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Bordetella pertussis is a Gram-negative bacterium that is the causative agent of the respiratory disease known as pertussis. Since the switch to the acellular vaccines of DTaP and Tap, pertussis cases in the US have risen and cyclically fallen. We have observed that mRNA pertussis vaccines are immunogenic and protective in mice. Here, we further evaluated the pertussis toxoid mRNA antigen and refined the formulation based on optimal pertussis toxin neutralization in vivo. We next evaluated the mRNA pertussis vaccine in Sprague-Dawley rats using an aerosol B. pertussis challenge model paired with whole-body plethysmography to monitor coughing and respiratory function. Female Sprague-Dawley rats were primed and boosted with either commercially available vaccines (DTaP or wP-DTP), an mRNA-DTP vaccine, or mock-vaccinated. The mRNA-DTP vaccine was immunogenic in rats and induced antigen-specific IgG antibodies comparable to DTaP. Rats were then aerosol challenged with a streptomycin-resistant emerging clinical isolate D420Sm1. Bacterial burden was assessed at days 1 and 9 post-challenge, and the mRNA vaccine reduced burden equal to both DTaP and wP-DTP. Whole-body plethysmography revealed that mRNA-DTP vaccinated rats were well protected against coughing which was comparable to the non-challenged group. These data suggest that an mRNA-DTP vaccine is immunogenic in rats and provides protection against aerosolized B. pertussis challenge in Sprague-Dawley rats.
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Bordetella pertussis , Ratos Sprague-Dawley , Coqueluche , Animais , Coqueluche/prevenção & controle , Coqueluche/imunologia , Feminino , Ratos , Bordetella pertussis/imunologia , Bordetella pertussis/genética , Anticorpos Antibacterianos/sangue , Anticorpos Antibacterianos/imunologia , Vacina contra Difteria, Tétano e Coqueluche/imunologia , Vacina contra Difteria, Tétano e Coqueluche/administração & dosagem , Imunoglobulina G/sangue , Vacinas de mRNA , ImunizaçãoRESUMO
TOPIC: Sympathetic ophthalmia (SO) is a sight-threatening granulomatous panuveitis caused by a sensitizing event. Primary enucleation or primary evisceration, versus primary repair, as a risk management strategy after open-globe injury (OGI) remains controversial. CLINICAL RELEVANCE: This systematic review was conducted to report the incidence of SO after primary repair compared with that of after primary enucleation or primary evisceration. This enabled the reporting of an estimated number needed to treat. METHODS: Five journal databases were searched. This review was registered with International Prospective Register of Systematic Reviews (identifier, CRD42021262616). Searches were carried out on June 29, 2021, and were updated on December 10, 2022. Prospective or retrospective studies that reported outcomes (including SO or lack of SO) in a patient population who underwent either primary repair and primary enucleation or primary evisceration were included. A systematic review and meta-analysis were carried out in accordance with Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Random effects modelling was used to estimate pooled SO rates and absolute risk reduction (ARR). RESULTS: Eight studies reporting SO as an outcome were included in total. The included studies contained 7500 patients and 7635 OGIs. In total, 7620 OGIs met the criteria for inclusion in this analysis; SO developed in 21 patients with OGI. When all included studies were pooled, the estimated SO rate was 0.12% (95% confidence interval [CI], 0.00%-0.25%) after OGI. Of 779 patients who underwent primary enucleation or primary evisceration, no SO cases were reported, resulting in a pooled SO estimate of 0.05% (95% CI, 0.00%-0.21%). For primary repair, the pooled estimate of SO rate was 0.15% (95% CI, 0.00%-0.33%). The ARR using a random effects model was -0.0010 (in favour of eye removal; 95% CI, -0.0031 [in favor of eye removal] to 0.0011 [in favor of primary repair]). Grading of Recommendations, Assessment, Development, and Evaluations analysis highlighted a low certainty of evidence because the included studies were observational, and a risk of bias resulted from missing data. DISCUSSION: Based on the available data, no evidence exists that primary enucleation or primary evisceration reduce the risk of secondary SO. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
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OBJECTIVE: To assess the characteristics and financial conflicts of interest of presenters, panellists and moderators at haematology and oncology workshops held jointly with or hosted by the US FDA. SETTING: We included information on all publicly available haematology or oncology FDA workshop agendas held between 1 January 2018 and 31 December 2022. EXPOSURE: General and research payments reported on Open Payments, industry funding to patient advocacy organizations reported on their webpages or 990 tax forms and employment in both pharmaceutical and regulatory settings. RESULTS: Among physicians eligible for payments, 78% received at least one payment from the industry between 2017 and 2021. The mean general payment amount was $82,170 for all years ($16,434 per year) and the median was $14,906 for all years ($2981 per year). Sixty-nine per cent of patient advocacy speakers were representing organizations that received financial support from the pharmaceutical industry. Among those representing regulatory agencies or pharmaceutical companies, 16% had worked in both settings during their careers. CONCLUSIONS AND RELEVANCE: Our findings in this cross-sectional study show a majority of US-based physician presenters at haematology and oncology workshops held jointly with members of the US FDA have some financial conflict of interest with the pharmaceutical industry. These findings support the need for clear disclosures and suggest that a more balanced selection of presenters with fewer conflicts may help to limit bias in discussions between multiple stakeholders.
