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BACKGROUND: Reactivation of viruses such as Epstein-Barr virus (EBV) and cytomegalovirus (CMV) are common in critically ill patients and have been described in patients with severe COVID-19. However, it is unclear whether these reactivations are associated with increased mortality and whether targeted treatments are beneficial. METHODS: In a retrospective single-center cohort study, patients with severe COVID-19 treated on our intensive care unit (ICU) were screened for EBV and CMV reactivation as detected by polymerase chain reaction. If present, patient characteristics, temporal connections to severe acute respiratory syndrome coronavirus 2 diagnosis and corticosteroid use, the use of targeted treatments as well as the course of disease and outcome were analyzed. As control group, non-COVID-19 patients with sepsis, treated within the same time period on our ICU, served as control group to compare incidences of viral reactivation. RESULTS: In 19 (16%) of 117 patients with severe COVID-19 treated on our ICU EBV reactivations were identified, comparable 18 (14%) of 126 in the non-COVID-19 control group (P = .672). Similarly, in 11 (9%) of 117 patients CMV reactivations were identified, comparable to the 16 (13%) of 126 in the non-COVID-19 sepsis patients (P = .296). The majority of EBV (58%) and CMV reactivations (55%) were detected in patients under systemic corticosteroid treatment. 7 (37%) of 19 patients with EBV reactivation survived the ICU stay, 2 (29%) of 7 patients with rituximab treatment and 5 (42%) of 12 patients without treatment (P = .568). Five (50%) of 10 patients with CMV reactivation survived the ICU stay, 5 (83%) of 6 patients with ganciclovir treatment and 0 of 4 patients without treatment (P = .048). Follow-up analysis in these patients showed that the initiation of treatment lead to decrease in viral load. CONCLUSION: Critically ill patients with COVID-19 are at a high risk for EBV and CMV reactivations. Whether these reactivations are a cause of hyperinflammation and require targeted treatment remains uncertain. However, in patients with clinical deterioration or signs of hyperinflammation targeted treatment might be beneficial and warrants further studying.
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COVID-19 , Infecciones por Citomegalovirus , Infecciones por Virus de Epstein-Barr , Sepsis , COVID-19/complicaciones , Estudios de Cohortes , Enfermedad Crítica , Citomegalovirus/fisiología , Infecciones por Citomegalovirus/complicaciones , Infecciones por Citomegalovirus/tratamiento farmacológico , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/diagnóstico , Infecciones por Virus de Epstein-Barr/tratamiento farmacológico , Herpesvirus Humano 4/fisiología , Humanos , Estudios Retrospectivos , Sepsis/complicaciones , Activación Viral/fisiologíaRESUMEN
PURPOSE: To compare the current clinical scoring systems used to quantify the severity of symptoms of faecal incontinence (FI) to patients' subjective scoring of parameters of psychosocial well-being. METHODS: Patients referred to six European centres for investigation or treatment of symptoms of FI between June 2017 and September 2019 completed a questionnaire that captured patient demographics, incontinence symptoms using St. Mark's Incontinence score (SMIS) and ICIQ-B, psychological well-being (HADS, Hospital Anxiety and Depression Scale), and social interaction (a three-item loneliness scale). RESULTS: Three hundred eighteen patients completed questionnaires (62 men, mean age 58.7). Sixty percent of the respondents were aged under 65. Median SMIS was 15 (11-18), ICIQ-B bowel pattern was 8 (6-11) and bowel control was 17 (13-22), similar across all demographic groups; however, younger patients were more likely to experience symptoms of depression and anxiety (HADS score > 10, 65.2% of patients age < 65 vs 54.9% of those ages > = 65, p = 0.03) with lower quality of life (ICIQ-B QoL, median score 19 (14-23)) vs age > = 65 (16 (11-21) (p < 0.005)). On loneliness score 25.5% reported often feeling isolated from others. One of the most significant concerns by patients was the fear and embarrassment related to unpredictable episodes of incontinence. CONCLUSION: The SMIS remains a useful tool for quantifying incontinence symptoms but may underestimate the psychosocial morbidity associated with unpredictable episodes of incontinence. Interventions aimed at decreasing anxiety and to address feelings of disgust may be helpful for a significant number of patients requiring treatment for FI.
