RESUMEN

This review summarizes the effectiveness of scalable mind-body internet and mobile-based interventions (IMIs) on depression and anxiety symptoms in adults living with chronic physical conditions. Six databases (MEDLINE, PsycINFO, SCOPUS, EMBASE, CINAHL, and CENTRAL) were searched for randomized controlled trials published from database inception to March 2023. Mind-body IMIs included cognitive behavioral therapy, breathwork, meditation, mindfulness, yoga or Tai-chi. To focus on interventions with a greater potential for scale, the intervention delivery needed to be online with no or limited facilitation by study personnel. The primary outcome was mean change scores for anxiety and depression (Hedges' g). In subgroup analyses, random-effects models were used to calculate pooled effect size estimates based on personnel support level, intervention techniques, chronic physical condition, and survey type. Meta-regression was conducted on age and intervention length. Fifty-six studies met inclusion criteria (sample size 7691, mean age of participants 43 years, 58% female): 30% (n = 17) neurological conditions, 12% (n = 7) cardiovascular conditions, 11% cancer (n = 6), 43% other chronic physical conditions (n = 24), and 4% (n = 2) multiple chronic conditions. Mind-body IMIs demonstrated statistically significant pooled reductions in depression (SMD = -0.33 [-0.40, -0.26], p<0.001) and anxiety (SMD = -0.26 [-0.36, -0.17], p<0.001). Heterogeneity was moderate. Scalable mind-body IMIs hold promise as interventions for managing anxiety and depression symptoms in adults with chronic physical conditions without differences seen with age or intervention length. While modest, the effect sizes are comparable to those seen with pharmacological therapy. The field would benefit from detailed reporting of participant demographics including those related to technological proficiency, as well as further evaluation of non-CBT interventions. Registration: The study is registered with PROSPERO ID #CRD42022375606.

RESUMEN

Biological processes in development and disease are controlled by the abundance, localization and modification of cellular proteins. We have developed versatile tools based on recombinant E3 ubiquitin ligases that are controlled by light or drug induced heterodimerization for nanobody or DARPin targeted depletion of endogenous proteins in cells and organisms. We use this rapid, tunable and reversible protein depletion for functional studies of essential proteins like PCNA in DNA repair and to investigate the role of CED-3 in apoptosis during Caenorhabditis elegans development. These independent tools can be combined for spatial and temporal depletion of different sets of proteins, can help to distinguish immediate cellular responses from long-term adaptation effects and can facilitate the exploration of complex networks.

Asunto(s)

Proteínas de Caenorhabditis elegans/metabolismo , Técnicas Citológicas , Luz , Ubiquitina-Proteína Ligasas/efectos de los fármacos , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitina-Proteína Ligasas/efectos de la radiación , Animales , Apoptosis , Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/efectos de los fármacos , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/efectos de la radiación , Caspasas/efectos de los fármacos , Caspasas/metabolismo , Caspasas/efectos de la radiación , Ingeniería Celular/métodos , Daño del ADN , ADN Ligasa (ATP) , Reparación del ADN , Proteínas de Unión al ADN/metabolismo , Regulación del Desarrollo de la Expresión Génica , Proteínas Fluorescentes Verdes , Células HeLa , Humanos , Lamina Tipo A/metabolismo , Antígeno Nuclear de Célula en Proliferación/metabolismo , Factores de Transcripción/metabolismo , Ubiquitina-Proteína Ligasas/genética

RESUMEN

Protein transfection is a versatile tool to study or manipulate cellular processes and also shows great therapeutic potential. However, the repertoire of cost effective techniques for efficient and minimally cytotoxic delivery remains limited. Mesoporous silica nanoparticles (MSNs) are multifunctional nanocarriers for cellular delivery of a wide range of molecules, they are simple and economical to synthesize and have shown great promise for protein delivery. In this work we present a general strategy to optimize the delivery of active protein to the nucleus. We generated a bimolecular Venus based optical sensor that exclusively detects active and bioavailable protein for the performance of multi-parameter optimization of protein delivery. In conjunction with cell viability tests we maximized MSN protein delivery and biocompatibility and achieved highly efficient protein transfection rates of 80%. Using the sensor to measure live-cell protein delivery kinetics, we observed heterogeneous timings within cell populations which could have a confounding effect on function studies. To address this problem we fused a split or dimerization dependent protein of interest to chemically induced dimerization (CID) components, permitting control over its activity following cellular delivery. Using the split Venus protein we directly show that addition of a small molecule dimerizer causes synchronous activation of the delivered protein across the entire cell population. This combination of cellular delivery and triggered activation provides a defined starting point for functional studies and could be applied to other protein transfection methods.

