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1.
Implement Sci Commun ; 5(1): 50, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38702751

RESUMO

BACKGROUND: Patient navigation is an individualized intervention to facilitate comprehensive care which has not yet been fully implemented in obstetric or postpartum care. METHODS: We aimed to develop and evaluate a mechanism to incorporate feedback regarding implementation of postpartum patient navigation for low-income birthing individuals at an urban academic medical center. This study analyzed the role of an Implementation Advisory Board (IAB) in supporting an ongoing randomized trial of postpartum navigation. Over the first 24 months of the trial, the IAB included 11 rotating obstetricians, one clinic resource coordinator, one administrative leader, two obstetric nurses, one primary care physician, one social worker, and one medical assistant. Members completed serial surveys regarding program implementation, effects on patient care, and areas for improvement. Quarterly IAB meetings offered opportunities for additional feedback. Survey responses and meeting notes were analyzed using the constant comparative method and further interpreted within the Exploration, Preparation, Implementation, Sustainment (EPIS) Framework. RESULTS: Members of the IAB returned 37 surveys and participated in five meetings over 24 months. Survey analysis revealed four themes among the inner context: reduced clinician burden, connection of care teams, communication strategies, and clinic workflow. Bridging factors included improved patient access to care, improved follow-up, and adding social context to care. Innovation factors included availability of navigators, importance of consistent communication, and adaptation over time. Meeting notes highlighted the importance of bidirectional feedback regarding implementation, and members expressed positive opinions regarding navigators' effects on patient care, integration into clinic workflow, and responsiveness to feedback. IAB members initially suggested changes to improve implementation; later survey responses demonstrated successful program adaptations. CONCLUSIONS: Members of an implementation advisory board provided key insights into the implementation of postpartum patient navigation that may be useful to promote dissemination of navigation and establish avenues for the engagement of implementing partners in other innovations. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03922334 . Registered April 19, 2019. The results here do not present the results of the primary trial, which is ongoing.

2.
Nat Commun ; 15(1): 3059, 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38637500

RESUMO

The 2023 monkeypox (mpox) epidemic was caused by a subclade IIb descendant of a monkeypox virus (MPXV) lineage traced back to Nigeria in 1971. Person-to-person transmission appears higher than for clade I or subclade IIa MPXV, possibly caused by genomic changes in subclade IIb MPXV. Key genomic changes could occur in the genome's low-complexity regions (LCRs), which are challenging to sequence and are often dismissed as uninformative. Here, using a combination of highly sensitive techniques, we determine a high-quality MPXV genome sequence of a representative of the current epidemic with LCRs resolved at unprecedented accuracy. This reveals significant variation in short tandem repeats within LCRs. We demonstrate that LCR entropy in the MPXV genome is significantly higher than that of single-nucleotide polymorphisms (SNPs) and that LCRs are not randomly distributed. In silico analyses indicate that expression, translation, stability, or function of MPXV orthologous poxvirus genes (OPGs), including OPG153, OPG204, and OPG208, could be affected in a manner consistent with the established "genomic accordion" evolutionary strategies of orthopoxviruses. We posit that genomic studies focusing on phenotypic MPXV differences should consider LCR variability.


Assuntos
Mpox , Orthopoxvirus , Poxviridae , Humanos , Monkeypox virus/genética , Genômica , Mpox/genética
3.
Health Sci Rep ; 7(3): e1965, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38524774

