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OBJECTIVE: Placental insufficiency contributes to many obstetric pathologies however there is no bedside clinical tool to evaluate placental perfusion. We have developed a method to acquire multiple three-dimensional power Doppler ultrasound (3D PD-US) volumes of placental vasculature with infrared camera tracking providing global coordinates. These are automatically reconstructed ('stitched') into a model of the entire placenta. The purpose of the study was to evaluate the accuracy of automated reconstruction in an US phantom and apply this technique to human placentas. METHODS: A custom-designed acrylic phantom was constructed with dimensions mimicking a third-trimester placenta, containing 12 quadrilateral towers of varying heights submersed in tissue-mimicking solution. Triplicated three-dimensional ultrasound volumes of this phantom were acquired at three different acquisition angles using infrared camera tracking. Data was transformed into a three-dimensional cartesian volume and automatically stitched. A single-centre, cross-sectional feasibility study was conducted on uncomplicated second-to-third trimester singleton pregnancies using standardised obstetric settings. Multiple 3D PD-US and grayscale volumes of the placenta were acquired with infrared camera tracked coordinates. Volumes were stitched to create a model of placental vasculature. RESULTS: 6 phantom datasets were reconstructed at each of 3 volume angles with a median of 9 volumes required. Perfect volume alignment occurred in 66.7% of 648 datapoints. Mean distance error for volume misalignment was 2.92mm. Measurements of 210 distances in each stitched volume (2160 total distances) differed an average of 1.51mm from true measurements. These compare favourably with recent literature, though for a substantially larger phantom. 17 participants were scanned with 92% reconstruction success per placental volume set and 100% participant achievability. Median reconstruction time was 10 minutes. Placental vasculature was qualitatively assessed to be present, continuous, and detailed throughout. Volume measurement of entire segmented placentas was highly repeatable (ICC 0.96). CONCLUSION: We present an automated method to model the entire structure and vasculature of second-to-third trimester placentas, with verified accuracy and clinical feasibility for grayscale and power Doppler. This study builds the foundation to develop a practical screening tool for detecting placental insufficiency, and expansion to adult organ perfusion evaluation. This article is protected by copyright. All rights reserved.
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OBJECTIVE: The study aimed to investigate the feasibility of a remote mindfulness based self-management intervention for individuals with type 2 diabetes. It is important to further our understanding of how to improve self-management to improve health outcomes and low levels of uptake to self-management courses. METHOD: 29 participants with type 2 diabetes were recruited from the University Hospital Coventry and Warwickshire NHS trust. Three groups of participants engaged with a remote mindfulness based self-management intervention, which were delivered sequentially. After each intervention was complete, patient feedback was retrieved and implemented into the following intervention. The quantitative analysis comprised of descriptive statistics, independent sample t-test, paired sample t-test and multiple regression analysis. A qualitative analysis was also conducted through reflexive thematic analysis (RTA) to understand participant's perspective on the intervention. RESULTS: There was a total of 17 who attended the course (59 %) and a total drop out of 12 participants over the three courses (41 %). The qualitative findings reported three main themes: (1) Eating to manage my emotions rather than my diabetes (2) Implementing mindfulness has helped me manage my emotions (3) Medication rather than self-management behaviours control my diabetes. The focus group feedback included participants' appreciation of the community aspect of the intervention and their perception that the current course was more interactive compared to previous interventions. In addition, participants highlighted the importance of offering the course at an earlier stage of diagnosis to provide further support at the beginning of their diabetes journey. No significant findings were reported for the independent sample t-test, paired sample t-test and multiple regression analysis. CONCLUSION: The qualitative findings suggested that the course was beneficial, especially in demonstrating how mindfulness could aid self-management for individuals living with type 2 diabetes. Further funding and trials are warranted to improve the quality of technology used and to assess impact on diabetes control and mental health.
