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Indigenous perspectives of quality of life (QoL) are different to that of non-Indigenous populations. Determining how to identify and value what is important to QoL for people from diverse cultural backgrounds is crucial for assessing effective outcomes for quality assessment and health economic evaluation to guide evidence-based decision making. This is particularly important for older Indigenous people who have complex care and support needs within health and aged-care systems. This scoping review aims to assess the existing literature in this field by firstly identifying preference based instruments that have been applied with older Indigenous peoples and secondly, exploring the extent to which existing preference based instruments applied with older Indigenous peoples encompass older Indigenous peoples QoL perspectives in their design and application. The inclusion criteria for the review were studies using preference based QoL instruments with an Indigenous population where the cohort was aged 50 years or over. This resulted in the critical analysis of 12 studies. The review identified that preference based QoL instruments have rarely been applied to date with older Indigenous populations with most instruments found to be designed for non-Indigenous adults. Typically, instruments have not incorporated Indigenous worldviews of QoL into either the content of the descriptive system or the elicitation techniques and corresponding value sets generated. To encapsulate Indigenous cultural perspectives accurately in economic evaluation, further research is required as to how QoL domains in preference based instruments for Indigenous peoples can be reflective of Indigenous perspectives. It is imperative that the QoL preferences of older Indigenous peoples are adequately captured within preference based QoL instruments applied with this population.
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Cultura , Calidad de Vida , Adulto , Humanos , Pueblos Indígenas , Grupos de PoblaciónRESUMEN
Introduction: Reported confirmed cases represent a small portion of overall true cases for many infectious diseases. The undercounting of true cases can be considerable when a significant portion of infected individuals are asymptomatic or minimally symptomatic, as is the case with COVID-19. Seroprevalence studies are an efficient way to assess the extent to which true cases are undercounted during a large-scale outbreak and can inform efforts to improve case identification and reporting. Methods: A longitudinal seroprevalence study of active duty U.S. military members was conducted from May 2020 through June 2021. A random selection of service member serum samples submitted to the Department of Defense Serum Repository was analyzed for the presence of antibodies reactive to SARS-CoV-2. The monthly seroprevalence rates were compared with those of cumulative confirmed cases reported during the study period. Results: Seroprevalence was 2.3% in May 2020 and increased to 74.0% by June 2021. The estimated true case count based on seroprevalence was 9.3 times greater than monthly reported cases at the beginning of the study period and fell to 1.7 by the end of the study. Conclusions: In our sample, confirmed case counts significantly underestimated true cases of COVID-19. The increased availability of testing over the study period and enhanced efforts to detect asymptomatic and minimally symptomatic cases likely contributed to the fall in the seroprevalence to reported case ratio.
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Microneedle Array Patches (MAPs) are an emerging dosage form that creates transient micron-sized disruptions in the outermost physical skin barrier, the stratum corneum, to facilitate delivery of active pharmaceutical ingredients to the underlying tissue. Numerous MAP products are proposed and there is significant clinical potential in priority areas such as vaccination. However, since their inception scientists have hypothesized about the risk of a clinically significant MAP-induced infection. Safety data from two major Phase 3 clinical trials involving hundreds of participants, who in total received tens of thousands of MAP applications, does not identify any clinically significant infections. However, the incumbent data set is not extensive enough to make definitive generalizable conclusions. A comprehensive assessment of the infection risk is therefore advised for MAP products, and this should be informed by clinical and pre-clinical data, theoretical analysis and informed opinions. In this article, a group of key stakeholders identify some of the key product- and patient-specific factors that may contribute to the risk of infection from a MAP product and provide expert opinions in the context of guidance from regulatory authorities. Considerations that are particularly pertinent to the MAP dosage form include the specifications of the finished product (e.g. microbial specification), it's design features, the setting for administration, the skill of the administrator, the anatomical application site, the target population and the clinical context. These factors, and others discussed in this article, provide a platform for the development of MAP risk assessments and a stimulus for early and open dialogue between developers, regulatory authorities and other key stakeholders, to expedite and promote development of safe and effective MAP products.
