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The objective of this study was to explore the effectiveness of a passive back-support exosuit at reducing low back muscle fatigue during an 18-minute trunk posture maintenance task. On two separate days sixteen participants performed an 18-minute trunk posture profile that reflected trunk flexion postures observed during a challenging vascular surgery procedure. On one day they performed the procedure with the support of the exosuit, on the other day without. Test contractions were performed every three minutes to capture the time-dependent electromyographic activity of the bilateral erector spinae muscles. Time domain (amplitude) and frequency domain (median frequency) measures of erector spinae muscle fatigue were assessed. Results revealed that the exosuit significantly reduced the measures of erector spinae muscle fatigue in terms of both amplitude (6.1%) and median frequency (5.3%), demonstrating a fatigue reduction benefit of the exosuit in a realistic surgical posture maintenance task.
To examine the potential adoption of a back-support exosuit system in the surgical environment, this study used an 18-minute posture maintenance task that reflected trunk flexion postures observed during a vascular surgery procedure and suggests that the exosuit system can effectively reduce low back muscle fatigue during a vascular surgical procedure.
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Electromiografía , Fatiga Muscular , Músculos Paraespinales , Postura , Torso , Humanos , Fatiga Muscular/fisiología , Postura/fisiología , Masculino , Adulto , Femenino , Músculos Paraespinales/fisiología , Torso/fisiología , Adulto Joven , Dispositivo ExoesqueletoRESUMEN
Push polls are an insidious means of disseminating information under the guise of a legitimate information-gathering poll (e.g., "Would you be more or less likely to vote for X if you heard they were being investigated for tax fraud?"). While previous research has shown that push polls can affect attitudes, the current study assessed whether exposure to push polls can increase false memories for corresponding fake news stories. Across four studies, we found that participants (N = 1,290) were significantly more likely to report a false memory for a corresponding fabricated news story after push poll exposure. This was true for positive and negative stories, concerning both fictitious characters and well-known public figures. Furthermore, this effect was stronger after a delay of one week between the push poll and the news story. Our findings suggest that push polls are a potent applied example of the misinformation effect and can significantly increase susceptibility to fake news stories.
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Decepción , Memoria , Comunicación , Audición , Humanos , PolíticaRESUMEN
The aim of this research was to determine the color stability of 3 gingival shades of dental restorative materials, Amaris Gingiva, Beautiful II Gingiva, and PermaFlo Pink, compared to a tooth-colored nanohybrid composite, Filtek Z250. Twenty-five specimens of each composite were fabricated in polytetrafluoroethylene-coated stainless steel molds and polished using a 4-step polishing regimen. The specimens were randomly assigned to groups for immersion in 1 of 5 solutions (n = 5): distilled water (control), red wine, tea, coffee, or curry (curry powder [containing turmeric] in a solution with distilled water). A desktop spectrophotometer was used to perform color measurements within the Commission Internationale de l'Eclairage L*a*b* color space, and mean overall color (E*) was calculated for each group before and after immersion for 7 days. The mean E* values of each composite before and after immersion were compared using paired t tests at the P < 0.05 level of significance. For all of the tested restorative materials, immersion in a solution of curry produced the greatest increase in mean E* values (P < 0.0001), with E* increasing 32-fold for Amaris Gingiva specimens, 27-fold for Beautiful II Gingiva, 34-fold for PermaFlo Pink, and 2-fold for Filtek Z250. There were smaller, but still significant, increases in E* for Amaris Gingiva, Beautiful II Gingiva, and PermaFlo Pink when immersed in coffee (P < 0.05). Curry caused the greatest change in E* values for all of the tested restorative materials, indicating that curry seasonings based on turmeric can cause unacceptable color change in all of the tested materials and such change can happen in a relatively short time. Coffee also has the potential to cause unacceptable color change in gingival shades of composite materials.
