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Pregnancy is associated with neural and behavioral plasticity, systemic inflammation, and oxidative stress, yet the impact of inflammation and oxidative stress on maternal neural and behavioral plasticity during pregnancy is unclear. We hypothesized that healthy pregnancy transiently reduces learning and memory and these deficits are associated with pregnancy-induced elevations in inflammation and oxidative stress. Cognitive performance was tested with novel object recognition (recollective memory), Morris water maze (spatial memory), and open field (anxiety-like) behavior tasks in female Sprague-Dawley rats of varying reproductive states [nonpregnant (nulliparous), pregnant (near term), and 1-2 mo after pregnancy (primiparous); n = 7 or 8/group]. Plasma and CA1 proinflammatory cytokines were measured with a MILLIPLEX magnetic bead assay. Plasma oxidative stress was measured via advanced oxidation protein products (AOPP) assay. CA1 markers of oxidative stress, neuronal activity, and apoptosis were quantified via Western blot analysis. Our results demonstrate that CA1 oxidative stress-associated markers were elevated in pregnant compared with nulliparous rats (P ≤ 0.017) but there were equivalent levels in pregnant and primiparous rats. In contrast, reproductive state did not impact CA1 inflammatory cytokines, neuronal activity, or apoptosis. Likewise, there was no effect of reproductive state on recollective or spatial memory. Even so, spatial learning was impaired (P ≤ 0.007) whereas anxiety-like behavior (P ≤ 0.034) was reduced in primiparous rats. Overall, our data suggest that maternal hippocampal CA1 is protected from systemic inflammation but vulnerable to peripartum oxidative stress. Peripartum oxidative stress elevations, such as in pregnancy complications, may contribute to peripartum neural and behavioral plasticity.NEW & NOTEWORTHY Healthy pregnancy is associated with elevated maternal systemic and brain oxidative stress. During postpregnancy, brain oxidative stress remains elevated whereas systemic oxidative stress is resolved. This sustained maternal brain oxidative stress is associated with learning impairments and decreased anxiety-like behavior during the postpregnancy period.
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Estrés Oxidativo , Ratas Sprague-Dawley , Animales , Femenino , Embarazo , Ratas , Inflamación/metabolismo , Inflamación/fisiopatología , Memoria , Región CA1 Hipocampal/metabolismo , Región CA1 Hipocampal/fisiopatología , Memoria Espacial , Citocinas/metabolismo , Citocinas/sangre , Ansiedad/metabolismo , Neuronas/metabolismo , Aprendizaje por Laberinto , Mediadores de Inflamación/metabolismo , Mediadores de Inflamación/sangreRESUMEN
PURPOSE: The Brain Injury associated Visual Impairment - Impact Questionnaire (BIVI-IQ) was developed to assess the impact of post-stroke visual impairment. The development of the questionnaire used robust methods involving stroke survivors and clinicians. The aim of this study was to assess the validity of the BIVI-IQ in a stroke population. METHODS: Stroke survivors with visual impairment were recruited from stroke units, outpatient clinics and non-healthcare settings. Participants were asked to complete questionnaire sets on three separate occasions; the BIVI-IQ at each visit with additional questionnaires at baseline and visit 2. Vision assessment and anchor questions from participants and clinicians were collected. The analysis included assessment of missing data, acceptability, Rasch model analysis, test-retest reliability, construct validity (NEI VFQ-25, EQ-5D-5L) and responsiveness to change. RESULTS: 316 stroke survivors completed at least one questionnaire of the 326 recruited. Mean age was 67 years and 64% were male. Adequate fit statistics to the Rasch model were reached (χ2 = 73.12, p = 0.02) with two items removed and thresholds of two adjusted, indicating validity and unidimensionality. Excellent test-retest reliability was demonstrated (ICC = 0.905) with a 3-month interval. Construct validity was demonstrated with a strong significant correlation to the NEI VFQ-25 (r = 0.837, p < 0.01). The BIVI-IQ also demonstrated responsiveness to change with significant differences identified between groups based on participant and clinician anchor questions (X2 = 23.29, p < 0.001; X2 = 24.56, p < 0.001). CONCLUSION: The BIVI-IQ has been shown to be valid and practical for 'everyday' use by clinicians and researchers to monitor vision-related quality of life in stroke survivors with visual impairment.