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Incontinencia Fecal , Incontinencia Urinaria , Anciano , Ansiedad , Humanos , Masculino , Persona de Mediana Edad , Calidad de Vida , Índice de Severidad de la Enfermedad , Encuestas y CuestionariosRESUMEN
BACKGROUND: Resting motor threshold is an objective measure of cortical excitability. Numerous studies indicate that the success of motor recovery after stroke is significantly determined by the direction and extent of cortical excitability changes. A better understanding of this topic (particularly with regard to the level of motor impairment and the contribution of either cortical hemisphere) may contribute to the development of effective therapeutical strategies in this cohort. OBJECTIVES: This systematic review collects and analyses the available evidence on resting motor threshold and hand motor recovery in stroke patients. METHODS: PubMed was searched from its inception through to 31/10/2020 on studies investigating resting motor threshold of the affected and/or the non-affected hemisphere and motor function of the affected hand in stroke cohorts. RESULTS: Overall, 92 appropriate studies (including 1978 stroke patients and 377 healthy controls) were identified. The analysis of the data indicates that severe hand impairment is associated with suppressed cortical excitability within both hemispheres and with great between-hemispheric imbalance of cortical excitability. Favorable motor recovery is associated with an increase of ipsilesional motor cortex excitability and reduction of between-hemispheric imbalance. The direction of change of contralesional motor cortex excitability depends on the amount of hand motor impairment. Severely disabled patients show an increase of contralesional motor cortex excitability during motor recovery. In contrast, recovery of moderate to mild hand motor impairment is associated with a decrease of contralesional motor cortex excitability. CONCLUSIONS: This data encourages a differential use of rehabilitation strategies to modulate cortical excitability. Facilitation of the ipsilesional hemisphere may support recovery in general, whereas facilitation and inhibition of the contralesional hemisphere may enhance recovery in severe and less severely impaired patients, respectively.
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Corteza Motora , Rehabilitación de Accidente Cerebrovascular , Accidente Cerebrovascular , Potenciales Evocados Motores/fisiología , Lateralidad Funcional/fisiología , Mano , Humanos , Recuperación de la Función , Estimulación Magnética TranscranealRESUMEN
BACKGROUND: Noninvasive brain stimulation can modulate neural processing within the motor cortex and thereby might be beneficial in the rehabilitation of hemispatial neglect after stroke. METHODS: We review the pertinent literature regarding the use of transcranial direct current stimulation (tDCS) and transcranial magnetic stimulation in order to facilitate recovery of hemispatial neglect after stroke. RESULTS: Twenty controlled trials (including 443 stroke patients) matched our inclusion criteria. Methodology and results of each study are presented in a comparative approach. Current data seem to indicate a better efficiency of repetitive transcranial magnetic stimulation, compared to tDCS to ameliorate hemispatial neglect after stroke. CONCLUSIONS: Noninvasive brain stimulation has the potential to facilitate recovery of hemispatial neglect after stroke, but until today, there are not enough data to claim its routine use.
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Trastornos de la Percepción/terapia , Rehabilitación de Accidente Cerebrovascular/métodos , Accidente Cerebrovascular/complicaciones , Estimulación Transcraneal de Corriente Directa/métodos , Estimulación Magnética Transcraneal/métodos , Ensayos Clínicos como Asunto , Humanos , Trastornos de la Percepción/etiología , Trastornos de la Percepción/rehabilitaciónRESUMEN
OBJECTIVES: We investigated the effectiveness of cycle ergometer training and resistance training to enhance the efficiency of standard care to improve walking ability, muscular strength of the lower limbs, cardiovascular endurance and health-related quality of life during inpatient rehabilitation in intensive care unit acquired weakness. MATERIALS & METHODS: Thirty-nine patients with severe to moderate walking disability were enrolled in one of the three experimental groups: (a) ergometer training group, (b) resistance training group and (c) control group (standard care only). Intervention was applied 5 days a week over a 4-week period during inpatient neurological rehabilitation. We evaluated walking ability (Functional Ambulation Category test, timed up and go test, 10-metre walk test and 6-minute walk test), muscle strength (Medical Research Council and maximum muscle strength tests), cardiovascular endurance and muscular endurance of the lower limbs at the fatigue threshold (physical working capacity at fatigue threshold) and quality of life (medical outcomes study SF-36 form). All tests were performed at baseline, after two weeks of treatment and at the end of the 4-week intervention period. RESULTS: Ergometer training and resistance training enhanced the effectiveness of standard care in order to improve (a) lower limb muscle strength, (b) walking ability and (c) cardiorespiratory fitness during inpatient rehabilitation of intensive care acquired weakness. In addition, ergometer training may be superior to resistance training. CONCLUSIONS: Our data encourage more research to develop and implement these training tools in rehabilitation programmes for intensive care acquired weakness.
