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1.
J Pathol ; 261(3): 256-268, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37565350

RESUMO

Adenoid cystic carcinoma (ACC) is a MYB-driven head and neck malignancy with high rates of local recurrence and distant metastasis and poor long-term survival. New effective targeted therapies and clinically useful biomarkers for patient stratification are needed to improve ACC patient survival. Here, we present an integrated copy number and transcriptomic analysis of ACC to identify novel driver genes and prognostic biomarkers. A total of 598 ACCs were studied. Clinical follow-up was available from 366 patients, the largest cohort analyzed to date. Copy number losses of 1p36 (70/492; 14%) and of the tumor suppressor gene PARK2 (6q26) (85/343; 25%) were prognostic biomarkers; patients with concurrent losses (n = 20) had significantly shorter overall survival (OS) than those with one or no deletions (p < 0.0001). Deletion of 1p36 independently predicted short OS in multivariate analysis (p = 0.02). Two pro-apoptotic genes, TP73 and KIF1B, were identified as putative 1p36 tumor suppressor genes whose reduced expression was associated with poor survival and increased resistance to apoptosis. PARK2 expression was markedly reduced in tumors with 6q deletions, and PARK2 knockdown increased spherogenesis and decreased apoptosis, indicating that PARK2 is a tumor suppressor in ACC. Moreover, analysis of the global gene expression pattern in 30 ACCs revealed a transcriptomic signature associated with short OS, multiple copy number alterations including 1p36 deletions, and reduced expression of TP73. Taken together, the results indicate that TP73 and PARK2 are novel putative tumor suppressor genes and potential prognostic biomarkers in ACC. Our studies provide new important insights into the pathogenesis of ACC. The results have important implications for biomarker-driven stratification of patients in clinical trials. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.


Assuntos
Carcinoma Adenoide Cístico , Neoplasias de Cabeça e Pescoço , Humanos , Carcinoma Adenoide Cístico/genética , Carcinoma Adenoide Cístico/patologia , Prognóstico , Genes Supressores de Tumor , Neoplasias de Cabeça e Pescoço/genética , Transcriptoma , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo
2.
Int J Mol Sci ; 25(7)2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38612650

RESUMO

Chagas disease (CD) is a vector-borne Neglected Zoonotic Disease (NZD) caused by a flagellate protozoan, Trypanosoma cruzi, that affects various mammalian species across America, including humans and domestic animals. However, due to an increase in population movements and new routes of transmission, T. cruzi infection is presently considered a worldwide health concern, no longer restricted to endemic countries. Dogs play a major role in the domestic cycle by acting very efficiently as reservoirs and allowing the perpetuation of parasite transmission in endemic areas. Despite the significant progress made in recent years, still there is no vaccine against human and animal disease, there are few drugs available for the treatment of human CD, and there is no standard protocol for the treatment of canine CD. In this review, we highlight human and canine Chagas Disease in its different dimensions and interconnections. Dogs, which are considered to be the most important peridomestic reservoir and sentinel for the transmission of T. cruzi infection in a community, develop CD that is clinically similar to human CD. Therefore, an integrative approach, based on the One Health concept, bringing together the advances in genomics, immunology, and epidemiology can lead to the effective development of vaccines, new treatments, and innovative control strategies to tackle CD.


Assuntos
Doenças dos Animais , Doença de Chagas , Doenças do Cão , Trypanosoma cruzi , Humanos , Cães , Animais , Doença de Chagas/epidemiologia , Doença de Chagas/veterinária , Animais Domésticos , Doenças do Cão/epidemiologia , Mamíferos
3.
Virol J ; 20(1): 103, 2023 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-37237382