RESUMO

Background and Aim: Until the May 2022 Monkeypox (MPXV) outbreak, which spread rapidly to many non-endemic countries, the virus was considered a viral zoonosis limited to some African countries. The Andalusian circuit of genomic surveillance was rapidly applied to characterize the MPXV outbreak in the South of Spain. Methods: Whole genome sequencing was used to obtain the genomic profiles of samples collected across the south of Spain, representative of all the provinces of Andalusia. Phylogenetic analysis was used to study the relationship of the isolates and the available sequences of the 2022 outbreak. Results: Whole genome sequencing of a total of 160 MPXV viruses from the different provinces that reported cases were obtained. Interestingly, we report the sequences of MPXV viruses obtained from two patients who died. While one of the isolates bore no noteworthy mutations that explain a potential heightened virulence, in another patient the second consecutive genome sequence, performed after the administration of tecovirimat, uncovered a mutation within the A0A7H0DN30 gene, known to be a prime target for tecovirimat in its Vaccinia counterpart. In general, a low number of mutations were observed in the sequences reported, which were very similar to the reference of the 2022 outbreak (OX044336), as expected from a DNA virus. The samples likely correspond to several introductions of the circulating MPXV viruses from the last outbreak. The virus sequenced from one of the two patients that died presented a mutation in a gene that bears potential connections to drug resistance. This mutation was absent in the initial sequencing before treatment.

4.
Health Equity ; 8(1): 132-137, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38435025

RESUMO

Background: The current approach to increasing diversity in medical education fails to consider local community demographics when determining medical school matriculation. Purpose: We propose that medical schools better reflect their surrounding community, both because racially/ethnically concordant physicians have been shown to provide better care and to repair the historical and current racist impacts of these institutions that have criminalized, displaced, and excluded local Black and Brown communities. Methods and Results: In this study, we used geospatial analysis to determine that medical school enrollments generally fail to reflect their surrounding community, represented as their core-based statistical area, within which the individual medical schools reside.

5.
Environ Sci Pollut Res Int ; 31(13): 20461-20476, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38376785

RESUMO

In the last few decades, there has been a growing interest in understanding the behavior of personal care products (PCPs) in the aquatic environment. In this regard, the aim of this study is to estimate the accumulation and effects of four PCPs within the clam Ruditapes philippinarum. The PCPs selected were triclosan, OTNE, benzophenone-3, and octocrylene. A progressive uptake was observed and maximum concentrations in tissues were reached at the end of the exposure phase, up to levels of 0.68 µg g-1, 24 µg g-1, 0.81 µg g-1, and 1.52 µg g-1 for OTNE, BP-3, OC, and TCS, respectively. After the PCP post-exposure period, the removal percentages were higher than 65%. The estimated logarithm bioconcentration factor ranged from 3.34 to 2.93, in concordance with the lipophobicity of each substance. No lethal effects were found although significant changes were observed for ethoxyresorufin O-demethylase activity, glutathione S-transferase activity, lipid peroxidation, and DNA damage.


Assuntos
Bivalves , Cosméticos , Poluentes Químicos da Água , Animais , Peroxidação de Lipídeos , Dano ao DNA , Alimentos Marinhos , Poluentes Químicos da Água/análise
6.
Nutr. clín. diet. hosp ; 44(1): 303-309, Feb. 2024. tab
Artigo em Inglês | IBECS | ID: ibc-231299

RESUMO

Introduction: Depression is related with poor musclestrength, and deficiencies of microelements such as Zinc (Zn).Otherwise, Zn is related with muscle strength, but there is noevidence of the relations between muscle strength and Znlevels in depression. Objective: To determine the association between serum Zn levels, handgrip muscle strength, and depression. Methods: An observational, analytical case-control study. 102 depressive patients hospitalized at the San Juan de DiosClinic in Manizales, and 36 controls with no personal historyof mental illness were evaluated for depression severity,serum Zn levels, and handgrip muscle strength. The groupswere matched by sex, age, educational level, and socioeco-nomic stratum. The severity of depression was assessed us-ing the Montgomery–Asberg Rating Scale (MADRS). Serum Znlevels were determined, and handgrip muscle strength wasassessed using dynamometer. Descriptive analysis, logistic reression and linear models were performed with depressionand severity of depression as dependent variables. Results: Lower Zn levels and reduced handgrip musclestrength were related to the presence of depression with thelogistic model. Lower handgrip muscle strength and severityof depression were associated with the linear model. Conclusion: An association was found between depressionand low Zn levels, and an inverse association between severityof depression and handgrip muscle strength. Future studiesshould investigate causality, and to evaluate the relationshipbetween depression, muscle strength and nutritional status.(AU)