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Conflito de Interesses , Indústria Farmacêutica , Hematologia , Oncologia , United States Food and Drug Administration , Estados Unidos , Humanos , Indústria Farmacêutica/economia , Hematologia/economia , Estudos Transversais , Defesa do Paciente , Médicos/economia , Educação/economia , RevelaçãoRESUMO
BACKGROUND: Current treatments for Tourette syndrome (TS) and persistent tic disorder (PTD) are often insufficiently effective, inaccessible, and frequently associated with adverse events. Thus, we must continue to develop and test effective, accessible, and safe treatment options. OBJECTIVE: We aimed to conduct a pilot randomized controlled trial (RCT) comparing a novel, videoconference-delivered group mindfulness-based intervention for tics (MBIT) to videoconference-delivered group psychoeducation, relaxation, and supportive therapy (PRST) for adults with TS or PTD. METHODS: Thirty-two adults with TS or PTD were randomly assigned to receive 8 weeks of either MBIT or PRST. Tic severity, tic-related impairment, and global improvement were assessed by a trained, independent evaluator who was masked to treatment condition at baseline (week 0), posttreatment (week 9), 1-month follow-up, and 6-month follow-up. All study procedures were conducted online via secure videoconferencing. RESULTS: Twenty-eight participants began treatment and were included in analyses. MBIT, relative to PRST, was associated with a significantly greater decline in tic severity (d = 0.85) and tic-related impairment (d = 0.99) from baseline to posttreatment. Treatment response was significantly higher in MBIT (69%) than in PRST (13%). Neither treatment resulted in serious adverse effects. The durability of treatment outcomes is also reported and discussed. CONCLUSIONS: The results from this pilot RCT suggest that videoconference-delivered group MBIT may be an efficacious, accessible, and safe intervention for adults with tics. Future research is necessary to confirm these preliminary findings. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder that exhibits striking sex differences in symptoms, prevalence, and associated problems across development. Etiological factors and mechanisms underlying these sex differences remain one of the most understudied aspects of this disorder. The current paper seeks to provide a novel theoretical framework for understanding this phenomenon by reviewing evidence that females with ADHD may experience a "double whammy" of organizational and activational pubertal hormonal effects. We propose a novel theory of activational effects of cyclical circulating ovarian hormones on ADHD with increasing risk at times of rapid declines in estrogen. These declines may decrease executive function and trait control at two points of the cycle characterized by biphasic affective risk: (1) increases in approach/risk-taking behaviors at mid-cycle (periovulatory) and (2) increases in avoidance/negative affect perimenstrually. Low estrogen and control may then interact with increases in positive and negative affect, respectively, to increase hyperactivity-impulsivity symptoms post-ovulation and inattention symptoms perimenstrually. These interactions may be exacerbated by organizational pubertal effects on relatively overdeveloped limbic circuitry and adolescent-specific social pressures magnified in females with ADHD.