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Resinas Compuestas , Encía , Café , Color , Materiales Dentales , Ensayo de Materiales , Espectrofotometría , Propiedades de SuperficieRESUMEN
Secondary lymphedema in humans is a common consequence of lymph node dissection (LND) to treat breast cancer. A peculiar characteristic of the disease is that lifelong swelling often precipitously appears several years after the surgical treatment, often due to an inflammatory stimulus. Although the incidence of secondary lymphedema dramatically increases after radiation therapy, the relationship between fibrotic scarring and the eventual appearance of lymphedema remains unclear. To clarify the role of fibrosis in secondary lymphedema initiation, we chemically increased fibrosis in rodent tissues with bleomycin and assessed the ability of the local lymphatic system to prevent lymphedema, either acutely or in a chronic state induced by inflammation. We found that bleomycin injections exacerbated fibrotic matrix deposition in an acute mouse tail lymphedema model (P < 0.005), reduced wound closure (P < 0.005), and impaired the ability of tail lymphatics to regenerate (P < 0.005) and reduce the swelling (P < 0.05). When fibrosis was worsened with bleomycin after axillary LND in the rat foreleg, the ability of the foreleg lymphatic system to reduce the chronic state swelling induced by stimulated inflammation was severely impaired (P < 0.005). Indocyanine green lymphography in axillary LND-recovered rat forelegs revealed a worsened lymphatic drainage due to inflammation and bleomycin pretreatment. Although inflammation reduced the drainage of dextran fluid tracer from control forelegs (P < 0.05), the reduction in fluid drainage was more severe after axillary LND when fibrosis was first increased (P < 0.005). These findings demonstrate that fibrosis reduces the lymphatic capacity to functionally regenerate and prevent the chronic appearance of lymphedema.
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Sistema Linfático/fisiopatología , Linfedema/fisiopatología , Animales , Bleomicina/toxicidad , Femenino , Fibrosis/etiología , Fibrosis/patología , Fibrosis/fisiopatología , Inflamación/patología , Inflamación/fisiopatología , Escisión del Ganglio Linfático/efectos adversos , Sistema Linfático/efectos de los fármacos , Sistema Linfático/patología , Linfedema/patología , Ratones , Ratones Endogámicos BALB C , Ratas , Ratas Sprague-DawleyRESUMEN
PURPOSE OF REVIEW: A pregnant healthcare worker (HCW) may be at risk of occupational exposure to pathogens associated with increased maternal morbidity and mortality as well as perinatal complications. In this article, we review recent literature on infectious diseases commonly encountered in the healthcare setting and of highest concern for a pregnant HCW, focusing on prevention and management of exposures. RECENT FINDINGS: Pregnancy does not seem to be an independent risk factor for occupationally acquired infectious diseases. Vaccination and standard precautions continue to be the most effective means of preventing transmission to HCWs. Pandemic 2009 influenza A (H1N1) is associated with increased risk of fetal death, highlighting the importance of influenza vaccination. A recent meta-analysis highlights the safety of influenza vaccination during pregnancy. New treatments for hepatitis C have not been studied in pregnancy but pose an important area for research and advancement. Cytomegalovirus immunoglobulin may play a role in postexposure prophylaxis but recent results are inconclusive. SUMMARY: Primary prevention with vaccination and use of appropriate infection control precautions is imperative for prevention of occupationally acquired infectious diseases. Pregnant HCWs with occupational exposure to communicable diseases should be evaluated immediately for appropriate postexposure prophylaxis and followed for development of active infection.
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Personal de Salud , Control de Infecciones/métodos , Transmisión de Enfermedad Infecciosa de Paciente a Profesional/prevención & control , Exposición Profesional/prevención & control , Embarazo , Femenino , Humanos , Vacunación/métodos , Vacunación/estadística & datos numéricosRESUMEN
Some individuals are susceptible to chronic stress, and others are more resilient. While many brain regions implicated in learning are dysregulated after stress, little is known about whether and how neural teaching signals during stress differ between susceptible and resilient individuals. Here, we seek to determine if activity in the lateral habenula (LHb), which encodes a negative teaching signal, differs between susceptible and resilient mice during stress to produce different outcomes. After (but not before) chronic social defeat stress, the LHb is active when susceptible mice are in proximity of the aggressor strain. During stress, activity is higher in susceptible mice during aggressor interactions, and activation biases mice toward susceptibility. This manipulation generates a persistent and widespread increase in the balance of subcortical vs. cortical activity in susceptible mice. Taken together, our results indicate that heightened activity in the LHb during stress produces lasting brainwide and behavioral substrates of susceptibility.