Introducción: La depresión se encuentra relacionada con una disminución de la fuerza muscular y deficiencia de microelementos como el Zinc (Zn). De otra parte, el Zn está relacionado con la fuerza muscular, sin embargo, no hay evidencia si existe una asociación entre fuerza muscular y Zn en depresión. Objetivo: Determinar la asociación entre niveles séricos de Zn, fuerza muscular y depresión. Metodología: Se realizó un estudio observacional, analítico de casos y controles. Participaron 102 pacientes hospitalizados en la Clínica San Juan de Dios de Manizales y 36 controles sin historia personal de enfermedad mental. Fueron evaluados la severidad de la depresión, los niveles séricos de Zn y la fuerza de agarre manual. Los grupos fueron pareados por edad, sexo, escolaridad y estrato socioeconómico. La severidad de la depresión se evaluó con la escala de depresión Montgomery-Asberg (MADRS), se determinaron niveles séricos de Zn y la fuerza muscular fue evaluada con por dinamometría. Se realizo un análisis descriptivo, y modelos de regresión logística y regresión lineal con depresión y severidad de la depresión como variables dependientes.Resultados: El modelo de regresión logística encontró una asociación entre los niveles bajos de Zn y la fuerza muscular con la presencia de depresión. El modelo de regresión lineal encontró una relación entre menor fuerza de agarre y severidad de la depresión.Conclusión: Existe una asociación entre depresión y niveles bajos de Zn, y una relación inversamente proporcional entre severidad de la depresión y menor fuerza muscular. Estudios en el futuro deben investigar relaciones de causalidad y evaluar la relación entre depresión, fuerza muscular y estado nutricional.(AU)


Assuntos
Humanos , Masculino , Feminino , Força Muscular , Zinco/administração & dosagem , Transtorno Depressivo Maior , Depressão , Coleta de Amostras Sanguíneas , Estudos de Casos e Controles , Colômbia
7.
EMBO Rep ; 25(1): 168-197, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38225354

RESUMO

Cell commitment to tumourigenesis and the onset of uncontrolled growth are critical determinants in cancer development but the early events directing tumour initiating cell (TIC) fate remain unclear. We reveal a single-cell transcriptome profile of brain TICs transitioning into tumour growth using the brain tumour (brat) neural stem cell-based Drosophila model. Prominent changes in metabolic and proteostasis-associated processes including ribogenesis are identified. Increased ribogenesis is a known cell adaptation in established tumours. Here we propose that brain TICs boost ribogenesis prior to tumour growth. In brat-deficient TICs, we show that this dramatic change is mediated by upregulated HEAT-Repeat Containing 1 (HEATR1) to promote ribosomal RNA generation, TIC enlargement and onset of overgrowth. High HEATR1 expression correlates with poor glioma patient survival and patient-derived glioblastoma stem cells rely on HEATR1 for enhanced ribogenesis and tumourigenic potential. Finally, we show that HEATR1 binds the master growth regulator MYC, promotes its nucleolar localisation and appears required for MYC-driven ribogenesis, suggesting a mechanism co-opted in ribogenesis reprogramming during early brain TIC development.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Antígenos de Histocompatibilidade Menor , Proteínas Proto-Oncogênicas c-myc , Proteínas de Ligação a RNA , Animais , Humanos , Encéfalo/metabolismo , Neoplasias Encefálicas/metabolismo , Carcinogênese/patologia , Transformação Celular Neoplásica/patologia , Proteínas de Ligação a DNA/metabolismo , Drosophila/genética , Drosophila/metabolismo , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Glioblastoma/metabolismo , Glioma/patologia , Antígenos de Histocompatibilidade Menor/metabolismo , Células-Tronco Neoplásicas/metabolismo , Proteínas de Ligação a RNA/metabolismo , Proteínas Proto-Oncogênicas c-myc/metabolismo
8.
Pers Soc Psychol Bull ; : 1461672231219719, 2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38284645

