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BACKGROUND: Firefighters have occupational and environmental exposures to per- and polyfluoroalkyl substances (PFAS). The goal of this study was to compare serum PFAS concentrations across multiple United States fire departments to National Health and Nutrition Examination Survey (NHANES) participants. METHODS: Nine serum PFAS were compared in 290 firefighters from four municipal fire departments (coded A-D) and three NHANES participants matched to each firefighter on sex, ethnicity, age, and PFAS collection year. Only Departments A and C had sufficient women study participants (25 and six, respectively) to compare with NHANES. RESULTS: In male firefighters compared with NHANES, geometric mean perfluorohexane sulfonate (PFHxS) was elevated in Departments A-C, sum of branched perfluoromethylheptane sulfonate isomers (Sm-PFOS) was elevated in all four departments, linear perfluorooctane sulfonate (n-PFOS) was elevated in Departments B and C, linear perfluorooctanoate (n-PFOA) was elevated in Departments B-D, and perfluorononanoate (PFNA) was elevated in Departments B-D, but lower in A. In male firefighters compared with NHANES, perfluoroundecanoate (PFUnDA) was more frequently detected in Departments B and D, and 2-(N-methyl-perfluorooctane sulfonamido) acetate (MeFOSAA) was less frequently detected in Departments B-D. In female firefighters compared with NHANES, PFHxS and Sm-PFOS concentrations were elevated in Departments A and C. Other PFAS concentrations were elevated and/or reduced in only one department or not significantly different from NHANES in any department. CONCLUSIONS: Serum PFHxS, Sm-PFOS, n-PFOS, n-PFOA, and PFNA concentrations were increased in at least two of four fire departments in comparison to NHANES.
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Contaminantes Ambientales , Fluorocarburos , Humanos , Masculino , Femenino , Estados Unidos , Encuestas Nutricionales , Fluorocarburos/análisis , Exposición a Riesgos Ambientales , AlcanosulfonatosRESUMEN
Improving equity in women's health requires gender-specific and empowering approaches. However, health programs often disempower women by adopting a 'one-size-fits-all' approach that emphasizes diet, exercise and weight loss over other important aspects like sleep and mental wellbeing. This article reports on the design of Next Level Health (NLH), a program that aims to empower women through developing a wide range of health behaviors to support their holistic wellbeing. NLH is grounded by ethics, theory and evidence to support women to make achievable, sustainable changes that are relevant to their everyday lives. Women utilized the NLH framework to develop an integrative health routine across six domains: physical activity, sleep, nutrition, eating behavior, self-care and stress management. The framework guided them to set small, incremental goals that were adaptive to their needs and built from their existing circumstances. Participants reflected on their progress with a facilitator during monthly meetings, accessed a social media support page and received monthly text messages. Health programs remain an essential approach to improving women's health alongside community- and policy-level strategies. The development of NLH exemplifies how evidence may partner with modern health promotion values to inform relevant and ethical program design for women.
In western societies, health programs often focus on weight loss through exercise and diet to promote women's health. Such approaches disempower women by undervaluing important factors affecting their health like stress and sleep and narrow their scope for 'health success'. This article reports on the development of Next Level Health (NLH) that aims to help women gain greater health-related control by broadening their approach to health. The program is designed to support women to set small, achievable goals across six domains (physical activity, sleep, nutrition, eating behavior, self-care, and stress management) toward developing positive and sustainable health behaviors. Although women work with a facilitator each month to set goals, they are ultimately in control of formulating their health plans and their progression through NLH. Women can support each other by joining a community of other NLH participants through a social media group. NLH offers a novel program that is responsive to women's individual health needs and broadens their potential for health success.
