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1.
Proc Natl Acad Sci U S A ; 121(29): e2400666121, 2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-38976738

RESUMEN

Urinary tract infection (UTI) commonly afflicts people with diabetes. This augmented infection risk is partly due to deregulated insulin receptor (IR) signaling in the kidney collecting duct. The collecting duct is composed of intercalated cells (ICs) and principal cells (PCs). Evidence suggests that ICs contribute to UTI defenses. Here, we interrogate how IR deletion in ICs impacts antibacterial defenses against uropathogenic Escherichia coli. We also explore how IR deletion affects immune responses in neighboring PCs with intact IR expression. To accomplish this objective, we profile the transcriptomes of IC and PC populations enriched from kidneys of wild-type and IC-specific IR knock-out mice that have increased UTI susceptibility. Transcriptomic analysis demonstrates that IR deletion suppresses IC-integrated stress responses and innate immune defenses. To define how IR shapes these immune defenses, we employ murine and human kidney cultures. When challenged with bacteria, murine ICs and human kidney cells with deregulated IR signaling cannot engage central components of the integrated stress response-including activating transcriptional factor 4 (ATF4). Silencing ATF4 impairs NFkB activation and promotes infection. In turn, NFkB silencing augments infection and suppresses antimicrobial peptide expression. In diabetic mice and people with diabetes, collecting duct cells show reduced IR expression, impaired integrated stress response engagement, and compromised immunity. Collectively, these translational data illustrate how IR orchestrates collecting duct antibacterial responses and the communication between ICs and PCs.


Asunto(s)
Ratones Noqueados , Receptor de Insulina , Infecciones Urinarias , Escherichia coli Uropatógena , Animales , Ratones , Infecciones Urinarias/microbiología , Infecciones Urinarias/metabolismo , Infecciones Urinarias/inmunología , Humanos , Receptor de Insulina/metabolismo , Escherichia coli Uropatógena/inmunología , Infecciones por Escherichia coli/inmunología , Infecciones por Escherichia coli/metabolismo , Infecciones por Escherichia coli/microbiología , Riñón/metabolismo , Transducción de Señal , Túbulos Renales Colectores/metabolismo , Inmunidad Innata , Ratones Endogámicos C57BL
2.
Proc Natl Acad Sci U S A ; 120(4): e2213363120, 2023 01 24.
Artículo en Inglés | MEDLINE | ID: mdl-36652479

RESUMEN

With the emergence of antibiotic-resistant bacteria, innovative approaches are needed for the treatment of urinary tract infections. Boosting antimicrobial peptide expression may provide an alternative to antibiotics. Here, we developed reporter cell lines and performed a high-throughput screen of clinically used drugs to identify compounds that boost ribonuclease 4 and 7 expression (RNase 4 and 7), peptides that have antimicrobial activity against antibiotic-resistant uropathogens. This screen identified histone deacetylase (HDAC) inhibitors as effective RNase 4 and RNase 7 inducers. Validation studies in primary human kidney and bladder cells confirmed pan-HDAC inhibitors as well as the HDAC class I inhibitor, MS-275, induce RNase 4 and RNase 7 to protect human kidney and bladder cells from uropathogenic Escherichia coli. When we administered MS-275 to mice, RNase 4 and 7 expression increased and mice were protected from acute transurethral E. coli challenge. In support of this mechanism, MS-275 treatment increased acetylated histone H3 binding to the RNASE4 and RNASE7 promoters. Overexpression and knockdown of HDAC class I proteins identified HDAC3 as a primary regulator of RNase 4 and 7. These results demonstrate the protective effects of enhancing RNase 4 and RNase 7, opening the door to repurposing medications as antibiotic conserving therapeutics for urinary tract infection.