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Sistemas de Liberación de Medicamentos , Piel , Humanos , Administración Cutánea , Epidermis , Agujas , Preparaciones Farmacéuticas , Medición de Riesgo , Ensayos Clínicos Fase III como AsuntoRESUMEN
OBJECTIVE: Improving the quality of life (QoL) of older people is a key priority for governments, clinicians, researchers and service providers worldwide. However, the lack of culturally appropriate QoL tools for First Nations people is a major barrier to such efforts. The purpose of this study was to evaluate the psychometric properties of the Good Spirit, Good Life (GSGL) QoL tool for older Aboriginal Australians. METHODS: One hundred and twenty older Aboriginal people living in Perth and Melbourne, Australia, were administered the GSGL tool, along with several other instruments assessing cognition (KICA-Cog), depression (KICA-Dep), anxiety (GAI-SF), health and well-being (EQ-5D-5L and ICECAP-O) and resilience (ARRQ-25). Associations between these instruments and the GSGL tool were explored to determine concurrent and known-groups validity. Internal consistency was assessed with split-half reliability and Cronbach's alpha. Exploratory factor analysis was performed to investigate construct validity. RESULTS: GSGL scores were positively correlated with ICECAP-O and ARRQ-25 scores, and negatively correlated with EQ-5D-5L score. GSGL scores differed significantly between participants with a probable anxiety disorder or depression, but not those with cognitive impairment. The Spearman-Brown prophecy estimate was 0.83 and Cronbach's alpha was 0.75. Principal component analysis identified two factors, which were labelled foundation and external. CONCLUSIONS: The GSGL tool is a valid tool to assess quality of life in older Aboriginal Australians. The tool demonstrates acceptable convergent, concurrent and known-groups validity. It was co-designed at all stages with older Aboriginal people contributing to its strong face and content validity.
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Aborigenas Australianos e Isleños del Estrecho de Torres , Salud Mental , Calidad de Vida , Anciano , Humanos , Australia , Aborigenas Australianos e Isleños del Estrecho de Torres/psicología , Calidad de Vida/psicología , Reproducibilidad de los Resultados , Encuestas y Cuestionarios , Psicometría , Competencia Cultural , Salud Mental/etnología , Salud Mental/estadística & datos numéricosRESUMEN
This report describes SARS-CoV-2 genomic surveillance conducted by the Department of Defense (DoD) Global Emerging Infections Surveillance Branch and the Next-Generation Sequencing and Bioinformatics Consortium (NGSBC) in response to the COVID-19 pandemic. Samples and sequence data were from SARS-CoV-2 infections occurring among Military Health System (MHS) beneficiaries from 1 March to 31 December 2020. There were 1,366 MHS samples sequenced from 10 countries, 36 U.S states or territories, and 5 Geographic Combatant Commands, representing approximately 2% of DoD cases in 2020. Genomes from these samples were compared with other public sequences; observed trends were similar to those of Centers for Disease Control and Prevention national surveillance in the U.S. with B.1, B.1.2, and other sub-lineages comprising the dominant variants of SARS-CoV-2. Sequence data were used to monitor transmission dynamics on U.S. Navy ships and at military training centers and installations. As new variants emerge, DoD medical and public health practitioners should maximize the use of genomic surveillance resources within DoD to inform force health protection measures.
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COVID-19 , Servicios de Salud Militares , Personal Militar , COVID-19/epidemiología , Genómica , Humanos , Pandemias , SARS-CoV-2/genéticaRESUMEN
Objective: Previous studies have reported conflicting findings regarding aldosterone levels in patients hospitalised with COVID-19. We therefore used the gold-standard technique of liquid chromatography-tandem mass spectrometry (LCMSMS) to address this uncertainty. Design: All patients admitted to Cambridge University Hospitals with COVID-19 between 10 March 2020 and 13 May 2021, and in whom a stored blood sample was available for analysis, were eligible for inclusion. Methods: Aldosterone was measured by LCMSMS and by immunoassay; cortisol and renin were determined by immunoassay. Results: Using LCMSMS, aldosterone was below the limit of detection (<70 pmol/L) in 74 (58.7%) patients. Importantly, this finding was discordant with results obtained using a commonly employed clinical immunoassay (Diasorin LIAISON®), which over-estimated aldosterone compared to the LCMSMS assay (intercept 14.1 (95% CI -34.4 to 54.1) + slope 3.16 (95% CI 2.09-4.15) pmol/L). The magnitude of this discrepancy did not clearly correlate with markers of kidney or liver function. Solvent extraction prior to immunoassay improved the agreement between methods (intercept -14.9 (95% CI -31.9 to -4.3) and slope 1.0 (95% CI 0.89-1.02) pmol/L) suggesting the presence of a water-soluble metabolite causing interference in the direct immunoassay. We also replicated a previous finding that blood cortisol concentrations were often increased, with increased mortality in the group with serum cortisol levels > 744 nmol/L (P = 0.005). Conclusion: When measured by LCMSMS, aldosterone was found to be profoundly low in a significant proportion of patients with COVID-19 at the time of hospital admission. This has likely not been detected previously due to high levels of interference with immunoassays in patients with COVID-19, and this merits further prospective investigation.
