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Genomic architecture appears to play crucial roles in health and a variety of diseases. How nuclear structures reorganize over different timescales is elusive, partly because the tools needed to probe and perturb them are not as advanced as needed by the field. To fill this gap, the National Institutes of Health Common Fund started a program in 2015, called the 4D Nucleome (4DN), with the goal of developing and ultimately applying technologies to interrogate the structure and function of nuclear organization in space and time.
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Núcleo Celular , Genoma , Estados Unidos , Núcleo Celular/genética , GenômicaRESUMO
Violence disproportionately impacts Black American youth, representing a major health disparity. Addressing the possible root causes of structural inequities to reduce violence may increase the impact of prevention strategies. However, efforts to evaluate the impact of such interventions pose numerous methodological challenges, particularly around selecting an effective evaluation design to detect change at the community level, with adequate power and sampling, and appropriate constructs and measurement strategies. We propose a multiple baseline experimental design to evaluate the impact of a community-level youth violence and suicidality prevention strategy. A multiple baseline experimental design with multiple community units balances the need for scientific rigor with practical and values-based considerations. It includes randomization and plausible counterfactuals without requiring large samples or placing some communities in the position of not receiving the intervention. Considerations related to the conceptualization of the logic model, mechanisms of change, and health disparity outcomes informed the development of the measurement strategy. The strengths and weaknesses of a multiple baseline experimental design are discussed in comparison to versions of randomized clinical trials. Future health disparity intervention evaluation research will benefit from (1) building a shared sense of urgent public need to promote health; (2) respecting the validity of values- and partnership-based decision-making; and (3) promoting community-based and systems-level partnerships in scientific grant funding. The described study has been registered prospectively at clinicaltrials.gov, Protocol Record 21-454.
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Violência , Humanos , Adolescente , Violência/prevenção & controle , Negro ou Afro-Americano , Avaliação de Programas e Projetos de Saúde , Projetos de PesquisaRESUMO
The purpose of this study was to examine adolescents' beliefs about fighting as mediators of longitudinal relations between perceptions of parental support for fighting and nonviolence and changes in adolescents' physical aggression. Participants were 2,575 middle school students (Mage = 12.20, SD = 1.02; 52% female; 83% African American) from the southeastern U.S. attending schools in communities with high rates of violence. Participants completed four waves of assessments every 3 months (i.e., fall, winter, spring, and summer). Each belief subscale mediated relations between perceptions of parental support for fighting and nonviolence and changes in aggression. Parental support for nonviolence was negatively associated with beliefs supporting reactive aggression and positively associated with beliefs against fighting. Parental support for retaliation was positively associated with beliefs supporting reactive and proactive aggression, and negatively associated with beliefs against fighting. Parental support for fighting as sometimes necessary was positively associated with beliefs supporting reactive aggression and beliefs that fighting is sometimes necessary. Beliefs supporting reactive and proactive aggression and beliefs that fighting is sometimes necessary were positively associated with aggression, whereas beliefs against fighting was negatively associated with aggression. Parents' support for fighting and for nonviolence may directly and indirectly reduce adolescents' physical aggression by influencing beliefs about the appropriateness of using aggression for self-defense and to attain a goal. This highlights the importance of jointly investigating multiple types of parental messages and types of beliefs about fighting.
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Comportamento do Adolescente , Agressão , Relações Pais-Filho , Violência , Humanos , Adolescente , Feminino , Agressão/psicologia , Masculino , Comportamento do Adolescente/psicologia , Criança , Violência/psicologia , Poder Familiar/psicologia , Pais/psicologia , Estudos LongitudinaisRESUMO
This mixed methods study had two aims: (1) to examine the effectiveness of a jail diversion program in reducing recidivism and promoting educational and employment outcomes; and (2) to qualitatively explore mechanisms through which the program was effective. Participants were 17 individuals arrested for drug offenses who participated in an intensive, law enforcement-based jail diversion program, and 17 individuals in a comparison group. Arrests were extracted from police records, and education and employment were extracted from program data. Four intervention participants completed qualitative interviews. Arrest rates in the intervention group decreased significantly postintervention, and arrest rates in the intervention group were numerically lower than those in the comparison group. Participants experienced significant increases in employment and driver's license status. Participants also identified mechanisms through which the program was effective. This jail diversion program shows promise in reducing recidivism and promoting adaptive functioning. Jail diversion programs that include mentorship, peer support, and removal of barriers to success may be particularly effective.
