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1.
Chemistry ; 26(3): 629-633, 2020 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-31702073

RESUMO

The formal insertion of alkenes into aromatic chloro- and bromoalkynes takes place under cationic gold catalysis. This haloalkynylation reaction can be performed with cyclic, gem-disubstituted and monosubstituted alkenes, using BINAP, triazolo[4,3-b]isoquinolin-3-ylidene ligands or SPhos, respectively. The products were isolated in moderate to excellent yields and with complete diastereo- and regioselectivity; the halogen atom bonding the more substituted carbon of the alkene. Preliminary experiments showed that the enantioselective haloalkynylation of cyclopentene can be performed with (S)-BINAP to afford the insertion products with moderate to good enantioselectivities.

2.
J Neurooncol ; 143(3): 515-523, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31054099

RESUMO

BACKGROUND: Contrast enhancement (CE) is found in 10-60% of low-grade gliomas. Its prognostic significance is controversial, and its correlation with IDH mutations and 1p/19q codeletion is elusive. The aim of this study is to investigate whether CE is associated with molecular characteristics of low-grade gliomas and uncover its prognostic value. MATERIALS AND METHODS: All confirmed histological cases of low-grade gliomas diagnosed at our institution between years 2000-2016 were reviewed (n = 102). Spinal and brainstem localization, only-biopsied tumours with ring-like enhancement and incomplete medical records were excluded. RESULTS: Mean age was 42 years ( ± 13.9 years), and 63.6% were male. The median follow-up time was 79.8 months. CE was present on 25% of preoperative MRI, and 25% of patients were considered high-risk according to Pignatti score. Most were astrocytomas (67%) and 87.2% were surgically removed. IDH mutation was found in 64.6% of tumour samples, and 18.8% had a 1p/19q codeletion. No subgroup differences were observed according to CE except for presurgical performance status and postoperative chemotherapy. IDH status and 1p/19q codeletion were evenly distributed. On univariate analysis, age, size > 6 cm, CE, extent of resection, Pignatti score, IDH mutation and 1p/19q codeletion were significantly associated to OS. On multivariate analysis, only CE and IDH status were independently associated to OS. CE remained a significant prognostic factor in IDH-mutant non-codeleted tumours when analysed by tumour subtype. CONCLUSION: CE in low-grade gliomas provides prognostic information in IDH-mutant non-codeleted tumours, although its meaning remains uncertain in IDH-wildtype gliomas.


Assuntos
Deleção Cromossômica , Meios de Contraste , Glioma/patologia , Aumento da Imagem/métodos , Isocitrato Desidrogenase/genética , Mutação , Adulto , Biomarcadores Tumorais/genética , Cromossomos Humanos Par 1/genética , Cromossomos Humanos Par 19/genética , Terapia Combinada , Feminino , Seguimentos , Glioma/genética , Glioma/terapia , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Taxa de Sobrevida
3.
Hum Brain Mapp ; 40(11): 3233-3242, 2019 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-30938027

RESUMO

Cognitive decline is a major disabling feature in Parkinson's disease (PD). Multimodal imaging studies have shown functional disruption in neurocognitive networks related to cognitive impairment. However, it remains unknown whether these changes are related to gray matter loss, or whether they outline network vulnerability in the early stages of cognitive impairment. In this work, we intended to assess functional connectivity and graph theoretical measures and their relation to gray matter loss in Parkinson's disease with mild cognitive impairment (PD-MCI). We recruited 53 Parkinson's disease patients and classified them for cognitive impairment using Level-1 Movement Disorders Society-Task Force Criteria. Voxel-based morphometry, functional connectivity and graph theoretical measures were obtained on a 3-Tesla MRI scanner. Loss of gray matter was observed in the default mode network (bilateral precuneus), without a corresponding disruption of functional or graph theoretical properties. However, functional and graph theoretical changes appeared in salience network nodes, without evidence of gray matter loss. Global cognition and executive scores showed a correlation with node degree in the right anterior insula. We also found a correlation between visuospatial scores and right supramarginal gyrus node degree. Our findings highlight the loss of functional connectivity and topological features without structural damage in salience network regions in PD-MCI. They also underline the importance of multimodal hubs in the transition to mild cognitive impairment. This functional disruption in the absence of gray matter atrophy suggests that the salience network is a key vulnerable system at the onset of mild cognitive impairment in PD.