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Animals learn the value of foods based on their postingestive effects and thereby develop aversions to foods that are toxic1-6 and preferences to those that are nutritious7-14. However, it remains unclear how the brain is able to assign credit to flavors experienced during a meal with postingestive feedback signals that can arise after a substantial delay. Here, we reveal an unexpected role for postingestive reactivation of neural flavor representations in this temporal credit assignment process. To begin, we leverage the fact that mice learn to associate novel15-18, but not familiar, flavors with delayed gastric malaise signals to investigate how the brain represents flavors that support aversive postingestive learning. Surveying cellular resolution brainwide activation patterns reveals that a network of amygdala regions is unique in being preferentially activated by novel flavors across every stage of the learning process: the initial meal, delayed malaise, and memory retrieval. By combining high-density recordings in the amygdala with optogenetic stimulation of genetically defined hindbrain malaise cells, we find that postingestive malaise signals potently and specifically reactivate amygdalar novel flavor representations from a recent meal. The degree of malaise-driven reactivation of individual neurons predicts strengthening of flavor responses upon memory retrieval, leading to stabilization of the population-level representation of the recently consumed flavor. In contrast, meals without postingestive consequences degrade neural flavor representations as flavors become familiar and safe. Thus, our findings demonstrate that interoceptive reactivation of amygdalar flavor representations provides a neural mechanism to resolve the temporal credit assignment problem inherent to postingestive learning.
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OBJECTIVES: The primary objective of this 2-year pilot study was to evaluate the effectiveness of a culturally adapted family intervention in improving family communication among African American parents coping with cancer and their school-age children. A secondary objective was to determine its impact on other symptoms of psychosocial distress (depression and anxiety). The third objective was to assess for acceptability and feasibility. METHODS: Using a two-arm pre-intervention and post-intervention prospective design, 12 African American families received five bi-monthly sessions of either a culturally adapted family intervention (n=7 families) or psycho-education treatment (n=5 families). Parents and their children completed pre-intervention and post-intervention questionnaires assessing perceptions of family communication, quality of their relationship, and symptoms of depression. School-age children additionally completed a questionnaire assessing their levels of anxiety. Consumer satisfaction was also evaluated at post-intervention. RESULTS: Parents and school-age children who completed the culturally adapted family intervention reported significantly better communication with each other and were more satisfied compared with the psycho-education control group. No changes were noted in symptoms of anxiety or depression. The culturally adapted family intervention was acceptable based on our findings, families' feedback, and rates of retention. Feasibility is uncertain because our oncology clinic approach to recruitment was slower than expected. CONCLUSIONS: Providing culturally adapted family intervention programs to African American families who are coping with parental cancer may result in improved family communication. This pilot study serves as the first step in the development of culturally adapted family intervention programs to help African American families cope with parental cancer.
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Adaptación Psicológica , Cultura , Familia/etnología , Neoplasias/psicología , Padres/psicología , Negro o Afroamericano/psicología , Comunicación , Consejo , Familia/psicología , Femenino , Humanos , Masculino , Neoplasias/diagnóstico , Neoplasias/etnología , Proyectos Piloto , Estudios Prospectivos , Apoyo Social , Factores Socioeconómicos , Encuestas y Cuestionarios , Estados UnidosRESUMEN
Whole-brain clearing and imaging methods are becoming more common in mice but have yet to become standard in rats, at least partially due to inadequate clearing from most available protocols. Here, we build on recent mouse-tissue clearing and light-sheet imaging methods and develop and adapt them to rats. We first used cleared rat brains to create an open-source, 3D rat atlas at 25 µm resolution. We then registered and imported other existing labeled volumes and made all of the code and data available for the community (https://github.com/emilyjanedennis/PRA) to further enable modern, whole-brain neuroscience in the rat. Key features ⢠This protocol adapts iDISCO (Renier et al., 2014) and uDISCO (Pan et al., 2016) tissue-clearing techniques to consistently clear rat brains. ⢠This protocol also decreases the number of working hours per day to fit in an 8 h workday. Graphical overview.
