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1.
Gait Posture ; 111: 59-64, 2024 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-38643633

RESUMO

BACKGROUND: Different tasks and proxy measurements have been employed to evaluate dynamic balance in older individuals. However, due to inherent limitations, results from most evaluations could hardly be taken as valid measurements of dynamic balance. RESEARCH QUESTION: Is the Equidyn smartphone application-based protocol valid and sensitive for assessment of dynamic balance in older adults? METHODS: Dynamic balance was evaluated in 52 physically active individuals, age range 60-80 years (M = 69.36). The dynamic tasks were one-leg sway either in the mediolateral (ML) or anteroposterior (AP) direction while supported on the contralateral leg, and cyclic sit-to-stand with a narrow support base. These tasks were performed under standardized movement amplitude and rhythm. Outcomes were correlated with unipedal quiet standing. A smartphone was attached to the trunk backside, and a custom-made application (Equidyn) was employed to provide guidance throughout evaluation, timed beeps to pace the movements, and three-dimensional trunk acceleration measurement for balance evaluation. RESULTS: Our data showed (a) that both ML and AP leg sway tasks were sensitive to aging and to direction of leg sway movements; (b) referenced to quiet unipedal stance, moderate/strong correlations for the ML/AP leg sway tasks and moderate correlations for the sit-to-stand task; and (c) moderate/strong correlations between the ML and AP leg sway tasks, and moderate correlations between the sit-to-stand and the two unipedal dynamic tasks in the ML acceleration direction. SIGNIFICANCE: The current results support the conclusion that the Equidyn protocol is a sensitive and valid tool to evaluate dynamic balance in healthy older individuals. The protocol tasks standardized in amplitude and rhythm favor their reproducibility and trunk acceleration data interpretation. As the whole assessment is made through a smartphone application, this dynamic balance evaluation could be made in a low-cost simple way both in the laboratory and clinical settings.

2.
Chemosphere ; : 142074, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38657693

RESUMO

The objective of this study was to assess the photolysis-mediated degradation of malathion in standard and commercial formulations, and to determine the toxicity of these degraded formulations. Degradation tests were carried out with 500 µg L-1 of malathion and repeated three times. The initial and residual toxicity was assessed by using Lactuca sativa seeds for phytotoxicity, Stegomyia aegypti larvae for acute toxicity, and Stegomyia aegypti mosquitoes (cultivated from the larval stage until emergence as mosquitoes) to evaluate the biochemical markers of sublethal concentrations. For the standard formulations the photolytic process efficiently reduced the initial concentration of malathion to levels below the regulatory limits however, the formation of byproducts was revealed by chromatography, which allowed for a more complete proposal of photolytic-mediated malathion degradation route. The degraded formulations inhibited the growth of L. sativa seeds, while only the untreated formulations showed larvicidal activity and mortality. Both formulations slightly inhibited acetylcholinesterase activity in S. aegypti mosquitoes , while the standard formulation decreased and the commercial formulation increased glutathione S-transferase activity. However, there were no significant differences for superoxide dismutase, esterase-α, esterase-ß and lipid peroxidation. These findings indicate that in the absence of the target compound, the presence of byproducts can alter the enzymatic activity. In general, photolysis effectively degrade malathion lower than the legislation values; however, longer treatment times must be evaluated for the commercial formulation.

3.
Cells ; 13(6)2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38534317

RESUMO

Mitochondria provide energy for all cellular processes, including reactions associated with cell cycle progression, DNA damage repair, and cilia formation. Moreover, mitochondria participate in cell fate decisions between death and survival. Nek family members have already been implicated in DNA damage response, cilia formation, cell death, and cell cycle control. Here, we discuss the role of several Nek family members, namely Nek1, Nek4, Nek5, Nek6, and Nek10, which are not exclusively dedicated to cell cycle-related functions, in controlling mitochondrial functions. Specifically, we review the function of these Neks in mitochondrial respiration and dynamics, mtDNA maintenance, stress response, and cell death. Finally, we discuss the interplay of other cell cycle kinases in mitochondrial function and vice versa. Nek1, Nek5, and Nek6 are connected to the stress response, including ROS control, mtDNA repair, autophagy, and apoptosis. Nek4, in turn, seems to be related to mitochondrial dynamics, while Nek10 is involved with mitochondrial metabolism. Here, we propose that the participation of Neks in mitochondrial roles is a new functional axis for the Nek family.