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Transtorno do Deficit de Atenção com Hiperatividade , Adolescente , Humanos , Masculino , Feminino , Transtorno do Deficit de Atenção com Hiperatividade/etiologia , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Ciclo Menstrual , Função Executiva , Cognição , EstrogêniosRESUMO
OBJECTIVE: Youth living with HIV (YLHIV) in the southern United States experience poor outcomes across the HIV care continuum and are at high-risk for virologic failure. This study used a qualitative, community-engaged approach to inform the development of a tailored mobile Health (mHealth) tool for YLHIV in South Carolina (SC). METHODS: Semistructured qualitative interviews were conducted with YLHIV in SC (n = 16) and their HIV care providers (n = 15). Focus group discussions (FGDs) were also conducted with HIV-focused community-based organization staff (n = 23). Interviews and FGDs queried desired components for a future mHealth tool tailored for YLHIV. Data were analyzed using a team-based rapid qualitative approach. RESULTS: Across informants, key themes emerged related to medical management of HIV, including a desire for connections with medical providers, appointment and medication reminders, and accurate HIV information. In addition, informants voiced a desire for mental health resources to be integrated into the app. Connection with HIV-positive peers also emerged as a key desire from youth informants. In terms of app design, informants emphasized the need for strict privacy practices, a youth-friendly design, compensation for use, and integration with existing healthcare systems. CONCLUSIONS: mHealth interventions developed for YLHIV should meet the mental health and social needs of YLHIV in addition to their medical needs. In addition, the highly stigmatized nature of HIV requires careful consideration when designing digital tools-youth want their privacy prioritized, but also express strong desire for social support to help cope with the isolation and stigma of this chronic health condition.
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Introduction: Asthma is one of the most chronic noncommunicable diseases of childhood, affecting 1 in 12 children in the United States. The use of telemedicine for the management of pediatric asthma has shown improved health outcomes; however, it is important to understand what can impact its acceptance. The purpose of this review was to identify the facilitators and barriers to pediatric asthma management, as viewed by stakeholders. Methods: An electronic literature search was performed using PubMed, Scopus, and Cumulative Index to Nursing and Allied Health Literature Complete. Articles included in the review contained perceptions of the use of telemedicine for the management of pediatric asthma, as viewed by stakeholders. The socioecological model was used as the theoretical framework to extract data based on its five levels. Results: After reviewing full texts of 143 articles, 118 were excluded, leaving 25 articles included in this review. A majority of included articles focused on mobile health (m-Health) studies for the management of pediatric asthma, with the remaining articles studying synchronous telemedicine or a combination of modalities. Common themes were identified; however, most were focused on the use of m-Health and few studies contained the viewpoints of the caregiver, children, or providers regarding synchronous telemedicine. Discussion: This integrative review identified a number of facilitators and barriers for the management of asthma using telemedicine. However, more qualitative studies are needed to evaluate the perceptions of caregivers, patients, and primary providers regarding synchronous telehealth. It was also recognized that telemedicine may increase instead of reduce health care disparities.
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Asma , Telemedicina , Humanos , Criança , Estados Unidos , Asma/terapia , Monitorização Fisiológica , Cuidadores , Pesquisa QualitativaRESUMO
Cancer screenings aid in the early detection of cancer and can help reduce cancer-related mortality. The current model of care for cancer screening is often siloed, based on the targeted cancer site. We tested the acceptability of a new model of care, called the One-Stop-Shop Cancer Screening Clinic, that centralizes cancer screenings and offers patients the option to complete all their recommended cancer screenings within one to two visits. We administered surveys to 59 community members and 26 healthcare providers to gather feedback about the One-Stop-Shop model of care. Both community members and providers identified potential benefits (e.g., decreased patient burden, increased completion of cancer screenings) and also potential challenges (e.g., challenges with workflow and timing of care) of the model of care. The results of the study support the acceptability of the model of care. Of the community members surveyed, 89.5% said, if offered, they would be interested in participating in the One-Stop-Shop Cancer Screening Clinic. Future studies are needed to formally evaluate the impact and cost effectiveness of the One-Stop-Shop Cancer Screening Clinic.
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Antimicrobial susceptibility testing (AST) in RPMI 1640, a more physiologically relevant culture medium, revealed that a substantial proportion of carbapenem-resistant Acinetobacter baumannii isolates were susceptible to azithromycin, a macrolide antibiotic not currently considered effective against A. baumannii. Experiments using Galleria mellonella validated these in vitro data. Our finding that RPMI 1640's predictive accuracy for in vivo outcomes is superior to that of Mueller-Hinton II broth also supports the use of more physiologically relevant AST culturing conditions.
