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1.
Am J Transplant ; 24(1): 104-114, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37666457

RESUMO

Face transplantation is a viable reconstructive approach for severe craniofacial defects. Despite the evolution witnessed in the field, ethical aspects, clinical and psychosocial implications, public perception, and economic sustainability remain the subject of debate and unanswered questions. Furthermore, poor data reporting and sharing, the absence of standardized metrics for outcome evaluation, and the lack of consensus definitions of success and failure have hampered the development of a "transplantation culture" on a global scale. We completed a 2-round online modified Delphi process with 35 international face transplant stakeholders, including surgeons, clinicians, psychologists, psychiatrists, ethicists, policymakers, and researchers, with a representation of 10 of the 19 face transplant teams that had already performed the procedure and 73% of face transplants. Themes addressed included patient assessment and selection, indications, social support networks, clinical framework, surgical considerations, data on patient progress and outcomes, definitions of success and failure, public image and perception, and financial sustainability. The presented recommendations are the product of a shared commitment of face transplant teams to foster the development of face transplantation and are aimed at providing a gold standard of practice and policy.


Assuntos
Transplante de Face , Alotransplante de Tecidos Compostos Vascularizados , Humanos , Transplante de Face/métodos , Consenso , Técnica Delphi , Projetos de Pesquisa
2.
J Pediatr ; 271: 114057, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38614257

RESUMO

OBJECTIVE: To evaluate the effectiveness of a new model, Case Analysis and Translation to Care in Hospital (CATCH), for the review of pediatric inpatient cases when an adverse event or "close call" had occurred. STUDY DESIGN: The curricular intervention consisted of an introductory podcast/workshop, mentorship of presenters, and monthly CATCH rounds over 16 months. The study was conducted with 22 pediatricians at a single tertiary care center. Intervention assessment occurred using participant surveys at multiple intervals: pre/post the intervention, presenter experience (post), physicians involved and mentors experience (post), and after each CATCH session. Paired t-tests and thematic analysis were used to analyze data. Time required to support the CATCH process was used to assess feasibility. RESULTS: Our overall experience and data revealed a strong preference for the CATCH model, high levels of engagement and satisfaction with CATCH sessions, and positive presenter as well as physicians-involved and mentor experiences. Participants reported that the CATCH model is feasible, engages physicians, promotes a safe learning environment, facilitates awareness of tools for case analysis, and provides opportunities to create "CATCH of the Day" recommendations to support translation of learning to clinical practice. CONCLUSIONS: The CATCH model has significant potential to strengthen clinical case rounds in pediatric hospital medicine. Future research is needed to assess the effectiveness of the model at additional sites and across medical specialities.


Assuntos
Hospitais Pediátricos , Melhoria de Qualidade , Humanos , Visitas de Preceptoria/métodos , Segurança do Paciente , Pediatria/educação , Medicina Hospitalar/educação , Modelos Educacionais , Cultura Organizacional , Masculino , Feminino
3.
Mol Pharm ; 21(5): 2383-2393, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38551360

RESUMO

Nanocone clusters (NCCs) have been developed as clusters with inclusion complexes of FDA-approved ß-cyclodextrin (ßCD) and perfluorocarbons (PFC) (i.e., perfluoropentane (PFP) and perfluorohexane (PFH)) and have shown promise in nanoparticle-mediated histotripsy (NMH) applications owing to their lowered cavitation threshold, ease of production, and fluorocarbon quantification. However, there is still a lack of information on the best conditions of the synthesis of NCCs as a product that can have a maximum determinable fluorocarbon content and maintain the stability of the NCC during synthesis and when used as histotripsy agents or exposed to physiological conditions. These concerns about the stability of the clusters and the best possible formulation are investigated in the current work. The cluster formation potential was tested taking into consideration the nature of both PFCs and ßCD by employing different synthesis conditions in terms of solution and environmental parameters such as concentration of solvent, stoichiometry between ßCD and PFCs, temperature, pH, solvent type, etc. The best route of synthesis was then translated into various batch sizes and investigated in terms of the PFC loading and yield. These studies revealed that preparing NCCs in double-distilled water in an ice bath at the optimized solution concentration gave the highest yields and optimal PFC loading, as determined from gas chromatography. Furthermore, the stability of the clusters with different stoichiometries was scrutinized in varying concentrations, mechanical disruption times, pH levels, and temperature conditions, showing effects on each cluster's particle size in dynamic light scattering, visualized in transmission electron microscopy, and cavitation behavior in agarose gel tissue phantoms. These studies revealed stable clusters for all formulations, with PFH-containing NCCs emerging to be the most stable in terms of their cluster size and bubble formation potential in histotripsy. Finally, the shelf life of these clusters was investigated using DLS, which revealed a stable cluster. In conclusion, NCCs have shown high stability in terms of both synthesis, which can be replicated in gram-level production, and the cluster itself, which can be exposed to harsher conditions and still form stable bubbles in histotripsy.


