RESUMEN
BACKGROUND: Chronic respiratory diseases (CRDs) affect at least 545 million people globally, leading to symptoms such as dyspnoea, fatigue and limited physical activity. Pulmonary rehabilitation (PR) programmes aim to improve the exercise capacity and quality of life of patients with CRD through exercise training. High-flow nasal cannula (HFNC) therapy shows potential as an adjunct treatment during exercise, but its effects on CRD populations are unclear. The purpose of this systematic review was to evaluate the effects of HFNC during exercise in people with CRD. METHODS: A systematic review was conducted and eight databases and other resources were searched from inception (28 June 2022) to 4 April 2023. Studies that used adult patients with CRD and randomised controlled trial that compared the effect of HFNC versus standard care (conventional oxygen therapy or room air) during exercise were included. Two authors independently selected trials, extracted the data, assessed risks of bias and employed the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach to judging the certainty of evidence. We pooled trials using random-effect models and inverse variance estimation. RESULTS: Seventeen studies (n=8406) were included in the review (570 patients). The evidence suggests that HFNC increases exercise time after multiple training sessions (weighted mean difference (WMD)=160.58 s; 95% 95% CI=67.32-253.83, 2 studies) and increase after a single session (WMD=72.10 s; 95% CI=28.95-115.24, 11 studies). HFNC may result in little improvements in secondary outcomes (quality of life, dyspnoea, comfort, complications and adherence). DISCUSSION: The evidence suggests that HFNC may increase functional exercise capacity and positively enhance secondary outcomes. Continued research is justified to elucidate the role of HFNC in PR during exercise training. PROSPERO REGISTRATION NUMBER: CRD42022336263.
Asunto(s)
Cánula , Terapia por Inhalación de Oxígeno , Humanos , Terapia por Inhalación de Oxígeno/métodos , Enfermedad Crónica , Ejercicio Físico/fisiología , Calidad de Vida , Tolerancia al Ejercicio , Adulto , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
Anti-double-stranded DNA antibodies (anti-dsDNA) serve as a crucial serological indicator for systemic lupus erythematosus (SLE). Chemiluminescent immunoassay (CIA) is mainly used in clinical diagnosis of SLE, but suffers from low specificity, partially because the use of dsDNA antigens of varied sources in current CIA kits that sometimes led to controversial results. On the basis that anti-dsDNA in healthy individuals tend to selectively bind with dsDNA originating from pathogens, whereas pathogenic anti-dsDNA in SLE patients bind all forms of dsDNA, here we proposed the use of dsDNA fragment derived from human genome as antigen (synthesized via PCR using the human genomic DNA as the template). A magnetic bead-based immunofluorescence assay (IFA) was thus developed for SLE diagnosis, which exhibited improved sensitivity and specificity over CIA using the WHO reference reagent (15/174) as standard. For clinical serum sample analysis (n = 590), IFA exhibited an accuracy of 71.9% that was higher than CIA (65.3%). Crucially, the IFA results exhibited stronger correlations with the activity of SLE, renal involvement, and its prognosis. Besides the improved clinical diagnosis, the proposed IFA also holds great promise in assay standardization due to the high homogeneity of the synthetic dsDNA.
RESUMEN
From early on, infants show a preference for infant-directed speech (IDS) over adult-directed speech (ADS), and exposure to IDS has been correlated with language outcome measures such as vocabulary. The present multi-laboratory study explores this issue by investigating whether there is a link between early preference for IDS and later vocabulary size. Infants' preference for IDS was tested as part of the ManyBabies 1 project, and follow-up CDI data were collected from a subsample of this dataset at 18 and 24 months. A total of 341 (18 months) and 327 (24 months) infants were tested across 21 laboratories. In neither preregistered analyses with North American and UK English, nor exploratory analyses with a larger sample did we find evidence for a relation between IDS preference and later vocabulary. We discuss implications of this finding in light of recent work suggesting that IDS preference measured in the laboratory has low test-retest reliability.
