RESUMO
This in vitro study aims at clarifying the relation between the oscillatory flow of cerebrospinal fluid (CSF) in the cerebral aqueduct, a narrow conduit connecting the third and fourth ventricles, and the corresponding interventricular pressure difference. Dimensional analysis is used in designing an anatomically correct scaled model of the aqueduct flow, with physical similarity maintained by adjusting the flow frequency and the properties of the working fluid. The time-varying pressure difference across the aqueduct corresponding to a given oscillatory flow rate is measured in parametric ranges covering the range of flow conditions commonly encountered in healthy subjects. Parametric dependences are delineated for the time-averaged pressure fluctuations and for the phase lag between the transaqueductal pressure difference and the flow rate, both having clinical relevance. The results are validated through comparisons with predictions obtained with a previously derived computational model. The parametric quantification in this study enables the derivation of a simple formula for the relation between the transaqueductal pressure and the stroke volume. This relationship can be useful in the quantification of transmantle pressure differences based on non-invasive magnetic-resonance-velocimetry measurements of aqueduct flow for investigation of CSF-related disorders.
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HIV infection is now almost 40 years old. In this time, along with the catastrophe and tragedy that it has entailed, it has also represented the capacity of modern society to take on a challenge of this magnitude and to transform an almost uniformly lethal disease into a chronic illness, compatible with a practically normal personal and relationship life. This anniversary seemed an ideal moment to pause and reflect on the future of HIV infection, the challenges that remain to be addressed and the prospects for the immediate future. This reflection has to go beyond merely technical approaches, by specialized professionals, to also address social and ethical aspects. For this reason, the Health Sciences Foundation convened a group of experts in different aspects of this disease to discuss a series of questions that seemed pertinent to all those present. Each question was presented by one of the participants and discussed by the group. The document we offer is the result of this reflection.
Assuntos
Infecções por HIV , Adulto , Prova Pericial , Infecções por HIV/epidemiologia , HumanosRESUMO
Background: Dual therapy (DT) with a ritonavir-boosted PI (PI/r) plus lamivudine has proven non-inferior (12% margin) to triple therapy (TT) with PI/r plus two nucleos(t)ide reverse transcriptase inhibitors [N(t)RTIs] in four clinical trials. It remains unclear whether DT is non-inferior based on the US FDA endpoint (virological failure with a margin of 4%) or in specific subgroups. Methods: We performed a systematic search (January 1990 to March 2017) of randomized controlled trials that compared switching of maintenance ART from TT to DT. The principal investigators were contacted and agreed to share study databases. The primary endpoint was non-inferiority of DT to TT based on the current FDA endpoint (4% non-inferiority margin for virological failure at week 48). We also analysed whether efficacy was modified by gender, active HCV infection and type of PI. Effect estimates and 95% CIs were calculated using generalized estimating equation-based models. Results: We found 881 references that yielded eight articles corresponding to four clinical trials (1051 patients). At week 48, 4% of patients on DT versus 3.04% on TT had experienced virological failure (difference 0.9%; 95% CI -1.2% to 3.1%), and 84.7% of patients on DT versus 83.2% on TT had <50 copies of HIV RNA/mL (FDA snapshot algorithm) (difference 1.4%; 95% CI -2.8% to 5.8%). Gender, active HCV infection and type of PI had no effect on differences in treatment efficacy between DT and TT. Conclusions: DT was non-inferior to TT using both current and past FDA endpoints. The efficacy of DT was not influenced by gender, active HCV infection status, or type of PI.
Assuntos
Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/uso terapêutico , Lamivudina/uso terapêutico , Ritonavir/uso terapêutico , Carga Viral/efeitos dos fármacos , Interpretação Estatística de Dados , HIV-1/efeitos dos fármacos , Humanos , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Guidelines recommend evaluating persistent alteration of liver tests in HCV-infected patients after sustained virological response (SVR) and its influence on liver disease progression. We studied the prevalence, etiology, associated factors and evolutionary implications of persistent alteration of liver tests in HCV patients after direct-acting antivirals (DAA)-induced SVR. This was a prospective study of HCV-infected patients and SVR after DAA. Those with another previously diagnosed liver disease were excluded. Persistent alteration of liver tests was defined as any increase in ALT, AST or GGT at SVR12 and SVR24. Causes were determined according to standard clinical practice, including liver biopsy and follow-up transient elastography. A total of 1112 patients were included (70.8% males, median age 53 years, 38.8% cirrhosis, 34.9% interferon-experienced, 56.8% HIV-coinfected). Persistent alteration of liver tests was detected in 130/1112 patients (11.7% [95%CI: 9.7-13.6]). Its frequency differed between HCV-monoinfected (45/480: 9.4% [95%CI: 6.7-12.1]) and HIV-coinfected (85/632: 13.5% [95%CI: 10.7-16.2]) (P = .046). In multivariable analysis, cirrhosis (OR 2.12; 95%CI: 1.28-3.53; P = .004) and baseline transient elastography values (OR 1.03; 95%CI: 1.01-1.04; P = .000) were associated with persistent alteration of liver tests. The main etiologies were clinical diagnosis suggestive of nonalcoholic fatty liver disease in 47 (36.2%), alcohol in 30 (23.1%) and drug consumption in 19 (14.6%). Baseline and follow-up transient elastography was performed in 594 patients and showed a significantly different decrease in patients who did or did not have a persistent alteration of liver tests (-21.1% vs -30%, respectively; P = .003), independently of sex, HIV status or baseline TE value. In conclusion, persistent alteration of liver tests is not infrequent after SVR. It is associated with cirrhosis and baseline transient elastography, and the main cause is fatty liver. According to transient elastography changes, persistent alteration of liver tests seems to affect the course of liver disease.
