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1.
J Res Adolesc ; 2024 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-38698712

RESUMEN

The goals of this article are to (a) describe and contrast conceptual characteristics of periods of developmental sensitivity, disturbance, and stasis, and (b) translate these concepts to testable analytic models with an example dataset. Although the concept of developmental sensitivity is widely known, the concepts of developmental stasis and disturbance have received less attention. We first define the concepts and their principles and then, using repeated measures data on impulsivity and alcohol use from adolescence to young adulthood, propose the dual latent change score (LCS) growth model as one analytic approach for evaluating evidence for key characteristics of these developmental concepts via examination of intraindividual time-varying associations.

2.
Sleep ; 2024 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-38758702

RESUMEN

STUDY OBJECTIVES: We examined growth trajectories of four actigraphy-derived sleep parameters (sleep minutes, sleep efficiency, and variability in sleep minutes and efficiency across a week of assessments) across childhood and adolescence and examined individual differences in trajectories according to participants' race/ethnicity and sex. We also assessed the predictive effect of growth trajectories of sleep parameters on growth trajectories of mental health outcomes and moderation by race and sex. METHOD: Youth (N=199, 49% female, 65% White, 32% Black, 3% biracial) and their parents participated in five waves of data (M ages were 9, 10, 11, 17, and 18 across waves). Participants were from a diverse range of socioeconomic backgrounds. RESULTS: Across participants, sleep minutes, sleep efficiency, and variability in sleep minutes and efficiency demonstrated significant linear change across childhood and adolescence. Whereas sleep duration shortened over time, sleep efficiency improved. Youth exhibited increases in night-to-night variability in sleep minutes and reductions in night-to-night variability in sleep efficiency. Highlighting the importance of individual differences, some race- and sex-related effects emerged. Black youth and male youth experienced steeper declines in their sleep duration across development relative to their respective counterparts. Black youth also demonstrated smaller improvements in sleep efficiency and greater variability in sleep efficiency compared to White youth. Finally, trajectories of sleep efficiency and variability in sleep minutes predicted trajectories of internalizing symptoms and externalizing behaviors. CONCLUSIONS: Findings showed significant changes in developmental trajectories of four sleep parameters across childhood and adolescence. We discuss empirical and translational implications of the findings.

3.
Transl Anim Sci ; 8: txae034, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38562215

RESUMEN

The National Beef Quality Audit (NBQA) has been conducted regularly since 1991 to assess and benchmark quality in the U.S. beef industry, with the most recent iteration conducted in 2022. The goal of NBQA Phase I is to evaluate what needs to be managed to improve beef quality and demand. Interviews (n = 130) of industry personnel were conducted with the aid of routing software. In total, packers (n = 24), retailers (n = 20), further processors (n = 26), foodservice (n = 18), and allied government agencies and trade organizations (n = 42) were interviewed. Interviews were routed in software based on interviewee involvement in either the fed steer and heifer market cow and bull sectors, or both. Interviews were structured to elicit random responses in the order of determining "must-have" criteria (quality factors that are required to make a purchase), best/worst ranking (of quality factors based on importance), how interviewees defined quality terms, a strength, weakness, opportunities, threats (SWOT) analysis, general beef industry questions, and sustainability goals (the latter four being open-ended). Quality factors were 1) visual characteristics, 2) cattle genetics, 3) food safety, 4) eating satisfaction, 5) animal well-being, 6) weight and size, and 7) lean, fat, and bone. Best/worst analysis revealed that "food safety" was the most (P < 0.05) important factor in beef purchasing decisions for all market sectors and frequently was described as "everything" and "a way of business." Culture surrounding food safety changed compared to previous NBQAs with interviewees no longer considering food safety as a purchasing criterion, but rather as a market expectation. The SWOT analysis indicated that "eating quality of U.S. beef" was the greatest strength, and cited that educating both consumers and producers on beef production would benefit the industry. Irrespective of whether companies' products were fed or market cow/bull beef, respondents said that they believed "environmental concerns" were among the major threats to the industry. Perceived image of the beef industry in the market sectors has improved since NBQA-2016 for both fed cattle and market cow/bull beef.