RESUMO

Using data from 15 countries, this article investigates whether descriptive and prescriptive gender norms concerning housework and child care (domestic work) changed after the onset of the COVID-19 pandemic. Results of a total of 8,343 participants (M = 19.95, SD = 1.68) from two comparable student samples suggest that descriptive norms about unpaid domestic work have been affected by the pandemic, with individuals seeing mothers' relative to fathers' share of housework and child care as even larger. Moderation analyses revealed that the effect of the pandemic on descriptive norms about child care decreased with countries' increasing levels of gender equality; countries with stronger gender inequality showed a larger difference between pre- and post-pandemic. This study documents a shift in descriptive norms and discusses implications for gender equality-emphasizing the importance of addressing the additional challenges that mothers face during health-related crises.

9.
Artigo em Inglês | MEDLINE | ID: mdl-38265478

RESUMO

Background: Although the postpartum period is an opportunity to address long-term health, fragmented care systems, inadequate attention to social needs, and a lack of structured transition to primary care threaten patient wellbeing, particularly for low-income individuals. Postpartum patient navigation is an emerging innovation to address these disparities. Methods: This mixed-methods analysis uses data from the first year of an ongoing randomized controlled trial to understand the needs of low-income postpartum individuals through 1 year of patient navigation. We designed standardized logs for navigators to record their services, tracking mode, content, intensity, and target of interactions. Navigators also completed semistructured interviews every 3 months regarding relationships with patients and care teams, care system gaps, and navigation process. Log data were categorized, quantified, and mapped temporally through 1 year postpartum. Qualitative data were analyzed using the constant comparative method. Results: Log data from 50 participants who received navigation revealed the most frequent needs related to health care access (45.4%), health and wellness (18.2%), patient-navigator relationship building (14.8%), parenting (13.6%), and social determinants of health (8.0%). Navigation activities included supporting physical and mental recovery, accomplishing health goals, connecting patients to primary and specialty care, preparing for health system utilization beyond navigation, and referring individuals to community resources. Participant needs fluctuated, yielding a dynamic timeline of the first postpartum year. Conclusion: Postpartum needs evolved throughout the year, requiring support from various teams. Navigation beyond the typical postpartum care window may be useful in mitigating health system barriers, and tracking patient needs may be useful in optimizing postpartum care. Clinical Trial Registration: Registered April 19, 2019, enrollment beginning January 21, 2020, NCT03922334, https://clinicaltrials.gov/ct2/show/NCT03922334.

10.
Cureus ; 15(11): e48401, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38074021

RESUMO

Objectives Stereotactic radiosurgery combined with pharmacological treatment is currently one of the most acceptable alternatives for the treatment of trigeminal neuralgia (TN). Our primary endpoint was to report the short-term response (one month) outcomes of 10 patients with refractory TN after CyberKnife® (CK) radiosurgery; secondary endpoints were to assess early side effects and complications. Methods Ten female patients with TN refractory to pharmacological and/or non-pharmacological treatment received a single dose of 90 Gy with CyberKnife® radiosurgery. Clinical and demographic characteristics were obtained from medical records. The visual analog scale (VAS) was used to assess facial pain before as well as seven, 15, and 30 days after treatment. Friedman test was performed to evaluate pain relief in treated patients. Results All patients responded well to the CK and experienced initial adequate pain relief during the first 30 days (p<0.001). No significant differences (p=0.661) were found between six patients who received CK radiosurgery as the first treatment option and those who underwent other non-pharmacological treatments. One patient was re-irradiated with 75 Gy. Transient facial paresthesia was observed in 3/10 patients without any other complications. Conclusion High-tech CK treatment is safe, non-invasive, fast, with minimal side effects, and effective in achieving short-term pain relief in patients with refractory TN, even in those with multiple previous interventions. Given these results, we recommend evaluating CK radiosurgery as the first-line treatment of choice for trigeminal neuralgia refractory to pharmacological treatment.