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Estado de Salud , Salud Holística , Femenino , Humanos , Nueva Zelanda , Salud de la Mujer , Promoción de la SaludRESUMEN
Purpose: Head and neck (HN) radiotherapy (RT) is complex, involving multiple target and organ at risk (OAR) structures delineated by the radiation oncologist. Site-agnostic peer review after RT plan completion is often inadequate for thorough review of these structures. In-depth review of RT contours is critical to maintain high-quality RT and optimal patient outcomes. Materials and Methods: In August 2020, the HN RT Quality Assurance Conference, a weekly teleconference that included at least one radiation oncology HN specialist, was activated at our institution. Targets and OARs were reviewed in detail prior to RT plan creation. A parallel implementation study recorded patient factors and outcomes of these reviews. A major change was any modification to the high-dose planning target volume (PTV) or the prescription dose/fractionation; a minor change was modification to the intermediate-dose PTV, low-dose PTV, or any OAR. We analysed the results of consecutive RT contour review in the first 20 months since its initiation. Results: A total of 208 patients treated by 8 providers were reviewed: 86·5% from the primary tertiary care hospital and 13·5% from regional practices. A major change was recommended in 14·4% and implemented in 25 of 30 cases (83·3%). A minor change was recommended in 17·3% and implemented in 32 of 36 cases (88·9%). A survey of participants found that all (n = 11) strongly agreed or agreed that the conference was useful. Conclusion: Dedicated review of RT targets/OARs with a HN subspecialist is associated with substantial rates of suggested and implemented modifications to the contours.
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BACKGROUND: Previous studies have suggested improved efficiency and patient outcomes with 125I seed compared with hookwire localization (HWL) in breast-conserving surgery, but high-level evidence of superior surgical outcomes is lacking. The aim of this multicentre pragmatic RCT was to compare re-excision and positive margin rates after localization using 125I seed or hookwire in women with non-palpable breast cancer. METHODS: Between September 2013 and March 2018, women with non-palpable breast cancer eligible for breast-conserving surgery were assigned randomly to preoperative localization using 125I seeds or hookwires. Randomization was stratified by lesion type (pure ductal carcinoma in situ (DCIS) or other) and study site. Primary endpoints were rates of re-excision and margin positivity. Secondary endpoints were resection volumes and weights. RESULTS: A total of 690 women were randomized at eight sites; 659 women remained after withdrawal (125I seed, 327; HWL, 332). Mean age was 60.3 years in the 125I seed group and 60.7 years in the HWL group, with no difference between the groups in preoperative lesion size (mean 13.2 mm). Lesions were pure DCIS in 25.9 per cent. The most common radiological lesion types were masses (46.9 per cent) and calcifications (28.2 per cent). The localization modality was ultrasonography in 65.5 per cent and mammography in 33.7 per cent. The re-excision rate after 125I seed localization was significantly lower than for HWL (13.9 versus 18.9 per cent respectively; P = 0.019). There were no significant differences in positive margin rates, or in specimen weights and volumes. CONCLUSION: Re-excision rates after breast-conserving surgery were significantly lower after 125I seed localization compared with HWL. Registration number: ACTRN12613000655741 (http://www.ANZCTR.org.au/).
