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1.
J Contemp Dent Pract ; 25(4): 295-302, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38956842

RESUMO

AIM: The purpose of this study was to evaluate the mandibular growth and/or projection following maxillary incisor proclination, overbite correction, and maxillary dentoalveolar expansion without the use of any class II mechanics, in growing class II division 2 patients treated with clear aligners. MATERIALS AND METHODS: Before and after treatment cone-beam computed tomographic (CBCT) generated lateral and posteroanterior cephalograms of thirty-two patients with skeletal class II division 2, 16 in the treatment group and 16 in the untreated group, were reviewed to evaluate treatment-related changes. Upper incisors were proclined and protruded, as well as upper arch expansion and overbite correction were performed as part of their regular treatment. Cephalometric analysis was performed to evaluate skeletal and dental changes. Unpaired statistical t-tests were performed to determine if significant skeletal class II correction was achieved in the treatment group. RESULTS: In the treatment group, after treatment, the upper incisors became more proclined and protruded, and the inter-molar width increased while the overbite was reduced compared to the control group. An increase in skeletal mandibular growth and forward projection was also observed, thus contributing to an improvement of the sagittal skeletal relationship as evidenced by ANB and Wits values compared to the control group. CONCLUSION: A combination of upper incisor proclination, correction of deep overbite, and maxillary dentoalveolar expansion using clear aligners appears to contribute to an improvement of the skeletal class II relationship in growing patients with class II division 2. CLINICAL SIGNIFICANCE: This study shows that unlocking the mandible by correcting a deep overbite, proclining upper incisors, and expanding the upper arch in growing class II division 2 patients can improve skeletal class II using clear aligners. How to cite this article: Mirzasoleiman P, El-Bialy T, Wiltshire WA, et al. Evaluation of Mandibular Projection in Class II Division 2 Subjects Following Orthodontic Treatment Using Clear Aligners. J Contemp Dent Pract 2024;25(4):295-302.


Assuntos
Cefalometria , Tomografia Computadorizada de Feixe Cônico , Má Oclusão Classe II de Angle , Mandíbula , Humanos , Má Oclusão Classe II de Angle/terapia , Má Oclusão Classe II de Angle/diagnóstico por imagem , Mandíbula/crescimento & desenvolvimento , Mandíbula/diagnóstico por imagem , Feminino , Masculino , Adolescente , Criança , Incisivo/diagnóstico por imagem , Sobremordida/terapia , Ortodontia Corretiva/métodos , Ortodontia Corretiva/instrumentação
2.
Trials ; 25(1): 442, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38961460

RESUMO

BACKGROUND: Neck pain is a prevalent global musculoskeletal issue, significantly contributing to the loss of years of healthy life due to disability. Chronic nonspecific neck pain (CNNP) involves diverse symptoms impacting mobility and quality of life. While therapeutic exercises demonstrate efficacy, the role of photobiomodulation therapy (PBMT) remains uncertain. This study aims to assess the additional effects of PBMT within a multimodal therapeutic intervention for CNNP. METHODS: A randomized, two-arm, controlled, blind clinical trial follows CONSORT and SPIRIT guidelines. Participants diagnosed with CNNP will receive a stand-alone multimodal therapeutic intervention or the same program with additional PBMT. The primary outcomes will be assessed by the functional disability identified through applying the NDI (Neck Disability Index). Secondary outcomes will be pain intensity during rest and active neck movement, catastrophizing and kinesiophobia, functionality, and disability assessed at baseline, after 8 weeks, and at a 4-week follow-up. Both groups receive pain education before personalized interventions, including resistance exercises, neuromuscular activities, mobility, and body balance. The PBMT group undergoes low-level light therapy. Intention-to-treat analysis, using linear mixed models, employs data presented as mean, standard deviation, and differences with a 95% confidence interval. Non-normally distributed variables transform. Statistical significance is set at 5%. DISCUSSION: This study addresses a critical gap in understanding the combined effects of PBMT and therapeutic exercises for CNNP. The findings aim to guide clinicians, researchers, and CNNP sufferers through rigorous methodology and diverse outcome assessments, offering valuable insights into evidence-based practices for CNNP management. Data confidentiality is maintained throughout, ensuring participant privacy during statistical analysis. TRIAL REGISTRATION: Effects of adding photobiomodulation to a specific therapeutic exercise program for the treatment of individuals with chronic nonspecific neck pain, registration number: NCT05400473, on 2022-05-27.