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Diabetes Mellitus Tipo 2 , Estudos de Viabilidade , Atenção Plena , Autogestão , Humanos , Diabetes Mellitus Tipo 2/terapia , Diabetes Mellitus Tipo 2/psicologia , Atenção Plena/métodos , Projetos Piloto , Masculino , Pessoa de Meia-Idade , Feminino , Idoso , AdultoRESUMO
The geological units on the floor of Jezero crater, Mars, are part of a wider regional stratigraphy of olivine-rich rocks, which extends well beyond the crater. We investigated the petrology of olivine and carbonate-bearing rocks of the Séítah formation in the floor of Jezero. Using multispectral images and x-ray fluorescence data, acquired by the Perseverance rover, we performed a petrographic analysis of the Bastide and Brac outcrops within this unit. We found that these outcrops are composed of igneous rock, moderately altered by aqueous fluid. The igneous rocks are mainly made of coarse-grained olivine, similar to some martian meteorites. We interpret them as an olivine cumulate, formed by settling and enrichment of olivine through multistage cooling of a thick magma body.
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INTRODUCTION: Polycystic ovary syndrome (PCOS) is a common condition characterized by reproductive, hyperandrogenic and dysmetabolic features, and often becomes clinically manifest during adolescence, particularly with weight-gain. SOURCES OF DATA: Pubmed search. AREAS OF AGREEMENT: PCOS is heritable and closely associates with obesity (based on data from both epidemiological and genetic studies). Furthermore, insulin resistance forms a central cornerstone of the pathogenesis of PCOS and mediates a close association between obesity and the severity of the phenotypic features of PCOS. AREAS OF CONTROVERSY: Our understanding of the pathogenesis of PCOS remains incomplete, especially regarding its missing heritability (with only a small fraction having been identified from the genome-wide association studies reported to date), and its developmental origins. GROWING POINTS: A challenge for the future is to explore a role for epigenetic modifications in the development of PCOS, and implications for the in utero environment and novel therapeutic opportunities.
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Resistência à Insulina , Síndrome do Ovário Policístico , Adolescente , Epigênese Genética , Feminino , Estudo de Associação Genômica Ampla , Humanos , Resistência à Insulina/genética , Masculino , Obesidade/complicações , Obesidade/epidemiologia , Obesidade/genética , Síndrome do Ovário Policístico/complicações , Síndrome do Ovário Policístico/epidemiologia , Síndrome do Ovário Policístico/genéticaRESUMO
Erythroderma (exfoliative dermatitis) is associated with important metabolic changes that include an enhancement in energy expenditure. The key components to total energy expenditure (TEE) include basal metabolic rate (~68% of TEE), physical activity (~22% of TEE) and thermic effect of food (~10% of TEE). In the erythrodermic state, there are likely multiple contributors to the increase in basal metabolic rate, such as 'caloric drain' resulting from increased evaporation of water from enhanced transepidermal water loss, increased activity of the cardiovascular system (including high-output cardiac failure), increased nonshivering thermogenesis and hormonal changes such as hypercortisolaemia. A change in the patient's level of physical activity and appetite as a result of ill health status may further impact on their TEE and energy consumption. In Part 2 of this two-part concise review, we explore the key constituents of energy homeostasis and the potential mechanisms influencing energy homeostasis in erythroderma, and suggest much-needed dietetic management strategies for this important condition.
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Dermatite Esfoliativa/dietoterapia , Dermatite Esfoliativa/metabolismo , Apetite , Metabolismo Basal , Débito Cardíaco , Síndrome de Cushing/fisiopatologia , Dermatite Esfoliativa/fisiopatologia , Metabolismo Energético , Exercício Físico , Homeostase , Humanos , Hipertireoidismo/fisiopatologia , Hipotireoidismo/fisiopatologia , Proteínas/metabolismo , Termogênese , Perda Insensível de ÁguaRESUMO
Erythroderma (exfoliative dermatitis), first described by Von Hebra in 1868, manifests as a cutaneous inflammatory state, with associated skin barrier and metabolic dysfunctions. The annual incidence of erythroderma is estimated to be 1-2 per 100 000 population in Europe with a male preponderance. Erythroderma may present at birth, or may develop acutely or insidiously (due to progression of an underlying primary pathology, including malignancy). Although there is a broad range of diseases that associate with erythroderma, the vast majority of cases result from pre-existing and chronic dermatoses. In the first part of this two-part concise review, we explore the underlying causes, clinical presentation, pathogenesis and investigation of erythroderma, and suggest potential treatment targets for erythroderma with unknown causes.
