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La tuberculosis es una enfermedad infecciosa respiratoria que afecta a un tercio de la población mundial y es una amenaza significativa para la salud global. La detección de la tuberculosis de manera temprana es crucial para un tratamiento eficaz y prevenir su propagación. Una solución para mejorar el diagnóstico y abordar la resistencia a los medicamentos antituberculosos es el uso de pruebas moleculares de alto rendimiento para la identificación del Mycobacterium tuberculosis y su susceptibilidad. Este estudio de revisión narrativa busca describir las generalidades, la eficacia, la sensibilidad, las ventajas y las limitaciones de las principales pruebas moleculares; Truenat® MTB, MTB plus y MTB-RIF, Abbott RealTime MTB y MTB RIF/INH en el sistema m2000sp y m2000rt y FluoroType MTBDR, además, de compararlas con GeneXpert MTB/RIF o Xpert Ultra, utilizadas para la detección del patógeno resistente a medicamentos tuberculosos. Estas pruebas utilizan diversas técnicas para la detección del ADN del Mycobacterium tuberculosis y la cuantificación de la carga bacteriana con alta sensibilidad y especificidad, resultados rápidos, reducción de los errores humanos, así como la detección temprana de cepas drogo-resistentes. A pesar de que requieren infraestructura especializada y competencias profesionales para su implementación, representan avances significativos con el potencial de mejorar la atención sanitaria y la gestión de la tuberculosis. Estas pruebas moleculares, comparadas con el GeneXpert, son una alternativa viable, aunque esta última tecnología sigue siendo la preferida en áreas con recursos limitados
Tuberculosis is a respiratory infectious disease that affects one third of the world's population and is a significant threat to global health. Detecting tuberculosis early is crucial for effective treatment and preventing its spread. One solution to improve diagnosis and address antituberculosis drug resistance is the use of high-throughput molecular tests for the identification of Mycobacterium tuberculosis and its susceptibility. This narrative review study seeks to describe the generalities, efficacy, sensitivity, advantages and limitations of the main molecular tests: Truenat® MTB, MTB plus and MTB-RIF, Abbott RealTime MTB and MTB RIF/INH on the m2000sp and m2000rt system and FluoroType MTBDR, and to compare them with GeneXpert MTB/RIF or Xpert Ultra, used for the detection of the tuberculosis drug-resistant pathogen. These tests use various techniques for the detection of Mycobacterium tuberculosis DNA and quantification of bacterial load with high sensitivity and specificity, rapid results, reduction of human error, as well as early detection of drug-resistant strains
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El SalvadorRESUMO
Large-scale studies and burdened clinical settings require precise, efficient measures that assess multiple domains of psychopathology. Computerized adaptive tests (CATs) can reduce administration time without compromising data quality. We examined feasibility and validity of an adaptive psychopathology measure, GOASSESS, in a clinical community-based sample (N = 315; ages 18-35) comprising three groups: healthy controls, psychosis, mood/anxiety disorders. Assessment duration was compared between the Full and CAT GOASSESS. External validity was tested by comparing how the CAT and Full versions related to demographic variables, study group, and socioeconomic status. The relationships between scale scores and criteria were statistically compared within a mixed-model framework to account for dependency between relationships. Convergent validity was assessed by comparing scores of the CAT and the Full GOASSESS using Pearson correlations. The CAT GOASSESS reduced interview duration by more than 90 % across study groups and preserved relationships to external criteria and demographic variables as the Full GOASSESS. All CAT GOASSESS scales could replace those of the Full instrument. Overall, the CAT GOASSESS showed acceptable psychometric properties and demonstrated feasibility by markedly reducing assessment time compared to the Full GOASSESS. The adaptive version could be used in large-scale studies or clinical settings for intake screening.