Asunto(s)

Núcleo Celular/efectos de los fármacos , Núcleo Celular/metabolismo , Sistemas de Liberación de Medicamentos , Nanopartículas/administración & dosificación , Proteínas/metabolismo , Bibliotecas de Moléculas Pequeñas/administración & dosificación , Bibliotecas de Moléculas Pequeñas/farmacología , Núcleo Celular/química , Células HeLa , Humanos , Tamaño de la Partícula , Porosidad , Proteínas/química , Dióxido de Silicio/química , Propiedades de Superficie

RESUMEN

While calcium signaling in excitable cells, such as muscle or neurons, is extensively characterized, calcium signaling in epithelial tissues is little understood. Specifically, the range of intercellular calcium signaling patterns elicited by tightly coupled epithelial cells and their function in the regulation of epithelial characteristics are little explored. We found that in Drosophila imaginal discs, a widely studied epithelial model organ, complex spatiotemporal calcium dynamics occur. We describe patterns that include intercellular waves traversing large tissue domains in striking oscillatory patterns as well as spikes confined to local domains of neighboring cells. The spatiotemporal characteristics of intercellular waves and oscillations arise as emergent properties of calcium mobilization within a sheet of gap-junction coupled cells and are influenced by cell size and environmental history. While the in vivo function of spikes, waves and oscillations requires further characterization, our genetic experiments suggest that core calcium signaling components guide actomyosin organization. Our study thus suggests a possible role for calcium signaling in epithelia but importantly, introduces a model epithelium enabling the dissection of cellular mechanisms supporting the initiation, transmission and regeneration of long-range intercellular calcium waves and the emergence of oscillations in a highly coupled multicellular sheet.

Asunto(s)

Calcio/metabolismo , Drosophila melanogaster/metabolismo , Epitelio/fisiología , Discos Imaginales/citología , Animales , Señalización del Calcio , Tamaño de la Célula , Células Cultivadas , Proteínas de Drosophila/genética , Drosophila melanogaster/genética , Discos Imaginales/metabolismo , Modelos Biológicos

RESUMEN

Natural disasters, such as hurricanes, tornadoes, cyclones, earthquakes, volcanic eruptions, wildfires, and floods, have a profound impact on healthcare by limiting healthcare providers' ability to effectively provide patient care in the affected areas and respond to myriad healthcare needs of the affected population. The situation can potentially be exacerbated if healthcare providers do not have effective mechanisms in place for disaster response. The response to Hurricane Katrina, a Category 3 hurricane that made landfall in August 2005 and affected several states in the southwestern U.S., was a vivid example of how the lack of effective planning and responsiveness can affect healthcare services. In this paper, based on an extensive case study, which included a rigorous examination of the Veterans Health Administration's information technology (IT) infrastructure and its response to Hurricane Katrina, we present five strategies that healthcare organizations can undertake to develop and leverage IT-enabled disaster response. These include the development of: 1) an integrated IT architecture; 2) a universal data repository; 3) web-based disaster communication and coordination; 4) an IT-enabled disaster support system; and 5) standardized and integrated IT-enabled disaster response processes. We discuss how these strategies can help healthcare providers manage continuity and offer quality healthcare during natural disasters.

Asunto(s)

Planificación en Desastres/métodos , Informática Médica/métodos , Humanos , Internet

RESUMEN

Health care has lagged behind other industries in its use of advanced analytics. The Veterans Health Administration (VHA) has three decades of experience collecting data about the veterans it serves nationwide through locally developed information systems that use a common electronic health record. In 2006 the VHA began to build its Corporate Data Warehouse, a repository for patient-level data aggregated from across the VHA's national health system. This article provides a high-level overview of the VHA's evolution toward "big data," defined as the rapid evolution of applying advanced tools and approaches to large, complex, and rapidly changing data sets. It illustrates how advanced analysis is already supporting the VHA's activities, which range from routine clinical care of individual patients--for example, monitoring medication administration and predicting risk of adverse outcomes--to evaluating a systemwide initiative to bring the principles of the patient-centered medical home to all veterans. The article also shares some of the challenges, concerns, insights, and responses that have emerged along the way, such as the need to smoothly integrate new functions into clinical workflow. While the VHA is unique in many ways, its experience may offer important insights for other health care systems nationwide as they venture into the realm of big data.

Asunto(s)

Interpretación Estadística de Datos , Minería de Datos/métodos , Conjuntos de Datos como Asunto , Sistemas de Registros Médicos Computarizados , United States Department of Veterans Affairs , Salud de los Veteranos , Registros Electrónicos de Salud/normas , Humanos , Informática Médica , Programas Informáticos , Estados Unidos , United States Department of Veterans Affairs/organización & administración

RESUMEN

OBJECTIVES: We describe electronic health data use by the Department of Veterans Affairs (VA) in the month after Katrina, including supporting technologies, the extent and nature of information accessed, and lessons learned. METHODS: We conducted a retrospective study using cross-sectional panels of data collected sequentially over time. RESULTS: By September 30, 2005, clinical data were accessed electronically for at least 38% (14941 of 39910) of patients cared for prior to Hurricane Katrina by New Orleans-area VA medical facilities. Approximately 1000 patients per day had data accessed during the month following Hurricane Katrina, a rate approximately two thirds of pre-Katrina values. Health care data were transmitted to more than 200 sites in 48 states and to at least 2300 users. CONCLUSIONS: The VA electronic health records supported continuity of care for evacuated veterans after Katrina. Our findings suggest that pharmacy and laboratory computerization alone will not be sufficient for future disaster support systems.

Asunto(s)

Desastres , Hospitales de Veteranos , Sistemas de Registros Médicos Computarizados , Refugiados , Estudios Transversales , Femenino , Humanos , Louisiana , Masculino , Evaluación de Necesidades , Sistemas de Socorro , Estudios Retrospectivos