4.
bioRxiv ; 2024 Mar 12.
Artículo en Inglés | MEDLINE | ID: mdl-38559188

RESUMEN

Systemic lupus erythematosus (SLE) is a highly heterogenous autoimmune disease that affects multiple organs, including the heart. The mechanisms by which myocardial injury develops in SLE, however, remain poorly understood. Here we engineered human cardiac tissues and cultured them with IgG fractions containing autoantibodies from SLE patients with and without myocardial involvement. We observed unique binding patterns of IgG from two patient subgroups: (i) patients with severe myocardial inflammation exhibited enhanced binding to apoptotic cells within cardiac tissues subjected to stress, and (ii) patients with systolic dysfunction exhibited enhanced binding to the surfaces of viable cardiomyocytes. Functional assays and RNA sequencing (RNA-seq) revealed that IgGs from patients with systolic dysfunction exerted direct effects on engineered tissues in the absence of immune cells, altering tissue cellular composition, respiration and calcium handling. Autoantibody target characterization by phage immunoprecipitation sequencing (PhIP-seq) confirmed distinctive IgG profiles between patient subgroups. By coupling IgG profiling with cell surface protein analyses, we identified four pathogenic autoantibody candidates that may directly alter the function of cells within the myocardium. Taken together, these observations provide insights into the cellular processes of myocardial injury in SLE that have the potential to improve patient risk stratification and inform the development of novel therapeutic strategies.

5.
Transl Anim Sci ; 8: txae033, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38616995

RESUMEN

The National Beef Quality Audit (NBQA)-2022 serves as a benchmark of the current market cow and bull sectors of the U.S. beef industry and allows comparison to previous audits as a method of monitoring industry progress. From September 2021 through May 2022, livestock trailers (n = 125), live animals (n = 5,430), and post-slaughter hide-on animals (n = 6,674) were surveyed at 20 commercial beef processing facilities across the U.S. Cattle were transported in a variety of trailer types for an average distance of 490.6 km and a mean transport time of 6.3 h. During transit, cattle averaged 2.3 m2 of trailer space per animal indicating sufficient space was provided according to industry guidelines. Of all trailers surveyed, 55.3% transported cattle from an auction barn to a processing facility. When surveyed, 63.6% of all truck drivers reported to be Beef Quality Assurance certified. The majority (77.0%) of cattle were sound when evaluated for mobility. Mean body condition scores (9-point scale) for beef cows and bulls were 3.8 and 4.4, respectively, whereas mean body condition scores (5-point scale) for dairy cows and bulls were 2.3 and 2.6, respectively. Of the cattle surveyed, 45.1% had no visible live animal defects, and 37.9% had only a single defect. Of defects present in cows, 64.6% were attributed to an udder problem. Full udders were observed in 47.5% of all cows. Nearly all cattle were free of visible abscesses and knots (97.9% and 98.2%, respectively). No horns were observed in 89.4% of all cattle surveyed. Beef cattle were predominantly black-hided (68.9% and 67.4% of cows and bulls, respectively). Holstein was the predominant dairy animal observed and accounted for 85.7% of the cows and 98.0% of the bulls. Only 3.1% of all animals had no form of identification. Findings from the NBQA-2022 show improvements within the industry and identify areas that require continued education and research to improve market cow and bull welfare and beef quality.

6.
J Forensic Sci ; 2024 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-38600623

RESUMEN

In forensic anthropology, osteological sex estimation methods are continuously reevaluated and updated to improve classification accuracies. Therefore, to gain a comprehensive understanding of recent trends in sex estimation research in forensic anthropology, a content analysis of articles published between 2000 and 2022 in Forensic Science International, the Journal of Forensic Sciences, the International Journal of Legal Medicine, the American Journal of Biological Anthropology, and Forensic Anthropology, was performed. The main goals of this content analysis were to (1) examine trends in metric versus morphological research, (2) examine which areas of the skeleton have been explored, (3) examine which skeletal collections and population affinities have been most frequently utilized, and (4) determine which statistical methods were commonly implemented. A total of 440 articles were coded utilizing MAXQDA and the resulting codes were exported for analysis. Statistical analyses were conducted utilizing the Cochran-Armitage and Jonckheere-Terpstra tests for trends, as well as Fisher-Freeman-Halton tests. The results demonstrate that sex estimation research published in these journals has prioritized metric over morphological methods. Further, the most utilized skeletal regions continue to be the skull and pelvis, while the most popular classification statistics continue to be discriminant function analysis and logistic regression. This study also demonstrates that a substantial portion of research has been conducted utilizing U.S. and Europe-based collections and limited populations. Based on these results, future sex estimation research must continue exploring the use of long bones and other postcranial elements, testing newer methods of analysis, as well as developing population-inclusive methods.