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Transtornos de Ansiedade , Transtornos Psicóticos , Humanos , Transtornos de Ansiedade/psicologia , Psicopatologia , Transtornos do Humor/diagnóstico , Ansiedade , Psicometria , Reprodutibilidade dos TestesRESUMO
This study was designed to test whether the single appended phosphonate group in GdDOTA-1AmP is sufficient for catalyzing the exchange of proton from the single inner-sphere water-exchanging molecule. Unlike the other phosphonate derivatives in this series, GdDOTA-1AmP showed a surprisingly smooth increase in r1 relaxivity from 3.0 to 6.3 mM-1 s-1 at 20 MHz as the pH was lowered from 9 to 2.5. In comparison to the bis-, tris-, and tetrakis-phosphonate analogues, which all show a biphasic dependence of r1 with changes in pH, the unique r1 versus pH characteristics of GdDOTA-1AmP are shown to closely parallel deprotonation of the single appended phosphonate group. Although the tissue biodistribution and clearance rates of GdDOTA-1AmP are more favorable than the other more highly charged phosphonate derivatives, the pH dependency of r1 is substantially reduced at magnetic fields typically used for small animal imaging (7 and 9.4T), so the attractiveness of this new molecule for quantitative imaging of tissue pH is diminished. However, this study provides some new insights into the feasibility of designing pH-responsive MRI contrast agents based upon fundamental acid-base prototropic mechanisms.
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Social dominance encompasses winning dyadic contests and gaining priority access to resources and reproduction. Dominance is influenced by environmental factors, particularly during early postnatal life and adolescence. A disinhibitory medial prefrontal cortex (mPFC) microcircuit has been implicated in the expression of dominance in the "tube test" social competition paradigm in mice, but the neuroplasticity underlying dominance is not known. We previously reported that male pups raised by physically active (wheel-running, as opposed to sedentary) dams exhibit tube test dominance and increased reproductive fitness, and here we show that social isolation from weaning also increases dominance. By using single cell transcriptomics, we tested if increased dominance in these models is associated with a specific transcriptional profile in one or more cell-types in the mPFC. The preweaning maternal effect, but not postweaning social isolation, caused gene expression changes in pyramidal neurons. However, both the effect of maternal exercise and social isolation induced the coordinated downregulation of synaptic channel, receptor, and adhesion genes in parvalbumin positive (PV) interneurons, suggesting that development of dominance is accompanied by impaired PV interneuron-mediated inhibition of pyramidal cells. This study may help understand environmentally induced transcriptional plasticity in the PFC and its relationship to tube test dominance.
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Interneurônios , Córtex Pré-Frontal , Camundongos , Animais , Masculino , Córtex Pré-Frontal/fisiologia , Interneurônios/metabolismo , Predomínio Social , Meio Social , Perfilação da Expressão Gênica , Parvalbuminas/metabolismoRESUMO
BACKGROUND: The Penn Computerized Neurocognitive Battery is an efficient tool for assessing brain-behavior domains, and its efficiency was augmented via computerized adaptive testing (CAT). This battery requires validation in a separate sample to establish psychometric properties. METHODS: In a mixed community/clinical sample of N = 307 18-to-35-year-olds, we tested the relationships of the CAT tests with the full-form tests. We compared discriminability among recruitment groups (psychosis, mood, control) and examined how their scores relate to demographics. CAT-Full relationships were evaluated based on a minimum inter-test correlation of 0.70 or an inter-test correlation within at least 0.10 of the full-form correlation with a previous administration of the full battery. Differences in criterion relationships were tested via mixed models. RESULTS: Most tests (15/17) met the minimum criteria for replacing the full-form with the updated CAT version (mean r = 0.67; range = 0.53-0.80) when compared to relationships of the full-forms with previous administrations of the full-forms (mean r = 0.68; range = 0.50-0.85). Most (16/17) CAT-based relationships with diagnostics and other validity criteria were indistinguishable (interaction p > 0.05) from their full-form counterparts. CONCLUSIONS: The updated CNB shows psychometric properties acceptable for research. The full-forms of some tests should be retained due to insufficient time savings to justify the loss in precision.