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PURPOSE: The COVID-19 pandemic has had deleterious effects on oncologist professional and personal well-being, the optimal delivery of quality cancer care, and the future cancer care workforce, with many departing the field. Hence, the identification of evidence-based approaches to sustain oncologists is essential to promote well-being. MATERIALS AND METHODS: We developed a brief, oncologist-centered, virtual group peer support program and tested its feasibility, acceptability, and preliminary impact on well-being. Trained facilitators provided support to peers on the basis of burnout research in oncology with available resources to enhance oncologist resilience. Peers completed pre- and postsurvey assessment of well-being and satisfaction. RESULTS: From April to May 2022, 11 of 15 (73%) oncologists participated in its entirety: mean age 51.1 years (range, 33-70), 55% female, 81.8% Ca, 82% medical oncologists, 63.6% trained ≥15 years, average 30.3 patients/wk (range, 5-60), and 90.9% employed in hospital/health system practice. There was a statistically significant difference in pre- and postintervention well-being (7.0 ± 3.6 v 8.2 ± 3.0, P = .03) with high satisfaction with postgroup experience (9.1 ± 2.5). These quantitative improvements were affirmed by qualitative feedback. These themes included (1) an enhanced understanding of burnout in oncology, (2) shared experience in practice of oncology, and (3) fostering connections with diverse colleagues. Future recommendations proposed included (1) restructuring group format and (2) tailoring groups according to practice setting (academic v community). CONCLUSION: Preliminary results suggest that a brief, innovative oncologist-tailored group peer support program is feasible, acceptable, and beneficial for enhancing well-being dimensions including burnout, engagement, and satisfaction. Additional study is required to refine program components (optimal timing, format) to support oncologist well-being, now during the pandemic and well into recovery.
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Agotamiento Profesional , COVID-19 , Oncólogos , Humanos , Femenino , Persona de Mediana Edad , Masculino , COVID-19/epidemiología , Pandemias , Estudios de Factibilidad , Oncología Médica , Agotamiento Profesional/terapiaRESUMEN
Secondary lymphedema in humans is a common consequence of axillary lymph node dissection (ALND) to treat breast cancer. Remarkably, secondary lymphedema generally first appears following a delay of over a year and can be triggered suddenly by an inflammatory insult. However, it remains unclear why the apparently functional lymphatic system is unable to accommodate an inflammatory trigger. To provide mechanistic insight into the delayed and rapid secondary lymphedema initiation, we compared the ability of the ALND-recovered rat foreleg lymphatic system to prevent edema during an inflammatory challenge with that of the uninjured lymphatic system. At 73 days postsurgery, the forelegs of ALND(-)- and ALND(+)-sensitized rats were exposed to the proinflammatory agent oxazolone, which was found to reduce fluid drainage and increase skin thickness in both ALND(-) and ALND(+) forelegs (P < 0.05). However, drainage in the ALND-recovered forelegs was more severely impaired than ALND(-) forelegs, as visualized by indocyanine green lymphography and quantified by interstitial transport of fluid marker (P < 0.05). Although both ALND(+) and ALND(-) forelegs experienced significant inflammation-induced edema with the oxazolone exposure (P < 0.05), the peak tissue swelling in the ALND(+) group was significantly greater than that of the ALND(-) forelegs (arm area peaked at â¼13.4 vs. â¼5.7% swelling, respectively, P < 0.005; wrist diameter peaked at 9.7 vs. 2.2% swelling, respectively, P < 0.005). The findings demonstrate that outward recovery from ALND in the rat foreleg masks an ensuing chronic and latent lymphatic insufficiency, which reduces the ability of the foreleg lymphatic system to prevent edema during an acute inflammatory process.
