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1.
Mol Psychiatry ; 2024 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-39152331

RESUMO

Parkinson's disease (PD) is a multifaceted disease characterized by degeneration of nigrostriatal dopaminergic neurons, which results in motor and non-motor dysfunctions. Accumulation of α-synuclein (αSYN) in Lewy bodies is a key pathological feature of PD. Although the exact cause of PD remains unknown, accumulating evidence suggests that brain infiltration of T cells plays a critical role in the pathogenesis of disease, contributing to neuroinflammation and dopaminergic neurodegeneration. Here, we used a mouse model of brain-infused aggregated αSYN, which recapitulates motor and non-motor dysfunctions seen in PD patients. We found that αSYN-induced motor dysfunction in mice is accompanied by an increased number of brain-residing Th17 (IL17+ CD4+) cells, but not CD8+ T cells. To evaluate whether the modulation of T cell response could rescue αSYN-induced damage, we chronically treated animals with abatacept (8 mg/kg, sc, 3x per week), a selective T-cell co-stimulation modulator. We found that abatacept treatment decreased Th1 (IFNƔ+ CD4+) and Th17 (IL17+ CD4+) cells in the brain, rescued motor function and prevented dopaminergic neuronal loss in αSYN-infused mice. These results highlight the significance of effector CD4+ T cells, especially Th17, in the progression of PD and introduce novel possibilities for repurposing immunomodulatory drugs used for arthritis as PD-modifying therapies.

2.
Tree Physiol ; 2024 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-39046271

RESUMO

Considerable attention has been paid to address methodological concerns related to measurements of embolism in conduits of angiosperm xylem. A fast, easy, and cheap method is based on gas extraction measurements from dehydrating samples to obtain pneumatic vulnerability curves (VCs). Here, we tested the assumption that cutting open conduits leads to gas-filled lumina when these are cut in air at fairly high water potentials, which is required to detect embolism in intact conduits. We performed VCs with the Pneumatron for 12 angiosperm species, and extracted sap from cut-open vessels in branches of nine species under early stages of branch dehydration. The optical method was applied to Citrus plants as an alternative reference method to estimate embolism resistance. We found an increase in gas discharge during early stages of dehydration, which affected the pneumatic VCs for most of the species studied. Xylem sap residue was not absorbed immediately by surrounding tissue in cut-open conduits in six of the nine species, but gradually disappeared over time during progressive dehydration. The amount of gas discharged increased until all residual sap was absorbed, and was not related to embolism. We conclude that residual xylem sap in cut-open conduits affects early stages of pneumatic VCs, and represents a novel artefact that can easily be corrected for. Yet, it remains unclear why exactly the air-water meniscus in cut-open conduits did not fully withdraw to the conduit end wall in most species. By analysing the slope of VCs over time, we could improve estimations of embolism resistance, as evidenced by a strong agreement between the pneumatic and the optical methods. Since residual sap in cut-open conduits of some species could slightly underestimate embolism resistance, we propose to apply a correction for this artefact based on the high time resolution measurements taken with a Pneumatron.

3.
Nutrients ; 16(12)2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38931299

RESUMO

Carpal tunnel syndrome (CTS) is the most common cause of peripheral compressive neuropathy and consists of compression of the median nerve in the wrist. Although there are several etiologies, idiopathic is the most prevalent origin, and among the forms of treatment for CTS, conservative is the most indicated. However, despite the high prevalence in and impact of this syndrome on the healthcare system, there are still controversies regarding the best therapeutic approach for patients. Therefore, noting that some studies point to vitamin D deficiency as an independent risk factor, which increases the symptoms of the syndrome, this study evaluated the role of vitamin D supplementation and its influence on pain control, physical examination and response electroneuromyography to conservative treatment of carpal tunnel syndrome. For this, the sample consisted of 14 patients diagnosed with CTS and hypovitaminosis D, who were allocated into two groups. The control group received corticosteroid treatment, while the experimental group received corticosteroid treatment associated with vitamin D. Thus, from this study, it can be concluded that patients who received vitamin D, when compared to those who did not receive it, showed improvement in the degree of pain intensity, a reduction in symptom severity and an improvement in some electroneuromyographic parameters.


