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1.
Lancet ; 397(10275): 642-643, 2021 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-33545098
2.
mBio ; 12(1)2021 02 09.
Artigo em Inglês | MEDLINE | ID: mdl-33563830

RESUMO

Viral interactions during multiple viral infections were examined in Agaricus bisporus cultures harboring 9 viruses (comprising 18 distinct viral RNAs) by statistically analyzing their relative abundance in fruitbodies. Four clusters of viral RNA were identified that suggested synergism and coreplication. Pairwise correlations revealed negative and positive correlations between clusters, indicating further synergisms and an antagonism involving a group containing a putative hypovirus and four nonhost ORFan RNAs (RNAs with no similarity to known sequences) possibly acting as defective interfering RNAs. The disease phenotype was observed in 10 to 15% of the fruitbodies apparently randomly located among asymptomatic fruitbodies. The degree of symptom expression consistently correlated with the levels of the multipartite virus AbV16. Diseased fruitbodies contained very high levels of AbV16 and AbV6 RNA2; these levels were orders of magnitude higher than those in asymptomatic tissues and were shown statistically to be discretely higher populations of abundance, indicating an exponential shift in the replicative capacity of the virus. High levels of AbV16 replication were specific to the fruitbody and not found in the underlying mycelium. There appeared to be a stochastic element occurring in these viral interactions, as observed in the distribution of diseased symptoms across a culture, differences in variance between experiments, and a number of additional viruses undergoing the step-jump in levels between experiments. Possible mechanisms for these multiple and simultaneous viral interactions in single culture are discussed in relation to known virus-host regulatory mechanisms for viral replication and whether additional factors could be considered to account for the 1,000-fold increase in AbV16 and AbV6 RNA2 levels.IMPORTANCE How viruses interact in a multiple-virus infection was examined by quantifying the levels of 18 viral RNAs in fruiting cultures of the agriculturally cultivated fungus Agaricus bisporus and statistically analyzing and modeling their abundance. Synergistic, antagonistic, and neutral interactions occurred simultaneously in cultures. The viral RNAs were grouped into four clusters, each displaying similar relative abundance, and between clusters, further interactions were found with positive, negative, or no correlations. Mushroom fruitbodies showing disease symptoms were distributed apparently randomly across the culture. These symptoms were associated with the presence of viral RNAs from two different clusters at very high levels, 1,000-fold higher than asymptomatic fruitbodies. The role of viral interaction together with stochastic factors and the regulation of host antiviral defenses in pathogenesis are discussed.

3.
Artigo em Inglês | MEDLINE | ID: mdl-33484297

RESUMO

PURPOSE: The aim of this study was to investigate the associations between quality of life and both perceived and objective availability of local green and blue spaces in people with dementia, including potential variation across rural/urban settings and those with/without opportunities to go outdoors. METHODS: This study was based on 1540 community-dwelling people with dementia in the Improving the experience of Dementia and Enhancing Active Life (IDEAL) programme. Quality of life was measured by the Quality of Life in Alzheimer's Disease (QoL-AD) scale. A list of 12 types of green and blue spaces was used to measure perceived availability while objective availability was estimated using geographic information system data. Regression modelling was employed to investigate the associations of quality of life with perceived and objective availability of green and blue spaces, adjusting for individual factors and deprivation level. Interaction terms with rural/urban areas or opportunities to go outdoors were fitted to test whether the associations differed across these subgroups. RESULTS: Higher QoL-AD scores were associated with higher perceived availability of local green and blue spaces (0.82; 95% CI 0.06, 1.58) but not objective availability. The positive association between perceived availability and quality of life was stronger for urban (1.50; 95% CI 0.52, 2.48) than rural residents but did not differ between participants with and without opportunities to go outdoors. CONCLUSIONS: Only perceived availability was related to quality of life in people with dementia. Future research may investigate how people with dementia utilise green and blue spaces and improve dementia-friendliness of these spaces.

