RESUMEN
Herpes simplex virus encephalitis (HSE) is the most common cause of sporadic viral encephalitis, and despite targeted antiviral therapy, outcomes remain poor. Although the innate immune system is critical for restricting herpes simplex virus type I (HSV-1) in the brain, there is evidence that prolonged neuroinflammation contributes to HSE pathogenesis. In this study, we investigated the contribution of inflammasomes to disease pathogenesis in a murine model of HSE. Inflammasomes are signaling platforms that activate the pro-inflammatory cytokines interleukin-1ß (IL-1ß) and IL-18. We found that mice deficient in the inflammasome adaptor protein, apoptosis-associated speck-like protein containing a caspase activation and recruitment domain (ASC), had significantly improved survival and lower levels of IL-1ß and IL-18 in the brain. Importantly, this difference in survival was independent of viral replication in the central nervous system (CNS). We found that microglia, the resident macrophages of the CNS, are the primary mediators of the ASC-dependent inflammasome response during infection. Using in vitro glial infections and a murine HSE model, we demonstrate that inflammasome activation contributes to the expression of chemokine (C-C motif) ligand 6 (CCL6), a leukocyte chemoattractant. The lower concentration of CCL6 in the brains of ASC-/- mice correlated with lower numbers of infiltrating macrophages during infection. Together, these data suggest that inflammasomes contribute to pathogenic inflammation in HSE and provide a mechanistic link between glial inflammasome activation and leukocyte infiltration. The contribution of inflammasomes to survival was independent of viral replication in our study, suggesting a promising new target in combating harmful inflammation in HSE.
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Proteínas Adaptadoras de Señalización CARD/inmunología , Encefalitis por Herpes Simple/inmunología , Encefalitis por Herpes Simple/mortalidad , Inflamasomas/inmunología , Animales , Encéfalo/inmunología , Células Cultivadas , Quimiocinas CC/inmunología , Chlorocebus aethiops , Modelos Animales de Enfermedad , Femenino , Mediadores de Inflamación/inmunología , Interleucina-1beta/inmunología , Macrófagos/inmunología , Masculino , Ratones , Ratones Endogámicos C57BL , Microglía/inmunología , Células VeroRESUMEN
Herpes simplex virus (HSV) infection of the neonatal brain causes severe encephalitis and permanent neurologic deficits. However, infants infected with HSV at the time of birth follow varied clinical courses, with approximately half of infants experiencing only external infection of the skin rather than invasive neurologic disease. Understanding the cause of these divergent outcomes is essential to developing neuroprotective strategies. To directly assess the contribution of viral variation to neurovirulence, independent of human host factors, we evaluated clinical HSV isolates from neonates with different neurologic outcomes in neurologically relevant in vitro and in vivo models. We found that isolates taken from neonates with encephalitis are more neurovirulent in human neuronal culture and mouse models of HSV encephalitis, as compared to isolates collected from neonates with skin-limited disease. These findings suggest that inherent characteristics of the infecting HSV strain contribute to disease outcome following neonatal infection.
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Enfermedades Transmisibles , Encefalitis por Herpes Simple , Herpes Simple , Animales , Ratones , Recién Nacido , Humanos , Herpesvirus Humano 2 , EncéfaloRESUMEN
Arsenite interferes with DNA repair protein function resulting in the retention of UV-induced DNA damage. Accumulated DNA damage promotes replication stress which is bypassed by DNA damage tolerance pathways such as translesion synthesis (TLS). Rad18 is an essential factor in initiating TLS through PCNA monoubiquitination and contains two functionally and structurally distinct zinc fingers that are potential targets for arsenite binding. Arsenite treatment displaced zinc from endogenous Rad18 protein and mass spectrometry analysis revealed arsenite binding to both the Rad18 RING finger and UBZ domains. Consequently, arsenite inhibited Rad18 RING finger dependent PCNA monoubiquitination and polymerase eta recruitment to DNA damage in UV exposed keratinocytes, both of which enhance the bypass of cyclobutane pyrimidine dimers during replication. Further analysis demonstrated multiple effects of arsenite, including the reduction in nuclear localization and UV-induced chromatin recruitment of Rad18 and its binding partner Rad6, which may also negatively impact TLS initiation. Arsenite and Rad18 knockdown in UV exposed keratinocytes significantly increased markers of replication stress and DNA strand breaks to a similar degree, suggesting arsenite mediates its effects through Rad18. Comet assay analysis confirmed an increase in both UV-induced single-stranded DNA and DNA double-strand breaks in arsenite treated keratinocytes compared to UV alone. Altogether, this study supports a mechanism by which arsenite inhibits TLS through the altered activity and regulation of Rad18. Arsenite elevated the levels of UV-induced replication stress and consequently, single-stranded DNA gaps and DNA double-strand breaks. These potentially mutagenic outcomes support a role for TLS in the cocarcinogenicity of arsenite.