Assuntos
Dor Crônica , Terapia com Luz de Baixa Intensidade , Cervicalgia , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos , Cervicalgia/terapia , Cervicalgia/fisiopatologia , Cervicalgia/diagnóstico , Terapia com Luz de Baixa Intensidade/métodos , Dor Crônica/terapia , Dor Crônica/fisiopatologia , Dor Crônica/diagnóstico , Terapia Combinada , Resultado do Tratamento , Medição da Dor , Avaliação da Deficiência , Adulto , Feminino , Masculino , Pessoa de Meia-Idade , Terapia por Exercício/métodos , Fatores de Tempo , Qualidade de Vida
3.
Best Pract Res Clin Rheumatol ; : 101973, 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-38997822

RESUMO

Rheumatic diseases (RDs) are characterized by autoimmunity and autoinflammation and are recognized as complex due to the interplay of multiple genetic, environmental, and lifestyle factors in their pathogenesis. The rapid advancement of genome-wide association studies (GWASs) has enabled the identification of numerous single nucleotide polymorphisms (SNPs) associated with RD susceptibility. Based on these SNPs, polygenic risk scores (PRSs) have emerged as promising tools for quantifying genetic risk in this disease group. This chapter reviews the current status of PRSs in assessing the risk of RDs and discusses their potential to improve the accuracy of the diagnosis of these complex diseases through their ability to discriminate among different RDs. PRSs demonstrate a high discriminatory capacity for various RDs and show potential clinical utility. As GWASs continue to evolve, PRSs are expected to enable more precise risk stratification by integrating genetic, environmental, and lifestyle factors, thereby refining individual risk predictions and advancing disease management strategies.

4.
Musculoskelet Sci Pract ; 73: 103141, 2024 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-39018751

RESUMO

PURPOSE: Characterize heart rate and cardiac autonomic response to painful stimulus on neck pain. METHODS: Twenty-five individuals with neck pain and 25 healthy subjects were included. Heart rate variability and heart rate were assessed in the conditioned pain modulation test at pretest rest, during testing and in recovery. Heart rate variability indices were obtained using linear and nonlinear methods. RESULTS: No significant differences were observed between groups regarding heart rate and the linear methods (p > 0.05). However, significant difference was observed between groups regarding nonlinear methods (standard deviation of the instantaneous variability of beat-to-beat interval variability, p = 0.005) CONCLUSIONS: Individuals with chronic neck pain showed autonomic responses similar to those of their healthy counterparts during the conditioning stimulus.

5.
J Bodyw Mov Ther ; 39: 423-430, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38876662

RESUMO

INTRODUCTION: Patellofemoral pain (PFP) patients often show an altered lower limb alignment during the single-leg squat (SLS). There is evidence that proximal and distal-to-the-knee muscle alterations can modify the lower limb alignment in PFP patients. However, we observed a lack of studies investigating the possible association between the thickness and strength of proximal and distal-to-the-knee muscles and lower limb alignment during SLS in women with PFP. Therefore, this study aimed to investigate the association between the thickness and strength of lower limb muscles and dynamic knee valgus (DKV) during SLS in women with PFP. METHODS: Cross-sectional study, where fifty-five women with PFP were submitted to the following evaluations: (1) muscle thickness (MT) of Gluteus Medius (GMed), Gluteus Maximus (GMax), Vastus Lateralis (VL), and Tibialis Anterior (TA); (2) isometric peak torque of hip abductors, hip external rotators, knee extensors, and foot inversors; and (3) DKV during SLS. RESULTS: There was a significant negative association between GMax's MT and DKV (r = -0.32; p = 0.01), and between TA's MT and DKV (r = -0.28; p = 0.03). No significant correlations were observed between isometric torques and DKV. Regression analysis found that GMax's MT explained 10% of the DKV's variance during SLS. DISCUSSION: Poor lower limb alignment during SLS is weakly associated with proximal and distal-to-the-knee muscle thicknesses, with no association with isometric torque in PFP women. CONCLUSION: Our results suggest that other factors besides strength and muscle thicknesses may explain and improve lower limb alignment in women with PFP.


