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1.
Int J Obes (Lond) ; 48(6): 808-814, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38297029

RESUMO

INTRODUCTION: Bariatric surgery is effective in reversing adverse cardiac remodelling in obesity. However, it is unclear whether the three commonly performed operations; Roux-en-Y Gastric Bypass (RYGB), Laparoscopic Sleeve Gastrectomy (LSG) and Laparoscopic Adjustable Gastric Band (LAGB) are equal in their ability to reverse remodelling. METHODS: Fifty-eight patients underwent CMR to assess left ventricular mass (LVM), LV mass:volume ratio (LVMVR) and LV eccentricity index (LVei) before and after bariatric surgery (26 RYGB, 22 LSG and 10 LAGB), including 46 with short-term (median 251-273 days) and 43 with longer-term (median 983-1027 days) follow-up. Abdominal visceral adipose tissue (VAT) and epicardial adipose tissue (EAT) were also assessed. RESULTS: All three procedures resulted in significant decreases in excess body weight (48-70%). Percentage change in VAT and EAT was significantly greater following RYGB and LSG compared to LAGB at both timepoints (VAT:RYGB -47% and -57%, LSG -47% and -54%, LAGB -31% and -25%; EAT:RYGB -13% and -14%, LSG -16% and -19%, LAGB -5% and -5%). Patients undergoing LAGB, whilst having reduced LVM (-1% and -4%), had a smaller decrease at both short (RYGB: -8%, p < 0.005; LSG: -11%, p < 0.0001) and long (RYGB: -12%, p = 0.009; LSG: -13%, p < 0.0001) term timepoints. There was a significant decrease in LVMVR at the long-term timepoint following both RYGB (-7%, p = 0.006) and LSG (-7%, p = 0.021), but not LAGB (-2%, p = 0.912). LVei appeared to decrease at the long-term timepoint in those undergoing RYGB (-3%, p = 0.063) and LSG (-4%, p = 0.015), but not in those undergoing LAGB (1%, p = 0.857). In all patients, the change in LVM correlated with change in VAT (r = 0.338, p = 0.0134), while the change in LVei correlated with change in EAT (r = 0.437, p = 0.001). CONCLUSIONS: RYGB and LSG appear to result in greater decreases in visceral adiposity, and greater reverse LV remodelling with larger reductions in LVM, concentric remodelling and pericardial restraint than LAGB.


Assuntos
Cirurgia Bariátrica , Obesidade Mórbida , Remodelação Ventricular , Humanos , Feminino , Masculino , Remodelação Ventricular/fisiologia , Adulto , Pessoa de Meia-Idade , Cirurgia Bariátrica/métodos , Cirurgia Bariátrica/estatística & dados numéricos , Obesidade Mórbida/cirurgia , Obesidade Mórbida/fisiopatologia , Resultado do Tratamento , Derivação Gástrica/métodos , Derivação Gástrica/estatística & dados numéricos , Redução de Peso/fisiologia , Gordura Intra-Abdominal , Gastrectomia/métodos , Laparoscopia/métodos
2.
J Eur Acad Dermatol Venereol ; 35(5): 1094-1098, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33274462

RESUMO

BACKGROUND: Screening for skin cancer can be cost-effective if focused on high-risk groups. Risk prediction tools have been developed for keratinocyte cancers and melanoma to optimize advice and management. However, few have been validated in a clinical setting over the past few years. OBJECTIVES: To assess the clinical utility of risk assessment tools to identify individuals with prevalent skin cancers in a volunteer-based screening clinic. METHODS: Participants were adults presenting for a skin check at a volunteer-based skin cancer screening facility. We used previously published tools, based on questionnaire responses, to predict melanoma and keratinocyte cancers [KCs; basal cell carcinoma (BCC) and squamous cell carcinoma (SCC)] and classified each participant into one of five risk categories. Participants subsequently underwent a full skin examination by a dermatologist. All suspicious lesions were biopsied, and all cancers were histopathologically confirmed. RESULTS: Of 789 people who presented to the clinic, 507 (64%) consented to the study. Twenty-two BCCs, 19 SCCs and eight melanomas were diagnosed. The proportion of keratinocyte cancers diagnosed increased according to risk category from <1% in the lowest to 24% in the highest risk category (P < 0.001). Subtype analysis revealed similar proportionate increases in BCC or SCC prevalence according to risk category. However, a similar proportion of melanoma cases were detected in the low-risk and high-risk groups. CONCLUSION: The risk prediction model for keratinocyte cancers can reliably identify individuals with a significant skin cancer burden prior to a skin examination in the community setting. The prediction tool for melanoma needs to be tested in a larger sample exposed to a wider range of environmental risk factors.