Asunto(s)
Inhibidores de Histona Desacetilasas , Infecciones Urinarias , Humanos , Ratones , Animales , Inhibidores de Histona Desacetilasas/farmacología , Escherichia coli/metabolismo , Reposicionamiento de Medicamentos , Ribonucleasas/metabolismo , Infecciones Urinarias/tratamiento farmacológico , Infecciones Urinarias/microbiología , Antibacterianos
3.
Pediatr Blood Cancer ; 71(4): e30892, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38302730

RESUMEN

BACKGROUND: Pediatric hematopoietic stem cell transplantation (HCT) is an intensive medical procedure that places substantial financial and logistical burdens on families and is associated with significant health risks, such as graft-versus-host disease (GVHD), and infections. The influence of the social determinants of health (SDoH) on outcomes following pediatric HCT is understudied. This study aimed to examine whether SDoH predicts outcomes following pediatric HCT. PROCEDURE: Data were collected from 84 children who received HCT (Mage  = 5.8 years, SD = 3.7) and their primary caregiver. Detailed demographic information was collected from caregivers at baseline, and child health information was extracted from the electronic medical records. Multivariate logistic regression was used to examine the association between SDoH and health outcomes within a 24-month period following pediatric HCT. RESULTS: After controlling for malignancy as reason for transplant and donor type, lower family income predicted the incidence of chronic GVHD. Neighborhood deprivation, total family income, public health insurance, caregiver relationship status, caregiver educational attainment, and perceived family financial difficulties did not predict acute GVHD or the number of infections. CONCLUSIONS: Total family income is a simple family indicator of SDoH that predicts chronic GVHD after pediatric allogeneic HCT. These findings provide further support for the importance of screening of child and family SDoH risks to ensure that fundamental needs can be met to mitigate potential health disparities for up to 2 years following pediatric HCT.


Asunto(s)
Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Humanos , Niño , Preescolar , Determinantes Sociales de la Salud , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Células Madre Hematopoyéticas/métodos , Enfermedad Injerto contra Huésped/epidemiología , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/patología , Evaluación de Resultado en la Atención de Salud
4.
Am J Physiol Renal Physiol ; 320(5): F972-F983, 2021 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-33818125

RESUMEN

Antimicrobial peptides are essential host defense mechanisms that prevent urinary tract infections. Recent studies have demonstrated that peptides in the ribonuclease A superfamily have antimicrobial activity against uropathogens and protect the urinary tract from uropathogenic Escherichia coli (UPEC). Little is known about the antibacterial function or expression of ribonuclease 4 (RNase 4) in the human urinary tract. Here, we show that full-length recombinant RNase 4 peptide and synthetic amino-terminal RNase 4 peptide fragment have antibacterial activity against UPEC and multidrug-resistant (MDR)-UPEC. RNASE4 transcript expression was detected in human kidney and bladder tissue using quantitative real-time PCR. Immunostaining or in situ hybridization localized RNase 4 expression to proximal tubules, principal and intercalated cells in the kidney's collecting duct, and the bladder urothelium. Urinary RNase 4 concentrations were quantified in healthy controls and females with a history of urinary tract infection. Compared with controls, urinary RNase 4 concentrations were significantly lower in females with a history of urinary tract infection. When RNase 4 was neutralized in human urine or silenced in vitro using siRNA, urinary UPEC replication or attachment to and invasion of urothelial and kidney medullary cells increased. These data show that RNase 4 has antibacterial activity against UPEC, is expressed in the human urinary tract, and can contribute to host defense against urinary tract infections.NEW & NOTEWORTHY Ribonuclease 4 (RNase 4) is a newly identified host defense peptide in the human kidney and bladder. RNase 4 kills uropathogenic Escherichia coli (UPEC) and multidrug-resistant UPEC. RNase 4 prevents invasive UPEC infection and suppressed RNase 4 expression may be a risk factor for more severe or recurrent urinary tract infection.


Asunto(s)
Regulación Enzimológica de la Expresión Génica/fisiología , Riñón/enzimología , Ribonucleasas/metabolismo , Vejiga Urinaria/enzimología , Adolescente , Péptidos Catiónicos Antimicrobianos , Niño , Células Endoteliales/enzimología , Células Endoteliales/metabolismo , Femenino , Silenciador del Gen , Historia Antigua , Historia Medieval , Humanos , Riñón/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa , Ribonucleasas/genética , Ribonucleasas/orina , Vejiga Urinaria/metabolismo , Escherichia coli Uropatógena , Urotelio/citología
5.
Psychooncology ; 30(4): 536-545, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33227159

