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1.
Orthop J Sports Med ; 12(5): 23259671241243345, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38708007

RESUMO

Background: Hamstring strains are common among elite athletes, but their effect on return to the same level of play in American football has been incompletely characterized. Purpose: Data on National Collegiate Athletics Association Division I college football players with acute hamstring strains were gathered to identify the effects these injuries have on both return to play and athletic performance regarding velocity, workload, and acceleration. Study Design: Case Series; Level of evidence, 4. Methods: Injury data for a single Division I football team were prospectively recorded over a 4-year period. Players wore global navigation satellite system and local positioning system (GNSS/LPS) devices to record movement data in practices and games. The practice and game data were cross-referenced to evaluate players with isolated acute hamstring strains. Comparisons were made regarding players' pre- and postinjury ability to maintain high velocity (>12 mph [19.3 kph]), maximal velocity, triaxial acceleration, and inertial movement analysis (IMA). There were 58 hamstring injuries in 44 players, of which 25 injuries from 20 players had GNSS/LPS data. Results: Players were able to return to play from all 25 injury incidences at a mean of 9.2 days. At the final mean follow-up of 425 days, only 4 players had reached preinjury function in all measurements; 12 players were able to return in 2 of the 4 metrics; and only 8 players reached their preinjury ability to maintain high velocity. For those who did not achieve this metric, there was a significant difference between pre- and postinjury values (722 vs 442 m; P = .016). A total of 14 players were able to regain their IMA. Players who returned to prior velocity or acceleration metrics did so at a mean of 163 days across all metrics. Conclusion: While players may be able to return to play after hamstring strain, many players do not reach preinjury levels of acceleration or velocity, even after 13.5 months. Further studies are needed to confirm these findings, assess clinical relevance on imaging performance, and improve hamstring injury prevention and rehabilitation.

2.
Mol Pharm ; 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38709860

RESUMO

The dramatic effectiveness of recent mRNA (mRNA)-based COVID vaccines delivered in lipid nanoparticles has highlighted the promise of mRNA therapeutics in general. In this report, we extend our earlier work on self-amplifying mRNAs delivered in spherical in vitro reconstituted virus-like particles (VLPs), and on drug delivery using cylindrical virus particles. In particular, we carry out separate in vitro assemblies of a self-amplifying mRNA gene in two different virus-like particles: one spherical, formed with the capsid protein of cowpea chlorotic mottle virus (CCMV), and the other cylindrical, formed from the capsid protein of tobacco mosaic virus (TMV). The mRNA gene is rendered self-amplifying by genetically fusing it to the RNA-dependent RNA polymerase (RdRp) of Nodamura virus, and the relative efficacies of cell uptake and downstream protein expression resulting from their CCMV- and TMV-packaged forms are compared directly. This comparison is carried out by their transfections into cells in culture: expressions of two self-amplifying genes, enhanced yellow fluorescent protein (EYFP) and Renilla luciferase (Luc), packaged alternately in CCMV and TMV VLPs, are quantified by fluorescence and chemiluminescence levels, respectively, and relative numbers of the delivered mRNAs are measured by quantitative real-time PCR. The cellular uptake of both forms of these VLPs is further confirmed by confocal microscopy of transfected cells. Finally, VLP-mediated delivery of the self-amplifying-mRNA in mice following footpad injection is shown by in vivo fluorescence imaging to result in robust expression of EYFP in the draining lymph nodes, suggesting the potential of these plant virus-like particles as a promising mRNA gene and vaccine delivery modality. These results establish that both CCMV and TMV VLPs can deliver their in vitro packaged mRNA genes to immune cells and that their self-amplifying forms significantly enhance in situ expression. Choice of one VLP (CCMV or TMV) over the other will depend on which geometry of nucleocapsid is self-assembled more efficiently for a given length and sequence of RNA, and suggests that these plant VLP gene delivery systems will prove useful in a wide variety of medical applications, both preventive and therapeutic.