12.
J Clin Immunol ; 43(8): 2076-2089, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37740092

RESUMO

Variants of uncertain significance (VUS) in CTLA4 are frequently identified in patients with antibody deficiency or immune dysregulation syndromes including, but not limited to, patients with multi-organ autoimmunity and autoinflammation. However, to ascertain the diagnosis of CTLA4 insufficiency, the functional relevance of each variant needs to be determined. Currently, various assays have been proposed to assess the functionality of CTLA4 VUS, including the analysis of transendocytosis, the biological function of CTLA4 to capture CD80 molecules from antigen presenting cells. Challenges of this assay include weak fluorescence intensity of the internalized ligand, poor reproducibility, and poor performance upon analyzing thawed cells. In addition, the distinction of pathogenic from non-pathogenic variants and from wild-type CTLA4, and the classification of the different VUS according to its level of CTLA4 dysfunction, would be desirable. We developed a novel CD80-expressing cell line for the evaluation of CD80-transendocytosis and compared it to the published transendocytosis assay. Our approach showed lower inter-assay variability and better robustness regardless the type of starting material (fresh or thawed peripheral mononuclear cells). In addition, receiver operating characteristic analysis showed 100% specificity, avoiding false positive results and allowing for a clear distinction between pathogenic and non-pathogenic variants in CTLA4-variant carriers. With our transendocytosis assay, we assessed the pathogenicity of 24 distinct CTLA4 variants from patients submitted to our diagnostic unit. Significantly impaired transendocytosis was demonstrated for 17 CTLA4 variants, whereas seven variants tested normal. In conclusion, our upgraded transendocytosis assay allows a reliable assessment of newly identified variants in CTLA4.


Assuntos
Células Apresentadoras de Antígenos , Autoimunidade , Humanos , Antígeno CTLA-4/genética , Citometria de Fluxo , Reprodutibilidade dos Testes
13.
Int J Mol Sci ; 24(16)2023 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-37628979

RESUMO

Marine ecosystems are among the richest in terms of biodiversity, and at present, still remain largely unknown today. In the molecular biology era, several analyses have been conducted to unravel the biological processes in this ecosystem. These systems have provided biotechnological solutions to current problems, including the treatment of diseases, as well as for the development of new biotechnological tools with applications in biomedicine and/or agri-food. In addition, in the context of climate change and global warming, these studies become even more necessary for the development of molecular tools that allow a reliable follow-up of this situation to anticipate alterations and responses of bioindicator species and to create a database to prevent and predict the environmental and climatic changes before the damage is irreversible. Proteomics approaches have revealed their potential use to obtain the set of biological effectors that lead to the real biological station on a specific stage, the proteins. In addition, proteomics-based algorithms have allowed the discovery of proteins with new potential biotechnological applications from proteome data through "applied proteomics". In this project, the first proteome analysis of the sea anemone, Anemonia sulcata, and its symbiont has been developed. These organisms present a wide distribution sea ecosystem. In Spain, it is accepted as a fishing and aquaculture species. Moreover, Anemonia sulcate has a symbiotic relation with autotroph Dinoflagellates, Symbiodinium spp., that allows the study of its relation at the molecular level. For the first characterization of A. sulcata proteome, three independent biological replicates were used, and proteins were extracted and analyzed by LC-MS/MS, allowing the quantification of 325 proteins, 81 from Symbiodinium spp. proteins and 244 from A. sulcata proteins. These proteins were subjected to gene ontology categorization by Cellular Component, Molecular Function and Biological Process. These analyzes have allowed the identification of biomarkers of gene expression as potential powerful emerging diagnostic tools to identify and characterize the molecular drivers of climate change stresses and improve monitoring techniques. In addition, through the application of novel algorithms for the detection of bioactive compounds based on the analysis of molecules of marine origin, the proteome has allowed the identification of proteins with potential applications in the fields of biomedicine and agri-food.