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Arsénico , Arsenitos , Arsénico/metabolismo , Arsenitos/metabolismo , Arsenitos/toxicidad , Cromatina , Daño del ADN , Reparación del ADN , Replicación del ADN , ADN de Cadena Simple , Antígeno Nuclear de Célula en Proliferación/metabolismo , Dímeros de Pirimidina/metabolismo , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitinación , Zinc/metabolismoRESUMEN
BACKGROUND: Partnering with a public transport (PT) provider, state government, and local government, the single-blinded randomised controlled trial, trips4health, investigated the impact of PT use incentives on transport-related physical activity (PA) in Tasmania, Australia. The intervention involved 16-weeks of incentives (bus trip credits) for achieving weekly PT use targets, supported by weekly text messages. This study objective was to conduct a process evaluation of the COVID-19 disrupted trips4health study. METHODS: The Medical Research Council UK's framework for complex public health interventions guided the process evaluation. Participant reach, acceptability, fidelity and feasibility were evaluated. Administrative and post-intervention survey data were analysed descriptively. Semi-structured interviews with intervention participants (n = 7) and PT provider staff (n = 4) were analysed thematically. RESULTS: Due to COVID-19, trips4health was placed on hold (March 2020) then stopped (May 2020) as social restrictions impacted PT use. At study cessation, 116 participants (approximately one third of target sample) had completed baseline measures, 110 were randomised, and 64 (n = 29 in the intervention group; n = 35 in the control group) completed post-intervention measures. Participants were 18 - 80 years (average 44.5 years) with females (69%) and those with tertiary education (55%) over-represented. The intervention was delivered with high fidelity with 96% of bus trip credits and 99% of behavioural text messages sent as intended. Interviewed PT staff said implementation was highly feasible. Intervention participant acceptability was high with 90% reporting bus trip incentives were helpful and 59% reporting the incentives motivated them to use PT more. From a total of 666 possible bus trip targets, 56% were met with 38% of intervention participants agreeing and 41% disagreeing that 'Meeting the bus trip targets was easy'. Interviews and open-ended survey responses from intervention participants revealed incentives motivated bus use but social (e.g., household member commitments) and systemic (e.g., bus availability) factors made meeting bus trip targets challenging. CONCLUSIONS: trips4health demonstrated good acceptability and strong fidelity and feasibility. Future intervention studies incentivising PT use will need to ensure a broader demographic is reached and include more supports to meet PT targets. TRIAL REGISTRATION: ACTRN12619001136190 .