Assuntos
Fluorocarbonos , Nanopartículas , beta-Ciclodextrinas , Fluorocarbonos/química , beta-Ciclodextrinas/química , Nanopartículas/química , Solventes/química , Temperatura , Concentração de Íons de Hidrogênio , Pentanos
4.
Eur J Nutr ; 63(4): 1315-1327, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38409436

RESUMO

PURPOSE: Evidence is growing that high salt intake is an independent risk factor for obesity, but the mechanisms are unknown. Our novel working hypothesis is that high salt intake drives cortisol production, which in turn, drives obesity. The current study aimed to demonstrate an acute cortisol response following a single high salt meal. METHODS: Eight participants (age 30.5 ± 9.8 years [mean ± SD], 50% female), consumed high salt (3.82 g; 1529 mg sodium) and low salt (0.02 g; 9 mg sodium) meals in a randomized cross-over design. RESULTS: Urinary and salivary cortisol and plasma adrenocorticotropic hormone (ACTH) demonstrated order effects. When high salt was given second, there was a peak above baseline for urinary cortisol (26.3%), salivary cortisol (9.4%) and plasma ACTH (4.1%) followed by a significant decline in each hormone (treatment*time, F[9, 18] = 2.641, p = 0.038, partial η2 = 0.569; treatment*time, F[12, 24] = 2.668, p = 0.020, partial η2 = 0.572; treatment*time, F[12, 24] = 2.580, p = 0.023, partial η2 = 0.563, respectively), but not when high salt was given first (p > 0.05 for all). CONCLUSION: These intriguing findings provide partial support for our hypothesis and support a need for further research to elucidate the role of high salt intake in cortisol production and, in turn, in the aetiology of obesity. TRIAL REGISTRATION NUMBER: ACTRN12623000490673; date of registration 12/05/2023; retrospectively registered.


Assuntos
Estudos Cross-Over , Hidrocortisona , Obesidade , Cloreto de Sódio na Dieta , Humanos , Hidrocortisona/sangue , Feminino , Projetos Piloto , Adulto , Obesidade/metabolismo , Cloreto de Sódio na Dieta/administração & dosagem , Masculino , Adulto Jovem , Saliva/metabolismo , Hormônio Adrenocorticotrópico/sangue
5.
J Deaf Stud Deaf Educ ; 29(2): 170-186, 2024 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-38160399

RESUMO

Deaf patients who communicate in American Sign Language (ASL) experience communication challenges leading to medical errors, treatment delays, and health disparities. Research on Deaf patient communication preferences is sparse. Researchers conducted focus groups based on the Health Belief Model with culturally Deaf patients and interpreters. The ASL focus groups were interpreted and transcribed into written English, verified by a third-party interpreting agency, and uploaded into NVivo. Deductive coding was used to identify communication methods and inductive coding was used to identify themes within each. Writing back-and-forth introduced challenges related to English proficiency, medical terminology, poor penmanship, and tendencies of providers to abbreviate. Participants had various speechreading abilities and described challenges with mask mandates. Multiple issues were identified with family and friends as proxy interpreters, including a lack of training, confidentiality issues, emotional support, and patient autonomy. Video remote interpreter challenges included technical, environmental, and interpreter qualification concerns. Participants overwhelmingly preferred on-site interpreters for communication clarity. While there was a preference for direct care, many acknowledged this is not always feasible due to lack of providers fluent in ASL. Access to on-site interpreters is vital for many Deaf patients to provide full access to critical medical information. Budget allocation for on-call interpreters is important in emergency settings.