Assuntos
Alanina Transaminase/sangue , Antivirais/uso terapêutico , Aspartato Aminotransferases/sangue , Hepatite C Crônica/tratamento farmacológico , Testes de Função Hepática , Resposta Viral Sustentada , gama-Glutamiltransferase/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Técnicas de Imagem por Elasticidade , Feminino , Hepatite C Crônica/patologia , Hepatite C Crônica/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Prospectivos , Adulto JovemRESUMO
Background: In Spain, migrants are disproportionately affected by HIV and experience high rates of late diagnosis. We investigated barriers to health care access among migrants living with HIV (MLWH) in Spain. Methods: Cross sectional electronic survey of 765 adult HIV-positive migrants recruited within 18 health care settings between July 2013 and July 2015. We collected epidemiological, demographic, behavioral and clinical data. We estimated the prevalence and risk factors of self-reported barriers to health care using multivariable logistic regression. Results: Of those surveyed, 672 (88%) had information on health care access barriers: 23% were women, 63% from Latin America and Caribbean, 14% from Sub-Saharan Africa and 15% had an irregular immigration status. Men were more likely to report barriers than women (24% vs. 14%, P = 0.009). The main barriers were: lengthy waiting times for an appointment (9%) or in the clinic (7%) and lack of a health card (7%). Having an irregular immigration status was a risk factor for experiencing barriers for both men (OR: (4.0 [95%CI: 2.2-7.2]) and women (OR: 10.5 [95%CI: 3.1-34.8]). Men who experienced racial stigma (OR: 3.1 [95%CI: 1.9-5.1]) or food insecurity (OR: 2.1 [95%CI: 1.2-3.4]) were more likely to report barriers. Women who delayed treatment due to medication costs (6.3 [95%CI: 1.3-30.8]) or had a university degree (OR: 5.8 [95%CI: 1.3-25.1]) were more likely to report barriers. Conclusion: Health care barriers were present in one in five5 MLWH, were more common in men and were associated to legal entitlement to access care, perceived stigma and financial constraints.
Assuntos
Infecções por HIV/terapia , Acessibilidade aos Serviços de Saúde/estatística & dados numéricos , Migrantes , Adolescente , Adulto , Estudos Transversais , Feminino , Infecções por HIV/epidemiologia , Pesquisas sobre Atenção à Saúde , Humanos , Masculino , Fatores de Risco , Espanha/epidemiologia , Migrantes/estatística & dados numéricos , Adulto JovemRESUMO
We explored if baseline CD4/CD8 T-cell ratio is associated with immunodiscordant response to antiretroviral therapy in HIV-infected subjects. Comparing immunodiscordant and immunoconcordant subjects matched by pretreatment CD4 counts, we observed a lower pretreatment CD4/CD8 T-cell ratio in immunodiscordant subjects. Furthermore, pretreatment CD4/CD8 T-cell ratio, but not CD4 counts, correlated with the main immunological alterations observed in immunodiscordants, including increased regulatory T-cell (Treg) frequency and T-cell turnover-related markers. Then, in a larger cohort, only baseline CD4/CD8 T-cell ratio was independently associated with immunodiscordance, after adjusting by the viral CXCR4-tropic HIV variants. Our results suggest that the CD4/CD8 T-cell ratio could be an accurate biomarker of the subjacent immunological damage triggering immunodiscordance.
