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In this study, we describe Nakazawaea atacamensis f. a., sp. nov., a novel species obtained from Neltuma chilensis plant samples in Chile's hyperarid Atacama Desert. In total, three strains of N. atacamensis were obtained from independent N. chilensis samples (synonym Prosopis chilensis, Algarrobo). Two strains were obtained from bark samples, while the third strain was obtained from bark-exuded gum from another tree. The novel species was defined using molecular characteristics and subsequently characterized with respect to morphological, physiological, and biochemical properties. A neighbor-joining analysis using the sequences of the D1/D2 domains of the large subunit ribosomal RNA gene revealed that N. atacamensis clustered with Nakazawaea pomicola. The sequence of N. atacamensis differed from closely related species by 1.3%-5.2% in the D1/D2 domains. A phylogenomic analysis based on single-nucleotide polymorphism's data confirms that the novel species belongs to the genus Nakazawaea, where N. atacamensis clustered with N. peltata. Phenotypic comparisons demonstrated that N. atacamensis exhibited distinct carbon assimilation patterns compared to its related species. Genome sequencing of the strain ATA-11A-BT revealed a genome size of approximately 12.4 Mbp, similar to other Nakazawaea species, with 5116 protein-coding genes annotated using InterProScan. In addition, N. atacamensis exhibited the capacity to ferment synthetic wine must, representing a potential new yeast for mono or co-culture wine fermentations. This comprehensive study expands our understanding of the genus Nakazawaea and highlights the ecological and industrial potential of N. atacamensis in fermentation processes. The holotype of N. atacamensis sp. nov. is CBS 18375T . The Mycobank number is MB 849680.
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Saccharomycetales , Vinho , Fermentação , Filogenia , Saccharomycetales/genética , Pichia/genética , Sequência de Bases , Análise de Sequência de DNA , DNA Fúngico/genética , DNA Espaçador Ribossômico/genéticaRESUMO
Tropical rainforests and related biomes are found in Asia, Australia, Africa, Central and South America, Mexico, and many Pacific Islands. These biomes encompass less than 20% of Earth's terrestrial area, may contain about 50% of the planet's biodiversity, and are endangered regions vulnerable to deforestation. Tropical rainforests have a great diversity of substrates that can be colonized by yeasts. These unicellular fungi contribute to the recycling of organic matter, may serve as a food source for other organisms, or have ecological interactions that benefit or harm plants, animals, and other fungi. In this review, we summarize the most important studies of yeast biodiversity carried out in these biomes, as well as new data, and discuss the ecology of yeast genera frequently isolated from tropical forests and the potential of these microorganisms as a source of bioinnovation. We show that tropical forest biomes represent a tremendous source of new yeast species. Although many studies, most using culture-dependent methods, have already been carried out in Central America, South America, and Asia, the tropical forest biomes of Africa and Australasia remain an underexplored source of novel yeasts. We hope that this review will encourage new researchers to study yeasts in unexplored tropical forest habitats.