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COVID-19 , Femenino , Humanos , COVID-19/prevención & control , Motivación , Ejercicio Físico , Conductas Relacionadas con la Salud , Encuestas y CuestionariosRESUMEN
BACKGROUND: Sudden smell loss is a specific early symptom of COVID-19, which, prior to the emergence of Omicron, had estimated prevalence of ~40% to 75%. Chemosensory impairments affect physical and mental health, and dietary behavior. Thus, it is critical to understand the rate and time course of smell recovery. The aim of this cohort study was to characterize smell function and recovery up to 11 months post COVID-19 infection. METHODS: This longitudinal survey of individuals suffering COVID-19-related smell loss assessed disease symptoms and gustatory and olfactory function. Participants (n=12,313) who completed an initial survey (S1) about respiratory symptoms, chemosensory function and COVID-19 diagnosis between April and September 2020, were invited to complete a follow-up survey (S2). Between September 2020 and February 2021, 27.5% participants responded (n=3,386), with 1,468 being diagnosed with COVID-19 and suffering co-occurring smell and taste loss at the beginning of their illness. RESULTS: At follow-up (median time since COVID-19 onset ~200 days), ~60% of women and ~48% of men reported less than 80% of their pre-illness smell ability. Taste typically recovered faster than smell, and taste loss rarely persisted if smell recovered. Prevalence of parosmia and phantosmia was ~10% of participants in S1 and increased substantially in S2: ~47% for parosmia and ~25% for phantosmia. Persistent smell impairment was associated with more symptoms overall, suggesting it may be a key marker of long-COVID illness. The ability to smell during COVID-19 was rated slightly lower by those who did not eventually recover their pre-illness ability to smell at S2. CONCLUSIONS: While smell ability improves for many individuals who lost it during acute COVID-19, the prevalence of parosmia and phantosmia increases substantially over time. Olfactory dysfunction is associated with broader persistent symptoms of COVID-19, and may last for many months following acute COVID-19. Taste loss in the absence of smell loss is rare. Persistent qualitative smell symptoms are emerging as common long-term sequelae; more research into treatment options is strongly warranted given that even conservative estimates suggest millions of individuals may experience parosmia following COVID-19. Healthcare providers worldwide need to be prepared to treat post COVID-19 secondary effects on physical and mental health.
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Ageusia , COVID-19 , Trastornos del Olfato , Masculino , Humanos , Femenino , COVID-19/complicaciones , Olfato , Anosmia/etiología , SARS-CoV-2 , Estudios de Cohortes , Prueba de COVID-19 , Estudios de Seguimiento , Síndrome Post Agudo de COVID-19 , Trastornos del Olfato/epidemiología , Trastornos del Olfato/etiología , Trastornos del Olfato/diagnósticoRESUMEN
Health-related fear is a normal and common response in the face of the global pandemic of COVID-19. Children and young people are frequently being exposed to messages about the threat to health, including from the media and authorities. Whilst for most, their anxiety will be proportionate to the threat, for some, existing pre-occupation with physical symptoms and illness will become more problematic. There is a growing body of evidence that health anxiety may occur in childhood, however much of the literature is taken from research using adult samples. This practitioner review aims to give an overview of the assessment and treatment of health-related worries in children and young people in the context of the COVID-19 pandemic. This review is based on the limited existing evidence in this population and the more substantial evidence base for treating health anxiety in adults. We consider the adaptations needed to ensure such interventions are developmentally appropriate.
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COVID-19 , Pandemias , Adolescente , Adulto , Ansiedad , Trastornos de Ansiedad/epidemiología , Niño , Humanos , SARS-CoV-2RESUMEN
OBJECTIVE: To compare standard (native tissue) repair with synthetic mesh inlays or mesh kits. DESIGN: Randomised controlled trial. SETTING: Thirty-three UK hospitals. POPULATION: Women having surgery for recurrent prolapse. METHODS: Women recruited using remote randomisation. MAIN OUTCOME MEASURES: Prolapse symptoms, condition-specific quality-of-life and serious adverse effects. RESULTS: A Mean Pelvic Organ Prolapse Symptom Score at 1 year was similar for each comparison (standard 6.6 versus mesh inlay 6.1, mean difference [MD] -0.41, 95% CI -2.92 to 2.11: standard 6.6 versus mesh kit 5.9, MD -1.21 , 95% CI -4.13 to 1.72) but the confidence intervals did not exclude a minimally important clinical difference. There was no evidence of difference in any other outcome measure at 1 or 2 years. Serious adverse events, excluding mesh exposure, were similar at 1 year (standard 7/55 [13%] versus mesh inlay 5/52 [10%], risk ratio [RR] 1.05 [0.66-1.68]: standard 3/25 [12%] versus mesh kit 3/46 [7%], RR 0.49 [0.11-2.16]). Cumulative mesh exposure rates over 2 years were 7/52 (13%) in the mesh inlay arm, of whom four women required surgical revision; and 4/46 in the mesh kit arm (9%), of whom two required surgical revision. CONCLUSIONS: We did not find evidence of a difference in terms of prolapse symptoms from the use of mesh inlays or mesh kits in women undergoing repeat prolapse surgery. Although the sample size was too small to be conclusive, the results provide a substantive contribution to future meta-analysis. TWEETABLE ABSTRACT: There is not enough evidence to support use of synthetic mesh inlay or mesh kits for repeat prolapse surgery.