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Neoplasias de la Mama/cirugía , Radioisótopos de Yodo , Márgenes de Escisión , Mastectomía Segmentaria/métodos , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/patología , Carcinoma Intraductal no Infiltrante/diagnóstico , Carcinoma Intraductal no Infiltrante/patología , Carcinoma Intraductal no Infiltrante/cirugía , Femenino , Humanos , Persona de Mediana Edad , Cirugía Asistida por Computador/métodos , Resultado del TratamientoRESUMEN
PURPOSE: This multicenter service evaluation explores the efficacy and tolerability of brivaracetam (BRV) in an unselected, consecutive population in 'real-life' clinical settings. METHOD: We retrospectively collected data from patient records at 11 UK hospitals and epilepsy centers. Consecutive patients prescribed BRV with at least 3â¯months of follow-up (FU) were included. Apart from reporting effectiveness and tolerability of BRV across the whole cohort, we compared treatment outcomes depending on previous levetiracetam use (LEV+ versus LEV-), comorbid learning disability (LD+ versus LD-), and epilepsy syndrome (focal versus generalized epilepsy). RESULTS: Two hundred and ninety patients (46% male, median age: 38â¯years, range: 15 to 77) with ≥3â¯months of FU were included. The median duration of BRV exposure was 12â¯months (range: 1â¯day to 72â¯months). Overall BRV retention was 71.1%. While 56.1% of patients improved in terms of seizure frequency category (daily, weekly, monthly, yearly seizures), 23.1% did not improve on this measure and 20.8% deteriorated. In terms of seizure frequency, 21% of patients experienced a ≥50% reduction, with 7.0% of all patients becoming seizure-free. Treatment-emergent adverse events (AEs) were reported by 107 (36.9%) patients, but there were no serious AEs. The commonest AEs were sedation/fatigue (18.3%), mood changes (9.0%), and irritability/aggression (4.8%). There were no significant differences in drug retention, seizure frequency outcomes, or AEs between the LEV+ and LEV- subgroups, or between patients with generalized or focal epilepsies. Although 15.5% of patients in the LD+ group achieved a ≥50% reduction, this rate was lower than in the LD- group. CONCLUSIONS: This 'real-life' evaluation suggests that reductions in seizure frequency can be achieved with BRV in patients with highly refractory epilepsy. Brivaracetam may be a useful treatment option in patients who have previously failed to respond to or tolerate LEV, those with LD, or (off-label) those with generalized epilepsies.
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Anticonvulsivantes/uso terapéutico , Epilepsias Parciales/tratamiento farmacológico , Epilepsias Parciales/epidemiología , Epilepsia Generalizada/tratamiento farmacológico , Epilepsia Generalizada/epidemiología , Pirrolidinonas/uso terapéutico , Adolescente , Adulto , Anciano , Anticonvulsivantes/efectos adversos , Estudios de Cohortes , Fatiga/inducido químicamente , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Pirrolidinonas/efectos adversos , Estudios Retrospectivos , Convulsiones/tratamiento farmacológico , Convulsiones/epidemiología , Resultado del Tratamiento , Reino Unido/epidemiología , Adulto JovenRESUMEN
The neutron-capture reaction plays a critical role in the synthesis of the elements in stars and is important for societal applications including nuclear power generation and stockpile-stewardship science. However, it is difficult-if not impossible-to directly measure neutron capture cross sections for the exotic, short-lived nuclei that participate in these processes. In this Letter we demonstrate a new technique which can be used to indirectly determine neutron-capture cross sections for exotic systems. This technique makes use of the (d,p) transfer reaction, which has long been used as a tool to study the structure of nuclei. Recent advances in reaction theory, together with data collected using this reaction, enable the determination of neutron-capture cross sections for short-lived nuclei. A benchmark study of the ^{95}Mo(d,p) reaction is presented, which illustrates the approach and provides guidance for future applications of the method with short-lived isotopes produced at rare isotope accelerators.
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Hidradenitis suppurativa (HS)/acne inversa is a debilitating chronic disease that remains poorly understood and difficult to manage. Clinical practice is variable, and there is a need for international, evidence-based and easily applicable consensus on HS management. We report here the findings of a systematic literature review, which were subsequently used as a basis for the development of international consensus recommendations for the management of patients with HS. A systematic literature review was performed for each of nine clinical questions in HS (defined by an expert steering committee), covering comorbidity assessment, therapy (medical, surgical and combinations) and response to treatment. Included articles underwent data extraction and were graded according to the Oxford Centre for Evidence-based Medicine criteria. Evidence-based recommendations were then drafted, refined and voted upon, using a modified Delphi process. Overall, 5310 articles were screened, 171 articles were analysed, and 65 were used to derive recommendations. These articles included six randomized controlled trials plus cohort studies and case series. The highest level of evidence concerned dosing recommendations for topical clindamycin in mild disease (with systemic tetracyclines for more frequent/widespread lesions) and biologic therapy (especially adalimumab) as second-line agents (following conventional therapy failure). Good-quality evidence was available for the hidradenitis suppurativa clinical response (HiSCR) as a dichotomous outcome measure in inflammatory areas under treatment. Lower-level evidence supported recommendations for topical triclosan and oral zinc in mild-to-moderate HS, systemic clindamycin and rifampicin in moderate HS and intravenous ertapenem in selected patients with more severe disease. Intralesional or systemic steroids may also be considered. Local surgical excision is suggested for mild-to-moderate HS, with wide excision for more extensive disease. Despite a paucity of good-quality data on management decisions in HS, this systematic review has enabled the development of robust and easily applicable clinical recommendations for international physicians based on graded evidence.