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Dermatite Esfoliativa/diagnóstico , Dermatite Esfoliativa/etiologia , Dermatite Esfoliativa/epidemiologia , Dermatite Esfoliativa/terapia , Europa (Continente)/epidemiologia , Feminino , Humanos , Incidência , MasculinoRESUMO
Due to a production error the bottom portion of Figure 1 was omitted. The corrected figure is given below.
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BACKGROUND AND PURPOSE: Apathy is an important neuropsychiatric feature of Parkinson's disease (PD), which often emerges before the onset of motor symptoms. Patients with rapid eye movement sleep behaviour disorder (RBD) have a high probability of developing PD in future. Neuropsychiatric problems are common in RBD, but apathy has not previously been detailed in this key prodromal population. METHODS: Eighty-eight patients with polysomnographically proven RBD, 65 patients with PD and 33 controls were assessed for apathy using the Lille Apathy Rating Scale. Cognition and depression were also quantified. The sensitivity of the Unified Parkinson's Disease Rating Scale screening questions for apathy and depression was calculated. RESULTS: A total of 46% of patients with RBD were apathetic, compared with 31% of patients with PD in our sample. Most patients with RBD with depression were apathetic but more than half of apathetic patients were not depressed. The sensitivity of the single Unified Parkinson's Disease Rating Scale screening question was only 33% for mild apathy and 50% for severe apathy. CONCLUSIONS: Apathy is common in RBD and is underestimated by a single self-report question. Recognition of apathy as a distinct neuropsychiatric feature in RBD could aid targeted treatment interventions and might contribute to the understanding of prodromal PD.
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Apatia , Transtorno do Comportamento do Sono REM/psicologia , Idoso , Idoso de 80 Anos ou mais , Cognição , Estudos de Coortes , Depressão/psicologia , Agonistas de Dopamina/uso terapêutico , Emoções , Feminino , Humanos , Levodopa/uso terapêutico , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Testes Neuropsicológicos , Doença de Parkinson/complicações , Doença de Parkinson/tratamento farmacológico , PolissonografiaRESUMO
CINAMMON is a phase IV, open-label, single-arm, pilot study assessing maraviroc (MVC) in the central nervous system (CNS) when added to darunavir/ritonavir monotherapy (DRV/r) in virologically suppressed HIV-infected subjects. CCR5 tropic participants on DRV/r were recruited. Participants remained on DRV/r for 12 week (w) (control phase). MVC 150 mg qd was added w12-w36 (intervention phase). Lumbar puncture (LP) and neurocognitive function (Cogstate) examinations scheduled at baseline, w12 and w36; MRI before w12, again at w36. Primary endpoint was CSF inflammatory marker changes during intervention phase. Secondary endpoints included changes in NC function and MRI parameters. CSF/plasma DRV/r concentrations measured at w12 and w36, MVC at w36. Nineteen patients recruited, 15 completed (17M, 2F). Dropouts: headache (2), knee problem (could not attend, 1), personal reasons (1). Mean age (range) 45.4 years (27.2-65.1), 13/19 white, 10/19 MSM. No changes in selected CSF markers were seen w12-w36. Overall NC function did not improve w12-w36: total age adjusted z score improved by 0.27 (weighted paired t test; p = 0.11); for executive function only, age adjusted z score improved by 0.54 (p = 0.03). MRI brain parameters unchanged. DRV plasma:CSF concentration ratio unchanged between w12 (132) and w36 (112; p = 0.577, Wilcoxon signed-rank). MVC plasma:CSF concentration ratio was 35 at w36. No changes in neuroinflammatory markers seen. In this small study, addition of 24w MVC 150 mg qd to stable DRV/r monotherapy showed possible improvement in executive function with no global NC effect. Learning effect cannot be excluded. This effect should be further evaluated.