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Teste Adaptativo Computadorizado , Transtornos Mentais , Humanos , Encéfalo , Psicometria , Cognição , Reprodutibilidade dos TestesRESUMO
Objective: Supporting patient-clinician communication is key to implementing tailored, risk-based screening for older adults. Objectives of this multiphase mixed methods study were to identify factors that primary care clinicians consider influential when making screening mammography recommendations for women ≥ 75 years, develop a patient decision aid that incorporates these factors, and gather feasibility and acceptability from the patients' perspective. Methods: Clinicians from a Mid-Atlantic practice network completed online surveys. Women in the same network completed surveys before and after receiving a tailored booklet that included information about the benefits and harms of screening for women ≥ 75 years, a breast cancer risk-estimate, and a question prompt list to support patient-clinician communication. Results: Clinicians (N = 21) were primarily women [57.1%] and practiced family medicine [81.0%]. They cited patients' age ≥ 75 years [95.4%], comorbidity [86.4%], functional status [77.3%], cancer family history [63.6%], U.S. Preventive Services Task Force guidelines [81.8%] and new research [77.3%] as factors influencing their recommendations. Fourteen women completed baseline surveys and received personalized decision aids (Mean age = 79.1 years). Eleven completed the post-intervention survey. All were satisfied with the booklet length, 81.8% found the booklet easy to understand and 72.7% helpful in decision-making Perceived lifetime breast cancer risk decreased significantly from pre- to post-intervention (p = 0.02). Conclusions: Results suggest this decision aid, which incorporates key decisional factors from the clinician's perspective, is feasible and acceptable to patients. Innovation: A tailored decision aid booklet is innovative as it provides information on personalized risk and potential benefits and harms to older women considering screening.
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BACKGROUND: Traditional paper-and-pencil neurocognitive evaluations and semi-structured mental health interviews can take hours to administer and score. Computerized assessment has decreased that burden substantially, and contemporary psychometric tools such as item response theory and computerized adaptive testing (CAT) allow even further abbreviation. NEW METHOD: The goal of this paper was to describe the application of CAT and related methods to the Penn Computerized Neurocognitive Battery (CNB) and a well-validated clinical assessment in order to increase efficiency in assessment and relevant domain coverage. To calibrate item banks for CAT, N = 5053 participants (63% female; mean age 45 years, range 18-80) were collected from across the United States via crowdsourcing, providing item parameters that were then linked to larger item banks and used in individual test construction. Tests not amenable to CAT were abbreviated using complementary short-form methods. RESULTS: The final "CAT-CCNB" battery comprised 21 cognitive tests (compared to 14 in the original) and five adaptive clinical scales (compared to 16 in the original). COMPARISON WITH EXISTING METHODS: This new battery, derived with contemporary psychometric approaches, provides further improvements over existing assessments that use collections of fixed-length tests developed for stand-alone administration. The CAT-CCNB provides an improved version of the CNB that shows promise as a maximally efficient tool for neuropsychiatric assessment. CONCLUSIONS: We anticipate CAT-CCNB will help satisfy the clear need for broad yet efficient measurement of cognitive and clinical domains, facilitating implementation of large-scale, "big science" approaches to data collection, and potential widespread clinical implementation.
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Transtornos Mentais , Feminino , Masculino , Humanos , Psicometria , Testes Neuropsicológicos , Reprodutibilidade dos TestesRESUMO
BACKGROUND: Recent studies have investigated dogs with presumed diet-associated dilated cardiomyopathy (daDCM), but prospective studies of multiple breeds are needed. HYPOTHESIS/OBJECTIVES: To evaluate baseline features and serial changes in echocardiography and cardiac biomarkers in dogs with DCM eating nontraditional diets (NTDs) or traditional diets (TDs), and in dogs with subclinical cardiac abnormalities (SCA) eating NTD. ANIMALS: Sixty dogs with DCM (NTD, n = 51; TDs, n = 9) and 16 dogs with SCA eating NTDs. METHODS: Echocardiography, electrocardiography, and measurement of taurine, cardiac troponin I, and N-terminal pro-B-type natriuretic peptide were performed in dogs with DCM or SCA. Diets were changed for all dogs, taurine was supplemented in most, and echocardiography and cardiac biomarkers were reassessed (3, 6, and 9 months). RESULTS: At enrollment, there were few differences between dogs with DCM eating NTDs or TDs; none had low plasma or whole blood taurine concentrations. Improvement in fractional shortening over time was significantly associated with previous consumption of a NTD, even after adjustment for other variables (P = .005). Median survival time for dogs with DCM was 611 days (range, 2-940 days) for the NTD group and 161 days (range, 12-669 days) for the TD group (P = .21). Sudden death was the most common cause of death in both diet groups. Dogs with SCA also had significant echocardiographic improvements over time. CONCLUSIONS AND CLINICAL IMPORTANCE: Dogs with DCM or SCA previously eating NTDs had small, yet significant improvements in echocardiographic parameters after diet changes.