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Enfermedad Crítica/rehabilitación , Ejercicio Físico , Debilidad Muscular/etiología , Debilidad Muscular/rehabilitación , Entrenamiento de Fuerza/métodos , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Unidades de Cuidados Intensivos , Masculino , Persona de Mediana Edad , Limitación de la Movilidad , Calidad de Vida , Resultado del TratamientoRESUMEN
Objective. To investigate the relationship between changes of cortical hand motor representation and motor recovery of the affected hand in subacute stroke. Methods. 17 patients with motor impairment of the affected hand were enrolled in an in-patient neurological rehabilitation program. Hand motor function tests (Wolf Motor Function Test, Action Research Arm Test) and neurophysiological evaluations (resting motor threshold, motor evoked potentials, motor map area size, motor map area volume, and motor map area location) were obtained from both hands and hemispheres at baseline and two, four, and six weeks of in-patient rehabilitation. Results. There was a wide spectrum of hand motor impairment at baseline and hand motor recovery over time. Hand motor function and recovery correlated significantly with (i) reduction of cortical excitability, (ii) reduction in size and volume of cortical hand motor representation, and (iii) a medial and anterior shift of the center of gravity of cortical hand motor representation within the contralesional hemisphere. Conclusion. Recovery of motor function of the affected hand after stroke is accompanied by definite changes in excitability, size, volume, and location of hand motor representation over the contralesional primary motor cortex. These measures may serve as surrogate markers for the outcome of hand motor rehabilitation after stroke.
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Mano/fisiopatología , Corteza Motora/fisiopatología , Recuperación de la Función , Accidente Cerebrovascular/fisiopatología , Adulto , Anciano , Anciano de 80 o más Años , Excitabilidad Cortical , Potenciales Evocados Motores , Femenino , Lateralidad Funcional , Mano/inervación , Humanos , Masculino , Persona de Mediana Edad , Actividad Motora , Plasticidad Neuronal , Pruebas Neuropsicológicas , Estimulación Magnética TranscranealRESUMEN
BACKGROUND: No specific early biomarker is available to measure kidney injury after kidney transplantation (KT). Both neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury marker 1 (KIM-1) increase after oxidative injury. Their potential as early biomarkers was evaluated in this one-arm pilot study. MATERIALS AND METHODS: Twenty consecutive KT patients receiving a kidney from a donation after circulatory death donor were included. Graft perfusate was collected, as well as serum samples before transplantation, at the end of surgery, and 1, 4, and 7 days after transplantation. NGAL and KIM-1 were measured using ELISA. Kidney function and delayed graft function (DGF) were monitored. RESULTS: In this cohort, 85% of the KT patients developed DGF. Perfusate NGAL correlated with donor age (r2 = 0.094, p = 0.01) and serum creatinine (r2 = 0.243, p = 0.05). A cardiac cause of death was associated with higher NGAL in the perfusate (p = 0.03). Serum NGAL at day 1 was significantly higher in patients with DGF (730 ng/ml, range 490-1,655, vs. 417 ng/ml, range 232-481; p = 0.01). Serum NGAL levels at day 1, 4, and 7 correlated with the duration of DGF. KIM-1 was not detectable in the perfusate or in the serum until postoperative day 4 in 80% of patients. CONCLUSIONS: NGAL in the perfusate correlates with known donor risk factors for DGF. For the first time, we describe that serum NGAL at day 1 can discriminate between DGF and immediate graft function. Also, serum NGAL levels at day 1, 4, and 7 correlate with the duration of DGF. No association with KIM-1 was found. These data suggest that NGAL may be used as an early biomarker to detect DGF and warrants further study.