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Procedimientos Quirúrgicos Ginecológicos/métodos , Satisfacción del Paciente/estadística & datos numéricos , Prolapso de Órgano Pélvico/cirugía , Mallas Quirúrgicas , Incontinencia Urinaria/cirugía , Prolapso Uterino/cirugía , Adulto , Coito , Femenino , Estudios de Seguimiento , Procedimientos Quirúrgicos Ginecológicos/instrumentación , Humanos , Persona de Mediana Edad , Prolapso de Órgano Pélvico/fisiopatología , Prolapso de Órgano Pélvico/psicología , Calidad de Vida , Reoperación/estadística & datos numéricos , Resultado del Tratamiento , Incontinencia Urinaria/fisiopatología , Incontinencia Urinaria/psicología , Prolapso Uterino/fisiopatología , Prolapso Uterino/psicologíaRESUMEN
Despite pelvic organ prolapse being a universal problem experienced in nearly 50% of parous women, the surgical management of vaginal prolapse remains an enigma to many, with wide variation in the rates and types of intervention performed. As part of the 6th International Consultation on Incontinence (ICI) our committee, charged with producing an evidence-based report on the surgical management of prolapse, produced a pathway for the surgical management of prolapse. The 2017 ICI surgical management of prolapse evidence-based pathway will be presented and summarized. Weaknesses of the data and pathway will be discussed and avenues for future research proposed.
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Procedimientos Quirúrgicos Ginecológicos/estadística & datos numéricos , Prolapso de Órgano Pélvico/cirugía , Factores de Edad , Toma de Decisiones , Femenino , Humanos , IncidenciaAsunto(s)
Astrocitos/inmunología , Encefalitis por Herpes Simple/inmunología , Interferón Tipo I/inmunología , Animales , Astrocitos/virología , Encéfalo/inmunología , Encéfalo/virología , Modelos Animales de Enfermedad , Encefalitis por Herpes Simple/virología , Herpesvirus Humano 1/fisiología , Estimación de Kaplan-Meier , Ratones , Ratones Noqueados , Microglía/inmunología , Microglía/virología , Receptor de Interferón alfa y beta/deficiencia , Receptor de Interferón alfa y beta/inmunología , Transducción de Señal , Carga ViralRESUMEN
To understand increasing rates of hepatitis C virus (HCV) infection in Tennessee, we conducted testing, risk factor analysis and a nested case-control study among persons who use drugs. During June-October 2016, HCV testing with risk factor assessment was conducted in sexually transmitted disease clinics, family planning clinics and an addiction treatment facility in eastern Tennessee; data were analysed by using multivariable logistic regression. A nested case-control study was conducted to assess drug-using risks and behaviours among persons who reported intranasal or injection drug use (IDU). Of 4753 persons tested, 397 (8.4%) were HCV-antibody positive. HCV infection was significantly associated with a history of both intranasal and IDU (adjusted odds ratio (aOR) 35.4, 95% confidence interval (CI) 24.1-51.9), IDU alone (aOR 52.7, CI 25.3-109.9), intranasal drug use alone (aOR 2.6, CI 1.8-3.9) and incarceration (aOR 2.7, CI 2.0-3.8). By 4 October 2016, 574 persons with a reported history of drug use; 63 (11%) were interviewed further. Of 31 persons who used both intranasal and injection drugs, 26 (84%) reported previous intranasal drug use, occurring 1-18 years (median 5.5 years) before their first IDU. Our findings provide evidence that reported IDU, intranasal drug use and incarceration are independent indicators of risk for past or present HCV infection in the study population.