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Cardiomiopatia Dilatada , Doenças do Cão , Animais , Cardiomiopatia Dilatada/veterinária , Dieta/veterinária , Cães , Ecocardiografia/veterinária , Estudos ProspectivosRESUMO
PURPOSE: Most studies of adherence to treatment for breast cancer have focused on early-stage patients. Findings from these studies may not generalize to patients with metastatic breast cancer (MBC). The objective of this study was to identify barriers and facilitators of adherence to cyclin-dependent kinase 4/6 (CDK4/6) inhibitors among patients with MBC, guided by the social ecologic model (SEM). METHODS: Patients with MBC (N = 25), their caregivers (N = 9), and oncology providers (N = 13) completed semi-structured qualitative interviews exploring their experiences with CDK4/6 inhibitors. Interviews were audio-recorded, transcribed verbatim, and analyzed by three raters using a combined deductive and inductive approach. RESULTS: Qualitative analysis identified barriers and facilitators of adherence at each SEM level. Intrapersonal and interpersonal factors were most frequently discussed. Intrapersonal factors included knowledge/beliefs about CDK4/6 inhibitors, side effects, and establishing a routine. Interpersonal factors included effective communication with/coordination by the care team, support from family and friends, and information from other patients with MBC. Although less frequently discussed, policy factors (i.e., cost of CDK4/6 inhibitors) were of great concern to patients, caregivers, and providers. CONCLUSION: Barriers to adherence to CDK4/6 inhibitors exist at multiple levels. Our results underscore the potential value of a multilevel intervention (e.g., patient education, evidence-based strategies for symptom management, tips for open and assertive communication with providers, information about financial resources/support available, and so on) to support adherence in this population.
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Neoplasias da Mama , Quinase 6 Dependente de Ciclina/metabolismo , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Cuidadores , Quinase 4 Dependente de Ciclina , Feminino , Humanos , Pesquisa QualitativaRESUMO
BACKGROUND: The epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-susceptible S. aureus (MSSA) has changed in recent years. The present article is intended to establish differences between clinical, laboratory and imaging findings and outcomes of MSSA and MRSA infections, as well as among subgroups of infection such as skin and soft tissue infection, osteoarticular, bacteremia or pneumonia in a pediatric population from Bogota, Colombia. METHODS: Retrospective cohort study using clinical records of patients under 18 years of age treated at the participating centers in Bogota, Colombia, between 2014 and 2018. The first positive S. aureus culture was studied. MSSA and MRSA were compared. The χ2 test, Fisher exact test, and Kruskal-Wallis test were calculated, and the statistical significance was presented using the difference and its 95% CI. RESULTS: Five hundred fifty-one patients were included; 211 (38%) corresponded to MRSA and 340 (62%) to MSSA for a total of 703 cultures. A significantly higher probability of having an MSSA infection than MRSA was found in patients with previous heart disease (3.3% vs. 0.5%), neurologic disease (5.9% vs. 2.5%), recent major surgeries (11% vs. 5%) or who has an implanted device (11% vs. 4%). In contrast, in severe MRSA infections (bacteremia, osteoarticular infections and pneumonia), a higher rate of complications was seen (admission to the pediatric intensive care unit, mechanical ventilation and vasoactive support), and in osteoarticular MRSA, more than 1 surgery per case was seen (89% vs. 61%). Laboratory results and mortality were similar. CONCLUSIONS: MRSA was associated with a more severe course in bacteremia, osteoarticular infections and pneumonia. Some classical risk factors associated with MRSA infections were found to be related to MSSA. In general, with the exception of skin and soft tissue infection, there was an increased risk of pediatric intensive care unit admission and mechanical and inotropic support with MRSA in a pediatric population.