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BACKGROUND: Effective handoffs in the intensive care unit (ICU) are key to patient safety. PURPOSE: This article aims to raise awareness of the significance of structured and thorough handoffs and highlights possible challenges as well as means for improvement. MATERIALS AND METHODS: Based on the available literature, the evidence regarding handoffs in ICUs is summarized and suggestions for practical implementation are derived. RESULTS: The quality of handoffs has an impact on patient safety. At the same time, communication in the intensive care setting is particularly challenging due to the complexity of cases, a disruptive work environment, and a multitude of inter- and intraprofessional interactions. Hierarchical team structures, deficiencies in feedback and error-management culture, (technical) language barriers in communication, as well as substantial physical and psychological stress may negatively influence the effectiveness of handoffs. Sets of interventions such as the implementation of checklists, mnemonics, and communication workshops contribute to a more structured and thorough handoff process and have the potential to significantly improve patient safety. CONCLUSION: Effective handoffs are the cornerstone of high-quality and safe patient care but face particular challenges in ICUs. Interventional measures such as structuring handoff concepts and periodic communication trainings can help to improve handoffs and thus increase patient safety.
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Unidades de Cuidados Intensivos , Pase de Guardia , Seguridad del Paciente , Humanos , Pase de Guardia/organización & administración , Pase de Guardia/normas , Alemania , Lista de Verificación , Comunicación Interdisciplinaria , Errores Médicos/prevención & control , Grupo de Atención al Paciente/organización & administración , Cuidados Críticos/normasRESUMEN
The principal component analysis (PCA), non-metric multidimensional scaling (MDS) and analysis of similarity (ANOSIM) are multivariate statistical techniques that graphically represent numerical measures of several factors and display multiple relationships that may exist between them. In this study, we evaluated the applicability of these techniques to analyze the nutritional quality of diet, using as model, the bioassay rice weevil. The diets tested were: corn starch, potato starch, 5% glucose, peas, starved and starved with water supply. The variables studied were: survival, weight change and body composition. The PCA and MDS showed positive relationships of survival and weight change with body fat and carbohydrate parameters. Fat and carbohydrates were greater in starches diets, similar to the positive control. The PCA showed differences between populations fed with different diets, whereas the MDS showed similarity between diets. Both studies defined a gradient of the nutritive value of diets in the x-axis. The ANOSIM indicate significant (p < 0.05) differences between groups. This test is necessary to support the results obtained in the PCA and MDS. The application of these statistical tools is promising to analyze complex processes such as interaction of differents variables to measure the nutritional quality of diets.
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Alimentación Animal , Bioensayo , Modelos Biológicos , Gorgojos/crecimiento & desarrollo , Animales , Composición Corporal , Análisis Multivariante , Análisis de Componente Principal , Reproducibilidad de los Resultados , Factores de Tiempo , Gorgojos/fisiología , Aumento de PesoRESUMEN
BACKGROUND: Metabolic surgery is the most effective treatment for obesity and may improve obesity-related pain syndromes. However, the effect of surgery on the persistent use of opioids in patients with a history of prior opioid use remains unclear. OBJECTIVE: To determine the effect of metabolic surgery on opioid use behaviors in patients with prior opioid use. SETTING: A consortium of public and private hospitals in Michigan. METHODS: Using a statewide metabolic-specific data registry, we identified 16,820 patients who self-reported opioid use before undergoing metabolic surgery between 2006 and 2020 and analyzed the 8506 (50.6%) patients who responded to 1-year follow-up. We compared patient characteristics, risk-adjusted 30-day postoperative outcomes, and weight loss between patients who self-reported discontinuing opioid use 1 year after surgery and those who did not. RESULTS: Among patients who self-reported using opioids before metabolic surgery, 3864 (45.4%) discontinued use 1 year after surgery. Predictors of persistent opioid use included an annual income of <$10,000 (odds ratio [OR] = 1.24; 95% confidence interval [CI], 1.06-1.44; P = .006), Medicare insurance (OR = 1.48; 95% CI, 1.32-1.66; P < .0001), and preoperative tobacco use (OR = 1.36; 95% CI, 1.16-1.59; P = .0001). Patients with persistent use were more likely to have a surgical complication (9.6% versus 7.5%, P = .0328) and less percent excess weight loss (61.6% versus 64.4%, P < .0001) than patients who discontinued opioids after surgery. There were no differences in the morphine milligram equivalents prescribed within the first 30 days following surgery between groups (122.3 versus 126.5, P = .3181). CONCLUSIONS: Nearly half of patients who reported taking opioids before metabolic surgery discontinued use at 1 year. Targeted interventions aimed at high-risk patients may increase the number of patients who discontinue opioid use after metabolic surgery.