4.
PLoS One ; 14(3): e0213403, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30917142

RESUMO

OBJECTIVES: To test the heterogeneity of the effect of a change in pharmaceutical cost-sharing by therapeutic groups in a Spanish region. METHODS: Data: random sample (provided by the Canary Islands Health Service) of 40,471 people covered by the Spanish National Health System (SNHS) in the Canary Islands. The database includes individualised monthly-dispensed medications (prescribed by the SNHS) from one year before (August 2011) to one year after (June 2013) the Royal Decree Law 16/2012 (RDL 16/2012). Sample: two intervention groups (low-income pensioners and middle-income working population) and one control group (low-income working population). Empirical model: quasi-experimental difference-in-differences design to study the change in consumption (measured in number of monthly Defined Daily Dose (DDDs) per individual) among 13 therapeutic groups. The policy break indicator (three-level categorical variable) tested the existence of stockpiling between the reform's announcement and its implementation. We ran 16 linear regression models (general, by therapeutic groups and by comorbidities) that considered whether the exclusion of some drugs from public provision impacted on consumption more than the co-payment increase. RESULTS: General: Reduction (-13.04) in consumption after the reform's implementation, which was fully compensated by a previous increase (16.60 i.e., stockpiling) among low-income pensioners. The middle-income working population maintained its trend of increasing consumption. Therapeutic groups: Reductions in consumption after the reform's implementation among low-income pensioners in 7 of the 13 groups, which were fully compensated for by a previous increase (i.e., stockpiling) in 4 groups and partially compensated for in the remaining 3. The analysis without the excluded medicines provided fewer negative coefficients. Comorbidities: Reduction in consumption that was only slightly compensated for by a previous increase (i.e., stockpiling). CONCLUSIONS: The negative impact of cost-sharing produced, among low-income pensioners, a risk of loss of adherence to treatments, which could deteriorate the health status of individuals, especially among pensioners within the most inelastic therapeutic groups (associated with chronic diseases) and patients with comorbidities (also, associated with chronic diseases). Notwithstanding the above, this risk was more related to the exclusion of some drugs from provision than to the cost-sharing increase.


Assuntos
Dedutíveis e Cosseguros , Custos de Medicamentos , Medicamentos sob Prescrição/economia , Dedutíveis e Cosseguros/legislação & jurisprudência , Dedutíveis e Cosseguros/estatística & dados numéricos , Dedutíveis e Cosseguros/tendências , Custos de Medicamentos/legislação & jurisprudência , Custos de Medicamentos/estatística & dados numéricos , Custos de Medicamentos/tendências , Feminino , Humanos , Modelos Lineares , Masculino , Programas Nacionais de Saúde/economia , Programas Nacionais de Saúde/legislação & jurisprudência , Programas Nacionais de Saúde/estatística & dados numéricos , Cooperação do Paciente/estatística & dados numéricos , Pobreza/economia , Pobreza/estatística & dados numéricos , Medicamentos sob Prescrição/provisão & distribução , Espanha
5.
Mov Disord ; 34(1): 78-86, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30536829

RESUMO

BACKGROUND: Minor hallucinations and well-structured hallucinations are considered in the severity continuum of the psychotic spectrum associated with Parkinson's disease. Although their chronological relationship is largely unknown, the spatial patterns of brain atrophy in these 2 forms of hallucinations partially overlap, suggesting they share similar pathophysiological processes. Functional connectivity studies show that disruption of functional networks involved in perception and attention could be relevant in the emergence of well-structured hallucinations. However, functional neuroimaging studies in patients with isolated minor hallucinations are lacking. The objectives of this study were to explore the structural and functional changes underlying minor hallucinations. METHODS: We compared patients with (n = 18) and without (n = 14) minor hallucinations using a multimodal structural (gray-matter volume voxel-based morphometry) and functional (seed-to-whole-brain resting-state functional MRI) neuroimaging study. RESULTS: Coincident with previously described structural changes in well-structured hallucinations in Parkinson's disease, patients with minor hallucinations exhibited gray-matter atrophy with significant voxel-wise differences in visuoperceptual processing areas and core regions of the default mode network. Functional connectivity changes consisted of altered connectivity within the default mode network, reduced negative correlation with task-positive network, and aberrant connectivity between posterior regions of the default mode network and visual-processing areas. These changes are in accordance with the attentional networks hypothesis proposed for well-structured hallucinations. CONCLUSIONS: Although longitudinal studies are needed to assess the potential role of minor hallucinations as an early clinical biomarker of progression to well-structured hallucinations, the present findings show that the 2 phenomena share similar structural and functional brain correlates. © 2018 International Parkinson and Movement Disorder Society.