7.
bioRxiv ; 2024 Mar 31.
Artículo en Inglés | MEDLINE | ID: mdl-38585970

RESUMEN

Haemophilus parainfluenzae ( Hp ) is a Gram-negative, pleomorphic rod, highly prevalent and abundant as a commensal in the human oral cavity, and an infrequent extraoral opportunistic pathogen. Hp occupies multiple niches in the oral cavity, including the tongue dorsum, keratinized gingiva, and the supragingival plaque biofilm. As a member of the HACEK group, Hp is also known to cause infective endocarditis. Additionally, case reports have identified Hp as the causative agent of meningitis, septic arthritis, chronic osteomyelitis, septicemia, and a variety of other infectious diseases. Little is known about how Hp interacts with its neighbors in the healthy biofilm nor about its mechanisms of pathogenesis as an extraoral opportunistic pathogen. To address these unknowns, we identified the essential genomes of two Hp strains and the conditionally essential genes for their growth in in vitro biofilms aerobically and anaerobically. Using transposon insertion sequencing (TnSeq) with a highly saturated mariner transposon library in two strains, the ATCC33392 type-strain ( Hp 392) and a commensal oral isolate EL1 ( Hp EL1), we show that the essential genome of Hp 392 and Hp EL1 is composed of 395 and 384 genes, respectively. The core essential genome, consisting of 341 essential genes conserved between both strains, was composed of genes associated with genetic information processing, carbohydrate, protein, and energy metabolism. We also identified conditionally essential genes for aerobic and anaerobic biofilm growth, which were associated with carbohydrate and energy metabolism in both strains of Hp . Additionally, RNAseq analysis determined that most genes upregulated during anaerobic growth are not essential for Hp 392 anaerobic biofilm survival. The completion of this library and analysis under these conditions gives us a foundational insight into the basic biology of H. parainfluenzae in differing oxygen conditions, similar to its in vivo oral habitat. Further, the creation of this library presents a valuable tool for further investigation into conditionally essential genes for an organism that lives in close contact with many microbial species in the human oral habitat.

8.
Dev Psychol ; 2024 Apr 22.
Artículo en Inglés | MEDLINE | ID: mdl-38647472

RESUMEN

There is a well-documented interdependency between destructive interparental conflict (IPC) and parenting difficulties (i.e., spillover effect), yet little is known about the mechanisms that "carry" spillover between IPC and parenting. Guided by a cascade model framework, the current study used a longitudinal, multimethod, multi-informant design to examine a process model of spillover that tested whether parental executive functioning (working memory, cognitive flexibility, inhibitory control) served as a mediator of the prospective associations between IPC and subsequent changes in parenting over a 2-year period. Mothers and fathers were separated into differentiated models and multiple domains of parenting were examined (i.e., authoritarian discipline and scaffolding behavior). Participants included 231 families (both mothers and fathers of preschoolers). Race was reported as White (62%), Black (21%), Mixed (8%), Asian (3%), or Other (6%) and 14% considered their ethnicity to be Hispanic/Latino. Median household income was $65,000. Results indicated that for fathers, IPC indirectly predicted domain-general parenting difficulties (increased authoritarian parenting and decreased scaffolding) via deficits in paternal cognitive flexibility (but not inhibitory control or working memory). In mothers, IPC directly predicted domain-specific parenting difficulties (decreased scaffolding only) that did not operate via maternal executive functions. Notably, these effects occurred over and above the influence of parental socioeconomic status. This study constitutes a first step toward documenting parental executive functioning as a mechanism underlying the spillover of IPC to the parent-child relationship. Family interventions intended to interrupt IPC spillover should emphasize father involvement and consider targeting parental executive functions as change mechanisms. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