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Lesiones Encefálicas , Baja Visión , Humanos , Masculino , Anciano , Femenino , Calidad de Vida/psicología , Reproducibilidad de los Resultados , Encuestas y Cuestionarios , Psicometría/métodos , Perfil de Impacto de EnfermedadRESUMEN
INTRODUCTION: While the natural history of adolescent idiopathic scoliosis (AIS) and adult idiopathic scoliosis (AdIS) is well documented in the literature, the impact of age on postoperative outcomes remains an active area of research. We performed a systematic review and meta-analysis to compare patients undergoing surgery for AIS and AdIS with respect to: (1) postoperative Cobb correction, (2) perioperative variables, and (3) postoperative complications. METHODS: A systematic literature search was performed in accordance with preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. INCLUSION CRITERIA: studies published between 2002 and 2022, retrospective, and comparing AIS vs. AdIS patients undergoing deformity surgery. The primary outcome was postoperative Cobb correction. Secondary outcomes included estimated blood loss (EBL), operative time, total instrumented levels, length of stay (LOS), and postoperative complications. Random-effects models were performed according to the method of DerSimonian and Laird. RESULTS: Of 190 identified articles, 14 fit the inclusion criteria. A total of 1788 patients were included, 1275(71.3%) with AIS, and 513(28.7%) with AdIS. There was a significant age difference between AIS and AdIS (15.3 vs. 36.7 years, mean difference (MD) = 21.3 years, 95%CI = 14.3-28.4,p < 0.001). Mean postoperative Cobb percentage correction was reported in 5 articles and was significantly higher in AIS (68.4%) vs. AdIS (61.4%) (MD = -7.2, 95%CI = -11.6,-2.7,p = 0.001). EBL was not significantly different between AIS and AdIS (695.6 mL vs 817.7 mL,p = 0.204). Furthermore, no difference was found in operative time (MD = 37.9 min,95%CI = -10.7;86.6,p = 0.127), total instrumented level (MD = 0.88,95%CI = -0.7,2.4,p = 0.273), and LOS (MD = 0.5, 95%CI = -0.2;1.2, p = 0.188). Four articles reported postoperative complications in AIS vs AdIS, with no difference in neurological deficit, instrumentation-related complications, and medical complications. CONCLUSION: AIS patients had better radiographic correction compared to AdIS. Though no difference was found in perioperative outcomes and complications, these findings emphasize the importance of counseling patients regarding the optimal timing of surgical correction.
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Escoliosis , Humanos , Escoliosis/cirugía , Escoliosis/diagnóstico por imagen , Adolescente , Adulto , Resultado del Tratamiento , Complicaciones Posoperatorias/epidemiología , Fusión Vertebral/métodosRESUMEN
Making sense of social situations requires social cognitive skills, which can be impaired after acquired brain injury (ABI), yet few evidence-based treatment options are available. This study aimed to evaluate the feasibility of a multi-faceted social cognition group treatment programme, SIFT IT, for people after ABI using an RCT design. Twenty-eight participants were recruited, and 23 were randomized into either Treatment or Waitlist. SIFT IT consisted of 14 weekly 90-minute small group sessions facilitated by a Clinical Psychologist. Topics included: emotion self-awareness, emotion perception, perspective taking, and choosing adaptive social responses. Preliminary efficacy outcomes were assessed at baseline, post-treatment, and three-month follow-up. Demand for treatment was evident with 61% recruitment and 91% post-treatment retention rates, with 63% attending at least 13/14 sessions. Large between-group treatment effects (with non-zero 95% confidence intervals) were observed for emotion perception, detecting hints, and informant ratings of social cognitive deficits. Implementation challenges recruiting to groups and maintaining group allocation fidelity, with a small sample size does, however, raise questions about the appropriateness of an RCT design in a future efficacy trial. Overall, this study showed there is demand for social cognitive interventions after ABI and the SIFT IT programme was practicable and acceptable to participants.Trial registration: Australian New Zealand Clinical Trials Registry identifier: ACTRN12617000405314.