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Antibacterianos/uso terapéutico , Hidradenitis Supurativa/tratamiento farmacológico , Hidradenitis Supurativa/epidemiología , Fumar/epidemiología , Adalimumab/uso terapéutico , Antiinflamatorios/uso terapéutico , Productos Biológicos/uso terapéutico , Comorbilidad , Consenso , Técnica Delphi , Hidradenitis Supurativa/cirugía , Humanos , Guías de Práctica Clínica como AsuntoRESUMEN
Background: The optimal regimen of chemotherapy and reirradiation (re-XRT) for recurrent head and neck squamous cell carcinoma (HNSCC) is controversial. We report the final outcomes of a multicenter phase II trial evaluating cetuximab and cisplatin-based chemotherapy concurrent with re-XRT for patients with recurrent HNSCC. Materials and methods: Patients with unresectable recurrent disease or positive margins after salvage surgery arising within a previously irradiated field with KPS ≥ 70 were eligible for this trial. Cetuximab 400 mg/m2 was delivered as a loading dose in week 1 followed by weekly cetuximab 250 mg/m2 and cisplatin 30 mg/m2 concurrent with 6 weeks of intensity-modulated radiotherapy to a dose of 60-66 Gy in 30 daily fractions. Patients who previously received both concurrent cetuximab and cisplatin with radiation or who received radiotherapy less than 6 months prior were ineligible. Results: From 2009 to 2013, 48 patients enrolled on this trial, 2 did not receive any protocol treatment. Of the remaining 46 patients, 34 were male and 12 female, with a median age of 62 years (range 36-85). Treatment was feasible and only 1 patient did not complete the treatment course. Common grade 3 or higher acute toxicities were lymphopenia (46%), pain (22%), dysphagia (13%), radiation dermatitis (13%), mucositis (11%) and anorexia (11%). There were no grade 5 acute toxicities. Eight grade 3 late toxicities were observed, four of which were swallowing related. With a median follow-up of 1.38 years, the 1-year overall survival (OS) was 60.4% and 1-year recurrence-free survival was 34.1%. On univariate analysis, OS was significantly improved with young age (P = 0.01). OS was not associated with radiation dose, surgery before re-XRT or interval from prior XRT. Conclusions: Concurrent cisplatin and cetuximab with re-XRT is feasible and offers good treatment outcomes for patients with high-risk features. Younger patients had significantly improved OS. ClinicalTrials.Gov Identifier: NCT00833261.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Cetuximab/administración & dosificación , Cisplatino/administración & dosificación , Neoplasias de Cabeza y Cuello/terapia , Neoplasias Primarias Secundarias/terapia , Carcinoma de Células Escamosas de Cabeza y Cuello/terapia , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Quimioradioterapia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Recurrencia , Análisis de SupervivenciaRESUMEN
Background: Adding abiraterone acetate with prednisolone (AAP) or docetaxel with prednisolone (DocP) to standard-of-care (SOC) each improved survival in systemic therapy for advanced or metastatic prostate cancer: evaluation of drug efficacy: a multi-arm multi-stage platform randomised controlled protocol recruiting patients with high-risk locally advanced or metastatic PCa starting long-term androgen deprivation therapy (ADT). The protocol provides the only direct, randomised comparative data of SOC + AAP versus SOC + DocP. Method: Recruitment to SOC + DocP and SOC + AAP overlapped November 2011 to March 2013. SOC was long-term ADT or, for most non-metastatic cases, ADT for ≥2 years and RT to