4.
Nurs Health Sci ; 2021 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-33389812

RESUMO

Physical activity post-myocardial infarction has numerous health benefits, yet uptake through cardiac rehabilitation is poor. Whilst family support can facilitate patients' recovery, little is known about the role family may play in supporting physical activity for post-myocardial infarction patients. This qualitative study used semistructured interviews with 14 cardiac rehabilitation practitioners to explore their perceptions about the role of the family in supporting post-myocardial infarction patients' physical activity. Data were transcribed verbatim and analyzed thematically. Three familial roles were identified: "family as a second pair of ears," "family as physical activity regulators," and "family as social support." A fourth theme, "factors that influence family support," described how family health beliefs and perceptions could influence the physical activity support provided. Practitioner perceptions suggest families play an important role in post-myocardial infarction patients' physical activity, which is enhanced when families personally value physical activity. Integrating the family into cardiac rehabilitation may help facilitate physical activity-related interactions and promote positive engagement for patients.

5.
Health Econ Policy Law ; : 1-18, 2021 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-33455616

RESUMO

Public reporting of clinical performance is increasingly used in many countries to improve quality and enhance accountability of the health system. The assumption is that greater transparency will stimulate improvements by clinicians in response to peer pressure, patient choice or competition. The international diffusion of public reporting might suggest greater similarity between health systems. Alternatively, national and local contexts (including health system imperatives, professional power and organisational culture) might continue to shape its form and impact, implying continued divergence. The paper considers public reporting in the USA and England through the lens of Scott's 'pillars' institutional framework. The USA was arguably the first country to adopt public reporting systematically in the late 1980s. England is a more recent adopter; it is now being widely adopted through the National Health Service (NHS). Drawing on qualitative data from California and England, this paper compares the behavioural and policy responses to public reporting by health system stakeholders at micro, meso and macro levels and through the intersection of ideas, interests, institutions and individuals through. The interplay between the regulative, normative and cultural-cognitive pillars helps explain the observed patterns of on-going divergence.

6.
J Acoust Soc Am ; 148(5): 3141, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33261390

RESUMO

Noise is a stressor to wildlife, yet the precise sound sensitivity of individuals and populations is often unknown or unmeasured. Cook Inlet, Alaska belugas (CIBs) are a critically endangered and declining marine mammal population. Anthropogenic noise is a primary threat to these animals. Auditory evoked potentials were used to measure the hearing of a wild, stranded CIB as part of its rehabilitation assessment. The beluga showed broadband (4-128 kHz) and sensitive hearing (<80 dB) for a wide-range of frequencies (16-80 kHz), reflective of a healthy odontocete auditory system. Data were similar to healthy, adult belugas from the comparative Bristol Bay population (the only other published data set of healthy, wild marine mammal hearing). Repeated October and December 2017 measurements were similar, showing continued auditory health of the animal throughout the rehabilitation period. Hearing data were compared to pile-driving and container-ship noise measurements made in Cook Inlet, two sources of concern, suggesting masking is likely at ecologically relevant distances. These data provide the first empirical hearing data for a CIB allowing for estimations of sound-sensitivity in this population. The beluga's sensitive hearing and likelihood of masking show noise is a clear concern for this population struggling to recover.

7.
Nat Commun ; 11(1): 6377, 2020 12 11.
Artigo em Inglês | MEDLINE | ID: mdl-33311448

RESUMO

Building trust in science and evidence-based decision-making depends heavily on the credibility of studies and their findings. Researchers employ many different study designs that vary in their risk of bias to evaluate the true effect of interventions or impacts. Here, we empirically quantify, on a large scale, the prevalence of different study designs and the magnitude of bias in their estimates. Randomised designs and controlled observational designs with pre-intervention sampling were used by just 23% of intervention studies in biodiversity conservation, and 36% of intervention studies in social science. We demonstrate, through pairwise within-study comparisons across 49 environmental datasets, that these types of designs usually give less biased estimates than simpler observational designs. We propose a model-based approach to combine study estimates that may suffer from different levels of study design bias, discuss the implications for evidence synthesis, and how to facilitate the use of more credible study designs.