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Florestas , Clima Tropical , Animais , Biodiversidade , Ecossistema , PlantasRESUMO
INTRODUCTION: Characterization of 2-year progression of different risk phenotypes in eyes with mild and moderate nonproliferative diabetic retinopathy (NPDR) in type 2 diabetes (T2D). METHODS: A 2-year prospective longitudinal cohort study (CORDIS, NCT03696810) was conducted. Ophthalmological examinations were performed including best corrected visual acuity, color fundus photography and optical coherence tomography (OCT and OCTA). OCT metrics, central retinal thickness and ganglion cell layer + inner plexiform layer (GCL + IPL) thickness were analyzed. OCTA metrics, vessel density (VD), perfusion density (PD) and area of intercapillary spaces (AIS) were obtained from superficial and deep capillary plexus (SCP, DCP). Only phenotype C identified by decreased VD ≥ 2 SD of healthy controls and phenotype B identified by subclinical macular edema with decreased VD < 2 SD of healthy controls were included. RESULTS: One hundred twenty-two eyes from T2D individuals were included in study; 65 eyes (53%) were classified as phenotype B and 57 eyes (47%) as phenotype C. For phenotype B, progression was associated with thinning of the GCL + IPL (ETDRS 35, 1 year p = 0.013, 2 year p < 0.001; ETDRS 43-47, 2 year p = 0.003) and vessel closure involving mainly the DCP for both ETDRS grades (ETDRS 35, 1 year p = 0.025, 2 year p = 0.034; ETDRS 43-47, 1 year p = 0.011). For phenotype C there was also progressive thinning of the GCL + IPL (ETDRS 35, in both years p ≤ 0.001; ETDRS 43-47, 1 year p = 0.002, 2 year p = 0.001), with vessel closure involving mainly SCP (ETDRS 35, 1 year p = 0.012, 2 year p = 0.023 in full-retina), which appeared to stabilize at maximal values in ETDRS grade 43-47 at the end of 2 years. ETDRS severity changes at the end of the 2-year period showed that worsening was associated with phenotype C with changes involving predominantly the SCP (VD, p = 0.005; PD, p = 0.008; AIS, p = 0.005). CONCLUSIONS: Association between ETDRS classification of NPDR severity and identification of different risk phenotypes offers new perspective to predict disease progression in T2D individuals with NPDR.
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INTRODUCTION: To characterize the two-year progression of risk phenotypes of nonproliferative diabetic retinopathy (NPDR) in type 2 diabetes (T2D) Phenotype C, or ischemic phenotype, identified by decreased skeletonized retinal vessel density (VD), ≥ 2 SD over normal values, and Phenotype B, or edema phenotype, identified by increased retinal thickness, i.e. subclinical macular edema, and no significant decrease in VD. METHODS: A prospective longitudinal cohort study (CORDIS, NCT03696810) was conducted with 4 visits (baseline, 6-months, one-year and two-year). Ophthalmological examinations included best corrected visual acuity, color fundus photography (CFP) and optical coherence tomography (OCT) and OCT Angiography. Early Treatment Diabetic Retinopathy Study grading was performed at the baseline and last visits based on 7-fields CFP. RESULTS: One hundred and twenty-two eyes from T2D individuals with NPDR fitted in the categories of phenotype B and C and completed the two-years follow-up. Sixty-five (53%) of the eyes were classified as phenotype B and 57 (47%) eyes as phenotype C. Neurodegeneration represented by thinning of the ganglion cell layer and inner plexiform layer was present in both phenotypes and showed significant progression over the two-year period (p<0.001). In phenotype C, significant progression in the two-year period was identified in decreased skeletonized VD (p=0.01), whereas in phenotype B microvascular changes involved preferentially decreases in perfusion density (PD, p=0.012). Phenotype B with changes in VD and PD (flow) and preferential involvement of the deep capillary plexus (p<0.001) is associated with development of center-involved macular edema. DISCUSSION: In the two-year period of follow-up both phenotypes B and C showed progression in retinal neurodegeneration, with changes at the microvascular level characterized by decreases in PD in phenotype B and decreases in VD in phenotype C.
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The authors present a unique case of osteonecrosis of a cortical half of a fibula free flap that has not been reported in the literature yet. This complication was associated with the impairment of the vascularization of periosteum in the cortical half of fibula that was fixated with a nonlocking reconstructive 2.0-mm plate and screws but other factors could have been involved. The patient was submitted to excision of a cemento-ossifying fibroma that resulted in a left hemimaxilectomy mesoinfrastructure defect classified as the Cordeiro type 2B. The 42-year-old female patient was submitted to reconstruction with an osteomusculocutaneous fibula free flap plus a segment of fibula graft. The two bone segments of the free flap used to reconstruct the anterior and left alveolar crest were fixated with a reconstructive 2.0-mm plate of matrixMANDIBLE system. The only reported complication was an oronasal fistula that healed with conservative treatment and the referred osteonecrosis of the external cortical half of the fibula free flap with plate exposure at 2.5 years postoperatively. Surgical excision of the osteonecrosed cortical half of the fibula with the plate and screws was performed, while the other cortical underwent bone union as corroborated by computed tomography scans.