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OBJECTIVES: The aim of this study was to determine the appropriate transport and storage conditions for blood taken for direct renin concentration and plasma renin activity measurement, and whether cryoactivation of prorenin is seen at time points relevant to clinical practice. METHODS: Blood was extracted from n=10 volunteers into K2-EDTA tubes. Stability of renin was assessed in whole blood stored at room temperature (15-25 °C) and in the refrigerator (2-8 °C) at 0 h, 8 h, and 24 h. The stability of renin in plasma was determined under the same conditions at 0 h, 24 h and 72 h. RESULTS: Stability of plasma renin activity and direct renin concentration in whole blood stored at room temperature was found to be acceptable for up to 24 h. At refrigerated temperature, whole blood stability was acceptable for measurement of direct renin concentration up to 8 h and plasma renin activity up to 24 h. In contrast, plasma renin activity was not stable in plasma stored at either room or refrigerated temperatures up to 24 h; however, direct renin concentration had acceptable stability in plasma stored at room temperature for up to 24 h, but stability was unacceptable at refrigerated temperatures. CONCLUSIONS: Samples collected for plasma renin activity and direct renin concentration should be transported as whole blood to optimise stability. After sample processing, plasma can be kept at room temperature for up to 24 h for direct renin concentration, however, for determination of plasma renin activity separated plasma should be analysed or frozen as soon as possible.
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Plasma , Renina , Recolección de Muestras de Sangre , Ácido Edético , Humanos , TemperaturaRESUMEN
HYPOTHESIS: External beam radiation therapy (XRT) is a commonly used treatment adjunct in patients with breast cancer and is known to cause soft tissue dysfunction. However, data on XRT as a preoperative risk factor for shoulder surgery is limited. The purpose of this study was to assess whether prior history of breast cancer treated with XRT has an impact on surgical complications or outcomes. We hypothesize that patients treated with XRT will have a higher rate of surgical complications and lower outcomes. METHODS: A 20-year retrospective chart review across a large, academic health care system was performed. Inclusion criterion comprised any patient with history of breast cancer of the upper-outer or axillary region treated with XRT. Patients also must have undergone a surgical procedure to the ipsilateral shoulder with at least 1-year postoperative follow-up. Patients were stratified by demographics, hand dominance, and surgery type. Postoperative outcomes including range of motion (ROM) and visual analog scale (VAS) scores for pain were also collected. RESULTS: Eighteen patients were identified (100% female) with an average age of 66.3 years (standard deviation 10.5 years). Ten shoulders underwent rotator cuff repair (RCR), 4 total shoulder arthroplasty (TSA), 3 reverse shoulder arthroplasty (RSA), and 1 arthroscopic superior labrum anterior to posterior (SLAP) repair. Four patients treated with RCR (40%) experienced postoperative complications related to their procedure. These included scapular winging, adhesive capsulitis, stiffness, and one retear. Two patients treated with shoulder arthroplasty (28.6%) experienced postoperative complications that included lymphedema and periprosthetic fracture following a mechanical fall in one RSA patient and periprosthetic infection in a TSA patient. ROM across all groups improved, most significantly in forward flexion and internal rotation among RCR patients (P < .001). Furthermore, a statistically significant improvement in VAS scores was achieved in each group (6.2 ± 2.14 preoperation, 1.06 ± 1.75 postoperation; P < .001). CONCLUSION: When compared to national averages, complication rates in our cohort were higher (40% vs. 10%-17% in RCR patients and 28.6% vs. 4%-14% in arthroplasty patients). On further scrutiny, many of these complications were independent of a history of XRT and many resolved with appropriate therapy. Most importantly, functional outcomes as measured by ROM and pain scores showed appropriate improvement consistent with normal populations without history of XRT. Thus, our results suggest that performing shoulder surgery after ipsilateral XRT for breast cancer is likely safe and may offer improved pain and ROM compared to forgoing surgery without necessarily increasing the risk for postoperative complication.