Assuntos
Carcinoma Basocelular , Melanoma , Neoplasias Cutâneas , Adulto , Carcinoma Basocelular/diagnóstico , Carcinoma Basocelular/epidemiologia , Detecção Precoce de Câncer , Humanos , Melanoma/diagnóstico , Melanoma/epidemiologia , Fatores de Risco , Sensibilidade e Especificidade , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/epidemiologia
3.
Br J Dermatol ; 183(2): 357-366, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-31794051

RESUMO

BACKGROUND: Skin phenotype, host genotype and ultraviolet (UV) damage play a role in the development of melanoma. OBJECTIVES: To ascertain whether the level of UV damage at the site of melanomas was associated with genetic polymorphisms. METHODS: Deep phenotyping was performed on 1244 individuals; 281 with multiple primary melanomas (MPMs), 304 with single primary melanoma (SPM) and 659 convenience controls. Genotype data was generated using the Illumina CoreExome microarray platform, assaying over 500 000 single-nucleotide polymorphisms. A subset of variants were combined to assess a polygenic risk score (PRS) for melanoma. RESULTS: Most MPM cases were diagnosed in patients aged > 40 years, in sites with visible chronic UV damage. Women and those diagnosed at age ≤ 40 years were less likely to have perilesional UV damage. Patients with MPM had higher frequencies of MITF E318K, MC1R R-alleles and the ASIP risk haplotype. Individuals who had melanoma in a visibly UV-damaged site were more likely to carry MC1R rs75570604 [odds ratio (OR) 2·5], 9q31.2 rs10816595 (OR 1·4) and MTAP rs869329 (OR 1·4). These same alleles were more common in patients with MPM who were diagnosed at age ≤ 40 years. The mean PRS was significantly higher in MPM than in SPM and controls. Naevus count was comparable in early-onset MPM cases and those diagnosed at age > 40 years. CONCLUSIONS: Our cohort demonstrated higher frequencies of previously reported alleles associated with melanoma. MPM melanomas more commonly occur in UV-damaged areas, and these individuals are more likely to carry MC1R red hair colour alleles. Awareness of the interplay of genetic vulnerability with UV damage can stratify risk and guide recommendations for melanoma screening. What's already known about this topic? Skin phenotype, host genotype and ultraviolet (UV) damage all play a role in melanoma development. One of the main risk factors is a personal history of melanoma; second and subsequent primary melanomas account for over 20% of all melanomas registered in Queensland. Multiple loci are associated with melanoma risk, including many low-penetrance loci, which may have a cumulatively significant risk. Population-wide screening programmes for melanoma are not yet economically viable. What does this study add? Patients diagnosed with melanoma at age ≤ 40 years were more likely than older patients to have melanomas in non-UV-damaged sites. Patients with multiple melanomas had higher frequencies of MITF E318K, MC1R R-alleles, and the ASIP extended risk haplotype than patients with single melanoma. CDKN2A, MC1R and MTAP variants were more frequent in patients who developed melanomas at a younger age, but also in those whose melanomas were all on visibly UV-damaged sites. What is the translational message? Incorporating these genetic findings into the known risk factors of skin phenotype and visible UV damage may allow for a more customized and economically feasible approach to early detection of melanoma, particularly in younger patients. Plain language summary available online.


Assuntos
Melanoma , Neoplasias Cutâneas , Adulto , Idoso , Proteína Agouti Sinalizadora/genética , Austrália/epidemiologia , Inibidor p16 de Quinase Dependente de Ciclina/genética , Feminino , Humanos , Melanoma/genética , Fator de Transcrição Associado à Microftalmia/genética , Purina-Núcleosídeo Fosforilase/genética , Queensland , Receptor Tipo 1 de Melanocortina/genética , Fatores de Risco , Neoplasias Cutâneas/genética
4.
Int J Obes (Lond) ; 43(8): 1652, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31227797

RESUMO

This Article was originally published under a CC BY NC-ND 4.0 license, but has now been made available under a CC BY 4.0 license.