RESUMEN

OBJECTIVE: Providing opportunities to communicate about possible cancer recurrence may be adaptive for youth in remission, yet parents may experience difficulty guiding discussions related to fears of cancer recurrence (FCR). This study aimed to characterize mother-child discussions about potential cancer recurrence during post-treatment survivorship and to determine predictors of maternal communication. METHODS: Families (N = 67) were recruited after the child's initial cancer diagnosis (age 5-17 years) and mothers self-reported their distress (post-traumatic stress symptoms; PTSS). During survivorship 3-5 years later, mothers were video-recorded discussing cancer with their children. Presence and length of discussion about potential cancer recurrence, triggers for FCR, expressed affect, and conversational reciprocity were examined. Hierarchical regressions were used to assess maternal PTSS near the time of cancer diagnosis and child age as predictors of maternal communication. RESULTS: Three-quarters of dyads spontaneously discussed risk for or fears about cancer recurrence; mothers initiated the topic more frequently than their children. Dyads discussed internal (bodily symptoms) and external (medical, social) triggers of FCR. Higher maternal PTSS at diagnosis predicted significantly lower levels of maternal positive affect (ß = -0.36, p = 0.02) and higher levels of maternal negative affect (ß = 0.30, p = 0.04) during discussion of recurrence 3-5 years later. Older child age significantly predicted higher levels of maternal negative affect (ß = 0.35, p = 0.02). Higher maternal PTSS at diagnosis predicted shorter discussions about recurrence for younger children (ß = 0.27, p = 0.02). CONCLUSIONS: Understanding predictors and characteristics of mother-child discussions about recurrence can guide family-based FCR interventions, particularly those promoting communication as a supportive tool. Both maternal PTSS and child age are important to consider when developing these interventions.


Asunto(s)
Neoplasias , Trastornos por Estrés Postraumático , Adolescente , Niño , Preescolar , Comunicación , Femenino , Humanos , Relaciones Madre-Hijo , Madres , Supervivencia
6.
Behav Sleep Med ; 19(4): 492-504, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-32746639

RESUMEN

OBJECTIVE/BACKGROUND: Fatigue is one of the most consistent and distressing symptoms reported by adolescent/young adult (AYA) oncology patients. Bright white light (BWL) is used to treat fatigue in adult oncology but has not been explored in AYA oncology patients. The purpose of the current study was to determine the feasibility and acceptability of BWL for AYA who were receiving cancer-directed therapy. PARTICIPANTS: 51 AYA patients with newly diagnosed solid tumors, including lymphoma. METHODS: Participants were randomized to dim red light (DRL, n = 25) or BWL (n = 26) from devices retrofitted with adherence monitors for 30 minutes upon awakening daily for 8 weeks. Side effects were assessed via modified Systematic Assessment for Treatment-Emergent Effects (SAFTEE). Participants completed the PedsQL Multidimensional Fatigue Scale. RESULTS: Of patients approached, 73% consented and participated. Mean adherence was 57% of days on study with 30.68 average daily minutes of usage. BWL did not cause more extreme treatment-emergent effects over DRL. Patients in the BWL group demonstrated significant improvement on all fatigue outcomes by both self-report and parent proxy report, which was not observed in the DRL group. CONCLUSIONS: This is the first study to evaluate the feasibility and acceptability of light therapy to reduce fatigue in AYA patients receiving cancer-directed therapy. These findings demonstrate the feasibility and acceptability of the intervention and provide preliminary evidence of the potential benefits of BWL, which warrants further study in a confirmatory efficacy trial.ClinicalTrials.gov Identifier Number: NCT02429063.


Asunto(s)
Fatiga/complicaciones , Fatiga/terapia , Neoplasias/complicaciones , Neoplasias/tratamiento farmacológico , Fototerapia , Adolescente , Niño , Estudios de Factibilidad , Femenino , Humanos , Masculino , Adulto Joven
7.
J Trauma Dissociation ; 22(5): 540-554, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33433303

RESUMEN

Associations between substance use and depression among women experiencing intimate partner violence (IPV) have received limited empirical attention. This study examined how demographics, frequency of IPV and problematic substance use were related to depressive symptoms among women exposed to recent IPV. Participants included 112 women (Mage = 32.26; 67% Black) recruited from community organizations in the U.S. Midsouth, many of whom had used substances (80.2%) and were living below the poverty threshold (71.3%). Results from a hierarchical multiple regression analysis revealed that, after accounting for age and income, more frequent IPV and more problematic tobacco use were associated with higher depressive symptoms. Neither alcohol nor illicit substance use were significantly associated with depressive symptoms. These findings highlight a meaningful connection between problematic tobacco use and depressive symptoms, indicating the potential benefits of incorporating tobacco use psychoeducation and cessation strategies into treatment programs for women experiencing depression in the context of IPV.