Assuntos
Surdez , Humanos , Comunicação , Língua de Sinais , Grupos Focais , Pessoal de Saúde , Barreiras de Comunicação , Tradução
6.
Proc Natl Acad Sci U S A ; 117(23): 12847-12855, 2020 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-32457163

RESUMO

Microtubule network remodeling is essential for fundamental cellular processes including cell division, differentiation, and motility. Microtubules are active biological polymers whose ends stochastically and independently switch between phases of growth and shrinkage. Microtubule treadmilling, in which the microtubule plus end grows while the minus end shrinks, is observed in cells; however, the underlying mechanisms are not known. Here, we use a combination of computational and in vitro reconstitution approaches to determine the conditions leading to robust microtubule treadmilling. We find that microtubules polymerized from tubulin alone can treadmill, albeit with opposite directionality and order-of-magnitude slower rates than observed in cells. We then employ computational simulations to predict that the combinatory effects of four microtubule-associated proteins (MAPs), namely EB1, XMAP215, CLASP2, and MCAK, can promote fast and sustained plus-end-leading treadmilling. Finally, we experimentally confirm the predictions of our computational model using a multi-MAP, in vitro microtubule dynamics assay to reconstitute robust plus-end-leading treadmilling, consistent with observations in cells. Our results demonstrate how microtubule dynamics can be modulated to achieve a dynamic balance between assembly and disassembly at opposite polymer ends, resulting in treadmilling over long periods of time. Overall, we show how the collective effects of multiple components give rise to complex microtubule behavior that may be used for global network remodeling in cells.


Assuntos
Proteínas Associadas aos Microtúbulos/metabolismo , Microtúbulos/metabolismo , Animais , Simulação de Dinâmica Molecular , Proteínas Recombinantes/metabolismo , Células Sf9 , Imagem com Lapso de Tempo
7.
J Appl Res Intellect Disabil ; 36(3): 547-557, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36738096

RESUMO

BACKGROUND: Adults with intellectual disabilities are living longer and experiencing retirement. However, research about retirement experiences is limited. METHOD: This qualitative study used semi-structured interviews with 10 retired/retiring U.S. adults with intellectual disabilities and an ally of their choice. RESULTS: Participants described factors that pushed or pulled them into retirement, such as health issues or wanting to spend more time with family. Individuals in community work settings described greater self-determination in their decision to retire. Regardless of reasons for retiring, all participants described initial difficulties with adjusting to retirement but over time people's situation, including their mental and physical health, reportedly improved. CONCLUSION: Retirement is a significant life transition. More attention is needed about planning and developing age-appropriate and person-cantered inclusive retirement options for older adults with intellectual disabilities, similar to the transition into adulthood and work life.


Assuntos
Deficiência Intelectual , Aposentadoria , Humanos , Idoso
8.
Br J Community Nurs ; 28(2): 96-101, 2023 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-36735365

RESUMO

BACKGROUND: the potential fire risk of fabrics impregnated with emollients has been described within the health service, including ignition of bandages. The role of emollients in fire fatalities have also been included in coroner reports, as accelerating fires when present. AIMS: although changes in burning behaviour is known, no standard tests have been carried out on bandages which are often used in conjunction with emollients. METHOD: using a standard vertical flammability test, the flammability of viscose bandage was compared to when impregnated with nine dried on emollients with low to high and non-paraffin content. FINDINGS: the time to ignition was significantly reduced with an emollient present and the glowing time was longer. CONCLUSIONS: the same safety advice applies to viscose bandages as other fabrics with emollients; do not expose them to naked flames or high heat sources or allow emollients to build up on bandages.


Assuntos
Emolientes , Incêndios , Humanos , Bandagens
9.
Biophys J ; 121(8): 1417-1423, 2022 04 19.
Artigo em Inglês | MEDLINE | ID: mdl-35314142

RESUMO

While it is established that the topology of lipid membranes plays an important role in biochemical processes, few direct observations exist regarding how the membranes are actively restructured and its consequences on subsequent reactions. In this work, we investigated how the two major components of bee venom, melittin and phospholipase A2 (PLA2), achieve activation by such membrane remodeling. Their membrane-disrupting functions have been reported to increase when both are present, but the mechanism of this synergism had not been established. Using membrane reconstitution, we found that melittin can form large-scale membrane deformities upon which PLA2 activity is 25-fold higher. Tracking of single-molecule PLA2 revealed that its processive behavior on these deformities underlies the enhanced activity. These results show how melittin and PLA2 work synergistically to enhance the lytic effects of the bee venom. More broadly, they also demonstrate how the membrane topology may be actively altered to modulate cellular membrane-bound reactions.