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Staphylococcus aureus Resistente à Meticilina/patogenicidade , Infecções Estafilocócicas/epidemiologia , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/patogenicidade , Adolescente , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Criança , Pré-Escolar , Estudos de Coortes , Colômbia/epidemiologia , Feminino , Hospitalização , Humanos , Lactente , Masculino , Meticilina/farmacologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Estudos Retrospectivos , Fatores de Risco , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus/efeitos dos fármacosRESUMO
PURPOSE: Social support is associated with breast cancer survivors' health-related quality of life (HRQoL). More nuanced information is needed regarding aspects of social support associated with different HRQoL domains among diverse populations. We assessed the association between emotional/informational and tangible support and five HRQoL domains and evaluated race as an effect modifier. METHODS: African American and White women (n = 545) diagnosed with hormone-receptor-positive breast cancer completed a survey that assessed sociodemographic, clinical, and psychosocial factors. We assessed bivariate relationships between emotional/informational and tangible support along with overall HRQoL and each HRQoL domain.We tested interactions between race and emotional/informational and tangible social support using linear regression. RESULTS: The sample included African American (29%) and White (71%) breast cancer survivors. Emotional/informational social support had a statistically significant positive association with emotional well-being (ß = .08, p = 0.005), social well-being (ß = 0.36, p < 0.001), functional well-being (ß = .22, p < .001), breast cancer concerns (ß = .16, p = 0.002), and overall HRQoL (ß = .83, p < .001). Similarly, tangible social support had a statistically significant positive association with emotional well-being (ß = .14, p = 0.004), social well-being (ß = .51, p < .001), functional well-being (ß = .39, p < .001), and overall HRQoL (ß = 1.27, p < .001). The interactions between race and social support were not statistically significant (p > 0.05). CONCLUSIONS: Results underscore the importance of the different social support types among breast cancer survivors, regardless of survivors' race. IMPLICATIONS FOR CANCER SURVIVORS: Population-based interventions can be standardized and disseminated to provide guidance on how to increase emotional/information and tangible support for all breast cancer survivors by caregivers, health providers, and communities.
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Neoplasias da Mama , Sobreviventes de Câncer , Feminino , Humanos , Sobreviventes de Câncer/psicologia , Negro ou Afro-Americano , Qualidade de Vida/psicologia , Neoplasias da Mama/psicologia , Sobreviventes/psicologia , Apoio SocialRESUMO
Cancer health disparities remain a significant problem in the USA, compounded by lack of access to care, language barriers and systemic biases in health care. These disparities are particularly evident in areas such as genetics/genomics. For example, Latinas at high risk for hereditary breast and ovarian cancer (HBOC) have extremely low rates of genetic counseling/testing. Long-standing barriers and inequities in access to services such as genetic counseling and testing require innovative solutions. One solution can involve training community outreach and education professionals (CORE-Ps) to bridge the gap between underserved communities and genetic specialists. We sought to develop and pilot test a training program for English-Spanish bilingual CORE-Ps to reduce disparities in access to and uptake of genetic services among Latino populations. Guided by Adult Learning Theory and with input from multiple stakeholders, we developed ÁRBOLES Familiares (Family Trees), an in-person and online training program for bilingual CORE-Ps to facilitate identification, referral, and navigation of Latinas to genetic counseling/testing. We conducted a pilot test of 24 CORE-Ps recruited from across the United States and assessed knowledge, genetic literacy, and self-efficacy at baseline and follow-up. At follow-up, participants in the pilot with complete baseline and follow-up data (N = 15) demonstrated significant improvements in HBOC knowledge, genetic literacy, self-efficacy and reports of fewer barriers to identify/navigate Latinas (ps < .05). Qualitative assessment identified ways to improve the training curriculum. Pilot results suggest ÁRBOLES is a promising approach for training CORE-Ps to identify and refer high-risk Latinas to genetic services. Next steps involve further refinement of ÁRBOLES, development of an online toolkit, and adaptation for virtual delivery.
Latinas at high risk for hereditary breast and ovarian cancer (HBOC) have low rates of genetic counseling and testing. Latinas may not have ready access to services like genetic counseling and testing, which need special solutions. One solution can involve training community health workers to bridge the gap between Latinas and genetic specialists. We developed an online and in person training program (ÁRBOLES Familiares or Family Trees) for English-Spanish bilingual community health workers that teaches them how to help Latinas get access to genetic services. We tested this program with a small group of community health workers. After the program, their HBOC knowledge, genetic literacy, and confidence to help Latinas get access to genetic services had improved. Trainees also made suggestions to improve the program, which will be used to help future trainees expand their knowledge and skills to work with Latinas at risk of HBOC.