3.
Ann Surg ; 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38726665

RESUMO

OBJECTIVE: Despite politically charged media coverage and legislation surrounding gender affirming care (GAC), many organizations have released position statements to provide scientifically backed clinical practice standards, combat misinformation, and inform medicolegal policies. The purpose of this study is to objectively assess the availability and the content of the official position statements of relevant medical professional organizations regarding GAC. SUMMARY BACKGROUND DATA: A list of U.S. medical professional organizations with likely involvement in GAC based on medical or surgical specialties was compiled. METHODS: For included organizations, we evaluated the availability, content, and publication year of positions on GAC through October 2023. When available, formal positions were categorized as supportive or unsupportive. RESULTS: A total of 314 professional medical organizations were screened for our study based on specialty, relevance to GAC, and issuance of patient guidelines or position statements. Inclusion criteria were met by 55 organizations. Most organizations (35, 63.6%) had formal position statements on GAC. Support for GAC was described in 97.1% (n=34). Further, 94.2% (n=33) of available statements explicitly addressed GAC in individuals less than 18 years old and were largely supportive (96.9%, n=32). CONCLUSIONS: This cross-sectional analysis demonstrates that a majority of multidisciplinary professional medical organizations with relevance to GAC have issued formal position statements on the topic. Available positions were overwhelmingly supportive of individualized access to gender-affirming therapies in adult and adolescent populations. However, silence from some organizations continues to represent a modifiable disparity in the provision of GAC.

4.
Ann Plast Surg ; 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38717157

RESUMO

BACKGROUND: Despite growing demand for gender-affirming surgery (GAS), there are few formal GAS fellowships in the United States. Paucity of online information about GAS fellowships may discourage potential applicants and decrease the visibility of the field. Thus, it is important to analyze the existing online information about GAS fellowships to improve fellow recruitment and patient outcomes. OBJECTIVE: To identify the number of GAS fellowship websites (GASFWs) and evaluate their robustness. Second, to report the social media presence of GAS fellowships. METHODS: To identify GASFWs, existing databases sponsored by plastic surgery associations and Google query were used between April and May 2023. Thirty-five independent variables based on previously published data were evaluated for presence in a bivariate fashion on GASFWs. Accounts on popular social media websites were also identified by Google query. Website and social media analysis were also done for GAS fellowships that were offered by departments/specialties other than plastic surgery. RESULTS: In total, only 6 GASFWs associated with plastic surgery departments were identified and analyzed. Eight nonplastic surgery GASFWs were included for analysis. Overall, both categories of GASFWs were not robust; key information such as previous fellow listing and selection criteria was often missing. Furthermore, important topics specifically related to GAS such as community engagement and programmatic building are often not found on GASFWs either. In addition, none of the fellowships had any independent Facebook, Instagram, or Twitter. CONCLUSIONS: To ensure patient safety and quality outcomes, it is important to promote GAS by recruiting more applicants for specialized training beyond residency. With increased Internet use, improving GASFWs and social media presence as well as considering the use of a centralized database or match system can foster the growth of the field.

5.
ChemMedChem ; : e202400262, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38718280

RESUMO

Quaternary ammonium compound (QAC) disinfectants represent one of our first lines of defense against pathogens. Their killing activities are usually tested through minimum inhibitory concentration (MIC) and time-kill assays, but these assays can become cumbersome when screening compounds. We investigated how the dynamic surface tension (DST) measurements of QACs correlate with these antimicrobial activities by testing a panel of potent and structurally varied QACs against the gram-positive Staphylococcus aureus and the gram-negative Pseudomonas aeruginosa. We found that DST values correlated well with bactericidal activity in real-world disinfection conditions but not with MIC values. Moreover, no correlation between these two antimicrobial activities of QACs was observed. We also observed that the bactericidal activity of our QAC panel against the gram-negative P. aeruginosa was severely affected in the presence of hard water. Interestingly, we found that the counterion of the QAC affects the killing of bacteria in these conditions, a phenomenon not observed in most MIC assessments. Moreover, some of our best-in-class QACs show enhanced bactericidal activity when combined with a commercially available QAC. In conclusion, we determined that DST can be used as a technique to screen for bactericidal activity of QACs in conditions that mimic real-world disinfection conditions.