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Analgésicos Opioides , Cirugía Bariátrica , Anciano , Estados Unidos , Humanos , Analgésicos Opioides/uso terapéutico , Medicare , Obesidad , Hospitales PrivadosRESUMEN
INTRODUCTION: Non-invasive brain stimulation can modulate both neural processing and behavioral performance. Its effects may be influenced by the stimulated area and hemisphere. In this study (EC no. 09083), repetitive transcranial magnetic stimulation (rTMS) was applied to the primary motor cortex (M1) or dorsal premotor cortex (dPMC) of either the right or left hemisphere, while evaluating cortical neurophysiology and hand function. METHODS: Fifteen healthy subjects participated in this placebo-controlled crossover study. Four sessions of real 1 Hz rTMS (110% of rMT, 900 pulses) over (i) left M1, (ii) right M1, (iii) left dPMC, (iv) right dPMC, and one session of (v) placebo 1 Hz rTMS (0% of rMT, 900 pulses) over the left M1 were applied in randomized order. Motor function of both hands (Jebsen-Taylor Hand Function Test (JTHFT)) and neural processing within both hemispheres (motor evoked potentials (MEPs), cortical silent period (CSP), and ipsilateral silent period (ISP)) were evaluated prior and after each intervention session. RESULTS: A lengthening of CSP and ISP durations within the right hemisphere was induced by 1 Hz rTMS over both areas and hemispheres. No such intervention-induced neurophysiological changes were detected within the left hemisphere. Regarding JTHFT and MEP, no intervention-induced changes ensued. Changes of hand function correlated with neurophysiological changes within both hemispheres, more often for the left than the right hand. CONCLUSIONS: Effects of 1 Hz rTMS can be better captured by neurophysiological than behavioral measures. Hemispheric differences need to be considered for this intervention.
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Saltmarshes are highly productive environments, exhibiting high abundances of organosulfur compounds. Dimethylsulfoniopropionate (DMSP) is produced in large quantities by algae, plants, and bacteria and is a potential precursor for dimethylsulfoxide (DMSO) and dimethylsulfide (DMS). DMSO serves as electron acceptor for anaerobic respiration leading to DMS formation, which is either emitted or can be degraded by methylotrophic prokaryotes. Major products of these reactions are trace gases with positive (CO2, CH4) or negative (DMS) radiative forcing with contrasting effects on the global climate. Here, we investigated organic sulfur cycling in saltmarsh sediments and followed DMSO reduction in anoxic batch experiments. Compared to previous measurements from marine waters, DMSO concentrations in the saltmarsh sediments were up to ~300 fold higher. In batch experiments, DMSO was reduced to DMS and subsequently consumed with concomitant CH4 production. Changes in prokaryotic communities and DMSO reductase gene counts indicated a dominance of organisms containing the Dms-type DMSO reductases (e.g., Desulfobulbales, Enterobacterales). In contrast, when sulfate reduction was inhibited by molybdate, Tor-type DMSO reductases (e.g., Rhodobacterales) increased. Vibrionales increased in relative abundance in both treatments, and metagenome assembled genomes (MAGs) affiliated to Vibrio had all genes encoding the subunits of DMSO reductases. Molar conversion ratios of <1.3 CH4 per added DMSO were accompanied by a predominance of the methylotrophic methanogens Methanosarcinales. Enrichment of mtsDH genes, encoding for DMS methyl transferases in metagenomes of batch incubations indicate their role in DMS-dependent methanogenesis. MAGs affiliated to Methanolobus carried the complete set of genes encoding for the enzymes in methylotrophic methanogenesis.