Asunto(s)
Violencia de Pareja , Trastornos Relacionados con Sustancias , Adulto , Depresión/epidemiología , Femenino , Humanos , Trastornos Relacionados con Sustancias/epidemiología
8.
Pediatr Nephrol ; 35(7): 1183-1192, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-31197473

RESUMEN

Urinary tract infections are a severe public health problem. The emergence and spread of antimicrobial resistance among uropathogens threaten to further compromise the quality of life and health of people who develop acute and recurrent upper and lower urinary tract infections. The host defense mechanisms that prevent invasive bacterial infection are not entirely delineated. However, recent evidence suggests that versatile innate immune defenses play a key role in shielding the urinary tract from invading uropathogens. Over the last decade, considerable advances have been made in defining the innate mechanisms that maintain immune homeostasis in the kidney and urinary tract. When these innate defenses are compromised or dysregulated, pathogen susceptibility increases. The objective of this review is to provide an overview of how basic science discoveries are elucidating essential innate host defenses in the kidney and urinary tract. In doing so, we highlight how these findings may ultimately translate into the clinic as new biomarkers or therapies for urinary tract infection.


Asunto(s)
Inmunidad Innata , Infecciones Urinarias/inmunología , Animales , Niño , Humanos , Ratones , Pielonefritis/inmunología , Pielonefritis/microbiología , Infecciones Urinarias/microbiología
9.
J Am Soc Nephrol ; 30(8): 1385-1397, 2019 08.
Artículo en Inglés | MEDLINE | ID: mdl-31239387

RESUMEN

BACKGROUND: Evidence suggests that antimicrobial peptides, components of the innate immune response, protect the kidneys and bladder from bacterial challenge. We previously identified ribonuclease 7 (RNase 7) as a human antimicrobial peptide that has bactericidal activity against uropathogenic Escherichia coli (UPEC). Functional studies assessing RNase 7's contributions to urinary tract defense are limited. METHODS: To investigate RNase 7's role in preventing urinary tract infection (UTI), we quantified urinary RNase 7 concentrations in 29 girls and adolescents with a UTI history and 29 healthy female human controls. To assess RNase 7's antimicrobial activity in vitro in human urothelial cells, we used siRNA to silence urothelial RNase 7 production and retroviral constructs to stably overexpress RNase 7; we then evaluated UPEC's ability to bind and invade these cells. For RNase 7 in vivo studies, we developed humanized RNase 7 transgenic mice, subjected them to experimental UTI, and enumerated UPEC burden in the urine, bladder, and kidneys. RESULTS: Compared with controls, study participants with a UTI history had 1.5-fold lower urinary RNase 7 concentrations. When RNase 7 was silenced in vitro, the percentage of UPEC binding or invading human urothelial cells increased; when cells overexpressed RNase 7, UPEC attachment and invasion decreased. In the transgenic mice, we detected RNase 7 expression in the kidney's intercalated cells and bladder urothelium. RNase 7 humanized mice exhibited marked protection from UPEC. CONCLUSIONS: These findings provide evidence that RNase 7 has a role in kidney and bladder host defense against UPEC and establish a foundation for investigating RNase 7 as a UTI prognostic marker or nonantibiotic-based therapy.