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Fármacos Anti-HIV/uso terapêutico , Darunavir/uso terapêutico , Função Executiva/efeitos dos fármacos , Infecções por HIV/tratamento farmacológico , Maraviroc/uso terapêutico , Ritonavir/uso terapêutico , Adulto , Idoso , Biomarcadores/líquido cefalorraquidiano , Sistema Nervoso Central/diagnóstico por imagem , Sistema Nervoso Central/efeitos dos fármacos , Sistema Nervoso Central/fisiopatologia , Sistema Nervoso Central/virologia , Cognição/efeitos dos fármacos , Quimioterapia Combinada , Feminino , Ferritinas/líquido cefalorraquidiano , Infecções por HIV/líquido cefalorraquidiano , Infecções por HIV/diagnóstico por imagem , Infecções por HIV/fisiopatologia , HIV-1/efeitos dos fármacos , HIV-1/fisiologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neopterina/líquido cefalorraquidiano , Projetos Piloto , Desempenho Psicomotor/efeitos dos fármacos , Subunidade beta da Proteína Ligante de Cálcio S100/líquido cefalorraquidianoRESUMO
Stenotic artery hemodynamics are often characertised by metrics including oscillatory shear index (OSI) and residence time (RT). This analysis was conducted to clarify the link between the near-wall flow behaviour and these resultant flow metrics. A computational simulation was conducted of a stenosed femoral artery, with an idealised representative geometry and a physiologically realistic inlet profile. The overall flow behaviour was characterised through consideration of the axial flow, which was non-dimensionalised against mean flow velocity. The OSI and RT metrics, which are a useful indicator of likely atherosclerotic sites, were explained through a discussion of the WSS values at different time points, the velocity behaviour and velocity profiles, with a particular focus on the near-wall behaviour which influences wall shear stress and the transient evolution of the wall shear stress. While, the stenosis throat experiences high values of wall shear stress, the smooth flow through this contracted region results in low variation in wall shear stress vectors and limited opportunity for any particle stasis. However, regions were noted distal and proximal (though to a lesser extent), where the change in recirculation zones over the cycle created highly elevated regions of both OSI and RT.
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Arteriopatias Oclusivas/patologia , Arteriopatias Oclusivas/fisiopatologia , Artéria Femoral/patologia , Artéria Femoral/fisiopatologia , Estresse Mecânico , Velocidade do Fluxo Sanguíneo , Humanos , Fluxo Sanguíneo Regional , SístoleRESUMO
A number of treatment approaches exist for excessive flowrate arteriovenous fistulae. Banding has a number of advantages, yet there is concern over its use due to reported high post-surgery thrombosis rates. A computational study is conducted of a new technique, to elucidate the hemodynamics present in the process. The key improvement involves the use of an adjustable band which can be used to optimise the flowrate during the surgery. The pressure and flowrate changes are apparent from the computational results and the computational results also demonstrate that further optimization may be possible. We then present a small cohort of five cases where the new banding procedure has been implemented with success. The new technique was combined with intra-operative ultrasound flow monitoring.