Assuntos
Projetos de Pesquisa , Ciências Sociais , Viés , Biodiversidade , Ecologia , Meio Ambiente , Humanos , Literatura , Prevalência
8.
Acta Oncol ; : 1-9, 2020 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-33377792

RESUMO

BACKGROUND: The restrictive eligibility criteria of therapy-focused cancer clinical trials can limit the external validity of the results. The characteristics and survival outcomes of patients enrolled in stand-alone biomarker studies have yet to be explored. We examined the characteristics of patients enrolled in a series of biomarker studies in stage II and III colorectal cancer (CRC) and of the broader patient population from which the study cohorts were recruited. MATERIAL AND METHODS: We examined three distinct trial scenarios: a retrospective cohort study (RCS) where archival tissue samples were analyzed, a prospective observational study (POS) where blood samples were collected but patients received standard treatment and a randomized clinical trial (RCT) where biomarker analysis could inform clinical care. Clinical data for each study time period were extracted from a prospective registry. RESULTS: For all CRC patients (n = 4033) in this study, the median age was 70 years and 54% were ECOG 0. For patients in the RCS (n = 450), POS (n = 284) and RCT (n = 230), the median age was 72, 65 and 64 years, with 45%, 74% and 79% being ECOG 0. For the POS and RCT, 33% and 36% of all patients with the relevant disease stage were enrolled over the study recruitment period. Survival outcomes were similar for patients in the RCS and POS. RCT outcome data are not available. CONCLUSION: As for therapy-based trials, enrollment in prospective biomarker studies may be selective, despite relatively broad eligibility criteria. Characteristics and recruitment were similar for POS and RCT patients, indicating study complexity may not necessarily limit patient recruitment. For the prospective biomarker study cohorts examined, the selective recruitment did not significantly impact survival outcomes, suggesting potential for high external validity.

9.
BJPsych Open ; 6(6): e139, 2020 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-33168126

RESUMO

BACKGROUND: Individuals with schizophrenia are at higher risk of physical illnesses, which are a major contributor to their 20-year reduced life expectancy. It is currently unknown what causes the increased risk of physical illness in schizophrenia. AIMS: To link genetic data from a clinically ascertained sample of individuals with schizophrenia to anonymised National Health Service (NHS) records. To assess (a) rates of physical illness in those with schizophrenia, and (b) whether physical illness in schizophrenia is associated with genetic liability. METHOD: We linked genetic data from a clinically ascertained sample of individuals with schizophrenia (Cardiff Cognition in Schizophrenia participants, n = 896) to anonymised NHS records held in the Secure Anonymised Information Linkage (SAIL) databank. Physical illnesses were defined from the General Practice Database and Patient Episode Database for Wales. Genetic liability for schizophrenia was indexed by (a) rare copy number variants (CNVs), and (b) polygenic risk scores. RESULTS: Individuals with schizophrenia in SAIL had increased rates of epilepsy (standardised rate ratio (SRR) = 5.34), intellectual disability (SRR = 3.11), type 2 diabetes (SRR = 2.45), congenital disorders (SRR = 1.77), ischaemic heart disease (SRR = 1.57) and smoking (SRR = 1.44) in comparison with the general SAIL population. In those with schizophrenia, carrier status for schizophrenia-associated CNVs and neurodevelopmental disorder-associated CNVs was associated with height (P = 0.015-0.017), with carriers being 7.5-7.7 cm shorter than non-carriers. We did not find evidence that the increased rates of poor physical health outcomes in schizophrenia were associated with genetic liability for the disorder. CONCLUSIONS: This study demonstrates the value of and potential for linking genetic data from clinically ascertained research studies to anonymised health records. The increased risk for physical illness in schizophrenia is not caused by genetic liability for the disorder.