Asunto(s)
Infecciones por Escherichia coli/enzimología , Riñón/enzimología , Ribonucleasas/genética , Vejiga Urinaria/enzimología , Infecciones Urinarias/enzimología , Infecciones Urinarias/microbiología , Escherichia coli Uropatógena , Adolescente , Animales , Antibacterianos/farmacología , Péptidos Catiónicos Antimicrobianos/genética , Niño , Preescolar , Femenino , Silenciador del Gen , Humanos , Inmunidad Innata , Lactante , Riñón/microbiología , Masculino , Ratones , Ratones Transgénicos , Fenotipo , Pronóstico , Vejiga Urinaria/microbiología , Urotelio/metabolismo , Urotelio/patología , Adulto Joven
10.
Death Stud ; 42(9): 537-547, 2018 10.
Artículo en Inglés | MEDLINE | ID: mdl-29393839

RESUMEN

Grief research has typically centered on one time point, without considering the impact of multiple losses over time. In this study, 546 bereaved emerging adults were divided into three groups: those who experienced a recent loss (0-2 years ago), a past loss (>2 years ago), or a combination of both recent and past losses. Differences between the groups on resilience, depression, and grief symptomatology were examined. Those who had experienced both losses (recent and past) and recent losses endorsed significantly more grief symptoms than those in the past loss group. Findings highlight how multiple losses impact grief.


Asunto(s)
Depresión/psicología , Pesar , Resiliencia Psicológica , Adulto , Femenino , Humanos , Masculino , Factores de Tiempo , Adulto Joven
11.
Crim Behav Ment Health ; 27(4): 341-353, 2017 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-27105014

RESUMEN

BACKGROUND: Previous research suggests that some types of childhood abuse and neglect are related to an increased likelihood of perpetrating criminal behaviour in adulthood. Little research, however, has examined associations between multiple different types of childhood victimisation and adult criminal behaviour. AIMS: We sought to examine the contribution of multiple and diverse childhood victimisations on adult criminal behaviour. Our central hypothesis was that, after controlling for gender, substance use and psychopathy, each type of childhood victimisation - specifically experience of property offences, physical violence, verbal abuse, sexual abuse, neglect and witnessed violence - would be positively and independently related to criminal behaviour in young adults. METHODS: We examined data from a large, nationally representative sample of 2244 young Swedish adults who reported at least one form of victimisation, using hierarchical regression analysis to also account for gender, substance use and psychopathy. RESULTS: Experiences of physical assaults, neglect and witnessing violence as a child were significantly associated with adult criminal behaviour, but not experiences of property, verbal or sexual victimizations. CONCLUSIONS: Our findings help to identify those forms of harm to children that are most likely to be associated with later criminality. Even after accounting for gender, substance misuse and psychopathology, childhood experience of violence - directly or as a witness - carries risk for adulthood criminal behaviour, so such children need targeted support and treatment. Copyright © 2016 John Wiley & Sons, Ltd.


Asunto(s)
Adultos Sobrevivientes del Maltrato a los Niños/psicología , Maltrato a los Niños/psicología , Víctimas de Crimen/psicología , Criminales/psicología , Delitos Sexuales/psicología , Violencia , Adolescente , Adulto , Acoso Escolar , Niño , Maltrato a los Niños/estadística & datos numéricos , Víctimas de Crimen/estadística & datos numéricos , Criminales/estadística & datos numéricos , Violencia Doméstica , Femenino , Humanos , Masculino , Factores de Riesgo , Conducta Sexual , Trastornos Relacionados con Sustancias , Suecia , Adulto Joven
12.
Psychooncology ; 25(7): 779-86, 2016 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-26216475

RESUMEN

OBJECTIVE: The purpose of this study was to prospectively examine adolescent and maternal posttraumatic stress symptoms (PTSS) and maternal communication from time near cancer diagnosis to 12-month follow-up to identify potential risk factors for adolescent PTSS. METHODS: Forty-one adolescents with cancer (10-17 years, 54% female) and their mothers self-reported PTSS at T1 (two months after cancer diagnosis) and T3 (1-year follow-up). At T2 (3 months after T1), mother-adolescent dyads were videotaped discussing cancer, and maternal communication was coded with macro (harsh and withdrawn) and micro (solicits and validations) systems. RESULTS: Adolescent PTSS at T1 was associated with adolescent PTSS at T3. Greater maternal PTSS at T1 predicted greater harsh maternal communication at T2. There was an indirect effect of maternal PTSS at T1 on adolescent PTSS at T3 through maternal validations at T2. CONCLUSIONS: Findings underscore the importance of maternal PTSS, maternal communication, and subsequent adolescent PTSS over the course of treatment of childhood cancer. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.