RESUMO

The European rabbit (Oryctolagus cuniculus) populations of the Iberian Peninsula have been severely affected by the emergence of the rabbit haemorrhagic disease virus (RHDV) Lagovirus europaeus/GI.2 (RHDV2/b). Bushflies and blowflies (Muscidae and Calliphoridae families, respectively) are important RHDV vectors in Oceania, but their epidemiological role is unknown in the native range of the European rabbit. In this study, scavenging flies were collected between June 2018 and February 2019 in baited traps at one site in southern Portugal, alongside a longitudinal capture-mark-recapture study of a wild European rabbit population, aiming to provide evidence of mechanical transmission of GI.2 by flies. Fly abundance, particularly from Calliphoridae and Muscidae families, peaked in October 2018 and in February 2019. By employing molecular tools, we were able to detect the presence of GI.2 in flies belonging to the families Calliphoridae, Muscidae, Fanniidae and Drosophilidae. The positive samples were detected during an RHD outbreak and absent in samples collected when no evidence of viral circulation in the local rabbit population was found. We were able to sequence a short viral genomic fragment, confirming its identity as RHDV GI.2. The results suggest that scavenging flies may act as mechanical vectors of GI.2 in the native range of the southwestern Iberian subspecies O. cuniculus algirus. Future studies should better assess their potential in the epidemiology of RHD and as a tool for monitoring viral circulation in the field.


Assuntos
Infecções por Caliciviridae , Dípteros , Vírus da Doença Hemorrágica de Coelhos , Lagovirus , Animais , Coelhos , Lagovirus/genética , Infecções por Caliciviridae/epidemiologia , Filogenia , Vírus da Doença Hemorrágica de Coelhos/genética
4.
Mol Pharm ; 18(3): 898-914, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33461296

RESUMO

Aiming to evaluate how the release profile of naproxen (nap) is influenced by its physical state, molecular mobility, and distribution in the host, this pharmaceutical drug was loaded in three different mesoporous silicas differing in their architecture and surface composition. Unmodified and partially silylated MCM-41 matrices, respectively MCM-41 and MCM-41sil, and a biphenylene-bridged periodic mesoporous organic matrix, PMOBph, were synthetized and used as drug carriers, having comparable pore sizes (∼3 nm) and loading percentages (∼30% w/w). The loaded guest was investigated by attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy, powder X-ray diffraction (XRD), differential scanning calorimetry (DSC), and dielectric relaxation spectroscopy (DRS). DSC and XRD confirmed amorphization of a nap fraction incorporated inside the pores. A narrower glass transition was detected for PMOBph_nap, taken as an indication of the impact of host ordering, which also hinders the guest molecular mobility inside the pores as probed by DRS. While the PMOBph matrix is highly hydrophobic, the unmodified MCM-41 readily adsorbs water, accelerating the nap relaxation rate in the respective composite. In the dehydrated state, the faster dynamics was found for the silylated matrix since guest-host hydrogen bond interactions were inhibited to some extent by methylation. Nevertheless, in all the prepared composites, bulk-like crystalline drug deposits outside pores in a greater extent in PMOBph_nap. The DRS measurements analyzed in terms of conductivity show that, upon melting, nap easily migrates into pores in MCM-41-based composites, while it stays in the outer surface in the ordered PMOBph, determining a faster nap delivery from the latter matrix. On the other side, the mobility enhancement in the hydrated state controls the drug delivery in the unmodified MCM-41 matrix vs the silylated one. Therefore, DRS proved to be a suitable technique to disclose the influence of the ordering of the host surface and its chemical modification on the guest behavior, and, through conductivity depletion, it provides a mean to monitor the guest entrance inside the pores, easily followed even by untrained spectroscopists.


Assuntos
Naproxeno/química , Dióxido de Silício/química , Adsorção/efeitos dos fármacos , Varredura Diferencial de Calorimetria , Cristalização/métodos , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Interações Hidrofóbicas e Hidrofílicas/efeitos dos fármacos , Tamanho da Partícula , Porosidade , Solubilidade/efeitos dos fármacos , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Água/química , Difração de Raios X/métodos
5.
BMC Vet Res ; 17(1): 21, 2021 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-33413330

RESUMO

BACKGROUND: The black stork (Ciconia nigra Linnaeus, 1758) is a recognized endangered species in Europe and most of the specimens from the Western Palearctic region breed in the Iberian Peninsula. Available works regarding parasites in black storks are scarce. This work reports the presence one ecto- and two endoparasite species from a black stork in Portugal. CASE PRESENTATION: A black stork was found in southern Portugal after colliding against electric cables. The specimen did not survive its sustained injuries and a post-mortem exam was performed. During the procedure, several ecto- and endoparasite specimens were found. The collected parasites were lice (Neophilopterus tricolor), nematodes (Desportesius sagittatus) and trematodes (Cathaemasia hians). CONCLUSIONS: Three different species of parasites are reported from a black stork in Portugal. Ecto- and endoparasites of C. nigra have not frequently been described in the literature, and this case report is a contribution to the field. Additional studies will be important to better understand the impact that parasites can have on C. nigra health and survival.