Assuntos
Extremidade Inferior , Força Muscular , Músculo Esquelético , Síndrome da Dor Patelofemoral , Humanos , Feminino , Estudos Transversais , Adulto , Síndrome da Dor Patelofemoral/fisiopatologia , Músculo Esquelético/fisiopatologia , Músculo Esquelético/fisiologia , Força Muscular/fisiologia , Adulto Jovem , Extremidade Inferior/fisiopatologia , Extremidade Inferior/fisiologia , Torque , Articulação do Joelho/fisiopatologia , Articulação do Joelho/fisiologia
6.
Heliyon ; 10(11): e32047, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38933938

RESUMO

Gamification involves using game design elements in non-game contexts. It is an emerging strategy that, being able to motivate consumer engagement with brands, has been increasingly used by companies in marketing activities. Recently, the application of gamification to marketing has become increasingly popular, with an increasing amount of research outputs. However, a clear overview of the field, a theoretical orientation or an agenda for research are still missing, which justifies the analysis of the existing literature joining these two fields of research. The motivation for conducting this review was twofold: Firstly, it is helpful to attain a broad overview of this developing field, synthesizing the existing knowledge in a structured way, understanding how gamification research in marketing has progressed and what type of knowledge has been acquired; secondly, it allows us to provide valuable information that will guide future research. Thus, this study provides a hybrid review, which integrates a bibliometric and TCCM analysis, of gamification in marketing by analyzing 114 articles. The data was retrieved from the Scopus scientific database. The bibliometric analysis showed the existence of 8 clusters, mostly representing current areas of research. It was found that the focus of the literature, so far, has been on studying which game elements should be implemented in a gamification system, as well as examining the impact of gamification experiences on engagement and consumer's behaviors. The TCCM analysis revealed the major theories and methodological approaches explored in published articles. The use of self-determination theory and quantitative methodology, based on primary data using online surveys, stands out. These complementary analyzes allowed to provide future research directions to scholars and practitioners working in this domain, promoting the advancement of scientific knowledge, contextual relevance and methodological rigor. Moreover, this review also helps marketers make more informed strategic decisions and supports successful gamification design.

7.
Artigo em Inglês | MEDLINE | ID: mdl-38935005

RESUMO

INTRODUCTION: This study evaluated the probability of developing malocclusions in mixed dentition. METHODS: A longitudinal study was conducted with 598 children (aged 5 years) in deciduous dentition. The children were followed for 3 years until mixed dentition (aged 8 years). Overjet, overbite, and transversal relations were evaluated. Bayesian models were used to analyze the data and estimate the parameters. RESULTS: The parameter θ was used for the distributions, indicating the probability of presenting a given condition with a credibility index (ICr) of 95%. After 3 years of follow-up, 121 children were reevaluated. The results showed that children have a high probability of malocclusion in mixed dentition. There was a higher probability of developing an increased overjet in the mixed dentition of 20.5% (ICr 95%, 13.6-28.4) to 48.3% (ICr 95%, 39.1-57.7) and a higher probability of having a normal overbite in the deciduous dentition and a lower probability in the mixed dentition (ICr 95%, 9.2-21.3). CONCLUSIONS: Considering the probabilistic model of Bayesian analysis, children with normal overjet in the deciduous dentition may show an increased overjet in the mixed dentition. Concerning overbite, children may present an anterior open bite during the transition between deciduous and mixed dentition, as well as self-correction of deep overbite in mixed dentition. Furthermore, they may present a posterior crossbite during the mixed dentition when there is a normal transverse relationship in the deciduous dentition.

8.
Biomedicines ; 12(6)2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38927540

RESUMO

Human leukocyte antigen (HLA) molecules and their relationships with natural killer (NK) cells, specifically through their interaction with killer-cell immunoglobulin-like receptors (KIRs), exhibit robust associations with the outcomes of diverse diseases. Moreover, genetic variations in HLA and KIR immune system genes offer limitless depths of complexity. In recent years, a surge of high-powered genome-wide association studies (GWASs) utilizing single nucleotide polymorphism (SNP) arrays has occurred, significantly advancing our understanding of disease pathogenesis. Additionally, advances in HLA reference panels have enabled higher resolution and more reliable imputation, allowing for finer-grained evaluation of the association between sequence variations and disease risk. However, it is essential to note that the majority of these GWASs have focused primarily on populations of Caucasian and Asian origins, neglecting underrepresented populations in Latin America and Africa. This omission not only leads to disparities in health care access but also restricts our knowledge of novel genetic variants involved in disease pathogenesis within these overlooked populations. Since the KIR and HLA haplotypes prevalent in each population are clearly modelled by the specific environment, the aim of this review is to encourage studies investigating HLA/KIR involvement in infection and autoimmune diseases, reproduction, and transplantation in underrepresented populations.