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Artroplastía de Reemplazo de Hombro , Neoplasias de la Mama , Lesiones del Manguito de los Rotadores , Articulación del Hombro , Anciano , Artroplastía de Reemplazo de Hombro/efectos adversos , Neoplasias de la Mama/etiología , Neoplasias de la Mama/radioterapia , Neoplasias de la Mama/cirugía , Femenino , Humanos , Masculino , Dolor/etiología , Complicaciones Posoperatorias/etiología , Rango del Movimiento Articular , Reoperación , Estudios Retrospectivos , Lesiones del Manguito de los Rotadores/cirugía , Hombro/cirugía , Articulación del Hombro/cirugía , Resultado del TratamientoRESUMEN
INTRODUCTION: We present an unusual case of rhabdomyolysis secondary to Mycoplasma pneumoniae in a healthy 27-year-old female. M. pneumoniae is associated with numerous extrapulmonary manifestations, including acute hepatitis, Stevens-Johnson syndrome, and rhabdomyolysis. Most documented cases affect the pediatric population, with only five cases in adults reported in the literature. CASE REPORT: The patient presented with complaints of myalgia and intractable cough. In this case the initial presentation demonstrated hypoxia requiring supplemental oxygen, and a creatine kinase of 7,646 units per liter (U/L) (reference range 26-192 U/L) with a peak of 29,427. During her hospitalization, she also remained persistently hypoxic for several days but ultimately was successfully weaned off all supplemental oxygen. She was discharged home after a seven-day hospitalization. CONCLUSION: This patient's presentation of an insidious, upper respiratory infection along with the subsequent development of rhabdomyolysis with reactive antibodies to M. pneumoniae demonstrates a link between these two clinically important conditions.
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Understanding the speciation and fate of radium during operational discharge from the offshore oil and gas industry into the marine environment is important in assessing its long term environmental impact. In the current work, 226Ra concentrations in marine sediments contaminated by produced water discharge from a site in the UK were analysed using gamma spectroscopy. Radium was present in field samples (0.1-0.3 Bq g-1) within International Atomic Energy Agency activity thresholds and was found to be primarily associated with micron sized radiobarite particles (≤2 µm). Experimental studies of synthetic/field produced water and seawater mixing under laboratory conditions showed that a significant proportion of radium (up to 97%) co-precipitated with barite confirming the radiobarite fate pathway. The results showed that produced water discharge into the marine environment results in the formation of radiobarite particles which incorporate a significant portion of radium and can be deposited in marine sediments.
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Radio (Elemento) , Contaminantes Radiactivos del Agua , Industrias , Radio (Elemento)/análisis , Agua de Mar , Agua , Contaminantes Radiactivos del Agua/análisisRESUMEN
BACKGROUND AND OBJECTIVES: The lack of appropriate quality of life (QoL) measures is a major barrier to planning and delivering health and aged care services for older Indigenous peoples worldwide. QoL is dependent on cultural values and priorities may vary between age groups. This project aims to develop a QoL tool for older Aboriginal Australians. RESEARCH DESIGN AND METHODS: The study was completed with Aboriginal Australians aged over 45 years living in Perth and Melbourne, Australia. Participatory Action Research methods were applied with an Indigenous research paradigm. Semistructured interviews were undertaken to identify the factors important to having a good life. Factors were further explored in yarning groups with older Aboriginal peoples to develop the draft QoL tool questions. Face validity of the tool was completed in two regions. RESULTS: The participants preferred the term "a good life" to QoL. Having a good spirit is at the core of having a good life. The protective factors for a good life were family and friends, health, culture, Elder role, respect, Country, spirituality, services and supports, community, future plans, safety and security, and basic needs. DISCUSSION AND IMPLICATIONS: Twelve factors were identified and developed into key questions for the Good Spirit, Good Life tool. The draft tool will undergo quantitative validity testing, prior to embedding in service provision to inform care for older Aboriginal peoples. With local adaptation, the tool, accompanying framework, and participatory methods for development may have wider applicability to other Indigenous populations worldwide.