Assuntos
Doenças das Aves/parasitologia , Infestações por Piolhos/veterinária , Infecções por Rhabditida/veterinária , Infecções por Trematódeos/veterinária , Animais , Aves , Echinostomatidae/isolamento & purificação , Ftirápteros , Portugal , Rabditídios/isolamento & purificação
6.
Parasitol Res ; 120(10): 3569-3580, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34476584

RESUMO

Columbiformes have a worldwide distribution, of which 166 species occur in Eurasia. They have been reported parasitized by coccidians recurrently in recent years; however, Eimeria labbeana (Labbé, 1896) Pinto, 1928, which is first Eimeria sp. from Columbiformes described in the late nineteenth century, is not taxonomically identified by its oocysts since the 1930s. In this context, the current study aimed to supplement the morphology of E. labbeana from Eurasian collared doves Streptopelia decaocto Frivaldszky, 1838 and from a common woodpigeon Columba palumbus Linnaeus, 1758 in Portugal, providing a preliminary genotypic characterization. Three of the four columbiforms were positive for oocysts identified as E. labbeana, which were morphologically revised as having micropyles, in addition to other minor adjustments. Oocysts from S. decaocto and C. palumbus were morphologically identical and equivalent in all morphometric aspects, besides having genotypic similarity of 99.5%. Phylogenetic analysis based on the mitochondrial cytochrome c oxidase subunit 1 gene resulted in a large clade with Eimeria spp. and Isospora spp. from different vertebrates and low similarity between Eimeria spp. from Columbiformes, whereas the phylogenetic analysis based on the small subunit ribosomal RNA gene resulted in well-supported monophyletic groups, including one with the coccidians of columbiform birds.


Assuntos
Coccidiose , Eimeria , Isospora , Animais , Coccidiose/veterinária , Columbidae , Eimeria/genética , Oocistos , Filogenia , Portugal
7.
Ren Fail ; 43(1): 1049-1059, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34187290

RESUMO

Background. Identifying trajectories of kidney disease progression in chronic kidney disease (CKD) patients may help to deliver better care. We aimed to identify and characterize trajectories of renal function decline in CKD patients and to investigate their association with mortality after dialysis.Methods. This retrospective cohort study included 378 CKD patients who initiated dialysis (aged 65 years and over) between 2009 and 2016. Were considered mixed models using linear quadratic and cubic models to define the trajectories, and we used probabilistic clustering procedures. Patient characteristics and care practices at and before dialysis were examined by multivariable multinomial logistic regression. The association of these trajectories with mortality after dialysis was examined using Cox models.Results. Four distinct groups of eGFR trajectories decline before dialysis were identified: slower decline (18.3%), gradual decline (18.3%), early rapid decline (41.2%), and rapid decline (22.2%). Patients with rapid eGFR decline were more likely to have diabetes, more cognitive impairment, to have been hospitalized before dialysis, and were less likely to have received pre-dialysis care compared to the patients with a slower decline. They had a higher risk of death within the first and fourth year after dialysis initiation, and after being more than 4 years in dialysis.Conclusions. There are different patterns of eGFR trajectories before dialysis initiation in the elderly, that may help to identify those who are more likely to experience an accelerated decline in kidney function, with impact on pre ESKD care and in the mortality risk after dialysis.


Assuntos
Progressão da Doença , Rim/fisiopatologia , Diálise Renal , Insuficiência Renal Crônica/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Taxa de Filtração Glomerular/fisiologia , Humanos , Masculino , Insuficiência Renal Crônica/mortalidade , Insuficiência Renal Crônica/terapia , Taxa de Sobrevida , Fatores de Tempo
8.
Molecules ; 26(4)2021 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-33672924

RESUMO

Presently, water quantity and quality problems persist both in developed and developing countries, and concerns have been raised about the presence of emerging pollutants (EPs) in water. The circular economy provides ways of achieving sustainable resource management that can be implemented in the water sector, such as the reuse of drinking water treatment sludges (WTSs). This study evaluated the potential of WTS containing a high concentration of activated carbon for the removal of two EPs: the steroid hormones 17ß-estradiol (E2) and 17α-ethinylestradiol (EE2). To this end, WTSs from two Portuguese water treatment plants (WTPs) were characterised and tested for their hormone adsorbance potential. Both WTSs showed a promising adsorption potential for the two hormones studied due to their textural and chemical properties. For WTS1, the final concentration for both hormones was lower than the limit of quantification (LOQ). As for WTS2, the results for E2 removal were similar to WTS1, although for EE2, the removal efficiency was lower (around 50%). The overall results indicate that this method may lead to new ways of using this erstwhile residue as a possible adsorbent material for the removal of several EPs present in wastewaters or other matrixes, and as such contributing to the achievement of Sustainable Development Goals (SDG) targets.