10.
J Nurs Res ; 2020 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-33136697

RESUMO

BACKGROUND: Regular physical activity is important for patients with established coronary heart disease as it favorably influences their coronary risk profile. General self-efficacy is a powerful predictor of health behavior change that involves increases in physical activity levels. Few studies have simultaneously measured physical activity and self-efficacy during early recovery after a first acute myocardial infarction (AMI). PURPOSE: The aims of this study were to assess changes in objectively measured physical activity levels at 2 weeks (T2) and 6 weeks (T3) and self-reported cardiac self-efficacy at hospital discharge (T1) and at T2 and T3 in patients recovering from AMI. METHODS: A repeated-measures design was used to recruit a purposive sample of patients from a single center in Jordan who were diagnosed with first AMI and who did not have access to cardiac rehabilitation. A body-worn activity monitor (activPAL) was used to objectively measure free-living physical activity levels for 7 consecutive days at two time points (T2 and T3). An Arabic version of the cardiac self-efficacy scale was administered at T1, T2, and T3. Paired t tests and analysis of variance were used to examine differences in physical activity levels and cardiac self-efficacy scores, respectively. RESULTS: A sample of 100 participants was recruited, of which 62% were male. The mean age of the sample was 54.5 ± 9.9 years. No statistically significant difference in physical activity levels was measured at 2 weeks (T2) and 6 weeks (T3). Cardiac self-efficacy scores improved significantly between T1, T2, and T3 across subscales and global cardiac self-efficacy. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: Participants recovering from AMI in Jordan did not increase their physical activity levels during the early recovery phase, although cardiac self-efficacy scores improved. This may be because the increase in cardiac self-efficacy was not matched by the practical skills and knowledge required to translate this positive psychological construct into behavioral change. This study provides a first step toward understanding the complex relationship between cardiac self-efficacy and physical activity in this population. The authors hope that these findings support the design of culturally appropriate interventions to increase physical activity levels in this population.

11.
Am J Emerg Med ; 38(10): 2065-2069, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33142176

RESUMO

COVID-19 has caused global dramatic change in medical practices including the introduction of temporary screening and assessment areas outside the footprint of the main hospital structures. Following the initial surge of patients with novel coronavirus (2019-nCoV) in the United States, our medical center rapidly designed and constructed an alternative assessment and treatment site in a converted parking garage deck for emergency department patients with suspected or confirmed 2019-nCoV. During the first month after opening, 651 patients were treated in this alternative assessment area including 54 patients who tested positive for 2019-nCoV. This accounted for 55% of the 98 patients with confirmed novel coronavirus (2019-nCoV) who were treated in our ED. This report provides a blueprint for the necessary steps, materials, labor needs and barriers, both anticipated and unanticipated, to rapidly construct an alternative ED treatment site during a pandemic.

12.
J Affect Disord ; 2020 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-33234286

RESUMO

BACKGROUND: Electronic self-report mood monitoring tools for individuals with bipolar disorder (BD) are rapidly emerging and predominately employ predefined symptom-based questions. Allowing individuals to additionally choose what they monitor in relation to their BD offers the unique opportunity to capture and gain a deeper insight into patient priorities in this context. METHODS: In addition to monitoring mood symptoms with two standardised self-rated questionnaires, 308 individuals with BD participating in the Bipolar Disorder Research Network True Colours electronic mood-monitoring tool for research chose to create and complete additional personalised questions. A content analysis approach was used to analyse the content of these questions. RESULTS: 35 categories were created based on the personalised questions with the most common being physical activity and exercise, anxiety and panic, sleep and coping/stress levels. The categories were grouped into six overarching themes 1) mental health; 2) behaviour and level of functioning; 3) physical wellbeing; 4) health behaviours; 5) active self-management; and, 6) interpersonal. LIMITATIONS: The average age of the sample was around 50 years meaning our findings may not be generalisable to younger individuals with BD. CONCLUSIONS: Aspects of BD important to patients in relation to longitudinal monitoring extend well beyond mood symptoms, highlighting the limitations of solely relying on standardised questions/mood rating scales based on symptoms primarily used for diagnosis. Additional symptoms and aspects of life not necessarily useful diagnostically for BD may be more important for individuals themselves to monitor and have more meaning in capturing their own experience of changes in BD severity.