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Artificial single-stranded DNA (ssDNA) with user-defined sequences and lengths up to the kilobase range is increasingly needed in mass quantities to realize the potential of emerging technologies such as genome editing and DNA origami. However, currently available biotechnological approaches for mass-producing ssDNA require dedicated, and thus costly, fermentation infrastructure, because of the risk of cross-contaminating manufacturer plants with self-replicating phages. Here we overcome this problem with an efficient, scalable, and cross-contamination-free method for the phage-free biotechnological production of artificial ssDNA with Escherichia coli. Our system utilizes a designed phagemid and an optimized helper plasmid. The phagemid encodes one gene of the M13 phage genome and a freely chosen custom target sequence, while the helper plasmid encodes the other genes of the M13 phage. The phagemid particles produced with this method are not capable of self-replication in the absence of the helper plasmid. This enables cross-contamination-free biotechnological production of ssDNA at any contract manufacturer. Furthermore, we optimized the process parameters to reduce by-products and increased the maximal product concentration up to 83 mg L-1 of ssDNA in a stirred-tank bioreactor, thus realizing up to a 40-fold increase in maximal product concentration over previous scalable phage-free ssDNA production methods.
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DNA de Cadeia Simples , Escherichia coli , Bacteriófago M13/genética , Reatores Biológicos , DNA de Cadeia Simples/genética , Escherichia coli/genética , Plasmídeos/genéticaRESUMO
Depression is a prevalent, socially burdensome disease. Different studies have demonstrated the important role of astrocytes in the pathophysiology of depression as modulators of neurotransmission and neurovascular coupling. This is evidenced by astrocyte impairments observed in brains of depressed patients and the appearance of depressive-like behaviors upon astrocytic dysfunctions in animal models. However, little is known about the importance of de novo generated astrocytes in the mammalian brain and in particular its possible involvement in the precipitation of depression and in the therapeutic actions of current antidepressants (ADs). Therefore, we studied the modulation of astrocytes and adult astrogliogenesis in the hippocampal dentate gyrus (DG) of rats exposed to an unpredictable chronic mild stress (uCMS) protocol, untreated and treated for two weeks with antidepressants-fluoxetine and imipramine. Our results show that adult astrogliogenesis in the DG is modulated by stress and imipramine. This study reveals that distinct classes of ADs impact differently in the astrogliogenic process, showing different cellular mechanisms relevant to the recovery from behavioral deficits induced by chronic stress exposure. As such, in addition to those resident, the newborn astrocytes in the hippocampal DG might also be promising therapeutic targets for future therapies in the neuropsychiatric field.
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Disfunção Cognitiva , Imipramina , Animais , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Disfunção Cognitiva/tratamento farmacológico , Modelos Animais de Doenças , Hipocampo , Humanos , Imipramina/farmacologia , Imipramina/uso terapêutico , Mamíferos , Neurônios , RatosRESUMO
Eight yeast isolates with an affinity to the genus Tremella were obtained from bromeliads from different locations in Brazil. Although the formation of basidia and basidiocarp were not observed, on the basis of the results of sequence analysis of the D1/D2 domain of the large subunit (LSU) rRNA gene and internal transcribed spacer (ITS) region, we suggest that these isolates represent two novel species of the genus Tremella. These yeasts are phylogenetically related to Tremella saccharicola and Tremella globispora. Therefore, we propose Tremella ananatis sp. nov. and Tremella lamprococci sp. nov. as novel yeast species of the order Tremellales (Agaricomycotina, Basidiomycota). Sequence analysis revealed that Tremella ananatis sp. nov. differs by 11 and 28 nucleotide substitutions from Tremella saccharicola in the D1/D2 sequence and ITS region, respectively. Moreover, Tremella lamprococci sp. nov. differs by 15 and 29 nucleotide substitutions from Tremella globispora in the D1/D2 sequence and ITS region, respectively. The holotypes of Tremella ananatis sp. nov. and Tremella lamprococci sp. nov. are CBS 14568T and CBS 14567T, and the MycoBank numbers are MB840480 and MB840481, respectively.