Assuntos
Síndrome do Túnel Carpal , Eletromiografia , Deficiência de Vitamina D , Vitamina D , Humanos , Síndrome do Túnel Carpal/tratamento farmacológico , Vitamina D/uso terapêutico , Feminino , Deficiência de Vitamina D/tratamento farmacológico , Deficiência de Vitamina D/complicações , Masculino , Pessoa de Meia-Idade , Adulto , Resultado do Tratamento , Suplementos Nutricionais , Corticosteroides/administração & dosagem , Nervo Mediano/fisiopatologia , Idoso
4.
Vet Sci ; 11(6)2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38922015

RESUMO

A one-year-old female miniature goat was presented to an emergency service after calving a dead goatling. Physical and ultrasonographic examination revealed the presence of a viable fetus; therefore, the goat was submitted to an emergency cesarean section. In the postoperative period, the animal had septic peritonitis caused by Enterococcus faecium and Enterococcus casseliflavus. Both bacterial strains showed contrasting antimicrobial resistance profiles. Laparohysterectomy and abdominal cavity lavage were performed, but, once the animal had adhesions and necrotic lesions in abdominal organs, euthanasia was executed. A post-mortem examination revealed fibrino-necrotic septic peritonitis secondary to uterine rupture. To the authors' knowledge, this is the first detailed report of polymicrobial septic peritonitis in a miniature goat and the first report of septic peritonitis caused by E. faecium and E. casseliflavus.

5.
J Hand Surg Glob Online ; 6(2): 164-168, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38903829

RESUMO

Purpose: Currently, there is a paucity of prior investigations and studies examining applications for artificial intelligence (AI) in upper-extremity (UE) surgical education. The purpose of this investigation was to assess the performance of a novel AI tool (ChatGPT) on UE questions on the Orthopaedic In-Training Examination (OITE). We aimed to compare the performance of ChatGPT to the examination performance of hand surgery residents. Methods: We selected questions from the 2020-2022 OITEs that focused on both the hand and UE as well as the shoulder and elbow content domains. These questions were divided into two categories: those with text-only prompts (text-only questions) and those that included supplementary images or videos (media questions). Two authors (B.K.F. and G.S.M.) converted the accompanying media into text-based descriptions. Included questions were inputted into ChatGPT (version 3.5) to generate responses. Each OITE question was entered into ChatGPT three times: (1) open-ended response, which requested a free-text response; (2) multiple-choice responses without asking for justification; and (3) multiple-choice response with justification. We referred to the OITE scoring guide for each year in order to compare the percentage of correct AI responses to correct resident responses. Results: A total of 102 UE OITE questions were included; 59 were text-only questions, and 43 were media-based. ChatGPT correctly answered 46 (45%) of 102 questions using the Multiple Choice No Justification prompt requirement (42% for text-based and 44% for media questions). Compared to ChatGPT, postgraduate year 1 orthopaedic residents achieved an average score of 51% correct. Postgraduate year 5 residents answered 76% of the same questions correctly. Conclusions: ChatGPT answered fewer UE OITE questions correctly compared to hand surgery residents of all training levels. Clinical relevance: Further development of novel AI tools may be necessary if this technology is going to have a role in UE education.