RESUMEN
Scientific literature on the health effects of air pollution is diverse, and broadly acknowledges the importance of human experience and social and economic precarity as modifying factors. Still, the inclusion of the embodied experience of air pollution has been limited. Also, the health effects of pollution are often studied at the group or population level, without adequately considering individual difference. This paper uses a Bio3Science framework, which integrates biology, biography, and biosphere, to explore how air pollution affects residents in Medellín, Colombia. By using qualitative research on individual experiences of air pollution (biography) to probe the intersection of individual health (biology) and environment (biosphere), we illustrate how pollution shapes lived rhythms at multiple scales. Our findings emphasize that air pollution's health impacts extend beyond measurable pollutants to include the complex synergies of smoke, noise, stress, and disruptions to daily life. This comprehensive approach provides a nuanced understanding of how air pollution materially shapes the lives of individuals and communities, advocating for research models that capture the subtle, everyday experiences often overlooked by traditional group or population-level analyses.
Asunto(s)
Contaminación del Aire , Material Particulado , Investigación Cualitativa , Humanos , Contaminación del Aire/efectos adversos , Colombia , Material Particulado/análisis , Material Particulado/efectos adversos , Exposición a Riesgos Ambientales/efectos adversos , Contaminantes Atmosféricos/análisis , Contaminantes Atmosféricos/efectos adversosRESUMEN
Rheumatoid arthritis (RA) is an inflammatory autoimmune disease mediated by immune cell dysfunction for which there is no universally effective prevention and treatment strategy. As primary effector cells, neutrophils are important in the inflammatory joint attack during the development of RA. Here, we used single-cell sequencing technology to thoroughly analyze the phenotypic characteristics of bone marrow-derived neutrophils in type II collagen (COL2)-induced arthritis (CIA) models, including mice primed and boosted with COL2. We identified a subpopulation of neutrophils with high expression of neutrophil cytoplasmic factor 1 (NCF1) in primed mice, accompanied by a characteristic reactive oxygen species (ROS) response, and a decrease in Ncf1 expression in boosted mice with the onset of arthritis. Furthermore, we found that after ROS reduction, arthritis occurred in primed mice but was attenuated in boosted mice. This bidirectional effect of ROS suggested a protective role of ROS during immune priming. Mechanistically, we combined functional assays and metabolomics identifying Ncf1-deficient neutrophils with enhanced migration, chemotactic receptor CXCR2 expression, inflammatory cytokine secretion, and Th1/Th17 differentiation. This alteration was mainly due to the metabolic reprogramming of Ncf1-deficient neutrophils from an energy supply pathway dominated by gluconeogenesis to an inflammatory immune pathway associated with the metabolism of histidine, glycine, serine, and threonine signaling, which in turn induced arthritis. In conclusion, we have systematically identified the functional and inflammatory phenotypic characteristics of neutrophils under ROS regulation, which provides a theoretical basis for understanding the pathogenesis of RA, to further improve prevention strategies and identify novel therapeutic targets.
RESUMEN
Carpal tunnel syndrome (CTS) is the most frequent entrapment neuropathy. Patients commonly experience neuropathic pain, leading them to seek medical advice. However, other symptoms experienced in patients with CTS, such as paresthesia, dysesthesia and allodynia, classed as positive sensory symptoms (PSS), are often under-reported. In the present study, patients with surgically-managed CTS were observed pre- and post-surgery to evaluate PSS, using the symptoms scale component of the Boston Carpal Tunnel Questionnaire (BCTQ) and the Sensory Frequency of Symptoms Scale. In total, 19 patients were included in the present study, with 79% female patients, and a mean age of 54±10.59 years. In addition, the mean follow-up was 63±29.91 months. The results of the present study revealed a pre-surgery BCTQ score of 3.52±0.63 and a post-surgery BCTQ score of 1.58±0.61. Notably, improvements in pain were observed, at 7.7±2.26 pre-surgery compared with 1.65±2.88 post-surgery. Compared with pre-surgery, post-surgery paresthesia scores were reduced from 2.94±0.82 to 0.47±0.45, dysesthesia scores were reduced from 2.52±0.84 to 0.47±0.39 and allodynia scores were reduced from 0.63±0.75 to 0.26±0.47. In conclusion, the results of the present study demonstrated that median nerve decompression ameliorated CTS symptoms, such as paresthesia and dysesthesia. However, further investigations are required to verify the benefits of surgery in relieving allodynia.