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Basidiomycota , Bromeliaceae/microbiologia , Filogenia , Composição de Bases , Basidiomycota/classificação , Basidiomycota/isolamento & purificação , DNA Fúngico/genética , DNA Espaçador Ribossômico/genética , Técnicas de Tipagem Micológica , Análise de Sequência de DNARESUMO
Four yeast isolates with an affinity to the genus Wickerhamiella were obtained from beach sand, a marine zoanthid and a tree exudate at different localities in Brazil. Two other isolates with almost identical ITS and D1/D2 sequences of the large subunit rRNA gene were isolated from the small intestine of cattle and a grease trap in Thailand. These isolates represent a novel species phylogenetically related to Wickerhamiella verensis, Wickerhamiella osmotolerans, Wickerhamiella tropicalis, Wickerhamiella sorbophila and Wickerhamiella infanticola. The novel species differs by 15-30 nucleotide differences from these species in the D1/D2 sequences. The name Wickerhamiella martinezcruziae f.a., sp. nov. is proposed. The holotype of Wickerhamiella martinezcruziae sp. nov. is CBS 16104T. The MycoBank number is MB 839328.
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Filogenia , Saccharomycetales , Animais , Composição de Bases , Brasil , Bovinos/microbiologia , DNA Fúngico/genética , DNA Espaçador Ribossômico/genética , Intestino Delgado/microbiologia , Técnicas de Tipagem Micológica , Exsudatos de Plantas , RNA Ribossômico 16S/genética , Saccharomycetales/classificação , Saccharomycetales/isolamento & purificação , Areia/microbiologia , Análise de Sequência de DNA , Tailândia , Clima TropicalRESUMO
Optical coherence tomography Angiography (OCT-A) represents a revolution in the noninvasive evaluation of retinal and choroidal circulation especially in detecting early clinical signs of diabetic retinal disease (DRD). With appropriate use, OCT-A characteristics and measurements have the potential to become new imaging biomarkers in managing and treating DRD. Major challenges include (a) provision of standardized outputs from different OCT-A instruments providing standardized terminology to correctly interpret data; (b) the presence of artifacts; (c) the absence of standardized grading or interpretation method in the evaluation of DRD, similar to that already established in fundus photography; and (d) establishing how OCT-A might be able to provide surrogate markers to demonstrate blood retinal barrier breakdown and vascular leakage, commonly associated with DRD. In fact, OCT-A guidelines for DRD are still evolving. The outputs of quantitative OCT-A data offer a unique opportunity to develop tools based on artificial intelligence to assist the clinicians in diagnosing, monitoring, and managing patients with diabetes. In addition, OCT-A has the potential to become a useful tool for the evaluation of cardiovascular diseases and different neurological diseases including cognitive impairment. This article written by the members of Diabetic Retinopathy expert committee of the European Vision Clinical Research network will review the available evidence on the use of OCT-A as an imaging biomarker in DRD and discuss the limits and the current application as well as future developments for its use in both clinical practice and research trials of DRD.