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Neoplasias da Mama , Neoplasias Ovarianas , Adulto , Neoplasias da Mama/genética , Neoplasias da Mama/psicologia , Feminino , Aconselhamento Genético/psicologia , Testes Genéticos , Hispânico ou Latino , Humanos , Neoplasias Ovarianas/genéticaRESUMO
OBJECTIVE: Women with early-stage, ER + breast cancer are recommend to receive genomic profiling tests, such as the 21-gene Recurrence Score (RS) test, to guide treatment decisions. We examined test- and treatment-related information discussed and the associations between RS categories and aspects of communication during patient-oncologist clinical encounters. METHODS: As part of a larger trial, clinical encounters (N = 46) were audiorecorded and coded for 1) RS- and treatment-related information, 2) shared decision making, 3) patient active participation, and 4) oncologist patient-centered communication. We examined differences by RS category using mixed models, adjusting for nesting within oncologist. RESULTS: Patients with a high RS were more likely to receive a chemotherapy recommendation (p < .01), hear about the risks/side effects of chemotherapy (p < .01), and offer their preferences (p = .02) than those with intermediate or low RS. Elements of shared decision making increased with RS. Oncologist patient-centered communication (M = 4.09/5, SD = .25) and patient active participation (M = 3.5/4, SD = 1.0) were high across RS. CONCLUSION: Findings suggest that disease severity, rather than clinical uncertainty, impact treatment recommendations and shared decision making. PRACTICE IMPLICATIONS: Oncologists adjust test- and treatment-related information and shared decision making by disease severity. This information provides a framework to inform decision making in complex cancer and genomics settings.
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Neoplasias da Mama , Oncologistas , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Tomada de Decisão Clínica , Comunicação , Tomada de Decisões , Feminino , Genômica , Humanos , Recidiva Local de Neoplasia/genética , IncertezaRESUMO
Regular physical activity improves physical and mental health. Here we found that the effect of physical activity extends to the next generation. Voluntary wheel running of dams, from postpartum day 2 to weaning, increased the social dominance and reproductive success, but not the physical/metabolic health, of their otherwise sedentary offspring. The individual's own physical activity did not improve dominance status. Maternal exercise did not disrupt maternal care or the maternal and offspring microbiota. Rather, the development of dominance behavior in the offspring of running mothers could be explained by the reduction of LIF, CXCL1, and CXCL2 cytokines in breast milk. These data reveal a cytokine-mediated lactocrine pathway that responds to the mother's postpartum physical activity and programs offspring social dominance. As dominance behaviors are highly relevant to the individual's survival and reproduction, lactocrine programming could be an evolutionary mechanism by which a mother promotes the social rank of her offspring.
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PURPOSE: The 21-gene recurrence score (RS) assay is used to guide breast cancer treatment decisions but can be poorly understood by patients. We examined the effects of a question prompt list (QPL) on knowledge, distress, and decisional conflict related to genomic testing and treatment in early-stage breast cancer. METHODS: We describe the feasibility and acceptability of the QPL and the impact of the QPL on knowledge, distress, and decisional conflict before and after the receipt of the QPL (MEND 2, N = 65). We also compared distress and decisional conflict between women who received the QPL (MEND 2, N = 65) and a comparable group of women who did not receive the QPL who participated in an earlier observational study within the same clinics (MEND 1, N = 136). RESULTS: MEND 2 participants indicated high acceptability and feasibility using the QPL. Knowledge increased post-QPL (P < .01) but did not decrease distress. Decisional conflict was lower among women in MEND 2 compared with those in MEND 1 (P < .01), with no statistically significant differences in distress. CONCLUSION: The findings suggest that the QPL is feasible, acceptable, can improve knowledge and decrease decisional conflict in the large group of women deciding treatment while integrating RS test results.