5.
J Eur Acad Dermatol Venereol ; 33(6): 1076-1083, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30680790

RESUMO

BACKGROUND: Amelanotic/hypomelanotic melanoma is associated with poorer outcomes due to a more advanced disease stage at diagnosis. OBJECTIVE: To determine phenotypic risks and genotypic associations with amelanotic/hypomelanotic melanoma to develop a clinical and genetic profile that could assist in identifying high-risk individuals. METHODS: The Brisbane Naevus Morphology Study conducted from 2009 to 2016 has recruited a core of 1254 participants. Participants were drawn from a combination of volunteers from dermatology outpatient clinics, private dermatology clinics, the Brisbane Longitudinal Twin Study and QSkin study. Case participants had a personal history of melanoma and control participants no personal history of melanoma. We specifically examined seven known candidate pigmentation and melanoma genes and pigmentary phenotypic characteristics in participants with amelanotic/hypomelanotic melanoma compared to pigmented melanomas. This assayed single nucleotide polymorphisms in MC1R, TYR, HERC/OCA2, IRF4, MTAP, PLA2G6 and MITF. RESULTS: Forty-seven participants had at least one amelanotic/hypomelanotic melanoma, and 389 had pigmented melanomas, with amelanotic/hypomelanotic melanoma patients significantly older than pigmented melanoma participants (63.3 ± 13.0 vs. 54.6 ± 15.3 years; P < 0.001). Amelanotic/hypomelanotic melanoma patients were more likely than pigmented melanoma patients to have red hair (34% vs. 15%; P = 0.01), severe hand freckling (13% vs. 5%; P = 0.01) and propensity to sunburn (63% vs. 44%; P = 0.01). MC1R R/R genotype was much more frequent in our amelanotic/hypomelanotic melanoma population (31.1% vs. 11%; P < 0.001; OR 26.4 vs. 5.9; control 1.0). Amelanotic/hypomelanotic melanoma was associated with TYR rs1126809*A/A [OR (CI 95%) 2.7 (1.1-6.8) vs. 1.2 (0.8-1.9)] and PLA2G6 rs11570734*A/A [OR (CI 95%) 3.7 (1.0-13.6) vs. 1.3 (0.9-2.0)]. The MTAP melanoma risk SNP genotype, associated with darker pigmentation, (rs4636294*A/A) was less common in amelanotic/hypomelanotic melanoma patients [OR (CI 95%) 0.8 (0.3-2.1) vs. 2.0 (1.3-3.1)]. CONCLUSIONS: Knowledge of phenotypic and genotypic associations of amelanotic/hypomelanotic melanoma can help predict risks and associations of this difficult to diagnose melanoma, which may ultimately assist clinical management and patient skin self-examination.


Assuntos
Genótipo , Melanoma Amelanótico/genética , Melanoma/genética , Fenótipo , Neoplasias Cutâneas/genética , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Melanoma Maligno Cutâneo
6.
Int J Obes (Lond) ; 42(3): 441-447, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-28974742

RESUMO

BACKGROUND: Obesity causes diastolic dysfunction, and is one of the leading causes of heart failure with preserved ejection fraction. Myocardial relaxation is determined by both active metabolic processes such as impaired energetic status and steatosis, as well as intrinsic myocardial remodelling. However, the relative contribution of each to diastolic dysfunction in obesity is currently unknown. METHODS: Eighty adult subjects (48 male) with no cardiovascular risk factors across a wide range of body mass indices (18.4-53.0 kg m-2) underwent magnetic resonance imaging for abdominal visceral fat, left ventricular geometry (LV mass:volume ratio) and diastolic function (peak diastolic strain rate), and magnetic resonance spectroscopy for PCr/ATP and myocardial triglyceride content. RESULTS: Increasing visceral obesity was related to diastolic dysfunction (peak diastolic strain rate, r=-0.46, P=0.001). Myocardial triglyceride content (ß=-0.2, P=0.008), PCr/ATP (ß=-0.22, P=0.04) and LV mass:volume ratio (ß=-0.61, P=0.04) all independently predicted peak diastolic strain rate (model R2 0.36, P<0.001). Moderated multiple regression confirmed the full mediating roles of PCr/ATP, myocardial triglyceride content and LV mass:volume ratio in the relationship between visceral fat and peak diastolic strain rate. Of the negative effect of visceral fat on diastolic function, 40% was explained by increased myocardial triglycerides, 39% by reduced PCr/ATP and 21% by LV concentric remodelling. CONCLUSIONS: Myocardial energetics and steatosis are more important in determining LV diastolic function than concentric hypertrophy, accounting for more of the negative effect of obesity on diastolic function than LV geometric remodelling. Targeting these metabolic processes is an attractive strategy to treat diastolic dysfunction in obesity.