Assuntos
Mitocôndrias , Proteínas Serina-Treonina Quinases , Quinases Relacionadas a NIMA/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Mitocôndrias/metabolismo , Homeostase , DNA Mitocondrial
4.
Antibiotics (Basel) ; 13(3)2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38534657

RESUMO

The importance of fungal infections, particularly those caused by yeasts, is increasing among the medical community. Candida albicans and Cryptococcus neoformans are amongst the high-priority fungal species identified by the World Health Organization (WHO) and are considered in the critical group, while Candida krusei is included in the medium-priority group. The cyclam salt H4[H2(4-CF3PhCH2)2Cyclam]Cl4 proved to be active against the growth of these three yeasts, and the aim of this work was to verify its interference with their virulence mechanisms, whether shared or unique. H4[H2(4-CF3PhCH2)2Cyclam]Cl4 significantly inhibited biofilm production and catalase activity, being able to interfere with C. albicans dimorphic transition and C. neoformans melanin production. At the minimal inhibitory concentration (MIC) values, H4[H2(4-CF3PhCH2)2Cyclam]Cl4 had no antioxidant effect, as determined by the DPPH method. When using the RAW264.7 macrophage cell line, H4[H2(4-CF3PhCH2)2Cyclam]Cl4 reduced nitric oxide (NO) detection (the Griess reaction), but this effect was associated with a significant toxic effect on the cells.

5.
Acta Med Port ; 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38489931

RESUMO

INTRODUCTION: Stroke is considered one of the greatest public health challenges worldwide, with the ischemic subtype being the most prevalent. Various acute stroke clinical guidelines recommend early rehabilitation interventions, including very early mobilization. However, despite the studies conducted in recent years regarding when to initiate mobilization after an acute stroke, there are few systematic and personalized protocols based on the factors for which patient mobilization should ideally be performed. We aim to conduct an umbrella review of systematic reviews and meta-analyses to study the early mobilization decision after an acute ischemic stroke in comparison with conventional care and correlate the different approaches with patient clinical outcomes. METHODS AND ANALYSIS: We will perform a systematic search on PubMed/MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Epistemonikos and Web of Science Core Collection databases. Retrieved studies will be independently reviewed by two authors and any discrepancies will be resolved by consensus or with a third reviewer. Reviewers will extract the data and assess the risk of bias in the selected studies. We will use the 16-item Assessment of Multiple Systematic Reviews 2 (AMSTAR2) checklist as the critical appraisal tool to assess cumulative evidence and risk of bias of the different studies. This will be the first umbrella review that compares early mobilization approaches in post-acute ischemic stroke. This study may help to define the optimal early mobilization strategy in stroke patients. PROSPERO registration number: CRD42023430494.