Assuntos
Atenção/fisiologia , Encéfalo/fisiopatologia , Rede Nervosa/fisiopatologia , Doença de Parkinson/fisiopatologia , Idoso , Encéfalo/patologia , Mapeamento Encefálico/métodos , Transtornos Cognitivos/fisiopatologia , Feminino , Humanos , Processamento de Imagem Assistida por Computador/métodos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos
6.
Neurosurgery ; 85(3): E448-E456, 2019 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-30407589

RESUMO

BACKGROUND: Adult IDH-wildtype astrocytomas with TERT promoter mutations (TERTp) are associated with a poor prognosis. OBJECTIVE: To analyze the radiological presentation and natural history of adult IDH-wildtype astrocytomas with TERTp. METHODS: We retrospectively reviewed the characteristics of 40 IDH-wildtype TERTp-mutant astrocytomas (grade II n = 19, grade III n = 21) and compared them to those of 114 IDH-mutant lower grade gliomas (LGG), of 92 IDH-wildtype TERTp-mutant glioblastomas, and of 15 IDH-wildtype TERTp-wildtype astrocytomas. RESULTS: Most cases of IDH-wildtype TERTp-mutant astrocytomas occurred in patients aged >50 yr (88%) and presented as infiltrative lesions without contrast enhancement (73%) that were localized in the temporal and/or insular lobes (37.5%) or corresponded to a gliomatosis cerebri (43%). Thalamic involvement (33%) and extension to the brainstem (27%) were frequently observed, as was gyriform infiltration (33%). This radiological presentation was different from that of IDH-mutant LGG, IDH-wildtype TERTp-mutant glioblastomas, and IDH-wildtype TERTp-wildtype astrocytomas. Tumor evolution before treatment initiation was assessable in 17 cases. Ten cases demonstrated a rapid growth characterized by the apparition of a ring-like contrast enhancement and/or a median velocity of diametric expansion (VDE) ≥8 mm/yr but 7 cases displayed a slow growth (VDE <8 mm/yr) that could last several years before anaplastic transformation. Median overall survival of IDH-wildtype TERTp-mutant astrocytomas was 27 mo. CONCLUSION: IDH-wildtype TERTp-mutant astrocytomas typically present as nonenhancing temporo-insular infiltrative lesions or as gliomatosis cerebri in patients aged >50 yr. In the absence of treatment, although rapid tumor growth is frequent, an initial falsely reassuring, slow growth can be observed.

7.
J Cancer Res Clin Oncol ; 144(9): 1793-1801, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29955956

RESUMO

BACKGROUND: Oxaliplatin (OXA) is a cornerstone in the treatment of colorectal cancer (CRC). Retreatment with OXA is frequently considered as salvage treatment. OXA-induced neuropathy (OIN) is the most frequent and feared long-term side effect. PATIENTS AND METHODS: CRC patients receiving at least twice OXA-based chemotherapy lines at our institution between June 2000 and July 2016 were reviewed. The aim of this study was to investigate whether retreatment with OXA increases the risk of developing new or worsening previous neuropathy. OIN was assessed by National Cancer Institute-Common Toxicity Criteria for Adverse Events (NCI), Total Neuropathy Score© (TNS) and nerve-conduction studies. RESULTS: 106 patients were included in the analysis. Median age at OXA-based retreatment was 61.5 (20-83) years. After the first OXA-based chemotherapy treatment, 63.4% of patients developed OIN, 30.7 and 8.9% grades 2 and 3, respectively, after a median of 11 (1-17) cycles. After 30 (11-90) months of median to retreatment with a median of 8 (1-14) OXA cycles, 39.6, 22.6, and 0% of patients developed grade 1, 2, and 3 OIN, respectively. Worsening of the previous OIN was observed in one-third (31.1%) of all patients. OXA-cumulative dose was independently associated with greater risk of worsening OIN (p < 0.001). Non-significant trend towards higher TNSc© scores after retreatment was observed [5 (0-11) vs 6 (3-13), p = 0.083]. CONCLUSION: Retreatment with OXA in CRC patients is a feasible option even in patients who previously developed moderate or severe OIN. One-third of patients' OIN was worsened by retreatment. Neurological monitoring should be considered.