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Alphaproteobacteria , Compuestos de Sulfonio , Dimetilsulfóxido/metabolismo , Oxidorreductasas/genética , Oxidorreductasas/metabolismo , Bacterias/genética , Bacterias/metabolismo , Alphaproteobacteria/metabolismo , Sulfuros/metabolismo , Compuestos de Sulfonio/metabolismoRESUMEN
The expression of pro-lymphangiogenic VEGF-C in primary tumors is associated with sentinel lymph node metastasis in most solid cancer types. However, the impact of VEGF-C on distant organ metastasis remains unclear. Perivascular tumor-associated macrophages (TAMs) play a crucial role in guiding hematogenous spread of cancer cells by establishing metastatic pathways within the tumor microenvironment. This process supports breast cancer cell intravasation and metastatic dissemination. We show here that VEGF-C-expressing TAMs reduce the dissemination of mammary cancer cells to the lungs while concurrently increasing lymph node metastasis. These TAMs express podoplanin and interact with normalized tumor blood vessels expressing VEGFR3. Moreover, clinical data suggest inverse association between VEGF-C-expressing TAMs and breast cancer malignancy. Thus, our study elucidates the paradoxical role of VEGF-C-expressing TAMs in redirecting cancer cells to preferentially disseminate to lymph nodes rather than to lungs, partially achieved by normalizing tumor blood vessels and promoting lymphangiogenesis.
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Neoplasias de la Mama , Humanos , Femenino , Metástasis Linfática , Neoplasias de la Mama/patología , Macrófagos Asociados a Tumores/metabolismo , Factor C de Crecimiento Endotelial Vascular/metabolismo , Linfangiogénesis , Microambiente TumoralRESUMEN
Murine syngeneic tumor models have been used extensively for cancer research for several decades and have been instrumental in driving the discovery and development of cancer immunotherapies. These tumor models are very simplistic cancer models, but recent reports have, however, indicated that the different inoculated cancer cell lines can lead to the formation of unique tumor microenvironments (TMEs). To gain more knowledge from studies based on syngeneic tumor models, it is essential to obtain an in-depth understanding of the cellular and molecular composition of the TME in the different models. Additionally, other parameters that are important for cancer progression, such as collagen content and mechanical tissue stiffness across syngeneic tumor models have not previously been reported. Here, we compare the TME of tumors derived from six common syngeneic tumor models. Using flow cytometry and transcriptomic analyses, we show that strikingly unique TMEs are formed by the different cancer cell lines. The differences are reflected as changes in abundance and phenotype of myeloid, lymphoid, and stromal cells in the tumors. Gene expression analyses support the different cellular composition of the TMEs and indicate that distinct immunosuppressive mechanisms are employed depending on the tumor model. Cancer-associated fibroblasts (CAFs) also acquire very different phenotypes across the tumor models. These differences include differential expression of genes encoding extracellular matrix (ECM) proteins, matrix metalloproteinases (MMPs), and immunosuppressive factors. The gene expression profiles suggest that CAFs can contribute to the formation of an immunosuppressive TME, and flow cytometry analyses show increased PD-L1 expression by CAFs in the immunogenic tumor models, MC38 and CT26. Comparison with CAF subsets identified in other studies shows that CAFs are skewed towards specific subsets depending on the model. In athymic mice lacking tumor-infiltrating cytotoxic T cells, CAFs express lower levels of PD-L1 and lower levels of fibroblast activation markers. Our data underscores that CAFs can be involved in the formation of an immunosuppressive TME.