9.
Int J Gynaecol Obstet ; 166(1): 90-98, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38873738

RESUMO

OBJECTIVE: The aim of the present study was to analyze the profile and trends of HIV mother-to-child transmission (MTCT) in the Brazilian land border strip (LBS). METHODS: This was a quantitative, ecological, and cross-sectional study using secondary data available in the information systems of the Brazilian Ministry of Health. All cases reported in the Notifiable Diseases Information System between 2010 and 2021 were studied. RESULTS: Between 2010 and 2021, 275 children were born infected through MTCT, and 6076 pregnant women were living with HIV in the Brazilian LBS. HIV detection rates in pregnant women increased in all border arcs. The northern arc experienced the highest increase (19.6%), followed by the central arc (11.4%), and the southern arc (6.1%). Despite historically high detection rates, the southern arc exhibited the smallest increase. While MTCT rate decreased by 37.7% in the border area, the central arc showed no statistically significant reduction. In 2021, the average age of pregnant women was 26.2 years, 25.7% had up to 8 years of schooling, and 55.8% identified as non-white. The majority (92.8%) received antenatal care, and 59.7% were diagnosed with HIV before prenatal care. The use of prophylactic antiretroviral therapy during prenatal care occurred in 69.6% of pregnant women, and infant prophylaxis was provided within first 24 h to 43.6% of live births. CONCLUSION: The results indicate progress in reducing MTCT cases in Brazilian LBS. Disparities in HIV detection rates may be influenced by differences in testing uptake, despite mandatory testing for all babies. It is crucial to continue implementing strategies to reach these women and ensure equitable access to healthcare services for MTCT prevention.


Assuntos
Infecções por HIV , Transmissão Vertical de Doenças Infecciosas , Complicações Infecciosas na Gravidez , Humanos , Feminino , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Transmissão Vertical de Doenças Infecciosas/estatística & dados numéricos , Gravidez , Brasil/epidemiologia , Infecções por HIV/transmissão , Infecções por HIV/epidemiologia , Estudos Transversais , Complicações Infecciosas na Gravidez/epidemiologia , Adulto , Recém-Nascido , Adulto Jovem , Cuidado Pré-Natal/estatística & dados numéricos , Adolescente
10.
11.
Environ Geochem Health ; 46(6): 202, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38696051

RESUMO

Determining the origin and pathways of contaminants in the natural environment is key to informing any mitigation process. The mass magnetic susceptibility of soils allows a rapid method to measure the concentration of magnetic minerals, derived from anthropogenic activities such as mining or industrial processes, i.e., smelting metals (technogenic origin), or from the local bedrock (of geogenic origin). This is especially effective when combined with rapid geochemical analyses of soils. The use of multivariate analysis (MVA) elucidates complex multiple-component relationships between soil geochemistry and magnetic susceptibility. In the case of soil mining sites, X-ray fluorescence (XRF) spectroscopic data of soils contaminated by mine waste shows statistically significant relationships between magnetic susceptibility and some base metal species (e.g., Fe, Pb, Zn, etc.). Here, we show how qualitative and quantitative MVA methodologies can be used to assess soil contamination pathways using mass magnetic susceptibility and XRF spectra of soils near abandoned coal and W/Sn mines (NW Portugal). Principal component analysis (PCA) showed how the first two primary components (PC-1 + PC-2) explained 94% of the sample variability, grouped them according to their geochemistry and magnetic susceptibility in to geogenic and technogenic groups. Regression analyses showed a strong positive correlation (R2 > 0.95) between soil geochemistry and magnetic properties at the local scale. These parameters provided an insight into the multi-element variables that control magnetic susceptibility and indicated the possibility of efficient assessment of potentially contaminated sites through mass-specific soil magnetism.


Assuntos
Monitoramento Ambiental , Poluentes do Solo , Espectrometria por Raios X , Poluentes do Solo/análise , Espectrometria por Raios X/métodos , Análise Multivariada , Monitoramento Ambiental/métodos , Mineração , Portugal , Análise de Componente Principal , Solo/química , Estanho/análise , Fenômenos Magnéticos , Minas de Carvão , Carvão Mineral
12.
J Oral Pathol Med ; 53(6): 341-357, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38782020