6.
Nat Commun ; 15(1): 4537, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38806470

RESUMO

The multidrug efflux transporter EmrE from Escherichia coli requires anionic residues in the substrate binding pocket for coupling drug transport with the proton motive force. Here, we show how protonation of a single membrane embedded glutamate residue (Glu14) within the homodimer of EmrE modulates the structure and dynamics in an allosteric manner using NMR spectroscopy. The structure of EmrE in the Glu14 protonated state displays a partially occluded conformation that is inaccessible for drug binding by the presence of aromatic residues in the binding pocket. Deprotonation of a single Glu14 residue in one monomer induces an equilibrium shift toward the open state by altering its side chain position and that of a nearby tryptophan residue. This structural change promotes an open conformation that facilitates drug binding through a conformational selection mechanism and increases the binding affinity by approximately 2000-fold. The prevalence of proton-coupled exchange in efflux systems suggests a mechanism that may be shared in other antiporters where acid/base chemistry modulates access of drugs to the substrate binding pocket.


Assuntos
Antiporters , Proteínas de Escherichia coli , Escherichia coli , Proteínas de Escherichia coli/metabolismo , Proteínas de Escherichia coli/química , Proteínas de Escherichia coli/genética , Escherichia coli/metabolismo , Escherichia coli/genética , Antiporters/metabolismo , Antiporters/química , Antiporters/genética , Sítios de Ligação , Ligação Proteica , Prótons , Conformação Proteica , Espectroscopia de Ressonância Magnética , Ácido Glutâmico/metabolismo , Ácido Glutâmico/química , Modelos Moleculares
7.
Artigo em Inglês | MEDLINE | ID: mdl-38781026

RESUMO

BACKGROUND: Partial occlusion of the aorta is a resuscitation technique designed to maximize proximal perfusion while allowing a graduated amount of distal flow to reduce the ischemic sequelae associated with complete aortic occlusion. The pREBOA catheter affords the ability to titrate perfusion as hemodynamics allows, however, the impact of this new technology for REBOA on blood use and other resuscitative requirements is currently unknown. We hypothesize pREBOA's ability to provide partial occlusion, when appropriate, decreases overall resuscitative requirements when compared to ER-REBOA. METHODS: The entire AAST AORTA Registry was used to compare resuscitation requirements between all ER-REBOA and pREBOA. Unpaired t-tests were used to compare resuscitation strategies including packed red blood cells (PRBCs), fresh frozen plasma (FFP), platelets, cryoprecipitate, crystalloids, and need for pressors. RESULTS: When comparing ER-REBOA (n=800) use to pREBOA (n=155), initial patient presentations were similar except for age (44 vs 40 p=0.026) and rates of blunt injury (78.4% vs 78.7% p<0.010). Zone-1 occlusion was used less often in ER-REBOA (65.8 vs 71.7 p=0.046). Partial occlusion was performed in 85% of pREBOA compared to 11% in ER-REBOA (p<0.050). Vitals at the time of REBOA were worse in ER-REBOA, and received significantly more units of PRBCs, FFP, platelets, and liters of crystalloids than pREBOA (p<0.05). Rates of ARDS and septic shock were lower in pREBOA (p<0.05). CONCLUSION: When comparing pREBOA to ER-REBOA, there has been a rise in Zone-1 and partial occlusion. In our pilot analysis of the AORTA Registry, there was a reduction in administration of pRBC, FFP, platelets, and crystalloids. Though further prospective studies are required, this is the first to demonstrate an association between pREBOA, partial occlusion, and reduced blood use and resuscitative requirements.

8.
Lancet Oncol ; 25(5): e217-e224, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38697167

RESUMO

Caribbean small island developing states are becoming increasingly vulnerable to compounding disasters, prominently featuring climate-related hazards and pandemic diseases, which exacerbate existing barriers to cancer control in the region. We describe the complexities of cancer prevention and control efforts throughout the Caribbean small island developing states, including the unique challenges of people diagnosed with cancer in the region. We highlight potential solutions and strategies that concurrently address disaster adaptation and cancer control. Because Caribbean small island developing states are affected first and worst by the hazards of compounding disasters, the innovative solutions developed in the region are relevant for climate mitigation, disaster adaptation, and cancer control efforts globally. In the age of complex and cascading disaster scenarios, developing strategies to mitigate their effect on the cancer control continuum, and protecting the health and safety of people diagnosed with cancer from extreme events become increasingly urgent. The equitable development of such strategies relies on collaborative efforts among professionals whose diverse expertise from complementary fields infuses the local community perspective while focusing on implementing solutions.