Assuntos
Esgotos/química , Poluentes Químicos da Água/isolamento & purificação , Purificação da Água , Elementos Químicos , Concentração de Íons de Hidrogênio , Minerais/análise , Termogravimetria
9.
Kidney Blood Press Res ; 45(1): 38-50, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31825925

RESUMO

AIM: Mortality in end-stage renal disease (ESRD) remains high, particularly among elderly, who represents the most rapidly growing segment of the ESRD population in wealthier countries. We developed and validated a risk score in elderly patients to predict 6-month mortality after dialysis initiation. METHODS: We used data from a cohort of 421 patients, aged 65 years and over who started dialysis between 2009 and 2016, in our Nephrology department. The predictive score was developed using a multivariable logistic regression analysis. A bootstrapping technique was used for internal validation. RESULTS: The overall mortality within 6 months was 14.0%. Five independent predictors were identified, and a points system was constructed: age 75 years or older (2 points), coronary artery disease (2), cerebrovascular disease with hemiplegia (2), time of nephrology care before dialysis (<3.0 months [2]; ≥3 to <12 months [1]), and serum albumin levels (3.0-3.49 g/dL [1]; <3.0 g/dL [2]). A score of 6 identified patients with a 70% risk of 6-month mortality. Model performance was good in both discrimination (area under the curve of 0.793; [95% CI 0.73-0.86]) and validation (concordance statistics of 0.791 [95% CI 0.73-0.85]). CONCLUSIONS: We developed a simple prediction score based on readily available clinical and laboratory data that can be a practical and useful tool to assess short-term prognosis in elderly patients starting dialysis. It may help to inform patients and their families about ESRD treatment options and provide a more patient-centered overall approach to care.


Assuntos
Diálise/estatística & dados numéricos , Falência Renal Crônica/mortalidade , Falência Renal Crônica/terapia , Fatores Etários , Idoso , Estudos de Coortes , Feminino , Humanos , Incidência , Masculino , Mortalidade , Portugal/epidemiologia , Prognóstico , Estudos Retrospectivos , Risco
10.
Parasite Immunol ; 41(4): e12617, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30735568

RESUMO

Leishmania infantum is the aetiological agent of human visceral leishmaniasis and canine leishmaniasis, both systemic and potentially fatal diseases. Polymorphonuclear neutrophils (PMN) are the first cells to phagocyte this parasite at the inoculation site, but macrophages (MØ) are the definitive host cells, ensuring parasite replication. The interaction between dog MØ, PMN and L infantum promastigotes was in vitro investigated. It was observed that promastigotes establish contact with blood monocyte-derived MØ mainly by the tip of the flagellum. These cells, that efficiently bind and internalize parasites, underwent major morphological changes, produced nitric oxide (NO) and released histone H1 in order to inactivate the parasite. Transfer of intracellular parasites from PMN to MØ was confirmed by flow cytometry, using L infantum expressing a green fluorescent protein. The interaction of MØ with L infantum-infected PMN lead to NO production and release of extracellular traps, which may contribute to parasite containment and inactivation. This study highlights for the first time the diversity of cellular and molecular events triggered by the interaction between canine PMN and MØ, which can promote a reduction of parasite burden in the early phase of L infantum infection.