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Escisión del Ganglio Linfático/efectos adversos , Sistema Linfático/fisiopatología , Linfedema/etiología , Linfedema/fisiopatología , Enfermedad Aguda , Animales , Femenino , Miembro Anterior , Inflamación/inducido químicamente , Inflamación/complicaciones , Sistema Linfático/efectos de los fármacos , Linfografía , Modelos Animales , Oxazolona/efectos adversos , Oxazolona/farmacología , Ratas , Ratas Sprague-DawleyRESUMEN
PURPOSE: Recent national guidelines encourage a trial of labor after cesarean (TOLAC) as a means of increasing vaginal births after cesarean (VBACs) and decreasing the high US cesarean birth rate and its consequences (2010 National Institute of Health Consensus Statement and American College of Obstetricians and Gynecologists revised guideline). A birthing center serving Amish women in Southwestern Wisconsin offered an opportunity to look at the effects of local culture and practices that support vaginal birth and TOLAC. This study describes childbirth and perinatal outcomes during a 17-year period in LaFarge, Wisconsin. METHODS: We undertook a retrospective analysis of the records of all women admitted to the birth center in labor. Main outcome measures include rates of cesarean deliveries, TOLAC and VBAC deliveries, and perinatal outcomes for 927 deliveries between 1993 and 2010. RESULTS: The cesarean rate was 4% (35 of 927), the TOLAC rate was 100%, and the VBAC rate was 95% (88 of 92). There were no cases of uterine rupture and no maternal deaths. The neonatal death rate of 5.4 of 1,000 was comparable to that of Wisconsin (4.6 of 1,000) and the United States (4.5 of 1,000). CONCLUSIONS: Both the culture of the population served and a number of factors relating to the management of labor at the birthing center have affected the rates of cesarean delivery and TOLAC. The results of the LaFarge Amish study support a low-technology approach to delivery where good outcomes are achieved with low cesarean and high VBAC rates.
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Cesárea/estadística & datos numéricos , Complicaciones del Trabajo de Parto/epidemiología , Parto/etnología , Parto Vaginal Después de Cesárea/estadística & datos numéricos , Adulto , Amish , Centros de Asistencia al Embarazo y al Parto , Femenino , Humanos , Mortalidad Infantil , Recién Nacido , Embarazo , Estudios Retrospectivos , Esfuerzo de Parto , Estados Unidos , WisconsinRESUMEN
Prior clinical research supports the effectiveness of cancer support groups for cancer patients and their families, yet African-American families continue to be underrepresented in cancer support groups and in cancer clinical research studies. In order to fill this gap, we developed and evaluated a culturally adapted family support group for African-American families coping with parental cancer. We encountered unexpected challenges in overcoming barriers to recruitment, partnering with oncology providers, and building trust with the African-American community and African-American families coping with parental cancer. We describe actions taken during the two phases of this study and lessons learned along the way about recruiting and engaging African-American families in cancer support group studies, partnering with oncology providers, networking with the African-American community, and the importance of demonstrating cultural sensitivity to overcome the understandable historical legacy of mistrust.