6.
Ticks Tick Borne Dis ; 15(4): 102333, 2024 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-38522220

RESUMO

Rhipicephalus (Boophilus) microplus, also known as the cattle tick, causes severe parasitism and transmits different pathogens to vertebrate hosts, leading to massive economic losses. In the present study, we performed a functional characterization of a ribosomal protein from R. microplus to investigate its importance in blood feeding, egg production and viability. Ribosomal protein S18 (RPS18) is part of the 40S subunit, associated with 18S rRNA, and has been previously pointed to have a secondary role in different organisms. Rhipicephalus microplus RPS18 (RmRPS18) gene expression levels were modulated in female salivary glands during blood feeding. Moreover, mRNA levels in this tissue were 10 times higher than those in the midgut of fully engorged female ticks. Additionally, recombinant RmRPS18 was recognized by IgG antibodies from sera of cattle naturally or experimentally infested with ticks. RNAi-mediated knockdown of the RmRPS18 gene was performed in fully engorged females, leading to a significant (29 %) decrease in egg production. Additionally, egg hatching was completely impaired, suggesting that no viable eggs were produced by the RmRPS18-silenced group. Furthermore, antimicrobial assays revealed inhibitory activities against gram-negative Escherichia coli and gram-positive Staphylococcus aureus bacteria, affecting bacterial growth. Data presented here show the important role of RmRPS18 in tick physiology and suggest that RmRPS18 can be a potential target for the development of novel strategies for tick control.

7.
Bioorg Med Chem ; 102: 117671, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38452407

RESUMO

The search for novel anticancer drugs is essential to expand treatment options, overcome drug resistance, reduce toxicity, promote innovation, and tackle the economic impact. The importance of these studies lies in their contribution to advancing cancer research and enhancing patient outcomes in the battle against cancer. Here, we developed new asymmetric hybrids containing two different naphthoquinones linked by a 1,2,3-1H-triazole nucleus, which are potential new drugs for cancer treatment. The antitumor activity of the novel compounds was tested using the breast cancer cell lines MCF-7 and MDA-MB-231, using the non-cancer cell line MCF10A as control. Our results showed that two out of twenty-two substances tested presented potential antitumor activity against the breast cancer cell lines. These potential drugs, named here 12g and 12h were effective in reducing cell viability and promoting cell death of the tumor cell lines, exhibiting minimal effects on the control cell line. The mechanism of action of the novel drugs was assessed revealing that both drugs increased reactive oxygen species production with consequent activation of the AMPK pathway. Therefore, we concluded that 12g and 12h are novel AMPK activators presenting selective antitumor effects.


Assuntos
Antineoplásicos , Neoplasias da Mama , Naftoquinonas , Humanos , Feminino , Células MCF-7 , Espécies Reativas de Oxigênio/metabolismo , Triazóis/farmacologia , Naftoquinonas/farmacologia , Proteínas Quinases Ativadas por AMP , Proliferação de Células , Apoptose , Linhagem Celular Tumoral , Antineoplásicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Ensaios de Seleção de Medicamentos Antitumorais
8.
Med Mycol ; 62(4)2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38533658

RESUMO

Chromoblastomycosis (CBM) and pheohyphomycosis (PHM) are the most common implantation mycoses caused by dematiaceous fungi. In the past, flucytosine (5-FC) has been used to treat CBM, but development of resistance is common. Carmofur belongs to the same class as 5-FC and has in vitro inhibitory activity against the main agents of CBM and PHM. The aim of this study was to compare the action of these two pyrimidine analog drugs against CBM and PHM agents. The minimum inhibitory concentration (MIC) and the selectivity index based on cytotoxicity tests of these two drugs against some agents of these mycoses were determined, with carmofur presenting a higher selectivity index than 5-FC. Carmofur demonstrated here synergistic interactions with itraconazole and amphotericin B against Exophiala heteromorpha, Fonsecaea pedrosoi, Fonsecaea monophora, and Fonsecaea nubica strains. Additionally, carmofur plus itraconazole demonstrated here synergism against a Phialophora verrucosa strain. To evaluate the development of carmofur resistance, passages in culture medium containing subinhibitory concentrations of this pyrimidine analog were carried out, followed by in vitro susceptibility tests. Exophiala dermatitidis quickly developed resistance, whereas F. pedrosoi took seven passages in carmofur-supplemented medium to develop resistance. Moreover, resistance was permanent in E. dermatitidis but transient in F. pedrosoi. Hence, carmofur has exhibited certain advantages, albeit accompanied by limitations such as the development of resistance, which was expected as with 5-FC. This underscores its therapeutic potential in combination with other drugs, emphasizing the need for a meticulous evaluation of its application in the fight against dematiaceous fungi.


