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BACKGROUND: Type 2 diabetes (T2D) and depression co-occur, and rates are on the rise in adolescents, disproportionately affecting teenagers in rural communities and those who identify as members of historically disadvantaged racial/ethnic groups. Addressing the promotion of health behaviors is important for prevention of these comorbid health concerns; however, disparities in their prevalence highlight that a healthy lifestyle is not equally accessible for all individuals. Thus, holistic and multi-level approaches that address structural inequities, leverage cultural and family assets, and are effectively integrated into the community are critically needed. This project is an initial phase of a broader community-academic collaboration that aims to address preventable chronic diseases and mental health in adolescents living in the rural Mountain West by tailoring an evidence-based health behavior and lifestyle intervention for these communities. METHOD: Interviewers conducted semi-structured interviews with N = 19 individuals (n = 11 adolescents, 11-17 years, n = 8 mothers) who lived in neighboring counties in the rural Mountain Western USA and had a family history of T2D. Interview schedules were developed by an interdisciplinary team, with community input, and covered topics such as food and staying active, stress, T2D risk, and community and culture. Using thematic analysis, data were reduced through coding, categorization, and development of themes. RESULTS: Data revealed three major themes: "Families Face Systemic Barriers to Health," "Family Routines Support Health," and "Connection is Crucial to Holistic Health." CONCLUSION: Findings reveal opportunities for addressing health inequities and developing effective, integrated T2D and depression prevention strategies within this specific community. They also potentially contain insights that may be applicable to others interested in adapting interventions for diverse groups.
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AIM: Sodium-glucose co-transporter-2 (SGLT2) inhibitors have revolutionized clinical medicine, but their association with urinary tract infection (UTI) risk remains debated. This study investigates the influence of dapagliflozin on UTI outcomes, focusing on kidney injury. MATERIALS AND METHODS: Female non-diabetic C57BL/6J and C3H/HeOuJ mice, along with diabetic db/db mice, were orally administered dapagliflozin (1 mg/kg or 10 mg/kg) for 7 days before transurethral uropathogenic Escherichia coli (UPEC) infection. Mice were killed either 24 h after UTI or after six additional days of dapagliflozin treatment. UPEC titers were enumerated, and kidney histopathology, injury, fibrosis and function were assessed. RESULTS: Vehicle- and dapagliflozin-treated C57BL/6J mice exhibited similar urine and bladder UPEC titers, with minimal kidney burden 24 h after UTI. In C3H/HeOuJ mice, UPEC burden was comparable in vehicle- and 1 mg/kg dapagliflozin-treated groups both 24 h and 7 days after UTI. However, C3H/HeOuJ mice receiving 10 mg/kg dapagliflozin had increased UPEC titers in the urine, bladder and kidneys at both endpoints. Kidney injury and fibrosis markers, as well as kidney function, were similar in vehicle and dapagliflozin groups. In diabetic db/db mice receiving dapagliflozin, UPEC strain UTI89 titers were reduced 7 days after UTI compared to vehicle-treated mice, but no difference in UPEC titers was observed when mice were infected with UPEC strain CFT073. Kidney injury and fibrosis markers and kidney function remained similar across treatment groups. CONCLUSIONS: Dapagliflozin does not consistently influence UTI susceptibility and shows limited impact on kidney injury or fibrosis, suggesting SGLT2 inhibitors have minimal effects on UTI-related kidney complications.
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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.
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Camundongos Knockout , Receptor de Insulina , Infecções Urinárias , Escherichia coli Uropatogênica , Animais , Humanos , Camundongos , Infecções por Escherichia coli/imunologia , Infecções por Escherichia coli/metabolismo , Infecções por Escherichia coli/microbiologia , Imunidade Inata , Rim/metabolismo , Túbulos Renais Coletores/metabolismo , Camundongos Endogâmicos C57BL , Receptor de Insulina/metabolismo , Transdução de Sinais , Infecções Urinárias/microbiologia , Infecções Urinárias/metabolismo , Infecções Urinárias/imunologia , Escherichia coli Uropatogênica/imunologiaRESUMO
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.
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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.
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Neoplasias , Adolescente , Humanos , Adulto Jovem , Estudos de Viabilidade , Adesão à Medicação , Neoplasias/tratamento farmacológico , Projetos Piloto , Projetos de Pesquisa , Ensaios Clínicos Fase II como AssuntoRESUMO
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.
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Receptor de Insulina , Transdução de Sinais , Bexiga Urinária , Infecções Urinárias , Urotélio , Receptor de Insulina/metabolismo , Infecções Urinárias/microbiologia , Infecções Urinárias/metabolismo , Infecções Urinárias/patologia , Animais , Urotélio/metabolismo , Urotélio/patologia , Urotélio/microbiologia , Humanos , Bexiga Urinária/microbiologia , Bexiga Urinária/patologia , Bexiga Urinária/metabolismo , Camundongos , Escherichia coli Uropatogênica/patogenicidade , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Feminino , Infecções por Escherichia coli/metabolismo , Infecções por Escherichia coli/microbiologia , Insulina/metabolismo , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , MasculinoRESUMO
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.