Assuntos
Neoplasias , Humanos , Neoplasias/epidemiologia , Neoplasias/diagnóstico , Neoplasias/prevenção & controle , Região do Caribe/epidemiologia , Desastres , Planejamento em Desastres/organização & administração
9.
Int J Part Ther ; 11: 100008, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38757074

RESUMO

Purpose: Adenoid cystic carcinoma (ACC) is a rare malignancy accounting for 1% of all head and neck cancers. Treatment for ACC has its challenges and risks, yet few outcomes studies exist. We present long-term outcomes of patients with ACC of the head and neck treated with proton therapy (PT). Materials and Methods: Under an institutional review board-approved, single-institutional prospective outcomes registry, we reviewed the records of 56 patients with de novo, nonmetastatic ACC of the head and neck treated with PT with definitive (n = 9) or adjuvant PT (n = 47) from June 2007 to December 2021. The median dose to the primary site was 72.6 gray relative biological equivalent (range, 64-74.4) delivered as either once (n = 19) or twice (n = 37) daily treatments. Thirty patients received concurrent chemotherapy. Thirty-one patients received nodal radiation, 30 electively and 1 for nodal involvement. Results: With a median follow-up of 6.2 years (range, 0.9-14.7), the 5-year local-regional control (LRC), disease-free survival, cause-specific survival, and overall survival rates were 88%, 85%, 89%, and 89%, respectively. Intracranial extension (P = .003) and gross residual tumor (P = .0388) were factors associated with LRC rates. While the LRC rate for those with a gross total resection was 96%, those with subtotal resection or biopsy alone were 81% and 76%, respectively. The 5-year cumulative incidence of clinically significant grade ≥3 toxicity was 15%, and the crude incidence at the most recent follow-up was 23% (n = 13). Conclusion: This is the largest sample size with the longest median follow-up to date of patients with ACC treated with PT. PT can provide excellent disease control for ACC of the head and neck with acceptable toxicity. T4 disease, intracranial involvement, and gross residual disease at the time of PT following either biopsy or subtotal resection were significant prognostic features for worse outcomes.

11.
JAMA Cardiol ; 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38748444

RESUMO

Importance: Prior cross-sectional studies have suggested that very high levels of physical activity (PA) are associated with a higher prevalence of coronary artery calcium (CAC). However, less is known regarding the association between high-volume PA and progression of CAC over time. Objective: To explore the association between PA (measured at baseline and during follow-up) and the progression of CAC over time. Design, Setting, and Participants: This cohort study included data from 8771 apparently healthy men and women 40 years and older who had multiple preventive medicine visits at the Cooper Clinic (Dallas, Texas), with a mean (SD) follow-up time of 7.8 (4.7) years between the first and last clinic visit. Participants with reported PA and CAC measurements at each visit during 1998 to 2019 were included in the study. Data were analyzed from March 2023 to February 2024. Exposures: PA reported at baseline and follow-up, examined continuously per 500 metabolic equivalent of task minutes per week (MET-min/wk) and categorically: less than 1500, 1500 to 2999, 3000 or more MET-min/wk. Main Outcomes and Measures: Negative binomial regression was used to estimate the rate of mean CAC progression between visits, with potential modification by PA volume, calculated as the mean of PA at baseline and follow-up. In addition, proportional hazards regression was used to estimate hazard ratios for baseline PA as a predictor of CAC progression to 100 or more Agatston units (AU). Results: Among 8771 participants, the mean (SD) age at baseline was 50.2 (7.3) years for men and 51.1 (7.3) years for women. The rate of mean CAC progression per year from baseline was 28.5% in men and 32.1% in women, independent of mean PA during the same time period. That is, the difference in the rate of CAC progression per year was 0.0% per 500 MET-min/wk for men and women (men: 95% CI, -0.1% to 0.1%; women: 95% CI, -0.4% to 0.5%). Moreover, baseline PA was not associated with CAC progression to a clinically meaningful threshold of 100 AU or more over the follow-up period. The hazard ratio for a baseline PA value of 3000 or more MET-min/wk vs less than 1500 MET-min/wk to cross this threshold was 0.84 (95% CI, 0.66 to 1.08) in men and 1.16 (95% CI, 0.57 to 2.35) in women. Conclusions and Relevance: This study found that PA volume was not associated with progression of CAC in a large cohort of healthy men and women who were initially free of overt cardiovascular disease.