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Servicios de Salud del Indígena , Calidad de Vida , Anciano , Australia , Investigación sobre Servicios de Salud , Humanos , Nativos de Hawái y Otras Islas del Pacífico , Proyectos de InvestigaciónRESUMEN
HYPOTHESIS: College pitchers with increased external rotation gain (ERG) produce increased medial elbow torque (elbow stress) whereas those with reduced total rotational range of motion (ROM) have reduced medial elbow torque during pitching. METHODS: Pitchers were recruited from 3 college baseball teams. Players with prior injury or on pitching restrictions because of pain were excluded. Players were evaluated within 2 weeks before their first game of the season. Pitchers completed an intake survey, and shoulder and arm measurements were taken. Pitchers were fitted with a baseball sleeve that included a sensor at the medial elbow. The sensor calculated elbow torque, arm speed, arm slot, and shoulder rotation for each pitch, while a radar gun measured peak ball velocity. After adequate warm-up, pitchers threw 5 fastballs in a standardized manner off the mound at game-speed effort. The primary outcome evaluated the relationship between shoulder ROM and medial elbow torque. Additional outcomes evaluated pitcher characteristics and demographic characteristics in the context of shoulder ROM. RESULTS: Twenty-eight pitchers were included in the preseason analysis. The average age and playing experience were 20.1 years (standard deviation [SD], 1.3 years) and 15.3 years (SD, 1.8 years), respectively, with 2.5 years (SD, 1.2 years) playing at collegiate level. The dominant shoulder showed decreased internal rotation and increased external rotation (ER) relative to the nondominant side (P < .001). The average glenohumeral internal rotation deficit and ERG were 11.3° (SD, 9.87°) and 5.71° (SD, 8.8°), respectively. ERG ≥ 5° was a significant predictor of elbow stress during pitching (47.4 Nm [SD, 0.7 Nm] vs. 45.1 Nm [SD, 0.6 Nm], P = .014). Univariate associations showed that each additional degree of ER resulted in increased elbow torque (ß estimate, 0.35 ± 0.06 Nm; P = .003). Conversely, decreased medial elbow torque was found in pitchers with reduced shoulder ROM (glenohumeral internal rotation deficit ≥ 20°: 43.5 Nm [SD, 1.1 Nm] vs. 46.6 Nm [SD, 0.5 Nm], P = .011; loss of total rotational ROM ≥ 5°: 43.6 Nm [SD, 1.1 Nm] vs. 46.6 Nm [SD, 0.5 Nm], P = .013) and in those with greater arm length (P < .05). CONCLUSIONS: College pitchers with increased ER produce greater medial elbow torque during the pitching movement. Each degree of increased ER was found to correlate with increased elbow torque and ball velocity. On the contrary, arm length and reduced shoulder ROM were associated with reduced medial elbow torque. This study suggests that increased ER in pitchers is associated with greater elbow stress during pitching.
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Béisbol , Articulación del Codo , Articulación del Hombro , Fenómenos Biomecánicos , Codo , Humanos , Rango del Movimiento Articular , Rotación , HombroRESUMEN
Induced pluripotent stem cell (iPSC)-derived neural cultures from amyotrophic lateral sclerosis (ALS) patients can model disease phenotypes. However, heterogeneity arising from genetic and experimental variability limits their utility, impacting reproducibility and the ability to track cellular origins of pathogenesis. Here, we present methodologies using single-cell RNA sequencing (scRNA-seq) analysis to address these limitations. By repeatedly differentiating and applying scRNA-seq to motor neurons (MNs) from healthy, familial ALS, sporadic ALS, and genome-edited iPSC lines across multiple patients, batches, and platforms, we account for genetic and experimental variability toward identifying unified and reproducible ALS signatures. Combining HOX and developmental gene expression with global clustering, we anatomically classified cells into rostrocaudal, progenitor, and postmitotic identities. By relaxing statistical thresholds, we discovered genes in iPSC-MNs that were concordantly dysregulated in postmortem MNs and yielded predictive ALS markers in other human and mouse models. Our approach thus revealed early, convergent, and MN-resolved signatures of ALS.