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The therapeutic approach to Wilms tumor (WT) is multidisciplinary and leads to significant patient impairment, increasing the risk of nutritional compromise and malnutrition. Children with cancer are vulnerable to sarcopenia which has been recognized as a negative impact of anticancer therapy. Recent studies have highlighted the reduction in the total psoas muscle area (TPMA) to be associated with a poor prognosis in many pediatric diseases, including cancer. This study aims to evaluate changes in the TPMA compartment during the treatment of children with WT. An observational, longitudinal, and retrospective study was undertaken in a single institution evaluating children (1 to 14 y, n=38) with WT between 2014 and 2020. TPMA was assessed by the analysis of previously collected, electronically stored computed tomography images of the abdomen obtained at 3 time points: diagnosis, preoperatively, and 1 year after surgery. For all patients, TPMA/age were calculated with a specific online calculator. Our data show a high incidence of sarcopenia (55.3%) at diagnosis which increased after 4 to 6 weeks of neoadjuvant chemotherapy (73.7%) and remained high (78.9%) 1 year after the surgical procedure. Using TPMA/age Z-score curves we have found significant and rapid muscle loss in children with WT, with little or no recovery in the study period.
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Neoplasias Renales , Desnutrición , Sarcopenia , Tumor de Wilms , Niño , Humanos , Neoplasias Renales/complicaciones , Desnutrición/complicaciones , Pronóstico , Estudios Retrospectivos , Sarcopenia/diagnóstico , Sarcopenia/etiología , Tumor de Wilms/complicaciones , Tumor de Wilms/terapia , Estudios LongitudinalesRESUMEN
BACKGROUND AND IMPORTANCE: To describe the first case of a thoracic perineural cyst successfully treated using a direct thoracic transforaminal endoscopic approach. METHODS: Case report. CLINICAL PRESENTATION: A 66-year-old male presented with right-sided radicular pain in a T4 distribution. MRI of the thoracic spine revealed a right T4 perineural cyst caudally displacing the root in the T4-5 foramen. He had failed attempts at nonoperative management. The patient underwent an all endoscopic transforaminal perineural cyst decompression and resection as a same-day surgical procedure. Postoperatively, the patient noted near complete resolution of the preoperative radicular pain. A thoracic MRI with and without contrast was performed 3 months after surgery and showed no evidence of the preoperative perineural cyst and no symptom recurrence was noted by the patient. CONCLUSION: This case report presents the first safe and successful report of an all endoscopic transforaminal decompression and resection of a perineural cyst in the thoracic spine.
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Quistes de Tarlov , Masculino , Humanos , Anciano , Quistes de Tarlov/complicaciones , Quistes de Tarlov/diagnóstico por imagen , Quistes de Tarlov/cirugía , Endoscopía/métodos , Columna Vertebral , Procedimientos Neuroquirúrgicos/métodos , Dolor/cirugíaRESUMEN
PURPOSE: The modified Japanese Orthopedic Association (mJOA) score consists of six sub-domains and is used to quantify the severity of cervical myelopathy. The current study aimed to assess for predictors of postoperative mJOA sub-domains scores following elective surgical management for patients with cervical myelopathy and develop the first clinical prediction model for 12-month mJOA sub-domain scores.Please confirm if the author names are presented accurately and in the correct sequence (given name, middle name/initial, family name). Author 1 Given name: [Byron F.] Last name [Stephens], Author 2 Given name: [Lydia J.] Last name [McKeithan], Author 3 Given name: [W. Hunter] Last name [Waddell], Author 4 Given name: [Anthony M.] Last name [Steinle], Author 5 Given name: [Wilson E.] Last name [Vaughan], Author 6 Given name: [Jacquelyn S.] Last name [Pennings], Author 7 Given name: [Jacquelyn S.] Last name [Pennings], Author 8 Given name: [Scott L.] Last name [Zuckerman], Author 9 Given name: [Kristin R.] Last name [Archer], Author 10 Given name: [Amir M.] Last name [Abtahi] Also, kindly confirm the details in the metadata are correct.Last Author listed should be Kristin R. Archer METHODS: A multivariable proportional odds ordinal regression model was developed for patients with cervical myelopathy. The model included patient demographic, clinical, and surgery covariates along with baseline sub-domain