9.
Int J Biochem Cell Biol ; 170: 106568, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38518980

RESUMEN

Regulatory T cells, characterized by their expression of the transcription factor Forkhead box P3, are indispensable in maintaining immune homeostasis. The respiratory system is constantly exposed to many environmental challenges, making it susceptible to various insults and infections. Regulatory T cells play essential roles in maintaining homeostasis in the lung and promoting repair after injury. Regulatory T cell function dysregulation can lead to inflammation, tissue damage, or aberrant repair. Research on regulatory T cell mechanisms in the lung has unveiled their influence on lung inflammation and repair mechanisms. In this review, our goal is to highlight the advances in regulatory T cell biology with respect to lung injury and resolution. We further provide a perspective that a deeper understanding of regulatory T cell interactions in the lung microenvironment in health and disease states offers opportunities for therapeutic interventions as treatments to promote lung health.


Asunto(s)
Lesión Pulmonar , Humanos , Lesión Pulmonar/terapia , Linfocitos T Reguladores , Pulmón/metabolismo , Inflamación/metabolismo , Homeostasis , Factores de Transcripción Forkhead/metabolismo
10.
Head Neck ; 2024 Mar 03.
Artículo en Inglés | MEDLINE | ID: mdl-38433326

RESUMEN

BACKGROUND: The impact of both COVID-19 infection and vaccination status on patients with head and neck squamous cell carcinoma (HNSCC) remains unknown. OBJECTIVE: To determine the impact of COVID-19 infection and vaccination status on 60-day mortality, cardiovascular, and respiratory complications in patients with a prior diagnosis of HNSCC. METHODS: This was a retrospective cohort study through the Veterans Affairs (VA) Corporate Data Warehouse of Veterans with HNSCC who were tested for COVID-19 during any inpatient VA medical center admission. A cohort of patients was created of Veterans with a diagnosis of HNSCC of the oral cavity,oropharynx, hypopharynx, larynx, and nasopharynx based on International Classification of Disease (ICD) codes. Data collected included clinical/demographic data, vaccination status, and incidence of 60-day mortality, 60-day cardiovascular complication (including myocardial infarction, venous thromboembolism, cerebrovascular accident), and 60-day respiratory complication (including acute respiratory failure, acute respiratory distress syndrome, and pneumonia). The interactions between COVID-19 infection, vaccination status, morbidity and mortality were investigated. RESULTS: Of the 14 262 patients with HNSCC who were tested for COVID-19 during inpatient admission, 4754 tested positive (33.3%), and 9508 (67.7%) tested negative. Patients who tested positive demonstrated increased 60-day mortality (4.7% vs. 2.0%, respectively; p < 0.001), acute respiratory failure (ARF; 15.4% vs. 7.1%, p < 0.001), acute respiratory distress syndrome (ARDS; 0.9% vs. 0.2%, p < 0.001), and pneumonia (PNA; 20.0% vs. 6.4%, p < 0.001) compared to those who never tested positive, respectively. Patients who received COVID-19 vaccination between 2 weeks and 6 months prior to a positive test demonstrated decreased rates of ARF (13.2% vs. 16.0%, p = 0.034) and PNA (16.7% vs. 20.9%, p = 0.003) compared to the unvaccinated group. A logistic regression of patients with COVID-19 infections who died within 60 days was performed, with no significant survival advantage among patients vaccinated between 2 weeks and 6 months prior to the positive test. CONCLUSION: COVID-19 infection may significantly increase rates of 60-day mortality and respiratory complications in patients with HNSCC. COVID-19 vaccination between 2 weeks and 6 months prior to infection may decrease severity of respiratory complications but did not show significant mortality benefits in this study. These data highlight the need for surveillance of respiratory infection and vaccination in this vulnerable population.