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Retinopatia Diabética , Inteligência Artificial , Biomarcadores , Diabetes Mellitus , Retinopatia Diabética/diagnóstico por imagem , Angiofluoresceinografia , Humanos , Padrões de Referência , Vasos Retinianos , Tomografia de Coerência ÓpticaRESUMO
Using a magnetron sputtering approach that allows size-controlled formation of nanoclusters, we have created palladium nanoclusters that combine the features of both heterogeneous and homogeneous catalysts. Here we report the atomic structures and electronic environments of a series of metal nanoclusters in ionic liquids at different stages of formation, leading to the discovery of Pd nanoclusters with a core of ca. 2 nm surrounded by a diffuse dynamic shell of atoms in [C4C1Im][NTf2]. Comparison of the catalytic activity of Pd nanoclusters in alkene cyclopropanation reveals that the atomically dynamic surface is critically important, increasing the activity by a factor of ca. 2 when compared to compact nanoclusters of similar size. Catalyst poisoning tests using mercury and dibenzo[a,e]cyclooctene show that dynamic Pd nanoclusters maintain their catalytic activity, which demonstrate their combined features of homogeneous and heterogeneous catalysts within the same material. Additionally, kinetic studies of cyclopropanation of alkenes mediated by the dynamic Pd nanoclusters reveal an observed catalyst order of 1, underpinning the pseudo-homogeneous character of the dynamic Pd nanoclusters.
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BACKGROUND: Assessing body weight in older adults may be challenging. Hence, the present study aimed to develop and cross-validate updated and reproducible equations to estimate body weight in a large sample of older adults, namely among the older-old. METHODS: In total, 1456 individuals aged ≥ 65 years, from the Nutrition UP 65 study, were included in the present analysis. The participants were randomly assigned to one of two sub-samples: development (n = 991) and validation samples (n = 465). Prediction equations using height, mid-upper arm circumference (MUAC), waist circumference (WC), calf circumference (CC) and triceps skinfold thickness (TST) were generated for the development sample using multiple regression analysis and then validated using the validation sample. RESULTS: The model with five predictor variables generated the following equations: females 65-79 years: -114.682 + 0.522 × height (cm) + 0.620 × MUAC (cm) + 0.517 × WC (cm) + 0.893 × CC (cm) + 0.111 × TST (mm) (adjusted r2 = 0.883, standard error of the estimate (SEE) = 4.4); females ≥ 80 years: -110.806 + 0.494 × height (cm) + 0.637 × MUAC (cm) + 0.500 × WC (cm) + 0.986 × CC (cm) + 0.021 × TST (mm) (adjusted r2 = 0.890, SEE = 3.9); males 65-79 years: -114.875 + 0.558 × height (cm) + 0.073 × MUAC (cm) + 0.671 × WC (cm) + 0.717 × CC (cm) + 0.182 × TST(mm) (adjusted r2 = 0.820, SEE=5.0); and males ≥ 80 years: -128.789 + 0.546 × height (cm) + 0.202 × MUAC (cm) + 0.612 × WC (cm) + 1.236 × CC (cm) + 0.093 × TST (mm) (adjusted r2 = 0.906, SEE = 3.5). CONCLUSIONS: Body weight can be estimated with good accuracy in older adults using these sex- and age-specific equations generated from regression models using three to five anthropometric predictor variables.
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Estatura , Estado Nutricional , Idoso , Antropometria , Braço/anatomia & histologia , Índice de Massa Corporal , Peso Corporal , Feminino , Humanos , Masculino , Circunferência da CinturaRESUMO
Astrocytes are now known to play crucial roles in the central nervous system, supporting and closely interacting with neurons and therefore able to modulate brain function. Both human postmortem studies in brain samples from patients diagnosed with Major Depressive Disorder and from animal models of depression reported numerical and morphological astrocytic changes specifically in the hippocampus. In particular, these studies revealed significant reductions in glial cell density denoted by a decreased number of S100B-positive cells and a decrease in GFAP expression in several brain regions including the hippocampus. To reveal plastic astrocytic changes in the context of recurrent depression, we longitudinally assessed dynamic astrocytic alterations (gene expression, cell densities and morphologic variations) in the hippocampal dentate gyrus under repeated exposure to unpredictable chronic mild stress (uCMS) and upon treatment with two antidepressants, fluoxetine and imipramine. Both antidepressants decreased astrocytic complexity immediately after stress exposure. Moreover, we show that astrocytic alterations, particularly an increased number of S100B-positive cells, are observed after recurrent stress exposure. Interestingly, these alterations were prevented at the long-term by either fluoxetine or imipramine treatment.