Assuntos
Doenças do Cão/imunologia , Leishmania infantum/imunologia , Leishmaniose Visceral/veterinária , Macrófagos/imunologia , Neutrófilos/imunologia , Animais , Doenças do Cão/parasitologia , Cães , Armadilhas Extracelulares/imunologia , Histonas/metabolismo , Óxido Nítrico/biossíntese
11.
Nephrology (Carlton) ; 24(3): 347-356, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29451342

RESUMO

AIM: Both donor-specific antibodies (DSA) and anti-angiotensin II type 1 receptor antibodies (AT1R-abs) have been associated with poor graft outcomes after kidney transplantation (KT). We aimed to understand the impact of pretransplant AT1R-abs with or without concomitant DSA on KT outcomes. METHODS: Seventy-six patients transplanted in 2009 were studied. DSA (MFI > 1000) and/or AT1R-abs (>10UI) were detected by solid-phase assays in pre-KT sera. Multivariable Cox regression models were used to determine independent predictors of outcomes: acute rejection (AR) and graft failure. RESULTS: At transplant, 48 patients were AT1R-abs (-)/DSA (-), 12 AT1R-abs (+)/DSA (-), 9 AT1R-abs (-)/DSA (+) and 7 AT1R-abs (+)/DSA (+). Incidence of acute rejection at 1-year increased from 6% in AT1R-abs (-)/DSA (-), to 35% in AT1R-abs (+)/DSA (-), 47% in AT1R-abs (-)/DSA (+) and 43% in AT1R-abs (+)/DSA (+) (P < 0.001). No difference in DSA strength and C1q-binding ability was observed between AT1R-abs (-) /DSA (+) and AT1R-abs (+)/DSA (+) patients. Graft survival at 6-years was the lowest in AT1R-abs (+)/DSA (+) (57%), followed by AT1R-abs (+)/DSA (-) (67%), and higher in AT1R-abs (-)/DSA (-) (94%) and AT1R-abs (-)/DSA (+) (89%) patients (P = 0.012). AT1R-abs (+)/DSA (-) (HR = 6.41, 95% CI: 1.43-28.68; P = 0.015) and AT1R-abs (+)/DSA (+) (HR = 7.75, 95% CI: 1.56-38.46; P = 0.012) were independent predictors of graft failure. CONCLUSION: Acute rejection incidence and graft failure were associated with both DSA and AT1R-abs. These results demonstrate a proper negative effect of AT1R-abs on graft outcomes, besides a synergistic one with DSA. Pretransplant AT1R-abs should be acknowledged to better stratify patients' immunological risk.


Assuntos
Rejeição de Enxerto , Sobrevivência de Enxerto/imunologia , Transplante de Rim , Receptor Tipo 1 de Angiotensina/imunologia , Medição de Risco/métodos , Adulto , Anticorpos/sangue , Feminino , Rejeição de Enxerto/epidemiologia , Rejeição de Enxerto/imunologia , Antígenos HLA/imunologia , Humanos , Testes Imunológicos/métodos , Transplante de Rim/efeitos adversos , Transplante de Rim/métodos , Masculino , Pessoa de Meia-Idade , Portugal , Cuidados Pré-Operatórios/métodos , Reprodutibilidade dos Testes , Fatores de Risco
12.
J Environ Manage ; 249: 109351, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31419673

RESUMO

Maize Cob Waste (MCW) is available worldwide in high amounts, as maize is the most produced cereal in the world. MCW is generally left in the crop fields, but due to its low biodegradability it has a negligible impact in soil fertility. Moreover, MCW can be used as substrate to balance the C/N ratio during the Anaerobic co-Digestion (AcoD) with other biodegradable substrates, and is an excellent precursor for the production of Activated Carbons (ACs). In this context, a biorefinery is theoretically discussed in the present review, based on the idea that MCW, after proper pre-treatment is valorised as precursor of ACs and as co-substrate in AcoD for biomethane generation. This paper provides an overview on different scientific and technological aspects that can be involved in the development of the proposed biorefinery; the major topics considered in this work are the following ones: (i) the most suitable pre-treatments of MCW prior to AcoD; (ii) AcoD process with regard to the critical parameters resulting from MCW pre-treatments; (iii) production of ACs using MCW as precursor, with the aim to use these ACs in biogas conditioning (H2S removal) and upgrading (biomethane production), and (iv) an overview on biogas upgrading technologies.