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Adaptación Psicológica , Negro o Afroamericano/psicología , Cultura , Familia/etnología , Conductas Relacionadas con la Salud , Neoplasias/psicología , Padres/psicología , Adolescente , Niño , Consejo , Familia/psicología , Femenino , Humanos , Masculino , Neoplasias/diagnóstico , Neoplasias/etnología , Proyectos PilotoRESUMEN
Justice-involved youth are at increased risk for coronavirus disease 2019 (COVID-19) infection, and structural barriers may limit their access to vaccination. We implemented a COVID-19 vaccination initiative for justice-involved youth residing at the county juvenile detention center and enrolled in local community-based monitoring programs. Our overarching goal was to increase COVID-19 vaccine access and uptake for justice-involved youth in Allegheny County, Pennsylvania. Our efforts incorporated: a virtual forum with youth, guardians, and community partners; one-on-one outreach to guardians; motivational interviewing with youth; and coordination with organizational leaders. We collaborated with a multidisciplinary medical team to offer individualized education and counseling to parents and youth expressing vaccine hesitancy. We developed a logistical framework to ensure complete COVID-19 vaccination series for all youth, including centralized tracking and implementation of multiple community-based vaccine clinics. Through our initiative, 31 justice-involved youth have received at least 1 dose of the Pfizer-BioNTech COVID-19 vaccine. A total of 50 doses have been administered as a result of this initiative. This work has reaffirmed hypothesized barriers to vaccine access among justice-involved youth, including limited parental involvement, inadequate transportation, vaccine misinformation, and distrust rooted in histories of medical mistreatment of communities of color. Best practices for promoting equitable vaccination efforts among vulnerable subgroups include partnering closely with diverse community members; offering individualized, strengths-based counseling on vaccine safety, efficacy, and importance; and demonstrating provider trustworthiness by recognizing histories of oppression.
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Vacunas contra la COVID-19 , COVID-19 , Adolescente , Vacuna BNT162 , COVID-19/prevención & control , Humanos , Justicia Social , VacunaciónRESUMEN
Objective: Comprehensive sexuality education (CSE) allows for informed and healthy decisions. College students often lack understanding of sexual and reproductive health (SRH). Conversations and Pizza (CAP), an interactive curriculum, was designed to address gaps in CSE and improve SRH outcomes. Participants: 66 fraternity affiliated undergraduate students. Methods: A six-session intervention discussed gender norms, biology, consent, harassment, and bystander intervention. Pre- and post-quantitative surveys assessed attitudes and behaviors; plus-delta format was used for qualitative feedback. Results: Qualitative data reflected engagement. Post-intervention, multiple measures improved (McNemar p < 0.05): perceived self-efficacy in consent and peer norms (4/8 measures), bystander intervention (5/6), and awareness of harassment (2/5). Participants reported more conversations with partners (pregnancy and STI prevention, 50% to 75%); human papillomavirus (HPV) vaccination receipt increased (60% to 93%, McNemar p < 0.001). Conclusion: Reproductive health outcomes improved in this pilot, laying the groundwork for continued testing. CAP is a successful pilot program that can be evaluated for a variety of groups and formats.
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Introduction: Social isolation is a modifiable risk factor for negative health outcomes among older adults. This work assessed the relationship between geography (i.e., urban vs. non-urban residence) and social isolation in a cohort of older drivers. Methods: The AAA LongROAD cohort with 2,989 older adult drivers from across the country were included. Social isolation was measured at baseline and at two subsequent annual follow-ups using PROMIS v2.0 Social Isolation 4a. The effect of geographic location with social isolation was assessed through with multivariable regression using a generalized estimating equation model. Results: The rate of social isolation in urban areas was 21% lower (adjusted RR 0.79, 95% CI 0.46, 1.36) compared to non-urban areas after adjusting for covariates, though not significant. Discussion: Social isolation is a predictor of poor health outcomes and geographic considerations have been lacking in the literature. The panel data in this analysis provides more evidence for causality though the under-representation of non-urban areas potentially reduces the power for the results. Conclusions: It is important to understand the needs and risk of social isolation in various geographic settings to ensure resources and interventions are appropriately modified for a greater public health impact.
