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1.
Nature ; 588(7839): 648-652, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33177719

RESUMO

The selectivity of neuronal responses arises from the architecture of excitatory and inhibitory connections. In the primary visual cortex, the selectivity of a neuron in layer 2/3 for stimulus orientation and direction is thought to arise from intracortical inputs that are similarly selective1-8. However, the excitatory inputs of a neuron can have diverse stimulus preferences1-4,6,7,9, and inhibitory inputs can be promiscuous10 and unselective11. Here we show that the excitatory and inhibitory intracortical connections to a layer 2/3 neuron accord with its selectivity by obeying precise spatial patterns. We used rabies tracing1,12 to label and functionally image the excitatory and inhibitory inputs to individual pyramidal neurons of layer 2/3 of the mouse visual cortex. Presynaptic excitatory neurons spanned layers 2/3 and 4 and were distributed coaxial to the preferred orientation of the postsynaptic neuron, favouring the region opposite to its preferred direction. By contrast, presynaptic inhibitory neurons resided within layer 2/3 and favoured locations near the postsynaptic neuron and ahead of its preferred direction. The direction selectivity of a postsynaptic neuron was unrelated to the selectivity of presynaptic neurons, but correlated with the spatial displacement between excitatory and inhibitory presynaptic ensembles. Similar asymmetric connectivity establishes direction selectivity in the retina13-17. This suggests that this circuit motif might be canonical in sensory processing.


Assuntos
Vias Neurais , Células Piramidais/fisiologia , Córtex Visual/citologia , Córtex Visual/fisiologia , Animais , Potenciais Pós-Sinápticos Excitadores , Feminino , Potenciais Pós-Sinápticos Inibidores , Masculino , Camundongos , Inibição Neural , Técnicas de Rastreamento Neuroanatômico , Terminações Pré-Sinápticas/fisiologia , Vírus da Raiva/metabolismo , Receptores Virais/metabolismo , Retina/citologia , Retina/fisiologia , Proteínas do Envelope Viral/genética , Proteínas do Envelope Viral/metabolismo
2.
J Stroke Cerebrovasc Dis ; 33(9): 107844, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38945415

RESUMO

PURPOSE: Transient ischemic attack (TIA) is defined as a transient episode of neurological dysfunction caused by focal brain, spinal cord, or retinal ischemia, with clinical symptoms typically lasting less than one hour, and without evidence of acute infarction. In this type of ischemic event, there are no data about a possible cardiac injury tested with troponin. After a stroke, it is well established the cardiac involvement due to a neuro-inflammatory response (recently defined as Stroke Heart Syndrome). The aim of this study is to compare the troponin elevation after a stroke with the troponin elevation after a TIA. MATERIALS AND METHODS: This is a retrospective, single center study on 565 patients (73 TIAs, 492 stroke). We collected demographic characteristics, cardiovascular risk factors, cardiac data such as troponin, NT-proBNP, left atrial dilatation, etiology of the ischemic event (TOAST classification). RESULTS: We compare IS and TIA for each TOAST subtype. In all groups no substantial differences were found in demographic and past medical history (p > 0.05). However, the maximum troponin level reached were significantly lower in TIAs than IS (p < 0.05), except in lacunar etiology were troponin elevation was low also in IS group. We found a trend in favor to IS in the rise and fall troponin elevation over 30% in all the TOAST subgroups, but only in the cryptogenic etiology the difference was significant. About the others cardiac markers of injury, a significant higher rate of elevated NT-proBNP was found in the IS cohort. CONCLUSIONS: Troponin level after TIAs is significantly lower than after IS. Troponin elevation after an ischemic event may be more relevant in patients with higher NT-proBNP levels and older age. More studies are needed to better understand the pathophysiology of this phenomenon after an ischemic event.

3.
Appl Opt ; 62(16): E70-E77, 2023 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-37706891

RESUMO

A phase sensitive optical time domain reflectometry sensing scheme employing a two-stage nonlinear optical preamplification system is proposed to reduce the blind spot effect in Rayleigh scattering by improving the optical power distribution and to enhance the resolution at locations of low-backscatter intensity measurements, providing a higher signal-to-noise ratio for distributed acoustic measurements; the developed system has been tested in-laboratory and on in-field monitoring of a survey well in Cottessen, The Netherlands. The characterization shows strain noise levels below 1 nɛ for a 10 kHz sampling rate.