Assuntos
Biocombustíveis , Zea mays , Anaerobiose , Reatores Biológicos , Carvão Vegetal , Metano
13.
Biochemistry ; 57(26): 3713-3721, 2018 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-29757624

RESUMO

Galactose is an abundant monosaccharide found exclusively in mammals as galactopyranose (Gal p), the six-membered ring form of this sugar. In contrast, galactose appears in many pathogenic microorganisms as the five-membered ring form, galactofuranose (Gal f). Gal f biosynthesis begins with the conversion of UDP-Gal p to UDP-Gal f catalyzed by the flavoenzyme UDP-galactopyranose mutase (UGM). Because UGM is essential for the survival and proliferation of several pathogens, there is interest in understanding the catalytic mechanism to aid inhibitor development. Herein, we have used kinetic measurements and molecular dynamics simulations to explore the features of UGM that control the rate-limiting step (RLS). We show that UGM from the pathogenic fungus Aspergillus fumigatus also catalyzes the isomerization of UDP-arabinopyranose (UDP-Ara p), which differs from UDP-Gal p by lacking a -CH2-OH substituent at the C5 position of the hexose ring. Unexpectedly, the RLS changed from a chemical step for the natural substrate to product release with UDP-Ara p. This result implicated residues that contact the -CH2-OH of UDP-Gal p in controlling the mechanistic path. The mutation of one of these residues, Trp315, to Ala changed the RLS of the natural substrate to product release, similar to the wild-type enzyme with UDP-Ara p. Molecular dynamics simulations suggest that steric complementarity in the Michaelis complex is responsible for this distinct behavior. These results provide new insight into the UGM mechanism and, more generally, how steric factors in the enzyme active site control the free energy barriers along the reaction path.


Assuntos
Aspergillus fumigatus/enzimologia , Transferases Intramoleculares/metabolismo , Aspergilose/microbiologia , Aspergillus fumigatus/química , Aspergillus fumigatus/metabolismo , Cristalografia por Raios X , Galactose/análogos & derivados , Galactose/metabolismo , Humanos , Transferases Intramoleculares/química , Isomerismo , Cinética , Modelos Moleculares , Conformação Proteica , Especificidade por Substrato , Difosfato de Uridina/análogos & derivados , Difosfato de Uridina/metabolismo , Uridina Difosfato Galactose/metabolismo , Açúcares de Uridina Difosfato/metabolismo
14.
Mod Pathol ; 31(7): 1064-1072, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29463883

RESUMO

Basal cell salivary neoplasms display similar cyto-morphologic features and are classified into adenoma and adenocarcinoma based on the presence or absence of tumor invasion at diagnosis. These neoplasms also share considerable phenotypic resemblance and co-exist with certain dermal adnexal tumors harboring the CYLD gene mutations inferring common genetic association. We sequenced the CYLD gene in both basal cell adenomas and adenocarcinomas and correlated the findings with CYLD, NF-κB, and ß-catenin expression levels and clinicopathologic factors. Twenty mutations were identified and comprised of 3 synonymous and 17 non-synonymous (missense) types involving the coding exons of the CYLD gene. Mutations in exons 9-11 were identified in both adenomas and adenocarcinomas, while mutations in exons 12-20, encoding the USP domain, were exclusively found in carcinomas. Although no significant correlation between CYLD mutations and expression levels of CYLD, NF-κB, and ß-catenin or clinicopathologic parameters was found, basal cell adenocarcinomas with multiple mutations showed reduction in CYLD protein expression and pursued aggressive clinical behavior. Our study revealed high incidence and sequential CYLD mutations in both basal cell adenoma and adenocarcinoma supporting a single neoplastic continuum for their evolution and provides evidence for potential diagnostic and therapeutic utility.


Assuntos
Adenocarcinoma/genética , Adenoma/genética , Transformação Celular Neoplásica/genética , Enzima Desubiquitinante CYLD/genética , Neoplasias das Glândulas Salivares/genética , Adenocarcinoma/patologia , Adenoma/patologia , Adulto , Idoso , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Neoplasias das Glândulas Salivares/patologia
15.
Clin Genet ; 94(5): 401-408, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30019395