6.
BMC Genomics ; 25(1): 623, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38902640

RESUMO

BACKGROUND: The genotype-by-environment interaction (GxE) in beef cattle can be investigated using reaction norm models to assess environmental sensitivity and, combined with genome-wide association studies (GWAS), to map genomic regions related to animal adaptation. Including genetic markers from whole-genome sequencing in reaction norm (RN) models allows us to identify high-resolution candidate genes across environmental gradients through GWAS. Hence, we performed a GWAS via the RN approach using whole-genome sequencing data, focusing on mapping candidate genes associated with the expression of reproductive and growth traits in Nellore cattle. For this purpose, we used phenotypic data for age at first calving (AFC), scrotal circumference (SC), post-weaning weight gain (PWG), and yearling weight (YW). A total of 20,000 males and 7,159 females genotyped with 770k were imputed to the whole sequence (29 M). After quality control and linkage disequilibrium (LD) pruning, there remained ∼ 2.41 M SNPs for SC, PWG, and YW and ∼ 5.06 M SNPs for AFC. RESULTS: Significant SNPs were identified on Bos taurus autosomes (BTA) 10, 11, 14, 18, 19, 20, 21, 24, 25 and 27 for AFC and on BTA 4, 5 and 8 for SC. For growth traits, significant SNP markers were identified on BTA 3, 5 and 20 for YW and PWG. A total of 56 positional candidate genes were identified for AFC, 9 for SC, 3 for PWG, and 24 for YW. The significant SNPs detected for the reaction norm coefficients in Nellore cattle were found to be associated with growth, adaptative, and reproductive traits. These candidate genes are involved in biological mechanisms related to lipid metabolism, immune response, mitogen-activated protein kinase (MAPK) signaling pathway, and energy and phosphate metabolism. CONCLUSIONS: GWAS results highlighted differences in the physiological processes linked to lipid metabolism, immune response, MAPK signaling pathway, and energy and phosphate metabolism, providing insights into how different environmental conditions interact with specific genes affecting animal adaptation, productivity, and reproductive performance. The shared genomic regions between the intercept and slope are directly implicated in the regulation of growth and reproductive traits in Nellore cattle raised under different environmental conditions.


Assuntos
Interação Gene-Ambiente , Estudo de Associação Genômica Ampla , Polimorfismo de Nucleotídeo Único , Reprodução , Sequenciamento Completo do Genoma , Animais , Bovinos/genética , Bovinos/crescimento & desenvolvimento , Reprodução/genética , Feminino , Masculino , Genótipo , Fenótipo , Locos de Características Quantitativas , Desequilíbrio de Ligação
7.
Mol Biol Rep ; 51(1): 767, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38878205

RESUMO

BACKGROUND: Esterases (EC 3.1.1.X) are enzymes that catalyze the hydrolysis ester bonds. These enzymes have large potential for diverse applications in fine industries, particularly in pharmaceuticals, cosmetics, and bioethanol production. METHODS AND RESULTS: In this study, a gene encoding an esterase from Thermobifida fusca YX (TfEst) was successfully cloned, and its product was overexpressed in Escherichia coli and purified using affinity chromatography. The TfEst kinetic assay revealed catalytic efficiencies of 0.58 s-1 mM-1, 1.09 s-1 mM-1, and 0.062 s-1 mM-1 against p-Nitrophenyl acetate, p-Nitrophenyl butyrate, and 1-naphthyl acetate substrates, respectively. Furthermore, TfEst also exhibited activity in a pH range from 6.0 to 10.0, with maximum activity at pH 8.0. The enzyme demonstrated a half-life of 20 min at 70 °C. Notably, TfEst displayed acetyl xylan esterase activity as evidenced by the acetylated xylan assay. The structural prediction of TfEst using AlphaFold indicated that has an α/ß-hydrolase fold, which is consistent with other esterases. CONCLUSIONS: The enzyme stability over a broad pH range and its activity at elevated temperatures make it an appealing candidate for industrial processes. Overall, TfEst emerges as a promising enzymatic tool with significant implications for the advancement of biotechnology and biofuels industries.