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Terapia Antirretroviral de Alta Atividade/métodos , Relação CD4-CD8 , Linfócitos T CD8-Positivos/imunologia , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , Linfócitos T Reguladores/imunologia , Adulto , Fármacos Anti-HIV/uso terapêutico , Biomarcadores/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Didanosina/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Receptores CXCR4/imunologia , Estavudina/uso terapêutico , Carga Viral , Zalcitabina/uso terapêutico , Zidovudina/uso terapêuticoRESUMO
Ecological limits to phenotypic plasticity (PP), induced by simultaneous biotic and abiotic factors, can prevent organisms from exhibiting optimal plasticity, and in turn lead to decreased fitness. Herbivory is an important biotic stressor and may limit plant functional responses to challenging environmental conditions such as shading. In this study we investigated whether plant functional responses and PP to shade are constrained by herbivory, and whether such constraints are due to direct effects based on resource limitation by considering ontogeny. We used as a model system the relict tree Prunus lusitanica and implemented an indoor experiment to quantify the response of saplings of different ages to shade and herbivory. We measured five functional traits and quantitatively calculated PP. Results showed that herbivory did not constrain functional responses or PP to shade except for shoot:root ratio (SR), which, despite showing a high PP in damaged saplings, decreased under shade instead of increasing. Damaged saplings of older age did not exhibit reduced constraints on functional responses to shade and generally presented a lower PP than damaged saplings of younger age. Our findings suggest that herbivory-mediated constraints on plant plasticity to shade may not be as widespread as previously thought. Nonetheless, the negative effect of herbivory on SR plastic expression to shade could be detrimental for plant fitness. Finally, our results suggest a secondary role of direct effects (resource-based) on P. lusitanica plasticity limitation. Further studies should quantify plant resources in order to gain a better understanding of this seldom-explored subject.
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Ontologias Biológicas , Herbivoria , Árvores/fisiologia , Ecologia , Luz , Modelos Biológicos , Fenótipo , Folhas de Planta/fisiologia , Folhas de Planta/efeitos da radiação , Raízes de Plantas/fisiologia , Raízes de Plantas/efeitos da radiação , Brotos de Planta/fisiologia , Brotos de Planta/efeitos da radiação , Plântula/fisiologia , Plântula/efeitos da radiação , Estresse Fisiológico , Árvores/efeitos da radiaçãoRESUMO
Depression is a common but frequently undiagnosed feature in individuals with HIV infection. To find a strategy to detect depression in a non-specialized clinical setting, the overall performance of the Hospital Anxiety and Depression Scale (HADS) and the depression identification questions proposed by the European AIDS Clinical Society (EACS) guidelines were assessed in a descriptive cross-sectional study of 113 patients with HIV infection. The clinician asked the two screening questions that were proposed under the EACS guidelines and requested patients to complete the HADS. A psychiatrist or psychologist administered semi-structured clinical interviews to yield psychiatric diagnoses of depression (gold standard). A receiver operating characteristic (ROC) analysis for the HADS-Depression (HADS-D) subscale indicated that the best sensitivity and specificity were obtained between the cut-off points of 5 and 8, and the ROC curve for the HADS-Total (HADS-T) indicated that the best cut-off points were between 12 and 14. There were no statistically significant differences in the correlations of the EACS (considering positive responses to one [A] or both questions [B]), the HADS-D ≥ 8 or the HADS-T ≥ 12 with the gold standard. The study concludes that both approaches (the two EACS questions and the HADS-D subscale) are appropriate depression-screening methods in HIV population. We believe that using the EACS-B and the HADS-D subscale in a two-step approach allows for rapid, assumable and accurate clinical diagnosis in non-psychiatric hospital settings.
Assuntos
Depressão , Infecções por HIV , Programas de Rastreamento/métodos , Adulto , Assistência Integral à Saúde/métodos , Estudos Transversais , Depressão/diagnóstico , Depressão/epidemiologia , Depressão/etiologia , Feminino , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Infecções por HIV/psicologia , Humanos , Entrevista Psicológica/métodos , Masculino , Pessoa de Meia-Idade , Curva ROC , Sensibilidade e Especificidade , Espanha/epidemiologiaRESUMO
BACKGROUND: Postmastectomy breast reconstruction involves the use of large amounts of hospital resources. This study provides comparative data on the clinical results and long-term economic costs of two methods of breast reconstruction in a public hospital. METHODS: A prospective cohort study was performed to evaluate the costs incurred by delayed unilateral breast reconstruction performed using either the two-stage sequence expander/prosthesis (E-P) or autologous deep inferior epigastric flap (DIEP) method during 2005-2013 in 134 patients. The major evaluated variables included previous clinical records, history of radiotherapy, and number of surgical procedures. Total costs accounted for both direct intra- and extra-hospital costs derived from the initial reconstruction and those resulting from associated reoperations due to aesthetic retouches and/or complications. RESULTS: Patients undergoing E-P reconstruction required a higher number of surgery sessions to complete the reconstruction (3.07 vs. 2.32, p < 0.001) and showed higher rates of surgery-related complications (40.29% vs. 32.82%). No statistically significant differences were found between the two surgical methods in terms of total costs (18857.77 DIEP vs. 20502.08 E-P; p = 0.89). In the E-P cohort, active smoking and history of radiotherapy were statistically significant risk factors of complications. In the DIEP group, only active smoking was significantly associated with complications. CONCLUSIONS: Compared to the E-P method, breast reconstruction using the DIEP method is more cost-effective and involves fewer serious complications that result in reconstruction failure or undesirable aesthetic results. E-P reconstruction presents a higher number of complications that may cause surgical failure or poor outcomes.