Assuntos
Diástole/fisiologia , Obesidade , Adulto , Índice de Massa Corporal , Estudos de Coortes , Feminino , Humanos , Gordura Intra-Abdominal/diagnóstico por imagem , Gordura Intra-Abdominal/fisiopatologia , Imageamento por Ressonância Magnética , Masculino , Obesidade/diagnóstico por imagem , Obesidade/epidemiologia , Obesidade/fisiopatologia , Triglicerídeos/sangue , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/fisiopatologia
7.
Parasitology ; 142 Suppl 1: S16-25, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24963725

RESUMO

SUMMARY Malaria remains one of the most significant global public health burdens, with nearly half of the world's population at risk of infection. Malaria is not however a monolithic disease - it can be caused by multiple different parasite species of the Plasmodium genus, each of which can induce different symptoms and pathology, and which pose quite different challenges for control. Furthermore, malaria is in no way restricted to humans. There are Plasmodium species that have adapted to infect most warm-blooded vertebrate species, and the genus as a whole is both highly successful and highly diverse. How, where and when human malaria parasites originated from within this diversity has long been a subject of fascination and sometimes also controversy. The past decade has seen the publication of a number of important discoveries about malaria parasite origins, all based on the application of molecular diagnostic tools to new sources of samples. This review summarizes some of those recent discoveries and discusses their implication for our current understanding of the origin and evolution of the Plasmodium genus. The nature of these discoveries and the manner in which they are made are then used to lay out a series of opportunities and challenges for the next wave of parasite hunters.


Assuntos
Malária/parasitologia , Plasmodium/genética , Evolução Biológica , Interações Hospedeiro-Parasita , Humanos , Filogenia , Plasmodium/fisiologia
8.
Int J Clin Pract ; 68(10): 1221-6, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25269950

RESUMO

In this review, we discuss right-sided heart valve disease, namely tricuspid regurgitation (TR), tricuspid stenosis, pulmonary regurgitation, pulmonary stenosis and right-sided endocarditis. These are frequently seen in conjunction with other diseases, making assessment of their significance more difficult, but it has become increasingly clear that moderate or severe right-sided heart valve disease, in particular TR, is associated with worse prognosis. There remain large gaps in our knowledge of medical and interventional treatment, but in this article we outline what is known about the causes, presentation and management of these commonly seen conditions.


Assuntos
Doenças das Valvas Cardíacas/patologia , Insuficiência da Valva Pulmonar/patologia , Insuficiência da Valva Tricúspide/patologia , Estenose da Valva Tricúspide/patologia , Doenças das Valvas Cardíacas/diagnóstico , Doenças das Valvas Cardíacas/cirurgia , Doenças das Valvas Cardíacas/terapia , Humanos , Prognóstico , Insuficiência da Valva Pulmonar/diagnóstico , Insuficiência da Valva Pulmonar/terapia , Insuficiência da Valva Tricúspide/diagnóstico , Insuficiência da Valva Tricúspide/cirurgia , Insuficiência da Valva Tricúspide/terapia , Estenose da Valva Tricúspide/diagnóstico , Estenose da Valva Tricúspide/cirurgia
9.
Int J Clin Pract ; 68(10): 1209-15, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24898790

RESUMO

Aortic valve disease is common and has significant impact on prognosis and quality of life. In this educational review, we cover the pathophysiology, presentation and assessment of aortic stenosis (AS) and aortic regurgitation (AR), including the role of imaging modalities beyond echocardiography. We review current treatment strategies and emphasise the use and indications for transcatheter aortic valve implantation (TAVI) in view of recent data highlighting its emergence as a novel treatment option for patients with AS, who are unsuitable for conventional aortic valve replacement (AVR). We also describe novel surgical approaches for AR and potential future strategies for percutaneous intervention.


Assuntos
Cateterismo Cardíaco/estatística & dados numéricos , Cardiopatias Congênitas/patologia , Doenças das Valvas Cardíacas/patologia , Implante de Prótese de Valva Cardíaca/efeitos adversos , Qualidade de Vida , Função Ventricular Esquerda/fisiologia , Valva Aórtica/patologia , Valva Aórtica/cirurgia , Estenose da Valva Aórtica/diagnóstico , Estenose da Valva Aórtica/diagnóstico por imagem , Doença da Válvula Aórtica Bicúspide , Cardiopatias Congênitas/diagnóstico , Cardiopatias Congênitas/cirurgia , Cardiopatias Congênitas/terapia , Doenças das Valvas Cardíacas/diagnóstico , Doenças das Valvas Cardíacas/cirurgia , Doenças das Valvas Cardíacas/terapia , Implante de Prótese de Valva Cardíaca/métodos , Humanos , Resultado do Tratamento , Ultrassonografia
10.
Front Endocrinol (Lausanne) ; 14: 1092777, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36761185