12.
J Arthroplasty ; 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38734327

RESUMO

INTRODUCTION: Cobalt-chromium-molybdenum (CoCrMo) and titanium alloys have been used for orthopaedic implants for decades. However, recent evidence has shown that inflammatory cell-induced corrosion (ICIC) can damage these metal alloys. This study aimed to investigate the mechanisms of ICIC by co-culturing macrophages with lymphocytes. We hypothesized that macrophages would be able to alter the surface oxide layer of CoCrMo and titanium alloy (Ti6Al4V) disks, with greater oxide layer damage occurring in groups with a co-culture compared to a macrophage monoculture and in groups with inflammatory activators compared to nonactivated groups. METHODS: Murine macrophages were cultured on American Society for Testing and Materials (ASTM) F1537 CoCrMo and ASTM F136 Ti6Al4V disks for 30 days and activated with interferon gamma and lipopolysaccharide. Interferon gamma and lipopolysaccharide were added to the culture medium to simulate local inflammation. Macrophages were either cultured alone or in a co-culture with T helper lymphocytes. After the 30-day experiment, scanning electron microscopy was used to examine the disk surfaces, and oxide levels were found using energy dispersive x-ray spectroscopy. RESULTS: Pitting features consistent with previous reports of ICIC were found on disks cultured with cells. Both CoCrMo and Ti6Al4V disks had significantly lower oxide levels in all groups with cells compared to control groups with no cells (P < 0.01). Additionally, CoCrMo disks had significantly lower oxide levels when cultured with activated macrophages and lymphocytes compared to nonactivated macrophages alone (P < 0.001), activated macrophages alone (P < 0.01), and nonactivated macrophages and lymphocytes (P < 0.05). No differences in the oxide levels were found among the Ti6Al4V groups. CONCLUSION: This study demonstrates the ability of macrophages to alter the surface chemistry of commonly used orthopaedic alloys. We found that the addition of lymphocytes and a simulated local inflammatory response may contribute to the ICIC of CoCrMo implants.

13.
Chem ; 10(2): 713-729, 2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38738169

RESUMO

Optoacoustic imaging has grown in clinical relevance due to inherent advantages in sensitivity, resolution, and imaging depth, but the development of contrast agents is lacking. This study assesses the influence of structural features of squaraine dyes on optoacoustic activity through computational models, in vitro testing, and in vivo experimentation. The squaraine scaffold was decorated with halogens and side-chain extensions. Extension of side chains and heavy halogenation of squaraines both increased optoacoustic signals individually, although they had a more significant effect in tandem. Density functional theory models suggest that the origin of the increased optoacoustic signal is the increase in transition dipole moment and vibrational entropy, which manifested as increased absorbance in near-infrared region (NIR) wavelengths and decreased fluorescence quantum yield. This study provides insight into the structure-function relationships that will lead guiding principles for optimizing optoacoustic contrast agents. Further developments of squaraines and other agents will further increase the relevance of optoacoustic imaging in a clinical setting.