Asunto(s)
Relaciones Madre-Hijo , Madres/psicología , Neoplasias/psicología , Trastornos por Estrés Postraumático/psicología , Sobrevivientes/psicología , Adaptación Psicológica , Adolescente , Adulto , Femenino , Humanos , Estudios Longitudinales , Masculino , Neoplasias/diagnóstico , Factores de Riesgo , Trastornos por Estrés Postraumático/diagnóstico
13.
R I Med J (2013) ; 107(4): 7-9, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38536130

RESUMEN

Hemolytic uremic syndrome (HUS) often causes neurologic symptoms, but they typically occur as a later symptom of the syndrome. In addition, the Shiga toxin- producing E. coli (STEC) which causes HUS rarely causes bacteremia. We present the case of a 10-year-old male with Smith-Magenis syndrome who was admitted to the hospital due to STEC gastroenteritis, who was initially improving with supportive care, and then subsequently developed fever and had multiple seizures which were different from his typical seizure semiology. Over the subsequent 48 hours he gradually developed microangiopathic hemolytic anemia consistent with HUS. His course was further complicated by E. coli bacteremia and oliguric renal failure requiring renal replacement therapy, depressed mental status, and difficult-to-control hypertension. This case demonstrates the importance of neurologic manifestations as a harbinger of developing HUS.


Asunto(s)
Bacteriemia , Síndrome Hemolítico-Urémico , Escherichia coli Shiga-Toxigénica , Masculino , Humanos , Niño , Fiebre , Convulsiones
14.
Nat Rev Urol ; 2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38714857

RESUMEN

Rising rates of antibiotic resistance in uropathogenic bacteria compromise patient outcomes and prolong hospital stays. Consequently, new strategies are needed to prevent and control the spread of antibiotic resistance in uropathogenic bacteria. Over the past two decades, sizeable clinical efforts and research advances have changed urinary tract infection (UTI) treatment and prevention strategies to conserve antibiotic use. The emergence of antimicrobial stewardship, policies from national societies, and the development of new antimicrobials have shaped modern UTI practices. Future UTI management practices could be driven by the evolution of antimicrobial stewardship, improved and readily available diagnostics, and an improved understanding of how the microbiome affects UTI. Forthcoming UTI treatment and prevention strategies could employ novel bactericidal compounds, combinations of new and classic antimicrobials that enhance bacterial killing, medications that prevent bacterial attachment to uroepithelial cells, repurposing drugs, and vaccines to curtail the rising rates of antibiotic resistance in uropathogenic bacteria and improve outcomes in people with UTI.

15.
Cell Rep ; 43(4): 114007, 2024 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-38517889

RESUMEN

Urinary tract infections (UTIs) commonly afflict people with diabetes. To better understand the mechanisms that predispose diabetics to UTIs, we employ diabetic mouse models and altered insulin signaling to show that insulin receptor (IR) shapes UTI defenses. Our findings are validated in human biosamples. We report that diabetic mice have suppressed IR expression and are more susceptible to UTIs caused by uropathogenic Escherichia coli (UPEC). Systemic IR inhibition increases UPEC susceptibility, while IR activation reduces UTIs. Localized IR deletion in bladder urothelium promotes UTI by increasing barrier permeability and suppressing antimicrobial peptides. Mechanistically, IR deletion reduces nuclear factor κB (NF-κB)-dependent programming that co-regulates urothelial tight junction integrity and antimicrobial peptides. Exfoliated urothelial cells or urine samples from diabetic youths show suppressed expression of IR, barrier genes, and antimicrobial peptides. These observations demonstrate that urothelial insulin signaling has a role in UTI prevention and link IR to urothelial barrier maintenance and antimicrobial peptide expression.


Asunto(s)
Receptor de Insulina , Transducción de Señal , Vejiga Urinaria , Infecciones Urinarias , Urotelio , Receptor de Insulina/metabolismo , Infecciones Urinarias/microbiología , Infecciones Urinarias/metabolismo , Infecciones Urinarias/patología , Animales , Urotelio/metabolismo , Urotelio/patología , Urotelio/microbiología , Humanos , Vejiga Urinaria/microbiología , Vejiga Urinaria/patología , Vejiga Urinaria/metabolismo , Ratones , Escherichia coli Uropatógena/patogenicidad , Ratones Endogámicos C57BL , FN-kappa B/metabolismo , Femenino , Infecciones por Escherichia coli/metabolismo , Infecciones por Escherichia coli/microbiología , Insulina/metabolismo , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patología , Masculino
16.
Contemp Clin Trials ; 139: 107483, 2024 04.
Artículo en Inglés | MEDLINE | ID: mdl-38431133