RESUMO

Introduction: Obesity affects cardiac geometry, causing both eccentric (due to increased cardiac output) and concentric (due to insulin resistance) remodelling. Following bariatric surgery, reversal of both processes should occur. Furthermore, epicardial adipose tissue loss following bariatric surgery may reduce pericardial restraint, allowing further chamber expansion. We investigated these changes in a serial imaging study of adipose depots and cardiac geometry following bariatric surgery. Methods: 62 patients underwent cardiac magnetic resonance (CMR) before and after bariatric surgery, including 36 with short-term (median 212 days), 37 medium-term (median 428 days) and 32 long-term (median 1030 days) follow-up. CMR was used to assess cardiac geometry (left atrial volume (LAV) and left ventricular end-diastolic volume (LVEDV)), LV mass (LVM) and LV eccentricity index (LVei - a marker of pericardial restraint). Abdominal visceral (VAT) and epicardial (EAT) adipose tissue were also measured. Results: Patients on average had lost 21kg (38.9% excess weight loss, EWL) at 212 days and 36kg (64.7% EWL) at 1030 days following bariatric surgery. Most VAT and EAT loss (43% and 14%, p<0.0001) occurred within the first 212 days, with non-significant reductions thereafter. In the short-term LVM (7.4%), LVEDV (8.6%) and LAV (13%) all decreased (all p<0.0001), with change in cardiac output correlated with LVEDV (r=0.35,p=0.03) and LAV change (r=0.37,p=0.03). Whereas LVM continued to decrease with time (12% decrease relative to baseline at 1030 days, p<0.0001), both LAV and LVEDV had returned to baseline by 1030 days. LV mass:volume ratio (a marker of concentric hypertrophy) reached its nadir at the longest timepoint (p<0.001). At baseline, LVei correlated with baseline EAT (r=0.37,p=0.0040), and decreased significantly from 1.09 at baseline to a low of 1.04 at 428 days (p<0.0001). Furthermore, change in EAT following bariatric surgery correlated with change in LVei (r=0.43,p=0.0007). Conclusions: Cardiac volumes show a biphasic response to weight loss, initially becoming smaller and then returning to pre-operative sizes by 1030 days. We propose this is due to an initial reversal of eccentric remodelling followed by reversal of concentric remodelling. Furthermore, we provide evidence for a role of EAT contributing to pericardial restraint, with EAT loss improving markers of pericardial restraint.


Assuntos
Cirurgia Bariátrica , Gordura Intra-Abdominal , Humanos , Gordura Intra-Abdominal/diagnóstico por imagem , Gordura Intra-Abdominal/patologia , Pericárdio/diagnóstico por imagem , Pericárdio/patologia , Obesidade/cirurgia , Obesidade/patologia , Redução de Peso
11.
J Contam Hydrol ; 248: 104007, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35405439

RESUMO

Long-term estimates of natural source zone depletion (NSZD) rates for petroleum LNAPL (light non-aqueous phase liquid) sites are not available. One-off measurements are often thought valid over the lifetime of LNAPL sites. In the context of site-wide LNAPL mass estimates, we report site-specific gasoline and diesel NSZD rates spanning 21-26 years. Using depth profiles of soil gases (oxygen, carbon dioxide, methane, volatiles) above LNAPL, NSZD rates were estimated in 1994, 2006 and 2020 for diesel and 1999, 2009 and 2020 for gasoline. Each date also had soil-core mass estimates, which together with NSZD rates allow estimation of the longevity for LNAPL presence. Site-wide coring (in 1992, 2002, 2007) estimated LNAPL mass reductions of 12,000 t. For diesel NSZD, the ratio of NSZD rates for 2006 (16,000-49,000 L/ha/y) to those in 2020 (2600-14,000 L/ha/y) was ~3-6. By 2020, the 1994 diesel NSZD rates would have predicted the entire removal of measured mass (16-42 kg/m2). For gasoline, NSZD rates in 1999 were extremely high (50,000-270,000 L/ha/y) but 9-27 times lower (5800-10,000 L/ha/y) a decade later. The gasoline NSZD rates in 1999 predicted near complete mass removal in 2-12 years, but 10-11 kg/m2 was measured 10 and 21 years later which is 26% of the initial mass in 1999. The outcomes substantiate the need to understand NSZD rate changes over the lifetime of LNAPL-impacted sites.