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Transtorno Depressivo Maior , Animais , Antidepressivos/farmacologia , Astrócitos , Giro Denteado , Depressão , Transtorno Depressivo Maior/tratamento farmacológico , Modelos Animais de Doenças , Hipocampo , HumanosRESUMO
The contamination of bodies of water by potentially hazardous elements has in recent decades become an environmental problem that poses serious risks to humans, fauna, flora and microbiota, compromising the quality of life of the present ecosystem. Therefore, effluents must be properly treated in a legally acceptable manner before their disposal in the environment. With this in mind, adsorption presents itself as an inexpensive efficient technique for the removal of potentially hazardous elements from effluents with excellent adsorption capacities when natural adsorbents are used. In this study, fava d'anta fodder was used in its crude and alkalinized form to remove Cu(II) and Pb(II) ions. Equilibrium studies were carried out using adsorption isotherms in batch systems with mono- and multi-elementary systems containing the two ions. The Langmuir and Freundlich models were applied to the isotherm studies, with the ions being better suited to the Langmuir model, with maximum adsorption capacities of 24.45 mg g-1 and 68.49 mg g-1 (crude form) and 11.12 mg g-1 and 35.34 mg g-1 (alkalinized form) in the mono-elementary system for Cu(II) and Pb(II) ions, respectively.
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Cobre/isolamento & purificação , Fabaceae/química , Chumbo/isolamento & purificação , Poluentes Químicos da Água/isolamento & purificação , Purificação da Água/métodos , Adsorção , Ecossistema , Humanos , Concentração de Íons de Hidrogênio , Cinética , Qualidade de Vida , Águas Residuárias , ÁguaRESUMO
Yeast communities associated with cacti were studied in three ecosystems of Southeast, Central and North Brazil. A total of 473 yeast strains belonging to 72 species were isolated from 190 samples collected. Cactophilic yeast species were prevalent in necrotic tissues, flowers, fruits and insects of cacti collected in Southeast and North Brazil. Pichia cactophila, Candida sonorensis and species of the Sporopachydermia complex were the most prevalent cactophilic species in Southeast and Central regions. Kodamaea nitidulidarum, Candida restingae and Wickerhamiella cacticola were frequently associated with cactus flowers and fruits. The diversity of yeasts associated with the substrates studied was high. Twenty-one novel species were found. One is described here as Kluyveromyces starmeri sp. nov. based on 21 isolates obtained from necrotic tissues, flowers, fruits and associated insects of the columnar cacti Cereus saddianus, Micranthocereus dolichospermaticus and Pilosocereus arrabidae in two different ecosystems in Brazil. Phylogenetic analyses of sequences encoding the gene of the small subunit (SSU) rRNA gene, the internal transcribed spacer, the 5.8S rRNA gene and the D1/D2 domains of the large subunit (LSU) rRNA showed that the species is related to Kluyveromyces dobzhanskii, Kluyveromyces lactis and Kluyveromyces marxianus. Phylogenomic analyses based on 1264 conserved genes shared among the new species and 19 other members of the Saccharomycetaceae confirmed this phylogenetic relationship. The holotype is K. starmeri sp. nov. CBS 16103T (=UFMG-CM-Y3682T ). The Mycobank number is MB 836817.