Assuntos
Dinoflagellida , Anêmonas-do-Mar , Animais , Proteômica , Ecossistema , Mudança Climática , Proteoma , Cromatografia Líquida , Espectrometria de Massas em Tandem , Biomarcadores
14.
Environ Health Perspect ; 131(8): 85001, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37610227

RESUMO

BACKGROUND: Increasingly, marginalized communities are disproportionately facing the worsening effects of environmental hazards, including air pollution, water pollution, and climate change. Language isolation and accessibility has been understudied as a determinant of health. Spanish, despite being the second-most common language in the United States with some 41.8 million speakers, has been neglected among environmental health scientists. Building capacity in high-quality Spanish-language science communication, both for scientific and nonscientific audiences, can yield improvements in health disparities research, public health literacy, international collaborations, and diversity and inclusion efforts. OBJECTIVES: In this article, we discuss the context of language diversity in environmental health sciences and offer recommendations for improving science communication in Spanish. DISCUSSION: English is currently the predominant language for scientific discourse, but Spanish and other non-English languages are routinely used by many environmental health science students and professionals, as well as much of the public. To more effectively conduct and communicate environmental health work in Spanish, we suggest that researchers and scientific institutions a) foster structural changes, b) train emerging scholars and support established researchers, c) tap into community ways of knowing, and d) leverage emerging technologies. https://doi.org/10.1289/EHP12306.


Assuntos
Poluição do Ar , Saúde Ambiental , Estados Unidos , Humanos , Comunicação , Poluição da Água , Justiça Social
16.
Dis Model Mech ; 16(7)2023 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-37382373

RESUMO

The Arp2/3 complex drives the formation of branched actin networks that are essential for many cellular processes. In humans, the ARPC5 subunit of the Arp2/3 complex is encoded by two paralogous genes (ARPC5 and ARPC5L) with 67% identity. Through whole-exome sequencing, we identified a biallelic ARPC5 frameshift variant in a female child who presented with recurrent infections, multiple congenital anomalies, diarrhea and thrombocytopenia, and suffered early demise from sepsis. Her consanguineous parents also had a previous child who died with similar clinical features. Using CRISPR/Cas9-mediated approaches, we demonstrate that loss of ARPC5 affects actin cytoskeleton organization and function in vitro. Homozygous Arpc5-/- mice do not survive past embryonic day 9 owing to developmental defects, including loss of the second pharyngeal arch, which contributes to craniofacial and heart development. Our results indicate that ARPC5 is important for both prenatal development and postnatal immune signaling, in a non-redundant manner with ARPC5L. Moreover, our observations add ARPC5 to the list of genes that should be considered when patients present with syndromic early-onset immunodeficiency, particularly if recessive inheritance is suspected.


Assuntos
Complexo 2-3 de Proteínas Relacionadas à Actina , Actinas , Humanos , Criança , Feminino , Camundongos , Animais , Complexo 2-3 de Proteínas Relacionadas à Actina/genética , Inflamação
17.
Front Sociol ; 8: 959765, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37250439