Assuntos
Cromoblastomicose , Micoses , Humanos , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Flucitosina/farmacologia , Itraconazol/farmacologia , Itraconazol/uso terapêutico , Fungos , Cromoblastomicose/microbiologia , Cromoblastomicose/veterinária , Micoses/tratamento farmacológico , Micoses/veterinária , Testes de Sensibilidade Microbiana/veterinária
9.
Interv Neuroradiol ; : 15910199241236819, 2024 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-38556254

RESUMO

INTRODUCTION: After several uncontrolled studies and one randomized clinical trial, there is still uncertainty regarding the role of endovascular treatment (EVT) in cerebral venous thrombosis (CVT). This study aims to describe and assess different acute management strategies in the treatment of CVT. METHODS: We performed a retrospective analysis of an international two-center registry of CVT patients admitted since 2019. Good outcome was defined as a return to baseline modified Rankin scale at three months. We described and compared EVT versus no-EVT patients. RESULTS: We included 61 patients. Only one did not receive systemic anticoagulation. EVT was performed in 13/61 (20%) of the cases, with a median time from diagnosis to puncture of 4.5 h (1.25-28.5). EVT patients had a higher median baseline NIHSS [6 (IQR 2-17) vs 0 (0-2.7), p = 0.002)] and a higher incidence of intracerebral hemorrhage (53.8% vs 20.3%, p = 0.03). Recanalization was achieved in 10/13 (77%) patients. Thrombectomy was performed in every case with angioplasty in 7 out of 12 patients and stenting in 3 cases. No postprocedural complication was reported. An improvement of the median NIHSS from baseline to discharge [6 (2-17) vs 1(0-3.75); p < 0.001] was observed in EVT group. A total of 31/60 patients (50.8%) had good outcomes. Adjusting to NIHSS and ICH, EVT had a non-significant increase in the odds of a good outcome [aOR 1.42 (95%CI 0.73-2.8, p = 0.307)]. CONCLUSIONS: EVT in combination with anticoagulation was safe in acute treatment of CVT as suggested by NIHSS improvement. Selected patients may benefit from this treatment.

10.
Braz J Microbiol ; 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38466550

RESUMO

The drugs available to treat sporotrichosis, an important yet neglected fungal infection, are limited. Some Sporothrix spp. strains present reduced susceptibility to these antifungals. Furthermore, some patients may not be indicated to use these drugs, while others may not respond to the therapy. The anthelmintic drug niclosamide is fungicidal against the Sporothrix brasiliensis type strain. This study aimed to evaluate whether niclosamide also has antifungal activity against Sporothrix globosa, Sporothrix schenckii and other S. brasiliensis strains with distinct genotypes and antifungal susceptibility status. Minimal inhibitory and fungicidal concentrations (MIC and MFC, respectively) were determined using the microdilution method according to the CLSI protocol. The checkerboard method was employed to evaluate niclosamide synergism with drugs used in sporotrichosis treatment. Metabolic activity of the strains under niclosamide treatment was evaluated using the resazurin dye. Niclosamide was active against all S. brasiliensis strains (n = 17), but it was ineffective (MIC > 20 µM) for some strains (n = 4) of other pathogenic Sporothrix species. Niclosamide MIC values for Sporothrix spp. were similar for mycelial and yeast-like forms of the strains (P = 0.6604). Niclosamide was fungicidal (MFC/MIC ratio ≤ 2) for most strains studied (89%). Niclosamide activity against S. brasiliensis is independent of the fungal genotype or non-wild-type phenotypes for amphotericin B, itraconazole, or terbinafine. These antifungal drugs presented indifferent interactions with niclosamide. Niclosamide has demonstrated potential for repurposing as a treatment for sporotrichosis, particularly in S. brasiliensis cases, instigating in vivo studies to validate the in vitro findings.