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Bacteriemia , Síndrome Hemolítico-Urêmica , Escherichia coli Shiga Toxigênica , Masculino , Humanos , Criança , Febre , ConvulsõesRESUMO
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.
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Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Humanos , Criança , Pré-Escolar , Determinantes Sociais da Saúde , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Doença Enxerto-Hospedeiro/epidemiologia , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/patologia , Avaliação de Resultados em Cuidados de SaúdeRESUMO
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.
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Escherichia coli , Pielonefrite , Humanos , Rim , Células EpiteliaisRESUMO
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.
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Neoplasias , Transtornos do Sono-Vigília , Adolescente , Humanos , Criança , Masculino , Sono , Neoplasias/complicações , Inquéritos e Questionários , Fadiga/etiologia , Fadiga/complicações , Comportamentos Relacionados com a Saúde , Transtornos do Sono-Vigília/complicaçõesRESUMO
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.
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Inibidores de Histona Desacetilases , Infecções Urinárias , Humanos , Camundongos , Animais , Inibidores de Histona Desacetilases/farmacologia , Escherichia coli/metabolismo , Reposicionamento de Medicamentos , Ribonucleases/metabolismo , Infecções Urinárias/tratamento farmacológico , Infecções Urinárias/microbiologia , AntibacterianosRESUMO
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.
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Aplicativos Móveis , Neoplasias , Autogestão , Humanos , Autogestão/métodos , Terapia Comportamental/métodos , Comportamentos Relacionados com a Saúde , Neoplasias/terapiaRESUMO
Youth-onset type 2 diabetes (T2D) is on the rise and may be associated with more adverse health outcomes than adult onset. Latinx adolescents are disproportionately at risk for T2D yet are underrepresented in prevention efforts. Extant interventions to prevent T2D in Latinx adolescents show limited effectiveness. Comprehensive understanding of Latinx adolescent/family needs is lacking, but necessary for cultural tailoring of T2D prevention. Researchers conducted focus groups with 32 Latinx adolescents (age 10-18 years) from Northern Colorado and 31 Spanish-speaking parents/caregivers, with 2.5-hr semistructured youth-specific and parent-specific discussions, respectively. No participants included in this study had T2D. Qualitative data were analyzed for emergent themes about barriers/facilitators of healthy living and T2D prevention preferences. Thematic content analysis yielded eight themes within three categories: barriers to healthy living, facilitators of healthy living, and program preferences. Barriers to healthy living included individual motivational factors/food preferences; financial cost and time demands of healthy eating/exercise; negative emotions; and external/relational factors such as parent feeding pressure and peer pressure/bullying. Facilitators of healthy living included individual motivational factors/enjoyment of healthy living and supportive family structure. Program preferences were for family-based programming with adolescent breakout sessions and for facilitation by culturally competent facilitators. T2D is recognized as a serious health concern among Latinx families. There is a need for culturally tailored prevention programming that, in order to be acceptable, should address cultural and socioeconomic considerations, provide coping skills for adolescent-specific psychosocial stressors, and utilize a family-based programming framework with adolescent breakout sessions and culturally competent facilitators.
La diabetes tipo 2 (DT2) que comienza en la juventud está en aumento y esta asociada con peores resultados en comparación con los de la edad adulta. Los adolescentes Latinx tienen un riesgo desproporcionado de DT2 sin embargo, no están representados en los esfuerzos de prevención. Las intervenciones existentes muestran una eficacia limitada. La comprensión sobre las necesidades de los adolescentes y las familias Latinx son escasas, pero son necesarias para prevenir DT2. Se realizaron grupos de enfoque con 32 adolescentes Latinx (de 10 a 18 añ3os) del Norte de Colorado y 31 padres de habla hispana, con sesiones de 2.5 horas para jóvenes y para padres. Ningún participante en este estudio tenía DT2. Se analizaron datos cualitativos que identificaron barreras/facilitadores para una vida sana y preferencias de programas para prevenir DT2. Las barreras incluyeron factores individuales; el costo y el tiempo para tener alimentación/ejercicio sano; emociones negativas; y factores externos como la presión de los padres/compañeros. Los facilitadores incluyeron factores individuales/disfrute de la salud y el apoyo familiar. Las preferencias fueron basada en la familia, con grupos de adolescentes y con facilitadores culturalmente competentes. La DT2 es un grave problema entre las familias Latinx. Se necesitan programas de prevención que consideren la cultura y factores socioeconómicos. También se deben proporcionar habilidades de afrontamiento de los estresores psicosociales para adolescentes, a través de facilitadores culturalmente competentes y utilizar programación basada en la familia, con actividades culturales para adolescentes.