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Infecções por Acinetobacter , Acinetobacter baumannii , Mariposas , Animais , Humanos , Azitromicina/farmacologia , Colistina , Infecções por Acinetobacter/tratamento farmacológico , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Carbapenêmicos/farmacologia , Testes de Sensibilidade Microbiana , Farmacorresistência Bacteriana MúltiplaRESUMO
BACKGROUND: Extremely low birth weight (ELBW) infants comprise a fragile population at risk for neurodevelopmental disabilities (NDD). Systemic steroids were previously associated with NDD, but more recent studies suggest hydrocortisone (HCT) may improve survival without increasing NDD. However, the effects of HCT on head growth adjusted for illness severity during NICU hospitalization are unknown. Thus, we hypothesize that HCT will protect head growth, accounting for illness severity using a modified neonatal Sequential Organ Failure Assessment (M-nSOFA) score. METHODS: We conducted a retrospective study that included infants born at 23-29 weeks gestational age (GA) and < 1000 g. Our study included 73 infants, 41% of whom received HCT. RESULTS: We found negative correlations between growth parameters and age, similar between HCT and control patients. HCT-exposed infants had lower GA but similar normalized birth weights; HCT-exposed infants also had higher illness severity and longer lengths of hospital stay. We found an interaction between HCT exposure and illness severity on head growth, such that infants exposed to HCT had better head growth compared to those not exposed to HCT when adjusted for illness severity. CONCLUSION: These findings emphasize the importance of considering patient illness severity and suggest that HCT use may offer additional benefits not previously considered. IMPACT: This is the first study to assess the relationship between head growth and illness severity in extremely preterm infants with extremely low birth weights during their initial NICU hospitalization. Infants exposed to hydrocortisone (HCT) were overall more ill than those not exposed, yet HCT exposed infants had better preserved head growth relative to illness severity. Better understanding of the effects of HCT exposure on this vulnerable population will help guide more informed decisions on the relative risks and benefits for HCT use.
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Hidrocortisona , Recém-Nascido de Peso Extremamente Baixo ao Nascer , Humanos , Recém-Nascido , Lactente , Hidrocortisona/uso terapêutico , Estudos Retrospectivos , Recém-Nascido Prematuro , Gravidade do PacienteRESUMO
We examine multi-generational impacts of positive in utero health interventions using a new research design that exploits sharp increases in prenatal Medicaid eligibility that occurred in some states. Our analyses are based on U.S. Vital Statistics Natality files, which enables linkages between individuals' early life Medicaid exposure and the next generation's health at birth. We find evidence that the health benefits associated with treated generations' early life program exposure extend to later offspring. Our results suggest that the returns on early life health investments may be substantively underestimated.
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Climate change is threatening an uncalculated number of archaeological sites globally, totaling perhaps hundreds of thousands of culturally and paleoenvironmentally significant resources. As with all archaeological sites, they provide evidence of humanity's past and help us understand our place in the present world. Coastal sites, clustered at the water's edge, are already experiencing some of the most dramatic damage due to anthropogenic climate change, and the situation is predicted to worsen in the future. In the face of catastrophic loss, organizations around the world are developing new ways of working with this threatened coastal resource. This paper uses three examples from Scotland, Florida, and Maine to highlight how new partnerships and citizen science approaches are building communities of practice to better manage threatened coastal heritage. It compares methods on either side of the Atlantic and highlights challenges and solutions. The approaches are applicable to the increasing number of heritage sites everywhere at risk from climate change; the study of coastal sites thus helps society prepare for climate change impacts to heritage worldwide.