4.
Strahlenther Onkol ; 198(3): 236-246, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34351452

RESUMO

BACKGROUND: Published treatment technique comparisons for postoperative left-sided whole breast irradiation (WBI) with deep-inspiration breath-hold (DIBH) are scarce, small, and inconclusive. In this study, fully automated multi-criterial plan optimization, generating a single high-quality, Pareto-optimal plan per patient and treatment technique, was used to compare for a large patient cohort 1) intensity modulated radiotherapy (IMRT) with two tangential fields and 2) volumetric modulated arc therapy (VMAT) with two small tangential subarcs. MATERIALS AND METHODS: Forty-eight randomly selected patients recently treated with DIBH and 16â€¯× 2.66 Gy were included. The optimizer was configured for the clinical planning protocol. Comparisons between IMRT and VMAT included dosimetric plan parameters, estimated excess relative risks (ERR) for toxicities, delivery times, MUs, and deliverability accuracy at a linac. RESULTS: The automatically generated IMRT and VMAT plans applied in this study were similar or higher in quality than the manually generated clinical plans. For equal PTVin V95% (98.4 ± 0.9%), VMAT had significant advantages compared to IMRT regarding breast dose homogeneity and doses in heart and ipsilateral lung, at the cost of some minor deteriorations for contralateral breast (few cases with larger deteriorations) and lung. Conformality improved from 1.38 to 1.18 (p < 0.001). With VMAT, ERR for major coronary events and ipsilateral lung tumors were reduced by 3% (range: -1-12%) and 16% (range: -3-38%), respectively. MUs and delivery times were higher for VMAT. There were no statistical differences in γ passing rates. CONCLUSION: For WBI in conservative therapy of left-sided breast patients treated with DIBH, VMAT with two tangential subarcs was generally dosimetrically superior to IMRT with two tangential static fields. Results need confirmation by robustness analyses.


Assuntos
Radioterapia de Intensidade Modulada , Neoplasias Unilaterais da Mama , Humanos , Órgãos em Risco/efeitos da radiação , Radiometria , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia de Intensidade Modulada/métodos , Neoplasias Unilaterais da Mama/radioterapia
5.
Soft Matter ; 17(9): 2354-2368, 2021 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-33514989

RESUMO

Hematite microparticles are becoming increasingly important components in the soft matter field. The remarkable combination of magnetic and photocatalytic properties that characterize them, coupled with the variety of uniform and monodisperse shapes that they can be synthesized in, makes them a one of a kind colloidal model system. Thanks to these properties, hematite microparticles have been recently applied in several important soft matter applications, spanning from novel colloidal building blocks for self-assembly to necessary tools to investigate and understand fundamental problems. In this review article we provide a detailed overview of the traditional methods available for the preparation of hematite microparticles of different shapes, devoting special attention on some of the most common hiccups that could hider a successful synthesis. We furthermore review the particles' most important physico-chemical properties and their most relevant applications in the soft matter field.

6.
Regul Toxicol Pharmacol ; 117: 104767, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32866543

RESUMO

Skin sensitising substances that induce contact allergy and consequently risk elicitation of allergic contact dermatitis (ACD) remain an important focus regarding the replacement of animal experimentation. Current in vivo methods, notably the local lymph node assay (LLNA) refined and reduced animal usage and led to a marked improvement in hazard identification, characterisation and risk assessment. Since validation, regulatory confidence in the LLNA approach has evolved until it became the first choice assay in most regulated sectors. Currently, hazard identification using the LLNA is being actively replaced by a toolbox of non-animal approaches. However, there remains a need to increase confidence in the use of new approach methodologies (NAMs) as replacements for LLNA sensitiser potency estimation. The EPAA Partners Forum exchanged the current state of knowledge on use of NAMs in various industry sectors and regulatory environments. They then debated current challenges in this area and noted several ongoing needs. These included a requirement for reference standards for potency, better characterisation of applicability domains/technical limitations of NAMs, development of a framework for weight of evidence assessments, and an increased confidence in the characterisation of non-sensitisers. Finally, exploration of an industry/regulator cross-sector user-forum on skin sensitisation was recommended.