Assuntos
Acetilesterase , Esterases , Thermobifida , Acetilesterase/metabolismo , Acetilesterase/genética , Acetilesterase/química , Concentração de Íons de Hidrogênio , Cinética , Especificidade por Substrato , Thermobifida/enzimologia , Thermobifida/genética , Esterases/metabolismo , Esterases/genética , Esterases/química , Estabilidade Enzimática , Temperatura , Escherichia coli/genética , Escherichia coli/metabolismo , Clonagem Molecular/métodos , Hidrólise , Xilanos/metabolismo , Butiratos/metabolismo , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/química , Nitrofenóis
8.
J Anim Breed Genet ; 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38853664

RESUMO

This study utilized Bayesian inference in a genome-wide association study (GWAS) to identify genetic markers associated with traits relevant to the adaptation of Hereford and Braford cattle breeds. We focused on eye pigmentation (EP), weaning hair coat (WHC), yearling hair coat (YHC), and breeding standard (BS). Our dataset comprised 126,290 animals in the pedigree. Out of these, 233 sires were genotyped using high-density (HD) chips, and 3750 animals with medium-density (50 K) single-nucleotide polymorphism (SNP) chips. Employing the Bayes B method with a prior probability of π = 0.99, we identified and tagged single nucleotide polymorphisms (Tag SNPs), ranging from 18 to 117 SNPs depending on the trait. These Tag SNPs facilitated the construction of reduced SNP panels. We then evaluated the predictive accuracy of these panels in comparison to traditional medium-density SNP chips. The accuracy of genomic predictions using these reduced panels varied significantly depending on the clustering method, ranging from 0.13 to 0.65. Additionally, we conducted functional enrichment analysis that found genes associated with the most informative SNP markers in the current study, thereby providing biological insights into the genomic basis of these traits.

9.
Clin Oral Investig ; 28(6): 344, 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38809444

RESUMO

OBJECTIVES: The aim of the present study was to assess the cytocompatibility of epoxy resin-based AH Plus Jet (Dentsply De Trey, Konstanz, Germany), Sealer Plus (MK Life, Porto Alegre, Brazil), calcium silicate-based Bio-C Sealer (Angelus, Londrina, PR, Brazil), Sealer Plus BC (MK Life) and AH Plus BC (Dentsply) through a tridimensional (3D) culture model of human osteoblast-like cells. METHODS: Spheroids of MG-63 cells were produced and exposed to fresh root canal sealers extracts by 24 h, and the cytotoxicity was assessed by the Lactate Dehydrogenase assay (LDH). The distribution of dead cells within the microtissue was assessed by fluorescence microscopy, and morphological effects were investigated by histological analysis. The secreted inflammatory mediators were detected in cell supernatants through flow luminometry (XMap Luminex). RESULTS: Cells incubated with AH Plus Jet, AH Plus BC, Sealer Plus BC and Bio-C Sealer extracts showed high rates of cell viability, while the Sealer Plus induced a significant reduction of cell viability, causing reduction on the spheroid structure. Sealer Plus and Seaker Plus BC caused alterations on 3D microtissue morphology. The AH Plus BC extract was associated with the downregulation of secretion of pro-inflammatory cytokines IL-5, IL-7, IP-10 and RANTES. CONCLUSIONS: The new AH Plus BC calcium silicate-based endodontic sealer did not reduce cell viability in vitro, while led to the downregulation of pro-inflammatory cytokines. CLINICAL SIGNIFICANCE: Choosing the appropriate endodontic sealer is a crucial step. AH Plus BC demonstrated high cell viability and downregulation of pro-inflammatory cytokines, appearing reliable for clinical use, while Sealer Plus presented lower cytocompatibility.


Assuntos
Compostos de Cálcio , Sobrevivência Celular , Resinas Epóxi , Teste de Materiais , Materiais Restauradores do Canal Radicular , Silicatos , Materiais Restauradores do Canal Radicular/farmacologia , Humanos , Compostos de Cálcio/farmacologia , Silicatos/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Técnicas de Cultura de Células em Três Dimensões/métodos , Mediadores da Inflamação/metabolismo , Microscopia de Fluorescência , Osteoblastos/efeitos dos fármacos
10.
Microbiol Spectr ; 12(6): e0396723, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38647345