Assuntos
Petróleo , Poluentes do Solo , Biodegradação Ambiental , Dióxido de Carbono/análise , Gasolina , Solo , Poluentes do Solo/análise
12.
Parasite Immunol ; 33(7): 401-10, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21585398

RESUMO

Malaria caused by Plasmodium falciparum is a major cause of global infant mortality, and there is currently no licensed vaccine that provides protection against infection or disease. Several P. falciparum vaccine targets have undergone early testing, but many more candidates remain with little data to support their development. Plasmodium falciparum Merozoite Surface Protein 6 (PfMSP6) is a candidate of particular interest because it is a member of the PfMSP3 multi-gene family, raising the possibility that vaccine-induced immune responses could cross-react across multiple family members. However, few immunoepidemiological studies of PfMSP6 have been carried out to measure domain-specific anti-PfMSP6 responses. This study investigated anti-PfMSP6 responses in P. falciparum-infected individuals from the Peruvian Amazon, using two different PfMSP6 N-terminal allele antigens and a single C-terminal domain antigen, and compared the responses with both PfMSP6 genotyping data and anti-PfMSP3 response data that had been previously generated for the same samples. Anti-PfMSP6 responses were detected despite the low transmission setting, but were less frequent and of considerably lower intensity than anti-PfMSP3 responses. There was a positive correlation between anti-PfMSP3 and PfMSP6 responses, suggesting that the possibility that PfMSP3 family antigens could induce cross-reactive responses requires further detailed investigation.


Assuntos
Anticorpos Antiprotozoários/sangue , Antígenos de Protozoários/imunologia , Malária Falciparum/epidemiologia , Malária Falciparum/imunologia , Proteínas de Membrana/imunologia , Plasmodium falciparum/imunologia , Proteínas de Protozoários/imunologia , Antígenos de Protozoários/genética , Reações Cruzadas , Ensaio de Imunoadsorção Enzimática , Humanos , Imunoglobulina G/sangue , Proteínas de Membrana/genética , Peru/epidemiologia , Plasmodium falciparum/genética , Proteínas de Protozoários/genética , Estudos Soroepidemiológicos
13.
J Exp Med ; 194(11): 1571-81, 2001 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-11733572

RESUMO

Invasion of erythrocytes by Plasmodium merozoites is an intricate process involving multiple receptor-ligand interactions. The glycophorins and an unknown trypsin sensitive factor are all erythrocyte receptors used during invasion by the major human pathogen Plasmodium falciparum. However, only one erythrocyte receptor, Glycophorin A, has a well-established cognate parasite ligand, the merozoite protein erythrocyte binding antigen-175 (EBA-175). The involvement of several other parasite proteins during invasion have been proposed, but no direct evidence links them with a specific invasion pathway. Here we report the identification and characterization of P. falciparum normocyte binding protein 1 (PfNBP1), an ortholog of Plasmodium vivax reticulocyte binding protein-1. PfNBP1 binds to a sialic acid dependent trypsin-resistant receptor on the erythrocyte surface that appears to be distinct from known invasion receptors. Antibodies against PfNBP1 can inhibit invasion of trypsinized erythrocytes and two P. falciparum strains that express truncated PfNBP1 are unable to invade trypsinized erythrocytes. One of these strain, 7G8, also does not invade Glycophorin B-negative erythrocytes. PfNBP1 therefore defines a novel trypsin-resistant invasion pathway and adds a level of complexity to current models for P. falciparum erythrocyte invasion.


Assuntos
Eritrócitos/metabolismo , Proteínas de Membrana/metabolismo , Plasmodium falciparum/metabolismo , Proteínas de Protozoários/metabolismo , Tripsina/metabolismo , Animais , Anticorpos Antiprotozoários/metabolismo , Sequência de Bases , DNA Complementar , Eritrócitos/parasitologia , Humanos , Proteínas de Membrana/genética , Dados de Sequência Molecular , Mutagênese , Plasmodium falciparum/genética , Plasmodium falciparum/patogenicidade , Plasmodium vivax/genética , Plasmodium vivax/metabolismo , Proteínas de Protozoários/genética
14.
Nature ; 424(6945): 165-8, 2003 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-12853949

RESUMO

Stellar occultations--the passing of a relatively nearby body in front of a background star--can be used to probe the atmosphere of the closer body with a spatial resolution of a few kilometres (ref. 1). Such observations can yield the scale height, temperature profile, and other information about the structure of the occulting atmosphere. Occultation data acquired for Pluto's atmosphere in 1988 revealed a nearly isothermal atmosphere above a radius of approximately 1,215 km. Below this level, the data could be interpreted as indicating either an extinction layer or the onset of a large thermal gradient, calling into question the fundamental structure of this atmosphere. Another question is to what extent Pluto's atmosphere might be collapsing as it recedes from the Sun (passing perihelion in 1989 in its 248-year orbital period), owing to the extreme sensitivity of the equilibrium surface pressure to the surface temperature. Here we report observations at a variety of visible and infrared wavelengths of an occultation of a star by Pluto in August 2002. These data reveal evidence for extinction in Pluto's atmosphere and show that it has indeed changed, having expanded rather than collapsed, since 1988.