Assuntos
Venenos de Abelha , Meliteno , Venenos de Abelha/química , Meliteno/farmacologia , Fosfolipases A2
10.
Am J Physiol Regul Integr Comp Physiol ; 322(2): R144-R151, 2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-34936501

RESUMO

Although the patterns of response within the sympathoadrenal medullary (SAM) system and hypothalamo-pituitary adrenal (HPA) axis are interesting and important in their own accord, the overall response to acute psychological stress involves reactivity of both pathways. We tested the hypothesis that consideration of the integrated response of these pathways may reveal dysregulation of the stress systems, which is not evident when considering either system alone. Age-matched lean and overweight/obese men were subjected to a Trier Social Stress Test and reactivity of the SAM system (salivary α-amylase, systolic blood pressure, diastolic blood pressure, and heart rate) and the HPA axis (salivary cortisol) were measured. Relative reactivity of SAM system and HPA axis was calculated as the ratio between the measures from each pathway. Although analysis of reactivity of individual stress pathways showed no evidence of dysfunction in overweight/obese compared with lean men, analysis of HPA/SAM reactivity revealed significantly lower cortisol over systolic blood pressure (CoSBP) and cortisol over diastolic blood pressure (CoDBP) reactivity in overweight/obese compared with lean men. Other measures of HPA/SAM reactivity and all measures of SAM/HPA reactivity were unaltered in overweight/obese compared with lean men. These findings suggest that the cortisol response per unit of blood pressure response is blunted in men with elevated adiposity. Furthermore, these findings support a notion of a coordinated overall approach to activation of the stress pathways with the degree of activation in one pathway being related to the degree of activation in the other.


Assuntos
Medula Suprarrenal/inervação , Sistema Hipotálamo-Hipofisário/fisiopatologia , Obesidade/fisiopatologia , Estresse Psicológico/fisiopatologia , Sistema Nervoso Simpático/fisiopatologia , Magreza/fisiopatologia , Adiposidade , Idoso , Biomarcadores/sangue , Pressão Sanguínea , Frequência Cardíaca , Humanos , Hidrocortisona/metabolismo , Sistema Hipotálamo-Hipofisário/metabolismo , Masculino , Pessoa de Meia-Idade , Obesidade/metabolismo , Obesidade/psicologia , Saliva/enzimologia , Estresse Psicológico/metabolismo , Estresse Psicológico/psicologia , Magreza/metabolismo , Magreza/psicologia , alfa-Amilases/metabolismo
11.
Mol Pharm ; 19(8): 2907-2921, 2022 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-35839291

RESUMO

Recently developed nanocones (NCs), which are inclusion complexes that are made up of cyclodextrins (CDs) and perfluorocarbons (PFCs), have shown promising results in nanoparticle-mediated histotripsy (NMH) applications due to stable inclusion complexation, PFC quantification, simple synthesis, and processing. FDA-approved ßCD and its modified versions such as low-degree methylated ßCD have been previously demonstrated as prime examples of structures capable of accommodating PFC molecules. However, the complex formation potential of different CDs with various cavity sizes in the presence of PFC molecules, and their consequent aggregation, needs to be explored. In the present study, the complexation and aggregation potential of some natural CDs and their respective derivatives either exposed to perfluoropentane (PFP) or perfluorohexane (PFH) were studied in the wet lab. Computational studies were also performed to account for the limitations faced in PFC quantification because of the low optical density of PFCs within the CD complex and to discover the best candidate for NMH applications. All results revealed that only ßCD and γCD (except HMγCD) derivatives form an inclusion complex with PFCs and only LMßCD, ßCD, and γCD form nanocone clusters (NCCs), which precipitate and can be collected for use. Furthermore, the data collectively show that ßCD and PFCs have the best complexation due to stable complex formation, ease of production, and product recovery, especially with PFH as a more suitable candidate due to its high boiling point, which allows workability during synthesis. Although simulations suggest that highly stable inclusion complexes exist, such as HPßCD, the cluster formation resulting in precipitation is hindered due to the high solubility of CDs in water, resulting in intangible yields to work with even after employing general laboratory recovery methods. Conclusively, histotripsy cavitation experiments successfully showed a decreased cavitation threshold among optimal NCC candidates that were identified, supporting their use in NMH.