the primary tumour. Stratified randomisation allocated pts 2 : 1 : 2 to SOC; SOC + docetaxel 75 mg/m2 3-weekly×6 + prednisolone 10 mg daily; or SOC + abiraterone acetate 1000 mg + prednisolone 5 mg daily. AAP duration depended on stage and intent to give radical RT. The primary outcome measure was death from any cause. Analyses used Cox proportional hazards and flexible parametric models, adjusted for stratification factors. This was not a formally powered comparison. A hazard ratio (HR) <1 favours SOC + AAP, and HR > 1 favours SOC + DocP. Results: A total of 566 consenting patients were contemporaneously randomised: 189 SOC + DocP and 377 SOC + AAP. The patients, balanced by allocated treatment were: 342 (60%) M1; 429 (76%) Gleason 8-10; 449 (79%) WHO performance status 0; median age 66 years and median PSA 56 ng/ml. With median follow-up 4 years, 149 deaths were reported. For overall survival, HR = 1.16 (95% CI 0.82-1.65); failure-free survival HR = 0.51 (95% CI 0.39-0.67); progression-free survival HR = 0.65 (95% CI 0.48-0.88); metastasis-free survival HR = 0.77 (95% CI 0.57-1.03); prostate cancer-specific survival HR = 1.02 (0.70-1.49); and symptomatic skeletal events HR = 0.83 (95% CI 0.55-1.25). In the safety population, the proportion reporting ≥1 grade 3, 4 or 5 adverse events ever was 36%, 13% and 1% SOC + DocP, and 40%, 7% and 1% SOC + AAP; prevalence 11% at 1 and 2 years on both arms. Relapse treatment patterns varied by arm. Conclusions: This direct, randomised comparative analysis of two new treatment standards for hormone-naïve prostate cancer showed no evidence of a difference in overall or prostate cancer-specific survival, nor in other important outcomes such as symptomatic skeletal events. Worst toxicity grade over entire time on trial was similar but comprised different toxicities in line with the known properties of the drugs. Trial registration: Clinicaltrials.gov: NCT00268476.
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Acetato de Abiraterona/administración & dosificación , Antagonistas de Andrógenos/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Docetaxel/administración & dosificación , Neoplasias de la Próstata/tratamiento farmacológico , Acetato de Abiraterona/efectos adversos , Anciano , Antagonistas de Andrógenos/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/normas , Supervivencia sin Enfermedad , Docetaxel/efectos adversos , Estudios de Seguimiento , Humanos , Estimación de Kaplan-Meier , Masculino , Metaanálisis en Red , Supervivencia sin Progresión , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/sangre , Neoplasias de la Próstata/mortalidad , Neoplasias de la Próstata/patología , Nivel de AtenciónRESUMEN
Obtaining reliable data for nuclear reactions on unstable isotopes remains an extremely important task and a formidable challenge. Neutron capture cross sections-crucial ingredients for models of astrophysical processes, national security applications, and simulations of nuclear energy generation-are particularly elusive, as both projectile and target in the reaction are unstable. We demonstrate a new method for determining cross sections for neutron capture on unstable isotopes, using ^{87}Y(n,γ) as a prototype. To validate the method, a benchmark experiment is carried out to obtain the known ^{90}Zr(n,γ) cross section analogously. Our approach, which employs an indirect ("surrogate") measurement combined with theory, can be generalized to a larger class of nuclear reactions. It can be used both with traditional stable-beam experiments and in inverse kinematics at rare-isotope facilities.