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Hepatitis C/epidemiología , Enfermedades de Transmisión Sexual/epidemiología , Adolescente , Adulto , Anciano , Estudios de Casos y Controles , Demografía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Factores de Riesgo , Tennessee/epidemiologíaRESUMEN
OBJECTIVE: To evaluate the long-term risk of further gynaecological surgery and cancer in women with endometriosis. DESIGN: Cohort study. SETTING: Scotland. PARTICIPANTS: 281 937 women with nearly 5 million person years (4 923 628) of follow up from 1981 to 2010. METHODS: In this national population-based study we compared 17 834 women with a new surgical diagnosis of endometriosis with 83 303 women with no evidence of endometriosis at laparoscopy, 162 966 women who underwent laparoscopic sterilisation, and 17 834 age-matched women from the general population. Cox proportional hazards regression was used to calculate crude and adjusted hazard ratios with 95% confidence intervals. MAIN OUTCOME MEASURES: Risk of further gynaecological surgery, number and type of repeat surgery and time to repeat surgery from the diagnosis of endometriosis. Cancer outcomes included subsequent risk of all cancer, gynaecological and non-gynaecological cancers. RESULTS: Women with endometriosis had a significantly higher risk of further surgery when compared with women with no evidence of endometriosis at laparoscopy [hazard ratio (HR) 1.69, 95% (confidence interval) CI 1.65-1.73], women who had undergone laparoscopic sterilisation (HR 3.30, 95% CI 3.23-3.37) and age-matched women from the general population (HR 5.95, 95% CI 5.71-6.20). They also have an increased risk of ovarian cancer when compared with general population counterparts (HR 1.77, 95% CI 1.08-2.89) or those with laparoscopic sterilisation (HR 1.75, 95% CI 1.2-2.45). CONCLUSION: Women with surgically diagnosed endometriosis face an increased risk of multiple surgery. They have a higher chance of developing ovarian cancer in comparison with the general population and women with laparoscopic sterilisation. TWEETABLE ABSTRACT: Women with endometriosis face an increased risk of recurrent surgery and developing ovarian cancer.
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Endometriosis/epidemiología , Procedimientos Quirúrgicos Ginecológicos/estadística & datos numéricos , Neoplasias/epidemiología , Adulto , Endometriosis/cirugía , Femenino , Estudios de Seguimiento , Humanos , Laparoscopía/estadística & datos numéricos , Masculino , Pronóstico , Reoperación/estadística & datos numéricos , Factores de Riesgo , Escocia/epidemiología , Segunda Cirugía/estadística & datos numéricos , Factores Socioeconómicos , Esterilización Reproductiva/estadística & datos numéricosRESUMEN
BACKGROUND: Initial management of children diagnosed with type 1 diabetes (T1D) varies worldwide with sparse high quality evidence regarding the impact of different models of care. AIM: To compare the inpatient model of care with a hybrid home-based alternative, examining metabolic and psychosocial outcomes, diabetes knowledge, length of stay, and patient satisfaction. SUBJECTS AND METHODS: The study design was a randomized-controlled trial. Inclusion criteria were: newly diagnosed T1D, aged 3 to 16 years, living within approximately 1 hour of the hospital, English-speaking, access to transport, absence of significant medical or psychosocial comorbidity. Patients were randomized to standard care with a 5 to 6 day initial inpatient stay or discharge after 2 days for home-based management. All patients received practical skills training in the first 48 hours. The intervention group was visited twice/day by a nurse for 2 days to assist with injections, then a multi-disciplinary team made 3 home visits over 2 weeks to complete education. Patients were followed up for 12 months. Clinical outcomes included HbA1c, hypoglycemia, and diabetes-related readmissions. Surveys measured patient satisfaction, diabetes knowledge, family impact, and quality of life. RESULTS: Fifty patients were recruited, 25 to each group. There were no differences in medical or psychosocial outcomes or diabetes knowledge. Average length of admission was 1.9 days shorter for the intervention group. Families indicated that with hindsight, most would choose home- over hospital-based management. CONCLUSIONS: With adequate support, children newly diagnosed with T1D can be safely managed at home following practical skills training.