RESUMEN
Humans can use the contents of memory to construct scenarios and events that they have not encountered before, a process colloquially known as imagination. Much of our current understanding of the neural mechanisms mediating imagination is limited by paradigms that rely on participants' subjective reports of imagined content. Here, we used a novel behavioral paradigm that was designed to systematically evaluate the contents of an individual's imagination. Participants first learned the layout of four distinct rooms containing five wall segments with differing geometrical characteristics, each associated with a unique object. During functional MRI, participants were then shown two different wall segments or objects on each trial and asked to first, retrieve the associated objects or walls, respectively (retrieval phase) and then second, imagine the two objects side-by-side or combine the two wall segments (imagination phase). Importantly, the contents of each participant's imagination were interrogated by having them make a same/different judgment about the properties of the imagined objects or scenes. Using univariate and multivariate analyses, we observed widespread activity across occipito-temporal cortex for the retrieval of objects and for the imaginative creation of scenes. Interestingly, a classifier, whether trained on the imagination or retrieval data, was able to successfully differentiate the neural patterns associated with the imagination of scenes from that of objects. Our results reveal neural differences in the cued retrieval of object and scene memoranda, demonstrate that different representations underlie the creation and/or imagination of scene and object content, and highlight a novel behavioral paradigm that can be used to systematically evaluate the contents of an individual's imagination.
Asunto(s)
Mapeo Encefálico , Imaginación , Imagen por Resonancia Magnética , Humanos , Imaginación/fisiología , Masculino , Femenino , Adulto Joven , Adulto , Recuerdo Mental/fisiología , Encéfalo/fisiología , Encéfalo/diagnóstico por imagenRESUMEN
The inducers of neutrophil extracellular trap (NET) formation are heterogeneous and consequently, there is no specific pathway or signature molecule indispensable for NET formation. But certain events such as histone modification, chromatin decondensation, nuclear envelope breakdown, and NET release are ubiquitous. During NET formation, neutrophils drastically rearrange their cytoplasmic, granular and nuclear content. Yet, the exact mechanism for decoding each step during NET formation still remains elusive. Here, we investigated the mechanism of nuclear envelope breakdown during NET formation. Immunofluorescence microscopic evaluation revealed a gradual disintegration of outer nuclear membrane protein nesprin-1 and alterations in nuclear morphology during NET formation. MALDI-TOF analysis of NETs that had been generated by various inducers detected the accumulation of nesprin-1 fragments. This suggests that nesprin-1 degradation occurs before NET release. In the presence of a calpain-1, inhibitor nesprin-1 degradation was decreased in calcium driven NET formation. Microscopic evaluation confirmed that the disintegration of the lamin B receptor (LBR) and the collapse of the actin cytoskeleton occurs in early and later phases of NET release, respectively. We conclude that the calpain-1 degrades nesprin-1, orchestrates the weakening of the nuclear membrane, contributes to LBR disintegration, and promoting DNA release and finally, NETs formation.
