIX scores was -0.06 at baseline, 0.25 at week 2, 0.12 at week 4 and 0.08 at week 6. LMS-611 concentrations of 10 and 20 mg/ml significantly reduced IPT times on saliva samples. CONCLUSIONS: Saliva becomes more visco-adhesive and RIX worsens as RT progresses. There is little correlation between objective and subjective measures of RIX. The addition of LMS-611 to thick, sticky saliva restores its fluidity ex vivo. This warrants in vivo analysis of the effect of LMS-611 upon RIX.


Assuntos
Materiais Biomiméticos/uso terapêutico , Neoplasias de Cabeça e Pescoço/radioterapia , Lipídeos/uso terapêutico , Lesões por Radiação/tratamento farmacológico , Saliva/efeitos dos fármacos , Saliva/efeitos da radiação , Xerostomia/tratamento farmacológico , Xerostomia/etiologia , Adulto , Idoso , Materiais Biomiméticos/química , Feminino , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Humanos , Lipídeos/química , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Lesões por Radiação/etiologia , Taxa Secretória/efeitos dos fármacos , Taxa Secretória/efeitos da radiação , Xerostomia/fisiopatologia
11.
Spinal Cord ; 54(4): 270-6, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26458974

RESUMO

STUDY DESIGN: A retrospective cohort study. OBJECTIVES: To review demographic trends in traumatic spinal cord injury (TSCI) and non-traumatic spinal cord injury (NTSCI). SETTING: The Queen Elizabeth National Spinal Injuries Unit (QENSIU), sole provider of treatment for TSCI in Scotland; a devolved region of the UK National Health Service. METHODS: A retrospective review of the QENSIU database was performed between 1994 and 2013. This database includes demographic and clinical data from all new TSCI patients in Scotland, as well as patients with severe NTSCI. RESULTS: Over this 20-year period there were 1638 new cases of TSCI in Scotland; 75.2% occurring in males. TSCI incidence increased non-significantly (13.3 per million population to 17.0), while there were significant increases in mean age at time of TSCI (44.1-52.6 years), the proportion of TSCIs caused by falls (41-60%), the proportion of TSCIs resulting in an American Spinal Injury Association Impairment Scale score of C and D on admission (19.7-28.6% and 34.5-39.5%, respectively) and the proportion of cervical TSCIs (58.4-66.3%). The increase in cervical TSCI was specifically due to an increase in C1-C4 lesions (21.7-31.2%). NTSCI patients (n=292) were 5 years older at injury, more likely to be female (68.1% male) and had a range of diagnoses. CONCLUSION: This study supports the suggestion that demographic profiles in SCI are subject to change. In this population, of particular concern is the increasing number of older patients and those with high level tetraplegia, due to their increased care needs. Prevention programmes, treatment pathways and service provision need to be adjusted for optimum impact, improved outcome and long-term care for their target population.


Assuntos
Demografia , Traumatismos da Medula Espinal/epidemiologia , Adolescente , Adulto , Distribuição por Idade , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Planejamento em Saúde Comunitária , Feminino , Humanos , Incidência , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Doenças do Sistema Nervoso/epidemiologia , Doenças do Sistema Nervoso/etiologia , Estudos Retrospectivos , Escócia/epidemiologia , Índice de Gravidade de Doença , Distribuição por Sexo , Fatores Sexuais , Traumatismos da Medula Espinal/complicações , Traumatismos da Medula Espinal/etiologia , Adulto Jovem
12.
Parasitology ; 142(8): 999-1015, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25731914

RESUMO

It is well established that pregnant women are at an increased risk of Plasmodium falciparum infection when compared to non-pregnant individuals and limited epidemiological data suggest Plasmodium vivax risk also increases with pregnancy. The risk of P. falciparum declines with successive pregnancies due to the acquisition of immunity to pregnancy-specific P. falciparum variants. However, despite similar declines in P. vivax risk with successive pregnancies, there is a paucity of evidence P. vivax-specific immunity. Cross-species immunity, as well as immunological and physiological changes that occur during pregnancy may influence the susceptibility to both P. vivax and P. falciparum. The period following delivery, the postpartum period, is relatively understudied and available epidemiological data suggests that it may also be a period of increased risk of infection to Plasmodium spp. Here we review the literature and directly compare and contrast the epidemiology, clinical pathogenesis and immunological features of P. vivax and P. falciparum in pregnancy, with a particular focus on studies performed in areas co-endemic for both species. Furthermore, we review the intriguing epidemiology literature of both P. falciparum and P. vivax postpartum and relate observations to the growing literature pertaining to malaria immunology in the postpartum period.