RESUMO

BACKGROUND: Head and neck cancer encompasses neoplasms affecting the oral cavity, pharynx, larynx, and thyroid. Identifying factors that modulate the carcinogenesis process can aid in identifying subgroups at higher risk of developing the disease, enabling implementation of prevention programs. Vitamin D receptor polymorphisms can affect the carcinogenesis of various tumors by altering vitamin D metabolism and cellular response. METHODS: To elucidate the role of vitamin D receptor polymorphisms in head and neck cancer, a systematic review was performed, searching the Embase, PubMed, Scopus, and Lilacs databases. A total of 19 articles met the inclusion criteria. The frequency of vitamin D receptors polymorphism alleles (FokI, ApaI, BsmI, TaqI, Cdx2, rs2107301, rs2238135) was recorded and pooled to calculate the odds ratio in a meta-analysis using the Review Manager software. RESULTS: Subgroup analysis demonstrated significant associations in the anatomical site of cancer (oral cancer in ApaI and BsmI, and unspecified subsites of head and neck cancer in TaqI), genotyping method (FokI and BsmI), and continent of the study (ApaI, FokI, and BsmI). CONCLUSION: Our findings were heterogeneous, as with other evidence available in the literature. Therefore, more clinical studies with larger sample sizes are needed to obtain more accurate results on the relationship between vitamin D receptor polymorphism and head and neck cancer.


Assuntos
Predisposição Genética para Doença , Neoplasias de Cabeça e Pescoço , Polimorfismo Genético , Receptores de Calcitriol , Receptores de Calcitriol/genética , Humanos , Neoplasias de Cabeça e Pescoço/genética , Fatores de Risco , Genótipo
13.
JAMA Netw Open ; 7(5): e2411717, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38787561

RESUMO

Importance: For patients with nonspine bone metastases, short-course radiotherapy (RT) can reduce patient burden without sacrificing clinical benefit. However, there is great variation in uptake of short-course RT across practice settings. Objective: To evaluate whether a set of 3 implementation strategies facilitates increased adoption of a consensus recommendation to treat nonspine bone metastases with short-course RT (ie, ≤5 fractions). Design, Setting, and Participants: This prospective, stepped-wedge, cluster randomized quality improvement study was conducted at 3 community-based cancer centers within an existing academic-community partnership. Rollout was initiated in 3-month increments between October 2021 and May 2022. Participants included treating physicians and patients receiving RT for nonspine bone metastases. Data analysis was performed from October 2022 to May 2023. Exposures: Three implementation strategies-(1) dissemination of published consensus guidelines, (2) personalized audit-and-feedback reports, and (3) an email-based electronic consultation platform (eConsult)-were rolled out to physicians. Main Outcomes and Measures: The primary outcome was adherence to the consensus recommendation of short-course RT for nonspine bone metastases. Mixed-effects logistic regression at the bone metastasis level was used to model associations between the exposure of physicians to the set of strategies (preimplementation vs postimplementation) and short-course RT, while accounting for patient and physician characteristics and calendar time, with a random effect for physician. Physician surveys were administered before implementation and after implementation to assess feasibility, acceptability, and appropriateness of each strategy. Results: Forty-five physicians treated 714 patients (median [IQR] age at treatment start, 67 [59-75] years; 343 women [48%]) with 838 unique nonspine bone metastases during the study period. Implementing the set of strategies was not associated with use of short-course RT (odds ratio, 0.78; 95% CI, 0.45-1.34; P = .40), with unadjusted adherence rates of 53% (444 lesions) preimplementation vs 56% (469 lesions) postimplementation; however, the adjusted odds of adherence increased with calendar time (odds ratio, 1.68; 95% CI, 1.20-2.36; P = .003). All 3 implementation strategies were perceived as being feasible, acceptable, and appropriate; only the perception of audit-and-feedback appropriateness changed before vs after implementation (19 of 29 physicians [66%] vs 27 of 30 physicians [90%]; P = .03, Fisher exact test), with 20 physicians (67%) preferring reports quarterly. Conclusions and Relevance: In this quality improvement study, a multicomponent set of implementation strategies was not associated with increased use of short-course RT within an academic-community partnership. However, practice improved with time, perhaps owing to secular trends or physician awareness of the study. Audit-and-feedback was more appropriate than anticipated. Findings support the need to investigate optimal approaches for promoting evidence-based radiation practice across settings.