Assuntos
Implantes de Mama/economia , Custos Hospitalares/estatística & dados numéricos , Hospitais Públicos/economia , Mamoplastia/instrumentação , Reto do Abdome/transplante , Retalhos Cirúrgicos , Dispositivos para Expansão de Tecidos/economia , Neoplasias da Mama/cirurgia , Análise Custo-Benefício , Feminino , Seguimentos , Humanos , Mamoplastia/economia , Mastectomia , Pessoa de Meia-Idade , Estudos Prospectivos , Desenho de Prótese , Espanha , Fatores de Tempo , Transplante AutólogoRESUMO
OBJECTIVES: Fat mass ratio (FMR) has been suggested as an objective indicator of abnormal body fat distribution in HIV infection. Although it could provide more comprehensive information on body fat changes than limb fat mass, FMR has scarcely been used in clinical trials examining body fat distribution in HIV-infected patients. METHODS: A subanalysis of a controlled, randomized clinical trial in virologically suppressed HIV-1-infected men switching from zidovudine (ZDV)/lamivudine (3TC) to emtricitabine (FTC)/tenofovir (TDF) versus continuing on ZDV/3TC was carried out. FMR was assessed by dual X-ray absorptiometry (DEXA) for a period of 72 weeks. Lipoatrophy was defined as FMR ≥ 1.5. Multivariate linear regression models for the change in FMR from baseline were fitted. RESULTS: Sixty-five men were randomized and treated (28 in the FTC/TDF arm and 37 in the ZDV/3TC arm), and 57 completed the study (25 and 32 in each arm, respectively). In the FTC/TDF arm, adjusted mean FMR decreased by 0.52 at week 72 (P = 0.014), and in the ZDV/3TC arm it increased by 0.13 (P = 0.491; P between arms = 0.023). Among subjects with lipoatrophy (baseline FMR ≥ 1.5), adjusted FMR decreased by 0.76 (P = 0.003) in the FTC/TDF arm and increased by 0.21 (P = 0.411; P between arms = 0.009) in the ZDV/3TC arm. Baseline FMR and treatment group were significant predictors (P < 0.05) of post-baseline changes in FMR. CONCLUSIONS: Switching from ZDV/3TC to FTC/TDF led to an improvement in FMR, compared with progressive worsening of FMR in subjects receiving ZDV/3TC, showing that fat mass not only increased but was also distributed in a healthier way after the switch.
Assuntos
Fármacos Anti-HIV/uso terapêutico , Distribuição da Gordura Corporal , Substituição de Medicamentos , Emtricitabina/uso terapêutico , Infecções por HIV/tratamento farmacológico , Lamivudina/uso terapêutico , Tenofovir/uso terapêutico , Zidovudina/uso terapêutico , Absorciometria de Fóton , Adulto , Terapia Antirretroviral de Alta Atividade , Combinação de Medicamentos , HIV-1 , Humanos , Masculino , Pessoa de Meia-Idade , Análise de RegressãoRESUMO
OBJECTIVE: To describe tuberculosis (TB) incidence, risk factors, clinical presentation, disease management and outcomes in human immunodeficiency virus (HIV) infected patients from the CoRIS cohort, Spain, 2004-2010. DESIGN: Open multicentre cohort of antiretroviral treatment (ART) naïve patients at entry. Incidence and risk factors were evaluated using multivariate Poisson regression. RESULTS: Among 6811 patients, 271 were eligible for the study and 198 for the estimation of the incidence rate; TB incidence ranged from 12.1 to 14.1/1000 person-years. TB was associated with low education level (rate ratio [RR] 2.65, 95%CI 1.73-4.07), being sub-Saharan African (RR 3.14, 95%CI 1.81-5.45), heterosexual (RR 2.01, 95%CI 1.22-3.29) or an injecting drug user (RR 2.11, 95%CI 1.20-3.69), not undergoing ART (RR 3.33, 95%CI 2.22-4.76), CD4 <200 cells/mm(3) (RR 5.20, 95%CI 3.25-8.33) and log-viral load of 4-5 (RR 5.44, 95%CI 3.28-9.02) or >5 (RR 13.10, 95%CI 8.27-20.76). Overall, 87% were new cases and 13% were previously treated cases; 175 (65%) were bacteriologically confirmed. Drug susceptibility testing was performed in 146 (83%) patients: resistance to first-line drugs was 11.1% in new and 36.4% in previously treated cases. Standard anti-tuberculosis treatment with four or three drugs was prescribed in respectively 55% and 36% of cases. Treatment default was 11%, and was higher among previously treated cases; 80% received ART during anti-tuberculosis treatment, 80% of new and 50% of previously treated cases were cured or completed treatment, and 18 (6.6%) died. CONCLUSION: TB incidence in HIV-infected patients remains high. Interventions should include early HIV diagnosis and access to ART, enhanced bacteriological confirmation, wider use of four-drug regimens and reduction in treatment default.