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Fístula Arteriovenosa/fisiopatologia , Hemodinâmica/fisiologia , Adulto , Idoso , Angiografia , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Pressão , Fluxo Sanguíneo RegionalRESUMO
This study aimed to determine the prevalence of HIV neurocognitive impairment in HIV-infected men who have sex with men aged 18-50 years, using a simple battery of screening tests in routine clinical appointments. Those with suspected abnormalities were referred on for further assessment. The cohort was also followed up over time to look at evolving changes. HIV-infected participants were recruited at three clinical sites in London during from routine clinical visits. They could be clinician or self-referred and did not need to be symptomatic. They completed questionnaires on anxiety, depression, and memory. They were then screened using the Brief Neurocognitive Screen (BNCS) and International HIV Dementia Scale (IHDS). Two hundred and five HIV-infected subjects were recruited. Of these, 59 patients were excluded as having a mood disorder and two patients were excluded due to insufficient data, leaving 144 patients for analysis. One hundred and twenty-four (86.1%) had a normal composite z score (within 1 SD of mean) calculated for their scores on the three component tests of the BNCS. Twenty (13.9%) had an abnormal z score, of which seven (35%) were symptomatic and 13 (65%) asymptomatic. Current employment and previous educational level were significantly associated with BNCS scores. Of those referred onwards for diagnostic testing, only one participant was found to have impairment likely related to HIV infection. We were able to easily screen for mood disorders and cognitive impairment in routine clinical practice. We identified a high level of depression and anxiety in our cohort. Using simple screening tests in clinic and an onward referral process for further testing, we were not able to identify neurocognitive impairment in this cohort at levels consistent with published data.
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Complexo AIDS Demência/diagnóstico , Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/epidemiologia , Infecções por HIV/complicações , Homossexualidade Masculina/psicologia , Homossexualidade Masculina/estatística & dados numéricos , Programas de Rastreamento/métodos , Complexo AIDS Demência/epidemiologia , Adolescente , Adulto , Ansiedade/complicações , Ansiedade/epidemiologia , Ansiedade/psicologia , Transtornos Cognitivos/psicologia , Depressão/complicações , Depressão/epidemiologia , Depressão/psicologia , Infecções por HIV/psicologia , Humanos , Londres , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Prevalência , Fatores de Risco , Inquéritos e QuestionáriosRESUMO
The feasibility of implementing magnetic struts into drug-eluting stents (DESs) to mitigate the adverse hemodynamics which precipitate stent thrombosis is examined. These adverse hemodynamics include platelet-activating high wall shear stresses (WSS) and endothelial dysfunction-inducing low wall shear stresses. By magnetizing the stent struts, two forces are induced on the surrounding blood: (1) magnetization forces which reorient red blood cells to align with the magnetic field and (2) Lorentz forces which oppose the motion of the conducting fluid. The aim of this study was to investigate whether these forces can be used to locally alter blood flow in a manner that alleviates the thrombogenicity of stented vessels. Two-dimensional steady-state computational fluid dynamics (CFD) simulations were used to numerically model blood flow over a single magnetic drug-eluting stent strut with a square cross section. The effects of magnet orientation and magnetic flux density on the hemodynamics of the stented vessel were elucidated in vessels transporting oxygenated and deoxygenated blood. The simulations are compared in terms of the size of separated flow regions. The results indicate that unrealistically strong magnets would be required to achieve even modest hemodynamic improvements and that the magnetic strut concept is ill-suited to mitigate stent thrombosis.