Assuntos
Neoplasias Ósseas , Melhoria de Qualidade , Humanos , Neoplasias Ósseas/secundário , Neoplasias Ósseas/radioterapia , Feminino , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Idoso , Fidelidade a Diretrizes/estatística & dados numéricos , Padrões de Prática Médica/estatística & dados numéricos
14.
Artigo em Inglês | MEDLINE | ID: mdl-38767935

RESUMO

BACKGROUND: Traumatic brain injury (TBI) induces cognitive deficits driven by neuroinflammation and cerebral edema. The commonly used atypical antipsychotic, quetiapine (QTP), has been recently shown to improve post-TBI outcomes. We hypothesized that QTP would thereby improve animal learning and memory 2 weeks after severe TBI. METHODS: CD1 male mice (n = 35) underwent severe TBI (controlled cortical impact, injury, I) or sham craniotomy (S), followed by BID saline (P, placebo) or QTP (10 or 20 mg/kg, IP) for 2 weeks. Animals underwent Morris Water Maze (MWM) exercises to gauge spatial learning and memory. The distance and time required for swimming animals to reach the platform area (Zone 5, Z5) located in quadrant 1 (Zone 1, Z1) was calculated from digital video recordings analyzed using Ethovision software. Animal bodyweights were recorded daily and on day 14, injured cerebral hemispheres were procured for edema determination (wet-to-dry ratio). Intergroup differences were evaluated with ANOVA/Bonferroni correction (p < 0.05). RESULTS: On day 14, animal weight loss recovery was lowest in I + P compared to I + QTP20 and I + QTP10 (p ≤ 0.01 for either). Cerebral edema was greatest in I + P, and only significantly decreased in I + QTP20 (p < 0.05). Both QTP doses similarly improved spatial learning by significantly reducing latency time and travel distance to target zones (p < 0.05). In probe memory trials, only I + QTP20 and not I + QTP10 significantly favored animal reaching or crossing into target zones (p < 0.05). CONCLUSION: Post-TBI QTP reduces brain edema and improves spatial learning and memory with a potential dose dependence impact benefiting memory up to 14 days. These data suggest an unanticipated QTP benefit following brain injury that should be specifically explored.

15.
Int J Mol Sci ; 25(10)2024 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-38791312

RESUMO

Glioblastomas (GBM) are the most common primary malignant brain tumors, comprising 2% of all cancers in adults. Their location and cellular and molecular heterogeneity, along with their highly infiltrative nature, make their treatment challenging. Recently, our research group reported promising results from a prospective phase II clinical trial involving allogeneic vaccination with dendritic cells (DCs). To date, six out of the thirty-seven reported cases remain alive without tumor recurrence. In this study, we focused on the characterization of infiltrating immune cells observed at the time of surgical resection. An analytical model employing a neural network-based predictive algorithm was used to ascertain the potential prognostic implications of immunological variables on patients' overall survival. Counterintuitively, immune phenotyping of tumor-associated macrophages (TAMs) has revealed the extracellular marker PD-L1 to be a positive predictor of overall survival. In contrast, the elevated expression of CD86 within this cellular subset emerged as a negative prognostic indicator. Fundamentally, the neural network algorithm outlined here allows a prediction of the responsiveness of patients undergoing dendritic cell vaccination in terms of overall survival based on clinical parameters and the profile of infiltrated TAMs observed at the time of tumor excision.


Assuntos
Neoplasias Encefálicas , Células Dendríticas , Glioblastoma , Imunoterapia , Humanos , Células Dendríticas/imunologia , Glioblastoma/terapia , Glioblastoma/imunologia , Glioblastoma/mortalidade , Glioblastoma/patologia , Imunoterapia/métodos , Neoplasias Encefálicas/imunologia , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/patologia , Masculino , Feminino , Pessoa de Meia-Idade , Antígeno B7-H1/metabolismo , Prognóstico , Adulto , Macrófagos Associados a Tumor/imunologia , Macrófagos Associados a Tumor/metabolismo , Idoso , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/metabolismo
16.
J Parkinsons Dis ; 14(4): 681-692, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38578903

RESUMO

Background: Alpha-synuclein (aSyn) is a key player in neurodegenerative diseases such as Parkinson's disease (PD), dementia with Lewy bodies, or multiple system atrophy. aSyn is expressed throughout the brain, and can also be detected in various peripheral tissues. In fact, initial symptoms of PD are non-motoric and include autonomic dysfunction, suggesting that the periphery might play an important role in early development of the disease. aSyn is expressed at relatively low levels in non-central tissues, which brings challenges for its detection and quantification in different tissues. Objective: Our goal was to assess the sensitivity of aSyn detection in central and peripheral mouse tissues through capillary electrophoresis (CE) immunoblot, considering the traditional SDS-PAGE immunoblot as the current standard. Methods: Tissues from central and non-central origin from wild type mice were extracted, and included midbrain, inner ear, and esophagus/stomach. aSyn detection was assessed through immunoblotting using Simple Western size-based CE and SDS-PAGE. Results: CE immunoblots show a consistent detection of aSyn in central and peripheral tissues. Through SDS-PAGE, immunoblots revealed a reliable signal corresponding to aSyn, particularly following membrane fixation. Conclusion: Our results suggest a reliable detection of aSyn in central and peripheral tissues using the CE Simple Western immunoblot system. These observations can serve as preliminary datasets when aiming to formally compare CE with SDS-PAGE, as well as for further characterization of aSyn using this technique.