Assuntos
Malária Falciparum/epidemiologia , Malária Vivax/epidemiologia , Plasmodium falciparum/imunologia , Plasmodium vivax/imunologia , Complicações Parasitárias na Gravidez/epidemiologia , Antimaláricos/uso terapêutico , Feminino , Humanos , Malária Falciparum/imunologia , Malária Vivax/imunologia , Plasmodium falciparum/genética , Plasmodium vivax/genética , Período Pós-Parto/imunologia , Gravidez , Complicações Parasitárias na Gravidez/imunologia
13.
Am J Transplant ; 14(1): 133-43, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24354873

RESUMO

In this study, we analyze the outcomes of transplant renal artery stenosis (TRAS), determine the different anatomical positions of TRAS, and establish cardiovascular and immunological risk factors associated with its development. One hundred thirty-seven of 999 (13.7%) patients had TRAS diagnosed by angiography; 119/137 (86.9%) were treated with angioplasty, of which 113/137 (82.5%) were stented. Allograft survival in the TRAS+ intervention, TRAS+ nonintervention and TRAS- groups was 80.4%, 71.3% and 83.1%, respectively. There was no difference in allograft survival between the TRAS+ intervention and TRAS- groups, p = 0.12; there was a difference in allograft survival between the TRAS- and TRAS+ nonintervention groups, p < 0.001, and between the TRAS+ intervention and TRAS+ nonintervention groups, p = 0.037. TRAS developed at the anastomosis, within a bend/kink or distally. Anastomotic TRAS developed in living donor recipients; postanastomotic TRAS (TRAS-P) developed in diabetic and older patients who received grafts from deceased, older donors. Compared with the TRAS- group, patients with TRAS-P were more likely to have had rejection with arteritis, odds ratio (OR): 4.83 (1.47-15.87), p = 0.0095, and capillaritis, OR: 3.03 (1.10-8.36), p = 0.033. Patients with TRAS-P were more likely to have developed de novo class II DSA compared with TRAS- patients hazard ratio: 4.41 (2.0-9.73), p < 0.001. TRAS is a heterogeneous condition with TRAS-P having both alloimmune and traditional cardiovascular risk factors.


Assuntos
Anticorpos/análise , Antígenos de Histocompatibilidade Classe II/imunologia , Transplante de Rim/efeitos adversos , Obstrução da Artéria Renal/imunologia , Doadores de Tecidos , Adulto , Idoso , Angiografia Digital/efeitos adversos , Feminino , Rejeição de Enxerto/etiologia , Sobrevivência de Enxerto , Humanos , Masculino , Pessoa de Meia-Idade , Obstrução da Artéria Renal/diagnóstico , Obstrução da Artéria Renal/cirurgia , Fatores de Risco , Stents , Resultado do Tratamento
14.
J Evol Biol ; 27(6): 1205-16, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24797307

RESUMO

Intergenerational effects can have either adaptive or nonadaptive impacts on offspring performance. Such effects are likely to be of ecological and evolutionary importance in animals with extended parental care, such as birds, mammals and some insects. Here, we studied the effects of exposure to microbial competition during early development on subsequent reproductive success in the burying beetle Nicrophorus vespilloides, an insect with elaborate parental care. We found that exposure to high levels of microbial competition both during a female's larval development and during her subsequent reproduction resulted in females rearing smaller broods than those exposed to lower levels of microbial competition. To determine whether these differences arose before or after offspring hatching, a cross-fostering experiment was conducted. Our results demonstrate that the impact of larval competition with microbes for resources extends into adult life and can negatively affect subsequent generations via impacts on the quality of parental care provided after hatching. However, we also find evidence for some positive effects of previous microbial exposure on prehatch investment, suggesting that the long-term results of competition with microbes may include altering the balance of parental investment between prehatch and post-hatch care.


Assuntos
Besouros/fisiologia , Animais , Exposição Ambiental , Comportamento Alimentar , Feminino , Fertilidade , Masculino , Dinâmica Populacional , Reprodução
15.
Eur J Appl Physiol ; 114(12): 2483-9, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25113093