scores. The model was internally validated using bootstrap resampling to estimate the likely performance on a new sample of patients. RESULTS: The model identified mJOA baseline sub-domains to be the strongest predictors of 12-month scores, with numbness in legs and ability to walk predicting five of the six mJOA items. Additional covariates predicting three or more items included age, preoperative anxiety/depression, gender, race, employment status, duration of symptoms, smoking status, and radiographic presence of listhesis. Surgical approach, presence of motor deficits, number of surgical levels involved, history of diabetes mellitus, workers' compensation claim, and patient insurance had no impact on 12-month mJOA scores. CONCLUSION: Our study developed and validated a clinical prediction model for improvement in mJOA scores at 12 months following surgery. The results highlight the importance of assessing preoperative numbness, walking ability, modifiable variables of anxiety/depression, and smoking status. This model has the potential to assist surgeons, patients, and families when considering surgery for cervical myelopathy. LEVEL OF EVIDENCE: Level III.
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Pueblos del Este de Asia , Enfermedades de la Médula Espinal , Humanos , Hipoestesia , Modelos Estadísticos , Resultado del Tratamiento , Estudios Prospectivos , Pronóstico , Vértebras Cervicales/cirugía , Enfermedades de la Médula Espinal/cirugíaRESUMEN
The substance use, violence, and AIDS (SAVA) syndemic framework is used to study risk for HIV/AIDS. As a secondary analysis from a large HIV/AIDS prevention study, we categorized participants into having from zero to three SAVA conditions based on the presence or absence of self-reported substance use in the past 4 months, history of lifetime sexual abuse, and intimate partner violence. We used Poisson regression models to examine the association between the number of SAVA conditions and sexual risk behavior. Among all participants (n = 195, median age, 20), 37.9%, 19.5%, and 6.7% reported occurrence of one, two, and all three SAVA conditions, respectively. We found that more than one SAVA condition experienced by women was significantly associated with having more than one sex partner (adjusted prevalence ratio [aPR] = 1.88; 95% confidence interval [CI] = 1.28, 2.76) and with substance use before sex (aPR = 1.61 95% CI = 1.06, 2.45).
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Síndrome de Inmunodeficiencia Adquirida , Infecciones por VIH , Violencia de Pareja , Trastornos Relacionados con Sustancias , Síndrome de Inmunodeficiencia Adquirida/epidemiología , Adulto , Femenino , Infecciones por VIH/epidemiología , Infecciones por VIH/prevención & control , Humanos , Prevalencia , Conducta Sexual , Parejas Sexuales , Trastornos Relacionados con Sustancias/epidemiología , Violencia , Adulto JovenRESUMEN
BACKGROUND: There is evidence of increased mental health problems during the early stages of the COVID-19 pandemic. We aimed to identify the factors that put certain groups of people at greater risk of mental health problems. METHODS: We took a participatory approach, involving people with lived experience of mental health problems and/or carers, to generate a set of risk factors and potential moderators of the effects of COVID on mental health. An online cross-sectional survey was completed by 1464 United Kingdom residents between 24th April and 27th June 2020. The survey had questions on whether respondents were existing mental health service users and or carers, level of depression (PHQ9) and anxiety (GAD7), demographics, threat and coping appraisals, perceived resilience (BRS), and specific coping behaviours (validated as part of this study). The relationship between responses and coping strategies was measured using tetrachoric correlations. Structural equation modelling was used to test the model. RESULTS: A model significantly fit our data (rel χ2 = 2.05, RMSEA = 0.029 95%, CI (0.016, 0.042), CFI = 0.99, TLI = 0.98, SRMR = 0.014). Age and coping appraisal predicted anxiety and depression. Whereas, threat appraisal and ethnicity only predicted anxiety, and resilience only predicted depression. Additionally, specific coping behaviours predicted anxiety and depression, with overlap on distraction. CONCLUSIONS: Some, but not all, risk factors significantly predict anxiety and depression. While there is a relationship between anxiety and depression, different factors may put people at greater risk of one or the other during the pandemic.