Assuntos
Eletroforese Capilar , alfa-Sinucleína , Animais , alfa-Sinucleína/metabolismo , alfa-Sinucleína/análise , Camundongos , Eletroforese Capilar/métodos , Camundongos Endogâmicos C57BL , Immunoblotting/métodos , Esôfago/metabolismo , Mesencéfalo/metabolismo
17.
J Bacteriol ; 206(4): e0045223, 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38551342

RESUMO

The wobble bases of tRNAs that decode split codons are often heavily modified. In bacteria, tRNAGlu, Gln, Asp contains a variety of xnm5s2U derivatives. The synthesis pathway for these modifications is complex and fully elucidated only in a handful of organisms, including the Gram-negative Escherichia coli K12 model. Despite the ubiquitous presence of mnm5s2U modification, genomic analysis shows the absence of mnmC orthologous genes, suggesting the occurrence of alternate biosynthetic schemes for the conversion of cmnm5s2U to mnm5s2U. Using a combination of comparative genomics and genetic studies, a member of the YtqA subgroup of the radical Sam superfamily was found to be involved in the synthesis of mnm5s2U in both Bacillus subtilis and Streptococcus mutans. This protein, renamed MnmL, is encoded in an operon with the recently discovered MnmM methylase involved in the methylation of the pathway intermediate nm5s2U into mnm5s2U in B. subtilis. Analysis of tRNA modifications of both S. mutans and Streptococcus pneumoniae shows that growth conditions and genetic backgrounds influence the ratios of pathway intermediates owing to regulatory loops that are not yet understood. The MnmLM pathway is widespread along the bacterial tree, with some phyla, such as Bacilli, relying exclusively on these two enzymes. Although mechanistic details of these newly discovered components are not fully resolved, the occurrence of fusion proteins, alternate arrangements of biosynthetic components, and loss of biosynthetic branches provide examples of biosynthetic diversity to retain a conserved tRNA modification in Nature.IMPORTANCEThe xnm5s2U modifications found in several tRNAs at the wobble base position are widespread in bacteria where they have an important role in decoding efficiency and accuracy. This work identifies a novel enzyme (MnmL) that is a member of a subgroup of the very versatile radical SAM superfamily and is involved in the synthesis of mnm5s2U in several Gram-positive bacteria, including human pathogens. This is another novel example of a non-orthologous displacement in the field of tRNA modification synthesis, showing how different solutions evolve to retain U34 tRNA modifications.


Assuntos
Escherichia coli K12 , RNA de Transferência , Humanos , RNA de Transferência/genética , Escherichia coli K12/genética , Bactérias/genética , Metilação , Bactérias Gram-Positivas/genética
18.
Neurocrit Care ; 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38443709

RESUMO

BACKGROUND: Early posttraumatic brain injury (TBI) tranexamic acid (TXA) may reduce blood-brain barrier (BBB) permeability, but it is unclear if this effect is fixed regardless of dose. We hypothesized that post-TBI TXA demonstrates a dose-dependent reduction of in vivo penumbral leukocyte mobilization, BBB microvascular permeability, and enhancement of neuroclinical recovery. METHODS: CD1 male mice (n = 40) were randomly assigned to TBI by controlled cortical impact (injury [I]) or sham TBI (S), followed by intravenous bolus of either saline (placebo [P]) or TXA (15, 30, or 60 mg/kg). At 48 h, in vivo pial intravital microscopy visualized live penumbral BBB microvascular leukocytes and albumin leakage. Neuroclinical recovery was assessed by Garcia Neurological Test scores and animal weight changes at 24 h and 48 h after injury. RESULTS: I + TXA60 reduced live penumbral leukocyte rolling compared with I + P (p < 0.001) and both lower TXA doses (p = 0.017 vs. I + TXA15, p = 0.012 vs. I + TXA30). Leukocyte adhesion was infrequent and similar across groups. Only I + TXA60 significantly reduced BBB permeability compared with that in the I + P (p = 0.004) group. All TXA doses improved Garcia Test scores relative to I + P at both 24 h and 48 h (p < 0.001 vs. I + P for all at both time points). Mean 24-h body weight loss was greatest in the I + P (- 8.7 ± 1.3%) group and lowest in the I + TXA15 (- 4.4 ± 1.0%, p = 0.051 vs. I + P) group. CONCLUSIONS: Only higher TXA dosing definitively abrogates penumbral leukocyte mobilization, preserving BBB integrity post TBI. Some neuroclinical recovery is observed, even with lower TXA dosing. Better outcomes with higher dose TXA after TBI may occur secondary to blunting of leukocyte-mediated penumbral cerebrovascular inflammation.