Assuntos
Coinfecção , Infecções por HIV/epidemiologia , Tuberculose/epidemiologia , Adulto , Fármacos Anti-HIV/uso terapêutico , Antituberculosos/uso terapêutico , Distribuição de Qui-Quadrado , Farmacorresistência Bacteriana Múltipla , Quimioterapia Combinada , Feminino , Infecções por HIV/diagnóstico , Infecções por HIV/tratamento farmacológico , Humanos , Incidência , Tuberculose Latente/diagnóstico , Tuberculose Latente/tratamento farmacológico , Tuberculose Latente/epidemiologia , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Análise Multivariada , Valor Preditivo dos Testes , Estudos Prospectivos , Fatores de Risco , Espanha/epidemiologia , Fatores de Tempo , Resultado do Tratamento , Tuberculose/diagnóstico , Tuberculose/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/diagnóstico , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologiaRESUMO
BACKGROUND: Discontinuation of thymidine nucleoside reverse transcriptase inhibitors (tNRTIs) is the only proven strategy for improving lipoatrophy. It is unclear whether switching to NRTI-sparing or to non-thymidine NRTI-containing therapy has differential effects on body fat recovery. METHODS: This was a 96 week, open-label, randomized study in suppressed patients with moderate/severe lipoatrophy and no prior virological failure while receiving a protease inhibitor and who had their triple NRTI regimen (zidovudine/lamivudine/abacavir) switched to lopinavir/ritonavir plus abacavir/lamivudine for a 1 month run-in period and then randomized to lopinavir/ritonavir plus abacavir/lamivudine versus lopinavir/ritonavir monotherapy. The KRETA trial is registered with ClinicalTrials.gov (number NCT00865007). RESULTS: Of 95 patients included, 88 were randomized to lopinavir/ritonavir plus abacavir/lamivudine (nâ=â44) or lopinavir/ritonavir monotherapy (nâ=â44). Median (IQR) baseline limb fat was 2.5 (1.6-3.7) kg in the lopinavir/ritonavir plus abacavir/lamivudine group and 2.5 (2.0-5.4) kg in the lopinavir/ritonavir monotherapy group. Six patients in the triple therapy group and 13 in the monotherapy group had discontinued study drugs by week 96. Although there were limb fat gains in each group at weeks 48/96 (+324/+358 g in lopinavir/ritonavir plus abacavir/lamivudine, Pâ=â0.09/0.07, versus +215/+416 g in the lopinavir/ritonavir monotherapy group, Pâ=â0.28/0.16), differences between groups were not significant [difference +109 g (95% CI -442, +660)/-57 g (95% CI -740, +625)]. CONCLUSIONS: In lipoatrophic patients treated with zidovudine/lamivudine/abacavir, switching to lopinavir/ritonavir monotherapy had no additional benefit in limb fat recovery relative to switching to lopinavir/ritonavir with abacavir/lamivudine. These data suggest that non-thymidine nucleosides such as abacavir/lamivudine are not an obstacle to limb fat recovery.