11.
Neurosci Lett ; 824: 137666, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38331019

RESUMO

Alcohol Use Disorder (AUD) presents a significant and challenging public health concern, marked by a dearth of effective pharmacological treatments. Understanding the neurobiological underpinnings of AUD is of paramount importance for the development of efficacious interventions. The process of addiction entails the acquisition of associative behaviors, prominently engaging the dorsal region of the hippocampus for encoding these associative memories. Nicotinic receptor systems have been implicated in mediating the rewarding effects of ethanol, as well as memory and learning processes. In our current investigation, we delved into the role of α4ß2 nicotinic acetylcholine receptors (nAChRs) within the dorsal hippocampus in the context of ethanol-induced conditioned place preference (CPP), a robust model for scrutinizing the rewarding properties and drug-associated behaviors. To establish CPP, ethanol (2 g/kg) was administered intraperitoneally during a 8-day conditioning phase. Fos immunohistochemistry was employed to assess the involvement of discrete subregions within the dorsal hippocampus in ethanol-induced CPP. Additionally, we probed the influence of α4ß2 nAChRs on CPP via microinjections of a selective nAChR antagonist, dihydro-ß-erythroidine (DHBE, at dosages of 6, 12, and 18 µg/0.5 µL per hemisphere) within the hippocampus. Our results unveiled that ethanol-induced CPP was associated with an increase Fos -positive cells in various subregions of the dorsal hippocampus, including CA1, CA2, CA3, and the dentate gyrus. Intrahippocampal administration of DHBE (at doses of 6 and 18 µg/0.50 µL per hemisphere) effectively blocked ethanol-induced CPP, while leaving locomotor activity unaffected. These findings underscore the critical involvement of the dorsal hippocampus and α4ß2 nAChRs in the acquisition of ethanol-associated learning and reward.


Assuntos
Etanol , Receptores Nicotínicos , Camundongos , Animais , Etanol/farmacologia , Receptores Nicotínicos/metabolismo , Hipocampo/metabolismo , Antagonistas Nicotínicos/farmacologia
12.
Int J Parasitol Drugs Drug Resist ; 24: 100525, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38359731

RESUMO

Leishmaniasis is a disease caused by Leishmania spp., affecting millions of people around the world. For decades, its treatment has been based on pentavalent antimonials, which notoriously cause toxic side effects in patients. In this study, epoxy-α-lapachone incorporated into an oil-in-water-type microemulsion (ELAP-ME) and meglumine antimoniate (MA) were assayed in monotherapy and in combination (ELAP-ME/MA) in BALB/c mice infected with Leishmania (Leishmania) amazonensis. In general, there was a reduction in paw lesion size (up to 37% reduction) and decreases of parasite loads in the footpad (∼40%) and lymph nodes (∼31%) of animals treated with ELAP-ME/MA, when compared to the non-treated control groups. Analyses of serum biochemical parameters revealed that the ELAP-ME/MA showed lower renal and hepatic toxicity when compared to MA 2-doses/week monotherapy. These findings indicate that the ELAP-ME/MA combination may be a promising approach for the treatment of cutaneous leishmaniasis.


Assuntos
Antiprotozoários , Leishmania , Leishmaniose Cutânea , Naftoquinonas , Compostos Organometálicos , Humanos , Animais , Camundongos , Antimoniato de Meglumina/uso terapêutico , Leishmaniose Cutânea/tratamento farmacológico , Leishmaniose Cutânea/parasitologia , Meglumina/uso terapêutico , Compostos Organometálicos/uso terapêutico , Camundongos Endogâmicos BALB C
13.
Arch Orthop Trauma Surg ; 144(3): 1149-1159, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38231206