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COVID-19 , Humanos , Pandemias , Estudios Transversales , Adaptación Psicológica , Ansiedad/psicología , Modelos Psicológicos , Depresión/epidemiología , Depresión/psicologíaRESUMEN
BACKGROUND: Public health organizations have inconsistent recommendations for screening adolescents and young adults for Chlamydia trachomatis and Neisseria gonorrhoeae infections. Guidelines suggest different combinations of anorectal, pharyngeal, and urogenital testing based on age, sex, and sexual activity. Further evaluation of how identity and behaviors impact the anatomic distribution of C. trachomatis and N. gonorrhoeae infection is needed to optimize future screening practices. METHODS: We assessed the positivity of C. trachomatis and N. gonorrhoeae infections at different anatomic sites in a cohort of at-risk sexually active adolescents and young adults aged 12-24 years in New Orleans, Louisiana and Los Angeles, California. Participants were tested for C. trachomatis and N. gonorrhoeae at 3 sites (anorectum, pharynx, and urethral/cervix) every 4 months using self-collected swabs. We stratified anatomic distributions of infection into 4 gender and sexual behavior categories: (1) cisgender men who have sex with men and transgender women (MSMTW); (2) cisgender heterosexual males; (3) cisgender heterosexual females; and (4) gender minorities assigned female at birth. RESULTS: While three-site testing detected all infections, two-site (anorectum and urethra/cervix) testing identified 92%-100% of C. trachomatis or N. gonorrhoeae infections in participants assigned female at birth and cisgender heterosexual males. For MSMTW, two-site anorectal and pharyngeal testing vs single-site anorectal testing increased the proportion of individuals with either infection from 74% to 93%. CONCLUSIONS: Sexual behavior and gender identity may influence detection of C. trachomatis and N. gonorrhoeae infections at specific anatomic testing sites. Testing guidelines should incorporate sexual behavior and gender identity. CLINICAL TRIALS REGISTRATION: NCT03134833.
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Infecciones por Chlamydia , Gonorrea , Minorías Sexuales y de Género , Adolescente , Infecciones por Chlamydia/diagnóstico , Infecciones por Chlamydia/epidemiología , Chlamydia trachomatis , Femenino , Identidad de Género , Gonorrea/diagnóstico , Gonorrea/epidemiología , Homosexualidad Masculina , Humanos , Recién Nacido , Los Angeles , Louisiana , Masculino , Neisseria gonorrhoeae , Nueva Orleans , Faringe , Prevalencia , Estados Unidos , Adulto JovenRESUMEN
A control theory perspective on determination of optimal dynamic treatment regimes is considered. The aim is to adapt statistical methodology that has been developed for medical or other biostatistical applications to incorporate powerful control techniques that have been designed for engineering or other technological problems. Data tend to be sparse and noisy in the biostatistical area and interest has tended to be in statistical inference for treatment effects. In engineering fields, experimental data can be more easily obtained and reproduced and interest is more often in performance and stability of proposed controllers rather than modeling and inference per se. We propose that modeling and estimation should be based on standard statistical techniques but subsequent treatment policy should be obtained from robust control. To bring focus, we concentrate on A-learning methodology as developed in the biostatistical literature and H∞ -synthesis from control theory. Simulations and two applications demonstrate robustness of the H∞ strategy compared to standard A-learning in the presence of model misspecification or measurement error.