Asunto(s)
Calpaína , Trampas Extracelulares , Receptor de Lamina B , Neutrófilos , Membrana Nuclear , Membrana Nuclear/metabolismo , Calpaína/metabolismo , Humanos , Trampas Extracelulares/metabolismo , Neutrófilos/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Proteínas Nucleares/metabolismo , Receptores Citoplasmáticos y Nucleares/metabolismo , Calcio/metabolismo , Proteínas del CitoesqueletoRESUMEN
The use of physical unclonable functions (PUFs) linked to the manufacturing process of the electronic devices supporting applications that exchange critical data over the Internet has made these elements essential to guarantee the authenticity of said devices, as well as the confidentiality and integrity of the information they process or transmit. This paper describes the development of a configurable PUF/TRNG module based on ring oscillators (ROs) that takes full advantage of the structure of modern programmable devices offered by Xilinx 7 Series families. The proposed architecture improves the hardware efficiency with two main objectives. On the one hand, we perform an exhaustive statistical characterization of the results derived from the exploitation of RO configurability. On the other hand, we undertake the development of a new version of the module that requires a smaller amount of resources while considerably increasing the number of output bits compared to other proposals previously reported in the literature. The design as a highly parameterized intellectual property (IP) module connectable through a standard interface to a soft- or hard-core general-purpose processor greatly facilitates its integration into embedded solutions while accelerating the validation and characterization of this element on the same electronic device that implements it. The studies carried out reveal adequate values of reliability, uniqueness, and unpredictability when the module acts as a PUF, as well as acceptable levels of randomness and entropy when it acts as a true random number generator (TRNG). They also illustrate the ability to obfuscate and recover identifiers or cryptographic keys of up to 4096 bits using an implementation of the PUF/TRNG module that requires only an array of 4×4 configurable logic blocks (CLBs) to accommodate the RO bank.
RESUMEN
The objective of this study was to determine prevalence and perform genomic analysis of Salmonella spp. and Campylobacter spp. isolated from different stages of an integrated NAE broiler complex. Environmental samples were screened with 3M-Molecular Detection System (MDS) and MDS positive samples were further processed for confirmation of results and identification. Core genome-based phylogenies were built for both bacteria isolated from this study along with selected NCBI genomes. The odds ratios and 95% confidence limits were compared among stages and sample types (α < 0.05) using multivariable model. Based on MDS results, 4% and 18% of total samples were positive for Salmonella spp. and Campylobacter spp. respectively. The odds of Salmonella detection in hatchery samples were 2.58 times as likely as compared to its detection in production farms' samples (P = 0.151) while the odds of Campylobacter detection in production farms' samples were 32.19 times as likely as its detection in hatchery (P = 0.0015). Similarly, the odds of Campylobacter detection in boot swabs, soil, water, and miscellaneous samples were statistically significant (P < 0.05) as compared with fly paper as reference group. The serovars identified for Salmonella were Typhimurium, Barranquilla, Liverpool, Kentucky, Enteritidis, Luciana, and Rough_O:r:1,5. For Campylobacter, the species identified were Campylobacter jejuni and Campylobacter coli. Phylogeny results show close genetic relatedness among bacterial strains isolated from different locations within the same stage and between different stages. The results show possibility of multiple entry points of such bacteria entering broiler complex and can potentially contaminate the final raw product in the processing plant. It suggests the need for a comprehensive control strategy with strict biosecurity measures and best management practices to minimize or eliminate such pathogens from the poultry food chain.