RESUMO

INTRODUCTION: Despite being the most used exam today, few studies have evaluated the accuracy of findings on non-contrast magnetic resonance imaging (MRI). The primary objective of the study was to evaluate the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of non-contrast MRI findings in frozen shoulder, isolated and in combination. The secondary objectives were to define the interobserver and intraobserver agreement of the assessments and the odds ratio for frozen shoulder because of the various findings of MRI. METHODS: A retrospective diagnostic accuracy study comparing non-contrast MRI findings between the frozen shoulder group and the control group. Sensitivity, specificity, positive and negative predictive value, accuracy, odds ratio, interobserver and intraobserver agreement were calculated for each finding and their possible associations. RESULTS: The hyperintensity on capsule in the axillary recess presented 84% sensitivity, 94% specificity, and 89% accuracy. The obliteration of the subcoracoid fat triangle in the rotator interval had sensitivity 34%, specificity 82% and accuracy 58%. For coracohumeral ligament thickness ≥ 2 mm had specificity 66%, 48% specificity and 57% accuracy. Capsule thickness in the axillary recess ≥ 4 mm resulted in 54% sensitivity, 82% specificity, and 68% accuracy. Regarding interobserver agreement, only the posteroinferior and posterosuperior quadrants showed moderate results, and all the others showed strong reliability. The odds ratio for hyperintensity in the axillary recess was 82.3 for frozen shoulder. The association of these findings increased specificity (95%). CONCLUSION: The accuracy of non-contrast magnetic resonance imaging is high for diagnosing frozen shoulder, especially when evaluating the hyperintensity of the axillary recess. The exam has high reliability and reproducibility. The presence of an association of signs increases the specificity of the test. LEVEL OF EVIDENCE: Level III, study of diagnostic test.


Assuntos
Bursite , Articulação do Ombro , Humanos , Estudos Retrospectivos , Reprodutibilidade dos Testes , Articulação do Ombro/patologia , Imageamento por Ressonância Magnética/métodos , Bursite/diagnóstico por imagem , Sensibilidade e Especificidade
14.
Future Med Chem ; 16(3): 253-269, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38193294

RESUMO

Background: Chagas disease is caused by the parasite Trypanosoma cruzi, and the lack of effective and safe treatments makes identifying new classes of compounds with anti-T. cruzi activity of paramount importance. Methods: Hit-to-lead exploration of a metabolically stable N-imidazoylpiperazine was performed. Results: Compound 2, a piperazine derivative active against T. cruzi, was selected to perform the hit-to-lead exploration, which involved the design, synthesis and biological evaluation of 39 new derivatives. Conclusion: Compounds 6e and 10a were identified as optimized compounds with low micromolar in vitro activity, low cytotoxicity and suitable preliminary absorption, distribution, metabolism and excretion and physicochemical properties. Both compounds reduced parasitemia in mouse models of Chagas disease, providing a promising opportunity for further exploration of new antichagasic compounds.


Assuntos
Doença de Chagas , Tripanossomicidas , Trypanosoma cruzi , Animais , Camundongos , Tripanossomicidas/farmacologia , Tripanossomicidas/química , Doença de Chagas/tratamento farmacológico , Doença de Chagas/parasitologia , Relação Estrutura-Atividade , Parasitemia/tratamento farmacológico
16.
Fungal Genet Biol ; 170: 103845, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38040325