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Fibroblastos Asociados al Cáncer , Neoplasias , Animales , Ratones , Antígeno B7-H1 , Microambiente Tumoral , Proteínas de la Matriz Extracelular , Inmunosupresores , Ratones Desnudos , Fenotipo , Neoplasias/genéticaRESUMEN
Rationale: Intrinsic brain tumors, such as gliomas are largely resistant to immunotherapies including immune checkpoint blockade. Adoptive cell therapies (ACT) including chimeric antigen receptor (CAR) or T cell receptor (TCR)-transgenic T cell therapy targeting glioma-associated antigens are an emerging field in glioma immunotherapy. However, imaging techniques for non-invasive monitoring of adoptively transferred T cells homing to the glioma microenvironment are currently lacking. Methods: Ultrasmall iron oxide nanoparticles (NP) can be visualized non-invasively by magnetic resonance imaging (MRI) and dedicated MRI sequences such as T2* mapping. Here, we develop a protocol for efficient ex vivo labeling of murine and human TCR-transgenic and CAR T cells with iron oxide NPs. We assess labeling efficiency and T cell functionality by flow cytometry and transmission electron microscopy (TEM). NP labeled T cells are visualized by MRI at 9.4 T in vivo after adoptive T cell transfer and correlated with 3D models of cleared brains obtained by light sheet microscopy (LSM). Results: NP are incorporated into T cells in subcellular cytoplasmic vesicles with high labeling efficiency without interfering with T cell viability, proliferation and effector function as assessed by cytokine secretion and antigen-specific killing assays in vitro. We further demonstrate that adoptively transferred T cells can be longitudinally monitored intratumorally by high field MRI at 9.4 Tesla in a murine glioma model with high sensitivity. We find that T cell influx and homogenous spatial distribution of T cells within the TME as assessed by T2* imaging predicts tumor response to ACT whereas incomplete T cell coverage results in treatment resistance. Conclusion: This study showcases a rational for monitoring adoptive T cell therapies non-invasively by iron oxide NP in gliomas to track intratumoral T cell influx and ultimately predict treatment outcome.
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Glioma , Linfocitos T , Humanos , Animales , Ratones , Glioma/diagnóstico por imagen , Glioma/terapia , Inmunoterapia Adoptiva , Receptores de Antígenos de Linfocitos T , Tratamiento Basado en Trasplante de Células y Tejidos , Microambiente TumoralRESUMEN
Benthic microbial communities of intertidal zones perform important biogeochemical processes and provide accessible nutrients for higher organisms. To unravel the ecosystem services of salt marsh microbial communities, we analyzed bacterial diversity and metabolic potential along the land-sea transition zone on seasonal scales on the German North Sea Island of Spiekeroog. Analysis of bacterial community was based on amplicon sequencing of 16S rRNA genes and -transcripts. Insights into potential community function were obtained by applying the gene prediction tool tax4fun2. We found that spatial variation of community composition was greater than seasonal variations. Alphaproteobacteria (15%), Gammaproteobacteria (17%) and Planctomycetes (11%) were the most abundant phyla across all samples. Differences between the DNA-based resident and RNA-based active communities were most pronounced within the Planctomycetes (17% and 5%) and Cyanobacteriia (3% and 12%). Seasonal differences were seen in higher abundance of Gammaproteobacteria in March 2015 (25%) and a cyanobacterial summer bloom, accounting for up to 70% of the active community. Taxonomy-based prediction of function showed increasing potentials for nitrification, assimilatory nitrate and sulfate reduction from sea to land, while the denitrification and dissimilatory sulfate reduction increased towards the sea. In conclusion, seasonal differences mainly occurred by blooming of individual taxa, while the overall community composition strongly corresponded to locations. Shifts in their metabolism could drive the salt marsh's function, e.g., as a potential nitrogen sink.
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BACKGROUND: Coronavirus disease 2019 created unintended but significant experiential barriers for surgical learners to interact at the bedside for teaching/case presentations. We hypothesized that an international grand rounds using the Microsoft HoloLens 2 extended reality (XR) headset would create an improved bedside-learning experience compared to traditional grand rounds formats. STUDY DESIGN: From December 2020 to March 2021, the world's first 2 international mixed reality grand rounds events using the HoloLens 2 headset were held, broadcasting transatlantically (between the University of Michigan and the Imperial College of London) bedside rounding experiences on 5 complex surgical patients to an international audience of 325 faculty, residents, and medical trainees. Participants completed pre- and post-event surveys to assess their experience. RESULTS: Of the 325 participants, 267 (80%) completed pre-surveys, and 95 (29%) completed both the pre- and post-surveys. Respondents (average age, 38 y; 44% women, 56% men; 211 US, 56 UK) included 92 (34%) medical students and residents and 175 faculty and staff. In the pre-event survey, 76% had little or no earlier experience with XR devices, and 94% thought implementation of XR into medical curricula was valuable. In the post-survey, 96% thought telerounding using XR technology was important for the current era, and 99% thought the ability to visualize the examination, imaging, and laboratory results at bedside via XR rounding was highly valuable and that this format was superior to traditional grand rounds. CONCLUSIONS: Almost all of the participants in the mixed reality international grand rounds felt the immersive XR experiences-allowing visualization of clinical findings, imaging, and laboratory results at the patient's bedside-were superior to a traditional grand rounds format, and that it could be a valuable tool for surgical teaching and telerounding.