Asunto(s)
Infecciones por Campylobacter , Campylobacter , Pollos , Enfermedades de las Aves de Corral , Salmonelosis Animal , Salmonella , Animales , Pollos/microbiología , Campylobacter/genética , Campylobacter/aislamiento & purificación , Salmonella/genética , Salmonella/aislamiento & purificación , Enfermedades de las Aves de Corral/microbiología , Enfermedades de las Aves de Corral/epidemiología , Estudios Longitudinales , Infecciones por Campylobacter/veterinaria , Infecciones por Campylobacter/microbiología , Infecciones por Campylobacter/epidemiología , Salmonelosis Animal/microbiología , Salmonelosis Animal/epidemiología , Prevalencia , Crianza de Animales Domésticos/métodos , FilogeniaRESUMEN
OBJECTIVE: Recently, autoantibodies directed against the epithelial adhesion protein integrin αVß6 have been identified which strongly associate with ulcerative colitis (UC). We aimed to elucidate whether anti-integrin αVß6 (anti- αVß6) is present in primary sclerosing cholangitis (PSC), its associated inflammatory bowel disease or other cholestatic liver diseases and their persistence after proctocolectomy. DESIGN: We detected anti- αVß6 by an enzyme-linked immunosorbent assay in sera collected at two German tertiary centers, including healthy controls (N=62), UC (N=36), Crohn's disease (CD, N=65), PSC-IBD (78 samples from N=41 patients), PSC without IBD (PSC, 41 samples from N=18 patients), primary biliary cholangitis (PBC, N=24), autoimmune hepatitis (AIH, N=32), secondary sclerosing cholangitis (SSC, N=12) and metabolic dysfunction-associated steatotic liver disease (MASLD, N=24). Additionally, sera after proctocolectomy were studied (44 samples / N= 10 patients). Immunofluorescent analyses were performed in tissue samples from liver, large bile duct from surgical resections and colon of PSC patients. RESULTS: Anti- αVß6 occurred in 91% of UC, 17% of CD, 73% of PSC-IBD, 39% of PSC, 4% of PBC, 14% of AIH, and 0% of healthy controls, SSC or MASLD. Integrin αVß6 is selectively expressed in disease-associated epithelia of both bile duct and colon. Anti- αVß6 levels correlate moderately with intestinal disease activity in PSC-IBD, but only weakly with biliary disease. CONCLUSION: Anti- αVß6 frequently occur in patients suffering from PSC, especially in PSC-IBD. Anti- αVß6 levels positively correlate to IBD activity in PSC-IBD, but may also occur in the absence of clinically manifest IBD in PSC.
RESUMEN
CONTEXT: The study of epidemiological changes of traumatic spinal cord injury (TSCI) is needed due to its highly variable incidence. OBJECTIVE: To determine the incidence of TSCI in Spain and to describe the trend of clinical and demographic characteristics according to age group during a 10-year period. METHODS: A prospective cohort study was conducted. A multidisciplinary team evaluated all individuals with new TSCI. The data were recorded according to the International Spinal Cord Injury Core Data Sets. RESULTS: In a 10-year period, 933 new patients with TSCI were admitted to the hospital. The annual incidence of TSCI was 6.2 per million. The leading causes of injury were traffic accidents (38.5%), low-level falls (20.6%), and high-level falls (19.1%). Males, age group of 31-45 years, and cervical level of injury were the most common profiles of TSCI. In patients over 60 years,71.5% were injured following a fall, particularly low-level falls (47.2%). In patients under 60 years old, the leading cause of SCI was traffic accidents (46%). The proportion of tetraplegia in patients above 60 years was 68.3%, compared to 43.7% in patients under 60 years of age. Patients in the age group above 60 years were hospitalized with a shorter duration of rehabilitation compared to younger age group. CONCLUSIONS: Compared with globally estimated data reported in previous studies, this research demonstrated a low incidence of TSCI in Spain, suggesting a decrease in the last years. Falls and traffic accidents were the most common causes of TSCI in elderly and youth, respectively. Prevention programs should focus on these issues.
RESUMEN
Background/Objectives: In patients diagnosed with uncomplicated acute appendicitis (UAA), the absence of calcified deposits or stones, called appendicoliths, often leads to consideration of non-operative treatment (NOT), despite the notable treatment failure rate associated with this approach. Previous research has indirectly estimated the prevalence of appendicoliths to range between 15% and 38% retrospectively by CT scan, intraoperative palpation, and pathology report, thereby potentially missing certain concrements. Our hypothesis proposes that this reported prevalence significantly underestimates the occurrence of appendicoliths, which could explain the high failure rate of 29% of patients with appendicitis observed with NOT. Methods: In our prospective study, conducted with a cohort of 56 adult patients diagnosed with acute appendicitis (AA), we employed intraoperative extracorporeal incisions of the vermiform appendix, in addition to standard diagnostic methods. Results: Our findings revealed 50% more appendicoliths by intraoperative incision (n = 36, p < 0.001) compared to preoperative imaging (n = 24). Appendicoliths were present in 71.4% (n = 40, p < 0.001) of AA patients. Conclusions: These results suggest that conventional diagnostic procedures plausibly underestimate the actual prevalence of appendicoliths, potentially elucidating the frequent treatment failures observed in NOT approaches applied to patients with UAA.