Assuntos
Antineoplásicos/efeitos adversos , Neoplasias Colorretais/tratamento farmacológico , Compostos Organoplatínicos/efeitos adversos , Compostos Organoplatínicos/uso terapêutico , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Oxaliplatina , Adulto Jovem
8.
Sci Rep ; 8(1): 8106, 2018 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-29802270

RESUMO

Type 1 diabetes can be overcome by regulatory T cells (Treg) in NOD mice yet an efficient method to generate and maintain antigen-specific Treg is difficult to come by. Here, we devised a combination therapy of peptide/MHC tetramers and IL-2/anti-IL-2 monoclonal antibody complexes to generate antigen-specific Treg and maintain them over extended time periods. We first optimized treatment protocols conceived to obtain an improved islet-specific Treg/effector T cell ratio that led to the in vivo expansion and activation of these Treg as well as to an improved suppressor function. Optimized protocols were applied to treatment for testing diabetes prevention in NOD mice as well as in an accelerated T cell transfer model of T1D. The combined treatment led to robust protection against diabetes, and in the NOD model, to a close to complete prevention of insulitis. Treatment was accompanied with increased secretion of IL-10, detectable in total splenocytes and in Foxp3- CD4 T cells. Our data suggest that a dual protection mechanism takes place by the collaboration of Foxp3+ and Foxp3- regulatory cells. We conclude that antigen-specific Treg are an important target to improve current clinical interventions against this disease.


Assuntos
Anticorpos Monoclonais/imunologia , Diabetes Mellitus Tipo 1/imunologia , Diabetes Mellitus Tipo 1/terapia , Antígenos de Histocompatibilidade/química , Interleucina-2/imunologia , Peptídeos/química , Linfócitos T Reguladores/imunologia , Sequência de Aminoácidos , Animais , Diabetes Mellitus Tipo 1/tratamento farmacológico , Feminino , Camundongos , Peptídeos/farmacologia , Fenótipo , Multimerização Proteica , Estrutura Quaternária de Proteína , Linfócitos T Reguladores/efeitos dos fármacos
9.
Dalton Trans ; 47(15): 5196-5206, 2018 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-29528072

RESUMO

The direct dialkylation of triazolo[4,3-b]isoquinolin-3-ylidene structures readily affords dicationic N-heterotricyclic azolium salts. These are suitable starting materials for the synthesis of transition metal complexes containing N-heterotricyclic, cationic ligands characterized by extended charge delocalization. Silver and gold complexes as well as mono- and dicationic rhodium(i) complexes have been prepared and characterized, and the electronic properties of the ligand have been evaluated by using the TEP parameter and by comparison with a non-cationic analogue. X-Ray diffraction analysis of several carbene-metal complexes shows a negligible effect of the charge on the structures of the complexes. The catalytic activity of a tricationic gold complex has been evaluated in the intramolecular hydroarylation of a terminal alkyne.

10.
J Neurol ; 265(3): 669-677, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29383516

RESUMO

OBJECTIVE: To identify the clinical and radiological features that should raise suspicion for the autoimmune encephalitis (AE)-like presentation of glioblastoma. METHODS: This is an observational, retrospective case series of patients referred to the French National Reference Center on Paraneoplastic Neurological Diseases for suspected AE (possible, probable or definite, using the 2016 criteria) who later received a final diagnosis of glioblastoma according to 2016 WHO criteria. An extensive literature search was also conducted for similar existing cases. RESULTS: Between 2014 and 2016, 306 patients were referred to our center for suspected AE. Six of these patients (2%) later developed pathologically confirmed glioblastoma. Thirteen patients (9 male) were included for analysis (6 from the present series and 7 from the literature); median age was 63. Initially, a diagnosis of AE was clinically suspected based on: working memory deficits (77%), seizures (62%) (including status epilepticus in 23%), and psychiatric symptoms (46%). Initial brain MRI was not in favor of a typical glioblastoma pattern and showed bilateral (54%) or unilateral selective limbic involvement. Five patients exhibited initial slight contrast enhancement. A clear inflammatory CSF was present in five patients and three from the literature showed autoantibody positivity (NMDAR, VGKC, GluRepsilon2). Median delay between suspicions of AE to GBM diagnosis was 3 months (range 1.5-24) and one patient from the literature was diagnosed post-mortem. CONCLUSIONS: An alternative diagnosis of glioblastoma should be considered in patients presenting initially as AE, especially in patients who do not fulfill the criteria for definite AE and in those with a poor clinical evolution despite initial improvement.