14.
bioRxiv ; 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38712123

RESUMO

Chronic spinal cord injury (SCI) lesions retain increased densities of microglia and macrophages. In acute SCI, macrophages induce growth cone collapse, facilitate axon retraction away from lesion boundaries, as well as play a key role in orchestrating the growth-inhibitory glial scar. Little is known about the role of sustained inflammation in chronic SCI, or whether chronic inflammation affects repair and regeneration. We performed transcriptional analysis using the Nanostring Neuropathology panel to characterize the resolution of inflammation into chronic SCI, to characterize the chronic SCI microenvironment, as well as to identify spinal cord responses to macrophage depletion and repopulation using the CSF1R inhibitor, PLX-5622. We determined the ability for macrophage depletion and repopulation to augment axon growth into chronic lesions both with and without regenerative stimulation using neuronal-specific PTEN knockout (PTEN-KO). PTEN-KO was delivered with spinal injections of retrogradely transported adeno associated viruses (AAVrg's). Both transcriptional analyses and immunohistochemistry revealed the ability for PLX-5622 to significantly deplete inflammation around and within chronic SCI lesions, with a return to pre-depleted inflammatory densities after treatment removal. Neuronal-specific transcripts were significantly elevated in mice after inflammatory repopulation, but no significant effects were observed with macrophage depletion alone. Axon densities significantly increased within the lesion after PLX-5622 treatment with a more consistent effect observed in mice with inflammatory repopulation. PTEN-KO did not further increase axon densities within the lesion beyond effects induced by PLX-5622. We identified that PLX-5622 increased axon densities within the lesion that are histologically identified as 5-HT+and CGRP+, both of which are not robustly transduced by AAVrg's. Our work identified that increased macrophage/microglia densities in the chronic SCI environment may be actively retained by homeostatic mechanisms likely affiliated with a sustained elevated expression of CSF1 and other chemokines. Finally, we identify a novel role of sustained inflammation as a prospective barrier to axon regeneration in chronic SCI.

15.
bioRxiv ; 2024 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-38712233

RESUMO

Myofibroblast differentiation, essential for driving extracellular matrix synthesis in pulmonary fibrosis, requires increased glycolysis. While glycolytic cells must export lactate, the contributions of lactate transporters to myofibroblast differentiation are unknown. In this study, we investigated how MCT1 and MCT4, key lactate transporters, influence myofibroblast differentiation and experimental pulmonary fibrosis. Our findings reveal that inhibiting MCT1 or MCT4 reduces TGFß-stimulated pulmonary myofibroblast differentiation in vitro and decreases bleomycin-induced pulmonary fibrosis in vivo. Through comprehensive metabolic analyses, including bioenergetics, stable isotope tracing, metabolomics, and imaging mass spectrometry in both cells and mice, we demonstrate that inhibiting lactate transport enhances oxidative phosphorylation, reduces reactive oxygen species production, and diminishes glucose metabolite incorporation into fibrotic lung regions. Furthermore, we introduce VB253, a novel MCT4 inhibitor, which ameliorates pulmonary fibrosis in both young and aged mice, with comparable efficacy to established antifibrotic therapies. These results underscore the necessity of lactate transport for myofibroblast differentiation, identify MCT1 and MCT4 as promising pharmacologic targets in pulmonary fibrosis, and support further evaluation of lactate transport inhibitors for patients for whom limited therapeutic options currently exist.

16.
medRxiv ; 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38699354

RESUMO

During the ongoing western equine encephalitis virus (WEEV) outbreak in South America, we described three fatal cases in horses from Rio Grande do Sul, Brazil. We sequenced WEEV strains and identified a novel lineage causing these cases. Continued surveillance and horse immunization are needed to mitigate the WEEV burden.

17.
Epigenetics ; 19(1): 2349980, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38716804

RESUMO

While epigenomic alterations are common in colorectal cancers (CRC), few epigenomic biomarkers that risk-stratify patients have been identified. We thus sought to determine the potential of ZNF331 promoter hypermethylation (mZNF331) as a prognostic and predictive marker in colon cancer. We examined the association of mZNF331 with clinicopathologic features, relapse, survival, and treatment efficacy in patients with stage III colon cancer treated within a randomized adjuvant chemotherapy trial (CALGB/Alliance89803). Residual tumour tissue was available for genomic DNA extraction and methylation analysis for 385 patients. ZNF331 promoter methylation status was determined by bisulphite conversion and fluorescence-based real-time polymerase chain reaction. Kaplan-Meier estimator and Cox proportional hazard models were used to assess the prognostic and predictive role of mZNF331 in this well-annotated dataset, adjusting for clinicopathologic features and standard molecular markers. mZNF331 was observed in 267/385 (69.4%) evaluable cases. Histopathologic features were largely similar between patients with mZNF331 compared to unmethylated ZNF331 (unmZNFF31). There was no significant difference in disease-free or overall survival between patients with mZNF331 versus unmZNF331 colon cancers, even when adjusting for clinicopathologic features and molecular marker status. Similarly, there was no difference in disease-free or overall survival across treatment arms when stratified by ZNF331 methylation status. While ZNF331 promoter hypermethylation is frequently observed in CRC, our current study of a small subset of patients with stage III colon cancer suggests limited applicability as a prognostic marker. Larger studies may provide more insight and clarity into the applicability of mZNF331 as a prognostic and predictive marker.