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Neoplasias da Mama/diagnóstico , Comunicação , Conhecimentos, Atitudes e Prática em Saúde , Relações Médico-Paciente , Angústia Psicológica , Neoplasias da Mama/genética , Neoplasias da Mama/psicologia , Tomada de Decisões , Estudos de Viabilidade , Feminino , Testes Genéticos , Humanos , Recidiva Local de Neoplasia/genéticaRESUMO
BACKGROUND: Long-term use of doxorubicin (DOX) is limited by cumulative dose-dependent cardiotoxicity. OBJECTIVES: Identify plasma extracellular vesicle (EV)-associated microRNAs (miRNAs) as a biomarker for cardiotoxicity in dogs by correlating changes with cardiac troponin I (cTnI) concentrations and, echocardiographic and histologic findings. ANIMALS: Prospective study of 9 client-owned dogs diagnosed with sarcoma and receiving DOX single-agent chemotherapy (total of 5 DOX treatments). Dogs with clinically relevant metastatic disease, preexisting heart disease, or breeds predisposed to cardiomyopathy were excluded. METHODS: Serum concentration of cTnI was monitored before each treatment and 1 month after the treatment completion. Echocardiography was performed before treatments 1, 3, 5, and 1 month after completion. The EV-miRNA was isolated and sequenced before treatments 1 and 3, and 1 month after completion. RESULTS: Linear mixed model analysis for repeated measurements was used to evaluate the effect of DOX. The miR-107 (P = .03) and miR-146a (P = .02) were significantly downregulated whereas miR-502 (P = .02) was upregulated. Changes in miR-502 were significant before administration of the third chemotherapeutic dose. When stratifying miRNA expression for change in left ventricular ejection fraction, upregulation of miR-181d was noted (P = .01). Serum concentration of cTnI changed significantly but only 1 month after treatment completion, and concentrations correlated with left ventricular ejection fraction and left ventricular internal dimension in diastole. CONCLUSION AND CLINICAL SIGNIFICANCE: Downregulation of miR-502 was detected before significant changes in cTnI concentrations or echocardiographic parameters. Further validation using a larger sample size will be required.
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Biomarcadores/sangue , Cardiotoxicidade/veterinária , Doenças do Cão/diagnóstico , Doxorrubicina/efeitos adversos , MicroRNAs/sangue , Animais , Cardiotoxicidade/sangue , Cardiotoxicidade/diagnóstico , Doenças do Cão/sangue , Cães , Ecocardiografia/veterinária , Vesículas Extracelulares/efeitos dos fármacos , Feminino , Masculino , Neoplasias/tratamento farmacológico , Neoplasias/veterinária , Estudos Prospectivos , Sarcoma/tratamento farmacológico , Sarcoma/veterinária , Troponina I/sangue , Função Ventricular Esquerda/efeitos dos fármacosRESUMO
The prefrontal cortex (PFC) comprises distinct regions and networks that vary in their trajectories across development. Further understanding these diverging trajectories may elucidate the neural mechanisms by which distinct PFC regions contribute to cognitive maturity. In particular, it remains unclear whether PFC regions of distinct network affiliations differ in topology and their relationship to cognition. We examined 615 individuals (8-21 years) to characterize age-related effects in participation coefficient of 28 PFC regions of distinct networks, evaluating connectivity profiles of each region to understand patterns influencing topological maturity. Findings revealed that PFC regions of attention, frontoparietal, and default mode networks (DMN) displayed varying rates of decline in participation coefficient with age, characterized by stronger connectivity with each PFC's respective network; suggesting that PFC regions largely aid network segregation. Conversely, PFC regions of the cinguloopercular/salience network increased in participation coefficient with age, marked by stronger between-network connections, suggesting that some PFC regions feature a distinctive ability to facilitate network integration. PFC topology of the DMN, in particular, predicted improvements in global cognition, including motor speed and higher order abilities. Together, these findings elucidate systematic differences in topology across PFC regions of different network affiliation, representing important neural signatures of typical brain development.
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Atenção/fisiologia , Mapeamento Encefálico/métodos , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/fisiologia , Córtex Pré-Frontal/diagnóstico por imagem , Córtex Pré-Frontal/fisiologia , Adolescente , Criança , Estudos de Coortes , Feminino , Seguimentos , Humanos , Masculino , Adulto JovemRESUMO
Disparities in genetic cancer risk assessment (GCRA) uptake persist between Latinas and Non-Hispanic Whites. This study utilized a mental model approach to interview 20 Latinas (10 affected, 10 unaffected) at increased risk for hereditary breast and ovarian cancer (HBOC). Participants were asked about their knowledge and perceptions of GCRA, HBOC, risk, benefits, motivators, barriers, challenges, and experiences with GCRA. Using the Consensual Qualitative Analysis Framework, two authors independently coded the interviews and applied the final codes upon consensus. Additionally, interviews were coded to identify whether participants spontaneously brought up certain topics without a prompt. Findings identified multiple barriers and facilitators to GCRA uptake in this population, including patient level psychosocial/cultural factors (e.g., limited knowledge, worry about relatives' risk) and healthcare system factors (e.g., receiving no referrals). There were notable differences in awareness and knowledge between affected and unaffected women (e.g., genetic testing awareness), as well as knowledge gaps that were evident in both groups (e.g., age of diagnosis as a risk factor). To reduce disparities in GCRA uptake, interventions should address identified facilitators and barriers. Differences in knowledge and awareness between affected and unaffected women support the development of targeted interventions that address specific knowledge gaps. This study was registered in ClinicalTrials.gov (NCT03075540) by Alejandra Hurtado de Mendoza, Ph.D.