RESUMO

Adult-onset, chronic, genetic diseases like transthyretin-related familial amyloid polyneuropathy Val30Met (TTR-FAP Val30Met), have a major psychosocial impact not only on patients, but also on families. Genetic risk may therefore be an increased factor in psychosocial impact of the disease on these families' functioning. To evaluate impact of genetic risk, a study was conducted to perceive the impact of the illness on families' functioning. Groups of TTR-FAP Val30Met patients, pre-symptomatic carriers, partners and patients with multiple sclerosis (MS), a non-hereditary disease, were studied. Sample included 190 adults: 87 patients and 28 pre-symptomatic carriers for TTR-FAP Val30Met, 41 partners and 34 patients with MS. Family Adaptability and Cohesion Scale IV (FACES IV) and a social-demographic questionnaire were applied. No significant differences were observed between patients and pre-symptomatic carriers and both these and their partners regarding cohesion and flexibility. MS patients scored significantly higher in median scores for balanced scales. Satisfaction and communication levels were also lower in patients with TTR-FAP Val30Met than with MS. Family functioning was perceived as balanced by most TTR-FAP Val30Met patients and pre-symptomatic carriers. These families may be considered as mostly healthy. Difficulties in family communication should be taken into account when caring for these families.


Assuntos
Substituição de Aminoácidos , Neuropatias Amiloides Familiares/diagnóstico , Neuropatias Amiloides Familiares/genética , Mutação , Pré-Albumina/genética , Adulto , Idoso , Alelos , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Adulto Jovem
16.
Pathobiology ; 85(1-2): 85-95, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-28930752

RESUMO

Salivary gland tumor classification encompasses a vast list of benign and malignant neoplasms. Their morphological diversity is recognized not only between different entities but also within individual tumors. Tumor categories as described by the World Health Organization reflect, in part, a true genetic heterogeneity (e.g., translocations involving CRTC1 and CRTC3-MAML2 genes in mucoepidermoid carcinoma and MYB-NFIB fusion in adenoid cystic carcinoma). Carcinoma ex pleomorphic adenoma shows diversity in its histological appearance, but recurrent rearrangements on PLAG1 and HMGA2 are common to its benign precursor. More recently, new categories have been defined, like secretory carcinoma with the t(12;15) (p13;q25) ETV6-NTRK3 translocation and clear-cell carcinoma with EWSR1-ATF1 fusion. Recent studies on cribriform adenocarcinoma of minor salivary gland origin and epithelial-myoepithelial carcinoma point to a correlation with their morphological features. All of these advances show that the search of a histogenetic and genetic basis for salivary gland tumors is helping to clarify morphological categories and unraveling new ones. Nevertheless, currently morphology is still the hallmark of tumor classification and the gold standard. The therapeutic options for advanced tumors remain very limited but the discovery of translocation-generated gene fusions and increased knowledge of the genomic information of salivary gland tumors is creating opportunities for the development of specific targeted therapies.


Assuntos
Biomarcadores Tumorais/genética , Heterogeneidade Genética , Neoplasias das Glândulas Salivares/genética , Rearranjo Gênico , Humanos , Neoplasias das Glândulas Salivares/classificação , Neoplasias das Glândulas Salivares/diagnóstico , Neoplasias das Glândulas Salivares/patologia , Translocação Genética
17.
Blood Purif ; 46(2): 94-102, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29672304

RESUMO

BACKGROUND: The definition of significant stenosis (SS) remains controversial. METHODS: We retrospectively reviewed 1,040 consultations. SS was defined in the presence of clinical and echo-Doppler (DDU) criteria: Qa <500 mL/min or Qa decrease >25%; RI >0.7 in the feeding artery or absolute minimal luminal stenosis diameter <2.0 mm. Stenosis without any additional criteria were considered borderline stenosis (BS). RESULTS: Two hundred twenty-one arteriovenous fistulas (AVFs) were included: 58.8% had SS, 18.6% had BS, and 22.6% had no dysfunctional access (ND). SS had a significantly higher thrombotic events than BS and ND (13.1 vs. 4.4%, p = 0.018). The annual thrombosis rate was 0.007, 0.037, and 0.004 in the ND, SS, and BS, respectively. AVF cumulative survival at 5 years was significantly lower in SS (89.5%) compared to BS (100%) and ND (97.4%; p = 0.03). BS had an HR for AVF failure of 1.1, p = 0.955, while the SS presented an HR of 5.9, p = 0.09. CONCLUSION: AVF clinical monitoring with additional DDU criteria appear to be appropriate for therapeutic referral.