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Diabetes Mellitus Tipo 1/terapia , Servicios de Atención de Salud a Domicilio , Hiperglucemia/prevención & control , Hipoglucemia/prevención & control , Padres/educación , Educación del Paciente como Asunto , Calidad de Vida , Adolescente , Niño , Preescolar , Terapia Combinada/enfermería , Complicaciones de la Diabetes/epidemiología , Complicaciones de la Diabetes/prevención & control , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 1/enfermería , Estudios de Seguimiento , Hemoglobina Glucada/análisis , Conocimientos, Actitudes y Práctica en Salud , Humanos , Hiperglucemia/epidemiología , Hipoglucemia/epidemiología , Hipoglucemia/fisiopatología , Nutricionistas , Satisfacción del Paciente , Sistemas de Apoyo Psicosocial , Riesgo , Índice de Severidad de la Enfermedad , Trabajadores Sociales , Australia Occidental/epidemiología , Recursos HumanosRESUMEN
OBJECTIVE: To determine pregnancy outcomes in women with endometriosis. DESIGN: A national population based cohort study using record linkage. SETTING: Scotland. PARTICIPANTS: A cohort of 14 655 women followed up over a 30-year period (1981-2010). METHODS: In a nationwide Scottish study, we compared pregnancy outcomes in 5375 women with surgically confirmed endometriosis with outcomes in 8710 women without endometriosis who were pregnant during the same time period. Data were analysed using univariable and multivariable logistic regression after adjusting for confounding factors. MAIN OUTCOME MEASURES: Outcome measures evaluated included miscarriage, ectopic pregnancy, stillbirths and other pregnancy complications such as hypertensive disorders of pregnancy, antepartum and postpartum haemorrhage, operative delivery and preterm births. The outcomes were presented as adjusted odds ratios (OR) with 95% confidence intervals (CI). RESULTS: On multivariable analysis, after adjusting for age, parity, socio-economic status and year of delivery, women with endometriosis when compared to women without endometriosis, had a significantly higher risk of early pregnancy complications with adjusted OR (95% CI) of 1.76 (1.44, 2.15) and 2.70 (1.09, 6.72) for miscarriage and ectopic pregnancy, respectively. A previous diagnosis of endometriosis was associated with a significantly increased risk of [adjusted OR (95% CI)] placenta praevia [2.24 (1.52, 3.31)], unexplained antepartum haemorrhage [1.67 (1.39, 2.00)], postpartum haemorrhage [1.30 (1.61, 1.46)] and preterm births [1.26 (1.07, 1.49)] in pregnancies progressing beyond 24 weeks. CONCLUSION: Endometriosis predisposes women to an increased risk of early pregnancy loss and later pregnancy complications. TWEETABLE ABSTRACT: Endometriosis predisposes women to an increased risk of early pregnancy loss and later pregnancy complications.
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Endometriosis/complicaciones , Complicaciones del Embarazo/epidemiología , Resultado del Embarazo/epidemiología , Adulto , Estudios de Cohortes , Femenino , Humanos , Recién Nacido , Embarazo , Escocia/epidemiología , Adulto JovenRESUMEN
OBJECTIVE: A pilot single-blinded randomised controlled trial (RCT) was conducted to examine concordance with and acceptability of electric stimulation therapy (EST) in patients with venous leg ulcers (VLUs) who had not tolerated moderate to high compression. METHOD: Participants were randomised to the intervention group (n=15) or a placebo control group (n=8) in which EST was used four times daily for 20 minutes per session. Participants were monitored for eight weeks during which time concordance with the treatment and perceptions of the treatment were assessed. RESULTS: Concordance with the total recommended treatment time was 71.4% for the intervention group and 82.9% for the control group; a difference that was not statistically significant. Participants rated EST as acceptable (84.6% intervention; 83.3% control), only two participants, both from the placebo control group, would not be willing to use EST again. The majority considered EST easier to use than compression (68.4%). CONCLUSION: EST was a practical and acceptable treatment among people who have been unable to tolerate moderate to high compression therapy.
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Terapia por Estimulación Eléctrica/métodos , Aceptación de la Atención de Salud , Úlcera Varicosa/terapia , Anciano , Anciano de 80 o más Años , Vendajes de Compresión , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Método Simple CiegoRESUMEN
OBJECTIVE: Compression therapy is a gold standard treatment to promote venous leg ulcer (VLU) healing. Concordance with compression therapy is, however, often sub-optimal. The aim of this study was to evaluate the effectiveness of electric stimulation therapy (EST) to facilitate healing of VLUs among people who do not use moderate-to-high levels of compression (>25 mmHg). METHOD: A pilot multicentre, single-blinded randomised controlled trial was conducted. Participants were randomised (2:1) to the intervention group or a control group where EST or a sham device was used 4 times daily for 20 minutes per session. Participants were monitored fortnightly for eight weeks. The primary outcome measure was percentage of area (wound size) change. RESULTS: In the 23 patients recruited, an average redution in wound size of 23.15% (standard deviation [SD]: 61.23) was observed for the control group compared with 32.67 % (SD: 42.54) for the intervention. A moderate effect size favouring the intervention group was detected from univariate [F(1,18)=1.588, p=0.224, partial eta squared=0.081] and multivariate repeated measures [F(1,18)=2.053, p=0.169, partial eta squared=0.102] analyses. CONCLUSION: The pilot study was not powered to detect statistical significance, however, the difference in healing outcomes are encouraging. EST may be an effective adjunct treatment among patients who have experienced difficulty adhering to moderate-to-high levels of compression therapy.