Assuntos
Ciclodextrinas , Fluorocarbonos , 2-Hidroxipropil-beta-Ciclodextrina , Análise por Conglomerados , Ciclodextrinas/química , Fluorocarbonos/química , Solubilidade
12.
Biomacromolecules ; 23(12): 5297-5311, 2022 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-36418020

RESUMO

Nanocone clusters (NCCs) are new-generation agents of nanoparticle-mediated histotripsy (NMH) recently developed to address the limitations of previously designed nanodroplets (NDs). NCCs can be obtained by simply mixing FDA-approved cyclodextrins (CD) and suitable perfluorocarbons (PFCs), which result in smaller size aggregates, detectable PFC amount, and more stable long-term storage since the obtained powder can be stored and redispersed as needed. Previous experimental and computational studies showed that NCCs consist of an organization of inclusion complexes of CD and PFC around free PFC droplets, and their aggregate behavior depends on the localization of PFC in the cavity and the water solubility of CD derivatives. It has been shown that ß-cyclodextrin (ßCD) and perfluorohexane (PFH) are ideal candidates for NCCs that can be isolated as a powder with high PFC content among various CD and PFC derivatives. This study focuses on the further development of the selected NCC composition to enhance the potential of NMH therapy while also enabling more detailed future experiments in vitro and in vivo. It is aimed to show the bioconjugation potential of NCCs through the example of the most commonly used functionalization methods such as targeting, PEGylation, and fluorescent labeling. For this purpose, ßCD as a building block was monofunctionalized with groups such as azide, alkyne, and amine groups that allow for effective coupling reactions such as the "click" reaction and N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride/N-hydroxysuccinimide (EDC/NHS) coupling. These monofunctional ßCDs were used as building blocks of NCCs in the presence of PFH to obtain functional NCCs as precursors of bioconjugation. EPPT1 as a synthetic peptide specific to uMUC1 and folic acid (FA) as the most commonly used targeting agent along with PEGylation were successfully shown as bioconjugation examples. Lastly, fluorescently labeled NCCs were obtained via fluorescein isothiocyanate (FITC) and alkyne functional NCC reaction through propargyl amine and isothiocyanate group reaction. The obtained bioconjugates were tested in vitro to validate the conjugation, and the ability to lower the histotripsy cavitation threshold, which is necessary for NMH, was demonstrated for all bioconjugates. Overall, the results showed that all obtained bioconjugates successfully lowered the cavitation threshold pressure while also fulfilling the desired bioconjugation metrics to serve as improved tools to enhance NMH as a targeted noninvasive ablation method.


Assuntos
Fluorocarbonos , Nanopartículas , beta-Ciclodextrinas , Fluorocarbonos/química , Nanopartículas/química , Aminas
13.
Clin Infect Dis ; 73(5): e1126-e1134, 2021 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-33289028

RESUMO

BACKGROUND: The Core Elements of Outpatient Antibiotic Stewardship provide a framework to improve antibiotic use. We report the impact of core elements implementation within Veterans Health Administration sites. METHODS: In this quasiexperimental controlled study, effects of an intervention targeting antibiotic prescription for uncomplicated acute respiratory tract infections (ARIs) were assessed. Outcomes included per-visit antibiotic prescribing, treatment appropriateness, ARI revisits, hospitalization, and ARI diagnostic changes over a 3-year pre-implementation period and 1-year post-implementation period. Logistic regression adjusted for covariates (odds ratio [OR], 95% confidence interval [CI]) and a difference-in-differences analysis compared outcomes between intervention and control sites. RESULTS: From 2014-2019, there were 16 712 and 51 275 patient visits within 10 intervention and 40 control sites, respectively. Antibiotic prescribing rates pre- and post-implementation within intervention sites were 59.7% and 41.5%, compared to 73.5% and 67.2% within control sites, respectively (difference-in-differences, P < .001). Intervention site pre- and post-implementation OR to receive appropriate therapy increased (OR, 1.67; 95% CI, 1.31-2.14), which remained unchanged within control sites (OR,1.04; 95% CI, .91-1.19). ARI-related return visits post-implementation (-1.3% vs -2.0%; difference-in-differences P = .76) were not different, but all-cause hospitalization was lower within intervention sites (-0.5% vs -0.2%; difference-in-differences P = .02). The OR to diagnose non-specific ARI compared with non-ARI diagnoses increased post-implementation forintervention (OR, 1.27; 95% CI, 1.21 -1.34) but not control (OR, 0.97; 95% CI, .94-1.01) sites. CONCLUSIONS: Implementation of the core elements was associated with reduced antibiotic prescribing for RIs and a reduction in hospitalizations. Diagnostic coding changes were observed.