RESUMEN

BACKGROUND: Medication non-adherence is common among adolescents and young adults (AYAs) with cancer and associated with poor health outcomes. AYAs with cancer endorse multiple barriers to adherence that differ across individuals, suggesting that tailoring intervention content to an AYA's specific barriers may have the potential to improve adherence. The purpose of this manuscript is to report on ORBIT-guided Phase I design efforts to create the first tailored adherence-promotion intervention for AYAs with cancer and the study protocol for the ongoing Phase II pilot feasibility trial. METHODS: Phase I design included qualitative interviews (n = 15 AYAs) to understand patient preferences for adherence-promotion care, development and refinement of a best-worst scaling exercise barriers tool (n = 5 AYAs), and development of intervention modules and a tailoring algorithm. In the ongoing Phase II pilot feasibility trial, AYAs (ages 15-24 years) with cancer currently taking oral chemotherapy or prophylactic medication will be recruited from three children's hospitals. Feasibility, acceptability, and usability will be assessed and these outcomes along with data on medication adherence will be used to inform the next phases of intervention development and testing. CONCLUSIONS: If promising, this program of research ultimately has the potential to equip clinicians with additional strategies for supporting adherence among AYAs with cancer. NCT05706610.


Asunto(s)
Neoplasias , Adolescente , Humanos , Adulto Joven , Estudios de Factibilidad , Cumplimiento de la Medicación , Neoplasias/tratamiento farmacológico , Proyectos Piloto , Proyectos de Investigación , Ensayos Clínicos Fase II como Asunto
17.
Prev Med ; 57(5): 461-5, 2013 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-23827724

RESUMEN

OBJECTIVE: Building on previous work indicating that mood instability is the hallmark of neuroticism, our aim was to examine whether changes in exercise, sleep duration and leisure predicted decreases in mood instability with time. METHODS: We used data from 3374 participants of the British Health and Lifestyle Study who answered the Eysenck Personality Inventory-Neuroticism subscale (EPI-N) and the General Health Questionnaire on two occasions 7 years apart. We predicted mood instability scores derived from the EPI-N at follow-up using self-reported changes in exercise, sleep duration and leisure hours between the two time points as independent variables. RESULTS: We confirmed the observation that mood instability decreases with age. Maintaining one's exercise at baseline level decreased mood instability (beta=-0.21) while sleeping less increased mood instability (beta=0.14). Change in leisure time was not independently related to mood instability after accounting for the two other lifestyle factors. CONCLUSION: Personality, at least with regard to mood instability, can be modified by lifestyle factors. Exercise and sleep support mood stability and could be important components of preventative mental health (as well as physical health) benefits.


Asunto(s)
Afecto , Trastornos de Ansiedad/prevención & control , Trastorno Depresivo/prevención & control , Ejercicio Físico/psicología , Privación de Sueño/prevención & control , Adulto , Factores de Edad , Trastornos de Ansiedad/psicología , Trastorno Depresivo/psicología , Extraversión Psicológica , Femenino , Estudios de Seguimiento , Conductas Relacionadas con la Salud , Encuestas Epidemiológicas , Humanos , Actividades Recreativas , Estilo de Vida , Masculino , Persona de Mediana Edad , Neuroticismo , Inventario de Personalidad , Privación de Sueño/psicología , Trastornos Somatomorfos/prevención & control , Trastornos Somatomorfos/psicología , Reino Unido
18.
Nat Rev Nephrol ; 19(10): 658-671, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37479904

RESUMEN

Urinary tract infections (UTIs) are among the most common bacterial infections seen in clinical practice. The ascent of UTI-causing pathogens to the kidneys results in pyelonephritis, which can trigger kidney injury, scarring and ultimately impair kidney function. Despite sizable efforts to understand how infections develop or are cleared in the bladder, our appreciation of the mechanisms by which infections develop, progress or are eradicated in the kidney is limited. The identification of virulence factors that are produced by uropathogenic Escherichia coli to promote pyelonephritis have begun to fill this knowledge gap, as have insights into the mechanisms by which kidney tubular epithelial cells oppose uropathogenic E. coli infection to prevent or eradicate UTIs. Emerging data also illustrate how specific cellular immune responses eradicate infection whereas other immune cell populations promote kidney injury. Insights into the mechanisms by which uropathogenic E. coli circumvent host immune defences or antibiotic therapy to cause pyelonephritis is paramount to the development of new prevention and treatment strategies to mitigate pyelonephritis and its associated complications.