RESUMO

Acylhydrazone (AH) derivatives represent a novel category of anti-fungal medications that exhibit potent activity against Sporothrix sp., both in vitro and in a murine model of sporotrichosis. In this study, we demonstrated the anti-fungal efficacy of the AH derivative D13 [4-bromo-N'-(3,5-dibromo-2-hydroxybenzylidene)-benzohydrazide] against both planktonic cells and biofilms formed by Sporothrix brasiliensis. In a clinical study, the effect of D13 was then tested in combination with itraconazole (ITC), with or without potassium iodide, in 10 cats with sporotrichosis refractory to the treatment of standard of care with ITC. Improvement or total clinical cure was achieved in five cases after 12 weeks of treatment. Minimal abnormal laboratory findings, e.g., elevation of alanine aminotransferase, were observed in four cats during the combination treatment and returned to normal level within a week after the treatment was ended. Although highly encouraging, a larger and randomized controlled study is required to evaluate the effectiveness and the safety of this new and exciting drug combination using ITC and D13 for the treatment of feline sporotrichosis. IMPORTANCE: This paper reports the first veterinary clinical study of an acylhydrazone anti-fungal (D13) combined with itraconazole against a dimorphic fungal infection, sporotrichosis, which is highly endemic in South America in animals and humans. Overall, the results show that the combination treatment was efficacious in ~50% of the infected animals. In addition, D13 was well tolerated during the course of the study. Thus, these results warrant the continuation of the research and development of this new class of anti-fungals.


Assuntos
Antifúngicos , Doenças do Gato , Quimioterapia Combinada , Itraconazol , Sporothrix , Esporotricose , Gatos , Animais , Itraconazol/uso terapêutico , Itraconazol/administração & dosagem , Itraconazol/farmacologia , Esporotricose/tratamento farmacológico , Esporotricose/veterinária , Antifúngicos/uso terapêutico , Antifúngicos/farmacologia , Antifúngicos/administração & dosagem , Doenças do Gato/tratamento farmacológico , Doenças do Gato/microbiologia , Sporothrix/efeitos dos fármacos , Hidrazonas/uso terapêutico , Hidrazonas/farmacologia , Feminino , Masculino , Testes de Sensibilidade Microbiana , Biofilmes/efeitos dos fármacos , Resultado do Tratamento
11.
Langmuir ; 40(21): 10856-10867, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38683600

RESUMO

Zwitterionic coatings are an efficient strategy for preventing biomolecule adsorption and enhancing nanoparticle stability in solution. The properties of zwitterions and other antifouling materials, including suppression of nonspecific adsorption and improved colloidal stability of nanoparticles, are believed to derive from their electroneutral and highly hydrophilic nature. Among different zwitterions, short sulfobetaines have been demonstrated to be effective in preventing protein adsorption onto several nanoparticles and providing enhanced colloidal stability. Although zwitterionic sulfobetaine silane (ZS) is electrically neutral, the negatively charged zwitterionic sulfobetaine-functionalized silica nanoparticles (ZS@SiO2NPs) exhibit a similar ζ-potential to nonfunctionalized silica nanoparticles (SiO2NPs). In this work, we present a thorough comprehension of the surface properties of ZS@SiO2NPs, which encompasses the development of meticulous functionalization procedures, detailed characterization approaches, and cutting-edge modeling to address the questions that persist regarding the surface features of ZS@SiO2NPs. The negative charge of ZS@SiO2NPs is due to the stabilization of siloxide from residual surface silanols by the quaternary amine in the sulfobetaine structure. Consequently, we infer that zero-charge ZS@SiO2NPs are unlikely to be obtained since this stabilization increases the dissociation degree of surface silanols, increasing the overall structure negative charge. Additionally, colloidal stability was evaluated in different pH and ionic strength conditions, and it was found that ZS@SiO2NPs are more stable at higher ionic strengths. This suggests that the interaction between ZS and salt ions prevents the aggregation of ZS@SiO2NPs. Together, these results shed light on the nature of the ZS@SiO2NP negative charge and possible sources for the remarkable colloidal stability of zwitterionic nanoparticles in complex media.