Assuntos
Gestão de Antimicrobianos , Infecções Respiratórias , Antibacterianos/uso terapêutico , Serviço Hospitalar de Emergência , Humanos , Prescrição Inadequada , Pacientes Ambulatoriais , Padrões de Prática Médica , Atenção Primária à Saúde , Infecções Respiratórias/tratamento farmacológico , Saúde dos Veteranos
14.
PLoS Genet ; 14(2): e1007219, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29447162

RESUMO

Environmental stress during early development in animals can have profound effects on adult phenotypes via programmed changes in gene expression. Using the nematode C. elegans, we demonstrated previously that adults retain a cellular memory of their developmental experience that is manifested by differences in gene expression and life history traits; however, the sophistication of this system in response to different environmental stresses, and how it dictates phenotypic plasticity in adults that contribute to increased fitness in response to distinct environmental challenges, was unknown. Using transcriptional profiling, we show here that C. elegans adults indeed retain distinct cellular memories of different environmental conditions. We identified approximately 500 genes in adults that entered dauer due to starvation that exhibit significant opposite ("seesaw") transcriptional phenotypes compared to adults that entered dauer due to crowding, and are distinct from animals that bypassed dauer. Moreover, we show that two-thirds of the genes in the genome experience a 2-fold or greater seesaw trend in gene expression, and based upon the direction of change, are enriched in large, tightly linked regions on different chromosomes. Importantly, these transcriptional programs correspond to significant changes in brood size depending on the experienced stress. In addition, we demonstrate that while the observed seesaw gene expression changes occur in both somatic and germline tissue, only starvation-induced changes require a functional GLP-4 protein necessary for germline development, and both programs require the Argonaute CSR-1. Thus, our results suggest that signaling between the soma and the germ line can generate phenotypic plasticity as a result of early environmental experience, and likely contribute to increased fitness in adverse conditions and the evolution of the C. elegans genome.


Assuntos
Caenorhabditis elegans , Meio Ambiente , Reprodução/genética , Estresse Fisiológico/fisiologia , Animais , Animais Geneticamente Modificados , Caenorhabditis elegans/genética , Caenorhabditis elegans/crescimento & desenvolvimento , Caenorhabditis elegans/fisiologia , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/fisiologia , Cromossomos/metabolismo , Cromossomos/fisiologia , Regulação da Expressão Gênica no Desenvolvimento , Interação Gene-Ambiente , Células Germinativas/fisiologia , Proteínas de Membrana/fisiologia , Fenótipo , Transdução de Sinais/genética
15.
Development ; 144(16): 2896-2906, 2017 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-28811311

RESUMO

The developmental accumulation of proliferative germ cells in the C. elegans hermaphrodite is sensitive to the organismal environment. Previously, we found that the TGFß signaling pathway links the environment and proliferative germ cell accumulation. Neuronal DAF-7/TGFß causes a DAF-1/TGFßR signaling cascade in the gonadal distal tip cell (DTC), the germline stem cell niche, where it negatively regulates a DAF-3 SMAD and DAF-5 Sno-Ski. LAG-2, a founding DSL ligand family member, is produced in the DTC and activates the GLP-1/Notch receptor on adjacent germ cells to maintain germline stem cell fate. Here, we show that DAF-7/TGFß signaling promotes expression of lag-2 in the DTC in a daf-3-dependent manner. Using ChIP and one-hybrid assays, we find evidence for direct interaction between DAF-3 and the lag-2 promoter. We further identify a 25 bp DAF-3 binding element required for the DTC lag-2 reporter response to the environment and to DAF-7/TGFß signaling. Our results implicate DAF-3 repressor complex activity as a key molecular mechanism whereby the environment influences DSL ligand expression in the niche to modulate developmental expansion of the germline stem cell pool.


Assuntos
Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/metabolismo , Nicho de Células-Tronco/fisiologia , Fator de Crescimento Transformador beta/metabolismo , Animais , Caenorhabditis elegans/citologia , Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/genética , Imunoprecipitação da Cromatina , Hibridização In Situ , Transdução de Sinais/genética , Transdução de Sinais/fisiologia , Nicho de Células-Tronco/genética , Fator de Crescimento Transformador beta/genética
16.
Stress ; 22(4): 436-445, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30935351