RESUMO

Sporotrichosis is a subcutaneous mycosis caused by pathogenic Sporothrix species. Among them, Sporothrix brasiliensis is the main species associated with endemic regions in South America, especially Brazil. It is highly virulent and can be spread through zoonotic transmission. Molecular epidemiological surveys are needed to determine the extent of genetic variation, to investigate outbreaks, and to identify genotypes associated with antifungal resistance and susceptibility. This study investigated the sequence variation of different constitutive genes and established a novel multilocus sequence typing (MLST) scheme for S. brasiliensis. Specific primers were designed for 16 genes using Primer-BLAST software based on the genome sequences of three S. brasiliensis strains (ATCC MYA-4823, A001 and A005). Ninety-one human, animal, and environmental S. brasiliensis isolates from different Brazilian geographic regions (South, Southeast, Midwest and Northeast) andtwo isolates from Paraguay were sequenced. The loci that presented the highest nucleotide diversity (π) were selected for the MLST scheme. Among the 16 studied genetic loci, four presented increased π value and were able to distinguish all S. brasiliensis isolates into seven distinct haplotypes. The PCR conditions were standardized for four loci. Some of the obtained haplotypes were associated with the geographic origin of the strains. This study presents an important advance in the understanding of this important agent of sporotrichosis in Brazil. It significantly increased the discriminatory power for genotyping of S. brasiliensis isolates, and enabled new contributions to the epidemiological studies of this human and animal pathogen in Brazil and in other countries.


Assuntos
Sporothrix , Esporotricose , Animais , Humanos , Esporotricose/epidemiologia , Esporotricose/microbiologia , Tipagem de Sequências Multilocus , Genótipo , Brasil/epidemiologia
17.
J Struct Biol ; 216(1): 108054, 2023 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-38065428

RESUMO

The discovery of new protein topologies with entanglements and loop-crossings have shown the impact of local amino acid arrangement and global three-dimensional structures. This phenomenon plays a crucial role in understanding how protein structure relates to folding and function, affecting the global stability, and biological activity. Protein entanglements encompassing knots and non-trivial topologies add complexity to their folding free energy landscapes. However, the initial native contacts driving the threading event for entangled proteins remains elusive. The Pierced Lasso Topology (PLT) represents an entangled topology where a covalent linker creates a loop in which the polypeptide backbone is threaded through. Compared to true knotted topologies, PLTs are simpler topologies where the covalent-loop persists in all conformations. In this work, the PLT protein leptin, is used to visualize and differentiate the preference for slipknotting over plugging transition pathways along the folding route. We utilize the Energy Landscape Visualization Method (ELViM), a multidimensional projection technique, to visualize and distinguish early threaded conformations that cannot be observed in an in vitro experiment. Critical contacts for the leptin threading mechanisms were identified where the competing pathways are determined by the formation of a hairpin loop in the unfolded basin. Thus, prohibiting the dominant slipknotting pathway. Furthermore, ELViM offers insights into distinct folding pathways associated with slipknotting and plugging providing a novel tool for de novo design and in vitro experiments with residue specific information of threading events in silico.

18.
Acta Ortop Bras ; 31(6): e268392, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38115873

RESUMO

Objective: To describe a protocol of obtention of mesenchymal stem cells and to report their use as a biological adjuvant in three patients undergoing arthroscopic rotator cuff repair. Methods: Case series of patients who underwent arthroscopic repair of isolated full-thickness supraspinatus tear using mesenchymal stem cells obtained from the bone marrow as a biological adjuvant. All patients were operated on at the same institution, by a surgeon with 13 years of experience. The cells were applied at the end of the procedure, at the tendon-bone interface, at an approximate concentration of 2,000,000 mesenchymal cells/mm3 and a total volume of 5 ml. Results: All patients improved with the procedure, with one excellent and two good results. All cases overcame the minimally important clinical difference. All cases reached tendon healing, without partial or complete re-tears. We observed no complications. Conclusion: Arthroscopic rotator cuff repair with added mesenchymal cells obtained from bone marrow and submitted to a cell expansion process led to good functional results and healing in all cases in the sample, with no complications. Level of Evidence IV, Case Series.