19.
BMC Musculoskelet Disord ; 25(1): 172, 2024 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-38402150

RESUMO

OBJECTIVE: To analyze the effects of using foam roller on pain intensity in individuals with chronic and acute musculoskeletal pain. METHODS: This systematic review was registered in the National Institute for Health Research's prospective online registry of systematic reviews (PROSPERO) under CRD42023456841. The databases Pubmed, Medline (via Ovid), Embase, BVS, and PEDro (Physiotherapy Evidence Database) were consulted to carry out this systematic review. Notably, the records of clinical trials characterized as eligible were manually searched. The search terms were: (foam rolling OR foam rolling vibration) AND (acute musculoskeletal pain) AND (chronic musculoskeletal pain). The search was performed until August 22, 2023. For the analysis of the methodological quality, the PEDro scale was used for each of the manuscripts included in the systematic review. Due to the heterogeneity in the studies included in this systematic review, performing a meta-analysis of the analyzed variables was impossible. RESULTS: Only six manuscripts were eligible for data analysis. The type of FR used was non-vibrational, being applied by a therapist in only one of the manuscripts. With an application time ranging from at least 45 s to 15 min, the non-vibrational FR was applied within a day up to six weeks. Using the PEDro scale, scores were assigned that varied between 4 and 8 points, with an average of 6 ± 1.29 points. Only two randomized clinical trials found a significant benefit in pain intensity of adding FR associated with a therapeutic exercise protocol in individuals with patellofemoral pain syndrome and chronic neck pain. CONCLUSION: The results of this systematic review do not elucidate or reinforce the clinical use of FR in pain intensity in individuals with chronic and acute musculoskeletal pain.


Assuntos
Dor Aguda , Dor Crônica , Dor Musculoesquelética , Humanos , Dor Musculoesquelética/diagnóstico , Dor Musculoesquelética/terapia , Medição da Dor , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Revisões Sistemáticas como Assunto , Dor Aguda/diagnóstico , Dor Aguda/terapia , Dor Crônica/diagnóstico , Dor Crônica/terapia
20.
Cureus ; 16(2): e53367, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38314392

RESUMO

Introduction  Environmental sustainability (ES) is a current issue related to natural resource scarcity, pollution and climate change. Although operating rooms (ORs) comprise a small proportion of the entire hospital infrastructure, they significantly impact the environment. Anesthesiologists are ideally positioned to assume leadership, mitigating this negative impact regarding OR waste in the environment. We created a Green Team, comprising multidisciplinary professionals from different areas of a tertiary Portuguese medical center, and conducted a survey that was sent to all the institution's anesthesiologists to assess the current state of ES. Results  From the sample of 133 participants, 101 responses were obtained. Concerning knowledge and training on ES, a significant portion of the respondents (66.7%) seem to attribute "great importance" to the subject. As to the greatest barrier to waste separation in the OR, several respondents highlighted the issues of "inadequate information/education/training" (62.6%) and "lack of support from hospital/OR in-chief/administration" (26.3%). Finally, among seven methods to raise awareness of ES, "training during residency" was the top choice for these professionals, with 52.5% of the votes. Discussion  Most anesthesiologists who responded to the survey recognize the utmost importance of ES and have perceived the environmental impact of their anesthetic practices in the OR. Overall, this tendency is consistent with other international studies. Moreover, most of those surveyed separate waste at home and want to extend this practice -in a more structured approach- to their workplace, with an effective separation of anesthetic and general waste in the OR. Conclusion Professionals perceive barriers to performing green practices, whether the lack of environmental education and awareness, the absence of recycling containers or waste separation bags, or the lack of protocols and guidelines implementing these circuits. With the publication of this work, we aim to encourage other institutions to implement ES projects in their hospitals and ORs.

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