RESUMO

Working on-call with a night call resulted in a depressed (lower) cortisol awakening response (CAR) peak and post-awakening cortisol area under the curve with respect to ground (AUCG) the following day compared to when off-call. This may be due to exposure to noise, physical exertion, and stressful events during night callouts. There was no anticipatory effect to working on-call in any of the cortisol measures examined. This study, of male fire and emergency service workers who operate on-call from home, had two aims: (1) examine CAR and diurnal cortisol profile following a night on-call with a call, on-call without a call, and off-call; and, (2) explore whether there is an anticipatory effect of working on-call from home on diurnal cortisol profiles. Participants wore activity monitors, completed sleep and work diaries and collected seven saliva samples a day (0 min, 30 min, 60 min, 3 h, 6 h, 9 h, and 12 h after final awakening) for one week. CAR peak, reactivity and area under the curve with respect to increase (AUCI), post-awakening cortisol AUCG, diurnal cortisol slope and AUCG, and mean 12-h cortisol concentrations were calculated. The final analysis included 26 participants for Aim 1 (22 off-call nights, 68 nights on-call without a call, and 20 nights on-call with a call) and 14 participants for Aim 2 (25 days leading up to a night off-call and 92 days leading up to a night on-call). Generalized estimating equations models were constructed for each variable of interest. Aim 1: CAR peak and post-awakening cortisol AUCG were 8.2 ± 3.4 nmol/L and 5.7 ± 2.4 units lower, respectively, following a night on-call with a call compared to an off-call night. Aim 2: the day before a night on-call was not a significant predictor in any model. The lower CAR peak and post-awakening cortisol AUCG following a night on-call with a call compared to following an off-call night may be due to exposure to noise, physical exertion, and stressful events during night callouts. The lack of difference between the day before a night on-call and the day before an off-call night suggests there may not be an anticipatory effect on cortisol when on-call from home.


Assuntos
Hidrocortisona/metabolismo , Estresse Psicológico/fisiopatologia , Adulto , Ritmo Circadiano/fisiologia , Depressão , Feminino , Humanos , Hidrocortisona/análise , Masculino , Pessoa de Meia-Idade , Saliva/metabolismo , Vigília/fisiologia
17.
Wound Repair Regen ; 27(4): 335-344, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30805987

RESUMO

Large bone injuries, defects, and chronic wounds present a major problem for medicine. Several therapeutic strategies are used clinically to precipitate bone including a combination therapy delivering osteoinductive bone morphogenetic protein 2 (rhBMP-2) via an osteoconductive scaffold (absorbable collagen sponge [ACS], i.e., INFUSE). Adverse side effects reportedly associated with rhBMP2 administration include rampant inflammation and clinical failures. Although acute inflammation is necessary for proper healing in bone, inflammatory cascade dysregulation can result in sustained tissue damage and poor healing. We hypothesized that a subclinical dose of rhBMP2 modeled in the murine calvarial defect would not precipitate alterations to inflammatory markers during acute phases of bone wound healing. We utilized the 5 mm critical size calvarial defect in C57BL6 wild-type mice which were subsequently treated with ACS and a subclinical dose of rhBMP2 shown to be optimal for healing. Three and 7-day postoperative time points were used to assess the role that rhBMP-2 plays in modulating inflammation vs. ACS alone by cytokine array and histological interrogation. Data revealed that rhBMP-2 delivery resulted in substantial modulation of several markers associated with inflammation, most of which decreased to levels similar to control by the 7-day time point. Additionally, while rhBMP-2 administration increased macrophage response, this peptide had a little noticeable effect on traditional markers of macrophage polarization (M1-iNOS, M2-Arg1). These results suggest that rhBMP-2 delivered at a lower dose does not precipitate rampant inflammation. Thus, an assessment of dosing for rhBMP-2 therapies may lead to better healing outcomes and less surgical failure.


Assuntos
Proteína Morfogenética Óssea 2/farmacologia , Colágeno/farmacologia , Fraturas Ósseas/patologia , Inflamação/patologia , Osteogênese/efeitos dos fármacos , Cicatrização/efeitos dos fármacos , Implantes Absorvíveis , Animais , Modelos Animais de Doenças , Fraturas Ósseas/tratamento farmacológico , Camundongos , Camundongos Endogâmicos C57BL , Osteogênese/fisiologia , Alicerces Teciduais , Cicatrização/fisiologia
18.
Arch Phys Med Rehabil ; 100(3): 464-473, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30092203