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Prisões Locais , Reincidência , Humanos , Aplicação da Lei/métodosRESUMO
Volume hyposensitivity resulting from impaired sympathetic detrusor relaxation during bladder filling contributes to detrusor underactivity (DU) associated with aging. Detrusor tension regulation provides an adaptive sensory input of bladder volume to the brainstem and is challenged by physiological stressors superimposed upon biological aging. We recently showed that HCN channels have a stabilizing role in detrusor sympathetic relaxation. While mature mice maintain homeostasis in the face of stressors, old mice are not always capable. In old mice, there is a dichotomous phenotype, in which resilient mice adapt and maintain homeostasis, while non-resilient mice fail to maintain physiologic homeostasis. In this DU model, we used cystometry as a stressor to categorize mice as old-responders (old-R, develop a filling/voiding cycle) or old-non-responders (old-NR, fail to develop a filling/voiding cycle; fluctuating high pressures and continuous leaking), while also assessing functional and molecular differences. Lamotrigine (HCN activator)-induced bladder relaxation is diminished in old-NR mice following HCN-blockade. Relaxation responses to NS 1619 were reduced in old-NR mice, with the effect lost following HCN-blockade. However, RNA-sequencing revealed no differences in HCN gene expression and electrophysiology studies showed similar percentage of detrusor myocytes expressing HCN (Ih) current between old-R and old-NR mice. Our murine model of DU further defines a role for HCN, with failure of adaptive recalibration of HCN participation and intensity of HCN-mediated stabilization, while genomic studies show upregulated myofibroblast and fibrosis pathways and downregulated neurotransmitter-degradation pathways in old-NR mice. Thus, the DU phenotype is multifactorial and represents the accumulation of age-associated loss in homeostatic mechanisms.
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Bexiga Inativa , Camundongos , Animais , Bexiga Urinária , Envelhecimento/fisiologiaRESUMO
AIMS: The Working Group (WG), initiated by the International Continence Society (ICS) Standardisation Steering Committee and supported by the Society of Urodynamics, Female Pelvic Medicine and Urogenital Reconstruction, has revised the ICS Standard for pressure-flow studies of 1997. METHODS: Based on the ICS standard for developing evidence-based standards, the WG developed this new ICS standard in the period from May 2020 to December 2022. A draft was posted on the ICS website in December 2022 to facilitate public discussion and the comments received have been incorporated into this final release. RESULTS: The WG has recommended analysis principles for the diagnosis of voiding dysfunction for adult men and women without relevant neurological abnormalities. New standard terms and parameters for objective and continuous grading of urethral resistance (UR), bladder outflow obstruction (BOO) and detrusor voiding contraction (DVC) are introduced in this part 2 of the standard. The WG has summarized the theory and recommendations for the practice of pressure-flow study (PFS) for patients in part 1. A pressure-flow plot is recommended for the diagnosis of every patient, in addition to time-based graphs. Voided percentage and post void residual volume should always be included in PFS analysis and diagnosis. Only parameters that represent the ratio or subtraction of pressure and synchronous flow are recommended to quantify UR and only parameters that combine pressure and flow in a product or sum are recommended to quantify DVC. The ICS BOO index and the ICS detrusor contraction index are introduced in this part 2 as the standard. The WG has suggested clinical PFS dysfunction classes for male and female patients. A pressure-flow scatter graph including every patient's pdet at maximum flow (pdetQmax ) with maximum flow rate (Qmax ) point should be included in all scientific reports considering voiding dysfunction. CONCLUSION: PFS is the gold standard used to objectively assess voiding function. Quantifying the dysfunction and grading of abnormalities are standardized for adult males and females.