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BACKGROUND: Hidradenitis suppurativa (HS), a chronic inflammatory disease that affects apocrine gland-bearing skin, has a significant impact on patients' quality of life. Estimates of the epidemiologic prevalence of HS are highly variable, and clinical data on disease characteristics and patient burden of disease remain limited. OBJECTIVE: The primary objective of this study was to determine the number of patients with HS attending dermatology clinics in a hospital setting in Ireland (within a 6-month time period). Secondary objectives included the assessment of disease characteristics and the collection of patient responses on disease burden and work productivity. METHODS: This was an epidemiologic, non-interventional, cross-sectional study across four dermatology clinics in Ireland over a 6-month time period. The disease prevalence was estimated by calculating the percentage of total patients with a diagnosis of HS (the primary population) across the selected sites. Secondary analyses were performed using the full analysis set, which consisted of eligible adults (≥18 years of age) from the primary population who provided informed consent. Data from these analyses are presented as descriptive summary statistics, with the use of an analysis of covariance for continuous endpoints. RESULTS: The prevalence of HS across the four selected sites was estimated at 1.4% (95% CI, 1.24-1.62). One hundred and fifty eligible patients comprised the full analysis set. The majority of participants were white (95.3%), female (70.0%), cigarette smokers (56.0%) and overweight or obese (body mass index ≥25 kg/m2 , 81.8%). Most patients for whom data were available presented with Hurley stage II (50.4%), and more than a third of the full analysis set had a relative with HS (34.7%). Questionnaire responses revealed a profound impact on quality of life, including diminished work productivity and various psychological comorbidities. CONCLUSION: This study offers insight into the clinical features and disease burden of hidradenitis suppurativa in an Irish population.
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Hidradenitis Supurativa/epidemiología , Actividades Cotidianas , Adulto , Costo de Enfermedad , Estudios Transversales , Eficiencia , Estudios Epidemiológicos , Femenino , Hidradenitis Supurativa/tratamiento farmacológico , Hidradenitis Supurativa/psicología , Humanos , Irlanda/epidemiología , Masculino , Prevalencia , Calidad de Vida , TrabajoRESUMEN
WHAT IS KNOWN AND OBJECTIVE: Prothrombin complex concentrate (PCC) is a plasma-derived concentrate used to replenish clotting factors. There are limited recommendations for treating coagulopathy induced by direct oral anticoagulants (DOAC). Data are limited regarding both total dose and repeated dosing with this population. CASE SUMMARY: We describe a case of an adult patient anticoagulated with apixaban who received two 35 unit/kg doses of PCC resulting in suspected pulmonary embolism. WHAT IS NEW AND CONCLUSION: Treatment of DOAC-induced bleeding remains an "off-label" indication for PCC. Additional doses should be given with caution if given at all and patients monitored closely.
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Factores de Coagulación Sanguínea/administración & dosificación , Inhibidores del Factor Xa/efectos adversos , Embolia Pulmonar/etiología , Pirazoles/efectos adversos , Piridonas/efectos adversos , Anciano , Factores de Coagulación Sanguínea/efectos adversos , Inhibidores del Factor Xa/administración & dosificación , Hemorragia/inducido químicamente , Hemorragia/terapia , Humanos , Masculino , Uso Fuera de lo Indicado , Embolia Pulmonar/patología , Pirazoles/administración & dosificación , Piridonas/administración & dosificaciónRESUMEN
Fasting of up to 24 hr has been shown to increase intestinal permeability (IP) in chickens. The aim of this study was to determine whether fasting duration of 4.5 and 9 hr increased IP and whether l-glutamine (a non-essential amino acid) supplementation before fasting provided some protection of barrier function as shown in other species. Ross 308 male broilers (n = 96) were fed either a control diet or the same diet supplemented with 1% glutamine from d0 to d38 post-hatch. On d37, the birds were assigned to single-bird metabolism cages and were fasted for either 0, 4.5, 9 or 19.5 hr. This study design was 2 × 4 factorial with two levels of glutamine and four levels of fasting. Birds in the 0-hr fasting group had free access to feed. All birds had ad libitum access to water. To measure IP on day 38, following their respective fasting periods, birds were administered two separate oral gavages of fluorescein isothiocyanate dextran (FITC-d) followed by lactulose, mannitol and rhamnose (LMR) sugars, 60 min apart. Whole blood was collected from the jugular vein 90 min post-LMR sugar gavage. FITC-d and L/M/R ratios were measured by spectrophotometry and high-performance ionic chromatography respectively. Lipopolysaccharide (LPS) endotoxins in plasma of the birds fed the control diet were also measured using chicken-specific LPS antibody ELISA. Serum FITC-d and plasma L/M and L/R ratios for 4.5, 9 and 19.5 hr were significantly (p < .05) higher compared to the non-fasting group. However, IP was not different in the glutamine-supplemented group (p > .05) compared to the control group. LPS concentrations measured by the ELISA were below the detectable range. We conclude that fasting periods of 4.5 and 9 hr increased IP compared to non-fasted birds and dietary glutamine supplementation did not ameliorate changes in IP.