RESUMO

OBJECTIVE: To investigate whether emotional intelligence (EI) skills measured via the Perceiving, Understanding, and Managing Emotions branches of the Mayer-Salovey-Caruso Emotional Intelligence Test V2.0 are associated with community integration (CI) and return to work (RTW) after moderate-to-severe acquired brain injury (ABI), after accounting for other established predictors. DESIGN: Retrospective cohort study. SETTING: Outpatient follow-up services within 2 specialist ABI rehabilitation centers in Melbourne, Australia. PARTICIPANTS: Individuals (N=82) with moderate-to-severe ABI discharged from inpatient rehabilitation and living in the community (2mo to 7y postinjury). INTERVENTION: Not applicable. MAIN OUTCOME MEASURES: Community Integration Questionnaire scores for the total sample (N=82; age range 18-80) and RTW status (employed vs not employed) for the subset of participants employed prior to ABI (n=71; age range 19-66). RESULTS: Hierarchical logistic and multiple regression analyses were used to examine the unique contribution of Perceiving, Understanding, and Managing Emotions scores to RTW and CI, after controlling for demographic, injury-related, psychological, and cognitive predictors. As a set, the 3 EI variables did not explain incremental variance in outcomes. However, individually, Understanding Emotions predicted RTW (adjusted odds ratio=3.10, P=.03), χ2 (12)=35.52, P<.001, and Managing Emotions predicted CI (ß=0.23, P=.036), F12,69=5.14, P<.001. CONCLUSION: Although the EI constructs in combination did not improve prediction beyond the effects of established variables, individual components of strategic EI may be important for specific participation outcomes after ABI.


Assuntos
Lesões Encefálicas/psicologia , Integração Comunitária/psicologia , Inteligência Emocional , Retorno ao Trabalho/psicologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Lesões Encefálicas/reabilitação , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Inquéritos e Questionários , Adulto Jovem
19.
Pediatr Blood Cancer ; 65(12): e27370, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30084207

RESUMO

We present five patients with coexistent von Willebrand disease (VWD) and Ehlers-Danlos syndrome and 21 with VWD and joint hypermobility. Females outnumbered males ten to three, Beighton scores were documented in 58% (15 of 26 patients), and several patients experienced moderately severe bleeding. We believe coexistent hypermobility disorder with VWD potentially affects bleeding severity and want to raise awareness among hematologists. Evaluation by geneticists is recommended because of the varying complexities observed across the disease spectrum, and the availability of new genetic tests should lead to more accurate diagnoses for the various hypermobility disorders.


Assuntos
Hemorragia/complicações , Instabilidade Articular/complicações , Doenças de von Willebrand/complicações , Adolescente , Adulto , Pré-Escolar , Feminino , Hemorragia/fisiopatologia , Humanos , Instabilidade Articular/fisiopatologia , Masculino , Fatores Sexuais , Doenças de von Willebrand/fisiopatologia
20.
Anesth Analg ; 126(4): 1225-1231, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-28632532

RESUMO

The parturient who requests postpartum sterilization has given consideration to and has made decisions regarding this aspect of her medical care long before her delivery. She arrives at parturition expecting the postpartum procedure to be performed as intended. The American Congress of Obstetricians and Gynecologists has reaffirmed its opinion that postpartum sterilization is an urgent procedure, owing to the safety and superior effectiveness of tubal sterilization via minilaparotomy in the immediate postpartum period, and the adverse consequences for mothers, babies, and society when the procedure is not actualized as desired and intended. In contrast, recent practice guidelines for obstetric anesthesia address anesthetic procedural aspects and short-term safety but overlook the long-term complications and considerations associated with failure to perform postpartum sterilization as planned. In practice, procedure completion rates are strikingly low, reportedly ranging from 31% to 52%. Reasons for failure to complete abound and include inadequate resources or inavailability of necessary personnel; obstetrician reluctance due to concerns for patient regret in younger women or medical comorbidities; barriers related to provision of obstetric care in a religiously affiliated hospital, or incomplete, improperly completed, or unavailable original federal consent forms among Medicaid-insured women. The federal requirement to wait 30 days after signing informed consent, and to retain the original signed document to be physically verified at time of the procedure, serves as a significant source of health care disparity for Medicaid-dependent mothers. This article reviews these larger issues of maternal health and comprehensive maternal care to broaden the anesthesiologist's appreciation of major benefits and potential risks of postpartum sterilization, including long-term effects, to promote an evidence-based, informed, and proactive role in delivering equitable, safe, and optimal care for these patients.


Assuntos
Atenção à Saúde , Saúde Materna , Cuidado Pós-Natal/métodos , Esterilização Tubária , Aborto Induzido , Adulto , Feminino , Disparidades em Assistência à Saúde , Humanos , Consentimento Livre e Esclarecido , Gravidez , Gravidez não Planejada , Gravidez não Desejada , Fatores de Risco , Fatores Socioeconômicos , Esterilização Tubária/efeitos adversos , Tempo para o Tratamento , Resultado do Tratamento , Adulto Jovem
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