15.
PLoS One ; 15(4): e0224909, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32352970

RESUMO

Sequence count data are commonly modelled using the negative binomial (NB) distribution. Several empirical studies, however, have demonstrated that methods based on the NB-assumption do not always succeed in controlling the false discovery rate (FDR) at its nominal level. In this paper, we propose a dedicated statistical goodness of fit test for the NB distribution in regression models and demonstrate that the NB-assumption is violated in many publicly available RNA-Seq and 16S rRNA microbiome datasets. The zero-inflated NB distribution was not found to give a substantially better fit. We also show that the NB-based tests perform worse on the features for which the NB-assumption was violated than on the features for which no significant deviation was detected. This gives an explanation for the poor behaviour of NB-based tests in many published evaluation studies. We conclude that nonparametric tests should be preferred over parametric methods.


Assuntos
Distribuição Binomial , RNA-Seq/métodos , Microbiota , Distribuição de Poisson , RNA Ribossômico 16S/genética , Análise de Regressão
16.
Science ; 167(3917): 368-70, 1970 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-17790146

RESUMO

Acquisition measurements of the round-trip travel time of light, from the McDonald Observatory to the Laser Ranging Retro-Reflector deployed on the moon by the Apollo 11 astronauts, were made on 20 August and on 3, 4, and 22 September 1969. The uncertainty in the round-trip travel time was +/- 15 nanoseconds, with the pulsed ruby laser and timing system used for the acquisition. The uncertainty in later measurements of a planned long-term sequence from this observatory is expected to be an order of magnitude smaller. The successful performance of the retro-reflector at several angles of solar illumination, as well as during and after a lunar night, confirms the prediction of thermal design analyses.

17.
West Indian Med J ; 58(2): 114-7, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21866595

RESUMO

OBJECTIVE: To determine the seroprevalence of Leptospira and the serovars responsible for Leptospira exposure in rats in Grenada in order to assess rats as a reservoir host for human infection. DESIGN AND METHODS: Rattus norvegicus rodents were collected from each of the six parishes on the island of Grenada. Serum from 237 rats was tested by the microscopic agglutination test (MAT) and an Immunoglobulin G (IgG) Enzyme-Linked Immunosorbent Assay (ELISA). Seroprevalence rates among parishes were compared using a chi-squared test of homogeneity. RESULTS: Of the 237 serum samples tested, 64 were positive by either MAT or ELISA for an overall seroprevalence of 27%. The ELISA identified 24.5% (57/233) of the rats positive at a titer of > or = 1:160. The MAT identified 7.1% (13/183) of the rats positive at a titer of > or = 1:100. Six of the 13 MAT positive samples had antibodies to multiple serovars. The serovars identified by the MAT with the greatest frequency were from the Icterohaemorrhagiae serogroup. Two rats had antibodies for serogroup Cynopteri, the first time this serogroup has been identified in Grenada. CONCLUSIONS: Our results for Leptospira exposure in rats in Grenada support R norvegicus as an important reservoir host for Leptospira, particularly those from the Icterohaemorrhagiae serogroup. Because this serogroup is the primary serogroup responsible for documented human exposure in Grenada, exposed rats represent a public health threat.


Assuntos
Leptospira/isolamento & purificação , Ratos/microbiologia , Animais , Granada
18.
Mol Cell Biol ; 14(2): 880-7, 1994 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-8289827