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Artérias/fisiologia , Artérias/efeitos da radiação , Velocidade do Fluxo Sanguíneo/fisiologia , Desenho Assistido por Computador , Stents Farmacológicos , Imãs , Modelos Cardiovasculares , Artérias/anatomia & histologia , Velocidade do Fluxo Sanguíneo/efeitos da radiação , Pressão Sanguínea/fisiologia , Pressão Sanguínea/efeitos da radiação , Simulação por Computador , Relação Dose-Resposta à Radiação , Desenho de Equipamento , Análise de Falha de Equipamento , Estudos de Viabilidade , Humanos , Campos Magnéticos , Desenho de Prótese , Doses de Radiação , Resistência ao Cisalhamento/fisiologia , Resistência ao Cisalhamento/efeitos da radiação , Estresse MecânicoRESUMO
BACKGROUND: Teaching and learning hypospadias repair is a major component of pediatric urology fellowship training. Educators must transfer skills to fellows, without increasing patient complications. Nevertheless, few studies report results of surgeons during their first years of independent practice. PURPOSE: To review outcomes of distal hypospadias repairs performed during the same 2-year period by consecutive, recently matriculated, surgeons in independent practice, and to compare them to results by their mentor (with >20 years of experience). MATERIALS: Exposure to hypospadias surgery during fellowship was determined from case logs of five consecutive fellows completing training from 2007-2011. TIP was the only technique used to repair distal hypospadias. No fellow operated independently or performed complete repairs under supervision. Instead, the first 3 months were spent assisting their mentor, observing surgical methodology and decision-making. Then, each performed selected portions under direct supervision, including: degloving, penile straightening, developing glans wings, incising and tubularizing the urethral plate, creating a barrier layer, sewing the glansplasty, and skin closure. Overall fellow participation in each case was <50%. In 2011-2012, urethroplasty complications (fistula, glans dehiscence, meatal stenosis, urethral stricture, diverticulum) were recorded for consecutive patients undergoing primary distal repair by these recent graduates in their independent practices. The fellow graduating in 2011 provided 1 year of data. All patients undergoing repair during the study period were included in the analysis, except those lost to follow-up after catheter removal. Composite urethroplasty complications were compared between junior surgeons, and between junior surgeons and their mentor, with Fisher's exact contingency test. RESULTS: Training logs indicated fellow participation ranged from 76-134 hypospadias repairs, including distal, proximal and reoperative surgeries. Post-graduation case volumes ranged from 25-68 by junior surgeons versus 136 by the mentor. With similar mean follow-up, urethroplasty complication rates were statistically the same between the former fellows, and between them versus the mentor, ranging from 5-13%. Nearly all were fistulas or glans dehiscence. Junior surgeons reported they performed TIP as learned during fellowship, with one exception who used 7-0 polydioxanone rather than polyglactin for urethroplasty. DISCUSSION: This is the first study directly comparing hypospadias surgical outcomes by recently graduated fellows in independent practice with those of their mentor. We found junior surgeons achieved similar results for distal TIP hypospadias repair. Although their participation during training largely comprised observation and surgical assistance, with discrete performance of key steps, skills sufficient to duplicate the mentor's results were transferred. These data suggest there should be no learning curve for distal hypospadias after training. This report raises several considerations for surgical educators. First, mentors should review their own results, to be certain that they are correctly performing and teaching procedures. Second, programs need to determine key steps for procedures they teach, and then emphasize their optimal performance. Finally, mentors should expect former fellows to report back their initial results of hypospadias repair to be certain lessons taught were learned. Otherwise, preventable complications resulting from technical errors will be multiplied in the children operated by their trainees as they enter independent practice.
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Competência Clínica , Bolsas de Estudo , Hipospadia/cirurgia , Mentores , Pediatria/educação , Procedimentos Cirúrgicos Urológicos Masculinos/educação , Urologia/educação , Pré-Escolar , Humanos , Hipospadia/patologia , Lactente , Masculino , Resultado do TratamentoRESUMO
BACKGROUND: Ongoing inflammation in controlled HIV infection contributes to non-AIDS comorbidities. High bilirubin appears to exhibit an anti-inflammatory effect in vivo. We therefore examined whether increased bilirubin in persons with HIV was associated with differences in markers of inflammation and cardiovascular, bone, renal disease, and neurocognitive (NC) impairment. METHODS: This cross-sectional study examined inflammatory markers in individuals with stable HIV infection treated with two nucleoside reverse transcriptase inhibitors and a boosted protease inhibitor. Individuals recruited were those with a normal bilirubin (NBR; 0-17 µmol/L) or high bilirubin (>2.5 × upper limit of normal). Demographic and anthropological data were recorded. Blood and urine samples were taken for analyses. Pulse wave velocity (PWV) measurement, carotid intimal thickness (CIT), and calcaneal stiffness (CSI) were measured. Males were asked to answer a questionnaire about sexual function; NC testing was performed using CogState. RESULTS: 101 patients were screened, 78 enrolled (43 NBR and 35 HBR). Atazanavir use was significantly higher in HBR. Whilst a trend for lower CIT was seen in those with HBR, no significant differences were seen in PWV, bone markers, calculated cardiovascular risk (Framingham), or erectile dysfunction score. VCAM-1 levels were significantly lower in the HBR group. HBR was associated with lower LDL and triglyceride levels. NBR was associated with a calculated FRAX significantly lower than HBR although no associations were found after adjusting for tenofovir use. No difference in renal markers was observed. Component tests of NC testing revealed differences favouring HBR but overall composite scores were similar. DISCUSSION: High bilirubin in the context of boosted PI therapy was found not to be associated with differences in with the markers examined in this study. Some trends were noted and, on the basis of these, a larger, clinical end point study is warranted.