Assuntos
Alérgenos/toxicidade , Alternativas aos Testes com Animais/normas , Congressos como Assunto/normas , Ensaio Local de Linfonodo , Relatório de Pesquisa/normas , Pele/efeitos dos fármacos , Alternativas aos Testes com Animais/métodos , Animais , Bélgica/epidemiologia , Dermatite Alérgica de Contato/diagnóstico , Dermatite Alérgica de Contato/epidemiologia , Humanos , Medição de Risco/métodos , Medição de Risco/normas
7.
Phys Rev Lett ; 123(2): 027205, 2019 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-31386536

RESUMO

We report on negative thermal expansion (NTE) in the high-field, half-magnetization plateau phase of the frustrated magnetic insulator CdCr_{2}O_{4}. Using dilatometry, we precisely map the phase diagram at fields of up to 30 T and identify a strong NTE associated with the collinear half-magnetization plateau for B>27 T. The resulting phase diagram is compared with a microscopic theory for spin-lattice coupling, and the origin of the NTE is identified as a large negative change in magnetization with temperature, coming from a nearly localized band of spin excitations in the plateau phase. These results provide useful guidelines for the discovery of new NTE materials.

8.
Parasitol Res ; 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31712894

RESUMO

In the Mediterranean basin, one of the most important agents of myiasis is Oestrus ovis Linnaeus 1758 (Diptera, Oestridae). Herein, we report a rare case of nasal myiasis with a secondary infection complication in a patient from northern Italy who had been visiting Corsica. A healthy, 39-year-old Italian woman spent 2 weeks of vacation in Corsica in June 2018. During her stay, she suddenly felt a foreign body inside her nose, followed by cough, pain, burning at the pharyngeal level, cephalalgia, and nasal congestion with secretions from the nostrils. The clinical examination showed a hyperemic and irritated mucosa and endoscopic examination of the patient's nose and right maxillary sinus revealed three tiny mobile larvae, morphologically and molecular identified as L1 instar larvae of Oestrus ovis. The patient's infestation was probably imported from Corsica, as Mediterranean islands are ideal geographical areas for the development of O. ovis, and the timing of infestation match with the period of O. ovis larviposition. Although rhinomyiasis is rare, it should be considered in people returning from abroad presenting with an acute-onset and foreign body sensation in the nose.

9.
J Helminthol ; 94: e88, 2019 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-31537202

RESUMO

Free-ranging grey wolves (Canis lupus), which are presently recolonizing Italy, can be parasitized by a diversity of helminths, but have rarely been subject to studies of their parasites. Therefore, this study aims to determine the prevalence of gastrointestinal helminths of road-killed grey wolves from the Piedmont region of Italy. Forty-two wolves were collected and examined for the presence of helminths. We recorded 12 helminth species: nine Nematoda and three Cestoda. The nematodes were: Ancylostoma caninum (7.1%), Capillaria sp. (2.4%), Molineus sp. (2.4%), Pterygodermatites affinis (11.9%), Physaloptera sibirica (9.5%), Toxocara canis (9.5%), Toxascaris leonina (2.4%) and Uncinaria stenocephala (26.2%); the cestodes were: Dipylidium caninum (4.8%), Mesocestoides sp. (4.8%) and Taenia multiceps (76.2%). Physaloptera sibirica had the highest mean intensity and T. multiceps had the highest prevalence. Based on age and sex, no differences in the intensity or prevalence of helminth species were found among the hosts. Molineus sp. was recorded for the first time in wolves from the Palearctic region; P. affinis and P. sibirica are respectively reported for the first time in wolves from Europe and Italy.