Assuntos
Tecido Adiposo/patologia , Terapia Antirretroviral de Alta Atividade/métodos , Didesoxinucleosídeos/uso terapêutico , Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/uso terapêutico , Lamivudina/uso terapêutico , Lipodistrofia/complicações , Lopinavir/uso terapêutico , Inibidores da Transcriptase Reversa/uso terapêutico , Ritonavir/uso terapêutico , Absorciometria de Fóton , Adulto , Terapia Antirretroviral de Alta Atividade/efeitos adversos , Atrofia , Composição Corporal/fisiologia , Química Farmacêutica , Didesoxinucleosídeos/efeitos adversos , Feminino , Infecções por HIV/virologia , Inibidores da Protease de HIV/efeitos adversos , Humanos , Análise de Intenção de Tratamento , Lamivudina/efeitos adversos , Lipídeos/sangue , Lopinavir/efeitos adversos , Masculino , Pessoa de Meia-Idade , Inibidores da Transcriptase Reversa/efeitos adversos , Ritonavir/efeitos adversos , Falha de TratamentoRESUMO
Refugia are expected to preserve genetic variation of relict taxa, especially in polyploids, because high gene dosages could prevent genetic erosion in small isolated populations. However, other attributes linked to polyploidy, such as asexual reproduction, may strongly limit the levels of genetic variability in relict populations. Here, ploidy levels and patterns of genetic variation at nuclear microsatellite loci were analysed in Prunus lusitanica, a polyploid species with clonal reproduction that is considered a paradigmatic example of a Tertiary relict. Sampling in this study considered a total of 20 populations of three subspecies: mainland lusitanica (Iberian Peninsula and Morocco), and island azorica (Azores) and hixa (Canary Islands and Madeira). Flow cytometry results supported an octoploid genome for lusitanica and hixa, whereas a 16-ploid level was inferred for azorica. Fixed heterozygosity of a few allele variants at most microsatellite loci resulted in levels of allelic diversity much lower than those expected for a high-order polyploid. Islands as a whole did not contain higher levels of genetic variation (allelic or genotypic) than mainland refuges, but island populations displayed more private alleles and higher genotypic diversity in old volcanic areas. Patterns of microsatellite variation were compatible with the occurrence of clonal individuals in all but two island populations, and the incidence of clonality within populations negatively correlated with the estimated timing of colonization. Our results also suggest that gene flow has been very rare among populations, and thus population growth following founder events was apparently mediated by clonality rather than seed recruitment, especially in mainland areas. This study extends to clonal taxa the idea of oceanic islands as important refugia for biodiversity, since the conditions for generation and maintenance of clonal diversity (i.e. occasional events of sexual reproduction, mutation and/or seed immigration) appear to have been more frequent in these enclaves than in mainland areas.
Assuntos
Biodiversidade , Variação Genética , Genética Populacional , Poliploidia , Prunus/genética , DNA de Plantas/genética , Evolução Molecular , Fluxo Gênico , Genoma de Planta , Genótipo , Geografia , Ilhas , Região do Mediterrâneo , Repetições de Microssatélites , Análise de Sequência de DNARESUMO
OBJECTIVES: Lipoatrophy is a long-term adverse effect of some antiretrovirals that affects quality of life, compromises adherence and may limit the clinical impact of HIV treatments. This paper explores the effect of tenofovir/emtricitabine (TDF/FTC) on the amount of limb fat in patients with virological suppression. METHODS: A randomized, prospective clinical trial was performed to compare continuation on a zidovudine/lamivudine (ZDV/3TC)-based regimen with switching to a TDF/FTC-based regimen in terms of the effect on limb fat mass as assessed by DEXA over a 72-week period. RESULTS: Eighty patients were included (39 in the TDF/FTC arm and 41 in the ZDV/3TC arm) and 73 completed the study (37 and 36, respectively). In the switch arm, limb fat increased by a median of 540 g from baseline (P = 0.022), while in the ZDV/3TC arm it decreased by a median of 379 g (P = 0.112; p between groups = 0.007). Subjects with baseline limb fat ≤ 7200 g, previous time on ZDV > 5 years or a body mass index > 25 kg/m(2) experienced higher limb fat gains than other subjects, and these differences were statistically significant. Haemoglobin increased by a median of 1.0 g/dL in the TDF/FTC arm (P < 0.001) and remained unchanged in the ZDV/3TC arm (p between groups = 0.0002). There were no significant differences between groups in other secondary endpoints (body weight, total body and trunk fat content, total body bone mineral density, laboratory parameters, CD4 cell count and viral load). CONCLUSIONS: Switching from a ZDV/3TC-based to a TDF/FTC-based regimen led to a statistically significant improvement in limb fat, in contrast to the progressive loss of limb fat in subjects continuing ZDV/3TC.