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Modelos EstadísticosRESUMEN
In the San Francisco Bay Area (SFBA), trans women of color are disproportionately affected by HIV and have poor HIV care outcomes. The Brandy Martell Project and TransAccess were two demonstration projects aimed at increasing HIV care engagement and retention among trans women of color in the SFBA. Both projects took place in clinics with a long history of providing trans health care and social services. Both also relied on peer navigation to address systems barriers and promote HIV care linkage and engagement. Our analysis was to identify associations between intervention exposure and primary HIV care visits, ART prescription, and retention in HIV care. Using GEE, we estimated the association between intervention exposure measures (receipt of intervention, intervention dose, intervention provider, and peer dose) and any primary HIV care visit or ART prescription over the 12-month period. Overall, the Brandy Martell Project and TransAccess interventions had significantly positive associations with HIV care outcomes measured. Peer navigation also had a significantly positive association with HIV care outcomes. These interventions demonstrate promise for engaging and retaining trans women of color in HIV care, and call for future investment in this highly underserved community.
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Infecciones por VIH , Pigmentación de la Piel , Atención a la Salud , Femenino , Identidad de Género , Infecciones por VIH/prevención & control , Humanos , San FranciscoRESUMEN
Visual analytics techniques are useful tools to support decision-making and cope with increasing data, particularly to monitor natural or artificial phenomena. When monitoring disease progression, visual analytics approaches help decision-makers to understand or even prevent dissemination paths. In this paper, we propose a new visual analytics tool for monitoring COVID-19 dissemination. We use k-nearest neighbors of cities to mimic neighboring cities and analyze COVID-19 dissemination based on comparing a city under consideration and its neighborhood. Moreover, such analysis is performed within periods, which facilitates the assessment of isolation policies. We validate our tool by analyzing the progression of COVID-19 in neighboring cities of São Paulo state, Brazil.
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COVID-19/epidemiología , Visualización de Datos , Brasil/epidemiología , COVID-19/transmisión , Ciudades , Humanos , SARS-CoV-2RESUMEN
BACKGROUND: While difficulties regulating emotions are almost ubiquitous after traumatic brain injury (TBI), remediation techniques are limited. Heart-rate variability (HRV) is a physiological measure of emotion regulation and can be modified using biofeedback training. The aim of the current study was to evaluate the efficacy of repeated biofeedback training for improving emotion regulation difficulties following TBI. DESIGN: Fifty adults with severe TBI were allocated to either biofeedback or waitlist conditions. Treatment consisted of six biofeedback sessions whereby participants were taught to breathe at their resonant frequency. Outcomes included changes in physiological and subjective reactivity to anger-induction, emotional well-being, and physiology at rest, together with symptoms of psychological distress and sleep disturbances (ACTRN12618002031246). RESULTS: While biofeedback led to reduced skin conductance, it did not affect any other objective or subjective response to the mood induction procedure. Biofeedback led to fewer sleep disturbances, and reduced negative mood valence and depression during follow-up. CONCLUSIONS: HRV biofeedback training is a feasible technique following TBI that transfers to improved symptoms of general emotional well-being, psychological distress, and sleep. Biofeedback does not transfer to a laboratory-based emotional provocation task. HRV biofeedback training may represent a novel adjunct for generalized emotional difficulties following injury.
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Biorretroalimentación Psicológica , Lesiones Traumáticas del Encéfalo , Adulto , Ira , Emociones , Frecuencia Cardíaca , HumanosRESUMEN
OBJECTIVES: Flooding is associated with increased psychological morbidity; however, the impact of living with the uncertainty of flood risk has not been explored. The aim of this study was to generate insight into individual experiences of living with persistent flood risk, how it affects psychological well-being, and the forms of support deemed appropriate to mitigate psychological risks. STUDY DESIGN: A qualitative study was conducted using semistructured interviews with participants who lived in a persistent flood risk area in Nottinghamshire, UK. METHODS: 40 participants were interviewed. The study adopted an interpretivist constructionist position, and the transcripts were analysed using inductive thematic analysis. RESULTS: Persistent flood risk was seen as a significant stressor, regardless of previous flood history. Some participants reported anxiety in anticipation of a future flood event and demonstrated low self-efficacy, with subsequent feelings of helplessness in responding to flood risk. Individuals who lacked acceptance of flood risk displayed higher anxiety and lower resilience. Recognition of flood risk as a psychological stressor was requested in future support. CONCLUSIONS: Living with the uncertainty of persistent flood risk can have significant psychological impacts. Interventions that facilitate the empowerment of individuals living with persistent flood risk may strengthen psychological resilience.