Assuntos
Trato Gastrointestinal/parasitologia , Helmintíase Animal/parasitologia , Helmintos/isolamento & purificação , Enteropatias Parasitárias/veterinária , Lobos/parasitologia , Animais , Europa (Continente)/epidemiologia , Feminino , Helmintíase Animal/epidemiologia , Helmintos/classificação , Enteropatias Parasitárias/epidemiologia , Itália/epidemiologia , Masculino , Prevalência
10.
Histochem Cell Biol ; 148(6): 651-657, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28702782

RESUMO

Histidine-rich glycoprotein (HRG) is a relatively abundant plasma protein that is synthesized by parenchymal liver cells. Using Western blot analysis and immunoperoxidase techniques, we have previously shown the presence of HRG in human skeletal muscle. This paper reports the results of immunofluorescence experiments carried out on sections of human normal skeletal muscle biopsies to investigate the subcellular localization of HRG. The HRG localization was also compared with that of skeletal muscle AMP deaminase (AMPD1), since we have previously described an association of the enzyme with the protein. The obtained results give evidence for a preferential localization of HRG at the I-band level, where it shows the same distribution of actin and where AMPD1 is present in major concentration.


Assuntos
Músculo Esquelético/química , Proteínas/análise , Sarcômeros/química , AMP Desaminase/metabolismo , Humanos , Imuno-Histoquímica , Músculo Esquelético/metabolismo , Proteínas/metabolismo , Sarcômeros/metabolismo
11.
Qual Life Res ; 26(1): 205-211, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27256291

RESUMO

PURPOSE: Burn patients may encounter social barriers and stigmatization. The objectives of this study were to adapt the Social Comfort Questionnaire (SCQ) into Brazilian Portuguese and to assess the psychometric properties of the adapted version. METHODS: Cross-cultural adaptation of the 8 items of the SCQ followed international guidelines. We interviewed 240 burn patients and verified the SCQ internal consistency, test-retest reliability and construct validity, correlating the scores with depression [Beck Depression Inventory (BDI)], affect/body image and interpersonal relationships [Burns Specific Health Scale-Revised (BSHS-R)] and self-esteem [Rosenberg's Self-Esteem Scale (RSES)]. We also performed a confirmatory factor analysis (CFA). RESULTS: The cross-cultural adaptation resulted in minor semantic modifications to the original SCQ version. After CFA, a reduced 6-item version showed satisfactory fit to the one-factor model (RMSEA = 0.05, CFI = 0.99, TLI = 0.99). Cronbach alpha's was 0.80, and test-retest intraclass correlation coefficient was 0.86. The final version presented a strong negative correlation with depression (BDI), and strong positive correlations with affect/body image (BSHS-R), interpersonal relationships (BSHS-R) and self-esteem (RSES) (all p < 0.001). CONCLUSION: The results showed that the SCQ Brazilian Portuguese adapted version complies with the validity and reliability criteria required for an instrument assessing social comfort in Brazilian burn patients. The Brazilian version yields a single score that is easy to interpret and well understood by patients.


Assuntos
Queimaduras/psicologia , Comparação Transcultural , Psicometria/instrumentação , Qualidade de Vida/psicologia , Adulto , Brasil , Feminino , Humanos , Masculino , Conforto do Paciente , Psicometria/métodos , Reprodutibilidade dos Testes , Inquéritos e Questionários , Sobreviventes
12.
J Neurosci ; 35(1): 53-63, 2015 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-25568102

RESUMO

Genetically encoded voltage indicators (GEVIs) promise to reveal the membrane potential of genetically targeted neuronal populations through noninvasive, chronic imaging of large portions of cortical space. Here we test a promising GEVI in mouse cortex during wakefulness, a challenging condition due to large hemodynamic activity, and we introduce a straightforward projection method to separate a signal dominated by membrane voltage from a signal dominated by hemodynamic activity. We expressed VSFP-Butterfly 1.2 plasmid in layer 2/3 pyramidal cells of visual cortex through electroporation in utero. We then used wide-field imaging with two cameras to measure both fluorophores of the indicator in response to visual stimuli. By taking weighted sums and differences of the two measurements, we obtained clear separation of hemodynamic and voltage signals. The hemodynamic signal showed strong heartbeat oscillations, superimposed on slow dynamics similar to blood oxygen level-dependent (BOLD) or "intrinsic" signals. The voltage signal had fast dynamics similar to neural responses measured electrically, and showed an orderly retinotopic mapping. We compared this voltage signal with calcium signals imaged in transgenic mice that express a calcium indicator (GCaMP3) throughout cortex. The voltage signal from VSFP had similar signal-to-noise ratios as the calcium signal, it was more immune to vascular artifacts, and it integrated over larger regions of visual space, which was consistent with its reporting mostly subthreshold activity rather than the spiking activity revealed by calcium signals. These results demonstrate that GEVIs provide a powerful tool to study the dynamics of neural populations at mesoscopic spatial scales in the awake cortex.