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Terapia por Estimulación Eléctrica , Úlcera de la Pierna/terapia , Medias de Compresión , Úlcera Varicosa/terapia , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Método Simple Ciego , Cicatrización de HeridasRESUMEN
BACKGROUND: Psoriasis is a chronic inflammatory disease of the skin and joints that may also have systemic inflammatory effects, including the development of cardiovascular disease (CVD). Multiple epidemiologic studies have demonstrated increased rates of CVD in psoriasis patients, although a causal link has not been established. A growing body of evidence suggests that sub-clinical systemic inflammation may develop in psoriasis patients, even from a young age. We aimed to evaluate the prevalence of atherosclerosis and identify specific clinical risk factors associated with early vascular inflammation. METHODS: We conducted a cross-sectional study of a tertiary care cohort of psoriasis patients using coronary artery calcium (CAC) score and carotid intima-media thickness (CIMT) to detect atherosclerosis, along with high sensitivity C-reactive protein (hsCRP) to measure inflammation. Psoriasis patients and controls were recruited from our tertiary care dermatology clinic. Presence of atherosclerosis was defined using validated numeric values within CAC and CIMT imaging. Descriptive data comparing groups was analyzed using Welch's t test and Pearson Chi square tests. Logistic regression was used to analyze clinical factors associated with atherosclerosis, and linear regression to evaluate the relationship between psoriasis and hsCRP. RESULTS: 296 patients were enrolled, with 283 (207 psoriatic and 76 controls) having all data for the hsCRP and atherosclerosis analysis. Atherosclerosis was found in 67.6 % of psoriasis subjects versus 52.6 % of controls; Psoriasis patients were found to have a 2.67-fold higher odds of having atherosclerosis compared to controls [95 % CI (1.2, 5.92); p = 0.016], after adjusting for age, gender, race, BMI, smoking, HDL and hsCRP. In addition, a non-significant trend was found between HsCRP and psoriasis severity, as measured by PASI, PGA, or BSA, again after adjusting for confounders. CONCLUSIONS: A tertiary care cohort of psoriasis patients have a high prevalence of early atherosclerosis, increased hsCRP, and psoriasis remains a risk factor for the presence of atherosclerosis even after adjustment of key confounding clinical factors. Psoriasis may contribute to an accelerated systemic inflammatory cascade resulting in increased risk of CVD and CV events.
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Aterosclerosis/complicaciones , Calcio/metabolismo , Grosor Intima-Media Carotídeo , Vasos Coronarios/metabolismo , Vasos Coronarios/patología , Psoriasis/complicaciones , Centros de Atención Terciaria , Aterosclerosis/epidemiología , Proteína C-Reactiva/metabolismo , Estudios de Cohortes , Estudios Transversales , Demografía , Femenino , Humanos , Masculino , Persona de Mediana Edad , PrevalenciaRESUMEN
We report the determination of the Q(EC) value of the mirror transition of (11)C by measuring the atomic masses of (11)C and (11)B using Penning trap mass spectrometry. More than an order of magnitude improvement in precision is achieved as compared to the 2012 Atomic Mass Evaluation (Ame2012) [Chin. Phys. C 36, 1603 (2012)]. This leads to a factor of 3 improvement in the calculated Ft value. Using the new value, Q(EC)=1981.690(61) keV, the uncertainty on Ft is no longer dominated by the uncertainty on the Q(EC) value. Based on this measurement, we provide an updated estimate of the Gamow-Teller to Fermi mixing ratio and standard model values of the correlation coefficients.