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Esclerosis Amiotrófica Lateral/genética , Células Madre Pluripotentes Inducidas/metabolismo , Neuronas Motoras/metabolismo , Animales , Modelos Animales de Enfermedad , Humanos , RatonesRESUMEN
Dutasteride, licensed as an oral medicine for the treatment of benign prostatic hypoplasia, has been investigated as a treatment for androgenic alopecia. In this study, the potential for dustasteride to be delivered topically in order to reduce systemic exposure, irritation of the skin, and also cytotoxicity was explored. Chitosan oligomer (CSO) was successfully synthesised with lauric acid as a coating for a dutasteride-loaded nanostructured lipid carriers (DST-NLCs) system. DST-NLCs were prepared using a combination of melt-dispersion and ultrasonication. These negatively charged NLCs (-18.0 mV) had a mean particle size of ~184 nm, which was not significantly increased (p > 0.05) when coated with lauric acid-chitosan oligomer (CSO-LA), whilst the surface charge changed to positive (+24.8 mV). The entrapment efficiency of DST-NLCs was 97%, and coated and uncoated preparations were physically stable for up to 180 days at 4-8 °C. The drug release was slower from DST-NLCs coated with CSO-LA than from uncoated NLCs, with no detectable drug permeation through full-thickness pig ear skin from either preparation. Considering the cytotoxicity, the IC50 values for the DST-NLCs, coated and uncoated with CSO-LA were greater than for dutasteride alone (p < 0.05). DST-NLCs and empty NLCs coated with CSO-LA at 25 µM increased the cell proliferation compared to the control, and no skin irritation was observed when the DST-NLC formulations were tested using EpiDerm™. The cell and skin uptake studies of coated and uncoated NLCs incorporating the fluorescent marker Coumarin-6 showed the time-dependent uptake of Coumarin-6. Overall, the findings suggest that DST-NLCs coated with CSO-LA represent a promising formulation strategy for dutasteride delivery for the treatment of androgenic alopecia, with a reduced cytotoxicity compared to that of the drug alone and lower irritancy than an ethanolic solution of dutasteride.
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A 23-year-old man and his grandmother with hyperthyroxinemia and hypercortisolemia were heterozygous for an ALB mutation (p. Arg218Pro), known to cause familial dysalbuminemic hyperthyroxinemia (FDH). However, serum-free cortisol levels in these individuals were normal and total cortisol concentrations fell markedly after depletion of albumin from their serum. We conclude that binding of steroid as well as iodothyronines to mutant albumin causes raised circulating cortisol as well as thyroid hormones in euthyroid euadrenal individuals with R218P FDH, with potential for misdiagnosis, unnecessary investigation, and inappropriate treatment.
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Hidrocortisona/sangre , Hipertiroxinemia Disalbuminémica Familiar/complicaciones , Hipertiroxinemia/complicaciones , Mutación , Albúmina Sérica Humana/genética , Albúminas/química , Genotipo , Heterocigoto , Humanos , Inmunoensayo , Masculino , Personal Militar , Unión Proteica , Albúmina Sérica/genética , Esteroides/química , Tironinas/sangre , Tiroxina/sangre , Adulto JovenRESUMEN
PURPOSE: To report outcomes of yttrium-90 (90Y) radioembolization in patients with unresectable intrahepatic cholangiocarcinoma (ICC). MATERIALS AND METHODS: Retrospective review was performed of 115 patients at 6 tertiary care centers; 92 were treated with resin microspheres (80%), 22 were treated with glass microspheres (19%), and 1 was treated with both. Postintervention outcomes were compared between groups with χ2 tests. Survival after diagnosis and after treatment was assessed by Kaplan-Meier method. RESULTS: Grade 3 laboratory toxicity was observed in 4 patients (4%); no difference in toxicity profile between resin and glass microspheres was observed (P = .350). Clinical toxicity per Society of Interventional Radiology criteria was noted in 29 patients (25%). Partial response per Response Evaluation Criteria In Solid Tumors 1.1 was noted in 25% of patients who underwent embolization with glass microspheres and 3% of patients who were treated with resin microspheres (P = .008). Median overall survival (OS) from first diagnosis was 29 months (95% confidence interval [CI], 21-37 mo) for all patients, and 1-, 3-, and 5-year OS rates were 85%, 31%, and 8%, respectively. Median OS after treatment was 11 months (95% CI, 8-13 mo), and 1- and 3-year OS rates were 44% and 4%, respectively. These estimates were not significantly different between resin and glass microspheres (P = .730 and P = .475, respectively). Five patients were able to undergo curative-intent resection after 90Y radioembolization (4%). CONCLUSIONS: This study provides observational data of treatment outcomes after 90Y radioembolization in patients with unresectable ICC.