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Aislamiento Social , Anciano , Estudios de Cohortes , Humanos , Factores de RiesgoRESUMEN
INTRODUCTION: Few studies have reviewed concurrent perspectives and experiences of parents, health care providers (HCPs), and adolescents themselves, when their Type 1 diabetes (T1D) is uncontrolled. We utilized a qualitative interview approach to explore these feelings and interactions. METHOD: Nine adolescents, age 13-18 years with T1D > 1 year and A1C > 9.0%, their parents, and 10 HCPs participated in semistructured interviews. The 7 girls and 2 boys were interviewed with their parents present and the 10 HCPs participated in separate interviews. Interviews were recorded, transcribed, and reviewed for themes relevant to the uncontrolled diabetes experience. RESULTS: Adolescents, parents, and providers shared similar feelings of frustration, guilt, anxiety, and anger related to uncontrolled diabetes, but described very different behavioral responses to these unexpressed feelings. Adolescents tended to rebel and became more nonadherent to diabetes-related tasks. Parents became angry, nagged, threatened, and often blamed and shamed their teen. Health care providers became less patient-focused, distancing themselves from patients and their parents. This resulted in misunderstandings, conflict, and often disengagement from diabetes. DISCUSSION: Adolescents with poorly controlled T1D, their parents, and HCPs, while attempting to do their best, often respond to their frustrations with visible behaviors "out of sync" with their unexpressed feelings. This resulted in conflict, continued poor blood sugars, and disengagement. Interventions to improve diabetes-related care and communication between adolescents, parents, and HCPs may result in improved diabetes self-management. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
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Diabetes Mellitus Tipo 1/psicología , Personal de Salud/psicología , Padres/psicología , Cumplimiento y Adherencia al Tratamiento/psicología , Adolescente , Estudios Transversales , Diabetes Mellitus Tipo 1/terapia , Femenino , Hemoglobina Glucada/análisis , Personal de Salud/estadística & datos numéricos , Humanos , Entrevistas como Asunto/métodos , Masculino , Relaciones Padres-Hijo , Pediatría/métodos , Pediatría/normas , Investigación Cualitativa , Automanejo/psicología , Cumplimiento y Adherencia al Tratamiento/estadística & datos numéricosRESUMEN
One of the intriguing questions regarding cell motility concerns the mechanism that makes stationary cells move. Here, we provide the first physical evidence that the onset of breast cancer cell motility in response to insulin-like growth factor I (IGF-I) correlates with lowering of adhesion strength from 2.52 +/- 0.20 to 1.52 +/- 0.13 microdynes/microm2 in cells attached to fibronectin via alpha5beta1 integrin. The adhesion strength depends on the dose of IGF-I and time of IGF-I treatment. Weakening of cell-matrix adhesion is blocked significantly (p < 0.01) by the catalytically inactive IGF-I receptor (IGF-IR) and the phosphoinositide 3-kinase (PI-3 kinase) inhibitor LY-294002, but it is unaffected by mitogen-activated protein kinase kinase inhibitor UO-126 and Src kinase inhibitor PP2. Sustained blockade of Rho-associated kinase (ROCK) with Y-27632 down-regulates adhesion strength in stationary, but not in IGF-I-treated, cells. Jasplakinolide, a drug that prevents actin filament disassembly, counteracts the effect of IGF-I on integrin-mediated cell adhesion. In the absence of growth factor signaling, ROCK supports a strong adhesion via alpha5beta1 integrin, whereas activation of the IGF-IR kinase reduces cell-matrix adhesion through a PI-3K-dependent, but ROCK-independent, mechanism. We propose that disassembly of the actin filaments via PI-3 kinase pathway contributes to weakening of adhesion strength and induction of cell movement. Understanding how cell adhesion and migration are coordinated has an important application in cancer research, developmental biology, and tissue bioengineering.