Assuntos
Fármacos Anti-HIV/efeitos adversos , Fármacos Anti-HIV/uso terapêutico , Terapia Antirretroviral de Alta Atividade/efeitos adversos , Terapia Antirretroviral de Alta Atividade/métodos , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Síndrome de Lipodistrofia Associada ao HIV/patologia , Absorciometria de Fóton , Adenina/efeitos adversos , Adenina/análogos & derivados , Adenina/uso terapêutico , Tecido Adiposo/patologia , Adulto , Desoxicitidina/efeitos adversos , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapêutico , Emtricitabina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Organofosfonatos/efeitos adversos , Organofosfonatos/uso terapêutico , Estudos Prospectivos , Tenofovir , Resultado do TratamentoRESUMO
OBJECTIVES: The objective of the study was to analyse key HIV-related outcomes in migrants originating from Latin America and the Spanish-speaking Caribbean (LAC) or sub-Saharan Africa (SSA) living in Spain compared with native Spaniards (NSP). METHODS: The Cohort of the Spanish AIDS Research Network (CoRIS) is an open, prospective, multicentre cohort of antiretroviral-naïve patients representing 13 of the 17 Spanish regions. The study period was 2004-2010. Multivariate logistic or Fine and Gray regression models were fitted as appropriate to estimate the adjusted effect of region of origin on the different outcomes. RESULTS: Of the 6811 subjects in CoRIS, 6278 were NSP (74.2%), LAC (19.4%) or SSA (6.4%). For these patients, the follow-up time was 15870 person-years. Compared with NSP, SSA and LAC under 35 years of age had a higher risk of delayed diagnosis [odds ratio (OR) 2.0 (95% confidence interval (CI) 1.5-2.8) and OR 1.7 (95% CI 1.4-2.1), respectively], as did LAC aged 35-50 years [OR 1.3 (95% CI 1.0-1.6)]. There were no major differences in time to antiretroviral therapy (ART) requirement or initiation. SSA exhibited a poorer immunological and virological response [hazard ratio (HR) [corrected] 0.8 (95% CI 0.7-1.0) and HR [corrected] 0.7 (95% CI 0.6-0.9), respectively], while no difference was found for LAC. SSA and LAC showed an increased risk of AIDS for ages between 35 and 50 years [HR 2.0 (95% CI 1.1-3.7) and HR [corrected] 1.6 (95% CI 1.1-2.4), respectively], which was attributable to a higher incidence of tuberculosis. However, no statistically significant differences were observed in mortality. CONCLUSIONS: Migrants experience a disproportionate diagnostic delay, but no meaningful inequalities were identified regarding initiation of treatment after diagnosis. A poorer virological and immunological response was observed in SSA. Migrants had an increased risk of AIDS, which was mainly attributable to tuberculosis.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Fármacos Anti-HIV/uso terapêutico , Soropositividade para HIV/epidemiologia , Disparidades em Assistência à Saúde/estatística & dados numéricos , Adesão à Medicação/estatística & dados numéricos , Migrantes , Tuberculose/epidemiologia , Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Infecções Oportunistas Relacionadas com a AIDS/etnologia , Infecções Oportunistas Relacionadas com a AIDS/imunologia , Adulto , África Subsaariana/epidemiologia , Contagem de Linfócito CD4 , Diagnóstico Tardio/estatística & dados numéricos , Atenção à Saúde , Progressão da Doença , Feminino , Soropositividade para HIV/tratamento farmacológico , Soropositividade para HIV/etnologia , Soropositividade para HIV/imunologia , Disparidades em Assistência à Saúde/etnologia , Humanos , América Latina/epidemiologia , Masculino , Adesão à Medicação/etnologia , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores Socioeconômicos , Espanha/epidemiologia , Análise de Sobrevida , Tuberculose/tratamento farmacológico , Tuberculose/etnologia , Tuberculose/imunologia , Carga ViralRESUMO
The study of the evolutions of different wine pigment families, copigmentation/polymerisation processes and colour characteristics during the first year of ageing in oak barrel has allowed the assessment of the ageing aptitude of Syrah wines from "Condado de Huelva D.O.", a warm climate region. A total of 32 anthocyanic pigments were identified, including 14 major compounds from grape and 18 minor derivatives formed during the vinification. The anthocyanin profile changed towards more chemical complexity, being vitisin-like pyranoanthocyanins the predominant minor pigments during the first month of ageing. As wine became older, a progressive increase on the content of 4-vinylcatechin, 4-vinylphenol and 4-vinylcatechol compounds took place. Results showed that copigmentation occurred during the whole process of ageing inducing visual perceptible colour effects. Simultaneously to the copigmentation decrease, the degree of polymerisation increased during ageing, being maximum at 9 months old wines (77%). The colour of wines evolved progressively in a positive way from 3 to 9 months of ageing, becoming darker and with more vivid colour. However, from 9 to 12 months of ageing, the chemical structure of wines was negatively affected resulting in lighter, with more red-orange hues and less vivid colours. The inclusion of the chemical and colorimetric information on the PCA model allows us to reach very good discriminations among the Syrah wines with different wood contact period.
