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SARS-CoV-2 vaccine response and rate of breakthrough infection in patients with hematological disorders.
No full textThe clinical efficacy of SARS-CoV-2 vaccines according to antibody response in immunosuppressed patients such as hematological patients has not yet been established. A prospective multicenter registry-based cohort study conducted from December 2020 to December 2021 by the Spanish transplant and cell therapy group was used to analyze the relationship of antibody response at 3-6 weeks after full vaccination (2 doses) with breakthrough SARS-CoV-2 infection in 1394 patients with hematological disorders. At a median follow-up of 165 days after complete immunization, 37 out of 1394 (2.6%) developed breakthrough SARS-CoV-2 infection at median of 77 days (range 7-195) after full vaccination. The incidence rate was 6.39 per 100 persons-year. Most patients were asymptomatic (19/37, 51.4%), whereas only 19% developed pneumonia. The mortality rate was 8%. Lack of detectable antibodies at 3-6 weeks after full vaccination was the only variable associated with breakthrough infection in multivariate logistic regression analysis (Odds Ratio 2.35, 95% confidence interval 1.2-4.6, p = 0.012). Median antibody titers were lower in cases than in non-cases [1.83 binding antibody units (BAU)/mL (range 0-4854.93) vs 730.81 BAU/mL (range 0-56,800), respectively (p = 0.007)]. We identified 250 BAU/mL as a cutoff above which incidence and severity of the infection were significantly lower. Our study highlights the benefit of developing an antibody response in these highly immunosuppressed patients. Level of antibody titers at 3 to 6 weeks after 2-dose vaccination links with protection against both breakthrough infection and severe disease for non-Omicron SARS-CoV-2 variants.S
Myostatin concentration is unreliable as a biomarker of disease progression in dysferlinopathy
No full textAversive memory formation in humans involves an amygdala-hippocampus phase code.
No full textMemory for aversive events is central to survival but can become maladaptive in psychiatric disorders. Memory enhancement for emotional events is thought to depend on amygdala modulation of hippocampal activity. However, the neural dynamics of amygdala-hippocampal communication during emotional memory encoding remain unknown. Using simultaneous intracranial recordings from both structures in human patients, here we show that successful emotional memory encoding depends on the amygdala theta phase to which hippocampal gamma activity and neuronal firing couple. The phase difference between subsequently remembered vs. not-remembered emotional stimuli translates to a time period that enables lagged coherence between amygdala and downstream hippocampal gamma. These results reveal a mechanism whereby amygdala theta phase coordinates transient amygdala -hippocampal gamma coherence to facilitate aversive memory encoding. Pacing of lagged gamma coherence via amygdala theta phase may represent a general mechanism through which the amygdala relays emotional content to distant brain regions to modulate other aspects of cognition, such as attention and decision-making.This project has received funding from the European Research Council
(ERC) under the European Union’s Horizon 2020 research and innovation programme (ERC-2018-COG 819814) and by the Swiss National Science
Foundation (funded by SNSF 204651 to J.S.). M.C. was supported by the
Comunidad de Madrid, Ayudas para la contratación de investigadores
predoctorales e investigadores postdoctorales cofinanciadas por Fondo
Social Europeo a través del Programa Operativo de Empleo Juvenil y la
Iniciativa de Empleo Juvenil (YEI) (PEJD-2017-POST/BMD-4763). L.K. was
supported by the German Research Foundation (DFG; KU 4060/1-1). We
thank the electroencephalography technicians at the Hospital Ruber
Internacional and the Swiss Epilepsy Center, as well as Isabel Montón
Quesada and Linda Zhang for technical assistance. We thank Dr. Rufin
VanRullen for providing helpful comments about the rationale behind
the phase opposition metrics.S
Morphofunctional and Molecular Assessment of Nutritional Status in Head and Neck Cancer Patients Undergoing Systemic Treatment: Role of Inflammasome in Clinical Nutrition.