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Carcinoma/metabolismo , Factor I del Crecimiento Similar a la Insulina/metabolismo , Integrina alfa5beta1/metabolismo , Actinas/metabolismo , Amidas/farmacología , Western Blotting , Neoplasias de la Mama/metabolismo , Butadienos/farmacología , Proteína Tirosina Quinasa CSK , Catálisis , Adhesión Celular , Línea Celular Tumoral , Movimiento Celular , Cromonas/farmacología , Medio de Cultivo Libre de Suero/farmacología , Depsipéptidos/farmacología , Regulación hacia Abajo , Fibronectinas/metabolismo , Citometría de Flujo , Humanos , Inmunoprecipitación , Péptidos y Proteínas de Señalización Intracelular , Sistema de Señalización de MAP Quinasas , Microscopía de Contraste de Fase , Modelos Biológicos , Morfolinas/farmacología , Nitrilos/farmacología , Fosfatidilinositol 3-Quinasas/metabolismo , Fosforilación , Proteínas Serina-Treonina Quinasas/metabolismo , Estructura Terciaria de Proteína , Proteínas Tirosina Quinasas/metabolismo , Piridinas/farmacología , Pirimidinas/farmacología , Transducción de Señal , Factores de Tiempo , Proteínas de Unión al GTP rho/metabolismo , Quinasas Asociadas a rho , Familia-src QuinasasRESUMEN
The ability of fibronectin (Fn) to mediate cell adhesion through binding to alpha(5)beta(1) integrins is dependent on the conditions of its adsorption to the surface. Using a model system of alkylsilane SAMs with different functional groups (X=OH, COOH, NH(2) and CH(3)) and an erythroleukemia cell line expressing a single integrin (alpha(5)beta(1)), the effect of surface properties on the cellular adhesion with adsorbed Fn layers was investigated. (125)I-labeled Fn, a modified biochemical cross-linking/extraction technique and a spinning disc apparatus were combined to quantify the Fn adsorption, integrin binding and adhesion strength, respectively. This methodology allows for a binding equilibrium analysis that more closely reflects cellular adhesion found in stable tissue constructs in vivo. Differences in detachment strength and integrin binding were explained in terms of changes in the adhesion constant (psi, related to affinity) and binding efficiency of the adsorbed Fn for the alpha(5)beta(1) integrins (CH(3) approximately NH(2)Asunto(s)
Materiales Biocompatibles/farmacología
, Adhesión Celular
, Fibronectinas/efectos de los fármacos
, Integrina alfa5beta1/efectos de los fármacos
, Silanos/farmacología
, Línea Celular Tumoral
, Reactivos de Enlaces Cruzados/farmacología
, Fibronectinas/metabolismo
, Humanos
, Integrina alfa5beta1/metabolismo
, Succinimidas/farmacología
, Propiedades de Superficie
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BACKGROUND: The Centers for Disease Control and Prevention recommends persons at high risk for HIV infection in the United States receive annual HIV testing to foster early HIV diagnosis and timely linkage to health care. Heterosexuals make up a significant proportion of incident HIV infections (>25%) but test for HIV less frequently than those in other risk categories. Yet factors that promote or impede annual HIV testing among heterosexuals are poorly understood. The present study examines individual/attitudinal-, social-, and structural-level factors associated with past-year HIV testing among heterosexuals at high risk for HIV. METHODS: Participants were African-American/Black and Hispanic heterosexual adults (N = 2307) residing in an urban area with both high poverty and HIV prevalence rates. Participants were recruited by respondent-driven sampling in 2012-2015 and completed a computerized structured assessment battery covering background factors, multi-level putative facilitators of HIV testing, and HIV testing history. Separate logistic regression analysis for males and females identified factors associated with past-year HIV testing. RESULTS: Participants were mostly male (58%), African-American/Black (75%), and 39 years old on average (SD = 12.06 years). Lifetime homelessness (54%) and incarceration (62%) were common. Half reported past-year HIV testing (50%) and 37% engaged in regular, annual HIV testing. Facilitators of HIV testing common to both genders included sexually transmitted infection (STI) testing or STI diagnosis, peer norms supporting HIV testing, and HIV testing access. Among women, access to general medical care and extreme poverty further predicted HIV testing, while recent drug use reduced the odds of past-year HIV testing. Among men, past-year HIV testing was also associated with lifetime incarceration and substance use treatment. CONCLUSION: The present study identified gaps in rates of HIV testing among heterosexuals at high risk for HIV, and both common and gender-specific facilitators of HIV testing. Findings suggest a number of avenues for increasing HIV testing rates, including increasing the number and types of settings offering high-quality HIV testing; promoting STI as well as HIV testing; better integrating STI and HIV testing systems; implementing peer-driven social/behavioral intervention approaches to harness the positive influence of social networks and reduce unfavorable shared peer norms; and specialized approaches for women who use drugs.