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Inundaciones , Resiliencia Psicológica , Ansiedad , Humanos , Estrés Psicológico/epidemiología , IncertidumbreRESUMEN
OBJECTIVE: The objective of the study is to identify the barriers to UK Black, Asian and Minority Ethnic (BAME) women attending breast screening and subsequently, support the growing evidence base providing solutions to the public health problem of ethnic variation within screening attendance. STUDY DESIGN: A systematic review and thematic analysis of UK-based, qualitative studies concerning BAME women. METHODS: The methodology of this review is based on Cochrane guidelines. A search strategy was applied to Embase, PubMed and Medline. Predefined inclusion and exclusion criteria yielded 8 final articles which were appraised and thematically analysed. RESULTS: The main findings of the review revealed three overarching themes: knowledge-related, access-related and cultural-related factors. The emphasis of the importance of knowledge was highlighted by all studies identifying a lack of knowledge as a key barrier to screening attendance. CONCLUSIONS: BAME women have disproportionally lower breast screening attendance and a lack of knowledge is an essential barrier to overcome when addressing this health inequality.
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Neoplasias de la Mama/psicología , Asistencia Sanitaria Culturalmente Competente , Etnicidad/estadística & datos numéricos , Conocimientos, Actitudes y Práctica en Salud/etnología , Promoción de la Salud/métodos , Accesibilidad a los Servicios de Salud , Disparidades en el Estado de Salud , Mamografía/psicología , Adulto , Negro o Afroamericano , Pueblo Asiatico , Población Negra , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/etnología , Cultura , Detección Precoz del Cáncer , Etnicidad/psicología , Femenino , Humanos , Aceptación de la Atención de Salud/etnologíaRESUMEN
Glioblastoma (GBM) is an aggressive cancer with a very poor prognosis. Generally viewed as weakly immunogenic, GBM responds poorly to current immunotherapies. To understand this problem more clearly we used a combination of natural killer (NK) cell functional assays together with gene and protein expression profiling to define the NK cell response to GBM and explore immunosuppression in the GBM microenvironment. In addition, we used transcriptome data from patient cohorts to classify GBM according to immunological profiles. We show that glioma stem-like cells, a source of post-treatment tumour recurrence, express multiple immunomodulatory cell surface molecules and are targeted in preference to normal neural progenitor cells by natural killer (NK) cells ex vivo. In contrast, GBM-infiltrating NK cells express reduced levels of activation receptors within the tumour microenvironment, with hallmarks of transforming growth factor (TGF)-ß-mediated inhibition. This NK cell inhibition is accompanied by expression of multiple immune checkpoint molecules on T cells. Single-cell transcriptomics demonstrated that both tumour and haematopoietic-derived cells in GBM express multiple, diverse mediators of immune evasion. Despite this, immunome analysis across a patient cohort identifies a spectrum of immunological activity in GBM, with active immunity marked by co-expression of immune effector molecules and feedback inhibitory mechanisms. Our data show that GBM is recognized by the immune system but that anti-tumour immunity is restrained by multiple immunosuppressive pathways, some of which operate in the healthy brain. The presence of immune activity in a subset of patients suggests that these patients will more probably benefit from combination immunotherapies directed against multiple immunosuppressive pathways.