13.
MMWR Morb Mortal Wkly Rep ; 69(47): 1762-1766, 2020 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-33237893

RESUMO

Most persons infected with SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), develop virus-specific antibodies within several weeks, but antibody titers might decline over time. Understanding the timeline of antibody decline is important for interpreting SARS-CoV-2 serology results. Serum specimens were collected from a convenience sample of frontline health care personnel at 13 hospitals and tested for antibodies to SARS-CoV-2 during April 3-June 19, 2020, and again approximately 60 days later to assess this timeline. The percentage of participants who experienced seroreversion, defined as an antibody signal-to-threshold ratio >1.0 at baseline and <1.0 at the follow-up visit, was assessed. Overall, 194 (6.0%) of 3,248 participants had detectable antibodies to SARS-CoV-2 at baseline (1). Upon repeat testing approximately 60 days later (range = 50-91 days), 146 (93.6%) of 156 participants experienced a decline in antibody response indicated by a lower signal-to-threshold ratio at the follow-up visit, compared with the baseline visit, and 44 (28.2%) experienced seroreversion. Participants with higher initial antibody responses were more likely to have antibodies detected at the follow-up test than were those who had a lower initial antibody response. Whether decay in these antibodies increases risk for reinfection and disease remains unanswered. However, these results suggest that serology testing at a single time point is likely to underestimate the number of persons with previous SARS-CoV-2 infection, and a negative serologic test result might not reliably exclude prior infection.


Assuntos
Anticorpos Antivirais/sangue , Betacoronavirus/imunologia , Infecções por Coronavirus/imunologia , Recursos Humanos em Hospital/estatística & dados numéricos , Pneumonia Viral/imunologia , Adulto , Infecções por Coronavirus/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/epidemiologia , Estados Unidos/epidemiologia
14.
Sci Rep ; 10(1): 20514, 2020 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-33239702

RESUMO

Globally, lake surface water temperatures have warmed rapidly relative to air temperatures, but changes in deepwater temperatures and vertical thermal structure are still largely unknown. We have compiled the most comprehensive data set to date of long-term (1970-2009) summertime vertical temperature profiles in lakes across the world to examine trends and drivers of whole-lake vertical thermal structure. We found significant increases in surface water temperatures across lakes at an average rate of + 0.37 °C decade-1, comparable to changes reported previously for other lakes, and similarly consistent trends of increasing water column stability (+ 0.08 kg m-3 decade-1). In contrast, however, deepwater temperature trends showed little change on average (+ 0.06 °C decade-1), but had high variability across lakes, with trends in individual lakes ranging from - 0.68 °C decade-1 to + 0.65 °C decade-1. The variability in deepwater temperature trends was not explained by trends in either surface water temperatures or thermal stability within lakes, and only 8.4% was explained by lake thermal region or local lake characteristics in a random forest analysis. These findings suggest that external drivers beyond our tested lake characteristics are important in explaining long-term trends in thermal structure, such as local to regional climate patterns or additional external anthropogenic influences.

15.
J Trauma Acute Care Surg ; 89(5): 915-919, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33108138

RESUMO

BACKGROUND: Persistent air leaks after thoracic trauma are associated with significant morbidity. To evaluate a novel pectin sealant in a swine model of traumatic air leaks, we compared a pectin biopolymer with standard surgical and fibrin-based interventions. METHODS: A standardized lung injury was created in male Yorkshire swine. Interventions were randomized to stapled wedge resection (n = 5), topical fibrin glue (n = 5), fibrin patch (n = 5), and a pectin sealant (n = 6). Baseline, preintervention and postintervention tidal volumes (TV) were recorded. Early success was defined as the return to near-normal TV (>95% of baseline). Late success was defined as no detectable air leak in the chest tube after chest closure. RESULTS: There were no differences in injury severity between groups (mean TV loss, 62 ± 17 mL, p = 0.2). Early success was appreciated in 100% (n = 6) of the pectin interventions which was significantly better than the fibrin sealant (20%, n = 1), fibrin patch (20%, n = 1), and stapled groups (80%, n = 4, p = 0.01). The percent of return to baseline TV after sealant intervention was significantly increased in the pectin (98%) and staple arms (97%) compared with the fibrin sealant (91%) and fibrin patch arms (90%) (p = 0.02; p = 0.03). Late success was also improved with the pectin sealant: no air leak was detected in 83% of the pectin group compared with 40% in the stapled group (p = 0.008)-90% of the fibrin-based interventions resulted in continuous air leaks (p = 0.001). CONCLUSION: Pectin-based bioadhesives effectively seal traumatic air leaks upon application in a porcine model. Further testing is warranted as they may provide a superior parenchymal-sparing treatment option for traumatic air leaks.