RESUMEN
OBJECTIVE: The metabolism of different cells within the same microenvironment can differ and dictate physiological or pathological adaptions. Current single-cell analysis methods of metabolism are not label-free. METHODS: The study introduces a label-free, live-cell analysis method assessing endogenous fluorescence of NAD(P)H and FAD in surface-stained cells by flow cytometry. RESULTS: OxPhos inhibition, mitochondrial uncoupling, glucose exposure, genetic inactivation of glucose uptake and mitochondrial respiration alter the optical redox ratios of FAD and NAD(P)H as measured by flow cytometry. Those alterations correlate strongly with measurements obtained by extracellular flux analysis. Consequently, metabolically distinct live B-cell populations can be resolved, showing that human memory B-cells from peripheral blood exhibit a higher glycolytic flexibility than naïve B cells. Moreover, the comparison of blood-derived B- and T-lymphocytes from healthy donors and rheumatoid arthritis patients unleashes rheumatoid arthritis-associated metabolic traits in human naïve and memory B-lymphocytes. CONCLUSIONS: Taken together, these data show that the optical redox ratio can depict metabolic differences in distinct cell populations by flow cytometry.
Asunto(s)
Linfocitos B , Flavina-Adenina Dinucleótido , Citometría de Flujo , NAD , Análisis de la Célula Individual , Humanos , Citometría de Flujo/métodos , NAD/metabolismo , Flavina-Adenina Dinucleótido/metabolismo , Análisis de la Célula Individual/métodos , Linfocitos B/metabolismo , Mitocondrias/metabolismo , Linfocitos T/metabolismo , Oxidación-Reducción , Fluorescencia , Artritis Reumatoide/metabolismo , Glucólisis , Fosforilación Oxidativa , Femenino , Masculino , Glucosa/metabolismoRESUMEN
Background: This report aims to describe the neuromodulation effect on seizure control in a patient with a left hippocampal migrated electrode to the Posterior Sylvian Junction (PSJ) during a follow-up of 17 years. Case Description: We report a case of a female patient with drug-resistant epilepsy who initiated at seven years old and underwent a stereotactic frame-based insertion of a left hippocampal electrode for deep brain stimulation (DBS). Posterior migration of the electrode was identified at PSJ by postoperative magnetic resonance imaging one month after surgery. A consistent seizure reduction (Engel IC) was obtained with 2v-120 uS-145 Hz, contacts 0-3 negative, casing positive DBS parameters and maintained to this day. Patient data were collected from electronic medical records preceded by obtaining an informed consent for research and publication purposes. Stimulation parameter adjustments were confirmed with the digital records of the local device provider (Medtronic). Results: PSJ is a connectivity confluence point of white matter pathways in the posterior quadrant of the hemispheres. White mater DBS could be considered for research as a potential complementary target for neuromodulation of refractory epilepsy.
RESUMEN
Flue Gas Desulfurization (FGD) gypsum is a byproduct of the coal-fired power plant process commonly used to remove sulfur dioxide emissions from the flue gas. FGD gypsum has numerous industrial, agricultural, and environmental applications. This study aimed to explore a novel approach involving the use of FGD gypsum combined with different litter treatments as bedding for broiler production. It focused on performance metrics, including adjusted feed conversion ratio (AFCR) and average body weight (BW), foot pad dermatitis (FPD), and fear response over 5 consecutive flocks. A total of 1,800 one-day-old Ross 708 chicks were randomly assigned to 24 pens (75 birds/pen), divided into 6 treatment groups (4 pens/treatment), with 5 replications and raised until 42 d old (d). Treatments were gypsum that was decaked (D), rotovated (E), and rotovated then windrowed (F) between flocks. Control treatments using pine shavings were decaked (A), rotovated (B), and windrowed postrotovating (C). AFCR, average BW, and mortality were used as a measure of production. Foot pad dermatitis scores were taken on d42 using a scale of 0 (absence), 1 (mild), and 2 (severe). Response to observer and human approach test were used to measure fear response. Data were analyzed as a 2-way ANOVA (Proc Glimmix) for the main effects of bedding type and litter treatment. Means were identified using Tukey's HSD. No effect of bedding type or litter treatment was found for AFCR, BW, or mortality. FPD scores 2 and 1, were higher with pine shavings than gypsum (P = 0.01 and P = 0.01, respectively). While FPD scores 0 were higher for gypsum than the pine shaving (P = 0.01). No difference in fear response was found among birds raised on any of the gypsum litter treatments and any of the pine shaving litter treatments. Overall, the use of gypsum as bedding results in equivalent production and fear response to pine shavings, while increasing FPD quality when compared to pine shaving.