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Biomarcadores , Doenças Ósseas/etiologia , Doenças Cardiovasculares/etiologia , Disfunção Cognitiva/etiologia , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Hiperbilirrubinemia/etiologia , Nefropatias/etiologia , Adulto , Terapia Antirretroviral de Alta Atividade/efeitos adversos , Densidade Óssea , Doenças Ósseas/epidemiologia , Doenças Cardiovasculares/epidemiologia , Estudos de Casos e Controles , Disfunção Cognitiva/epidemiologia , Comorbidade , Estudos Transversais , Feminino , Infecções por HIV/tratamento farmacológico , HIV-1 , Humanos , Hiperbilirrubinemia/epidemiologia , Nefropatias/epidemiologia , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Inibidores de Proteases/administração & dosagem , Inibidores de Proteases/efeitos adversos , Inibidores de Proteases/uso terapêutico , Fatores de RiscoRESUMO
The prediction of conditions that may result in thrombus formation is a useful application of computational fluid dynamics. A number of techniques exist, based on the consideration of wall shear stress and regions of low blood flow; however, no clear guideline exists for the best practice of their use. In this paper, the sensitivity of each parameter and the specific mechanical forces are explained, before the optimal indicator of thrombosis risk is outlined. An extracorporeal access device cavity provides a suitable geometry to test the methodology. The recommended method for thrombus prediction considers areas with a calculated residence time (RT) and shear strain rate (SSR) thresholds, here set to RT>1 and SSR < 10 s(- 1). Evidence of thrombosis was found for physiological waveforms with an absence of reverse flow, which is expected to 'wash out' the cavity. The predicted thrombosis sites compare well with evidence collected from explanted devices.
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Artéria Femoral/fisiopatologia , Trombose/fisiopatologia , Simulação por Computador , Hemodinâmica , Humanos , Hidrodinâmica , Imageamento Tridimensional , Oscilometria , Perfusão , Resistência ao Cisalhamento , Estresse Mecânico , ViscosidadeRESUMO
Studies have suggested CD8 lymphocytes may be a possible marker for inflammation, which is believed to be a contributing factor to neurocognitive impairment. Individuals enrolled in the MSM Neurocog Study were analysed. Those with depression, anxiety or mood disorders were excluded. Individuals with neurocognitive impairment were identified using the Brief NeuroCognitive Screen and compared to those with normal scores. CD4 and CD8 T cell values and CD4:CD8 ratios were compared between groups. In all, 144 men, aged 18-50 years, were included in the analysis. Twenty were diagnosed with neurocognitive impairment. We were unable to identify any significant difference between current, nadir or peak CD4 and CD8 counts. CD4:CD8 ratios and CD4:CD8 ratio inversion (<1) were also found to be similar between both groups. However, neurocognitive impairment subjects were 8% more likely to have inversion of CD4:CD8 ratio and higher median peak CD8 cell counts reported compared to non-impaired subjects. Analysis of data from the MSM Neurocog Study, demonstrated trends in peripheral CD8 counts and CD4:CD8 ratios. However, we are unable to demonstrate any significant benefit. Plasma biomarkers of neurocognitive impairment in HIV-infected subjects would be of great benefit over current methods of invasive CSF analysis and technical neuroimaging used in the diagnosis of neurocognitive impairment. Future, prospective, longitudinal work with large numbers of neurocognitive impairment subjects is required to further investigate the role of peripheral CD8 T cells as markers of neurocognitive impairment.