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Neoplasias de los Conductos Biliares/radioterapia , Colangiocarcinoma/radioterapia , Embolización Terapéutica , Radiofármacos/administración & dosificación , Radioisótopos de Itrio/administración & dosificación , Neoplasias de los Conductos Biliares/diagnóstico por imagen , Neoplasias de los Conductos Biliares/mortalidad , Neoplasias de los Conductos Biliares/patología , Colangiocarcinoma/diagnóstico por imagen , Colangiocarcinoma/mortalidad , Colangiocarcinoma/patología , Embolización Terapéutica/efectos adversos , Embolización Terapéutica/mortalidad , Femenino , Humanos , Masculino , Radiofármacos/efectos adversos , Estudios Retrospectivos , Factores de Tiempo , Resultado del Tratamiento , Radioisótopos de Itrio/efectos adversosRESUMEN
Here we describe the first automated fully integrated in-microscope broad ion beam (BIB) system. Ar+-BIB has several advantages over Ga+ focused ion beam (FIB) and Xe+ plasma-FIB (PFIB) methods inducing less beam damage, especially for ion beam sensitive materials. It can mill areas several orders of magnitude larger (up to millimetre scale), and is not confined to the edge of the sample with associated curtaining issues. BIB is shown to have sputter rates up to five times higher than comparable FIB techniques. This new coupled BIB-SEM system (commercial name 'iPrep™II') enables in-microscope surface polishing to remove contaminants or damage for two dimensional (2D) imaging, as well as automated serial section tomography (SST) by milling and imaging hundreds of slices, cost and time efficiently. The milled slice thickness can be controlled from a few nanometers up to a micrometre. A novel sample transfer, handling and interlock system allows automated and sequential BIB polishing, scanning electron microscopy (SEM) and analysis by secondary electron (SE) imaging, electron back scatter diffraction (EBSD) and energy dispersive spectroscopy (EDS) for 3D microstructure analysis. Furthermore, insulating surfaces can be sputter coated after milling each slice to reduce charging during SEM analysis. The performance of the instrument is demonstrated through a series of case studies across the materials, earth and life sciences exploiting the imaging, crystallographic and chemical mapping capabilities. These include the study of butterfly defects in bearing steels, meta-stable intermetallic phases in bronze bearings, shale gas rock, aluminium plasma electrolytic oxide (PEO) coatings as well as liver and mouse brain tissues.
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Automatización/métodos , Angiografía por Tomografía Computarizada/métodos , Imagenología Tridimensional/métodos , Iones/química , Animales , Encéfalo/citología , Encéfalo/ultraestructura , Técnicas Histológicas/métodos , Procesamiento de Imagen Asistido por Computador/métodos , Hígado/citología , Hígado/ultraestructura , Ciencia de los Materiales/métodos , Ratones , Microscopía Electrónica de Rastreo/métodos , Microtomía/métodosRESUMEN
Produced waters from hydraulically fractured shale formations give insight into the microbial ecology and biogeochemical conditions down-well. This study explores the potential for sulfide production by persistent microorganisms recovered from produced water samples collected from the Marcellus shale formation. Hydrogen sulfide is highly toxic and corrosive, and can lead to the formation of "sour gas" which is costly to refine. Furthermore, microbial colonization of hydraulically fractured shale could result in formation plugging and a reduction in well productivity. It is vital to assess the potential for sulfide production in persistent microbial taxa, especially when considering the trend of reusing produced waters as input fluids, potentially enriching for problematic microorganisms. Using most probable number (MPN) counts and 16S rRNA gene sequencing, multiple viable strains of bacteria were identified from stored produced waters, mostly belonging to the Genus Halanaerobium, that were capable of growth via fermentation, and produced sulfide when supplied with thiosulfate. No sulfate-reducing bacteria (SRB) were detected through culturing, despite the detection of relatively low numbers of sulfate-reducing lineages by high-throughput 16S rRNA gene sequencing. These results demonstrate that sulfidogenic produced water populations remain viable for years post production and, if left unchecked, have the potential to lead to natural gas souring during shale gas extraction.