12.
Plant Cell Environ ; 47(8): 3063-3075, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38660960

RESUMO

Embolism resistance of xylem tissue varies among species and is an important trait related to drought resistance, with anatomical attributes like pit membrane thickness playing an important role in avoiding embolism spread. Grafted Citrus trees are commonly grown in orchards, with the rootstock being able to affect the drought resistance of the whole plant. Here, we evaluated how rootstocks affect the vulnerability to embolism resistance of the scion using several rootstock/scion combinations. Scions of 'Tahiti' acid lime, 'Hamlin', 'Pera' and 'Valencia' oranges grafted on a 'Rangpur' lime rootstock exhibit similar vulnerability to embolism. In field-grown trees, measurements of leaf water potential did not suggest significant embolism formation during the dry season, while stomata of Citrus trees presented an isohydric response to declining water availability. When 'Valencia' orange scions were grafted on 'Rangpur' lime, 'IAC 1710' citrandarin, 'Sunki Tropical' mandarin or 'Swingle' citrumelo rootstocks, variation in intervessel pit membrane thickness of the scion was found. The 'Rangpur' lime rootstock, which is known for its drought resistance, induced thicker pit membranes in the scion, resulting in higher embolism resistance than the other rootstocks. Similarly, the rootstock 'IAC 1710' citrandarin generated increased embolism resistance of the scion, which is highly relevant for citriculture.


Assuntos
Citrus , Raízes de Plantas , Xilema , Citrus/fisiologia , Xilema/fisiologia , Raízes de Plantas/fisiologia , Água/metabolismo , Secas , Folhas de Planta/fisiologia , Folhas de Planta/anatomia & histologia , Estômatos de Plantas/fisiologia
13.
J Phys Chem B ; 128(18): 4396-4403, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38669439

RESUMO

pH-sensitive peptides bind and traverse lipid membranes in response to changes in pH. They can be used to target tumors and other acidic tissues. We investigate the influence of acidic lipids on the pH-driven adsorption of recently synthesized peptides. Using a statistical-thermodynamic theory that takes into account the acid-base chemistry of peptides and lipids, we find that the presence of acidic lipids amplifies changes in peptide surface concentration when transitioning from high to low pH. We study cyclic and linear peptides, containing tryptophan, glutamic acid, and arginine residues, examining their behavior in both neutral and acidic membranes. Membrane binding consistently results from the shallow insertion of tryptophan residues with hydrophilic residues facing the aqueous solution. Regardless of the pH, the peptide's geometry predominantly determines the orientation and distribution of residues. Notably, we find that not only the extent of adsorption is pH-sensitive but also the underlying adsorption mechanism: it is barrier-free at low pH but hindered by a large free energy barrier at high pH. Hence, under more acidic conditions, pH-sensitive peptides show facilitated adsorption both kinetically and thermodynamically.


Assuntos
Peptídeos , Termodinâmica , Concentração de Íons de Hidrogênio , Adsorção , Peptídeos/química
14.
J Chem Neuroanat ; 137: 102415, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38521203

RESUMO

Over time, the body undergoes a natural, multifactorial, and ongoing process named senescence, which induces changes at the molecular, cellular, and micro-anatomical levels in many body systems. The brain, being a highly complex organ, is particularly affected by this process, potentially impairing its numerous functions. The brain relies on chemical messengers known as neurotransmitters to function properly, with dopamine being one of the most crucial. This catecholamine is responsible for a broad range of critical roles in the central nervous system, including movement, learning, cognition, motivation, emotion, reward, hormonal release, memory consolidation, visual performance, sexual drive, modulation of circadian rhythms, and brain development. In the present review, we thoroughly examine the impact of senescence on the dopaminergic system, with a primary focus on the classic delimitations of the dopaminergic nuclei from A8 to A17. We provide in-depth information about their anatomy and function, particularly addressing how senescence affects each of these nuclei.