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Obstrução do Colo da Bexiga Urinária , Adulto , Humanos , Masculino , Feminino , Micção , Urodinâmica , Sociedades , Proteínas RepressorasRESUMO
AIMS: The working group (WG) initiated by the International Continence Society Standardization Steering Committee and supported by the Society of Urodynamics, Female Pelvic Medicine and Urogenital Reconstruction has revised the (1997) ICS Standard for pressure flow studies. METHODS: Based on the ICS standard for developing evidence-based standards, the WG developed this new ICS standard in the period from May 2020 to December 2022. A draft was posted on the ICS website in January 2023 to facilitate public discussion and the comments received have been incorporated into this final release. RESULTS: The WG summarizes the theory and recommends the practice and the terms used for the diagnosis of voiding dysfunction for adult female and male patients without relevant neurological abnormalities, in part 1 of this standard. The WG has also recommended standard principles and parameters for objective and continuous grading of urethral resistance and detrusor voiding contraction on the basis of pressure flow studies in part 2. The recommendations for practice in this part have also the aim to increase the understanding of the physiology as well as the psychology of voiding. The potential effects of the laboratory situation of the test on the voiding as well as the role of the urodynamicist in this regard are discussed. The WG has recommended to use for diagnosis only the voidings that are considered representative by the patient. CONCLUSION: A pressure flow study is the gold standard to assess voiding function and to quantify dysfunction. This part of the standard explains the clinical background, gives recommendations for the execution of a pressure flow study and lists relevant terms, parameters, and units of measurements.
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Doenças da Bexiga Urinária , Micção , Adulto , Humanos , Masculino , Feminino , Micção/fisiologia , Bexiga Urinária , Sociedades , Urodinâmica/fisiologia , Proteínas RepressorasRESUMO
OBJECTIVE: The purpose of this integrative review was to explore, appraise and synthesize the current literature on correlates of suicide risk in nurses. DESIGN: Integrative literature review. DATA SOURCES: Cumulative Index to Nursing and Allied Health Literature (CINAHL), Joanna Briggs Institute, PubMed, PsycInfo and Scopus electronic databases were searched for abstracts published between 2005 and 2020. Reference lists were hand searched. REVIEW METHODS: The integrative review was based on the Whittemore and Knafl review methodology. Primary qualitative and quantitative studies about suicidal behaviour in nurses published in peer-reviewed journals were included. The methodological quality of included articles was assessed using the Mixed Methods Assessment Tool. RESULTS: Separate correlates of risk and protective factors were identified for suicidal ideation, suicide attempt and death by suicide in nurses. IMPLICATIONS: Due to a number of factors at the individual, interpersonal and work levels, nurses are uniquely positioned to be at risk of dying by suicide. The ideation-to-action framework provides a theoretical guide to understand the interplay between correlates and the effect it has on increasing a nurses' capability for suicide. CONCLUSIONS: This review integrates the empirical literature to elucidate the concept of suicidal behaviour as it applies to nurses.
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Ideação Suicida , Tentativa de Suicídio , HumanosRESUMO
ABSTRACT: Poulos, N, Haff, GG, Nibali, M, Graham-Smith, P, and Newton, RU. Comparison of the potentiating effect of variable load jump squats on acute drop jump performance in rugby sevens athletes. J Strength Cond Res 37(1): 149-160, 2023-The effect of variable load jump squats (JSs) on acute drop jump (DJ) performance across multiple sets was examined. Seventeen elite rugby sevens athletes performed 3 DJs after 3 repetitions of a JS conditioning activity (CA) performed at 30 or 50% 1RM back squat loads. Acute postactivation performance enhancement (PAPE) in DJ kinetic and kinematic variables was assessed using a commercially available force platform (1,000 Hz). Postactivation performance enhancement was predominant after the 30% 1RM load with the greatest frequency of potentiation exhibited in set 3. The 50% 1RM CA resulted in substantial decrements in DJ performance with the exception of active stiffness, reactive strength index (flight:contact time), and contact time. Moderate differences were observed between the 50 and 30% 1RM loads for peak power (W), impulse (N·s), and force at zero velocity (N); active stiffness was the only variable where PAPE was greater in the 50% 1RM CA (ES: small). Active stiffness was the only variable to display favorable associations with relative strength in both the JS 30% 1RM (ES: 0.38 ± 0.20; moderate) and 50% 1RM (ES: 0.24 ± 0.23; small) CA loads. The JS 30% 1RM CA results in greater magnitude and frequency of PAPE of DJ kinetic and kinematic variables and is recommended if seeking to target PAPE in a range of DJ performance variables. Heavier JS loads may be appropriate if enhancement of muscle stiffness and stretch-shortening cycle efficiency is required. Consideration of targeted kinetic and kinematic variables when selecting CA intensity in complex training design is recommended.