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OBJECTIVE: Familial dysalbuminaemic hyperthyroxinaemia (FDH), most commonly due to an Arginine to Histidine mutation at residue 218 (R218H) in the albumin gene, causes artefactual elevation of free thyroid hormones in euthyroid individuals. We have evaluated the susceptibility of most current free thyroid hormone immunoassay methods used in the United Kingdom, Europe and Far East to interference by R218H FDH. METHODS: Different, one- and two-step immunoassay methods were tested, measuring free T4 (FT4) and free T3 (FT3) in 37 individuals with genetically proven R218H FDH. RESULTS: With the exception of Ortho VITROS, FT4 measurements were raised in all assays, with greatest to lowest susceptibility to interference being Beckman ACCESS > Roche ELECSYS > FUJIREBIO Lumipulse > Siemens CENTAUR > Abbott ARCHITECT > Perkin-Elmer DELFIA. Five different assays recorded high FT3 levels, with the Siemens CENTAUR method measuring high FT3 values in up to 30% of cases. However, depending on the assay method, FT4 measurements were unexpectedly normal in some, genetically confirmed, affected relatives of index FDH cases. CONCLUSIONS: All FT4 immunoassays evaluated are prone to interference by R218H FDH, with their varying susceptibility not being related to assay architecture but likely due to differing assay conditions or buffer composition. Added susceptibility of many FT3 assays to measurement interference, resulting in high FT4 and FT3 with non-suppressed TSH levels, raises the possibility of R218H FDH being misdiagnosed as resistance to thyroid hormone beta or TSH-secreting pituitary tumour, potentially leading to unnecessary investigation and inappropriate treatment.
Asunto(s)
Hipertiroxinemia Disalbuminémica Familiar/sangre , Pruebas de Función de la Tiroides/métodos , Hormonas Tiroideas/sangre , Humanos , Inmunoensayo , Tiroxina/sangre , Triyodotironina/sangreRESUMEN
PURPOSE: To determine the correlation between preoperative and postoperative opioid use in patients undergoing arthroscopic shoulder labral repair, as well as patient risk factors associated with increased postoperative opioid use after the procedure. METHODS: A retrospective review of all patients undergoing arthroscopic shoulder labral surgery at a single institution between August 2013 and November 2017 was performed. Patients were stratified as opioid nonusers, acute users, or chronic users based on preoperative consumption. Patient demographic characteristics, injury characteristics, surgical interventions, and postoperative opioid use for the first 12 months after surgery were then analyzed. RESULTS: A total of 340 patients were included in this study. The average age was 26.3 years (range, 13-68 years), and the average body mass index was 27.5 (range, 18.4-45.0). Preoperative opioid users (acute and chronic) were found to continue to receive opioid medications at extended time points beyond 2 months postoperatively compared with nonusers (P < .001). Patients with intraoperatively identified SLAP tears experienced more preoperative pain and required more postoperative opioid prescriptions (P = .018). On stratification for other common shoulder instability injury patterns, no differences were found between the number of postoperative opioid prescriptions filled and the presence of Bankart lesion, Hill-Sachs lesion, reverse Hill-Sachs lesion, anterior labroligamentous periosteal sleeve avulsion, glenolabral articular disruption, or humeral avulsion of the glenohumeral ligament (P > .05). CONCLUSIONS: In patients undergoing arthroscopic labral surgery, the chronicity of preoperative opioid use, number of concomitant procedures at the time of initial surgery, and presence of biceps tenodesis were found to significantly increase postoperative opioid demand. Orthopaedic surgeons should recognize risk factors for increased opioid use postoperatively and adapt treatment strategies and patient counseling accordingly. LEVEL OF EVIDENCE: Level III, retrospective cohort study.