16.
Nature ; 587(7835): 644-649, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33057195

RESUMO

Lineage-specific epigenomic changes during human corticogenesis have been difficult to study owing to challenges with sample availability and tissue heterogeneity. For example, previous studies using single-cell RNA sequencing identified at least 9 major cell types and up to 26 distinct subtypes in the dorsal cortex alone1,2. Here we characterize cell-type-specific cis-regulatory chromatin interactions, open chromatin peaks, and transcriptomes for radial glia, intermediate progenitor cells, excitatory neurons, and interneurons isolated from mid-gestational samples of the human cortex. We show that chromatin interactions underlie several aspects of gene regulation, with transposable elements and disease-associated variants enriched at distal interacting regions in a cell-type-specific manner. In addition, promoters with increased levels of chromatin interactivity-termed super-interactive promoters-are enriched for lineage-specific genes, suggesting that interactions at these loci contribute to the fine-tuning of transcription. Finally, we develop CRISPRview, a technique that integrates immunostaining, CRISPR interference, RNAscope, and image analysis to validate cell-type-specific cis-regulatory elements in heterogeneous populations of primary cells. Our findings provide insights into cell-type-specific gene expression patterns in the developing human cortex and advance our understanding of gene regulation and lineage specification during this crucial developmental window.

17.
Eur J Psychotraumatol ; 11(1): 1767349, 2020 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-33029311

RESUMO

Background: Sleep disturbance has been described as a 'hallmark' symptom of posttraumatic stress disorder (PTSD). Although there are robust findings of self-reported sleep disturbance in PTSD, evidence of sleep disturbance measured using actigraphy is less certain. Objective: To conduct a systematic review and meta-analysis to determine whether there are any significant differences between individuals with and without PTSD in actigraph-derived sleep measures. Method: Case-control studies comparing participants with current PTSD to those without PTSD were eligible for inclusion. Sleep parameters of interest were: (1) total sleep time; (2) sleep onset latency; (3) wake after sleep onset (WASO); and (4) sleep efficiency. Data were meta-analysed as standardised mean differences (SMDs) and potential sources of heterogeneity were explored through meta-regression. Six actigraphy studies with 405 participants were included. Results: There was no evidence of a statistically significant difference between those with and without PTSD in total sleep time (SMD 0.09, 95%CI -0.23 to 0.42); WASO (SMD 0.18, 95%CI -0.06 to 0.43); sleep latency (SMD 0.32, 95%CI -0.04 to 0.69); or sleep efficiency (SMD -0.28, 95%CI -0.78 to 0.21). Conclusions: Further high-quality research is required to determine whether there is a true difference in sleep between those with and without PTSD.

18.
Viruses ; 12(9)2020 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-32971895

RESUMO

Coronaviruses (CoVs) are enveloped, positive sense, single strand RNA viruses that cause respiratory, intestinal and neurological diseases in mammals and birds. Following replication, CoVs assemble on intracellular membranes including the endoplasmic reticulum Golgi intermediate compartment (ERGIC) where the envelope protein (E) functions in virus assembly and release. In consequence, E potentially contains membrane-modifying peptides. To search for such peptides, the E coding sequence of Mouse Hepatitis Virus (MHV) was inspected for its amino acid conservation, proximity to the membrane and/or predicted amphipathic helices. Peptides identified in silico were synthesized and tested for membrane-modifying activity in the presence of giant unilamellar vesicles (GUVs) consisting of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), sphingomyelin and cholesterol. To confirm the presence of membrane binding peptides identified in the context of a full-length E protein, the wild type and a number of mutants in the putative membrane binding peptide were expressed in Lenti-X-293T mammalian and insect cells, and the distribution of E antigen within the expressing cell was assessed. Our data identify a role for the post-transmembrane region of MHV E in membrane binding.