No full textMalnutrition in patients with head and neck cancer is frequent, multifactorial and widely associated with clinical evolution and prognosis. Accurate nutritional assessments allow for early identification of patients at risk of malnutrition in order to start nutritional support and prevent sarcopenia. We aimed to perform a novel morphofunctional nutritional evaluation and explore changes in inflammasome-machinery components in 45 patients with head and neck cancer who are undergoing systemic treatment. To this aim, an epidemiological/clinical/anthropometric/biochemical evaluation was performed. Serum RCP, IL6 and molecular expression of inflammasome-components and inflammatory-associated factors (NOD-like-receptors, inflammasome-activation-components, cytokines and inflammation/apoptosis-related components, cell-cycle and DNA-damage regulators) were evaluated in peripheral-blood mononuclear-cells (PBMCs). Clinical-molecular correlations/associations were analyzed. Coherent and complementary information was obtained in the morphofunctional nutritional assessment of the patients when bioimpedance, anthropometric and ultrasound data were analyzed. These factors were also correlated with different biochemical and molecular parameters, revealing the complementary aspect of the whole evaluation. Serum reactive C protein (RCP) and IL6 were the most reliable parameters for determining patients with decreased standardized phase angle, which is associated with increased mortality in patients with solid malignancies. Several inflammasome-components were dysregulated in patients with malnutrition, decreased phase angle and dependency grade or increased circulating inflammation markers. A molecular fingerprint based on gene-expression of certain inflammasome factors (p27/CCL2/ASC) in PBMCs accurately differentiated patients with and without malnutrition. In conclusion, malnutrition induces a profound alteration in the gene-expression pattern of inflammasome-machinery components in PBMCs. A comprehensive nutritional assessment including novel morphofunctional techniques and molecular markers allows a broad characterization of the nutritional status in cancer patients. Profile of certain inflammasome-components should be further studied as potential targets for nutrition-focused treatment strategies in cancer patients.S
Factors associated with atherosclerosis in radiographic and non-radiographic axial spondyloarthritis. A multicenter study on 838 patients.
No full textTo identify disease-related factors associated with subclinical atherosclerosis and cardiovascular (CV) events in a large series of patients with axial spondyloarthritis (axSpA) and to identify possible differences in the effect of the potential pro-atherogenic factors between ankylosing spondylitis (AS) non-radiographic axSpA (nr-axSpA). This is a cross-sectional observational study of the AtheSpAin cohort, a Spanish multicenter cohort to study atherosclerosis in axSpA. Subclinical atherosclerosis determined by carotid ultrasound included assessment of carotid intima-media thickness (cIMT) and plaque detection. 639 AS and 167 nr-axSpA patients were recruited. CV risk factors (CRF) and several disease-related factors showed a statistically significant association with subclinical atherosclerosis in the crude analysis. After adjustment for age, sex, and smoking (model 1), associations remained statistically significant for spinal mobility, inflammatory bowel disease, use of prednisone, and Disease-modifying antirheumatic drugs (DMARD) when assessing carotid plaques and for acute phase reactants (APR) at diagnosis, use of prednisone, DMARD, and TNF-inhibitors when measuring cIMT. In model 2, which also included classic CRF as confounding factors to identify axSpA features with a potential independent pro-atherogenic effect, the functional status was the only variable significantly associated with plaques and the use of prednisone and APR at diagnosis with cIMT. No association differences were found between both subtypes of patients. Besides, APR at diagnosis were also associated with subsequent development of CV events that had occurred in 33 patients. Apart from CRF, atherosclerotic disease in AxSpA is associated with disease-related factors such as inflammatory response and disease severity, with no differences between AS and nr-axSpA.S
The NDDG criteria versus the IADPSG or the ADA criteria for diagnosing early-onset gestational diabetes mellitus or abnormal glucose tolerance.
No full textTo analyze the effects of substituting the National Diabetes Data Group (NDDG) criteria with the International Association of Diabetes and Pregnancy Study Groups (IADPSG) or American Diabetes Association (ADA) criteria for the diagnosis of early-onset gestational diabetes mellitus (Early-GDM) or first trimester abnormal glucose tolerance (1 t-AGT). A retrospective cohort study was conducted of 3200 women: 400 with Early-GDM, 800 with GDM, and 2000 with Non-GDM, according to the NDDG criteria. Rates of women with missed and new Early-GDM according to the IADPSG or ADA criteria were calculated. Multivariate logistic regression analysis was used to compare perinatal outcomes between groups. Using the IADPSG criteria, 61.6% of women with Early-GDM according to the NDDG were undiagnosed (Missed-Early-GDM group), and 25.9% of women with GDM and 15.7% of women with Non-GDM were diagnosed with Early-GDM (New-Early-GDM groups). Perinatal outcomes were worse in Missed-Early-GDM than in Non-GDM and better in New-Early-GDM groups than in the Early-GDM group. According to the ADA recommendations, only 11.8% of women with Early-GDM according to the NDDG criteria were diagnosed. Replacing the NDDG recommendations for the diagnosis of Early-GDM with the IADPSG or ADA criteria would mean depriving a large number of women with AGT and higher risk of adverse perinatal outcomes from early treatment and treating others with lower risk.S
Laboratory protocol for the digital multiplexed gene expression analysis of nasopharyngeal swab samples using the NanoString nCounter system.