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Ciência do Cidadão , Mudança Climática , Arqueologia , Conservação dos Recursos Naturais , Florida , Humanos , Maine , EscóciaRESUMO
Background: In the United States, colorectal cancer (CRC) is the second leading cause of cancer death in men and women combined. The United States Preventive Services Task Force recommends that average risk adults have regular CRC screening to detect and prevent CRC. Despite published CRC screening guidelines, national CRC screening rates remain suboptimal. With the exponential increase in technology use and device ownership, many mobile health applications (apps) have been developed to improve health outcomes. There is great potential for smartphone or tablet apps to help improve CRC screening uptake, with the ultimate goal of reducing CRC morbidity and mortality. To date, there are no systematic reviews that have examined the publicly available, free apps that are related to CRC screening, and therefore, the quality and the content of these apps remain unknown. Objectives: The purpose of this study was to systematically review smartphone and tablet apps that could be used to improve CRC screening uptake. Methods: Apps available on the Google Play and Apple App stores that were compatible with smartphones and tablets were reviewed. Of the 2,790 apps reviewed, 20 met inclusion criteria. Results: Of the 20 apps that met inclusion criteria, most were informational in nature. Approximately half of the apps focused on colonoscopies and did not discuss other CRC screening options. Furthermore, more than half of the apps did not include video/audio content and the majority of the apps did not provide navigation support (e.g., reminders, instructions, maps). Conclusions: There are multiple free, publicly available apps that may encourage CRC screening uptake. Despite their promise, there is a paucity of empirical evidence evaluating the efficacy and usability of these apps. Future research efforts can evaluate the content, usability, accessibility, and potential impact of these apps.
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Neoplasias Colorretais , Detecção Precoce de Câncer , Aplicativos Móveis , Adulto , Feminino , Humanos , Masculino , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/prevenção & controle , Detecção Precoce de Câncer/métodos , Smartphone , Telemedicina , Estados Unidos/epidemiologia , Computadores de MãoRESUMO
Objective: To explore overall trends as well as racial/ethnic disparities in utilization of different telehealth modalities (telephone vs. televideo) at federally qualified health centers (FQHCs) during the COVID-19 pandemic. Methods: Using electronic health record data from a large New York-based FQHC system, we aggregated (separately) Behavioral Health and Family Practice visits per month occurring in-person, by telephone, or by televideo and graphed monthly trends in visits across the pre-pandemic, peak-pandemic, and post-peak-pandemic periods. We calculated fractions of visits conducted by modality for each patient demographic (race/ethnicity, primary language, age, gender, insurance type, and geography) and conducted bivariate assessments to test relationships between patient characteristics and modality. Results: Our data contained 121,072 unique patients and 811,105 visits overall. Telehealth use peaked in April 2020 but continued to account for a significant fraction of FQHC visits-nearly 25% (N = 4,908) of monthly Family Practice visits and a massive 98% (N = 14,173) of Behavioral Health visits as late as June 2021. Of all telehealth visits, nearly half were by telephone. Moreover, demographic factors differed between FQHC patients using telephone visits versus those using televideo: Black, non-English speaking, older, and Medicaid patients had significantly higher utilization of telephone visits than televideo visits (e.g., 25.9% of all Black patients' visits were via telephone vs. 17.1% via televideo; p < 0.001). In contrast, younger, Asian, and privately insured patients had significantly higher televideo visits. Conclusions: Our results suggest that telephone visits remain critical to the provision of health care for FQHC patients. They also suggest that disparities extend beyond the telehealth versus in-person dichotomy and inequities exist even within the type of telehealth used. This has implications for patient health, FQHC quality outcomes, as well as optimal Medicaid telehealth reimbursement policy.
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Pandemias , Telemedicina , Estados Unidos , Humanos , Programas Governamentais , Instalações de Saúde , MedicaidRESUMO
Objective: This study assessed barriers and facilitators to telehealth utilization among patients living in New York City public housing with chronic conditions and a gap in clinical care. Methods: Community health workers performed outreach to eligible patients by telephone between January and March 2021. Consenting respondents answered questions about telehealth barriers, including internet and cell phone access, ownership of digital devices, comfort with using digital devices, comfort with telehealth, cost, awareness, and availability of written materials in patients' preferred language. We obtained demographic and medical information from patients' electronic health records. We used multivariable logistic regression to estimate the association of barriers with the odds of self-reported prior telehealth utilization. Results: A total of 304 consenting patients participated in the program. The average patient had 3.1 telehealth barriers; 76% reported at least one barrier. Regression analysis showed sizable reductions in prior telehealth utilization associated with the barriers of unlimited cell phone minutes (odds ratio [OR]: 0.21 [0.05-0.88], p = 0.033), technological comfort (OR: 0.33 [0.13-0.82], p = 0.016), conceptual comfort with telehealth (OR: 0.15 [0.04-0.54], p = 0.004), and materials in the patient's preferred language (OR: 0.23 [0.07-0.79], p = 0.02). Discussion: With a high prevalence of telehealth barriers, patients with limited income, a chronic condition, and a care gap may benefit from greater technological access and supportive programs for awareness, telehealth comfort, and navigation support. Addressing telehealth barriers could increase the quality of medical care and improve health outcomes for this population.