RESUMO

cDNA expression cloning is a powerful method for the rescue and identification of genes that are able to confer a readily identifiable phenotype on specific cell types. Retroviral vectors provide several advantages over DNA-mediated gene transfer for the introduction of expression libraries into eukaryotic cells since they can be used to express genes in a wide range of cell types, including those that form important experimental systems such as the hemopoietic system. We describe here a straightforward and efficient method for generating expression libraries by using a murine retroviral vector. Essentially, the method involves the directional cloning of cDNA into the retroviral vector and the generation of pools of stable ecotropic virus producing cells from this DNA. The cells so derived constitute the library, and the virus they yield is used to infect appropriate target cells for subsequent functional screening. We have demonstrated the feasibility of this procedure by constructing several large retroviral libraries (10(5) to 10(6) individual clones) and then using one of these libraries to isolate cDNAs for interleukin-3 and granulocyte-macrophage colony-stimulating factor on the basis of the ability of these factors to confer autonomous growth on the factor-dependent hemopoietic cell line FDC-P1. Moreover, the frequency at which these factor-independent clones were isolated approximated the frequency at which they were represented in the original plasmid library. These results suggest that expression cloning with retroviruses is a practical and efficient procedure and should be a valuable method for the isolation of important regulatory genes.


Assuntos
Clonagem Molecular/métodos , DNA Complementar/metabolismo , Biblioteca Gênica , Vetores Genéticos , Retroviridae/metabolismo , Animais , Sequência de Bases , Northern Blotting , Southern Blotting , Divisão Celular/efeitos dos fármacos , Linhagem Celular , Primers do DNA , Fator Estimulador de Colônias de Granulócitos e Macrófagos/farmacologia , Camundongos , Dados de Sequência Molecular , Reação em Cadeia da Polimerase/métodos , Mapeamento por Restrição , Retroviridae/genética , Linfócitos T , Transfecção
19.
J Contam Hydrol ; 205: 1-11, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28797669

RESUMO

A model is presented to account for elevation-dependent residual and entrapped LNAPL above and below, respectively, the water-saturated zone when predicting subsurface LNAPL specific volume (fluid volume per unit area) and transmissivity from current and historic fluid levels in wells. Physically-based free, residual, and entrapped LNAPL saturation distributions and LNAPL relative permeabilities are integrated over a vertical slice of the subsurface to yield the LNAPL specific volumes and transmissivity. The model accounts for effects of fluctuating water tables. Hypothetical predictions are given for different porous media (loamy sand and clay loam), fluid levels in wells, and historic water-table fluctuations. It is shown the elevation range from the LNAPL-water interface in a well to the upper elevation where the free LNAPL saturation approaches zero is the same for a given LNAPL thickness in a well regardless of porous media type. Further, the LNAPL transmissivity is largely dependent on current fluid levels in wells and not historic levels. Results from the model can aid developing successful LNAPL remediation strategies and improving the design and operation of remedial activities. Results of the model also can aid in accessing the LNAPL recovery technology endpoint, based on the predicted transmissivity.


Assuntos
Água Subterrânea/análise , Hidrocarbonetos/análise , Poluentes Químicos da Água/análise , Monitoramento Ambiental/métodos , Modelos Teóricos , Porosidade , Poços de Água
20.
J Morphol ; 267(3): 341-6, 2006 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-16342078

RESUMO

By analyzing a homogenous dataset we show, in contradiction to a previous study, that the scaling of body frontal area (S(b)) with body mass (m(b)) does not differ between passerine and nonpasserine birds. It is likely that comparison of data collected from live passerines with data collected from frozen nonpasserines had led to the incorrect conclusion that the scaling of S(b) varied between the taxa. We suggest that body dimensions collected from frozen specimens, or specimens stored in alcohol, are not applicable to live birds, and that both the current equations presented in the literature for predicting S(b) from m(b) may lead to inaccurate estimates. Using data from preserved specimens, we found that S(b) scales isometrically with m(b) (S(b) proportional, variant m(b) (0.66)), and therefore we found no evidence for larger birds being more streamlined than smaller birds. S(b) scales with negative allometry against wingspan (b), however, and b scales with positive allometry against m(b), so larger birds have smaller S(b) relative to b. In addition, it appears that dorsoventral flattening of the body is a general characteristic of bird's bodies but that it is more pronounced in larger birds, suggesting perhaps a function in terms of increased lift during forward flight. It appears that bird's bodies obey the surface-to-area geometric scaling law, but bird body shape may vary in relation to aerodynamic function. We suggest that a large-scale study, simultaneously measuring S(b) and m(b) in live passerines and nonpasserines, is required to improve the predictive power of S(b) upon m(b) scaling equations, which play a key role in the estimation of mechanical power consumption in flight in birds. Furthermore, the relations between bird body shape and axial skeleton dimensions, with reference to aerodynamic adaptation, warrant further investigation.


Assuntos
Aves/anatomia & histologia , Voo Animal/fisiologia , Animais , Fenômenos Biomecânicos , Aves/fisiologia , Tamanho Corporal , Modelos Anatômicos , Asas de Animais
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