11.
J Clin Virol ; 171: 105653, 2024 04.
Artículo en Inglés | MEDLINE | ID: mdl-38408420

RESUMEN

BACKGROUND: Developing countries experience limited access to HCV laboratory tests for different reasons. Providing near to real-time HCV testing and results especially to at-risk populations including those in rural settings for timely initiation to treatment is key. Within a rural Myanmar setting, we compared HCV diagnostic detection and quantification of the GeneXpert, and Advanced Biological Laboratories UltraGene-HCV assays against the gold standard and reference method Roche real-time HCV in Myanmar. METHODS: Blood samples from 158 high-risk individuals were assessed using three different methods at baseline. Results were checked for normality and log transformed. Log differences and bias between methods were calculated and correlated. Pearson's correlation coefficient was used to determine the association of HCV viral loads across all methods. The level of agreement with the standard method (Roche real time HCV) was assessed using Bland-Altman analyses. RESULTS: There was a strong positive correlation coefficient between all three methods with GeneXpert and Roche having the strongest, r = 0.96, (p<0.001). Compared to Roche, ABL (mean difference, 95 % limits of agreement; -0.063 and -1.4 to 1.3 Log10IU/mL) and GeneXpert (mean difference, 95 % limits of agreement; -0.28 and -0.7 to 1.8 Log10IU/mL) showed a good level of agreement with the GeneXpert being slightly superior. CONCLUSION: We demonstrate the excellent performance and no-inferiority, in terms of levels of agreements of both GeneXpert and ABL compared to the Roche platform and supporting the use of the POC assays as alternative a cost-effective methods in HCV detection and diagnosis in developing and low resource settings countries.


Asunto(s)
Hepatitis C , Laboratorios , Humanos , Reacción en Cadena en Tiempo Real de la Polimerasa , Sensibilidad y Especificidad , Mianmar , Carga Viral/métodos , Hepacivirus/genética , Hepatitis C/diagnóstico , ARN Viral/genética
12.
Proc Natl Acad Sci U S A ; 121(9): e2312587121, 2024 Feb 27.
Artículo en Inglés | MEDLINE | ID: mdl-38381785

RESUMEN

To ensure a robust immune response to pathogens without risking immunopathology, the kinetics and amplitude of inflammatory gene expression in macrophages need to be exquisitely well controlled. There is a growing appreciation for stress-responsive membraneless organelles (MLOs) regulating various steps of eukaryotic gene expression in response to extrinsic cues. Here, we implicate the nuclear paraspeckle, a highly ordered biomolecular condensate that nucleates on the Neat1 lncRNA, in tuning innate immune gene expression in murine macrophages. In response to a variety of innate agonists, macrophage paraspeckles rapidly aggregate (0.5 h poststimulation) and disaggregate (2 h poststimulation). Paraspeckle maintenance and aggregation require active transcription and MAPK signaling, whereas paraspeckle disaggregation requires degradation of Neat1 via the nuclear RNA exosome. In response to lipopolysaccharide treatment, Neat1 KO macrophages fail to properly express a large cohort of proinflammatory cytokines, chemokines, and antimicrobial mediators. Consequently, Neat1 KO macrophages cannot control replication of Salmonella enterica serovar Typhimurium or vesicular stomatitis virus. These findings highlight a prominent role for MLOs in orchestrating the macrophage response to pathogens and support a model whereby dynamic assembly and disassembly of paraspeckles reorganizes the nuclear landscape to enable inflammatory gene expression following innate stimuli.


Asunto(s)
Paraspeckles , ARN Largo no Codificante , Humanos , Animales , Ratones , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Macrófagos/metabolismo
13.
Cell Rep ; 43(3): 113816, 2024 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-38393946

RESUMEN

Tight regulation of macrophage immune gene expression is required to fight infection without risking harmful inflammation. The contribution of RNA-binding proteins (RBPs) to shaping the macrophage response to pathogens remains poorly understood. Transcriptomic analysis reveals that a member of the serine/arginine-rich (SR) family of mRNA processing factors, SRSF7, is required for optimal expression of a cohort of interferon-stimulated genes in macrophages. Using genetic and biochemical assays, we discover that in addition to its canonical role in regulating alternative splicing, SRSF7 drives transcription of interferon regulatory transcription factor 7 (IRF7) to promote antiviral immunity. At the Irf7 promoter, SRSF7 maximizes STAT1 transcription factor binding and RNA polymerase II elongation via cooperation with the H4K20me1 histone methyltransferase KMT5a (SET8). These studies define a role for an SR protein in activating transcription and reveal an RBP-chromatin network that orchestrates macrophage antiviral gene expression.