RESUMO

PURPOSE: Abdominal functional electrical stimulation (AFES) is a technique intended to improve respiratory function in tetraplegia where breathing is affected due to abdominal muscle paralysis. Although it is known that optimal muscle contraction is achieved when electrical stimulation is applied close to the muscle motor point, AFES studies have used a variety of electrode positions. This study aims to investigate the feasibility of using Neuromuscular Electrical Stimulation to detect the motor points of the abdominal muscles, and to evaluate the intrasubject repeatability and intersubject uniformity of their positions, to find the most suitable AFES electrode location. METHODS: Low frequency stimulation (0.5 Hz) was applied to the abdominal muscles of 10 able bodied and five tetraplegic participants. The electrode positions which achieved the strongest muscle contractions were recorded as the motor point positions, with measurements repeated once. For five able bodied participants, assessments were repeated after 18 months, in seated and supine positions. RESULTS: Intersubject uniformity ranged from 2.8 to 8.8%. Motor point positions were identified with intrasubject repeatability of <1.7 cm, deemed adequate relative to standard AFES electrode size. Intrasubject repeatability shows motor point positions changed little (<1.7 cm) after 18 months but varied between seated and supine positions with repeatability of up to 3.1 cm. CONCLUSIONS: A simple technique to locate the motor points of the abdominal muscles is presented and shown to have an adequate intrasubject repeatability, enabling the optimum AFES electrode location to be identified for each user.


Assuntos
Músculos Abdominais/fisiopatologia , Terapia por Estimulação Elétrica/métodos , Contração Muscular/fisiologia , Quadriplegia/terapia , Adulto , Idoso , Estudos de Viabilidade , Feminino , Humanos , Masculino , Quadriplegia/fisiopatologia , Adulto Jovem
16.
Am J Transplant ; 13(2): 485-92, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23167441

RESUMO

In renal transplant patients with de novo donor-specific antibodies (dnDSA) we studied the value of microcirculation inflammation (MI; defined by the addition of glomerulitis (g) and peritubular capillaritis (ptc) scores) to assess long-term graft survival in a retrospective cohort study. Out of all transplant patients with standard immunological risk (n = 638), 79 (12.4%) developed dnDSA and 58/79 (73%) had an indication biopsy at or after dnDSA development. Based on the MI score on that indication biopsy patients were categorized, MI0 (n = 26), MI1 + 2 (n = 21) and MI ≥ 3 (n = 11). The MI groups did not differ significantly pretransplantation, whereas posttransplantation higher MI scores developed more anti-HLA class I + II DSA (p = 0.011), showed more TCMR (p < 0.001) and showed a trend to C4d-positive staining (p = 0.059). Four-year graft survival estimates from time of indication biopsy were MI0 96.1%, MI1 + 2 76.1% and MI ≥ 3 17.1%; resulting in a 24-fold increased risk of graft failure in the MI ≥ 3 compared to the MI0 group (p = 0.003; 95% CI [3.0-196.0]). When adjusted for C4d, MI ≥ 3 still had a 21-fold increased risk of graft failure (p = 0.005; 95% CI [2.5-180.0]), while C4d positivity on indication biopsy lost significance. In renal transplant patients with de novo DSA, microcirculation inflammation, defined by g + ptc, associates with graft survival.


Assuntos
Anticorpos/imunologia , Transplante de Rim/imunologia , Transplante de Rim/métodos , Rim/imunologia , Insuficiência Renal/terapia , Adulto , Biópsia , Complemento C4b/análise , Feminino , Rejeição de Enxerto/imunologia , Sobrevivência de Enxerto , Humanos , Imunossupressores/uso terapêutico , Inflamação , Masculino , Microcirculação , Pessoa de Meia-Idade , Modelos Estatísticos , Fragmentos de Peptídeos/análise , Estudos Retrospectivos , Fatores de Risco , Doadores de Tecidos
17.
Nat Genet ; 12(4): 427-30, 1996 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-8630499

RESUMO

The main clinical feature of bipolar affective disorder is a change of mood to depression or elation. Unipolar disorder, also termed major depressive disorder, describes the occurrence of depression alone without episodes of elevated mood. Little is understood about the underlying causes of these common and severe illnesses which have estimated lifetime prevalences in the region of 0.8% for bipolar and 6% for unipolar disorder. Strong support for a genetic aetiology is found in the familial nature of the condition, the increased concordance of monozygotic over dizygotic twins and adoption studies showing increased rates of illness in children of affected parents. However, linkage studies have met with mixed success. An initial report of linkage on the short arm of chromosome 11 (ref. 4) was revised and remains unreplicated. Reports proposing cosegregation of genes found on the X chromosome with bipolar illness have not been supported by others. More recently bipolar disorder has been reported to be linked with markers on chromosomes 18, 21, 16 and a region on the X chromosome different from those previously suggested. We have carried out a linkage study in twelve bipolar families. In a single family a genome search employing 193 markers indicated linkage on chromosome 4p where the marker D4S394 generated a two-point lod score of 4.1 under a dominant model of inheritance. Three point analyses with neighbouring markers gave a maximum lod score of 4.8. Eleven other bipolar families were typed using D4S394 and in all families combined there was evidence of linkage with heterogeneity with a maximum two-point lod score of 4.1 (theta = 0, alpha = 0.35).