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Força Muscular , Treinamento Resistido , Humanos , Força Muscular/fisiologia , Rugby , Atletas , Postura , Fenômenos Biomecânicos , Treinamento Resistido/métodos , Músculo Esquelético/fisiologiaRESUMO
Multiple sclerosis (MS) is a chronic, progressively debilitating demyelinating disease of the central nervous system (CNS). Nearly 80% of MS patients experience lower urinary tract dysfunction early in their diagnosis. This significantly affects the quality of life, and in latter stages of disease is a leading cause of hospitalization. Previously, animal models have shown that inflammatory demyelination in the CNS causes profound bladder dysfunction, but the confounding influence of systemic inflammation limits the potential interpretation of the contribution of CNS demyelination to bladder dysfunction. Since the micturition circuit has myelinated neuronal connections in the cortex, brainstem, and spinal cord, we examined alterations in bladder function in the cuprizone model characterized by demyelinating lesions in the cortex and corpus callosum that are independent of T-cell-mediated autoimmunity. Herein, we report that a 4-week dietary cuprizone treatment in C57Bl/6J mice induced alterations in voiding behavior with increased micturition frequency and reduced volume voided, similar to human MS bladder dysfunction. Subsequently, recovery from cuprizone treatment restored normal bladder function. Demyelination and remyelination were confirmed by Luxol Fast Blue staining of the corpus callosum. Additionally, we also determined that an 8-week cuprizone treatment, resulting in chronic demyelination lacking spontaneous remyelination potential, is associated with an exacerbated voiding phenotype. Interestingly, while cuprizone-induced CNS demyelination severely affected conscious (cortical) urinary behavior, the brainstem and spinal cord reflex remained unchanged, as confirmed by urethane-anesthetized cystometry. This is the first study to show that cortical demyelination independent of inflammation can negatively impact urinary function.
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Doenças Desmielinizantes , Esclerose Múltipla , Animais , Tronco Encefálico/patologia , Corpo Caloso/patologia , Cuprizona/toxicidade , Doenças Desmielinizantes/patologia , Modelos Animais de Doenças , Humanos , Inflamação/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Esclerose Múltipla/patologia , Bainha de Mielina/patologia , Oligodendroglia/metabolismo , Qualidade de Vida , Reflexo , MicçãoRESUMO
Control of urinary continence is predicated on sensory signaling about bladder volume. Bladder sensory nerve activity is dependent on tension, implicating autonomic control over detrusor myocyte activity during bladder filling. Hyperpolarization-activated cyclic nucleotide-gated (HCN) ion channels are known contributors to bladder control, but their mechanism of action is not well understood. The lack of a definitive identification of cell type(s) expressing HCN in the bladder presents a significant knowledge gap. We recently reported a complete transcriptomic atlas of the C57BL/6 mouse bladder showing the dominant HCN paralog in mouse bladder, Hcn1, is limited to a subpopulation of detrusor smooth myocytes (DSMs). Here, we report details of these findings, along with results of patch-clamp experiments, immunohistochemistry, and functional myobath/tension experiments in bladder strips. With the use of a transgenic mouse expressing fluorescence-tagged α-smooth muscle actin, our data confirmed location and function of DSM HCN channels. Despite previous associations of HCN with postulated bladder interstitial cells, neither evidence of specific interstitial cell types nor an association of nonmyocytes with HCN was discovered. We confirm that HCN activation participates in reducing sustained (tonic) detrusor tension via cAMP, with no effect on intermittent (phasic) detrusor activity. In contrast, blockade of HCN increases phasic activity induced by a protein kinase A (PKA) blocker or a large-conductance Ca2+-activated K+ (BK) channel opener. Our findings, therefore, suggest a central role for detrusor myocyte HCN in regulating and constraining detrusor myocyte activity during bladder filling.