RESUMO

Context: Puerto Rico experienced four natural disasters in 4 years (2017-2021): Hurricanes Irma and Maria, thousands of earthquakes reaching 6.4 magnitude, and the COVID-19 pandemic. In this context, our team sought to understand the impact of disaster aid distribution on poverty and economic inequality, and their relationship to the spread of COVID-19 across Puerto Rico. Rapid research was required to ensure we could collect perishable data within this ever-changing context. Challenges: Our mixed methods design relied on both secondary and primary data. Because analyses of the former were to inform where and how to collect the latter, timing was of the essence. The data sources identified were not readily available to the public, and thus required gaining access through direct requests to government agencies. The requests coincided with a transition between administrations after an election. This resulted in unexpected delays. Once in the field, the team had to balance the rapid nature of the research with the mindful work to avoid compounding traumas experienced by participants, heightened risk for re-traumatization and fatigue, the risk of COVID-19, the digital divide, and intermittent electrical and telecommunication services. Adaptations: In response to the delayed access to secondary data, we adjusted our research question. We continued to collect data as they became available, incorporating some immediately into analyses, and cleaning and storing others for future research opportunities. To overcome ongoing trauma challenges and prevent fatigue, we recruited and hired a large temporary team, including members of communities where we collected data. By recruiting participants and co-researchers at the same time and place, we both collapsed time between these activities and increased our team's contextual competency. To adapt to challenges presented by the pandemic, we created hybrid data collection procedures where some data were collected online, and some in person, while maintaining COVID-19 protections. We used similar adaptations for dissemination. Lessons: Rapid research needs to be agile. Working within a convergence framework to investigate wicked problems had the unexpected added benefit of providing our team with a variety of disciplinary approaches which proved helpful in adapting to the changing conditions in the field. In addition to the resourcefulness of a transdisciplinary team, it is important to be willing to pivot in response to changes and to collect data where and when you can. To increase participation, opportunities need to be designed with flexibility, mindful of competing demands faced by individuals willing to collaborate. Collecting and analyzing data iteratively and utilizing local resources can enable rapid research that is rigorous and yields rich data. Contributions: Our team applied the lessons learned to structure a rapid and iterative dissemination plan. We combined member-checking with community-level dissemination, enabling us to hone findings further before presenting to policy makers and media. Rapid research creates opportunities to make data-informed program and policy adjustments when they can be most impactful. Both the media and policy makers pay closer attention to research on current events. Hence, our recommendation is to do more rapid research! The more we do, the better we will get at it, and the more accustomed community leaders, policy makers, and program designers will become to using data to inform decisions.

18.
J Exp Clin Cancer Res ; 42(1): 55, 2023 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-36864434

RESUMO

Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous group of tumors that affect different anatomical locations. Despite this heterogeneity, HNSCC treatment depends on the anatomical location, TNM stage and resectability of the tumor. Classical chemotherapy is based on platinum-derived drugs (cisplatin, carboplatin and oxaliplatin), taxanes (docetaxel, paclitaxel) and 5-fluorouracil1. Despite advances in HNSCC treatment, the rate of tumor recurrence and patient mortality remain high. Therefore, the search for new prognostic identifiers and treatments targeting therapy-resistant tumor cells is vital. Our work demonstrates that there are different subgroups with high phenotypic plasticity within the CSC population in HNSCC. CD10, CD184, and CD166 may identify some of these CSC subpopulations with NAMPT as a common metabolic gene for the resilient cells of these subpopulations. We observed that NAMPT reduction causes a decrease in tumorigenic and stemness properties, migration capacity and CSC phenotype through NAD pool depletion. However, NAMPT-inhibited cells can acquire resistance by activating the NAPRT enzyme of the Preiss-Handler pathway. We observed that coadministration of the NAMPT inhibitor with the NAPRT inhibitor cooperated inhibiting tumor growth. The use of an NAPRT inhibitor as an adjuvant improved NAMPT inhibitor efficacy and reduced the dose and toxicity of these inhibitors. Therefore, it seems that the reduction in the NAD pool could have efficacy in tumor therapy. This was confirmed by in vitro assays supplying the cells with products of inhibited enzymes (NA, NMN or NAD) and restoring their tumorigenic and stemness properties. In conclusion, the coinhibition of NAMPT and NAPRT improved the efficacy of antitumor treatment, indicating that the reduction in the NAD pool is important to prevent tumor growth.