Asunto(s)
Escherichia coli , Pielonefritis , Humanos , Riñón , Células Epiteliales
19.
JCO Oncol Pract ; 19(2): e228-e237, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36446046

RESUMEN

PURPOSE: Apps have the potential to aid in cancer self-management, but there is limited guidance available for selecting among currently available options. The purpose of this study is to evaluate the behavior change techniques (BCTs) and quality of publicly available cancer self-management apps. METHODS: Cancer self-management apps were identified from the Apple and Google Play stores in April 2022. Trained study team members coded the BCTs included in each app and rated its quality using the Mobile App Rating Scale (MARS). BCTs supported by previous literature were coded as cancer management BCTs. RESULTS: The 39 apps meeting inclusion criteria included an average of 5.85 BCTs (standard deviation [SD], 3.49; range, 0-15) and 3.54 cancer management BCTs (SD, 1.90; range, 0-8). The most commonly included BCTs were educational or informational strategies: provide information about behavior-health link, provide instruction, and provide information on consequences. The overall app quality ranged from 1.69 to 4.20 (M, 3.29; SD, 0.67). CONCLUSION: No cancer self-management apps were of excellent quality, and less than half included multiple cancer management BCTs beyond education. Clinical implications are discussed, and opportunities to improve the content and quality of apps to address the critical self-management needs of patients diagnosed with cancer are highlighted.


Asunto(s)
Aplicaciones Móviles , Neoplasias , Automanejo , Humanos , Automanejo/métodos , Terapia Conductista/métodos , Conductas Relacionadas con la Salud , Neoplasias/terapia
20.
J Psychosom Res ; 172: 111413, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37354749

RESUMEN

OBJECTIVE: Disrupted sleep and fatigue are common symptoms in children with cancer, but little is known about this population's sleep health behaviors and how they may impact nighttime sleep. We aimed to describe the sleep health behaviors of children with newly diagnosed cancer and to determine if they changed over the next 8 weeks. METHODS: Our sample included 169 children with cancer (86 males) who were aged 2-18 years (mean [SD] = 8.14 [4.4] y), with parent proxy report for 140 children (71 male) aged 2-12 years (mean [SD] = 6.67 [3.2] y) and self-report for 78 children (39 male) aged 8-18 years (mean [SD] = 12.0 [2.9] y). Parents and patients completed sleep hygiene questionnaires within 30 days of oncology diagnosis (T1); follow-up questionnaires were collected 8 weeks later (T2). Descriptive analyses characterized the sample by sociodemographic characteristics, cancer diagnosis, treatments received, and prescribed medications. RESULTS: Age-related differences were found in sleep health behaviors, with adolescents reporting better overall sleep health behaviors than younger children at both time points. No differences in sleep health behaviors were found at T1 related to diagnosis, treatment, or medications. Some differences in sleep health behaviors were found at T2 related to gender, diagnosis, treatment, and medications. Sleep health behaviors and sleep problems remained relatively stable over 8 weeks. Fatigue was significantly associated with more pre-bedtime worries, insomnia, and lower rates of daytime sleepiness. CONCLUSIONS: These findings offer novel descriptive characteristics of sleep health behaviors in a pediatric oncology sample and show relatively stable yet somewhat poor sleep health behaviors across 8 weeks. Better understanding of sleep health behaviors as modifiable factors will help inform targeted interventions.


Asunto(s)
Neoplasias , Trastornos del Sueño-Vigilia , Adolescente , Humanos , Niño , Masculino , Sueño , Neoplasias/complicaciones , Encuestas y Cuestionarios , Fatiga/etiología , Fatiga/complicaciones , Conductas Relacionadas con la Salud , Trastornos del Sueño-Vigilia/complicaciones
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