Assuntos
Envelhecimento , Dopamina , Neurônios Dopaminérgicos , Humanos , Animais , Envelhecimento/metabolismo , Envelhecimento/fisiologia , Dopamina/metabolismo , Neurônios Dopaminérgicos/metabolismo , Encéfalo/metabolismo
15.
Front Oncol ; 14: 1350162, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38544834

RESUMO

Background: Breast and prostate cancers are the most common malignancies diagnosed in women and men respectively, and present with great clinical heterogeneity, even in tumors with the same histology and same site of origin. Somatic and germline molecular alterations in DNA may have prognostic and predictive impact, influencing response to therapies and overall survival. Our aim is to characterize the somatic and germline genomic landscape of women with locally advanced HER2-positive breast cancer and men with metastatic prostate cancer in Brazil. Secondarily, we aim to identify genetic variants associated with tumor prognosis and treatment response, identify patients carrying pathogenic alterations in cancer-predisposing genes, and characterize the genetic ancestry of the population included in the study. Methods: This observational multicenter cohort study will include 550 adult patients from the five macro-regions of Brazil, divided into two arms: 1) breast cancer and 2) prostate cancer. Clinical and pathological data will be collected, as well as DNA samples from peripheral blood and tumor samples. In arm 1, the inclusion criteria are a histological diagnosis of breast carcinoma with overexpression of HER-2, clinical stage II or III, and current neoadjuvant treatment with chemotherapy plus trastuzumab. In arm 2, the criterion is a histological diagnosis of prostate adenocarcinoma, clinical stage IV. Whole-exome sequencing (WES) will be performed to identify variants that may be drivers and/or actionable in a specific patient or tumor. These variants will be interpreted and classified according to their population frequencies, in silico predictors, functional studies, and literature data, following international guidelines proposed by expert societies. Discussion: This trial will contribute to the construction of a robust database that should provide a better understanding of the genomic profile of patients with breast and prostate cancer in Brazil. Considering the miscegenation of the Brazilian population, knowledge generated from these data will have implications for future studies of this specific population. Clinical trial registration: [clinicaltrial.gov], identifier [NCT05306600].

16.
Animals (Basel) ; 14(6)2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38540032

RESUMO

We verified the possibility of cooling peccary semen for 4, 24, and 48 h before cryopreservation, using different dilution media (TRIS + egg yolk (20%) and PRIMXcell Ultra). Ten ejaculates were divided equally into six aliquots and then diluted. Two aliquots were stored in a biological incubator (4 h), and the remaining aliquots were stored in a commercial container, the Botutainer® (24 and 48 h), both at 5 °C. The samples were cryopreserved and then evaluated for kinetic parameters, functionality, integrity, mitochondrial activity, morphology, and sperm binding capacity. After thawing, samples diluted in TRIS showed total motility of 43.4 ± 6.8%, 48.4 ± 6.2%, and 38.6 ± 5.0% after cooling for 4, 24, and 48 h before cryopreservation, respectively. Such results are significantly greater than those achieved with the use of PRIMXcell diluent for 4 (8.3 ± 2.8%), 24 (4.7 ± 1.4%), and 48 h (4.8 ± 2.9%) storage (p < 0.05). Furthermore, TRIS provided better preservation of sperm membrane integrity when samples were cooled for 24 h (44.5 ± 4.7%) before cryopreservation compared to those samples diluted in PRIMXcell Ultra stored for 24 (25.7 ± 4.0%) and 48 h (25.2 ± 4.0%) before freezing (p < 0.05). In summary, we suggest TRIS diluent + egg yolk (20%) as an effective option to allow semen to cool for 24 or 48 h in a transport container before cryopreservation.