Assuntos
Neoplasias Encefálicas/diagnóstico , Encefalite/diagnóstico , Glioblastoma/diagnóstico , Doença de Hashimoto/diagnóstico , Adulto , Idoso , Biomarcadores/líquido cefalorraquidiano , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/terapia , Diagnóstico Diferencial , Encefalite/terapia , Feminino , Glioblastoma/patologia , Glioblastoma/terapia , Doença de Hashimoto/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
11.
J Neurooncol ; 138(1): 141-145, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29388033

RESUMO

Rechallenge with temozolomide has been shown to be a valid option in selected patients with progressive glioblastoma. Herein, we assessed the efficacy of rechallenge with bevacizumab in glioblastoma patients progressing off therapy. We retrospectively identified and analyzed the characteristics of patients with glioblastoma rechallenged with a bevacizumab-based chemotherapy regimen after having received bevacizumab as first-line treatment in association with temozolomide radiochemotherapy or at recurrence in association with temozolomide, CCNU or irinotecan. Twenty-five patients were identified. In all included patients, the first bevacizumab treatment resulted in an objective response and was discontinued for reasons other than disease progression (adverse event n = 9, physician or patient decision n = 16). Median duration of first bevacizumab treatment was 6 months (range: 2-58 months). None of the patients presented a rebound effect after bevacizumab discontinuation. The median interval between discontinuation of first bevacizumab treatment and bevacizumab rechallenge was 8.9 months (range: 2-58 months). At this time, bevacizumab was given in association with lomustine (n = 17), temozolomide (n = 6), irinotecan (n = 1), or alone (n = 1). Bevacizumab rechallenge resulted in an objective response in 15 patients (60%). Median progression-free survival was 6.7 months and overall survival was 9.6 months after bevacizumab rechallenge. Timing of first bevacizumab treatment (as first-line treatment or at recurrence) was not associated with the duration of response after treatment rechallenge. In the present series, patients who responded to bevacizumab and in whom this treatment was discontinued in the absence of tumor progression seemed to benefit from rechallenge with a bevacizumab-based chemotherapy regimen.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Bevacizumab/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Glioblastoma/tratamento farmacológico , Idoso , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/genética , Progressão da Doença , Feminino , Seguimentos , Glioblastoma/diagnóstico por imagem , Glioblastoma/genética , Humanos , Isocitrato Desidrogenase/genética , Estimativa de Kaplan-Meier , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Mutação/genética , Intervalo Livre de Progressão , Estudos Retrospectivos , Resultado do Tratamento
12.
PLoS Comput Biol ; 14(1): e1005945, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29324768

RESUMO

Pungent chemical compounds originating from decaying tissue are strong drivers of animal behavior. Two of the best-characterized death smell components are putrescine (PUT) and cadaverine (CAD), foul-smelling molecules produced by decarboxylation of amino acids during decomposition. These volatile polyamines act as 'necromones', triggering avoidance or attractive responses, which are fundamental for the survival of a wide range of species. The few studies that have attempted to identify the cognate receptors for these molecules have suggested the involvement of the seven-helix trace amine-associated receptors (TAARs), localized in the olfactory epithelium. However, very little is known about the precise chemosensory receptors that sense these compounds in the majority of organisms and the molecular basis of their interactions. In this work, we have used computational strategies to characterize the binding between PUT and CAD with the TAAR6 and TAAR8 human receptors. Sequence analysis, homology modeling, docking and molecular dynamics studies suggest a tandem of negatively charged aspartates in the binding pocket of these receptors which are likely to be involved in the recognition of these small biogenic diamines.