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Realidad Aumentada , COVID-19/epidemiología , Cooperación Internacional , Procedimientos Quirúrgicos Operativos/educación , Rondas de Enseñanza , Realidad Virtual , Humanos , Londres , Michigan , Encuestas y Cuestionarios/estadística & datos numéricosRESUMEN
BACKGROUND: Public health campaigns aimed at curbing the spread of COVID-19 are important in reducing disease transmission, but traditional information-based campaigns have received unexpectedly extreme backlash. OBJECTIVE: This study aimed to investigate whether customizing of public service announcements (PSAs) providing health guidelines to match individuals' identities increases their compliance. METHODS: We conducted a within- and between-subjects, randomized controlled cross-sectional, web-based study in July 2020. Participants viewed two PSAs: one advocating wearing a mask in public settings and one advocating staying at home. The control PSA only provided information, and the treatment PSAs were designed to appeal to the identities held by individuals; that is, either a Christian identity or an economically motivated identity. Participants were asked about their identity and then provided a control PSA and treatment PSA matching their identity, in random order. The PSAs were of approximately 100 words. RESULTS: We recruited 300 social media users from Amazon Mechanical Turk in accordance with usual protocols to ensure data quality. In total, 8 failed the data quality checks, and the remaining 292 were included in the analysis. In the identity-based PSA, the source of the PSA was changed, and a phrase of approximately 12 words relevant to the individual's identity was inserted. A PSA tailored for Christians, when matched with a Christian identity, increased the likelihood of compliance by 12 percentage points. A PSA that focused on economic values, when shown to individuals who identified as economically motivated, increased the likelihood of compliance by 6 points. CONCLUSIONS: Using social media to deliver COVID-19 public health announcements customized to individuals' identities is a promising measure to increase compliance with public health guidelines. TRIAL REGISTRATION: ISRCTN Registry 22331899; https://www.isrctn.com/ISRCTN22331899.
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COVID-19/prevención & control , Adhesión a Directriz/estadística & datos numéricos , Comunicación Persuasiva , Avisos de Utilidad Pública como Asunto , Identificación Social , Adolescente , Adulto , Anciano , COVID-19/epidemiología , Estudios Transversales , Femenino , Guías como Asunto , Humanos , Masculino , Máscaras , Persona de Mediana Edad , Cuarentena , Medios de Comunicación Sociales , Estados Unidos/epidemiología , Adulto JovenRESUMEN
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RESUMEN
The alpha variant of the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is associated with higher transmissibility and possibly higher mortality compared with wild-type SARS-CoV-2. However, few data are available on the clinical course of infections with the alpha variant compared with wild-type SARS-CoV-2 in critically ill patients in intensive care units (ICUs). Therefore, we retrospectively analyzed patients admitted to our ICU due to SARS-CoV-2 Alpha variant infection and compared characteristics and course to patients with SARS-CoV-2 wild-type infection. The median age of patients with Alpha variant infections was 57 years compared to 62 years in the wild-type group. ICU survival was 41/80 (51%) in the Alpha variant group and 35/80 (44%) in the wild-type group (p = 0.429). Results of a matched-pair analysis based on age and sex illustrated that 45/58 patients (77.6%) in the Alpha variant group and 38/58 (65.5%) patients in the wild-type group required mechanical ventilation (p = 0.217). ICU survival was documented for 28/58 patients (48.3%) in the Alpha variant group and 27/58 patients (46.6%) in the wild-type group (p = 1). Thus, ICU mortality among patients with SARS-CoV-2 infections remains high. Although the Alpha variant group included younger patients requiring mechanical ventilation, no significant differences between patients with the SARS-CoV-2 Alpha variant and the SARS-CoV-2 wild-type, respectively, were detected with respect to clinical course and ICU mortality. For future VOCs, we believe it would be important to obtain valid and rapid data on the clinical course of critically ill patients who test positive for COVID-19 in order to perform appropriate epidemiological planning of intensive care capacity.