Assuntos
Sondas de DNA/análise , Eletroporação/métodos , Imagem Molecular/métodos , Estimulação Luminosa/métodos , Córtex Visual/química , Córtex Visual/fisiologia , Animais , Sondas de DNA/genética , Feminino , Corantes Fluorescentes/análise , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Gravidez
13.
Org Biomol Chem ; 14(6): 2015-24, 2016 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-26754878

RESUMO

Herein, we disclose a general and flexible access to spirocyclopropyl oxindoles by a domino Michael/intramolecular nucleophilic substitution pathway with variously substituted vinyl selenones and enolizable oxindoles in aqueous sodium hydroxide solution. The spirocyclopropyl oxindole being a privileged scaffold, some of the synthesized compounds were selected for biological evaluation. Compound showed selective anti-HIV-1 activity thanks to its ability to inhibit the reverse transcriptase.


Assuntos
Fármacos Anti-HIV/farmacologia , Transcriptase Reversa do HIV/antagonistas & inibidores , HIV/efeitos dos fármacos , HIV/enzimologia , Inibidores da Transcriptase Reversa/farmacologia , Fármacos Anti-HIV/síntese química , Fármacos Anti-HIV/química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Ciclopropanos/síntese química , Ciclopropanos/química , Ciclopropanos/farmacologia , Transcriptase Reversa do HIV/metabolismo , Humanos , Indóis/síntese química , Indóis/química , Indóis/farmacologia , Testes de Sensibilidade Microbiana , Conformação Molecular , Compostos Organosselênicos/química , Compostos Organosselênicos/farmacologia , Inibidores da Transcriptase Reversa/síntese química , Inibidores da Transcriptase Reversa/química , Compostos de Espiro/síntese química , Compostos de Espiro/química , Compostos de Espiro/farmacologia , Compostos de Vinila/química , Compostos de Vinila/farmacologia , Replicação Viral/efeitos dos fármacos
14.
J Endocrinol Invest ; 39(5): 529-35, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26403983

RESUMO

BACKGROUND AND AIMS: Branchial abnormalities occur when there is disturbance in the maturation of the branchial apparatus during fetal development. Branchial anomalies are congenital lesions usually present in childhood, even if they can be diagnosed later for enlargement or infection. A correct diagnosis will lead to proper management: complete surgical excision is the treatment of choice. The purpose of this article is to present clinical features, diagnostic methods and surgical treatment of branchial anomalies in childhood, based on a series of 50 patients. METHODS: We conducted a retrospective analysis of a total of 50 pediatric patients operated from June 2005 to June 2014 for the presence of branchial cleft anomalies. RESULTS: 27 cases (54 %) presented a second branchial cleft fistula and 11 cases (22 %) a second branchial cleft cyst and one case (2 %) presented both cyst and sinus of the second branchial cleft; four cases (8 %) presented first branchial cleft cyst whereas four cases (8 %) a first branchial cleft sinus and two cases (4 %) a first branchial cleft fistula; one case (2 %) presented a piriform sinus fistula (third branchial cleft). None of our patients presented anomalies of the fourth branchial cleft. All patients underwent surgical treatment and lesions have been removed by excision or fistulectomy. No post-surgical complication occurred. The rate of recurrence was 4 %. CONCLUSIONS: Pre-operative diagnosis supplies important information to the surgeon for a proper therapy: a complete excision of the lesion without inflammatory signs is essential to avoid re-intervention and to achieve a good outcome.