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Linfócitos T CD8-Positivos/patologia , Transtornos Cognitivos/patologia , Infecções por HIV/complicações , Homossexualidade Masculina , Adolescente , Adulto , Relação CD4-CD8 , Humanos , Londres , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Estudos Retrospectivos , Fatores de Risco , Inquéritos e Questionários , Adulto JovemRESUMO
UNLABELLED: The case is a 34-year-old woman with long-standing type 1 diabetes mellitus with existing follow-up in the outpatient clinic at the Warwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism, UHCW. She had maintained good glycaemic control and glycaemic stability with basal bolus regimen for many years. She had not developed any diabetes-related complications and had no other co-morbidities. Six months ago, she presented to A&E with sudden-onset, well-localised and severe pain in the right iliac fossa, just lateral to the para-umbilical area. Her biochemistry was normal. Ultrasound scan, however, revealed a right-sided ovarian cyst, which was thought to have caused pain to her. She was discharged from A&E with simple analgesia. On subsequent gynaecological follow-up 4 weeks later, her pain remained severe and examination revealed an exquisitely tender subcutaneous nodule at the same location measuring 2âcm in diameter. Magnetic resonance imaging (MRI) scan at the time revealed a 1âcm mass in the subcutaneous adipose tissue, which co-localised to her pain. The mass demonstrated a central fat signal surrounded by a peripheral ring: observations consistent with fat necrosis. There were other smaller subcutaneous nodules also observed in the left para-umbilical area. Subsequent surgical resection of the main area of fat necrosis was performed. The patient made an excellent recovery and her pain resolved post-operatively. Histology confirmed the presence of fat necrosis. Fat necrosis is a rare complication of s.c. insulin injection. This case illustrates the importance of considering this diagnosis in patients who inject insulin and develop localised injection-site pain. LEARNING POINTS: Fat necrosis is a rare complication of insulin injections that can manifest with severe, persistent and well-localised pain.Fat necrosis can masquerade as other pathologies causing diagnostic confusion.The imaging modality of choice for accurate diagnosis of fat necrosis is MRI.Histological confirmation of fat necrosis is important.Appropriate management of localised fat necrosis is surgical excision, with avoidance of further insulin injections into the affected area.
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Nelson syndrome is an important complication of treatment with total bilateral adrenalectomy (TBA) for patients with refractory Cushing's disease. Although early cases of Nelson syndrome often presented with the clinical features of large sellar masses, the modern face of Nelson syndrome has changed primarily due to earlier detection (with highly resolved magnetic resonance imaging (MRI) and sensitive ACTH assays) and greater awareness of the condition, resulting in reduced morbidity and mortality. Although lack of administration of neoadjuvant pituitary radiotherapy post-TBA surgery may predict future development of Nelson syndrome, other predictive factors remain controversial. Therefore, Nelson syndrome should be screened for closely and long-term in all patients with a history of Cushing's disease and TBA. The diagnosis of Nelson syndrome remains controversial, and the pathogenesis of this condition is incompletely understood. Current hypotheses include the "released negative feedback" mechansism (residual pituitary corticotropinoma cells are "released" from the negative feedback effects of cortisol following TBA), and the "aggressive corticotropinoma" mechanism (Nelson syndrome is most likely to develop in those patients with refractory treatments - including TBA - for an underlying aggressive corticotropinoma). Effective management of Nelson syndrome with pituitary surgery and radiotherapy is often a challenge. Other therapies (such as Gamma Knife surgery and temozolomide) play an important role and merit further research into their efficacy and placement in the management pathway of Nelson syndrome.