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Canais de Cátion Regulados por Nucleotídeos Cíclicos , Células Intersticiais de Cajal , Adrenérgicos , Animais , Canais de Cátion Regulados por Nucleotídeos Cíclicos/genética , Canais de Cátion Regulados por Nucleotídeos Cíclicos/metabolismo , Canais Disparados por Nucleotídeos Cíclicos Ativados por Hiperpolarização/genética , Canais Disparados por Nucleotídeos Cíclicos Ativados por Hiperpolarização/metabolismo , Células Intersticiais de Cajal/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Nucleotídeos Cíclicos/metabolismoRESUMO
BACKGROUND: An absent left ventricular ejection fraction (LVEF) reserve with vasodilator stress with PET cardiac imaging has been shown to provide significant independent and incremental value to the perfusion images for prediction of future cardiovascular adverse events. However, the prognostic value of LVEF reserve has not been well characterized with SPECT myocardial perfusion imaging (MPI). METHODS: We studied 858 consecutive patients with normal and abnormal perfusion pattern with regadenoson SPECT MPI. Change in LVEF was calculated as post-stress LVEF-rest LVEF. Absent LVEF reserve was defined as a drop in LVEF by 5% or more on the post-stress images. The primary outcome was a composite of cardiac death, non-fatal myocardial infarction and late coronary revascularization. RESULTS: An absent LVEF reserve was more common in patients with abnormal vs normal MPI (31% vs 19%, P = .001). During a median follow-up of 32 months, the primary outcome was experienced by 31% of the study population. An absent LVEF reserve was not associated with an increased risk of the primary outcome in patients with normal (hazard ratio 1.1, 95% CI .4-2.7, P = .8) or abnormal (.75, .56-1.00, P = .05) MPI. There was no significant correlation between extent of ischemia and post-stress change in LVEF (Pearson r = - .072, P = .07). CONCLUSIONS: In patients undergoing regadenoson SPECT MPI, absent LVEF reserve is not associated with worse cardiac outcomes. Thus, routine reporting of both post-stress and rest LVEF measurements in this setting may not be necessary.
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Imagem de Perfusão do Miocárdio , Humanos , Imagem de Perfusão do Miocárdio/métodos , Prognóstico , Purinas , Pirazóis , Volume Sistólico , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Função Ventricular EsquerdaRESUMO
AIMS: While most Alzheimer's disease (AD) research emphasizes cognitive and behavioral abnormalities, lower urinary tract symptoms (LUTS) are observed in a third of AD patients, contributing to morbidity, poor quality of life, and need for institutionalization. Alzheimer's disease-associated urinary dysfunction (ADUD) has been assumed to be due to cognitive decline alone. While mouse studies have suggested that bladder innervation and voiding behavior may be altered in AD models, technical challenges precluded voiding reflex assessments. This study seeks to establish a mouse model of ADUD, and it seeks to characterize the noncognitive sequelae involved in AD-pathology associated alterations in the voiding reflex. METHODS: Having developed techniques permitting the assessment of bladder volume, pressure, and flow in mice, we now provide evidence of alterations in involuntary bladder control and increased response heterogeneity in a transgenic amyloidosis mouse model of AD using cystometry and tissue pharmacomyography. Tg-APP/PS1DE9 (PA) mice and their wild-type (WT) littermates (n = 6-8 per group) were used before plaque onset in the PA mice (4-6 months) and after plaque accumulation in the PA mice (8-10 months) in comparison to their WT control littermates. RESULTS: Novel findings include data suggestive of sphincteric discoordination, with pharmacological evidence of altered adrenergic mechanisms. CONCLUSIONS: Together, these data highlight the importance of addressing noncognitive sequelae of AD and offer novel translational insights into the debilitating impact of AD on LUTS and incontinence.
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Doença de Alzheimer , Fenômenos Fisiológicos do Sistema Urinário , Doença de Alzheimer/complicações , Precursor de Proteína beta-Amiloide , Animais , Modelos Animais de Doenças , Progressão da Doença , Camundongos , Camundongos Transgênicos , Qualidade de Vida , Bexiga Urinária/patologiaRESUMO
Despite remarkable progress, tobacco control efforts are not equitably distributed, and tobacco-related disparities continue to contribute to significant health disparities. Our premise in this commentary is that Intersectionality can serve as a productive analytical framework for examining tobacco-related disparities across and within multiple marginalized populations. Intersectionality is a theoretical framework for understanding the multiple interlocking societal systems that bestow privilege and oppression and is increasingly being to the study of health inequities. We present a model and describe how tobacco-related disparities can be understood via critical elements of Intersectionality. We conclude that the application of Intersectionality to understanding tobacco-related disparities has potential to stimulate meaningful discussion and lead to new and innovative multilevel and cross-cutting interventions to eliminate tobacco-related disparities and foster culturally safe environment in which all people can thrive. IMPLICATIONS: This commentary describes how Intersectionality can serve as a productive analytic framework for examining the development and maintenance of tobacco-related disparities across and within many marginalized groups.