Asunto(s)
Interferón Tipo I , Humanos , Transcripción Genética , Regiones Promotoras Genéticas/genética , Macrófagos , Factores de Empalme de ARN , Empalme Alternativo/genética , Factores de Empalme Serina-Arginina/genética
14.
J Acoust Soc Am ; 155(2): 1437-1450, 2024 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-38364047

RESUMEN

Odontocetes produce clicks for echolocation and communication. Most odontocetes are thought to produce either broadband (BB) or narrowband high-frequency (NBHF) clicks. Here, we show that the click repertoire of Hector's dolphin (Cephalorhynchus hectori) comprises highly stereotypical NBHF clicks and far more variable broadband clicks, with some that are intermediate between these two categories. Both NBHF and broadband clicks were made in trains, buzzes, and burst-pulses. Most clicks within click trains were typical NBHF clicks, which had a median centroid frequency of 130.3 kHz (median -10 dB bandwidth = 29.8 kHz). Some, however, while having only marginally lower centroid frequency (median = 123.8 kHz), had significant energy below 100 kHz and approximately double the bandwidth (median -10 dB bandwidth = 69.8 kHz); we refer to these as broadband. Broadband clicks in buzzes and burst-pulses had lower median centroid frequencies (120.7 and 121.8 kHz, respectively) compared to NBHF buzzes and burst-pulses (129.5 and 130.3 kHz, respectively). Source levels of NBHF clicks, estimated by using a drone to measure ranges from a single hydrophone and by computing time-of-arrival differences at a vertical hydrophone array, ranged from 116 to 171 dB re 1 µPa at 1 m, whereas source levels of broadband clicks, obtained from array data only, ranged from 138 to 184 dB re 1 µPa at 1 m. Our findings challenge the grouping of toothed whales as either NBHF or broadband species.


Asunto(s)
Delfines , Ecolocación , Animales , Acústica , Vocalización Animal , Espectrografía del Sonido
15.
Forensic Sci Rev ; 36(1): 41-54, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38297426

RESUMEN

Advocates and researchers have made many recommendations for forensic science improvement in the United States. These proposals are often motivated by wrongful convictions related to false or misleading forensic evidence. In many cases, the connection between the proposals and the actual experience of wrongful convictions has not been well defined. Further, recommendations may not have been realizable given the structure of the criminal justice system in the United States and the practical realities of forensic science laboratories. Finally, limited attempts have been made to assess recommendations over time to determine the progress of forensic science improvement and elucidate continuing gaps. Reports from the Department of Justice, the National Academy of Sciences, and the President's Council of Advisors on Science and Technology are assessed to determine the extent to which their recommendations have been implemented, whether the recommendations align with the actual experience of wrongful convictions, and how the American forensic science community has implemented forensic science improvement. The most successful proposals reflect a broad movement toward quality assurance, improved standards, and organizational improvement in the forensic sciences. Less successful proposals are associated with calls for large federal investments, difficulties in community-wide implementation, or uncertain linkage to foundations in science and practice. Significant progress has been made in the standardization of reporting and testimony, assessment of the foundational reliability of the disciplines, and DNA mixture interpretation. Significant gaps remain to improve medicolegal death investigation, governance, and the implementation of standards. Improved allocation and use of resources will be required to meet continuing challenges in capacity building, training, and proficiency testing, although past experience indicates that both federal and non-federal funding will be required to address these issues. Continued improvement is needed to address the issues associated with wrongful convictions, although forensic science leaders have demonstrated the ability to prioritize improvement initiatives.