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Pollos/fisiología , Privación de Alimentos , Alimentación Animal/análisis , Animales , Dextranos , Dieta/veterinaria , Fluoresceína-5-Isotiocianato/análogos & derivados , Glutamina , Intestinos , Lactulosa/sangre , Masculino , Manitol/sangre , Permeabilidad , Ramnosa/sangre , Factores de TiempoRESUMEN
Short-term fasting for 4.5 and 9 hr has been demonstrated to increase intestinal permeability (IP) in chickens. This study aimed to investigate the effects of 0, 4.5, 9 and 19.5 hr fasting on intestinal gene expression and villus-crypt architecture of enterocytes in jejunal and ileal samples. On day 38, Ross-308 male birds were fasted according to their group and then euthanised. Two separate intestinal sections (each 2 cm long, jejunum and ileum) were collected. One section was utilised for villus height and crypt depth measurements. The second section was snap-frozen in liquid nitrogen for quantitative polymerase chain reaction (qPCR) analysis of tight junction proteins (TJP) including claudin-1, claudin-3, occludin, zonula occludens (ZO-1, ZO-2), junctional adhesion molecules (JAM) and E-cadherin. Additionally genes involved in enterocyte protection including glucagon-like peptide (GLP-2), heat-shock protein (HSP-70), intestinal alkaline phosphatase (IAP), mammalian target of rapamycin (mTOR), toll-like receptors (TLR-4), mucin (MUC-2), cluster differentiation (CD-36) and fatty acid-binding protein (FABP-6) were also analysed. Normally distributed data were analysed using one-way analysis of variance ANOVA. Other data were analysed by non-parametric one-way ANOVA. Villus height and crypt depth were increased (p < .05) only in the ileum after fasting for 4.5 and 9 hr compared with non-fasting group. mRNA expression of claudin-3 was significantly reduced in the ileum of birds fasted for 9 and 19.5 hr, suggesting a role in IP modulation. However, all other TJP genes examined were not statistically different from control. Nevertheless, ileal FABP-6 of all fasted groups was significantly reduced, which could possibly be due to reduced bile acid production during fasting.