Assuntos
Cadaverina/química , Diaminas/química , Putrescina/química , Olfato , Animais , Ácido Aspártico/química , Comportamento Animal , Proteínas de Ciclo Celular/química , Biologia Computacional , Simulação por Computador , Humanos , Ligantes , Simulação de Acoplamento Molecular , Proteínas Nucleares/química , Mucosa Olfatória/fisiologia , Filogenia , Poliaminas/química , Ligação Proteica , Receptores Acoplados a Proteínas-G/química , Peixe-Zebra
13.
Birth Defects Res ; 110(6): 495-501, 2018 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-29316356

RESUMO

BACKGROUND: Previous studies have reported an association between maternal zinc deficiency and increased risk of nonsyndromic cleft lip with or without cleft palate (NSCL/P) in offspring. A high prevalence of zinc deficiency and a high prevalence of NSCL/P have been reported in Ecuador. We postulated that mothers of infants with NSCL/P may have lower serum zinc levels than women from the general population. METHODS: A case series study was conducted from November 2013 to July 2016. Thirty-five healthy mothers of infants with NSCL/P were selected during surgical missions conducted by Operación Sonrisa Ecuador. A single blood sample along with pertinent medical history was collected during personal interviews after 3.6 months postpartum. The prevalence of plasma zinc concentration (PZn) deficiency among the participants was determined and analyzed along with the prevalence of PZn deficiency in Ecuadorian women of reproductive age from the general population. RESULTS: The mean PZn was 11.47 µmol/dm3 . The prevalence of PZn deficiency among the participants was 31.4% (95% CI: 17.1-48.6) and differed significantly from the prevalence of zinc deficiency observed among women from the general population (G2 = 8.66; p < .05). CONCLUSIONS: The results showed that the prevalence of PZn deficiency is lower in a cohort of healthy mothers of infants with NSCL/P than in women from the general population in Ecuador. More studies are required to confirm these findings and evaluate other factors related to NSCL/P pathophysiology in the Ecuadorian population.


Assuntos
Fenda Labial/sangue , Fissura Palatina/sangue , Mães , Zinco/sangue , Equador , Feminino , Humanos , Lactente , Masculino , Adulto Jovem
14.
Curr Opin Oncol ; 29(6): 434-442, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28901965

RESUMO

PURPOSE OF REVIEW: The current review summarizes recent advances on the oncogenesis, classification and treatment of adult anaplastic gliomas. RECENT FINDINGS: According to the 2016 WHO classification, three main molecular subgroups of adult diffuse anaplastic gliomas can be distinguished based on the 1p/19q codeletion and isocitrate dehydrogenase (IDH) mutation status. In the future, this classification may be further refined based on the telomerase reverse transcriptase promoter and alpha thalassemia/mental retardation syndrome X-linked mutation status, gene expression, DNA methylation and genomic profiling. Both newly diagnosed 1p/19q codeleted and 1p/19q-intact anaplastic gliomas benefit from the addition of chemotherapy to radiotherapy. However, in 1p/19q codeleted anaplastic gliomas, Procarbazine, CCNU and Vincristine chemotherapy seems more effective than temozolomide. At recurrence, 1p/19q-intact anaplastic gliomas do not benefit from the addition of bevacizumab to temozolomide. The use of poly(adenosine 5'-diphosphate-ribose) inhibitors may be another way of specifically targeting IDH-mutant gliomas in addition to specific inhibitors, demethylating agents and anti-IDH vaccines. v-raf murine sarcoma viral oncogene homolog B1 (BRAF)-mutant anaplastic xanthoastrocytomas and gangliogliomas may benefit from BRAF and mitogen-activated protein kinase inhibitors. SUMMARY: Molecular characterization is mandatory for integrated diagnosis and appropriate management of adult anaplastic gliomas. Both 1p/19q codeleted and 1p/19q-intact anaplastic diffuse gliomas benefit from early chemotherapy. At recurrence, preliminary data suggest a potential role for targeted therapies in specific molecular subgroups.


Assuntos
Neoplasias Encefálicas/classificação , Neoplasias Encefálicas/terapia , Glioma/classificação , Glioma/terapia , Adulto , Neoplasias Encefálicas/genética , Deleção Cromossômica , Cromossomos Humanos Par 1 , Cromossomos Humanos Par 19 , Glioma/genética , Humanos
15.
Rev. estomatol. Hered ; 27(1): 13-20, ene. 2017. ilus, graf, tab
Artigo em Espanhol | LILACS-Express | ID: biblio-991165