Assuntos
Biomarcadores Tumorais , Neoplasias do Colo , Metilação de DNA , Regiões Promotoras Genéticas , Humanos , Feminino , Neoplasias do Colo/genética , Neoplasias do Colo/patologia , Masculino , Pessoa de Meia-Idade , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Idoso , Prognóstico , Estadiamento de Neoplasias , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Adulto , Fator Trefoil-3
18.
Motor Control ; : 1-21, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38702047

RESUMO

The aim of this study was to examine the effect of attentional focus instructions on the biomechanical variables associated with the risk of anterior cruciate ligament injury of the knee joint during a drop landing task using a time series analysis. Ten female volleyball players (age: 20.4 ± 0.8 years, height: 169.7 ± 7.1 cm, mass: 57.6 ± 3.1 kg, experience: 6.3 ± 0.8 years) performed landings from a 50 cm height under three different attentional focus conditions: (1) external focus (focus on landing as soft as possible), (2) internal focus (focus on bending your knees when you land), and (3) control (no-focus instruction). Statistical parameter mapping in the sagittal plane during the crucial first 30% of landing time showed a significant effect of attentional focus instructions. Despite the similarity in landing performance across foci instructions, adopting an external focus instruction promoted reduced vertical ground reaction force and lower sagittal flexion moment during the first 30% of execution time compared to internal focus, suggesting reduced knee loading. Therefore, adopting an external focus of attention was suggested to reduce most biomechanical risk variables in the sagittal plane associated with anterior cruciate ligament injuries, compared to internal focus and control condition. No significant differences were found in the frontal and horizontal planes between the conditions during this crucial interval.

19.
Environ Sci Technol ; 58(20): 9000-9012, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38710661

RESUMO

Additive manufacturing (AM) offers a variety of material manufacturing techniques for a wide range of applications across many industries. Most efforts at process optimization and exposure assessment for AM are centered around the manufacturing process. However, identifying the material allocation and potentially harmful exposures in end-of-life (EoL) management is equally crucial to mitigating environmental releases and occupational health impacts within the AM supply chain. This research tracks the allocation and potential releases of AM EoL materials within the US through a material flow analysis. Of the generated AM EoL materials, 58% are incinerated, 33% are landfilled, and 9% are recycled by weight. The generated data set was then used to examine the theoretical occupational hazards during AM EoL material management practices through generic exposure scenario assessment, highlighting the importance of ventilation and personal protective equipment at all stages of AM material management. This research identifies pollution sources, offering policymakers and stakeholders insights to shape pollution prevention and worker safety strategies within the US AM EoL management pathways.


Assuntos
Exposição Ocupacional , Humanos , Reciclagem
20.
Curr Issues Mol Biol ; 46(5): 4203-4233, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38785525

RESUMO

The global demand for sustainable and nutritious food sources has catalyzed interest in legumes, known for their rich repertoire of health-promoting compounds. This review delves into the diverse array of bioactive peptides, protein subunits, isoflavones, antinutritional factors, and saponins found in the primary legume protein sources-soybeans, peas, chickpeas, and mung beans. The current state of research on these compounds is critically evaluated, with an emphasis on the potential health benefits, ranging from antioxidant and anticancer properties to the management of chronic diseases such as diabetes and hypertension. The extensively studied soybean is highlighted and the relatively unexplored potential of other legumes is also included, pointing to a significant, underutilized resource for developing health-enhancing foods. The review advocates for future interdisciplinary research to further unravel the mechanisms of action of these bioactive compounds and to explore their synergistic effects. The ultimate goal is to leverage the full spectrum of benefits offered by legumes, not only to advance human health but also to contribute to the sustainability of food systems. By providing a comprehensive overview of the nutraceutical potential of legumes, this manuscript sets a foundation for future investigations aimed at optimizing the use of legumes in the global pursuit of health and nutritional security.

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