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Enquadramento Interseccional , Nicotiana , Disparidades nos Níveis de Saúde , Humanos , Uso de TabacoRESUMO
The current study examined hypotheses related to the development of suicidal ideation as directed by the interpersonal theory within a sample of acutely suicidal psychiatric inpatients. Consistent with ideation-to-action models, we distinguished suicidal desire from resolved plans and preparations. Although thwarted belongingness and perceived burdensomeness were correlated with suicidal desire, only perceived burdensomeness was associated with suicidal desire controlling for depression and thwarted belongingness. Depression alone was related to plans and preparations. Findings are interpreted as challenging the mechanisms hypothesis of the interpersonal theory and suggest that alternative conceptualizations of the development of suicidal desire may be warranted.
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Ideação Suicida , Suicídio , Humanos , Pacientes Internados/psicologia , Relações Interpessoais , Teoria Psicológica , Fatores de Risco , Suicídio/psicologiaRESUMO
Programmed cell death promotes homeostatic cell turnover in the epithelium but is dysregulated in cancer. The glycosyltransferase ST6Gal-I is known to block homeostatic apoptosis through α2,6-linked sialylation of the death receptor TNFR1 in many cell types. However, its role has not been investigated in gastric epithelial cells or gastric tumorigenesis. We determined that human gastric antral epithelium rarely expressed ST6Gal-I, but the number of ST6Gal-I-expressing epithelial cells increased significantly with advancing premalignancy leading to cancer. The mRNA expression levels of ST6GAL-I and SOX9 in human gastric epithelial cells correlated positively with one another through the premalignancy cascade, indicating that increased epithelial cell expression of ST6Gal-I is associated with premalignant progression. To determine the functional impact of increased ST6Gal-I, we generated human gastric antral organoids from epithelial stem cells and differentiated epithelial monolayers from gastric organoids. Gastric epithelial stem cells strongly expressed ST6Gal-I, suggesting a novel biomarker of stemness. In contrast, organoid-derived epithelial monolayers expressed markedly reduced ST6Gal-I and underwent TNF-induced, caspase-mediated apoptosis, consistent with homeostasis. Conversely, epithelial monolayers generated from gastric cancer stem cells retained high levels of ST6Gal-I and resisted TNF-induced apoptosis, supporting prolonged survival. Protection from TNF-induced apoptosis depended on ST6Gal-I overexpression, because forced ST6Gal-I overexpression in normal gastric stem cell-differentiated monolayers inhibited TNF-induced apoptosis, and cleavage of α2,6-linked sialic acids from gastric cancer organoid-derived monolayers restored susceptibility to TNF-induced apoptosis. These findings implicate up-regulated ST6Gal-I expression in blocking homeostatic epithelial cell apoptosis in gastric cancer pathogenesis, suggesting a mechanism for prolonged epithelioid tumor cell survival.
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Antígenos CD/biossíntese , Células Epiteliais/metabolismo , Regulação Enzimológica da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Homeostase , Proteínas de Neoplasias/biossíntese , Organoides/metabolismo , Sialiltransferases/biossíntese , Neoplasias Gástricas/epidemiologia , Antígenos CD/genética , Linhagem Celular , Células Epiteliais/patologia , Humanos , Proteínas de Neoplasias/genética , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Organoides/patologia , Fatores de Transcrição SOX9/genética , Fatores de Transcrição SOX9/metabolismo , Sialiltransferases/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Células Tumorais CultivadasRESUMO
Lower urinary tract symptoms and dysfunction (LUTS/LUTD) contribute to loss of quality of life, morbidity, and need for medical intervention in most patients with multiple sclerosis (MS). Although MS is an inflammatory neurodegenerative disease, clinical manifestations including continence control disorders have traditionally been attributed to the loss of neural signaling due to neurodegeneration. Clinical approaches to MS-LUTS/LUTD have focused on addressing symptoms in the context of urodynamic dysfunctions as pathophysiologic understandings are incomplete. The mouse model provides a useful research platform for discovery of more detailed molecular, cellular, and tissue-level knowledge of the disease and its clinical manifestations. The aim of this two-part review is to provide a state-of-the-art update on the use of the mouse model for MS research, with a focus on lower urinary tract symptoms. Part I presents a summary of current understanding of MS pathophysiology, the impact on lower urinary tract symptoms, and briefly introduces the types of mouse models available to study MS. Part II presents the common animal models that are currently available to study MS, their mechanism, relevance to MS-LUTS/LUTD and their urinary pathophysiology, advantages and disadvantages.