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Telemedicina , Humanos , Doença Crônica , Cidade de Nova IorqueRESUMO
Ribosomal heterogeneity exists within cells and between different cell types, at specific developmental stages, and occurs in response to environmental stimuli. Mounting evidence supports the existence of specialized ribosomes, or specific changes to the ribosome that regulate the translation of a specific group of transcripts. These alterations have been shown to affect the affinity of ribosomes for certain mRNAs or change the cotranslational folding of nascent polypeptides at the exit tunnel. The identification of specialized ribosomes requires evidence of the incorporation of different ribosomal proteins or of modifications to rRNA and/or protein that lead(s) to physiologically relevant changes in translation. In this review, we summarize ribosomal heterogeneity and specialization in mammals and discuss their relevance to several human diseases.
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Biossíntese de Proteínas , Ribossomos , Animais , Humanos , Ribossomos/metabolismo , Proteínas Ribossômicas/genética , Proteínas Ribossômicas/metabolismo , RNA Ribossômico/genética , Peptídeos/metabolismo , Mamíferos/metabolismoRESUMO
OBJECTIVE: Two Cownose Rays Rhinoptera bonasus were presented for management of a severe capsalid monogenean infection Benedeniella posterocolpa in a mixed species habitat at an aquarium. METHODS: A series of freshwater (FW) dips were elected to mitigate parasite resistance to praziquantel due to the endemic monogenean population in the system. A pretreatment blood sample was opportunistically obtained, and subsequent samples were processed due to development of clinical signs. RESULT: While the first FW dip was tolerated well and did not induce abnormal behavior, the second led to one individual presenting with tachypnea, pallor, and lethargy. Marked hematological abnormalities requiring medical intervention occurred in both individuals after the second dip. After treatment with elasmobranch Ringer's fluid therapy, sodium bicarbonate, prednisolone acetate, and vitamin E/selenium in the more severely affected ray, and elasmobranch Ringer's alone in the second ray, hematologic derangements and symptoms resolved. Hemoconcentration, hyperproteinemia, hyperlactatemia, and hyperglycemia were attributed to a stress response. A selective loss of urea after exposure to FW resulted in decreased plasma osmolality. CONCLUSION: Given the severity of the stress response and associated complications observed, hyposalinity treatments should be utilized with caution in this species. If this therapy is employed, the clinician is advised to be prepared to administer supportive care coinciding with the FW dip if necessary.
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Inflammatory bowel disease (IBD) is a chronic gut inflammation with periods of acute flares and remission. Beneficial effects of a single dose of mesenchymal stem cell (MSC)-based treatment have been demonstrated in acute models of colitis. No studies investigated therapeutic effects of MSCs for the attenuation of enteric neuropathy in a chronic model of colitis. The short and long-term effects of MSC treatment in modulating inflammation and damage to the enteric nervous system (ENS) were studied in the Winnie mouse model of spontaneous chronic colitis highly representative of human IBD. Winnie mice received a single dose of either 1 × 106 human bone marrow-derived MSCs or 100µL PBS by intracolonic enema. C57BL/6 mice received 100µL PBS. Colon tissues were collected at 3 and 60 days post MSC administration to evaluate the short-term and long-term effects of MSCs on inflammation and enteric neuropathy by histological and immunohistochemical analyses. In a separate set of experiments, multiple treatments with 4 × 106 and 2 × 106 MSCs were performed and tissue collected at 3 days post treatment. Chronic intestinal inflammation in Winnie mice was associated with persistent diarrhea, perianal bleeding, morphological changes, and immune cell infiltration in the colon. Significant changes to the ENS, including impairment of cholinergic, noradrenergic and sensory innervation, and myenteric neuronal loss were prominent in Winnie mice. Treatment with a single dose of bone marrow-derived MSCs was ineffective in attenuating chronic inflammation and enteric neuropathy in Winnie.