Assuntos
Região Branquial/anormalidades , Anormalidades Congênitas/epidemiologia , Anormalidades Craniofaciais/epidemiologia , Fístula/epidemiologia , Doenças Faríngeas/epidemiologia , Adolescente , Região Branquial/cirurgia , Criança , Pré-Escolar , Anormalidades Congênitas/diagnóstico , Anormalidades Congênitas/cirurgia , Anormalidades Craniofaciais/diagnóstico , Anormalidades Craniofaciais/cirurgia , Feminino , Fístula/congênito , Fístula/cirurgia , Humanos , Lactente , Itália/epidemiologia , Doenças Faríngeas/diagnóstico , Doenças Faríngeas/cirurgia , Estudos Retrospectivos
15.
J Endocrinol Invest ; 39(9): 1055-9, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27129982

RESUMO

PURPOSE: The extent of surgery for pediatric papillary thyroid carcinoma is debatable. The aim of this study was to evaluate the feasibility of offering pediatric patients a tailored surgical approach based on certain clinical features. METHODS: A national multicenter retrospective review of 250 pediatric patients treated for papillary thyroid carcinoma in a 14-year period was performed. Outcomes of interest included tumor-related features, type of surgery, surgical morbidity, disease-free and overall survival rates. Recurrence was thoroughly analyzed with particular focus on how it correlated with certain patient- and tumor-related features. RESULTS: The majority of patients (58.8 %) had tumors >2 cm in size. Nodal involvement occurred in 115/250 (46 %) patients and distant metastasis in 4 % (10/250). Total thyroidectomy and lobectomy were performed in 90.4 % (226/250) and 9.6 % (24/250) of patients, respectively. The overall rate of surgical complications was 20.8 % (52/250). These included transient and permanent hypoparathyroidism (13.6 and 4.4 %, respectively), and vocal fold palsy (2.8 %). All surgical complications occurred exclusively in the total thyroidectomy group. The rate of recurrent disease was 12 % (30/250) with the vast majority of recurrences (96.6 %) occurring in the total thyroidectomy group. The risk of recurrence correlated significantly with certain tumor-related features (size > 2 cm, multifocality, extrathyroidal invasion, nodal positivity, and distant metastasis). However, it did not correlate with the patient's age or sex. Overall survival was 100 %. CONCLUSION: Pediatric patients are likely to benefit from a tailored surgical strategy. Uniformly offering patients total thyroidectomy seems to be an overly radical approach.


Assuntos
Carcinoma Papilar/cirurgia , Recidiva Local de Neoplasia/cirurgia , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia , Adolescente , Criança , Pré-Escolar , Gerenciamento Clínico , Feminino , Humanos , Itália , Masculino , Estudos Retrospectivos
16.
J Mater Sci Mater Med ; 27(6): 107, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27117793

RESUMO

Vascularization is a key factor in the successful integration of tissue engineered (TE) grafts inside the host body. Biological functions of the newly formed tissue depend, in fact, on a reliable and fast spread of the vascular network inside the scaffold. In this study, we propose a technique for evaluating vascularization in TE constructs assembled by a bottom-up approach. The rational, ordered assembly of building blocks (BBs) into a 3D scaffold can improve vessel penetration, and-unlike most current technologies-is compatible with the insertion of different elements that can be designed independently (e.g. structural units, growth factor depots etc.). Poly(ε-caprolactone) scaffolds composed of orderly and randomly assembled sintered microspheres were used to assess the degree of vascularization in a pilot in vivo study. Scaffolds were implanted in a rat subcutaneous pocket model, and retrieved after 7 days. We introduce three quantitative factors as a measure of vascularization: the total percentage of vascularization, the vessels diameter distribution and the vascular penetration depth. These parameters were derived by image analysis of microcomputed tomographic scans of biological specimens perfused with a radiopaque polymer. The outcome of this study suggests that the rational assembly of BBs helps the onset and organization of a fully functional vascular network.