Assuntos
Constrição Patológica/diagnóstico por imagem , Ultrassonografia Doppler/métodos , Idoso , Fístula Arteriovenosa/diagnóstico por imagem , Fístula Arteriovenosa/mortalidade , Fístula Arteriovenosa/patologia , Constrição Patológica/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Análise de Sobrevida , Trombose/etiologia
18.
Water Sci Technol ; 77(1-2): 456-466, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29377830

RESUMO

The adsorption of four phenolic compounds (gallic acid, protocatechuic acid, vanillic acid and syringic acid) is investigated using a synthesized mesoporous carbon on both single and multi-component synthetic solutions. Some correlation of the adsorption capacity of the carbon and the nature of adsorbate could be made, except for gallic acid whose concentration decrease seems to be not exclusively due to adsorption but also to polymerization reaction. In the multi-component mixture, negative effects in the adsorption capacity are observed probably due to competition for the active centers of the adsorbent surface. In desorption studies, ethanol presents better performance than water and acetonitrile. Vanillic acid is the compound with the higher adsorption and interestingly it is then possible to desorb a relatively high amount of it from the adsorbent, which may represent a possibility for a selective recovery of vanillic acid. These results present a potential way to treat the wastewater from the cork industry.


Assuntos
Carvão Vegetal/química , Formaldeído/química , Fenóis/análise , Resorcinóis/química , Poluentes Químicos da Água/análise , Purificação da Água/métodos , Adsorção , Modelos Teóricos , Quercus/química , Soluções , Águas Residuárias/química
19.
Mol Pharm ; 14(9): 3164-3177, 2017 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-28836790

RESUMO

The amorphization of the readily crystallizable therapeutic ingredient and food additive, menthol, was successfully achieved by inclusion of neat menthol in mesoporous silica matrixes of 3.2 and 5.9 nm size pores. Menthol amorphization was confirmed by the calorimetric detection of a glass transition. The respective glass transition temperature, Tg = -54.3 °C, is in good agreement with the one predicted by the composition dependence of the Tg values determined for menthol:flurbiprofen therapeutic deep eutectic solvents (THEDESs). Nonisothermal crystallization was never observed for neat menthol loaded into silica hosts, which can indicate that menthol rests as a full amorphous/supercooled material inside the pores of the silica matrixes. Menthol mobility was probed by dielectric relaxation spectroscopy, which allowed to identify two relaxation processes in both pore sizes: a faster one associated with mobility of neat-like menthol molecules (α-process), and a slower, dominant one due to the hindered mobility of menthol molecules adsorbed at the inner pore walls (S-process). The fraction of molecular population governing the α-process is greater in the higher (5.9 nm) pore size matrix, although in both cases the S-process is more intense than the α-process. A dielectric glass transition temperature was estimated for each α (Tg,dielc(α)) and S (Tg,dielc(S)) molecular population from the temperature dependence of the relaxation times to 100 s. While Tg,dielc(α) agrees better with the value obtained from the linearization of the Fox equation assuming ideal behavior of the menthol:flurbiprofen THEDES, Tg,dielc(S) is close to the value determined by calorimetry for the silica composites due to a dominance of the adsorbed population inside the pores. Nevertheless, the greater fraction of more mobile bulk-like molecules in the 5.9 nm pore size matrix seems to determine the faster drug release at initial times relative to the 3.2 nm composite. However, the latter inhibits crystallization inside pores since its dimensions are inferior to menthol critical size for nucleation. This points to a suitability of these composites as drug delivery systems in which the drug release profile can be controlled by tuning the host pore size.


Assuntos
Mentol/química , Dióxido de Silício/química , Varredura Diferencial de Calorimetria , Cristalização , Flurbiprofeno/química , Solventes/química , Temperatura de Transição
20.
Mol Cell Probes ; 31: 61-64, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-28013043

RESUMO

A loop-mediated isothermal amplification (LAMP) assay was evaluated for the detection of Theileria annulata infection in cattle. The results were compared with a real-time PCR used for the quantification of T. annulata parasitaemia. One hundred bovine blood samples from 16 cattle farms were tested with LAMP and real-time PCR, with T. annulata DNA being detected in 66% and 67% of the samples, respectively. The results showed that the LAMP assay detects a parasitaemia as low as 0.00025%, indicating a high analytical sensitivity of LAMP for clinical diagnosis of bovine theileriosis.


Assuntos
Bovinos/parasitologia , Técnicas de Amplificação de Ácido Nucleico/métodos , Theileria annulata/genética , Theileria annulata/isolamento & purificação , Theileriose/parasitologia , Animais , Padrões de Referência
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