Asunto(s)
Ciencias Forenses , Aplicación de la Ley , Humanos , Estados Unidos , Reproducibilidad de los Resultados , Ciencias Forenses/educación , ADN , Incertidumbre
16.
Immunol Cell Biol ; 102(3): 211-224, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38288547

RESUMEN

CD4+ forkhead box P3 (FOXP3)+ regulatory T cells (Tregs) are essential in maintaining immune tolerance and suppressing excessive immune responses. Tregs also contribute to tissue repair processes distinct from their roles in immune suppression. For these reasons, Tregs are candidates for targeted therapies for inflammatory and autoimmune diseases, and in diseases where tissue damage occurs. MT-2 cells, an immortalized Treg-like cell line, offer a model to study Treg biology and their therapeutic potential. In the present study, we use clustered regularly interspaced palindromic repeats (CRISPR)-mediated knockdown of FOXP3 in MT-2 cells to understand the transcriptional and functional changes that occur when FOXP3 is lost and to compare MT-2 cells with primary human Tregs. We demonstrate that loss of FOXP3 affects the transcriptome of MT-2 cells and that FOXP3's potential downstream targets include a wide range of transcripts that participate in the cell cycle, promote growth and contribute to inflammatory processes, but do not wholly simulate previously reported human primary Treg transcriptional changes in the absence of FOXP3. We also demonstrate that FOXP3 regulates cell cycling and proliferation, expression of molecules crucial to Treg function and MT-2 cell-suppressive activities. Thus, MT-2 cells offer opportunities to address regulatory T-cell functions in vitro.


Asunto(s)
Terapia de Inmunosupresión , Linfocitos T Reguladores , Humanos , Línea Celular , Tolerancia Inmunológica , Factores de Transcripción Forkhead/metabolismo
17.
J Med Imaging (Bellingham) ; 11(1): 015001, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38196401

RESUMEN

Purpose: Computational methods for image-to-physical registration during surgical guidance frequently rely on sparse point clouds obtained over a limited region of the organ surface. However, soft tissue deformations complicate the ability to accurately infer anatomical alignments from sparse descriptors of the organ surface. The Image-to-Physical Liver Registration Sparse Data Challenge introduced at SPIE Medical Imaging 2019 seeks to characterize the performance of sparse data registration methods on a common dataset to benchmark and identify effective tactics and limitations that will continue to inform the evolution of image-to-physical registration algorithms. Approach: Three rigid and five deformable registration methods were contributed to the challenge. The deformable approaches consisted of two deep learning and three biomechanical boundary condition reconstruction methods. These algorithms were compared on a common dataset of 112 registration scenarios derived from a tissue-mimicking phantom with 159 subsurface validation targets. Target registration errors (TRE) were evaluated under varying conditions of data extent, target location, and measurement noise. Jacobian determinants and strain magnitudes were compared to assess displacement field consistency. Results: Rigid registration algorithms produced significant differences in TRE ranging from 3.8±2.4 mm to 7.7±4.5 mm, depending on the choice of technique. Two biomechanical methods yielded TRE of 3.1±1.8 mm and 3.3±1.9 mm, which outperformed optimal rigid registration of targets. These methods demonstrated good performance under varying degrees of surface data coverage and across all anatomical segments of the liver. Deep learning methods exhibited TRE ranging from 4.3±3.3 mm to 7.6±5.3 mm but are likely to improve with continued development. TRE was weakly correlated among methods, with greatest agreement and field consistency observed among the biomechanical approaches. Conclusions: The choice of registration algorithm significantly impacts registration accuracy and variability of deformation fields. Among current sparse data driven image-to-physical registration algorithms, biomechanical simulations that incorporate task-specific insight into boundary conditions seem to offer best performance.