Asunto(s)
Sulfato de Calcio , Pollos , Miedo , Enfermedades del Pie , Vivienda para Animales , Enfermedades de las Aves de Corral , Animales , Pollos/fisiología , Sulfato de Calcio/química , Sulfato de Calcio/administración & dosificación , Sulfato de Calcio/farmacología , Enfermedades del Pie/veterinaria , Pisos y Cubiertas de Piso , Distribución Aleatoria , Masculino , Crianza de Animales Domésticos/métodos , Dermatitis/veterinariaRESUMEN
BACKGROUND: Treatment for autoimmune diseases such as systemic lupus erythematosus (SLE), idiopathic inflammatory myositis, and systemic sclerosis often involves long-term immune suppression. Resetting aberrant autoimmunity in these diseases through deep depletion of B cells is a potential strategy for achieving sustained drug-free remission. METHODS: We evaluated 15 patients with severe SLE (8 patients), idiopathic inflammatory myositis (3 patients), or systemic sclerosis (4 patients) who received a single infusion of CD19 chimeric antigen receptor (CAR) T cells after preconditioning with fludarabine and cyclophosphamide. Efficacy up to 2 years after CAR T-cell infusion was assessed by means of Definition of Remission in SLE (DORIS) remission criteria, American College of Rheumatology-European League against Rheumatism (ACR-EULAR) major clinical response, and the score on the European Scleroderma Trials and Research Group (EUSTAR) activity index (with higher scores indicating greater disease activity), among others. Safety variables, including cytokine release syndrome and infections, were recorded. RESULTS: The median follow-up was 15 months (range, 4 to 29). The mean (±SD) duration of B-cell aplasia was 112±47 days. All the patients with SLE had DORIS remission, all the patients with idiopathic inflammatory myositis had an ACR-EULAR major clinical response, and all the patients with systemic sclerosis had a decrease in the score on the EUSTAR activity index. Immunosuppressive therapy was completely stopped in all the patients. Grade 1 cytokine release syndrome occurred in 10 patients. One patient each had grade 2 cytokine release syndrome, grade 1 immune effector cell-associated neurotoxicity syndrome, and pneumonia that resulted in hospitalization. CONCLUSIONS: In this case series, CD19 CAR T-cell transfer appeared to be feasible, safe, and efficacious in three different autoimmune diseases, providing rationale for further controlled clinical trials. (Funded by Deutsche Forschungsgemeinschaft and others.).