Assuntos
Colorimetria , Vinho/análise , Antocianinas/química , Clima , Cor , Fenóis/química , Quercus/química , Espanha , Fatores de TempoRESUMO
Chagas disease (CD) is an emergent disease in Europe that can behave as an opportunistic infection in HIV positive patients. The objective of this study was to evaluate the implementation of a CD screening programme in an HIV unit. An immunochromatography (ICT) of Trypanosoma cruzi was performed as a screening tool in HIV-positive patients born in CD endemic countries. ELISA and IFAT were used to confirm the diagnosis. A total of 155 patients, 116 males and 38 females, were included. Mean age was 36.9 years (± 8.4) and mean length of stay in Spain at the screening was 7.1 years (± 4.7). T. cruzi ICT was positive in four cases (2.6%), being confirmed (by ELISA and IFAT) in three of those (1.9%). Factors associated with confirmed positive T.cruzi serology were: Bolivia origin (p=0.016), Bolivia or Argentina origin (p=0.002), Southern Cone origin (p=0.015), rural origin (p=0.023), previously living in an adobe-made (p=0.001) or thatch-roofed house (p<0.0001), having a previous CD test (p=0.015), previous knowledge about CD (p=0.019), about vector (p=0.009) or recorded seeing vectors at home (p=0.012). Units dealing with HIV patients from endemic areas of American trypanosomiasis should implement CD screening protocols. Interviews of patients coming from endemic areas should include CD epidemiological questions.
Assuntos
Doença de Chagas/diagnóstico , Doença de Chagas/epidemiologia , Emigrantes e Imigrantes , Infecções por HIV/complicações , Adulto , Cromatografia de Afinidade/métodos , Estudos Transversais , Ensaio de Imunoadsorção Enzimática/métodos , Feminino , Imunofluorescência/métodos , Hispânico ou Latino , Humanos , Masculino , Programas de Rastreamento/métodos , Pessoa de Meia-Idade , Parasitologia/métodos , EspanhaRESUMO
BACKGROUND: On January 26, 2010, our team performed a facial transplant for a patient with neurofibromatosis type 1. We detail the perioperative surgical strategies for the composite tissue allograft (CTA) of the lower parts of the face to restore a severe defect after excision of bilateral massive plexiform neurofibromas. The main distinctive feature included an innovative provisional heterotopic transplantation (PHT) technique of the facial allograft to the femoral vessels before its final orthotopic transplantation. CASE REPORT: A 35-year-old Caucasian man received a CTA of the lower two-thirds of the face, including a chin osseous segment. The face was obtained from a non-heart-beating donor. The sequence of microsurgical procedures began by performing a PHT of the CTA to the recipient's femoral vessels in the right thigh. Intraoperatively, he experienced considerable blood loss that required transfusion of 24 units of packed cells. Surgical revision was required at day 7 to remove an extensive hematoma in the right side of the CTA. The maintenance immunosuppressive regimen included steroids, mycophenolate mofetil, and tacrolimus. CONCLUSION: We have reported a case of successful provisional transplantation of a human facial allograft onto the thigh as an alternative technique in human face transplantation. PHT was a reliable alternative procedure to obtain the facial allograft from a cadaveric donor.
Assuntos
Transplante de Face , Neurofibromatose 1/cirurgia , Adulto , Humanos , Imunossupressores/administração & dosagem , Masculino , Ácido Micofenólico/administração & dosagem , Ácido Micofenólico/análogos & derivados , Tacrolimo/administração & dosagemRESUMO
BACKGROUND: The high prevalence of classic cardiovascular risk factors in patients undergoing dialysis therapy or transplantation is associated with a 3.5- to 50-fold higher risk than in the general population. The primary cause of death in transplant recipients is cardiovascular disease. OBJECTIVE: To report echocardiographic findings using a screening protocol to detect heart disease in candidates for kidney transplantation. METHODS: Between November 2005 and December 2009, we examined 356 patients using 2-dimensional color Doppler echocardiography. RESULTS: A high prevalence of left ventricular hypertrophy, left ventricular diastolic dysfunction, valvulopathy, and valve calcification was observed. There was a positive correlation between valve calcification and female sex, age (P<.001), duration of renal replacement therapy (P=.01), peripheral arterial disease (P=.02), cerebrovascular disease (P=.005), and high concentration of lipoprotein(a) (P=.02). CONCLUSION: An echocardiographic study should be part of the initial evaluation in candidates for renal transplantation.