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Pollos/fisiología , Privación de Alimentos , Regulación de la Expresión Génica/fisiología , Mucosa Intestinal/fisiología , Animales , Masculino , Permeabilidad , Reacción en Cadena de la Polimerasa/métodos , Reacción en Cadena de la Polimerasa/veterinaria , Factores de Tiempo , TranscriptomaRESUMEN
BACKGROUND: One in three patients hospitalised due to acute exacerbation of COPD (AECOPD) is readmitted within 90â days. No tool has been developed specifically in this population to predict readmission or death. Clinicians are unable to identify patients at particular risk, yet resources to prevent readmission are allocated based on clinical judgement. METHODS: In participating hospitals, consecutive admissions of patients with AECOPD were identified by screening wards and reviewing coding records. A tool to predict 90-day readmission or death without readmission was developed in two hospitals (the derivation cohort) and validated in: (a) the same hospitals at a later timeframe (internal validation cohort) and (b) four further UK hospitals (external validation cohort). Performance was compared with ADO, BODEX, CODEX, DOSE and LACE scores. RESULTS: Of 2417 patients, 936 were readmitted or died within 90â days of discharge. The five independent variables in the final model were: Previous admissions, eMRCD score, Age, Right-sided heart failure and Left-sided heart failure (PEARL). The PEARL score was consistently discriminative and accurate with a c-statistic of 0.73, 0.68 and 0.70 in the derivation, internal validation and external validation cohorts. Higher PEARL scores were associated with a shorter time to readmission. CONCLUSIONS: The PEARL score is a simple tool that can effectively stratify patients' risk of 90-day readmission or death, which could help guide readmission avoidance strategies within the clinical and research setting. It is superior to other scores that have been used in this population. TRIAL REGISTRATION NUMBER: UKCRN ID 14214.
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Readmisión del Paciente/tendencias , Enfermedad Pulmonar Obstructiva Crónica/mortalidad , Medición de Riesgo , Enfermedad Aguda , Anciano , Causas de Muerte/tendencias , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Pronóstico , Enfermedad Pulmonar Obstructiva Crónica/terapia , Curva ROC , Factores de Riesgo , Tasa de Supervivencia/tendencias , Reino Unido/epidemiologíaRESUMEN
Hidradenitis suppurativa (HS) is a cutaneous disease associated with systemic inflammation, obesity and metabolic syndrome. Effective treatment options are limited. The antidiabetic agents, incretins, have been used successfully to treat psoriasis - a disease also associated with metabolic syndrome. We report the use of liraglutide, a glucagon-like peptide-1 agonist, in a patient with HS, leading to subsequent weight loss and improvement in disease control. To our knowledge, this is the first report of liraglutide used in the treatment of HS.
Asunto(s)
Hidradenitis Supurativa/tratamiento farmacológico , Hipoglucemiantes/uso terapéutico , Liraglutida/uso terapéutico , Adulto , Femenino , Humanos , Resultado del Tratamiento , Pérdida de Peso/efectos de los fármacosRESUMEN
Plant invasion typically occurs within a landscape-scale framework of abiotic and biotic conditions, often resulting in emergent feedbacks among environment, ecosystem functions, and the dominance of invasive species. Understanding the mechanisms underlying successful invasions is an important component of conservation and management efforts, but this has been poorly investigated in a spatially explicit manner. Knowing where and why invasion patterns change throughout the landscape enables managers to use context-specific controls on the spread of invasive species. Using high-resolution airborne imaging spectroscopy, we studied plant performance in growth within and across landscapes to examine the dominance and spatial distribution of an invasive tree, Psidium cattleianum (strawberry guava), in heterogeneous environmental conditions of a submontane Hawaiian tropical forest. We assessed invader performance using the GPP ratio index, which is the relative difference in remotely sensed estimates of gross primary productivity between canopies of guava and canopies of the invaded plant community. In addition, we used airborne LiDAR data to evaluate the impacts of guava invasion on the forest aboveground carbon density in different environments. Structural equation modeling revealed that substrate type and elevation above sea level interact and amplify landscape-scale differences in productivity between the invasive species and the host plant community (GPP ratio); differences that ultimately control levels of dominance of guava. We found shifts in patterns of forest carbon storage based on both gradual increase of invader dominance and changes in environmental conditions. Overall, our results demonstrate that the remotely sensed index defined as the GPP ratio provided an innovative spatially explicit approach to track and predict the success of invasive plants based in their canopy productivity, particularly within a landscape-scale framework of varying environmental factors such as soils and elevation. This approach may help managers accurately predict where invaders of forests, scrublands, or grasslands are likely to exhibit high levels of dominance before the environment is fully invaded.