No full textThis paper describes a laboratory protocol to perform the NanoString nCounter Gene Expression Assay from nasopharyngeal swab samples. It is urgently necessary to identify factors related to severe symptoms of respiratory infectious diseases, such as COVID-19, in order to assess the possibility of establishing preventive or preliminary therapeutic measures and to plan the services to be provided on hospital admission. At present, the samples recommended for microbiological diagnosis are those taken from the upper and/or the lower respiratory tract. The NanoString nCounter Gene Expression Assay is a method based on the direct digital detection of mRNA molecules by means of target-specific, colour-coded probe pairs, without the need for mRNA conversion to cDNA by reverse transcription or the amplification of the resulting cDNA by PCR. This platform includes advanced analysis tools that reduce the need for bioinformatics support and also offers reliable sensitivity, reproducibility, technical robustness and utility for clinical application, even in RNA samples of low RNA quality or concentration, such as paraffin-embedded samples. Although the protocols for the analysis of blood or formalin-fixed paraffin-embedded samples are provided by the manufacturer, no corresponding protocol for the analysis of nasopharyngeal swab samples has yet been established. Therefore, the approach we describe could be adopted to determine the expression of target genes in samples obtained from nasopharyngeal swabs using the nCOUNTER technology.This research was supported by grants from Instituto de Salud Carlos III through the project REDISSEC COV20/0059 awarded to MR; Consejería de Economía, Conocimiento, Empresas y Universidad de la Junta de Andalucía through the projects CV207697_COVID to MR and CV20-62050_COVID to IB, as well as by donations from Fundación Fuerte (Marbella, Spain) and Ms Isabel María Luque Bardón to the Research and Innovation Unit at Hospital Costa del Sol.S
Supramolecular Systems for Gene and Drug Delivery.
No full textSeveral biomaterial-based supramolecular systems (cyclodextrins [1], calixarenes [2,3], polymers [4], carbon nanotubes [5], nanoparticles [6,7], liposomes [3,8], nanogels [9], and nanocomplexes [10], among others) have been widely used for biomedical applications, such as gene and drug delivery. Numerous researchers have developed novel supramolecular systems for enhancing their biocompatibility and pharmacological activity, thus increasing their therapeutic properties. These nanosystems are considered to be promising platforms in gene therapy and drug delivery due to their higher transfection (or encapsulation) efficiency and low cytotoxicity.S
Trajectory Analysis of Suicidal Ideation in Spanish College Students Using Ecological Momentary Assessment.
No full textSuicide is a preventable death in young people. It is well known that suicide behavior is a multicausal phenomenon. However, suicidal ideation (SI) commonly underlies suicide, and Ecological Momentary Assessment (EMA) can help us to better characterize it and its risk and protective factors in the short term. We aimed, first, to investigate the estimated prevalence and trajectories of SI in a community sample of Spanish college students using an EMA methodology and, second, explore the associations between risk and protective factors and SI categorized as moderate or low. A total of 737 participants followed the EMA during a period of 6 months. We estimated the prevalence and trajectories of SI and the associations between depressive symptoms, positive and negative affect, thwarted belongingness, perceived burdensomeness, cognitive reappraisal, emotional suppression, and purpose in life with the MEmind smartphone App. SI was assessed 14 times during this period. Twenty-eight participants referred to SI at least once in longitudinal assessments. We found a lack of curvature and, thus, a relatively stable trajectory of SI. Two groups of latent dimensions were observed related to risk and protective factors of SI. One latent dimension of the risk factors (higher levels of thwarted belongingness, perceived burdensomeness, depressive symptoms, negative affect, and emotional suppression) best represented the group with moderate levels of SI, and a second latent dimension of protective variables (positive affect, cognitive reappraisal, and purpose in life) best represented the group with lower levels of SI. These findings may indicate that students with a sense of having a life worth living, in addition to having the ability to reevaluate their negative beliefs, are less likely to experience high levels of SI. Therefore, purpose in life would be a protective factor against the presence of SI
Acute Colon Inflammation Triggers Primary Motor Cortex Glial Activation, Neuroinflammation, Neuronal Hyperexcitability, and Motor Coordination Deficits.
No full textNeuroinflammation underlies neurodegenerative diseases. Herein, we test whether acute colon inflammation activates microglia and astrocytes, induces neuroinflammation, disturbs neuron intrinsic electrical properties in the primary motor cortex, and alters motor behaviors. We used a rat model of acute colon inflammation induced by dextran sulfate sodium. Inflammatory mediators and microglial activation were assessed in the primary motor cortex by PCR and immunofluorescence assays. Electrophysiological properties of the motor cortex neurons were determined by whole-cell patch-clamp recordings. Motor behaviors were examined using open-field and rotarod tests. We show that the primary motor cortex of rats with acute colon inflammation exhibited microglial and astrocyte activation and increased mRNA abundance of interleukin-6, tumor necrosis factor-alpha, and both inducible and neuronal nitric oxide synthases. These changes were accompanied by a reduction in resting membrane potential and rheobase and increased input resistance and action potential frequency, indicating motor neuron hyperexcitability. In addition, locomotion and motor coordination were impaired. In conclusion, acute colon inflammation induces motor cortex microglial and astrocyte activation and inflammation, which led to neurons' hyperexcitability and reduced motor coordination performance. The described disturbances resembled some of the early features found in amyotrophic lateral sclerosis patients and animal models, suggesting that colon inflammation might be a risk factor for developing this disease.S