Objetivo: Descrever o protocolo de obtenção de células mesenquimais e relatar seu uso como adjuvante biológico em três pacientes submetidos ao reparo artroscópico do manguito rotador. Métodos: Série de casos de pacientes submetidos ao reparo artroscópico de rotura transfixante do músculo supraespinal utilizando como adjuvante biológico células mesenquimais obtidas da medula óssea. Todos ospacientes foram operados na mesma instituição por um cirurgião com 13 anos de experiência. As células foram aplicadas ao final do procedimento, na interface do tendão com o osso, na concentração aproximada de 2 milhões de células mesenquimais/mm3 e volume total de 5 ml. Resultados: Todos os pacientes melhoraram após o procedimento, havendo um resultado excelente e dois bons. Todos superaram a diferença clínica minimamente importante. Em todos os casos ocorreu cicatrização tendínea, sem a presença de rerroturas parciais ou completas. Não observamos complicações. Conclusão: O reparo do manguito rotador artroscópico com adição de células mesenquimais obtidas da medula óssea e submetidas a processo de expansão celular levou a bons resultados funcionais e cicatrização, sem complicações, em todos os casos da amostra. Nível de Evidência IV, Série de Casos.

19.
Injury ; 54 Suppl 6: 110746, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38143119

RESUMO

OBJECTIVE: To compare the results of surgical treatment of midshaft clavicle fractures, treated with the technique of minimally invasive plate osteosynthesis (MIPO) with locking compression plate versus open reduction and internal fixation (ORIF) with locked plate. METHODS: Quasi-randomized comparative study, evaluating displaced midshaft clavicle fractures treated with MIPO versus ORIF, with procedures performed by a single surgeon. We evaluated patients at 12 months using the University of California at Los Angeles (UCLA) scale and radiographically at 8, 12, 26 and 52 weeks, in addition to describing complications. RESULTS: We evaluated 44 patients; 22 submitted to MIPO and 22 to ORIF. The median UCLA scores at 12 months were 35 in the ORIF group and 35 in the MIPO group (p = 0.712). All patients had fracture healing at 3 months (p > 0.999). The mean surgery time was 87.5 min in the ORIF group and 47.5 in the MIPO (p < 0.001) group. As complications, 1 suture dehiscence (4.5%), 2 protruding plates (9.1%) and 1 change in sensitivity around the surgical wound (4.5%) were observed in the MIPO group, while in the ORIF group, 15 changes in sensitivity (68.2%) and 3 hypertrophic scars (13.6%) were observed. The only complication that showed a difference between the groups was the change in sensitivity (p < 0.001). No cases of pseudarthrosis or failure of osteosynthesis were identified in either technique. CONCLUSION: This study demonstrated that the two treatments, ORIF and MIPO, are equally effective in the treatment of displaced middle third clavicle fractures. However, MIPO is superior to ORIF in regard to reduced surgical time and preservation of supraclavicular nerve sensitivity.


Assuntos
Clavícula , Fraturas Ósseas , Humanos , Placas Ósseas , Clavícula/diagnóstico por imagem , Clavícula/lesões , Clavícula/cirurgia , Fixação Interna de Fraturas/métodos , Consolidação da Fratura , Fraturas Ósseas/diagnóstico por imagem , Fraturas Ósseas/cirurgia , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Estudos Retrospectivos , Resultado do Tratamento
20.
RSC Adv ; 13(49): 34852-34865, 2023 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-38035251

RESUMO

This study presents a comprehensive analysis encompassing the synthesis, structural elucidation, photophysical behavior, and electrochemical properties of a novel series of chalcogen-naphthoquinone-1,2,3-triazole hybrids. Employing a meticulously designed protocol, the synthesis of these hybrids, denoted as 11a-j, was achieved with remarkable efficiency (yielding up to 81%). This synthesis used a regioselective copper-catalyzed azide-alkyne cycloaddition reaction (CuAAC). Furthermore, a detailed investigation into the photophysical characteristics, TDDFT calculations, electrochemical profiles, and photobiological attributes of compounds 11a-j was conducted. This exploration aimed to unravel insights into the excited state behaviors of these molecules, as well as their redox properties. Such insights are crucial for future applications of these derivatives in diverse biological assays.

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