Assuntos
Regeneração Tecidual Guiada , Neovascularização Fisiológica/fisiologia , Poliésteres/química , Alicerces Teciduais , Animais , Adesão Celular , Células Cultivadas , Células Endoteliais/fisiologia , Humanos , Teste de Materiais , Ratos
17.
Br J Cancer ; 113(7): 996-1002, 2015 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-26379080

RESUMO

BACKGROUND: Inconsistencies between mitotic index (MI) and Ki67 measures have been identified in many breast tumour samples. The aim of this study was to describe the prognosis of hormone receptor-positive (HR+) HER2- tumours having discrepant MI and Ki67. METHODS: We included a cohort of breast cancer patients initially treated by surgery between 2001 and 2005 in the Institut Curie. Breast cancer-specific survival (BCSS) and disease-free survival (DFS) were analysed according to three proliferation groups: high MI/high Ki67 (MI=3, Ki67>20%), low MI/low Ki67 (MI<3, Ki67⩽20%) and discrepant (high MI/low Ki67 or low MI/high Ki67). RESULTS: Among the 1430 patients, 19.6% had discrepant Ki67 and MI, 11.6% had high markers and 68.8% had low markers. The 5-year BCSS was 95.8%, 95% CI (0.93-0.98) in the discrepant group, 99.3%, 95% CI (0.993-0.999) in the low-proliferation group and 91.8%, 95% CI (0.88-0.96) in the high-proliferation group. In multivariate analysis, the survival of the discrepant group was lower than that of the low-proliferation group: BCSS hazard ratio (HR)=3.01 (1.32-6.84; P=0.008) and DFS HR=2.07, 95% CI (1.31-3.26; P=0.002). Among grade 2 tumours in multivariate analysis, DFS of the discrepant group was lower than that of the low MI/low Ki67 group: HR=1.98, 95% CI (1.14-3.46), P=0.02. Regarding BCSS, the obtained results were similar. CONCLUSION: The prognosis of patients with discrepant MI and Ki67 appears intermediate between that of low MI/low Ki67 and high MI/high Ki67 groups. These markers should be jointly analysed to clarify prognosis.


Assuntos
Neoplasias da Mama/patologia , Antígeno Ki-67/análise , Neoplasias da Mama/metabolismo , Neoplasias da Mama/mortalidade , Feminino , Humanos , Índice Mitótico , Prognóstico , Receptor ErbB-2/metabolismo , Receptores de Esteroides/metabolismo , Análise de Sobrevida
18.
Br J Cancer ; 112(10): 1717-24, 2015 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-25897673

RESUMO

BACKGROUND: This study aimed to investigate copy number variations (CNVs) of CYP17A1 and androgen receptor (AR) genes in serum cell-free DNA collected before starting abiraterone in 53 consecutive patients with castration-resistant prostate cancer (CRPC). METHODS: Serum DNA was isolated and CNVs were analysed for AR and CYP17A1 genes using Taqman copy number assays. The association between CNVs and progression-free/overall survival (PFS/OS) was evaluated by the Kaplan-Meier method and log-rank test. RESULTS: Median PFS of patients with AR gene gain was 2.8 vs 9.5 months of non-gained cases (P < 0.0001). Patients with CYP17A1 gene gain had a median PFS of 2.8 months vs 9.2 months in the non-gained patients (P = 0.0014). A lower OS was reported in both cases (AR: P < 0.0001; CYP17A1: P = 0.0085). Multivariate analysis revealed that PSA decline ⩾ 50%, AR and CYP17A1 CNVs were associated with shorter PFS (P < 0.0001, P = 0.0004 and P = 0.0450, respectively), while performance status, PSA decline ⩾ 50%, AR CNV and DNA concentration were associated with OS (P = 0.0021, P = 0.0014, P = 0.0026 and P = 0.0129, respectively). CONCLUSIONS: CNVs of AR and CYP17A1 genes would appear to be associated with outcome of CRPC patients treated with abiraterone.


Assuntos
Androstenos/uso terapêutico , Variações do Número de Cópias de DNA , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/genética , Receptores Androgênicos/sangue , Esteroide 17-alfa-Hidroxilase/sangue , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , DNA/genética , Intervalo Livre de Doença , Humanos , Calicreínas/sangue , Masculino , Pessoa de Meia-Idade , Antígeno Prostático Específico/sangue , Neoplasias de Próstata Resistentes à Castração/sangue , Neoplasias de Próstata Resistentes à Castração/enzimologia , Receptores Androgênicos/genética , Estudos Retrospectivos , Esteroide 17-alfa-Hidroxilase/genética
19.
Soft Matter ; 11(12): 2461-8, 2015 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-25671653