Asunto(s)
Antígenos CD19 , Inmunoterapia Adoptiva , Lupus Eritematoso Sistémico , Agonistas Mieloablativos , Miositis , Esclerodermia Sistémica , Humanos , Antígenos CD19/administración & dosificación , Síndrome de Liberación de Citoquinas/etiología , Estudios de Seguimiento , Lupus Eritematoso Sistémico/terapia , Miositis/terapia , Esclerodermia Sistémica/terapia , Agonistas Mieloablativos/administración & dosificación , Ciclofosfamida/administración & dosificación , Infecciones/etiología , Resultado del TratamientoRESUMEN
BACKGROUND: Rehabilitation following anterior cruciate ligament (ACL) reconstruction surgery is essential to regain functionality and return to previous activity level. Electromyographic biofeedback may be an effective intervention for rehabilitation of patients following ACL surgery. OBJECTIVE: To synthesize the available evidence on the effect of electromyographic biofeedback in the treatment of quadriceps strength following ACL surgery. DESIGN: Systematic review with meta-analysis. DATA SOURCES: PubMed, EMBASE, CENTRAL and Epistemonikos were searched. ELIGIBILITY CRITERIA: Randomized clinical trials with patients undergoing ACL reconstruction surgery comparing biofeedback with a standard rehabilitation control group. DATA EXTRACTION AND DATA SYNTHESIS: Two authors selected articles and performed data extraction. The analysed outcomes were strength, function, pain, knee extension and balance. The risk of bias of individual studies was assessed using the Cochrane Risk of Bias Tool. Results were combined through random-effects meta-analysis, reporting mean differences. RESULTS: Eight articles were included in the qualitative analysis, and four articles were included in the quantitative analysis. The interventions lasted between 4 and 12 weeks. Three studies evaluated the effect of biofeedback on quadriceps strength; of these, two studies showed a significant difference in favour of the biofeedback group. In addition, biofeedback was found to improve knee extension [standardized mean difference -â¯1.3, 95% confidence interval (CI) -â¯1.74 to -0.86] and balance (one study). There was no significant difference in Lysholm score (mean difference -6.21, 95% CI -17.51 to 5.08; I2 =59%) or pain between the biofeedback group and the control group. CONCLUSION: Electromyographic biofeedback in knee rehabilitation could be useful following ACL reconstruction surgery. KEY MESSAGES: SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO (CRD42020193768).
Asunto(s)
Reconstrucción del Ligamento Cruzado Anterior , Biorretroalimentación Psicológica , Electromiografía , Fuerza Muscular , Músculo Cuádriceps , Humanos , Reconstrucción del Ligamento Cruzado Anterior/rehabilitación , Fuerza Muscular/fisiología , Lesiones del Ligamento Cruzado Anterior/cirugía , Lesiones del Ligamento Cruzado Anterior/rehabilitaciónRESUMEN
Pacifier use during childhood has been hypothesized to interfere with language processing, but, to date, there is limited evidence revealing detrimental effects of prolonged pacifier use on infant vocabulary learning. In the present study, parents of 12- and 24-month-old infants were recruited in Oslo (Norway). The sample included 1187 monolingual full-term born (without visual, auditory, or cognitive impairments) infants: 452 (230 girls; 222 boys) 12-month-olds and 735 (345 girls; 390 boys) 24-month-olds. Parents filled out an online Norwegian Communicative Development Inventory (CDI), which assesses the vocabulary in comprehension and production for 12-month-old infants and in production only for 24-month-old infants. CDI scores were transformed into age- and sex-adjusted percentiles using Norwegian norms. Additionally, parents retrospectively reported their child's daytime pacifier use, in hours, at 2-month intervals, from birth to the assessment date. Maternal education was used to control, in the analyses, for the socio-economic status. We found that greater pacifier use in an infant's lifespan was associated with lower vocabulary size. Pacifier use later in life was more negatively associated with vocabulary size than precocious use, and increased the odds of being a low language scorer. In sum, our study moves beyond the findings of momentary effects of experimentally induced "impairment" in articulators' movement on speech perception and suggests that, from 12 months of age, constraints on the infant's speech articulators (pacifier use) may be negatively associated with word comprehension and production. RESEARCH HIGHLIGHT: We examined the relationship between pacifier use and vocabulary sizes in production at 24 months of age and comprehension and production at 12 months of age. Lifespan Pacifier Use (LPU) was negatively correlated with vocabulary sizes in comprehension and production among 12-month-old infants and negatively correlated with production for 24-month-olds. Later pacifier use was found to be more negatively correlated with vocabulary size in infants, as compared to more precocious use. The amount of pacifier use in the 2 months prior to a child's second birthday was predictive of a higher prevalence of low vocabulary scores in 24-month-olds.