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Sintomas do Trato Urinário Inferior , Esclerose Múltipla , Animais , Sintomas do Trato Urinário Inferior/etiologia , Camundongos , Esclerose Múltipla/complicações , Doenças Neurodegenerativas , Qualidade de Vida , UrodinâmicaRESUMO
Lower urinary tract symptoms and dysfunction (LUTS/LUTD) contribute to loss of quality of life, morbidity, and need for medical intervention in most patients with multiple sclerosis (MS). Although MS is an inflammatory neurodegenerative disease, clinical manifestations including continence control disorders have traditionally been attributed to the loss of neural signaling due to neurodegeneration. Clinical approaches to MS-LUTS/LUTD have focused on addressing symptoms in the context of urodynamic dysfunctions as pathophysiologic understandings are incomplete. The mouse model provides a useful research platform for the discovery of more detailed molecular, cellular, and tissue-level knowledge of the disease and its clinical manifestations. The aim of this two-part review is to provide a state-of-the-art update on the use of the mouse model for MS research, with a focus on lower urinary tract symptoms. Part I presents a summary of the current understanding of MS pathophysiology, the impact on lower urinary tract symptoms, and briefly introduces the types of mouse models available to study MS. Part II presents the common animal models that are currently available to study MS, their mechanism, relevance to MS-LUTS/LUTD and their urinary pathophysiology, advantages, and disadvantages.
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Sintomas do Trato Urinário Inferior , Esclerose Múltipla , Sistema Urinário , Animais , Sintomas do Trato Urinário Inferior/etiologia , Camundongos , Esclerose Múltipla/complicações , Doenças Neurodegenerativas , Qualidade de VidaRESUMO
The current study examined patterns of endorsement of Interpersonal Theory of Suicide constructs in a group of patients with cancer (N = 133) via Latent Profile Analysis. Four profiles were identified: (1) Interpersonally Distressed (n = 7; 5.2%), (2) Burdened (n = 11; 8.3%), (3) Fearless About Death (n = 40; 30.1%), (4) Non-Distressed (n = 75; 56.4%). Profiles with higher levels of thwarted belongingness, perceived burdensomeness, and hopelessness were associated with greater suicide ideation. Results also suggest there may be characteristics of patients with cancer that require unique consideration about the potential meaning and relevance of such constructs.
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INTRODUCTION: Widely accepted consensus terminology and calculations of detrusor contractility in females do not exist but may be useful. We report the output of a proposal session at the International Consultation on Incontinence Research Society meeting 2019, addressing the title topic. METHODS: Three formal presentations and a lively discussion addressed several questions including: which is the optimal cutoff value of female bladder voiding efficiency during uroflow to suspect obstruction or detrusor underactivity? Is there a definition of pure underactive and pure obstructed voiding in females? Is there a place to distinguish those relatively obstructed from those relatively underactive females especially in those cases of equivocal obstruction? Current measures of contractility were reviewed for their usefulness in women. RESULTS: No recommendation for a specific index or calculation can be made based on current knowledge. "Contractility" may be context-dependent regarding clinical care, clinical prognostication, and physiologic research. CONCLUSIONS: This group proposes that context-sensitive definitions of "Contractility" deserve attention by international leadership. Cooperative clinical and physiologic expertise will be needed to achieve this goal. Following initial recommendations based on expert opinion, the development of final definitions and measures of contractility should be iterative, based upon validation studies to be considered as part of the definitional process.