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Objective Few studies have explored the impact of insecure attachment on college student mental health. The present study examined how anxious and avoidant attachment to a mother, father, and best friend were related to depression and resilience in emerging adults exposed to trauma. Participants: Participants included 372 trauma-exposed emerging adults, aged 18-24 (Mage=19.64, SD = 1.62), from a university in the Midsouth, United States. Method: Participants completed an assessment battery of self-report measures to determine how maternal, paternal, and best friend insecure attachment each uniquely contribute to the variance in depression and resilience. Results: Hierarchical linear regression analyses revealed that anxious and avoidant attachment to a best friend were associated with lower resilience, but only anxious attachment to a best friend was associated with more depressive symptoms. Discussion: Findings highlight the importance of cultivating healthy relationships in a university setting to foster secure peer attachments for emerging adults exposed to adversity.
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Depressão , Apego ao Objeto , Adulto , Ansiedade/psicologia , Depressão/diagnóstico , Humanos , Estudantes , UniversidadesRESUMO
Intimate partner violence (IPV) is experienced by one in four women in the United States, and a wealth of quantitative research has underscored its detrimental effects on women's mental health and parenting practices. Little research, however, has considered ways in which women exposed to IPV retain and foster parenting strengths and ways in which motherhood serves as a source of resilience for these women. The objective of the current study was to conduct a thematic analysis of IPV-exposed women's parenting strengths and concerns as reported through focus groups conducted with IPV-exposed women (n = 22) and service providers (n = 31) in two urban areas in the Mid-West and Mid-South. Results of the thematic analysis indicated the emergence of three core themes: resilience and challenges of parenting in the context of IPV, leaving the violent partner, and intergenerational processes. Overall, service providers recognized far fewer strengths in parenting on all dimensions than did women, suggesting that service providers may be conceptualizing parenting in the context of IPV from a deficit model that underestimates the resilience demonstrated by these women. This has important consequences for the extent to which women may feel stigmatized or blamed when receiving resources and services critical to their families. Future research on parenting among women experiencing IPV would be enhanced by capturing the dynamic interplay between women's parenting strengths and challenges, and the ways in which these capacities are affected by resource access within and across social ecological contexts.
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Violência por Parceiro Íntimo , Poder Familiar , Criança , Medo , Feminino , Humanos , Violência por Parceiro Íntimo/psicologia , Masculino , Saúde Mental , Poder Familiar/psicologia , Saúde da MulherRESUMO
BACKGROUND: For ischaemic stroke, outcome severity is heavily time dependent. Systems of care need to be in place to ensure that patients with stroke are treated quickly and appropriately across entire health regions. Prior to this study, the province of Saskatchewan, Canada did not have a provincial stroke strategy in place. METHODS: A quality improvement project was undertaken to create and evaluate a provincial stroke strategy. The Saskatchewan Acute Stroke Pathway was created using a multidisciplinary team of experts, piloted at five stroke centres and then implemented provincially. The number of stroke alerts, door-to-imaging, door-to-needle, door-to-groin puncture times and treatment rates were collected at all centres. Improvements over time were analysed using run charts and individuals control charts. RESULTS: The number of stroke alerts province-wide trended upwards in the last 6 months of the study. There were no clear trends or shifts in the proportion of stroke alerts treated with alteplase or endovascular therapy. Across the province, the weighted mean door-to-imaging time decreased from 21 to 15 min, the weighted mean door-to-needle time decreased from 62 to 47 min and the mean door-to-groin puncture time decreased from 83 to 70 min. There was high variability in the degree of improvement from centre to centre. CONCLUSIONS: The implementation of a province wide acute stroke pathway has led to improvement in stroke care on a provincial basis. Further work addressing intercentre variability is ongoing.
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Isquemia Encefálica , Acidente Vascular Cerebral , Isquemia Encefálica/tratamento farmacológico , Humanos , Saskatchewan/epidemiologia , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/terapia , Terapia Trombolítica , Tempo para o TratamentoRESUMO
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.
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Regulação Enzimológica da Expressão Gênica/fisiologia , Rim/enzimologia , Ribonucleases/metabolismo , Bexiga Urinária/enzimologia , Adolescente , Peptídeos Catiônicos Antimicrobianos , Criança , Células Endoteliais/enzimologia , Células Endoteliais/metabolismo , Feminino , Inativação Gênica , História Antiga , História Medieval , Humanos , Rim/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Ribonucleases/genética , Ribonucleases/urina , Bexiga Urinária/metabolismo , Escherichia coli Uropatogênica , Urotélio/citologiaRESUMO
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.
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Violência por Parceiro Íntimo , Transtornos Relacionados ao Uso de Substâncias , Adulto , Depressão/epidemiologia , Feminino , Humanos , Transtornos Relacionados ao Uso de Substâncias/epidemiologiaRESUMO
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.
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Fadiga/complicações , Fadiga/terapia , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Fototerapia , Adolescente , Criança , Estudos de Viabilidade , Feminino , Humanos , Masculino , Adulto JovemRESUMO
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.