RESUMO

Objetivos: Determinar el nivel de ruido producido durante los procedimientos clínicos odontológicos en las Áreas de Operatoria dental, Prótesis fija, Endodoncia y Odontopediatría de la Facultad de Odontología de la Universidad Nacional Mayor de San Marcos, Centro Médico Naval y Hospital Nacional Hipólito Unanue. Material y métodos: Se tomó una muestra por conveniencia de 80 registros sonoros de procedimientos clínicos odontológicos en prótesis fija, operatoria dental, odontopediatría y endodoncia usando un sonómetro digital, el cual fue colocado a nivel del oído y a una distancia de 45 cm del procedimiento clínico odontológico. Resultados: Se encontró que el mayor promedio de nivel de ruido a la altura del oído fue en operatoria dental con 83,13 decibeles(dB) y el menor fue en endodoncia con 65,57 dB. A 45 cms., el mayor promedio fue en prótesis fija con 76,99 dB y el menor fue en Endodoncia con 61,62 dB. Conclusiones: Los procedimientos clínicos odontológicos de operatoria dental, prótesis fija, endodoncia y odontopediatría se encontraron dentro de los límites permisibles sonoros del Ministerio de Salud del Perú.


Objetives: to determine the noise level made during odontological clinical procedures at the areas of operative dentistry, fixed prosthetics, endodontics and pediatric dentistry, at the Faculty of Dentistry at San Marcos University, Navy Medical Center and Hipolito Unanue National Hospital. Material and methods:A convenience sample of 80 sound records were registered at Dental Operatory, Fixed Prosthetic, Endodoncy, and Pediatric Dentistry clinics using a digital sound meter, which were located at ear level and at 45cm from the clinical dental procedure. Results: The highest average noise record at ear level was 83.13 decibels (dB) at dental operatory, and the lowest average noise record was 65.57 dB at endodoncy. The highest average noise record at 45 cm from de clinical dental procedure was 76.99 dB at Fixed Prosthetics, and the lowest average noise record was 61.62 dB at endodoncy. Conclusions: The sound level of dental operatory, fixed prosthetic, endodoncy, and pediatric dentistry were within the permissible limits by the Health Ministry of Peru.

16.
Dalton Trans ; 45(25): 10113-7, 2016 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-27254732

RESUMO

The benzoannulation of the most common families of aromatic NHCs, imidazol-2-ylidenes and 1,2,4-triazol-3-ylidenes, results in heterobicyclic imidazo[1,5-a]pyridin-3-ylidenes ('s) and [1,2,4]triazolo[4,3-a]pyridin-3-ylidenes ('s), characterized by a bridged N atom. These are versatile platforms that offer multiple possibilities for the modulation of the steric and electronic properties of the carbene ligand and/or organocatalyst, and offer also diverse opportunities for the introduction of several types of chiralities. In this paper the different families of chiral and carbenes and their application in asymmetric catalysis will be discussed.

17.
Nature ; 530(7591): 434-40, 2016 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-26886799

RESUMO

Regulatory T cells hold promise as targets for therapeutic intervention in autoimmunity, but approaches capable of expanding antigen-specific regulatory T cells in vivo are currently not available. Here we show that systemic delivery of nanoparticles coated with autoimmune-disease-relevant peptides bound to major histocompatibility complex class II (pMHCII) molecules triggers the generation and expansion of antigen-specific regulatory CD4(+) T cell type 1 (TR1)-like cells in different mouse models, including mice humanized with lymphocytes from patients, leading to resolution of established autoimmune phenomena. Ten pMHCII-based nanomedicines show similar biological effects, regardless of genetic background, prevalence of the cognate T-cell population or MHC restriction. These nanomedicines promote the differentiation of disease-primed autoreactive T cells into TR1-like cells, which in turn suppress autoantigen-loaded antigen-presenting cells and drive the differentiation of cognate B cells into disease-suppressing regulatory B cells, without compromising systemic immunity. pMHCII-based nanomedicines thus represent a new class of drugs, potentially useful for treating a broad spectrum of autoimmune conditions in a disease-specific manner.