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Cactaceae/microbiologia , Ecossistema , Kluyveromyces/classificação , Kluyveromyces/genética , Micobioma/genética , Filogenia , Leveduras/genética , Brasil , DNA Fúngico/genética , DNA Espaçador Ribossômico/genética , Variação Genética , Genoma Fúngico , Geografia , Técnicas de Tipagem Micológica , RNA Ribossômico/genética , Leveduras/classificaçãoRESUMO
Introduction: The patients' perception of how communication dysfunction may cause a disadvantage is important information for the clinical decision-making process.Objectives: This study aimed to translate the self-evaluation of communication experiences after laryngectomy (SECEL) to the European Portuguese (EP) and to assess its feasibility, acceptability, reliability, and validity.Material and methods: A cross-sectional study was carried out, and a cluster sample of seven ENT outpatient clinics was drawn. The EP-SECEL was filled in by 129 people with laryngectomy, aged 29-81 years and 25 of those completed it in the second time. Patients have also filled in the European Organization for Research Treatment of Cancer Quality of Life Questionnaire (EORCT), the core quality of life questionnaire (QLQ-C30) and the 35-item Head and Neck module (H&N35).Results: The EP-SECEL has the same conceptual meaning, semantics, idiomatic, format and score equivalence as the original one. Psychometric analyses revealed that it is feasible (missing <1%, to fill out took about 15 minutes for most patients), acceptable (floor and ceiling effects inferior to 15%), reliable (excellent internal consistency, Cronbach's alpha = 0.90, and moderate test-retest, Spearman's rhô = 0.64), well-constructed (66% of the total variance is explained by exploratory factor analysis), significantly convergent (correlates with the EORTC QLQ-C30 and H&N35) and validly discriminates people with total and partial laryngectomy as well as people with different primary means-of-communication.Conclusions: This study supports that the EP-SECEL has sufficient psychometric qualities to be considered an adequate tool to be recommended for assessing health-related quality of life among laryngectomy patients.
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Transtornos da Comunicação/etiologia , Comunicação , Laringectomia/efeitos adversos , Medidas de Resultados Relatados pelo Paciente , Psicometria , Qualidade de Vida , Autorrelato , Tradução , Qualidade da Voz , Adulto , Idoso , Idoso de 80 Anos ou mais , Transtornos da Comunicação/fisiopatologia , Transtornos da Comunicação/psicologia , Estudos Transversais , Estudos de Viabilidade , Humanos , Pessoa de Meia-Idade , Portugal , Reprodutibilidade dos Testes , Resultado do TratamentoRESUMO
Tetrahydroisoquinoline (THIQ) is a key structural component in many biologically active molecules including natural products and synthetic pharmaceuticals. Here, we report on the use of transition-metal mediated [2 + 2 + 2] cyclotrimerisation of alkynes to generate tricyclic THIQs with potential to selectively inhibit AKR1C3.
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Triazenes are a very useful and diverse class of compounds that have been studied for their potential in the treatment of many tumors including brain tumor, leukemia and melanoma. Novel compounds of this class continue to be developed as either anticancer compounds or even with other therapeutic applications. This review focused on several types of triazenes from the simplest ones like 1,3-dialkyl-3-acyltriazenes to the more complex ones like combi-triazenes with an emphasis on how triazenes have been developed as effective antitumor agents.
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Antineoplásicos/farmacologia , Neoplasias/tratamento farmacológico , Triazenos/farmacologia , HumanosRESUMO
α-Synuclein (SNCA) is a presynaptic protein that is associated with the pathophysiology of synucleinopathies, including Parkinson's disease. SNCA is a naturally aggregation-prone protein, which may be degraded by the ubiquitin-proteasome system (UPS) and by lysosomal degradation pathways. Besides being a target of the proteolytic systems, SNCA can also alter the function of these pathways further, contributing to the progression of neurodegeneration. Deterioration of UPS and autophagy activities with aging further aggravates this toxic cycle. Caloric restriction (CR) is still the most effective non-genetic intervention promoting lifespan extension. It is known that CR-mediated lifespan extension is linked to the regulation of proteolytic systems, but the mechanisms underlying CR rescue of SNCA toxicity remain poorly understood. This study shows that CR balances UPS and autophagy activities during aging. CR enhances UPS activity, reversing the decline of the UPS activity promoted by SNCA, and keeps autophagy at homeostatic levels. Maintenance of autophagy at homeostatic levels appears to be relevant for UPS activity and for the mechanism underlying rescue of cells from SNCA-mediated toxicity by CR.