Assuntos
Neoplasias de Cabeça e Pescoço , NAD , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Recidiva Local de Neoplasia , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Células-Tronco Neoplásicas , Carcinogênese
19.
BMC Public Health ; 23(1): 575, 2023 03 28.
Artigo em Inglês | MEDLINE | ID: mdl-36978071

RESUMO

BACKGROUND: It is critical to assess implementation fidelity of evidence-based interventions and factors moderating fidelity, to understand the reasons for their success or failure. However, fidelity and fidelity moderators are seldom systematically reported. The study objective was to conduct a concurrent implementation fidelity evaluation and examine fidelity moderators of CHORD (Community Health Outreach to Reduce Diabetes), a pragmatic, cluster-randomized, controlled trial to test the impact of a Community Health Workers (CHW)-led health coaching intervention to prevent incident type 2 Diabetes Mellitus in New York (NY). METHODS: We applied the Conceptual Framework for Implementation Fidelity to assess implementation fidelity and factors moderating it across the four core intervention components: patient goal setting, education topic coaching, primary care (PC) visits, and referrals to address social determinants of health (SDH), using descriptive statistics and regression models. PC patients with prediabetes receiving care from safety-net patient-centered medical homes (PCMHs) at either, VA NY Harbor or at Bellevue Hospital (BH) were eligible to be randomized into the CHW-led CHORD intervention or usual care. Among 559 patients randomized and enrolled in the intervention group, 79.4% completed the intake survey and were included in the analytic sample for fidelity assessment. Fidelity was measured as coverage, content adherence and frequency of each core component, and the moderators assessed were implementation site and patient activation measure. RESULTS: Content adherence was high for three components with nearly 80.0% of patients setting ≥ 1 goal, having ≥ 1 PC visit and receiving ≥ 1 education session. Only 45.0% patients received ≥ 1 SDH referral. After adjusting for patient gender, language, race, ethnicity, and age, the implementation site moderated adherence to goal setting (77.4% BH vs. 87.7% VA), educational coaching (78.9% BH vs. 88.3% VA), number of successful CHW-patient encounters (6 BH vs 4 VA) and percent of patients receiving all four components (41.1% BH vs. 25.7% VA). CONCLUSIONS: The fidelity to the four CHORD intervention components differed between the two implementation sites, demonstrating the challenges in implementing complex evidence-based interventions in different settings. Our findings underscore the importance of measuring implementation fidelity in contextualizing the outcomes of randomized trials of complex multi-site behavioral interventions. TRIAL REGISTRATION: The trial was registered with ClinicalTrials.gov on 30/12/2016 and the registration number is NCT03006666 .


Assuntos
Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/prevenção & controle , Cidade de Nova Iorque , Terapia Comportamental , Hospitais , Atenção Primária à Saúde
20.
Nutrients ; 15(4)2023 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-36839213

RESUMO

Background: Enteral nutrition interruptions (ENI) are prevalent in the pediatric intensive care unit (PICU), but there is little evidence of their characteristics. Methods: This is a cross-sectional multicenter study including critically ill children on enteral nutrition. ENIs were classified as PICU procedures, procedures performed outside the PICU (PPOP), feeding intolerance and other criteria. The number and features of ENIs were collected. Results: A total of 75 children were enrolled. There were 41 interruptions affecting 37.3% of the patients with a median duration of 5 ± 9.4 h. The most common reason for ENI was PPOP (41.5%), followed by other criteria. Interruptions were considered preventable in 24.4% of the cases, but only eight were compensated. ENIs were more prevalent among children with cardiac disease (p = 0.047), higher PRISM (p = 0.047) and longer PICU stay (p = 0.035). There was association between PRISM and total interruption time (p = 0.02) and lower caloric intake (p = 0.035). Patients with respiratory illness (p = 0.022) and on noninvasive ventilation (p = 0,028) had fewer ENIs. ENI total time was associated with lower caloric (p = 0.001) and protein (p = 0.02) intake. Conclusions: ENIs are prevalent in PICU, especially in children with higher PRISM, longer PICU stays and cardiac disease, and result in lower caloric and protein intake.


Assuntos
Estado Terminal , Cardiopatias , Humanos , Criança , Prevalência , Estudos Transversais , Ingestão de Energia , Fatores de Risco
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