18.
J Int Neuropsychol Soc ; : 1-11, 2024 Jan 29.
Artículo en Inglés | MEDLINE | ID: mdl-38282390

RESUMEN

OBJECTIVE: Associations have been found between five-factor model (FFM) personality traits and risk of developing specific predementia syndromes such as subjective cognitive decline (SCD) and mild cognitive impairment (MCI). The aims of this study were to: 1) Compare baseline FFM traits between participants who transitioned from healthy cognition or SCD to amnestic MCI (aMCI) versus non-amnestic MCI (naMCI); and 2) Determine the relationship between FFM traits and risk of transition between predementia cognitive states. METHODS: Participants were 562 older adults from the Einstein Aging Study, 378 of which had at least one follow-up assessment. Baseline data collected included levels of FFM personality traits, anxiety and depressive symptoms, medical history, performance on a cognitive battery, and demographics. Follow-up cognitive diagnoses were also recorded. RESULTS: Mann-Whitney U tests revealed no differences in baseline levels of FFM personality traits between participants who developed aMCI compared to those who developed naMCI. A four-state multistate Markov model revealed that higher levels of conscientiousness were protective against developing SCD while higher levels of neuroticism resulted in an increased risk of developing SCD. Further, higher levels of extraversion were protective against developing naMCI. CONCLUSIONS: FFM personality traits may be useful in improving predictions of who is at greatest risk for developing specific predementia syndromes. Information on these personality traits could enrich clinical trials by permitting trials to target individuals who are at greatest risk for developing specific forms of cognitive impairment. These results should be replicated in future studies with larger sample sizes and younger participants.

19.
Ann R Coll Surg Engl ; 106(2): 140-149, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37218649

RESUMEN

INTRODUCTION: Consent is a fundamental aspect of surgery and expectations around the consent process have changed following the Montgomery vs Lanarkshire Health Board (2015) court ruling. This study aimed to identify trends in litigation pertaining to consent, explore variation in how consent is practised among general surgeons and identify potential causes of this variation. METHODS: This mixed-methods study examined temporal variation in litigation rates relating to consent (between 2011 and 2020), using data obtained from National Health Service (NHS) Resolutions. Semi-structured clinician interviews were then conducted to gain qualitative data regarding how general surgeons take consent, their ideologies and their outlook on the recent legal changes. The quantitative component included a questionnaire survey aiming to explore these issues with a larger population to improve the generalisability of the findings. RESULTS: NHS Resolutions litigation data showed a significant increase in litigation pertaining to consent following the 2015 health board ruling. The interviews demonstrated considerable variation in how surgeons approach consent. This was corroborated by the survey, which illustrated considerable variation in how consent is documented when different surgeons are presented with the same case vignette. CONCLUSION: A clear increase in litigation relating to consent was seen in the post-Montgomery era, which may be due to legal precedent being established and increased awareness of these issues. Findings from this study demonstrate variability in the information patients receive. In some cases, consent practices did not adequately meet current regulations and therefore are susceptible to potential litigation. This study identifies areas for improvement in the practice of consent.


Asunto(s)
Mala Praxis , Cirujanos , Humanos , Consentimiento Informado , Medicina Estatal , Encuestas y Cuestionarios
20.
Ann R Coll Surg Engl ; 106(1): 78-91, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37458196

RESUMEN

INTRODUCTION: Female carriers of BRCA1/2 genes have an increased lifetime risk of breast cancer. Options for managing risk include imaging surveillance or risk-reducing surgery (RRS). This mixed methods study aimed to identify factors affecting risk-management decisions and the psychosocial outcomes of these decisions for high-risk women and their partners. METHODS: Semi-structured qualitative interviews were performed with women at high breast cancer risk who had faced these choices. Partners were also interviewed. Analysis used a framework approach. A bespoke questionnaire was developed to quantify and explore associations. RESULTS: A total of 32 women were interviewed. Of these, 27 had partners of whom 7 (26%) agreed to be interviewed. Four main themes arose: perception of risk and impact of increased risk; risk-management strategy decision-making; impact of risk-management strategy; support needs and partner relationship issues. The questionnaire response rate was 36/157 (23%). Decision satisfaction was high in both surveillance and RRS groups. Relationship changes were common but not universal. Common causes of distress following RRS included adverse body image changes. Both groups experienced generalised and cancer-specific anxiety. Drivers for surgery included having children, deaths of close family from breast cancer and higher levels of cancer anxiety. CONCLUSIONS: Levels of psychosocial and decision satisfaction were high for women choosing both RRS and surveillance but, for a minority, risk-reducing measures result in long-term psychosocial morbidity. Efforts to recognise women at increased risk of psychological morbidity may allow targeted support.


Asunto(s)
Neoplasias de la Mama , Niño , Femenino , Humanos , Neoplasias de la Mama/genética , Neoplasias de la Mama/cirugía , Proteína BRCA1 , Proteína BRCA2 , Gestión de Riesgos
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