Assuntos
Vírus da Hepatite Murina/química , Peptídeos/química , Proteínas do Envelope Viral/química , Sequência de Aminoácidos , Animais , Linhagem Celular , Infecções por Coronavirus , Humanos , Membranas Intracelulares/metabolismo , Camundongos , Vírus da Hepatite Murina/genética , Vírus da Hepatite Murina/metabolismo , Mutação , Peptídeos/síntese química , Peptídeos/metabolismo , Células Sf9 , Spodoptera , Lipossomas Unilamelares/metabolismo , Proteínas do Envelope Viral/genética , Proteínas do Envelope Viral/metabolismo
19.
Clin Transl Immunology ; 9(7): e1155, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32953115

RESUMO

Objectives: Tumor-infiltrating lymphocytes (TIL), particularly CD8+ TILs in patients with colorectal cancer (CRC), are highly prognostic in the early-disease stages (I-II). In metastatic disease (stage IV; mCRC), their influence is less well defined. It has presumably failed to contain tumor cells to the primary site; however, is this evident? We explored the prognostic impact of TILs at the primary site in patients who presented de novo with mCRC. Methods: Treatment-naïve patients (109) with mCRC were assessed for CD8+ TILs and PD-L1 expression. Microsatellite instability (MSI) was evaluated by IHC for PMS2 and MSH6 proteins and/or by PCR using the Bethesda panel. Results: Microsatellite instability-high tumors had significantly more CD8+ TILs, with no significant survival advantage observed between MSI-H and microsatellite stable (MSS) tumors (12 vs 19 months, P = 0.304). TIL density for all cases had no impact on OS (low: 20 vs high: 13 months, P = 0.426), while PD-L1 of 1% or higher was associated with reduced mean survival (9.6 vs 18.9 months; P = 0.038). MSI-H tumors and associated immune cells had higher PD-L1 expression than in MSS cases. A positive correlation between PD-L1 on immune cells and CD8+ve TILs was found. A subset of MSS tumors had relatively high TILs approximating that of MSI-H tumors. Conclusion: In contrast to early-stage CRC, the immune response in primary tumors of patients with de novo mCRC does not appear to influence survival. A subgroup of MSS tumors was identified with increased TILs/PD-L1 comparable to MSI-H tumors, traditionally not be considered for immune checkpoint blockade and perhaps should be.

20.
Clin Kidney J ; 13(4): 674-683, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32905314

RESUMO

Background: The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation is routinely used to assess renal function but exhibits varying accuracy depending on patient characteristics and clinical presentation. The overall aim of the present study was to assess if and to what extent glomerular filtration rate (GFR) estimation based on creatinine can be improved. Methods: In a cross-sectional analysis covering the years 2003-17, CKD-EPI was validated against measured GFR (mGFR; using various tracer methods) in patients with high likelihood of chronic kidney disease (CKD; five CKD cohorts, n = 8365) and in patients with low likelihood of CKD (six community cohorts, n = 6759). Comparisons were made with the Lund-Malmö revised equation (LMR) and the Full Age Spectrum equation. Results: 7In patients aged 18-39 years old, CKD-EPI overestimated GFR with 5.0-16 mL/min/1.73 m2 in median in both cohort types at mGFR levels <120 mL/min/1.73 m2. LMR had greater accuracy than CKD-EPI in the CKD cohorts (P30, the percentage of estimated GFR within 30% of mGFR, 83.5% versus 76.6%). CKD-EPI was generally the most accurate equation in the community cohorts, but all three equations reached P30 above the Kidney Disease Outcomes Quality Initiative benchmark of 90%. Conclusions: None of the evaluated equations made optimal use of available data. Prospects for improved GFR estimation procedures based on creatinine exist, particularly in young adults and in settings where patients with suspected or manifest CKD are investigated.

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