Assuntos
Autoantígenos/imunologia , Autoimunidade/imunologia , Linfócitos T Reguladores/imunologia , Animais , Células Apresentadoras de Antígenos/imunologia , Linfócitos B/citologia , Linfócitos B/imunologia , Antígenos CD11/imunologia , Diferenciação Celular , Citocinas/imunologia , Feminino , Antígenos de Histocompatibilidade Classe II/química , Antígenos de Histocompatibilidade Classe II/genética , Antígenos de Histocompatibilidade Classe II/imunologia , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos NOD , Camundongos Transgênicos , Nanomedicina , Nanopartículas/química , Nanopartículas/uso terapêutico , Especificidade de Órgãos , Prevalência , Solubilidade , Linfócitos T Reguladores/citologia
18.
Eur J Hosp Pharm ; 23(3): 141-144, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-31156835

RESUMO

Objectives: To evaluate the level of concordance between the 2007 PRETEMED guidelines and the 2012 American College of Chest Physicians (ACCP) guidelines in medical patients at admission. Methods: A cross-sectional, observational and descriptive study was designed and included all adult medical patients admitted from an emergency department. Firstly, patients classified as low-moderate risk and high risk according to PRETEMED were compared to those classified by ACCP as low and high risk. Secondly, the same analysis was performed but this time low and moderate-high risk patients according to PRETEMED were compared to ACCP low and high risk patients. The level of concordance was calculated using the kappa concordance index. The study was approved by the Ethics Committee for Clinical Research of the hospital. Results: The analysis was performed with 207 patients; 53.1% were male and the median age was 75.3 years (minimum 18, maximum 100 years old). The most common diagnosis at admission was related to a respiratory disease (37.2%). The level of concordance was 0.59 (95% CI 0.48 to 0.70) when moderate risk patients were grouped with low-risk patients and 0.53 (95% CI 0.42 to 0.65) when moderate risk patients were grouped with high-risk patients. Conclusions: The level of concordance between both guides is moderate. It would be helpful to confirm whether the level of agreement improves when the patient's condition stabilises after several days of hospitalisation.

19.
Neuro Oncol ; 18(5): 707-15, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-26415875

RESUMO

BACKGROUND: Primary central nervous system lymphomas may present as diffuse, nonenhancing infiltrative lesions. This rare variant is termed lymphomatosis cerebri (LC). We did a systematic review and analysis of the literature, adding our own cases, to better characterize LC in order to improve early diagnosis and treatment. METHODS: PubMed, ISI Web of Knowledge, and hospital databases were reviewed. Information was extracted regarding demographic, clinical, histological, cerebrospinal fluid (CSF), neuroimaging, and treatment variables. The impact of single parameters on overall survival (OS) was determined by applying univariate and multivariate analyses. RESULTS: Forty-two patients were included (median age: 58 y; range: 28-80 y). At consultation, 52% of patients had a poor KPS. The most common presenting symptom was cognitive decline (59.5%). Imaging studies showed supratentorial and infratentorial infiltration in 55% of patients and bilateral hemispheric involvement in 95%. CSF pleocytosis was present in 51.5% of the patients. Median time to diagnosis was 4.5 (range: 1-30) months, and the diagnosis was not established until autopsy for 33% of patients. The median OS was 2.95 (range: 0.33-56) months; however, those patients who received methotrexate had a median OS of 13.8 (range: 0.7-56) months. Analysis identified KPS ≥ 70 (HR: 0.32; 95% CI: 0.114-0.894; P = .03) and treatment with methotrexate (HR: 0.19; 95% CI: 0.041-0.886; P = .034) as independent favorable prognostic factors, whereas T-cell lymphoma was independently related with a worse outcome (HR: 6.62; 95% CI: 1.317-33.316; P = .022). CONCLUSIONS: LC is a misdiagnosed entity associated with considerable diagnostic delay. MRI evidence of bilateral hemispheric involvement and CSF pleocytosis should be alerts for this diagnosis. Treatment with methotrexate-based chemotherapy must be considered, especially for patients with good KPS.


Assuntos
Neoplasias do Sistema Nervoso Central/patologia , Linfoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Neoplasias do Sistema Nervoso Central/mortalidade , Neoplasias do Sistema Nervoso Central/terapia , Feminino , Humanos , Estimativa de Kaplan-Meier , Linfoma/mortalidade , Linfoma/terapia , Masculino , Pessoa de Meia-Idade , Radioterapia
20.
Org Lett ; 18(1): 92-5, 2016 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-26652478

RESUMO

The first asymmetric cycloaddition of nonstabilized azomethine ylide and N-sulfinylimines is presented. In reactions with aryl-alkyl and heteroaryl-alkyl ketimines, excellent diastereoselectivities and good yields are obtained in all cases, regardless of the electronic character of the substituents at the aromatic rings. Moreover, the cycloadducts obtained can easily be deprotected in acid media, giving access to free 1,2-diamines which are prevalent in many natural and pharmaceutical products.

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