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BACKGROUND: The mechanisms by which stress hormones impact triple-negative breast cancer (TNBC) etiology and treatment are unclear. We have previously shown that stress hormones, cortisol, and catecholamines induce rapid DNA damage and impact DNA repair in NIH 3T3 fibroblasts. This study investigates whether stress hormones increase DNA damage in breast cancer cells and if this impacts drug efficacy. METHODS: We first screened a panel of 39 breast cancer cell lines for expression of adrenergic and glucocorticoid receptors and examined if stress hormones induce DNA damage and alter cell cycle regulation in vitro. A TNBC xenograft model was used to assess the impact of restraint stress on tumour growth and chemosensitivity to paclitaxel. RESULTS: We found that stress hormones induced DNA damage, phosphorylation of ATR, which was accompanied by an up-regulation of the G1 cell kinase inhibitor p21 and a cell cycle halt of TNBCs in the G1 phase. p21 knockdown abrogated G1 arrest by stress hormones. We also demonstrated that stress significantly decreased efficacy of paclitaxel. CONCLUSION: We describe a novel mechanism through which stress hormones can induce drug resistance to paclitaxel, which may have profound implications for treating drug resistance in patients with TNBC.
Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Catecolaminas/farmacología , Daño del ADN/efectos de los fármacos , Hidrocortisona/farmacología , Paclitaxel/farmacología , Estrés Fisiológico/efectos de los fármacos , Neoplasias de la Mama Triple Negativas/patología , Animales , Apoptosis/efectos de los fármacos , Western Blotting , Ciclo Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Reparación del ADN/efectos de los fármacos , Femenino , Citometría de Flujo , Humanos , Ratones , Ratones Desnudos , Receptores de Estrógenos/metabolismo , Transducción de Señal , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/genética , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
We report the first direct measurement of the (14)O superallowed Fermi ß-decay QEC value, the last of the so-called "traditional nine" superallowed Fermi ß decays to be measured with Penning trap mass spectrometry. (14)O, along with the other low-Z superallowed ß emitter, (10)C, is crucial for setting limits on the existence of possible scalar currents. The new ground state QEC value, 5144.364(25) keV, when combined with the energy of the 0(+) daughter state, Ex(0(+))=2312.798(11) keV [F. Ajzenberg-Selove, Nucl. Phys. A523, 1 (1991)], provides a new determination of the superallowed ß-decay QEC value, QEC(sa)=2831.566(28) keV, with an order of magnitude improvement in precision, and a similar improvement to the calculated statistical rate function f. This is used to calculate an improved Ft value of 3073.8(2.8) s.
RESUMEN
BACKGROUND: Sleep is important for growth and renewal of multiple physiological systems. The effects of chronic poor sleep quality on human skin function and visible signs of ageing have not been elucidated. AIM: To evaluate the effect of chronic poor sleep quality on measures of skin health and ageing. Self-perceived satisfaction with appearance was also assessed. METHODS: 60 healthy caucasian women, who were categorized as poor quality sleepers [Pittsburg Sleep Quality Index (PSQI) > 5, sleep duration ≤ 5 h] or good quality sleepers (PSQI ≤ 5, sleep duration 7-9 h). A validated clinical tool, SCINEXA(TM) , was used to assess intrinsic and extrinsic skin ageing. Dark under-eye circles were evaluated using standardized photos. Measurement of in vivo transepidermal water loss (TEWL) was used to assess recovery of the skin barrier after tape stripping. Subjects were exposed to simulated solar ultraviolet light, and recovery from erythema was monitored. Subjects also completed a questionnaire evaluating self-perception of attractiveness. RESULTS: Good sleepers had significantly lower intrinsic skin ageing scores by SCINEXA(TM) . At baseline, poor sleepers had significantly higher levels of TEWL. At 72 h after tape stripping, good sleepers had 30% greater barrier recovery compared with poor sleepers. At 24 h after exposure to ultraviolet light, good sleepers had significantly better recovery from erythema. Good sleepers also reported a significantly better perception of their appearance and physical attractiveness compared with poor sleepers. CONCLUSIONS: This study indicates that chronic poor sleep quality is associated with increased signs of intrinsic ageing, diminished skin barrier function and lower satisfaction with appearance.