Assuntos
Neoplasias da Mama/genética , Predisposição Genética para Doença , Testes Genéticos , Hispânico ou Latino/psicologia , Neoplasias Ovarianas/genética , Adulto , Estudos de Casos e Controles , Feminino , Genes BRCA1 , Genes BRCA2 , Humanos , Conhecimento , Pessoa de Meia-Idade , Motivação , Medição de RiscoRESUMO
OBJECTIVE: We aimed to determine the causes and predictors for 30-day re-admission following a hospitalization for diabetic ketoacidosis (DKA) in the United States. METHODS: This retrospective cohort study analyzed data from the National Re-admission Database. We included adult patients with a primary discharge diagnosis of DKA, from 2010 to 2014. Our primary objective was to determine the frequency and causes for 30-day re-admission after an index hospitalization for DKA. We also performed multivariate regression analyses using covariates from the index admission to identify predictors for 30-day re-admissions. RESULTS: Among 479,590 admissions for DKA, 58,961 (12.3%) were re-admitted within 30 days. Recurrent DKA represented 40.8% of all-cause re-admissions. In multivariate analysis, end-stage renal disease (odds ratio [OR], 2.13; 95% confidence interval [CI], 2.00 to 2.27; P<.001), Charlson Comorbidity Index ≥3 (OR, 2.49; 95% CI, 2.42 to 2.58; P<.001), discharge against medical advice (OR, 1.97; 95% CI, 1.86 to 2.09; P<.001), and drug use (OR, 1.78; 95% CI, 1.71 to 1.86; P<.001) were the most significant predictors for 30-day re-admission. About 50% of patients were re-admitted within 2 weeks after discharge. CONCLUSION: In the U.S., about one in every eight patients with DKA is re-admitted within 30 days, with 40.8% representing recurrent DKA episodes. Patients with end-stage renal disease, high comorbidity burden, drug use, and/or leaving against medical advice represented the highest risk group for re-admissions. Future studies with interventions focusing on high-risk population are critically needed. ABBREVIATIONS: AKI = acute kidney injury; BMI = body mass index; CCI = Charlson Comorbidity Index; CI = confidence interval; DKA = diabetic ketoacidosis; DM1 = type 1 diabetes mellitus; DM2 = type 2 diabetes mellitus; ESRD = end-stage renal disease; ICD-9-CM = International Classification of Diseases, Ninth Edition, Clinical Modification; IQR = interquartile range; LOS = length of stay; NRD = National Re-admission Database; OR = odds ratio.
Assuntos
Cetoacidose Diabética , Adulto , Diabetes Mellitus Tipo 2 , Hospitalização , Humanos , Alta do Paciente , Estudos Retrospectivos , Estados UnidosRESUMO
The cerebellum contains the majority of neurons in the human brain and is unique for its uniform cytoarchitecture, absence of aerobic glycolysis, and role in adaptive plasticity. Despite anatomical and physiological differences between the cerebellum and cerebral cortex, group-average functional connectivity studies have identified networks related to specific functions in both structures. Recently, precision functional mapping of individuals revealed that functional networks in the cerebral cortex exhibit measurable individual specificity. Using the highly sampled Midnight Scan Club (MSC) dataset, we found the cerebellum contains reliable, individual-specific network organization that is significantly more variable than the cerebral cortex. The frontoparietal network, thought to support adaptive control, was the only network overrepresented in the cerebellum compared to the cerebral cortex (2.3-fold). Temporally, all cerebellar resting state signals lagged behind the cerebral cortex (125-380 ms), supporting the hypothesis that the cerebellum engages in a domain-general function in the adaptive control of all cortical processes.