RESUMO

An ideal parallelogram platelet, although achiral in 3D, has an identifiable chirality when confined in a 2D monolayer. We lithographically fabricate microscale parallelogram platelets, disperse them in an aqueous surfactant solution, and allow them to settle towards a lower glass wall. To reduce the thermal-gravitational height, we add polystyrene nanospheres as a depletion agent to create a depletion attraction between the parallelograms and the wall. Surprisingly, by increasing the volume fraction of the depletion agent, we show that a nearly enantiopure monolayer can be created. We explain this by developing a model of 2D monolayer formation based on anisotropic facial attractions; one face of a platelet is more strongly attracted to the wall than the other as a consequence of an anisotropy introduced by the lithographic process. We study enantiopure Brownian systems of parallelograms as a function of particle area fraction and show that oblique chiral crystals form at high densities. By mixing parallelogram platelets printed in opposite senses, we also dictate the chiral ratio in the monolayer over the entire possible range. This approach is not limited to parallelograms and provides a means for tuning the chiral ratio in fluctuating 2D monolayers composed of a wide variety of chiral shapes.

20.
Eur J Vasc Endovasc Surg ; 50(2): 157-64, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25892319

RESUMO

OBJECTIVE: Endovascular aneurysm sealing (EVAS) has been proposed as a novel alternative to endovascular aneurysm repair (EVAR) in patients with infrarenal abdominal aortic aneurysms (AAA). The early clinical experience, technical refinements, and learning curve of EVAS in the treatment of AAA at a single institution are presented. METHODS: One-hundred and five patients were treated with EVAS between March 2013 and November 2014. Prospective data were recorded on consecutive patients receiving EVAS. Data included demographics, preoperative aneurysm morphology, and 30-day outcomes, including rates of endoleak, limb occlusion, reintervention, and death. Postoperative imaging consisted of duplex ultrasound and computed tomographic angiography. RESULTS: The mean age of the cohort was 76 ± 8 years and 12% were female. Adverse neck morphology was present in 72 (69%) patients, including aneurysm neck length <10 mm (20%), neck diameter >32 mm (18%), ß-angulation >60° (21%), and conical aneurysm neck (51%). There was one death within 30 days. The incidence of Type 1 endoleak within 30 days was 4% (n = 4); all were treated successfully with transcatheter embolisation. All four proximal endoleaks were associated with technical issues that resulted in procedure refinement, and all were in patients with adverse proximal aortic necks. The persistent Type 1 endoleak rate at 30 days was 0% and there were no Type 2 or Type 3 endoleaks. Angioplasty and adjunctive stenting were performed for postoperative limb stenosis in three patients (3%). CONCLUSIONS: EVAS appears to be associated with reasonable 30-day outcomes despite the necessity of procedural evolution in the early adoption of this technique. EVAS appears to be applicable to patients with challenging aortic morphology and endoleak rates should reduce with procedural experience. The utility of EVAS will be defined by the durability of the device in long-term follow-up, although the absence of Type 2 endoleaks is encouraging.


Assuntos
Angioplastia com Balão , Aneurisma da Aorta Abdominal/cirurgia , Implante de Prótese Vascular , Idoso , Idoso de 80 Anos ou mais , Angioplastia com Balão/efeitos adversos , Angioplastia com Balão/instrumentação , Angioplastia com Balão/mortalidade , Aneurisma da Aorta Abdominal/diagnóstico , Aneurisma da Aorta Abdominal/mortalidade , Aortografia/métodos , Prótese Vascular , Implante de Prótese Vascular/efeitos adversos , Implante de Prótese Vascular/instrumentação , Implante de Prótese Vascular/mortalidade , Embolização Terapêutica , Endoleak/diagnóstico , Endoleak/etiologia , Endoleak/terapia , Feminino , Oclusão de Enxerto Vascular/diagnóstico , Oclusão de Enxerto Vascular/etiologia , Oclusão de Enxerto Vascular/terapia , Humanos , Londres , Masculino , Estudos Prospectivos , Desenho de Prótese , Stents , Fatores de Tempo , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Ultrassonografia Doppler Dupla
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