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Colite , Doenças Inflamatórias Intestinais , Pseudo-Obstrução Intestinal , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Animais , Colite/patologia , Modelos Animais de Doenças , Inflamação/patologia , Doenças Inflamatórias Intestinais/complicações , Pseudo-Obstrução Intestinal/terapia , Camundongos , Camundongos Endogâmicos C57BLRESUMO
Tendon injuries are common and heal poorly, due in part to a lack of understanding of fundamental tendon cell biology. A major impediment to the study of tendon cells is the absence of robust, well-characterized in vitro models. Unlike other tissue systems, current tendon cell models do not account for how differences in isolation methodology may affect the activation state of tendon cells or the presence of various tendon cell subpopulations. The objective of this study was to characterize how common isolation methods affect the behavior, fate, and lineage composition of tendon cell cultures. Tendon cells isolated by explant exhibited reduced proliferative capacity, decreased expression of tendon marker genes, and increased expression of genes associated with fibroblast activation compared to digested cells. Consistently, explanted cells also displayed an increased propensity to differentiate to myofibroblasts compared to digested cells. Explanted cultures from multiple different tendons were substantially enriched for the presence of scleraxis-lineage (Scx-lin+) cells compared to digested cultures, while the overall percentage of S100a4-lineage (S100a4-lin+) cells was dependent on both isolation method and tendon of origin. Neither isolation methods preserved the ratios of Scx-lin+ or S100a4-lin+ to non-lineage cells seen in tendons in vivo. Combined, these data indicate that further refinement of in vitro cultures models is required in order to more accurately understand the effects of various stimuli on tendon cell behavior. Statement of clinical significance: The development of informed in vitro tendon cell models will facilitate enhanced screening of potential therapeutic candidates to improve tendon healing.
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Tendões/citologia , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Biomarcadores/metabolismo , Técnicas de Cultura de Células , Diferenciação Celular/fisiologia , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Miofibroblastos/citologia , Miofibroblastos/metabolismo , Traumatismos dos Tendões/metabolismo , Traumatismos dos Tendões/terapia , Tendões/metabolismo , Cicatrização/fisiologiaRESUMO
NEW FINDINGS: What is the central question of this study? Can bilateral knee extensor force accuracy be improved following 4 weeks of unilateral force accuracy training and are there any subsequent alterations to central and/or peripheral motor unit features? What is the main finding and its importance? In the trained limb only, knee extensor force tracking accuracy improved with reduced motor unit firing rate variability in the vastus lateralis, and there was no change to neuromuscular junction transmission instability. Interventional strategies to improve force accuracy may be directed to older/clinical populations where such improvements may aid performance of daily living activities. ABSTRACT: Muscle force output during sustained submaximal isometric contractions fluctuates around an average value and is partly influenced by variation in motor unit (MU) firing rates. MU firing rate (FR) variability seemingly reduces following exercise training interventions; however, much less is known with respect to peripheral MU properties. We therefore investigated whether targeted force accuracy training could lead to improved muscle functional capacity and control, in addition to determining any alterations of individual MU features. Ten healthy participants (seven females, three males, 27 ± 6 years, 170 ± 8 cm, 69 ± 16 kg) underwent a 4-week supervised, unilateral knee extensor force accuracy training intervention. The coefficient of variation for force (FORCECoV ) and sinusoidal wave force tracking accuracy (FORCESinu ) were determined at 25% maximal voluntary contraction (MVC) pre- and post-training. Intramuscular electromyography was utilised to record individual MU potentials from the vastus lateralis (VL) muscles at 25% MVC during sustained contractions, pre- and post-training. Knee extensor muscle strength remained unchanged following training, with no improvements in unilateral leg-balance. FORCECoV and FORCESinu significantly improved in only the trained knee extensors by â¼13% (P = 0.01) and â¼30% (P < 0.0001), respectively. MU FR variability significantly reduced in the trained VL by â¼16% (n = 8; P = 0.001), with no further alterations to MU FR or neuromuscular junction transmission instability. Our results suggest muscle force control and tracking accuracy is a trainable characteristic in the knee extensors, which is likely explained by the reduction in MU FR variability which was apparent in the trained limb only.