Assuntos
Transtorno Bipolar/genética , Mapeamento Cromossômico , Cromossomos Humanos Par 4/genética , Transtorno Depressivo/genética , Feminino , Marcadores Genéticos , Humanos , Escore Lod , Masculino , Modelos Genéticos , Linhagem , Transtornos Psicóticos/genética
18.
Am J Transplant ; 12(12): 3437-40, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22974244

RESUMO

Invasive fungal diseases are a major cause of death in renal allograft recipients. We previously reported that adjunctive recombinant human interferon-γ therapy has clinical utility for invasive fungal diseases after renal transplantation. We have now developed a rapid peripheral blood-based quantitative real-time PCR assay that enables accurate profiling of cytokine imbalances. Our preliminary studies in renal transplant patients with invasive fungal diseases suggest that they fail to mount an adequate interferon-γ response to the fungal infection. In addition, they have reduced IL-10 and increased TNF-α when compared to stable renal transplant patients. These preliminary cytokine profiling-based observations provide a possible explanation for the therapeutic benefit of adjunctive human interferon-γ therapy in renal allograft recipients with invasive fungal diseases.


Assuntos
Biomarcadores/sangue , Infecções por Citomegalovirus/diagnóstico , Rejeição de Enxerto/diagnóstico , Interferon gama/sangue , Transplante de Rim/efeitos adversos , Estudos de Casos e Controles , Citomegalovirus/genética , Infecções por Citomegalovirus/genética , Infecções por Citomegalovirus/microbiologia , DNA/sangue , DNA/genética , Seguimentos , Rejeição de Enxerto/sangue , Rejeição de Enxerto/etiologia , Humanos , Interferon gama/genética , Interleucina-10/sangue , Interleucina-10/genética , Reação em Cadeia da Polimerase em Tempo Real , Transplante Homólogo , Fator de Necrose Tumoral alfa/sangue , Fator de Necrose Tumoral alfa/genética
19.
Mol Phylogenet Evol ; 63(3): 668-78, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22426434

RESUMO

The chestnut-shouldered fairy-wrens comprise a subgroup of four species in the genus Malurus (Passeriformes: Maluridae). Collectively, they are widespread across the Australian continent but phenotypic variation is strongly structured geographically in just one species, M. lamberti. Earlier phylogenetic analyses of this group have been limited to one or two individuals for each species and have not represented all currently recognised subspecies of M. lamberti. Historically, the taxonomy and nomenclature of the M. lamberti complex has been debated, in part because of morphological similarities among its subspecies and another member of the group, M. amabilis. We reconstructed the phylogeny of all four species of chestnut-shouldered fairy-wrens including all four subspecies of M. lamberti using a mitochondrial gene (ND2), five anonymous nuclear loci and three nuclear introns. Phylogenetic analysis of the mitochondrial ND2 gene nests M. amabilis within M. lamberti rendering the latter paraphyletic. Individual nuclear gene trees failed to reliably resolve each of the species boundaries or the phylogenetic relationships found in the mtDNA tree. When combined, however, a strongly supported overall topology was resolved supporting the monophyly of M. lamberti and its sister species relationship to M. amabilis. Current subspecific taxonomy of M. lamberti was not concordant with all evolutionary lineages of M. lamberti, nominotypical M. l. lamberti being the only subspecies recovered as a monophyletic group from mtDNA. Some genetic structuring is evident and potential barriers to gene flow are discussed.


Assuntos
Especiação Genética , Fenótipo , Aves Canoras/genética , Animais , Antecipação Genética , Proteínas Aviárias/genética , Teorema de Bayes , DNA Mitocondrial/genética , Loci Gênicos , Variação Genética , Haplótipos , Funções Verossimilhança , Tipagem de Sequências Multilocus , Filogenia , Aves Canoras/classificação
20.
Phys Rev Lett ; 109(4): 045001, 2012 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-23006093

RESUMO

A significant fraction of high-harmonic fast-wave (HHFW) power applied to NSTX can be lost to the scrape-off layer (SOL) and deposited in bright and hot spirals on the divertor rather than in the core plasma. We show that the HHFW power flows to these spirals along magnetic field lines passing through the SOL in front of the antenna, implying that the HHFW power couples across the entire width of the SOL rather than mostly at the antenna face. This result will help guide future efforts to understand and minimize these edge losses in order to maximize fast-wave heating and current drive.

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