17.
Zootaxa ; 5418(3): 291-300, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38480355

RESUMO

A new species, Parahephaestion mimicus sp. nov., is described. Two species are newly recorded for the Brazilian state of Minas Gerais: Sphalloeme costipennis Melzer, 1928 (Cerambycinae, Oemini) and Oreodera omissa Melzer, 1932 (Lamiinae, Acrocinini). Six species are new records for the RPPN Sanctuary of Caraa, (Brazil, Minas Gerais): Thalusia atrata (Melzer, 1918) (Cerambycinae, Rhopalophorini), Trachelissa pustulata (Audinet-Serville, 1834) (Cerambycinae, Trachyderini), Ateralphus dejeani (Lane, 1973) (Lamiinae, Acanthoderini), Phacellocera plumicornis (Klug, 1825) (Lamiinae, Anisocerini), Oncideres impluviata (Germar, 1823), and Psyllotoxus griseocinctus Thomson, 1868 (Lamiinae, Onciderini).


Assuntos
Besouros , Vespas , Animais , Brasil
18.
J Fungi (Basel) ; 10(2)2024 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-38392831

RESUMO

Chromoblastomycosis (CBM) and phaeohyphomycosis (FEO) are infections caused by melanized filamentous fungal agents, primarily found in tropical and subtropical regions. Both infections pose significant challenges for the correct identification of the causative agent due to their morphological similarity, making conventional methods of morphological analysis highly subjective. Therefore, molecular techniques are necessary for the precise determination of these species. In this regard, this study aimed to contribute to a new methodology based on PCR-RFLP for the identification of agents causing CBM and FEO. Sequences from the Internal Transcribed Spacer (ITS) region were used to identify potential restriction enzyme sites in silico, followed by in vitro validation using the selected restriction enzymes. The obtained results were compared with species identification through morphological analyses and sequencing. The results demonstrated that the PCR-RFLP applied in this study accurately identified two major agents of chromoblastomycosis, Fonsecaea pedrosoi and Fonsecaea monophora, as well as Cladophialophora bantiana and Exophiala dermatitidis, both causative agents of phaeohyphomycosis. In this context, the proposed assay can complement current methods for identifying these species, aiding in diagnosis, and contributing to the proper management of these infections.

19.
Org Biomol Chem ; 22(12): 2359-2364, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38415828

RESUMO

We present a metal-free method to synthesize secondary and tertiary propargylamines from primary and secondary amines and alkynes using light-mediated persulfate activation and phase-transfer catalysis. Our method explores a tandem oxidative coupling/alkynylation reaction for the generation of diverse compounds, highlighting the sustainability of the process and its wide scope.

20.
Rheumatol Int ; 44(7): 1197-1207, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38421427

RESUMO

The objective of this study is to compare and contrast the quality statements and quality indicators across clinical care standards for low back pain. Searches were performed in Medline, guideline databases, and Google searches to identify clinical care standards for the management of low back pain targeting a multidisciplinary audience. Two independent reviewers reviewed the search results and extracted relevant information from the clinical care standards. We compared the quality statements and indicators of the clinical care standards to identify the consistent messages and the discrepancies between them. Three national clinical care standards from Australia, Canada, and the United Kingdom were included. They provided from 6 to 8 quality statements and from 12 to 18 quality indicators. The three standards provide consistent recommendations in the quality statements related to imaging, and patient education/advice and self-management. In addition, the Canadian and Australian standards also provide consistent recommendations regarding comprehensive assessment, psychological support, and review and patient referral. However, the three clinical care standards differ in the statements related to psychological assessment, opioid analgesics, non-opioid analgesics, and non-pharmacological therapies. The three national clinical care standards provide consistent recommendations on imaging and patient education/advice, self-management of the condition, and two standards (Canadian and Australian) agree on recommendations regarding comprehensive assessment, psychological support, and review and patient referral. The standards differ in the quality statements related to psychological assessment, opioid prescription, non-opioid analgesics, and non-pharmacological therapies.


Assuntos
Dor Lombar , Humanos , Dor Lombar/terapia , Dor Lombar/diagnóstico , Indicadores de Qualidade em Assistência à Saúde/normas , Austrália , Educação de Pacientes como Assunto/normas , Manejo da Dor/normas , Manejo da Dor/métodos
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