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Neoplasias Encefálicas/inmunología , Perfilación de la Expresión Génica/métodos , Glioblastoma/inmunología , Tolerancia Inmunológica/inmunología , Células Asesinas Naturales/inmunología , Células Madre Neoplásicas/inmunología , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patología , Línea Celular Tumoral , Células Cultivadas , Estudios de Cohortes , Citotoxicidad Inmunológica/genética , Citotoxicidad Inmunológica/inmunología , Regulación Neoplásica de la Expresión Génica/inmunología , Redes Reguladoras de Genes/inmunología , Glioblastoma/genética , Glioblastoma/patología , Humanos , Tolerancia Inmunológica/genética , Células Asesinas Naturales/metabolismo , Células Madre Neoplásicas/metabolismo , Fenotipo , Pronóstico , Transducción de Señal/genética , Transducción de Señal/inmunología , Microambiente Tumoral/genética , Microambiente Tumoral/inmunologíaRESUMEN
Provided in this paper is a theory of long-range electron transfer with near sound (supersonic or subsonic) velocity along one-dimensional crystal lattices. The theory represents the development of an earlier work by introducing Marcus formulation. To illustrate its application to a realistic case, the theory is used to offer an explanation of two puzzling observations made by Donovan and Wilson in transient photoconduction experiments with non-dopable perfectly crystalline polydiacetylene crystals in the presence of an electric field: transport velocity value close to sound velocity being independent of field for four orders of magnitude of field (102 V/m-106 V/m) and, in the low field values, an ultra-high mobility greater than 20 m2/V s. We also study factors eventually leading to lowering of the transport velocity.
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BACKGROUND: CHDs can be complicated by renal injury which worsens morbidity and mortality. Urinary neutrophil gelatinase-associated lipocalin, a sensitive and specific biomarker of renal tubular injury, has not been studied in children with uncorrected CHDs. This study evaluated renal injury in children with uncorrected CHDs using this biomarker. METHODS: The patients were children with uncorrected CHDs with significant shunt confirmed on echocardiogram with normal renal ultrasound scan, in the paediatric cardiology clinic of a tertiary hospital. The controls were age-matched healthy children recruited from general practice clinics. Information on bio-data and socio-demographics were collected and urine was obtained for measurement of urinary neutrophil gelatinase-associated lipocalin levels. RESULTS: A total of 65 children with uncorrected CHDs aged 2 to 204 months were recruited. Thirty-one (47.7%) were males while 36 (55.4%) had acyanotic CHDs. The median urinary neutrophil gelatinase-associated lipocalin level of patients of 26.10 ng/ml was significantly higher than controls of 16.90 ng/ml (U = 1624.50, p = 0.023). The median urinary neutrophil gelatinase-associated lipocalin level of patients with cyanotic and acyanotic CHDs were 30.2 ng/ml and 22.60 ng/ml respectively; (Mann-Whitney U = 368.50, p = 0.116). The prevalence of renal injury using 95th percentile cut-off value of urinary neutrophil gelatinase-associated lipocalin was 16.9%. Median age of patients with renalinjury was 16 (4-44) months. CONCLUSIONS: Children with uncorrected CHDs have renal injury detected as early as infancy. The use of urinary neutrophil gelatinase-associated lipocalin in early detection of renal injury in these children may enhance early intervention and resultant prevention of morbidity and reduction in mortality.
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Lesión Renal Aguda , Cardiopatías Congénitas , Lipocalinas , Lesión Renal Aguda/diagnóstico , Lesión Renal Aguda/epidemiología , Lesión Renal Aguda/etiología , Biomarcadores , Niño , Cardiopatías Congénitas/complicaciones , Humanos , Lactante , Riñón , Pruebas de Función Renal , Lipocalina 2 , Lipocalinas/uso terapéutico , MasculinoRESUMEN
OBJECTIVE: The aim of this study was to evaluate the predictors of mortality in childhood heart failure (HF) in 2 tertiary hospitals. METHODS: A 51-month retrospective review of case notes of children with HF admitted into children's emergency rooms of 2 tertiary centers in Southern Nigeria was done. Bio-data and certain sociodemographic variables including mortality were abstracted. Bivariate and multivariate analyses were done to evaluate the predictors of mortality in HF. RESULTS: The case notes of 289 children were analyzed, consisting of 153 males (52.9%) and 142 infants (49.1%). Lower respiratory tract infections, 121 (41.9%), were the commonest causes of HF. Twenty-eight children (9.7%) died. In multivariate analyses, only late presentation (P < 0.0001) was an independent predictor of mortality in HF. CONCLUSION: Education of the populace about early presentation to hospital is imperative to prevent unnecessary deaths associated with HF.